MR of the liver in Wilson's disease

International Nuclear Information System (INIS)

Vogl, T.J.; Steiner, S.; Hammerstingl, R.; Schwarz, S.; Kraft, E.; Weinzierl, M.; Felix, R.

1994-01-01

To show that Wilson's disease is one likely cause of multiple low-intensity nodules of the liver we obtained MR images in 16 patients with clinically and histopathologically confirmed Wilson's disease. Corresponding to morphological changes MRI enabled the subdivision of the patients into two groups. Using a T 2 -weighted spin-echo sequence (TR/TE=2000/45-90) liver parenchyma showed multiple tiny low-intensity-nodules surrounded by high-intensity septa in 10 out of 16 patients. 5 patients had also low-intensity nodules in T 1 -weighted images (TR/TE=600/20). In patients of this group histopathology revealed liver cirrhosis (n=7) and fibrosis (n=2). Common feature of this patient group was marked inflammatory cell infiltration into fibrous septa, increase of copper concentration in liver parenchyma and distinct pathological changes of laboratory data. In the remaining 6 patients no pathological change of liver morphology was demonstrated by MRI corresponding to slight histopathological changes of parenchyma and normal laboratory data. As low-intensity nodules surrounded by high intensity septa can be demonstrated in patients with marked inflammatory infiltration of liver parenchyma MRI may help to define Wilson patients with poorer prognosis. In patients with low-intensity nodules of the liver and unknown cause of liver cirrhosis laboratory data and histopathology should be checked when searching for disorders of copper metabolism. (orig.) [de

Epidemiology and introduction to the clinical presentation of Wilson disease.

Science.gov (United States)

Lo, Christine; Bandmann, Oliver

2017-01-01

Our understanding of the epidemiology of Wilson disease has steadily grown since Sternlieb and Scheinberg's first prevalence estimate of 5 per million individuals in 1968. Increasingly sophisticated genetic techniques have led to revised genetic prevalence estimates of 142 per million. Various population isolates exist where the prevalence of Wilson disease is higher still, the highest being 885 per million from within the mountainous region of Rucar in Romania. In Sardinia, where the prevalence of Wilson disease has been calculated at 370 per million births, six mutations account for around 85% of Wilson disease chromosomes identified. Significant variation in the patterns of presentation may however exist, even between individuals carrying the same mutations. At either extremes of presentation are an 8-month-old infant with abnormal liver function tests and individuals diagnosed in their eighth decade of life. Three main patterns of presentation have been recognized - hepatic, neurologic, and psychiatric - prompting their presentation to a diverse range of specialists. Deviations in the family history from the anticipated autosomal-recessive mode of inheritance, with apparent "pseudodominance" and mechanisms of inheritance that include uniparental isodisomy (the inheritance of both chromosomal copies from a single parent), may all further cloud the diagnosis. It can therefore take the efforts of an astute clinician with a high clinical index of suspicion to clinch the diagnosis of this eminently treatable condition. © 2017 Elsevier B.V. All rights reserved.

Wilson's disease in children: clinical and diagnostic features

International Nuclear Information System (INIS)

Ayesha, H.; Choudhry, A.A.; Javed, M.T.; Javed, F.

2002-01-01

Objective: To study the clinical and diagnostic laboratory features of Wilsons disease in children and adolescents. Design: A prospective cohort study. Place and Duration of study: The study included patients diagnosed as Wilson s disease at the Department of Pediatrics Allied Hospital, Punjab medical College, Faisalabad from May 1997 to June 2001. Patients and methods: Patients presenting with liver or suggestive neurological disease were investigated. Others were diagnosed as a result of family screening. Diagnosis of neurologic disease was made if two of the following were present: Typical neurological findings, Kayser Fleischer corneal rings and low serum ceruloplasmin ( 100 mu gm) free serum copper (>10 mu gm/dl). In other forms and for family screening, 24 hours. Urinary copper (> 100 mu gm), free serum copper (>10 mu gm/dl), and wherever possible liver biopsy for histopathology and cytochemical staining by rubeanic acid was also done. Results: Twenty-seven patients with a mean age of 10.2 years were diagnosed as suffering from Wilson disease. Mean age for hepatic and neurological disease was 9 years and 11.5 years respectively. Youngest patient (neurologic) was 6 years old. 48% cases presented with neurological, 41% with hepatic and 4% with skeletal manifestations while 7 % were asymptomatic. Mean duration of symptoms before diagnosis was 6.1 months. Dysarthria (84.6%), tremors (69.2%), rigidity and poor school performance and hand writing (61.5%), dysphagia (46.1%) and dystonia (38.5%), were the most common neurologic findings. Chronic liver disease was seen in 73 % while acute forms were seen in 27 % cases. Two cases presented with fulminant hepatic failure. Consanguineous marriage of the parents was found in 70 % and family history of disease was present in 65 % cases. K-F (Kayser Fleischer) rings and low serum ceruloplasmin(<20 mg/dl) was found in 85% of all patients. In non neurologic types other tests of copper metabolism were done. Elevated urinary

Wilson's disease in Southern Brazil: genotype-phenotype correlation and description of two novel mutations in ATP7B gene

Directory of Open Access Journals (Sweden)

Ricardo Schmitt de Bem

2013-08-01

Full Text Available OBJECTIVE: Wilson's disease (WD is an inborn error of metabolism caused by abnormalities of the copper-transporting protein encoding gene ATP7B. In this study, we examined ATP7B for mutations in a group of patients living in southern Brazil. METHODS: 36 WD subjects were studied and classified according to their clinical and epidemiological data. In 23 subjects the ATP7B gene was analyzed. RESULTS: Fourteen distinct mutations were detected in at least one of the alleles. The c.3207C>A substitution at exon 14 was the most common mutation (allelic frequency=37.1% followed by the c.3402delC at exon 15 (allelic frequency=11.4%. The mutations c.2018-2030del13 at exon 7 and c.4093InsT at exon 20 are being reported for the first time. CONCLUSION: The c.3207C>A substitution at exon 14, was the most common mutation, with an allelic frequency of 37.1%. This mutation is the most common mutation described in Europe.

Middle-aged heterozygous carriers of Wilson's disease do not ...

Indian Academy of Sciences (India)

957 Warsaw, Poland. 2Medical University of Warsaw, Department of Experimental and Clinical Pharmacology, 00–325 Warsaw, Poland. Introduction. Wilson disease (WD) is an autosomal recessive disor- der of copper (Cu) metabolism (OMIM ...

No increased risk of hepatocellular carcinoma in cirrhosis due to Wilson disease during long-term follow-up

NARCIS (Netherlands)

van Meer, Suzanne; de Man, Robert A.; van den Berg, Aad P.; Houwen, Roderick H. J.; Linn, Francisca H. H.; van Oijen, Martijn G. H.; Siersema, Peter D.; van Erpecum, Karel J.

Background and AimsData on risk of hepatocellular carcinoma (HCC) in patients with Wilson disease are scarce. We determine HCC risk in a well-defined cohort of Wilson patients. MethodsAll patients with a confirmed diagnosis of Wilson disease (Leipzig score4) in three Dutch university referral

Anesthesia in Mowat-Wilson syndrome: information on 11 Italian patients

OpenAIRE

Marianna Spunton; Livia Garavelli; Paola Cerutti Mainardi; Uta Emmig; Enrico Finale; Andrea Guala

2018-01-01

Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and characterized by typical clinical features. The congenital malformations typical of this syndrome call for early diagnostic and surgical procedures requiring general anesthesia, but few information about the anesthesiology management of such patients is available. We enrolled 11 families of patients with Mowat-Wilson syndrome who had undergone surgical or diagnostic procedures requiri...

The Wilson films--Huntington's chorea.

Science.gov (United States)

Klein, Christine

2011-12-01

Wilson's Queen Square Case 9 with Huntington's chorea shows a 68-year-old man with mild to moderate generalized chorea, impaired fixation, and probable cognitive decline in keeping with a diagnosis of Huntington's disease (HD). An age of onset in the late sixties and a negative family history suggest a relatively small expanded trinucleotide repeat in the HTT gene in the patient and reduced penetrance of an even shorter repeat allele in one of his parents. A highly sensitive and specific gene test has been offered worldwide for diagnostic testing of HD for almost two decades. This test, obviously unavailable at Wilson's times, became the historic frontrunner for guidelines of symptomatic, presymptomatic, and prenatal testing for an adult-onset neurodegenerative disorder. Regarding treatment of HD, however, we are still awaiting the successful translation of research results into the development of effective cause-directed, neuropreventive and neurorestaurative therapies. Copyright © 2011 Movement Disorder Society.

Hypopituitarism Presenting as Adrenal Insufficiency and Hypothyroidism in a Patient with Wilson's Disease: a Case Report.

Science.gov (United States)

Lee, Hae Won; Kang, Jin Du; Yeo, Chang Woo; Yoon, Sung Woon; Lee, Kwang Jae; Choi, Mun Ki

2016-08-01

Wilson's disease typically presents symptoms associated with liver damage or neuropsychiatric disturbances, while endocrinologic abnormalities are rare. We report an unprecedented case of hypopituitarism in a patient with Wilson's disease. A 40-year-old woman presented with depression, general weakness and anorexia. Laboratory tests and imaging studies were compatible with liver cirrhosis due to Wilson's disease. Basal hormone levels and pituitary function tests indicated secondary hypothyroidism and adrenal insufficiency due to hypopituitarism. Brain MRI showed T2 hyperintense signals in both basal ganglia and midbrain but the pituitary imaging was normal. She is currently receiving chelation therapy along with thyroid hormone and steroid replacement. There may be a relationship between Wilson's disease and hypopituitarism. Copper deposition or secondary neuronal damage in the pituitary may be a possible explanation for this theory.

Wilson's disease: start with psychiatric symptoms. Brain magnetic resonance findings

International Nuclear Information System (INIS)

Nagel, Jorge; Miralles, Sabrina

2007-01-01

Wilson's disease - hepatolenticular degeneration - is an autosomal recessive genetic disorder, characterized by an excessive and toxic accumulation of cooper in different tissues. This accumulation is produced by an inherited defect in cooper's biliary excretion. This rare disorder affects approximately one on 30.000 individuals. Signs and symptoms of hepatic, neurologic and psychiatric disease are the most common clinical presentations of symptomatic Wilson's disease. The diagnosis can usually be made by laboratory tests that find a decreased cooper binding protein in blood called ceruloplasmin, an increase in the excretion of cooper in 24 hour urine and the appearance of corneal Kayser-Fleischer ring. We present a 28 years patient who began with depression and panic attacks, followed by neurologic symptoms. Brain MRI was performed and showed different alterations suggesting the diagnosis of this infrequent sickness. (author) [es

Identification of p38 MAPK and JNK as New Targets for Correction of Wilson Disease-Causing ATP7B Mutants

NARCIS (Netherlands)

Chesi, Giancarlo; Hegde, Ramanath N.; Iacobacci, Simona; Concilli, Mafalda; Parashuraman, Seetharaman; Festa, Beatrice Paola; Polishchuk, Elena V.; Di Tullio, Giuseppe; Carissimo, Annamaria; Montefusco, Sandro; Canetti, Diana; Monti, Maria; Amoresano, Angela; Pucci, Piero; Sluis, van de Bart; Lutsenko, Svetlana; Luini, Alberto; Polishchuk, Roman S.

Wilson disease (WD) is an autosomal recessive disorder that is caused by the toxic accumulation of copper (Cu) in the liver. The ATP7B gene, which is mutated in WD, encodes a multitransmembrane domain adenosine triphosphatase that traffics from the trans-Golgi network to the canalicular area of

The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders

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Hille Fieten

2016-01-01

Full Text Available The deleterious effects of a disrupted copper metabolism are illustrated by hereditary diseases caused by mutations in the genes coding for the copper transporters ATP7A and ATP7B. Menkes disease, involving ATP7A, is a fatal neurodegenerative disorder of copper deficiency. Mutations in ATP7B lead to Wilson disease, which is characterized by a predominantly hepatic copper accumulation. The low incidence and the phenotypic variability of human copper toxicosis hamper identification of causal genes or modifier genes involved in the disease pathogenesis. The Labrador retriever was recently characterized as a new canine model for copper toxicosis. Purebred dogs have reduced genetic variability, which facilitates identification of genes involved in complex heritable traits that might influence phenotype in both humans and dogs. We performed a genome-wide association study in 235 Labrador retrievers and identified two chromosome regions containing ATP7A and ATP7B that were associated with variation in hepatic copper levels. DNA sequence analysis identified missense mutations in each gene. The amino acid substitution ATP7B:p.Arg1453Gln was associated with copper accumulation, whereas the amino acid substitution ATP7A:p.Thr327Ile partly protected against copper accumulation. Confocal microscopy indicated that aberrant copper metabolism upon expression of the ATP7B variant occurred because of mis-localization of the protein in the endoplasmic reticulum. Dermal fibroblasts derived from ATP7A:p.Thr327Ile dogs showed copper accumulation and delayed excretion. We identified the Labrador retriever as the first natural, non-rodent model for ATP7B-associated copper toxicosis. Attenuation of copper accumulation by the ATP7A mutation sheds an interesting light on the interplay of copper transporters in body copper homeostasis and warrants a thorough investigation of ATP7A as a modifier gene in copper-metabolism disorders. The identification of two new functional

Clinical investigation in Wilson's disease

International Nuclear Information System (INIS)

Mizutani, Naoki; Maehara, Mitsuo; Negoro, Tamiko; Watanabe, Kazuyoshi

1983-01-01

Wilson's disease of cerebral type with a chief complaint of tremor occurred in 3 brothers and sisters of a certain family line. Treatment with D-penicillamine produced remarkable clinical improvement as shown by the disappearance of tremor and Kayser-Fleischer ring. Cranial CT scans made before the treatment revealed abnormal findings such as low density areas in the (bilateral) thalamus and the lenticular nucleus, atrophy of the cerebral cortex, and enlargement of the ventricles. After the treatment, cranial CT revealed that the low density areas in the thalamus and the lenticular nucleus disappeared corresponding to the clinical improvement. However, the atrophy of the cerebral cortex and the enlargement of the ventricles were not ameliorated. (Ueda, J.)

Metabolism of 25-hydroxyvitamin D in copper-laden rat: A model of Wilson's disease

International Nuclear Information System (INIS)

Carpenter, T.O.; Pendrak, M.L.; Anast, C.S.

1988-01-01

Wilson's disease results in excess tissue accumulation of copper and is often complicated by skeletal and mineral abnormalities. The authors investigated vitamin D metabolism in rats fed a copper-laden diet rendering hepatic copper content comparable with that found in Wilson's disease. Injection of 25-hydroxyvitamin D 3 [25(OH)D 3 ] resulted in reduced 1,25--dihydroxyvitamin D [1,25(OH) 2 D] levels in copper-intoxicated rats. In vitro 25(OH)D-1α-hydroxylase activity was impaired in renal mitochondria from copper-intoxicated animals. Activity was also inhibited in mitochondrial from controls when copper was added to incubation media. Impaired conversion of 25(OH)D to 1,25(OH) 2 D occurs in copper intoxication and suggests that altered vitamin D metabolism is a potential factor in the development of bone and mineral abnormalities in Wilson's disease

Microstructure assessment of the thalamus in Wilson's disease using diffusion tensor imaging

International Nuclear Information System (INIS)

Li, G.; Zhou, X.; Xu, P.; Pan, X.; Chen, Y.

2014-01-01

Aim: To assess diffusion changes of the thalamus in Wilson's disease using diffusion tensor imaging (DTI). Materials and methods: Fifteen patients with Wilson's disease and an abnormal signal in the thalamus (designated as group 1) and 18 patients with Wilson's disease with a normal-appearing thalamus (designated as group 2) at conventional magnetic resonance imaging (MRI) were recruited. Fifteen age-matched and sex-matched healthy volunteers were also enrolled as the control group (designated as group 3). The fractional anisotropy (FA), primary eigenvalue (λ1), second eigenvalue (λ2), and third eigenvalue (λ3) of the thalamus were measured and the differences were compared. Results: The FA values of the thalamus were different in the three groups (group 1: 0.36 ± 0.02; group 2: 0.38 ± 0.02; group 3: 0.43 ± 0.02; F = 54.51, p 2 /s, 1.11 ± 0.06 mm 2 /s, and 1.10 ± 0.04 mm 2 /s of λ1 in group 1, group 2, and group 3, respectively; 0.82 ± 0.08 mm 2 /s, 0.78 ± 0.05 mm 2 /s, and 0.72 ± 0.02 mm 2 /s of λ2 in group 1, group 2, and group 3, respectively; 0.52 ± 0.05 mm 2 /s, 0.49 ± 0.06 mm 2 /s, and 0.42 ± 0.06 mm 2 /s of λ3 in group 1, group 2, and group 3, respectively; F = 1.65, p = 0.203 of λ1; F = 10.55, p < 0.001 of λ2; F = 4.21, p = 0.021 of λ3; respectively). A statistically significant difference in the λ2 value was observed between group 1 and group 3 (p < 0.001) and group 2 and group 3 (p = 0.005). A statistically significant difference in the λ3 value was also observed between group 1 and group 3 (p = 0.007). No significant difference in the λ1 value was noted between each of the two groups. Conclusions: Damage of the thalamus in Wilson's disease patients can be detected using DTI. DTI may provide information regarding thalamus damage in patients with Wilson's disease before abnormal signals on conventional MRI

Persistently and asymptomatic raised liver enzymes as a form of presentation of Wilson's disease at pediatric age

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Catarina Matos

2015-06-01

Full Text Available Background: Wilson`s disease is a rare autosomal recessive disorder characterized by a change in the transport of copper in the liver, with progressive accumulation in this and other organs such as brain, kidney and cornea. Phenotypic expression of the disease varies widely and can range from elevated liver enzymes, fatty liver or gallstones in asymptomatic patients, to cirrhosis and fulminant hepatic failure, or disabling neuropsychiatric disease. Aim: To characterize a sample of patients with Wilson´s disease. Patients and Methods: Retrospective survey including children diagnosed with Wilson´s disease between 2002 and 2011 according to the criteria of the European Association for the Study of the Liver (2012. We analyzed family history; age, clinical data, imaging and histology at the time of diagnosis; genetic analysis; treatment and side effects; follow-up and current status. Results: We identified five patients. Three had a family history of disease. All were asymptomatic and had maintained raised liver enzymes. No patient had clinical stigmata of chronic liver disease. One female patient had overweight. All were treated with D-penicillamine, withdrawn in two patients because of side effects. Currently all patients remain asymptomatic, without evidence of progression of liver disease, with a median follow-up of 5 years and 3 months. Discussion: Our series show that Wilson´s disease may be present with raised liver enzymes in asymptomatic children. The overweight patient alerts us to screen the disease in overweight/obese patients with raised liver enzymes and/or steatosis persisting for more than six months after weight loss.

Wilson disease: more than meets the eye.

Science.gov (United States)

Kelly, Claire; Pericleous, Marinos

2018-02-15

Wilson disease is a rare but important disorder of copper metabolism, with a failure to excrete copper appropriately into bile. It is a multisystem condition with presentations across all branches of medicine. Diagnosis can be difficult and requires a high index of suspicion. It should be considered in unexplained liver disease particularly where neuropsychiatric features are also present. Treatments are available for all stages of disease. A particularly important presentation not to overlook is acute liver failure which carries a high mortality risk and may require urgent liver transplantation. Here, we provide an overview of this complex condition. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Mismanagement of Wilson's disease as psychotic disorder.

Science.gov (United States)

Bidaki, Reza; Zarei, Mina; Mirhosseini, S M Mahdy; Moghadami, Samar; Hejrati, Maral; Kohnavard, Marjan; Shariati, Behnam

2012-01-01

Wilson's disease (WD) or hepatolenticular degeneration is an inherited neurodegenerative disorder of copper metabolism (autosomal recessive, chromosome13). Psychiatric disorders in WD include dementia, characterized by mental slowness, poor concentration, and memory impairment. Symptoms may progress rapidly, especially in younger patients, but are more often gradual in development with periods of remission and exacerbation. Delusional disorder and schizophrenia-like psychosis are rare forms of psychiatric presentation. In this report, the patient with WD presented by psychosis symptoms and treated mistaken as schizophrenia for almost ten years. Although he has treated with antipsychotics, he had periods of remissions and relapses and never was symptoms free. Since psychosis can be the manifestation of medical diseases such as WD, overall view of these patients is necessary and medical diseases should be considered as a differential diagnosis.

Mowat–Wilson syndrome – case study

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Kamil Faltin

2016-06-01

Full Text Available Mowat–Wilson syndrome is a rare genetic condition characterised by a number of congenital anomalies, including facial dysmorphia, heart and kidney anomalies, Hirschsprung’s disease, intellectual disability and abnormalities of reproductive organs. In the paper, we present a case of a girl who was admitted to the Department of Paediatrics, Immunology and Nephrology at the age of 3 months, with a suspicion of tubulointerstitial nephritis. The patient had facial dysmorphia, congenital malformations of the nervous system and Hirschsprung’s disease. During hospitalisation, congenital urinary anomalies (bilateral vesicoureteral reflux and heart defects were diagnosed. On the basis of the clinical picture, the diagnostics was expanded to genetic tests for Mowat–Wilson syndrome, which revealed an 857_858delAG pathogenic mutation in one of the ZEB2 gene alleles (exon 7 – one of the rarer causes of Mowat–Wilson syndrome. At present, the girl is 13 months old. Her development is delayed. Currently, the girl is under multidisciplinary care and she is undergoing intensive rehabilitation. The knowledge of the syndrome’s clinical features allows a faster diagnosis to be made and multispecialty care to be provided to the child.

Clinical presentation and mutations in Danish patients with Wilson disease

DEFF Research Database (Denmark)

Møller, Lisbeth Birk; Horn, Nina; Jeppesen, Tina Dysgaard

2011-01-01

This study describes the clinical presentation and diagnosis in all Danish patients (49, 41 unrelated) with Wilson disease (WND). On the basis of the number of diagnosed patients from 1990-2008, the prevalence was estimated to be 1:49¿500. Among routinely used diagnostic tests, none were...

Clinical presentation and mutations in Danish patients with Wilson disease

DEFF Research Database (Denmark)

Møller, Lisbeth Birk; Horn, Nina; Jeppesen, Tina Dysgaard

2011-01-01

This study describes the clinical presentation and diagnosis in all Danish patients (49, 41 unrelated) with Wilson disease (WND). On the basis of the number of diagnosed patients from 1990-2008, the prevalence was estimated to be 1:49 500. Among routinely used diagnostic tests, none were...

How Is Wilson Disease Inherited?

Science.gov (United States)

... News & Announcements Wilson's Warriors Events Back The Big WOW 2018 Annual Conference WDA Publications Back Downloads Corporate Sponsorship Forms Membership Forms Resources The Big WOW Newsletters News Copper Connection Newsletter Resources Centers of ...

How Is Wilson Disease Diagnosed?

Science.gov (United States)

... News & Announcements Wilson's Warriors Events Back The Big WOW 2018 Annual Conference WDA Publications Back Downloads Corporate Sponsorship Forms Membership Forms Resources The Big WOW Newsletters News Copper Connection Newsletter Resources Centers of ...

Cranial MRI in Wilson's disease

International Nuclear Information System (INIS)

Prayer, L.; Grimm, G.

1990-01-01

Thirty-eight patients with biochemically proven Wilson's disease underwent magnetic resonanceimaging (MRI) of the brain as well as neurological examinations. The patients were scanned using spin-echo (SE) sequences; the neurologist was looking for typical symptoms: Dysarthria, tremor, ataxia, rigidity/bradykinesia and chorea/dystonia. Pathological MR findings believed secondary to this uncommon inherited disorder of copper metabolism were found in twenty-two subjects. Focal abnormalities were seen in the lenticular, thalamic and caudate nuclei as well as in brain stem and white matter; these lesions were best demonstrated on T2-weighted sequences as hyperintense areas. In eight patients we found diffuse brain atrophy with consecutive widening of the ventricular system. Five subjects showed mild, nineteen severe neurologic deficits. Generally there was no correlation between MR findings and clinical neurological symptoms; the impairment of cell-metabolism causing functional alterations of the brain precedes morphological changes. During treatment with the copper chelator D-penicillamine there seemed to be a phased course of disease. Shortening of T1-relaxation due to paramagnetic influence of copper was not seen; a possible explanation could be intracellular deposition - a proton-electron-dipolar-dipolar-interaction would there for be impossible. (orig.)

Biopolymer strategy for the treatment of Wilson´s disease

Czech Academy of Sciences Publication Activity Database

Vetrík, Miroslav; Mattová, J.; Macková, Hana; Kučka, Jan; Poučková, P.; Kukačková, Olivia; Brus, Jiří; Eigner-Henke, S.; Sedláček, Ondřej; Šefc, L.; Štěpánek, Petr; Hrubý, Martin

2018-01-01

Roč. 273, 10 March (2018), s. 131-138 ISSN 0168-3659 R&D Projects: GA ČR(CZ) GA16-02870S; GA MZd(CZ) NV15-25781A; GA MŠk(CZ) LM2015064; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : Wilson's disease * copper chelators * biopolymers Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 7.786, year: 2016

Characterization of Timed Changes in Hepatic Copper Concentrations, Methionine Metabolism, Gene Expression, and Global DNA Methylation in the Jackson Toxic Milk Mouse Model of Wilson Disease

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Anh Le

2014-05-01

Full Text Available Background: Wilson disease (WD is characterized by hepatic copper accumulation with progressive liver damage to cirrhosis. This study aimed to characterize the toxic milk mouse from The Jackson Laboratory (Bar Harbor, ME, USA (tx-j mouse model of WD according to changes over time in hepatic copper concentrations, methionine metabolism, global DNA methylation, and gene expression from gestational day 17 (fetal to adulthood (28 weeks. Methods: Included liver histology and relevant biochemical analyses including hepatic copper quantification, S-adenosylmethionine (SAM and S-adenosylhomocysteine (SAH liver levels, qPCR for transcript levels of genes relevant to methionine metabolism and liver damage, and DNA dot blot for global DNA methylation. Results: Hepatic copper was lower in tx-j fetuses but higher in weanling (three weeks and adult tx-j mice compared to controls. S-adenosylhomocysteinase transcript levels were significantly lower at all time points, except at three weeks, correlating negatively with copper levels and with consequent changes in the SAM:SAH methylation ratio and global DNA methylation. Conclusion: Compared to controls, methionine metabolism including S-adenosylhomocysteinase gene expression is persistently different in the tx-j mice with consequent alterations in global DNA methylation in more advanced stages of liver disease. The inhibitory effect of copper accumulation on S-adenosylhomocysteinase expression is associated with progressively abnormal methionine metabolism and decreased methylation capacity and DNA global methylation.

Update on Wilson disease.

Science.gov (United States)

Aggarwal, Annu; Bhatt, Mohit

2013-01-01

Wilson disease (WD) is an inherited disorder of chronic copper toxicosis characterized by excessive copper deposition in the body, primarily in the liver and the brain. It is a progressive disease and fatal if untreated. Excessive copper accumulation results from the inability of liver to excrete copper in bile. Copper is an essential trace metal and has a crucial role in many metabolic processes. Almost all of the body copper is protein bound. In WD, the slow but relentless copper accumulation overwhelms the copper chaperones (copper-binding proteins), resulting in high levels of free copper and copper-induced tissue injury. Liver is the central organ for copper metabolism, and copper is initially accumulated in the liver but over time spills to other tissues. WD has protean clinical manifestations mainly attributable to liver, brain, and osseomuscular impairment. Diagnosis of WD is challenging and based on combination of clinical features and laboratory tests. Identification of various high-frequency mutations identified in different population studies across the world has revived interest in developing DNA chips for rapid genetic diagnosis of WD. All symptomatic and all presymptomatic patients require lifelong decoppering with careful clinical tracking. Decoppering ensures that presymptomatic individuals remain symptom free. With judicious decoppering, given time, even patients with severe neurological disability improve and can return to normal life and resume school or work at par with their peers. Treatment regimens and tracking patients using the WD-specific Global Assessment Scale for WD (GAS for WD) are discussed. © 2013 Elsevier Inc. All rights reserved.

Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease

International Nuclear Information System (INIS)

Oe, Shinji; Miyagawa, Koichiro; Honma, Yuichi; Harada, Masaru

2016-01-01

Copper is an essential trace element, however, excess copper is harmful to human health. Excess copper-derived oxidants contribute to the progression of Wilson disease, and oxidative stress induces accumulation of abnormal proteins. It is known that the endoplasmic reticulum (ER) plays an important role in proper protein folding, and that accumulation of misfolded proteins disturbs ER homeostasis resulting in ER stress. However, copper-induced ER homeostasis disturbance has not been fully clarified. We treated human hepatoma cell line (Huh7) and immortalized-human hepatocyte cell line (OUMS29) with copper and chemical chaperones, including 4-phenylbutyrate and ursodeoxycholic acid. We examined copper-induced oxidative stress, ER stress and apoptosis by immunofluorescence microscopy and immunoblot analyses. Furthermore, we examined the effects of copper on carcinogenesis. Excess copper induced not only oxidative stress but also ER stress. Furthermore, excess copper induced DNA damage and reduced cell proliferation. Chemical chaperones reduced this copper-induced hepatotoxicity. Excess copper induced hepatotoxicity via ER stress. We also confirmed the abnormality of ultra-structure of the ER of hepatocytes in patients with Wilson disease. These findings show that ER stress plays a pivotal role in Wilson disease, and suggests that chemical chaperones may have beneficial effects in the treatment of Wilson disease.

Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease

Energy Technology Data Exchange (ETDEWEB)

Oe, Shinji, E-mail: ooes@med.uoeh-u.ac.jp; Miyagawa, Koichiro, E-mail: koichiro@med.uoeh-u.ac.jp; Honma, Yuichi, E-mail: y-homma@med.uoeh-u.ac.jp; Harada, Masaru, E-mail: msrharada@med.uoeh-u.ac.jp

2016-09-10

Copper is an essential trace element, however, excess copper is harmful to human health. Excess copper-derived oxidants contribute to the progression of Wilson disease, and oxidative stress induces accumulation of abnormal proteins. It is known that the endoplasmic reticulum (ER) plays an important role in proper protein folding, and that accumulation of misfolded proteins disturbs ER homeostasis resulting in ER stress. However, copper-induced ER homeostasis disturbance has not been fully clarified. We treated human hepatoma cell line (Huh7) and immortalized-human hepatocyte cell line (OUMS29) with copper and chemical chaperones, including 4-phenylbutyrate and ursodeoxycholic acid. We examined copper-induced oxidative stress, ER stress and apoptosis by immunofluorescence microscopy and immunoblot analyses. Furthermore, we examined the effects of copper on carcinogenesis. Excess copper induced not only oxidative stress but also ER stress. Furthermore, excess copper induced DNA damage and reduced cell proliferation. Chemical chaperones reduced this copper-induced hepatotoxicity. Excess copper induced hepatotoxicity via ER stress. We also confirmed the abnormality of ultra-structure of the ER of hepatocytes in patients with Wilson disease. These findings show that ER stress plays a pivotal role in Wilson disease, and suggests that chemical chaperones may have beneficial effects in the treatment of Wilson disease.

Inhibitory rTMS applied on somatosensory cortex in Wilson's disease patients with hand dystonia.

Science.gov (United States)

Lozeron, Pierre; Poujois, Aurélia; Meppiel, Elodie; Masmoudi, Sana; Magnan, Thierry Peron; Vicaut, Eric; Houdart, Emmanuel; Guichard, Jean-Pierre; Trocello, Jean-Marc; Woimant, France; Kubis, Nathalie

2017-10-01

Hand dystonia is a common complication of Wilson's disease (WD), responsible for handwriting difficulties and disability. Alteration of sensorimotor integration and overactivity of the somatosensory cortex have been demonstrated in dystonia. This study investigated the immediate after effect of an inhibitory repetitive transcranial magnetic stimulation (rTMS) applied over the somatosensory cortex on the writing function in WD patients with hand dystonia. We performed a pilot prospective randomized double-blind sham-controlled crossover rTMS study. A 20-min 1-Hz rTMS session, stereotaxically guided, was applied over the left somatosensory cortex in 13 WD patients with right dystonic writer's cramp. After 3 days, each patient was crossed-over to the alternative treatment. Patients were clinically evaluated before and immediately after each rTMS session with the Unified Wilson's Disease rating scale (UWDRS), the Writers' Cramp Rating Scale (WCRS), a specifically designed scale for handwriting difficulties in Wilson's disease patients (FAR, flow, accuracy, and rhythmicity evaluation), and a visual analog scale (VAS) for handwriting discomfort. No significant change in UWDRS, WCRS, VAS, or FAR scores was observed in patients treated with somatosensory inhibitory rTMS compared to the sham protocol. The FAR negatively correlated with UWDRS (r = -0.6; P = 0.02), but not with the WCRS score, disease duration, MRI diffusion lesions, or with atrophy scores. In our experimental conditions, a single inhibitory rTMS session applied over somatosensory cortex did not improve dystonic writer cramp in WD patients.

Ophthalmologic abnormalities in Mowat-Wilson syndrome and a mutation in ZEB2.

Science.gov (United States)

Ariss, Michelle; Natan, Kristina; Friedman, Neil; Traboulsi, Elias I

2012-09-01

Mowat-Wilson syndrome is a genetic disorder characterized by a distinct facial appearance, moderate-to-severe mental retardation, microcephaly, agenesis of the corpus callosum, Hirschsprung disease, congenital heart disease, and genital anomalies. Ophthalmological abnormalities have been rarely described in patients with this condition which is caused by mutations in the ZEB2 gene. We report a 9-year-old female with this syndrome who has severe ocular abnormalities including bilateral microphthalmia, cataract, and retinal aplasia.

Increased cerebral iron uptake in Wilson's disease : A (52)Fe-citrate PET study

NARCIS (Netherlands)

Bruehlmeier, M; Leenders, KL; Vontobel, P; Calonder, C; Antonini, A; Weindl, A

Toxicity of abundant copper is the main cause of brain and liver tissue damage in patients with Wilson's disease (WD). However, there is also evidence of a disturbed iron metabolism in this genetically determined disorder. This PET study was undertaken to assess cerebral iron metabolism in WD

Importance and significance of liver echotomography in Wilson disease childhood

Energy Technology Data Exchange (ETDEWEB)

Corda, R; Nurchi, A M; Corrias, A; Corda, A; Giagheddu, M; Campisi, G

1987-01-01

We studed the hepatic echography patterns of young patients suffering from Wilson's Disease and compared these with results obtained from laboratory tests and parenchymal biopsy. Eight children, aged between 5 and 12 years (4 males and 4 females), were examined. The symptomatological pattern showed hepatomegaly and liver dysfunction with undetectable or very low serum ceruloplasmine levels and typical aspects of organic copper metabolism. In 50% of cases echography revealed a variable hyperreflection of the whole parenchyma, in connection with the presence of steatosis and aspects of intralobular inflammation. Fine and linear echoes were present, in 50% of the cases, with varying degrees of brightness, which was associated with the presence of fibrotic component or copper granules. Further echographic modifications were less frequent. Echography in close relatives of our patients was observed hepatomegaly and alteration of hepatic reflection associated with fibrotic component. In the evaluation of liver involvement in Wilson's Disease, these findings show that echotomography, when compared to hepatic biopsy, is less efficient in detecting different types of hepatic lesion but on a clinical basis it offers the possibility of evaluating their presence and gravity during the evolutive phase of the illness. This examination, unlike other methods, is completely non invasive; it may easily be repeated and may, in the future, come to be used as more precise diagnostic complement. 30 refs.

Wilson Disease Protein ATP7B Utilizes Lysosomal Exocytosis to Maintain Copper Homeostasis

NARCIS (Netherlands)

Polishchuk, Elena V.; Concilli, Mafalda; Iacobacci, Simona; Chesi, Giancarlo; Pastore, Nunzia; Piccolo, Pasquale; Paladino, Simona; Baldantoni, Daniela; van IJzendoorn, Sven C. D.; Chan, Jefferson; Chang, Christopher J.; Amoresano, Angela; Pane, Francesca; Pucci, Piero; Tarallo, Antonietta; Parenti, Giancarlo; Brunetti-Pierri, Nicola; Settembre, Carmine; Ballabio, Andrea; Polishchuk, Roman S.

2014-01-01

Copper is an essential yet toxic metal and its overload causes Wilson disease, a disorder due to mutations in copper transporter ATP7B. To remove excess copper into the bile, ATP7B traffics toward canalicular area of hepatocytes. However, the trafficking mechanisms of ATP7B remain elusive. Here, we

Disartria na doença de Wilson: análise de dois casos em fases distintas Dysarthria in Wilson's disease: analysis of two cases in different stages

Directory of Open Access Journals (Sweden)

Natália Casagrande Brabo

2010-06-01

Full Text Available TEMA: disartria na Doença de Wilson. PROCEDIMENTOS: estudo de caso de dois pacientes com o diagnóstico da doença, ambos adultos jovens, do sexo feminino e com seis anos de escolaridade. Quatro fonoaudiólogas realizaram a avaliação perceptivo-auditiva de modo independente, na qual foram investigados os seguintes parâmetros: tipo de voz, loudness, pitch, ataque vocal, instabilidade fonatória e ressonância. O grau de alteração de cada parâmetro foi mensurado através de uma escala analógico-visual. Além disso, foram obtidas medidas de inteligibilidade por transcrição ortográfica. A análise acústica foi realizada por meio do programa Praat, com a obtenção de medidas de frequência fundamental, de perturbação e ruído e medidas temporais. RESULTADOS: a fala de ambos os pacientes foi caracterizada por: redução do tempo máximo de fonação, voz soprosa e tensa, ataques vocais aspirados, instabilidade vocal, aumento de shimmer e proporção ruído-harmônico, hipernasalidade, redução da diadococinesia oral, da inteligibilidade e da velocidade da fala. Os resultados obtidos sugeriram que o paciente que cursa com a Doença de Wilson há mais tempo, apresentou prejuízo mais acentuado na maioria dos parâmetros perceptuais e acústicos analisados. CONCLUSÃO: foram identificadas manifestações comuns entre os casos, as quais podem constituir-se em traços característicos da fala de pacientes disártricos com Doença de Wilson. Todavia, diferenças também foram evidenciadas, as quais podem estar relacionadas ao tempo de evolução da doença.BACKGROUND: dysarthria in Wilson's disease. PROCEDURES: case study of two patients with disease's diagnosis, both young female adults, with six years of schooling. Perceptual analysis was done by four speech therapists. The following parameters were assessed: voice quality, loudness, pitch, vocal attack, vocal stability and resonance, as well as the degree of deviated parameters, measured

Cranial MR findings in Wilson's disease

International Nuclear Information System (INIS)

Saatci, I.; Topcu, M.; Baltaoglu, F.F.; Koese, G.; Yalaz, K.; Renda, Y.; Besim, A.

1997-01-01

Purpose: To define various cranial MR appearances in Wilson's disease (WD). Material and Methods: MR examinations of 30 patients (9-44 years old) with WD were retrospectively reviewed. Six patients were asymptomatic siblings. Three other patients had isolated hepatic involvement, one with no symptoms. The remaining 21 patients had neurological involvement, 7 of whom had the mixed form of the disease. Nine patients had hepatic dysfunction, the 3 with isolated hepatic involvement and 6 of the 7 with the mixed form. Results: All symptomatic patients (n=23) had abnormal MR examinations. Atrophy was present in the majority of them. The most frequently involved sites were putamen (18/21) and pons (18/21) in patients with neurological abnormality. The putaminal lesions showed a consistent pattern of symmetric, bilateral, concentric-laminar T2 hyperintensity. Putaminal lesions were lacking in only 3 patients with neurological involvement, all of whom were relatively old and had had the disease for a longer duration. Most of the patients with hepatic dysfunction (8/9) had increased T1 signal intensity in the basal ganglia, particularly in the globus pallidus. Pontine involvement always included the dorsal aspect of the pons, however, in some cases the central portion of pons was also affected but ventrolateral longitudinal fibers were spared. Midbrain (16/21), thalamic (10/21) and caudate nucleus lesions (9/21) were also encountered. In a few patients cortical and subcortical white matter lesions were present with a predilection to the frontal lobe, particularly the precentral region. In one patient, a hemorrhagic focus was identified within the white matter lesion. (orig./VHE)

Neuroimaging findings in Mowat-Wilson syndrome

DEFF Research Database (Denmark)

Garavelli, Livia; Ivanovski, Ivan; Caraffi, Stefano Giuseppe

2017-01-01

PURPOSE: Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency o...

Mowat-Wilson-syndrom hos tre danske børn

DEFF Research Database (Denmark)

Nissen, Karin Bækgaard; Søndergaard, Charlotte; Thelle, Thomas

2011-01-01

Mowat-Wilson syndrome (MWS) is an autosomal dominant intellectual disability syndrome characterised by unique facial features and congenital anomalies such as Hirschsprung disease, congenital heart defects, corpus callosum agenesis and urinary tract anomalies. Some cases also present epilepsy......, growth retardation and microcephaly. The syndrome is caused by mutations or deletions of the ZEB2 gene at chromosome 2q22-q23. MWS was first described in 1998 and until now approximately 180 cases have been reported worldwide. We report the first three molecularly confirmed Danish cases with MWS....

Doença de Wilson em crianças e adolescentes: diagnóstico e tratamento Wilson's disease in children and adolescents: diagnosis and treatment

Directory of Open Access Journals (Sweden)

Stephania de Andrade Sócio

2010-06-01

Full Text Available OBJETIVO: Descrever as formas de apresentação, as alterações laboratoriais ao diagnóstico e o tratamento de crianças e adolescentes com doença de Wilson. MÉTODOS: Estudo descritivo e retrospectivo de 17 crianças e adolescentes com doença de Wilson atendidos no Ambulatório de Hepatologia Pediátrica do Hospital das Clínicas da Universidade Federal de Minas Gerais no período de 1985 a 2008. Os dados foram coletados dos prontuários e durante as consultas ambulatoriais. RESULTADOS: A idade ao diagnóstico variou de 2,8 a 15,1 anos, com média de 8,8±0,9 anos. A forma de apresentação predominante foi hepática (53%, seguida por assintomáticos provenientes de triagem familiar. O anel de Kayser-Fleischer foi encontrado em 41% dos pacientes. A ceruloplasmina encontrava-se alterada em 15/17 pacientes e o cobre urinário variou de 24 a 1000mcg/24h (mediana: 184mcg/24h. O tratamento instituído foi a D-penicilamina. Observaram-se efeitos colaterais em cinco crianças, sem necessidade de interrupção ou troca da medicação. As respostas clínica e laboratorial, com níveis normais de aminotransferases, foram evidenciadas em 14 pacientes após mediana de 10,7 meses de tratamento. Três crianças morreram (uma por hepatite fulminante e duas com complicações da insuficiência hepática grave, apesar do tratamento. CONCLUSÕES: A doença de Wilson é rara na faixa etária pediátrica. A forma de apresentação predominante é a hepática. Seu diagnóstico se baseia principalmente em dosagem de ceruloplasmina baixa, cobre livre e cobre em urina de 24 horas elevados, mas exige alto grau de suspeição. Apresenta boa resposta e tolerância ao tratamento medicamentoso.OBJECTIVE: To describe clinical symptoms, laboratory findings at diagnosis and treatment of children and adolescents with Wilson's disease. METHODS: This is a descriptive and retrospective study of a series of 17 children and adolescents with Wilson's disease, assited at the

Anesthesia in Mowat-Wilson syndrome: information on 11 Italian patients

Directory of Open Access Journals (Sweden)

Marianna Spunton

2018-03-01

Full Text Available Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and characterized by typical clinical features. The congenital malformations typical of this syndrome call for early diagnostic and surgical procedures requiring general anesthesia, but few information about the anesthesiology management of such patients is available. We enrolled 11 families of patients with Mowat-Wilson syndrome who had undergone surgical or diagnostic procedures requiring general anesthesia, and sent them a retrospective questionnaire including 16 open questions about the procedures. They were further contacted by phone for a semi-structured interview. A total of 37 procedures requiring general anesthesia was reported in 11 patients. Only two patients reported anesthesia-related complications during the procedure. No true additional anesthesia-related risk was present for the patients with MW syndrome, besides difficult intubation, weaning and lower respiratory tract infection. Perception of risk, however, is derived by non-medical observation on the part of the parents.

Wilson's disease: cranial MRI observations and clinical correlation

International Nuclear Information System (INIS)

Sinha, S.; Taly, A.B.; Prashanth, L.K.; Venugopal, K.S.; Arunodaya, G.R.; Swamy, H.S.; Ravishankar, S.; Vasudev, M.K.

2006-01-01

Study of MRI changes may be useful in diagnosis, prognosis and better understanding of the pathophysiology of Wilson's disease (WD). We aimed to describe and correlate the MRI abnormalities of the brain with clinical features in WD. MRI evaluation was carried out in 100 patients (57 males, 43 females; mean age 19.3±8.9 years) using standard protocols. All but 18 patients were on de-coppering agents. Their history, clinical manifestations and scores for severity of disease were noted. The mean duration of illness and treatment were 8.3±10.8 years and 7.5±7.1 years respectively. MRI of the brain was abnormal in all the 93 symptomatic patients. The most conspicuous observations were atrophy of the cerebrum (70%), brainstem (66%) and cerebellum (52%). Signal abnormalities were also noted: putamen (72%), caudate (61%), thalami (58%), midbrain (49%), pons (20%), cerebral white matter (25%), cortex (9%), medulla (12%) and cerebellum (10%). The characteristic T2-W globus pallidal hypointensity (34%), ''Face of giant panda'' sign (12%), T1-W striatal hyperintensity (6%), central pontine myelinosis (7%), and bright claustral sign (4%) were also detected. MRI changes correlated with disease severity scores (P<0.001) but did not correlate with the duration of illness. MRI changes were universal but diverse and involved almost all the structures of the brain in symptomatic patients. A fair correlation between MRI observations and various clinical features provides an explanation for the protean manifestations of the disease. (orig.)

The plant decapeptide OSIP108 prevents copper-induced toxicity in various models for Wilson disease

Energy Technology Data Exchange (ETDEWEB)

Spincemaille, Pieter [Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, 3001 Heverlee (Belgium); Pham, Duc-Hung [Laboratory for Molecular Biodiscovery, KU Leuven, Campus Gasthuisberg, Herestraat 49, O and N2, 3000 Leuven (Belgium); Chandhok, Gursimran [Clinic for Transplantation Medicine, Münster University Hospital, Albert-Schweitzer-Campus 1, Building A14, D-48149 Münster (Germany); Verbeek, Jef [Department of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven (Belgium); Zibert, Andree [Clinic for Transplantation Medicine, Münster University Hospital, Albert-Schweitzer-Campus 1, Building A14, D-48149 Münster (Germany); Libbrecht, Louis [Department of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven (Belgium); Department of Pathology, University Hospital Ghent, De Pintelaan 185, 9000 Ghent (Belgium); Schmidt, Hartmut [Clinic for Transplantation Medicine, Münster University Hospital, Albert-Schweitzer-Campus 1, Building A14, D-48149 Münster (Germany); Esguerra, Camila V.; Witte, Peter A.M. de [Laboratory for Molecular Biodiscovery, KU Leuven, Campus Gasthuisberg, Herestraat 49, O and N2, 3000 Leuven (Belgium); Cammue, Bruno P.A., E-mail: bruno.cammue@biw.kuleuven.be [Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, 3001 Heverlee (Belgium); Department of Plant Systems Biology, VIB, Technologiepark 927, 9052 Ghent (Belgium); Cassiman, David [Department of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven (Belgium); Thevissen, Karin [Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, 3001 Heverlee (Belgium)

2014-10-15

Background: Wilson disease (WD) is caused by accumulation of excess copper (Cu) due to a mutation in the gene encoding the liver Cu transporter ATP7B, and is characterized by acute liver failure or cirrhosis and neuronal cell death. We investigated the effect of OSIP108, a plant derived decapeptide that prevents Cu-induced apoptosis in yeast and human cells, on Cu-induced toxicity in various mammalian in vitro models relevant for WD and in a Cu-toxicity zebrafish larvae model applicable to WD. Methods: The effect of OSIP108 was evaluated on viability of various cell lines in the presence of excess Cu, on liver morphology of a Cu-treated zebrafish larvae strain that expresses a fluorescent reporter in hepatocytes, and on oxidative stress levels in wild type AB zebrafish larvae. Results: OSIP108 increased not only viability of Cu-treated CHO cells transgenically expressing ATP7B and the common WD-causing mutant ATP7B{sup H1069Q}, but also viability of Cu-treated human glioblastoma U87 cells. Aberrancies in liver morphology of Cu-treated zebrafish larvae were observed, which were further confirmed as Cu-induced hepatotoxicity by liver histology. Injections of OSIP108 into Cu-treated zebrafish larvae significantly increased the amount of larvae with normal liver morphology and decreased Cu-induced production of reactive oxygen species. Conclusions: OSIP108 prevents Cu-induced toxicity in in vitro models and in a Cu-toxicity zebrafish larvae model applicable to WD. General significance: All the above data indicate the potential of OSIP108 as a drug lead for further development as a novel WD treatment. - Highlights: • Wilson disease (WD) is characterized by accumulation of toxic copper (Cu). • OSIP108 increases viability of Cu-treated cellular models applicable to WD. • OSIP108 injections preserve liver morphology of Cu-treated zebrafish larvae. • OSIP108 injections into zebrafish larvae abrogates Cu-induced oxidative stress.

Wilson's Disease in Children : A Position Paper by the Hepatology Committee of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition

NARCIS (Netherlands)

Socha, Piotr; Janczyk, Wojciech; Dhawan, Anil; Baumann, Ulrich; D'Antiga, Lorenzo; Tanner, Stuart; Iorio, Raffaele; Vajro, Pietro; Houwen, Roderick; Fischler, Björn; Dezsofi, Antal; Hadzic, Nedim; Hierro, Loreto; Jahnel, Jörg; McLin, Valérie; Nobili, Valerio; Smets, Francoise; Verkade, Henkjan J.; Debray, Dominique

BACKGROUND: Clinical presentations of Wilson's disease (WD) in childhood ranges from asymptomatic liver disease to cirrhosis or acute liver failure, whereas neurological and psychiatric symptoms are rare. The basic diagnostic approach includes serum ceruloplasmin and 24-hour urinary copper

Wilson's Disease in Children : A Position Paper by the Hepatology Committee of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition

NARCIS (Netherlands)

Socha, Piotr; Janczyk, Wojciech; Dhawan, Anil; Baumann, Ulrich; D'Antiga, Lorenzo; Tanner, Stuart; Iorio, Raffaele; Vajro, Pietro; Houwen, Roderick; Fischler, Björn; Dezsofi, Antal; Hadzic, Nedim; Hierro, Loreto; Jahnel, Jörg; McLin, Valérie; Nobili, Valerio; Smets, Francoise; Verkade, Henkjan J; Debray, Dominique

Background:Clinical presentations of Wilson's disease (WD) in childhood ranges from asymptomatic liver disease to cirrhosis or acute liver failure, whereas neurological and psychiatric symptoms are rare. The basic diagnostic approach includes serum ceruloplasmin and 24-hour urinary copper excretion.

On multivariate Wilson bases

DEFF Research Database (Denmark)

Bownik, Marcin; Jakobsen, Mads Sielemann; Lemvig, Jakob

2017-01-01

A Wilson system is a collection of finite linear combinations of time frequency shifts of a square integrable function. In this paper we give an account of the construction of bimodular Wilson bases in higher dimensions from Gabor frames of redundancy two.......A Wilson system is a collection of finite linear combinations of time frequency shifts of a square integrable function. In this paper we give an account of the construction of bimodular Wilson bases in higher dimensions from Gabor frames of redundancy two....

Discontinuation of penicillamine in the absence of alternative orphan drugs (trientine-zinc): a case of decompensated liver cirrhosis in Wilson's disease.

Science.gov (United States)

Ping, C C; Hassan, Y; Aziz, N A; Ghazali, R; Awaisu, A

2007-02-01

To report a case of early-decompensated liver cirrhosis secondary to discontinuation of penicillamine therapy in a patient with Wilson's disease. A 33-year-old Chinese female patient was diagnosed with Wilson's disease, for which penicillamine 250 mg p.o. once daily was prescribed. However, the patient developed intolerance and penicillamine was discontinued without alternative treatment. Five months later, she developed decompensated liver cirrhosis with hepatic encephalopathy. Eventually, the patient died because of the complications of sepsis and decompensated liver failure. Chelating agent is the mainstay of treatment in Wilson's disease, which is an inherited disorder of hepatic copper metabolism. Therapy must be instituted and continued for life once diagnosis is confirmed. Interruption of therapy can be fatal or cause irreversible relapse. Penicillamine given orally is the chelating agent of first choice. However, its unfavourable side-effects profile leads to discontinuation of therapy in 20-30% of patients. In most case reports, cessation of penicillamine without replacement treatment causes rapid progression to fulminant hepatitis, which is fatal unless liver transplantation is performed. In this, we highlight a case of discontinuation of penicillamine in a patient with Wilson's disease without substitution with alternative regimen. This was caused by unavailability of the alternative agents such as trientine in our country. Consequently, the patient progressed to decompensated liver cirrhosis with encephalopathy and eventually passed-away within 5 months. One recent study supports a combination of trientine and zinc in treating patient with decompensated liver cirrhosis. This combination is capable of reversing liver failure and prevents the need of liver transplantation. Both trientine and zinc are not registered in Malaysia. Therefore, liver transplantation was probably the only treatment option for this patient. Hence, non-availability of orphan drugs

[Differential gene expression in incompatible interaction between Lilium regale Wilson and Fusarium oxysporum f. sp. lilii revealed by combined SSH and microarray analysis].

Science.gov (United States)

Rao, J; Liu, D; Zhang, N; He, H; Ge, F; Chen, C

2014-01-01

Fusarium wilt, caused by a soilborne pathogen Fusarium oxysporum f. sp. lilii, is the major disease of lily (Lilium L.). In order to isolate the genes differentially expressed in a resistant reaction to F. oxysporum in L. regale Wilson, a cDNA library was constructed with L. regale root during F. oxysporum infection using the suppression subtractive hybridization (SSH), and a total of 585 unique expressed sequence tags (ESTs) were obtained. Furthermore, the gene expression profiles in the incompatible interaction between L. regale and F. oxysporum were revealed by oligonucleotide microarray analysis of 585 unique ESTs comparison to the compatible interaction between a susceptible Lilium Oriental Hybrid 'Siberia' and F. oxysporum. The result of expression profile analysis indicated that the genes encoding pathogenesis-related proteins (PRs), antioxidative stress enzymes, secondary metabolism enzymes, transcription factors, signal transduction proteins as well as a large number of unknown genes were involved in early defense response of L. regale to F. oxysporum infection. Moreover, the following quantitative reverse transcription PCR (QRT-PCR) analysis confirmed reliability of the oligonucleotide microarray data. In the present study, isolation of differentially expressed genes in L. regale during response to F. oxysporum helped to uncover the molecular mechanism associated with the resistance of L. regale against F. oxysporum.

A John Wilson

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education. A John Wilson. Articles written in Resonance – Journal of Science Education. Volume 11 Issue 7 July 2006 pp 70-76 Classroom. Inverting Matrices Constructed from Roots of Unity · A John Wilson · More Details Fulltext PDF ...

Wilson's disease: cranial MRI observations and clinical correlation

Energy Technology Data Exchange (ETDEWEB)

Sinha, S.; Taly, A.B.; Prashanth, L.K.; Venugopal, K.S.; Arunodaya, G.R.; Swamy, H.S. [National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neurology, Bangalore (India); Ravishankar, S.; Vasudev, M.K. [National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neuroimaging and Interventional Radiology, Bangalore (India)

2006-09-15

Study of MRI changes may be useful in diagnosis, prognosis and better understanding of the pathophysiology of Wilson's disease (WD). We aimed to describe and correlate the MRI abnormalities of the brain with clinical features in WD. MRI evaluation was carried out in 100 patients (57 males, 43 females; mean age 19.3{+-}8.9 years) using standard protocols. All but 18 patients were on de-coppering agents. Their history, clinical manifestations and scores for severity of disease were noted. The mean duration of illness and treatment were 8.3{+-}10.8 years and 7.5{+-}7.1 years respectively. MRI of the brain was abnormal in all the 93 symptomatic patients. The most conspicuous observations were atrophy of the cerebrum (70%), brainstem (66%) and cerebellum (52%). Signal abnormalities were also noted: putamen (72%), caudate (61%), thalami (58%), midbrain (49%), pons (20%), cerebral white matter (25%), cortex (9%), medulla (12%) and cerebellum (10%). The characteristic T2-W globus pallidal hypointensity (34%), ''Face of giant panda'' sign (12%), T1-W striatal hyperintensity (6%), central pontine myelinosis (7%), and bright claustral sign (4%) were also detected. MRI changes correlated with disease severity scores (P<0.001) but did not correlate with the duration of illness. MRI changes were universal but diverse and involved almost all the structures of the brain in symptomatic patients. A fair correlation between MRI observations and various clinical features provides an explanation for the protean manifestations of the disease. (orig.)

Liver failure with coagulopathy, hyperammonemia and cyclic vomiting in a toddler revealed to have combined heterozygosity for genes involved with ornithine transcarbamylase deficiency and Wilson disease.

Science.gov (United States)

Mira, Valerie; Boles, Richard G

2012-01-01

A girl with a 2 month history of cyclic episodes of vomiting, diarrhea, and lethargy lasting 2-3 days each presented with acute hepatopathy (ALT 3,500 IU/L) with coagulopathy (PT 55 s) and hyperammonemia (207 μmol/L) at age 1½ years. Biochemical and molecular analyzes revealed ornithine transcarbamylase (OTC) deficiency. While laboratory signs of mild hepatocellular dysfunction are common in OTC deficiency, substantial liver failure with coagulopathy is generally not seen, although four others cases have been reported, three of which presented with cyclic vomiting. Further evaluation in our case revealed elevated urine (198.8 μg/g creatinine) and liver (103 μg/g dry weight) copper content, and a heterozygous mutation in the Wilson disease gene, ATP7B. Our patient, now aged 5 years, has remained in excellent health with normal growth and development on fasting avoidance, a modified vegan diet, and sodium phenylbutyrate.These five cases demonstrate that generalized liver dysfunction/failure is a potential serious complication of OTC deficiency, although not a common one, and suggests that an ALT and PT should be obtained in OTC patients during episodes of hyperammonemia. Cyclic vomiting is a known presentation of OTC deficiency; it is not known if comorbid liver failure predisposes toward this phenotype. We propose that the heterozygote state in ATP7B increases the liver copper content, thus predisposing our patient with OTC deficiency to develop liver failure during a hyperammonemic episode. Our present case is an example of the opportunity of molecular diagnostics to identify putative modifier genes in patients with atypical presentations of genetic disorders.

The Wilson loop and some applications

International Nuclear Information System (INIS)

Bezerra, V.B.

1983-01-01

A simple relation between the classical Wilson loop and the angular deviation in the parallel shift is found. An example of potential which given field copies and which give the same classical Wilson loop for a given trajectory is exchibited. Afterwards, the asymptotic behaviour of the Wilson loop for the BPST instanton and meron is discussed. Using the dimensional regularization technique to calculate the second order term of Quantum Wilson loop, the influence of geometrical factors for the residue in the polo due to contact points, cusp and intersections, in function of the upsilon dimension of the space-time is investigated. Finally, the charge renormalization in Quantum Electrodynamics using Quantum Wilson loop is calculated. (L.C.) [pt

The Wilson loop and some applications

International Nuclear Information System (INIS)

Bezerra, V.B.

1983-04-01

A simple relation between the classical Wilson loop and the angular deviation in the parallel displacement is found. An example of potentials which give field copies and which suplly the same classical Wilson loop for a particular trajectory is exhibited. The asymptotic behaviour of the Wilson loop for the BPST instanton and the meron, is discussed. By using the dimensional regularization technique to calculate the second order term of the quantum Wilson loop, the influence of geometrical factors for the residue in the pole due to contact points, cuspides and intersections, in function of the space-time ν, is investigated. Charge renormalization in Quantum electrodynamics is finally calculated by using the quantum Wilson loop. (L.C.) [pt

Four-year follow-up of a Wilson disease pedigree complicated with epilepsy and hypopituitarism: Case report with a literature review.

Science.gov (United States)

Zhang, Qi-Jie; Xu, Liu-Qing; Wang, Chong; Hu, Wei; Wang, Ning; Chen, Wan-Jin

2016-12-01

Wilson's disease (WD) is an autosomal recessive inherited disorder of copper metabolism with excellent prognosis if treated timely. However, WD is usually prone to neglect and misdiagnosis at an early stage. We reported a rare WD pedigree, and the clinical features, laboratory tests, and gene mutations were analyzed in detail. The patient was a 17-year-old and 136-cm-tall girl who presented with limb weakness, combined with multi-organ disorders including blind eye, epilepsy, and hypopituitarism. Clinical tests showed a low serum ceruloplasmin level, high urinary copper excretion and Kayser-Fleischer (K-F) rings. She carried a compound heterozygous mutations in ATP7B gene (c.2828G>A and c.3884C>T). Her younger brother, as an asymptomatic patient, manifested with elevation of transaminases but without neurological and hepatic symptoms. They were diagnosed as WD finally. They were treated with sodium dimercaptosulphonate, supplemented with zinc gluconate, vitamin B6, vitamin C, as well as restriction of dietary copper. The urinary copper excretion and serum transaminase level decreased gradually. The abnormal signals in brainstem and basal ganglia were also remarkably decreased after 4-year of de-copper treatment. As to the patients with complicated clinical manifestations, the extrapyramidal symptom and basal ganglia signals should be concerned. The serum ceruloplasmin detection and ATP7B gene mutation screening are necessary.

[Jacqueline Wilson. Tracy Beakeri sari] / Krista Kivisalu

Index Scriptorium Estoniae

Kivisalu, Krista, 1968-

2016-01-01

Tutvustus: Wilson, Jacqueline. Tracy Beakeri lugu. [Tallinn] : Pegasus, 2015 ; Wilson, Jacqueline. Pühadeüllatus. [Tallinn] : Pegasus, c2015 ; Wilson, Jacqueline. Julgusmäng. [Tallinn] : Pegasus, c2015

Diffusion of Wilson loops

International Nuclear Information System (INIS)

Brzoska, A.M.; Lenz, F.; Thies, M.; Negele, J.W.

2005-01-01

A phenomenological analysis of the distribution of Wilson loops in SU(2) Yang-Mills theory is presented in which Wilson loop distributions are described as the result of a diffusion process on the group manifold. It is shown that, in the absence of forces, diffusion implies Casimir scaling and, conversely, exact Casimir scaling implies free diffusion. Screening processes occur if diffusion takes place in a potential. The crucial distinction between screening of fundamental and adjoint loops is formulated as a symmetry property related to the center symmetry of the underlying gauge theory. The results are expressed in terms of an effective Wilson loop action and compared with various limits of SU(2) Yang-Mills theory

Update on the clinical management of Wilson's disease

Directory of Open Access Journals (Sweden)

Hedera P

2017-01-01

Full Text Available Peter Hedera Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA Abstract: Wilson’s disease (WD, albeit relatively rare, is an important genetic metabolic disease because of highly effective therapies that can be lifesaving. It is a great imitator and requires a high index of suspicion for correct and timely diagnosis. Neurologic, psychiatric and hepatologic problems in WD are very nonspecific, and we discuss the most common clinical phenotypes. The diagnosis remains laboratory based, and here we review the most important challenges and pitfalls in laboratory evaluation of WD, including the emerging role of genetic testing in WD diagnosis. WD is a monogenic disorder but has very high allelic heterogeneity with >500 disease-causing mutations identified, and new insights into phenotype–genotype correlations are also reviewed. The gold standard of therapy is chelation of excessive copper, but many unmet needs exist because of possible clinical deterioration in treated patients and potential adverse effects associated with currently available chelating medications. We also review the most promising novel therapeutic approaches, including chelators targeting specific cell types, cell transplantation and gene therapy. Keywords: Wilson’s disease, copper, ATP7B, chelation, gene therapy

FERMILAB: Bob Wilson 80

Energy Technology Data Exchange (ETDEWEB)

Anon.

1994-06-15

On March 4, an international symposium and tribute was held at Fermilab in honour of the Laboratory's founding director Robert Rathbun Wilson on the occasion of his 80th birthday. The symposium - 'Celebrating an Era of Courage and Creativity' - featured talks and reflections by many of Wilson's colleagues and friends including Fermilab Director John Peoples and Director Emeritus Leon Lederman.

FERMILAB: Bob Wilson 80

International Nuclear Information System (INIS)

Anon.

1994-01-01

On March 4, an international symposium and tribute was held at Fermilab in honour of the Laboratory's founding director Robert Rathbun Wilson on the occasion of his 80th birthday. The symposium - 'Celebrating an Era of Courage and Creativity' - featured talks and reflections by many of Wilson's colleagues and friends including Fermilab Director John Peoples and Director Emeritus Leon Lederman

Successful Splenectomy for Hypersplenism in Wilson's Disease: A Single Center Experience from China.

Science.gov (United States)

Li, Liang-Yong; Yang, Wen-Ming; Chen, Huai-Zhen; Wu, Yun-Hu; Fang, Xiang; Zhang, Jing; Wang, Zhen; Han, Yong-Sheng; Wang, Yu

2015-01-01

Splenomegaly and pancytopenia are common in Wilson's disease (WD) and splenectomy is one of the conventional treatments for splenomegaly and the associated pancytopenia. However, splenectomy remained controversial for hypersplenism in WD as it was reported that splenectomy leaded to serious emotional and neurological deterioration in WD patients with hypersplenism. In the current study, we present our experiences in 70 WD patients with hypersplenism who had undergone splenectomy, outlining the safety and efficacy of splenectomy in WD. The clinical database of 70 WD patients with hypersplenism who had undergone splenectomy in our hospital between 2009 and 2013 were reviewed and followed-up regularly. Before splenectomy, all the patients accepted a short period of anti-copper treatment with intravenous sodium 2, 3-dimercapto-1-propane sulfonate (DMPS). All the patients demonstrated a marked improvement in platelet and leucocyte counts after splenectomy. No severe postoperative complication was observed. In particular, none of the 37 patients with mixed neurologic and hepatic presentations experienced neurological deterioration after splenectomy, and none of the patients with only hepatic presentations newly developed neurological symptoms. During the one year follow-up period, no patient presented hepatic failure or hepatic encephalopathy, no hepatic patient newly developed neurological presentations, and only 3 patients with mixed neurologic and hepatic presentations suffered neurological deterioration and these 3 patients had poor compliance of anti-copper treatment. Quantative analysis of the neurological symptoms in the 37 patients using the Unified Wilson's Disease Rating Scale (UWDRS) showed that the neurological symptoms were not changed in a short-term of one week after splenectomy but significantly improved in a long-term of one year after splenectomy. Additionally, compared to that before splenectomy, the esophageal gastric varices in most patients

String breaking with Wilson loops?

CERN Document Server

Kratochvila, S; Kratochvila, Slavo; Forcrand, Philippe de

2003-01-01

A convincing, uncontroversial observation of string breaking, when the static potential is extracted from Wilson loops only, is still missing. This failure can be understood if the overlap of the Wilson loop with the broken string is exponentially small. In that case, the broken string ground state will only be seen if the Wilson loop is long enough. Our preliminary results show string breaking in the context of the 3d SU(2) adjoint static potential, using the L\\"uscher-Weisz exponential variance reduction approach. As a by-product, we measure the fundamental SU(2) static potential with improved accuracy and see clear deviations from Casimir scaling.

The Universal Askey-Wilson Algebra

Directory of Open Access Journals (Sweden)

Paul Terwilliger

2011-07-01

Full Text Available In 1992 A. Zhedanov introduced the Askey-Wilson algebra AW=AW(3 and used it to describe the Askey-Wilson polynomials. In this paper we introduce a central extension Δ of AW, obtained from AW by reinterpreting certain parameters as central elements in the algebra. We call Δ the universal Askey-Wilson algebra. We give a faithful action of the modular group PSL_2(Z on Δ as a group of automorphisms. We give a linear basis for Δ. We describe the center of Δ and the 2-sided ideal Δ[Δ,Δ]Δ. We discuss how Δ is related to the q-Onsager algebra.

Mowat-Wilson syndrome

Science.gov (United States)

Garavelli, Livia; Mainardi, Paola Cerruti

2007-01-01

Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype (high forehead, frontal bossing, large eyebrows, medially flaring and sparse in the middle part, hypertelorism, deep set but large eyes, large and uplifted ear lobes, with a central depression, saddle nose with prominent rounded nasal tip, prominent columella, open mouth, with M-shaped upper lip, frequent smiling, and a prominent but narrow and triangular pointed chin), moderate-to-severe intellectual deficiency, epilepsy and variable congenital malformations including Hirschsprung disease (HSCR), genitourinary anomalies (in particular hypospadias in males), congenital heart defects, agenesis of the corpus callosum and eye anomalies. The prevalence of MWS is currently unknown, but 171 patients have been reported so far. It seems probable that MWS is under-diagnosed, particularly in patients without HSCR. MWS is caused by heterozygous mutations or deletions in the Zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1). To date, over 100 deletions/mutations have been reported in patients with a typical phenotype; they are frequently whole gene deletions or truncating mutations, suggesting that haploinsufficiency is the main pathological mechanism. Studies of genotype-phenotype analysis show that facial gestalt and delayed psychomotor development are constant clinical features, while the frequent and severe congenital malformations are variable. In a small number of patients, unusual mutations can lead to an atypical phenotype. The facial phenotype is particularly important for the initial clinical diagnosis and provides the hallmark warranting ZEB2 mutational analysis, even in the absence of HSCR. The majority of MWS cases reported so far were sporadic, therefore the recurrence risk is low. Nevertheless, rare cases of sibling recurrence have been observed. Congenital malformations and seizures require precocious clinical

Mowat-Wilson syndrome

Directory of Open Access Journals (Sweden)

Mainardi Paola

2007-10-01

Full Text Available Abstract Mowat-Wilson syndrome (MWS is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype (high forehead, frontal bossing, large eyebrows, medially flaring and sparse in the middle part, hypertelorism, deep set but large eyes, large and uplifted ear lobes, with a central depression, saddle nose with prominent rounded nasal tip, prominent columella, open mouth, with M-shaped upper lip, frequent smiling, and a prominent but narrow and triangular pointed chin, moderate-to-severe intellectual deficiency, epilepsy and variable congenital malformations including Hirschsprung disease (HSCR, genitourinary anomalies (in particular hypospadias in males, congenital heart defects, agenesis of the corpus callosum and eye anomalies. The prevalence of MWS is currently unknown, but 171 patients have been reported so far. It seems probable that MWS is under-diagnosed, particularly in patients without HSCR. MWS is caused by heterozygous mutations or deletions in the Zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1. To date, over 100 deletions/mutations have been reported in patients with a typical phenotype; they are frequently whole gene deletions or truncating mutations, suggesting that haploinsufficiency is the main pathological mechanism. Studies of genotype-phenotype analysis show that facial gestalt and delayed psychomotor development are constant clinical features, while the frequent and severe congenital malformations are variable. In a small number of patients, unusual mutations can lead to an atypical phenotype. The facial phenotype is particularly important for the initial clinical diagnosis and provides the hallmark warranting ZEB2 mutational analysis, even in the absence of HSCR. The majority of MWS cases reported so far were sporadic, therefore the recurrence risk is low. Nevertheless, rare cases of sibling recurrence have been observed. Congenital malformations and seizures require

Influence of IL-1RN intron 2 variable number of tandem repeats (VNTR) polymorphism on the age at onset of neuropsychiatric symptoms in Wilson's disease.

Science.gov (United States)

Gromadzka, Grazyna; Członkowska, Anna

2011-01-01

ABSTRACT Wilson's disease (WND) is an autosomal recessive copper storage disease characterized with diverse clinical pictures with the hepatic and/or neuropsychiatric symptoms manifesting at variable age. On the basis of the existing knowledge on possible copper-proinflammatory cytokines interactions, we hypothesized that in WND hereditary, over-/underexpression of PC or anti-inflammatory cytokines may have an impact on the course of the disease. We analyzed the clinical manifestations of WND in relationship to polymorphisms within genes for interleukin-1 receptor antagonist (IL1RN intron 2 VNTR polymorphism), interleukin-1α (IL1A G4845T), IL-1β (IL1B C-511T), IL-6 (IL6 G-174C), and tumor necrosis factor (TNF G-308A) in a total sample of 332 patients. The IL1B C-511T and IL1RN VNTR polymorphisms had an impact on copper metabolism parameters. None of the studied gene polymorphisms had effect on the mode of WND manifestation (neuropsychiatric vs. hepatic). Carriership of the IL1RN *2 allele was related to earlier WND onset, especially among patients with neuropsychiatric form of the disease (median 27.5 vs. 32.0 years, p = .003). Because of the crucial modulatory role of IL1ra on IL-1α and IL-1β proinflammatory functions, IL1ra and its interactions may play a role in the pathogenesis of the neurodegenerative process in WND; our results need to be replicated, possibly in different ethnic groups.

Spectrum of the Wilson Dirac operator at finite lattice spacings

DEFF Research Database (Denmark)

Akemann, G.; Damgaard, Poul Henrik; Splittorff, Kim

2011-01-01

We consider the effect of discretization errors on the microscopic spectrum of the Wilson Dirac operator using both chiral Perturbation Theory and chiral Random Matrix Theory. A graded chiral Lagrangian is used to evaluate the microscopic spectral density of the Hermitian Wilson Dirac operator...... as well as the distribution of the chirality over the real eigenvalues of the Wilson Dirac operator. It is shown that a chiral Random Matrix Theory for the Wilson Dirac operator reproduces the leading zero-momentum terms of Wilson chiral Perturbation Theory. All results are obtained for fixed index...... of the Wilson Dirac operator. The low-energy constants of Wilson chiral Perturbation theory are shown to be constrained by the Hermiticity properties of the Wilson Dirac operator....

Near BPS Wilson loop in β-deformed theories

International Nuclear Information System (INIS)

Chu, C-S; Giataganas, Dimitrios

2007-01-01

We propose a definition of the Wilson loop operator in the N = 1 β-deformed supersymmetric Yang-Mills theory. Although the operator is not BPS, it has a finite expectation value at least up to order (g 2 N) 2 . This does not happen generally for a generic non-BPS Wilson loop whose expectation value is UV divergent. For this reason we call this a near-BPS Wilson loop. We derive the general form of the boundary condition satisfied by the dual string worldsheet and find that it is deformed. Finiteness of the expectation value of the Wilson loop fixes the boundary condition to be one which is characterized by the vielbein of the deformed supergravity metric. The Wilson loop operators provide natural candidates as dual descriptions to some of the existing D-brane configurations in the Lunin-Maldacena background. We also construct the string dual configuration for a near-1/4 BPS circular Wilson loop operator. The string lies on a deformed three-sphere instead of a two-sphere as in the undeformed case. The expectation value of the Wilson loop operator is computed using the AdS/CFT correspondence and is found to be independent of the deformation. We conjecture that the exact expectation value of the Wilson loop is given by the same matrix model as in the undeformed case

Regional cerebral glucose consumption measured by positron emission tomography in patients with Wilson's disease

International Nuclear Information System (INIS)

Kuwert, T.; Scholz, D.; Milz, M.; Herzog, H.; Feinendegen, L.E.; Hefter, H.; Weiss, P.; Arendt, G.; Loken, M.; Minnesota Univ., Minneapolis, MN; Hennerici, M.

1992-01-01

Using positron emission tomography (PET), the regional cerebral metabolic rate of glucose consumption (rCMRGlc) was measured in 14 patients with Wilson's disease (WD) and 23 normal subjects. In WD patients, cerebellar, striatal and - to a lesser extent - cortical and thalamic rCMRGlc were significantly decreased compared with controls. Striatal rCMRGlc was significantly reduced in those 4 patients who had recently started decoppering therapy as compared with striatal rCMRGlc measured in those 10 patients with longer duration of medication. Caudate rCMRGlc correlated significantly with various signs of extrapyramidal dysfunction. Cerebellar, thalamic and cortical rCMRGlc correlated significantly with the severity of pyramidal signs. These data indicate that the PET measurement of rCMRGlc may be a useful tool to evaluate cerebral involvement in WD and to monitor the response to treatment. (orig.)

In Vivo Modeling of the Pathogenic Effect of Copper Transporter Mutations That Cause Menkes and Wilson Diseases, Motor Neuropathy, and Susceptibility to Alzheimer's Disease.

Science.gov (United States)

Mercer, Stephen W; Wang, Jianbin; Burke, Richard

2017-03-10

Copper is an essential biometal, and several inherited diseases are directly associated with a disruption to normal copper homeostasis. The best characterized are the copper deficiency and toxicity disorders Menkes and Wilson diseases caused by mutations in the p-type Cu-ATPase genes ATP7A and ATP7B , respectively. Missense mutations in the C-terminal portion of ATP7A have also been shown to cause distal motor neuropathy, whereas polymorphisms in ATP7B are associated with increased risk of Alzheimer's disease. We have generated a single, in vivo model for studying multiple pathogenic mutations in ATP7 proteins using Drosophila melanogaster , which has a single orthologue of ATP7A and ATP7B. Four pathogenic ATP7A mutations and two ATP7B mutations were introduced into a genomic ATP7 rescue construct containing an in-frame C-terminal GFP tag. Analysis of the wild type ATP7-GFP transgene confirmed that ATP7 is expressed at the basolateral membrane of larval midgut copper cells and that the transgene can rescue a normally early lethal ATP7 deletion allele to adulthood. Analysis of the gATP7-GFP transgenes containing pathogenic mutations showed that the function of ATP7 was affected, to varying degrees, by all six of the mutations investigated in this study. Of particular interest, the ATP7B K832R Alzheimer's disease susceptibility allele was found, for the first time, to be a loss of function allele. This in vivo system allows us to assess the severity of individual ATP7A / B mutations in an invariant genetic background and has the potential to be used to screen for therapeutic compounds able to restore function to faulty copper transport proteins. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Wilson's Disease

Science.gov (United States)

... yellowing of the skin and the whites of the eye (jaundice) Golden-brown eye discoloration (Kayser-Fleischer rings) Fluid buildup ... is inherited as an autosomal recessive trait, which means that to develop the disease you must inherit one copy of the ...

Compact lattice QED with Wilson fermions

International Nuclear Information System (INIS)

Hoferichter, A.

1994-08-01

We study the phase structure and the chiral limit of 4d compact lattice QED with Wilson fermions (both dynamical and quenched). We use the standard Wilson gauge action and also a modified one suppressing lattice artifacts. Different techniques and observables to locate the chiral limit are discussed. (orig.)

Chirally improving Wilson fermions I. O(a) improvement

International Nuclear Information System (INIS)

Frezzotti, R.; Rossi, G.C.

2004-01-01

We show that it is possible to improve the chiral behaviour and the approach to the continuum limit of correlation functions in lattice QCD with Wilson fermions by taking arithmetic averages of correlators computed in theories regularized with Wilson terms of opposite sign. Improved hadronic masses and matrix elements can be obtained by similarly averaging the corresponding physical quantities separately computed within the two regularizations. To deal with the problems related to the spectrum of the Wilson-Dirac operator, which are particularly worrisome when Wilson and mass terms are such as to give contributions of opposite sign to the real part of the eigenvalues, we propose to use twisted-mass lattice QCD for the actual computation of the quantities taking part to the averages. The choice ±π/2 for the twisting angle is particularly interesting, as O(a) improved estimates of physical quantities can be obtained even without averaging data from lattice formulations with opposite Wilson terms. In all cases little or no extra computing power is necessary, compared to simulations with standard Wilson fermions or twisted-mass lattice QCD. (author)

Wilson's Disease: a challenge of diagnosis. The 5-year experience of a tertiary centre.

Science.gov (United States)

Gheorghe, Liana; Popescu, Irinel; Iacob, Speranta; Gheorghe, Cristian; Vaidan, Roxana; Constantinescu, Alexandra; Iacob, Razvan; Becheanu, Gabriel; Angelescu, Corina; Diculescu, Mircea

2004-09-01

Because molecular diagnosis is considered impractical and no patognomonic features have been described, diagnosis of Wilson's disease (WD) using clinical and biochemical findings is still challenging. We analysed predictive factors for the diagnosis in 55 patients with WD diagnosed in our centre between 1st January 1999 and 1st April 2004. All patients presented predominant liver disease classified as: 1) asymptomatic, found incidentally, 2) chronic hepatitis or cirrhosis, or 3) fulminant hepatic failure. Diagnosis was considered as classic (two out of the three following criteria: 1) serum ceruloplasmin 250 mg/g dry weight liver tissue), and non-classic (clinical manifestations plus laboratory parameters suggesting impaired copper metabolism). The association between the predictive factors and non-classic diagnosis was assessed based on the level of statistical significance (p value18 years (p=0.03), increased copper excretion (p<0.0001), Coombs-negative hemolysis (p=0.03), absence of neurological manifestations (p<0.0001). Multivariate analysis identified age over 18 years, increased urinary copper, and isolated hepatic involvement as independent predictors. In clinical practice, WD should be considered also in patients who do not fulfil classic criteria. Independent factors associated with non-classic diagnosis were age over 18 years, increased cupruresis and isolated liver disease.

Magnetic resonance tomography and computed tomography of the brain for diagnosing Wilson's disease

International Nuclear Information System (INIS)

Uhlenbrock, D.; Straube, A.; Beyer, H.K.; Leopold, H.C.

1985-01-01

The authors report on two woman patients with confirmed Wilson's desease (hepatolenticular degeneration) who had neurological deficits and showed typical changes evident from laboratory data. Both computed tomography and magnetic resonance tomography revealed degenerative changes in the basal ganglia, especially of the lenticular nucleus, MR showing these defects more clearly than CT. There was a noticeable symmetrical enhancement of signals in the lenticular nucleus which was particularly evident on the image basing on the T 2 (spin-spin relaxation time constant) values. MR could be superior to CT with regard to showing up pathological changes in the basal ganglia. The future indication of MR could be the establishment of an exact correlation between clinical signs and symptoms on the one hand, and morphological findings on the other. Over and above this, it should be explored to what extent MR can already detect degenerative changes in the brain in primarily hepatic types of the disease even without prior neurological examination. (orig.) [de

Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care

DEFF Research Database (Denmark)

Ivanovski, Ivan; Djuric, Olivera; Caraffi, Stefano Giuseppe

2018-01-01

PurposeMowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to be...

Wilson lines in quantum field theory

Energy Technology Data Exchange (ETDEWEB)

Cherednikov, Igor Olegovich [Antwerpen Univ., Antwerp (Belgium). Fysica Dept.; Joint Institute of Nuclear Research, Moscow (Russian Federation). Bogoliubov Lab. of Theoretical Physics; Mertens, Tom; Veken, Frederik F. van der [Antwerpen Univ., Antwerp (Belgium). Fysica Dept.

2014-07-01

Wilson lines (also known as gauge links or eikonal lines) can be introduced in any gauge field theory. Although the concept of the Wilson exponentials finds an enormously wide range of applications in a variety of branches of modern quantum field theory, from condensed matter and lattice simulations to quantum chromodynamics, high-energy effective theories and gravity, there are surprisingly few books or textbooks on the market which contain comprehensive pedagogical introduction and consecutive exposition of the subject. The objective of this book is to get the potential reader acquainted with theoretical and mathematical foundations of the concept of the Wilson loops in the context of modern quantum field theory, to teach him/her to perform independently some elementary calculations with Wilson lines, and to familiarize him/her with the recent development of the subject in different important areas of research. The target audience of the book consists of graduate and postgraduate students working in various areas of quantum field theory, as well as researchers from other fields.

Wilson lines in quantum field theory

International Nuclear Information System (INIS)

Cherednikov, Igor Olegovich; Joint Institute of Nuclear Research, Moscow; Mertens, Tom; Veken, Frederik F. van der

2014-01-01

Wilson lines (also known as gauge links or eikonal lines) can be introduced in any gauge field theory. Although the concept of the Wilson exponentials finds an enormously wide range of applications in a variety of branches of modern quantum field theory, from condensed matter and lattice simulations to quantum chromodynamics, high-energy effective theories and gravity, there are surprisingly few books or textbooks on the market which contain comprehensive pedagogical introduction and consecutive exposition of the subject. The objective of this book is to get the potential reader acquainted with theoretical and mathematical foundations of the concept of the Wilson loops in the context of modern quantum field theory, to teach him/her to perform independently some elementary calculations with Wilson lines, and to familiarize him/her with the recent development of the subject in different important areas of research. The target audience of the book consists of graduate and postgraduate students working in various areas of quantum field theory, as well as researchers from other fields.

The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers : a new canine model for copper-metabolism disorders

NARCIS (Netherlands)

Fieten, Hille; Gill, Yadvinder; Martin, Alan J.; Concilli, Mafalda; Dirksen, Karen; van Steenbeek, Frank G.; Spee, Bart; van den Ingh, Ted S. G. A. M.; Martens, Ellen C. C. P.; Festa, Paola; Chesi, Giancarlo; Sluis, van de Bart; Houwen, Roderick H. J. H.; Watson, Adrian L.; Aulchenko, Yurii S.; Hodgkinson, Victoria L.; Zhu, Sha; Petris, Michael J.; Polishchuk, Roman S.; Leegwater, Peter A. J.; Rothuizen, Jan

2016-01-01

The deleterious effects of a disrupted copper metabolism are illustrated by hereditary diseases caused by mutations in the genes coding for the copper transporters ATP7A and ATP7B. Menkes disease, involving ATP7A, is a fatal neurodegenerative disorder of copper deficiency. Mutations in ATP7B lead to

The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders

NARCIS (Netherlands)

Fieten, Hille; Gill, Yadvinder; Martin, Alan J.; Concilli, Mafalda; Dirksen, Karen; van Steenbeek, Frank G.; Spee, Bart; van den Ingh, Ted S. G. A. M.; Martens, Ellen C. C. P.; Festa, Paola; Chesi, Giancarlo; van de Sluis, Bart; Houwen, Roderick H. J. H.; Watson, Adrian L.; Aulchenko, Yurii S.; Hodgkinson, Victoria L.; Zhu, Sha; Petris, Michael J.; Polishchuk, Roman S.; Leegwater, Peter A. J.; Rothuizen, Jan

2016-01-01

The deleterious effects of a disrupted copper metabolism are illustrated by hereditary diseases caused by mutations in the genes coding for the copper transporters ATP7A and ATP7B. Menkes disease, involving ATP7A, is a fatal neurodegenerative disorder of copper deficiency. Mutations in ATP7B lead to

Dystonic Dysarthria in Wilson Disease: Efficacy of Zolpidem

Directory of Open Access Journals (Sweden)

Aurélia Poujois

2017-10-01

Full Text Available Wilson disease (WD is a rare genetic disorder characterized by copper overload in the liver and the brain. Neurological presentations are mainly related to the accumulation of copper in the basal ganglia, the brainstem, and the cerebellum. Dysarthria is a frequent symptom, with dystonic, spastic, or parkinsonian components and is usually resistant to medical or voice rehabilitation therapies. Here, we report the case of a patient with WD diagnosed at the age of 12, who presented a severe and constant dysarthria from dystonic origin which was unresponsive to benzodiazepines and anticholinergic drugs. When she was 25-year-old, she tried zolpidem at bedtime for sleeping difficulties and reported a paradoxical effect of this drug on her voice. To confirm the effect of zolpidem on her dystonic dysarthria, we realized a full evaluation of her dysarthria at baseline without zolpidem and after 4 days of treatment by 10 mg twice a day. Lexical access was evaluated by the semantic fluency; dysarthria by the Intelligibility Score, the spontaneous speech and reading rates, the maximum phonation time on the sustained vowel [a] and by a perceptive evaluation. Two hours after the intake of zolpidem, improvement of all the parameters tested, with the exception of the maximum phonation time, was observed. Semantic fluency increased by 59%, the spontaneous speech rate by 88% and the reading rate by 76%. General dystonia remained unchanged and the tolerance of zolpidem was satisfactory. Since then, the patient takes zolpidem 5 mg five times a day, and 4 years later shows persistent improvement in oral communication and a good drug tolerance. In this single-case study, we showed that regular daytime intake of zolpidem could have a persisting effect on a complex dystonic dysarthria that was resistant to usual medical treatments.

Wilson lines in quantum field theory

CERN Document Server

Cherednikov, Igor O; Veken, Frederik F van der

2014-01-01

The objective of this book is to get the reader acquainted with theoretical and mathematical foundations of the concept of Wilson loops in the context of modern quantum field theory. It teaches how to perform independently with some elementary calculations on Wilson lines, and shows the recent development of the subject in different important areas of research.

Interacting open Wilson lines from noncommutative field theories

International Nuclear Information System (INIS)

Kiem, Youngjai; Lee, Sangmin; Rey, Soo-Jong; Sato, Haru-Tada

2002-01-01

In noncommutative field theories, it is known that the one-loop effective action describes the propagation of noninteracting open Wilson lines, obeying the flying dipole's relation. We show that the two-loop effective action describes the cubic interaction among 'closed string' states created by open Wilson line operators. Taking d-dimensional λ[Φ 3 ] * theory as the simplest setup, we compute the nonplanar contribution at a low-energy and large noncommutativity limit. We find that the contribution is expressible in a remarkably simple cubic interaction involving scalar open Wilson lines only and nothing else. We show that the interaction is purely geometrical and noncommutative in nature, depending only on the size of each open Wilson line

Conformal anomaly of super Wilson loop

Energy Technology Data Exchange (ETDEWEB)

Belitsky, A.V., E-mail: andrei.belitsky@asu.edu [Department of Physics, Arizona State University, Tempe, AZ 85287-1504 (United States)

2012-09-11

Classically supersymmetric Wilson loop on a null polygonal contour possesses all symmetries required to match it onto non-MHV amplitudes in maximally supersymmetric Yang-Mills theory. However, to define it quantum mechanically, one is forced to regularize it since perturbative loop diagrams are not well defined due to presence of ultraviolet divergences stemming from integration in the vicinity of the cusps. A regularization that is adopted by practitioners by allowing one to use spinor helicity formalism, on the one hand, and systematically go to higher orders of perturbation theory is based on a version of dimensional regularization, known as Four-Dimensional Helicity scheme. Recently it was demonstrated that its use for the super Wilson loop at one loop breaks both conformal symmetry and Poincare supersymmetry. Presently, we exhibit the origin for these effects and demonstrate how one can undo this breaking. The phenomenon is alike the one emerging in renormalization group mixing of conformal operators in conformal theories when one uses dimensional regularization. The rotation matrix to the diagonal basis is found by means of computing the anomaly in the Ward identity for the conformal boost. Presently, we apply this ideology to the super Wilson loop. We compute the one-loop conformal anomaly for the super Wilson loop and find that the anomaly depends on its Grassmann coordinates. By subtracting this anomalous contribution from the super Wilson loop we restore its interpretation as a dual description for reduced non-MHV amplitudes which are expressed in terms of superconformal invariants.

[A young boy with elevated aminotransferases in physical examination--Two novel missense mutations associated with Wilson's disease were found].

Science.gov (United States)

Zhu, Yu; Deng, Si-Yan; Wan, Chao-Min

2015-07-01

A 3-year-old boy had abnormal liver function, which was found in physical examination, for 5 months before admission. He had no symptoms such as anorexia, poor appetite, and jaundice, had normal growth and development, and showed no hepatosplenomegaly. Laboratory examination revealed significantly reduced ceruloplasmin (35 mg/L), as well as negative hepatotropic virus, cytomegalovirus, and Epstein-Barr virus. There were normal muscle enzymes, blood glucose, and blood ammonia and negative liver-specific autoantibodies. The boy had negative K-F ring and normal 24-hour urine copper (0.56 μmol/L). The ATP7B gene testing for the boy, his sister, and their parents detected two novel missense mutations in the boy and his sister, i.e., compound heterozygous mutations in exon 7 (c.2075T>C, p.L692P) and exon 13 (c.3044T>C, p.L1015P), which were inherited from their father and mother, respectively. Wilson's disease was confirmed by genetic diagnosis in the boy and his sister. The boy and his sister were given a low-copper diet. The boy was administered with penicillamine for decoppering and zinc supplement against copper uptake. His sister received zinc supplement alone because no clinical symptoms were observed. The boy showed normal liver function in the reexamination after 3 months of treatment.

Observing string breaking with Wilson loops

CERN Document Server

Kratochvila, S; Kratochvila, Slavo; Forcrand, Philippe de

2003-01-01

An uncontroversial observation of adjoint string breaking is proposed, while measuring the static potential from Wilson loops only. The overlap of the Wilson loop with the broken-string state is small, but non-vanishing, so that the broken-string groundstate can be seen if the Wilson loop is long enough. We demonstrate this in the context of the (2+1)d SU(2) adjoint static potential, using an improved version of the Luscher-Weisz exponential variance reduction. To complete the picture we perform the more usual multichannel analysis with two basis states, the unbroken-string state and the broken-string state (two so-called gluelumps). As by-products, we obtain the temperature-dependent static potential measured from Polyakov loop correlations, and the fundamental SU(2) static potential with improved accuracy. Comparing the latter with the adjoint potential, we see clear deviations from Casimir scaling.

Wilson's disease: 31P and 1H MR spectroscopy and clinical correlation

International Nuclear Information System (INIS)

Sinha, Sanjib; Taly, A.B.; Prashanth, L.K.; Ravishankar, S.; Vasudev, M.K.

2010-01-01

Proton ( 1 H) magnetic resonance spectroscopy (MRS) changes are noted in Wilson's disease (WD). However, there are no studies regarding membrane phospholipid abnormality using 31 P MRS in these patients. We aimed to analyze the striatal spectroscopic abnormalities using 31 P and 1 H MRS in WD. Forty patients of WD (treated, 29; untreated,11) and 30 controls underwent routine MR image sequences and in vivo 2-D 31 P and 1 H MRS of basal ganglia using an image-selected technique on a 1.5-T MRI scanner. Statistical analysis was done using Student's t test. The mean durations of illness and treatment were 6.2 ± 7.4 and 4.8 ± 5.9 years, respectively. MRI images were abnormal in all the patients. 1 H MRS revealed statistically significant reduction of N-acetyl aspartate (NAA)/choline (Cho) and NAA/creatine ratios in striatum ( 1 H MRS) of treated patients compared to controls. The mean values of phosphomonoesters (PME) (p 31 P MRS study. The duration of illness correlated well with increased PME/PDE [p < 0.001], PME/TPh [p < 0.05], and PDE/TPh [p < 0.05] and decreased NAA/Cho [p < 0.05] ratios. There was correlation of MRI score and reduced NAA/Cho ratio with disease severity. The PME/PDE ratio (right) was elevated in the treated group [p < 0.001] compared to untreated group. There is reduced breakdown and/or increased synthesis of membrane phospholipids and increased neuronal damage in basal ganglia in patients with WD. (orig.)

Monte Carlo calculation with unquenched Wilson-Fermions

International Nuclear Information System (INIS)

Montvay, I.

1984-01-01

A Monte Carlo updating procedure taking into account the virtual quark loops is described. It is based on high order hopping parameter expansion of the quark determinant for Wilson-fermions. In a first test run Wilson-loop expectation values are measured on 6 4 lattice at β=5.70 using 16sup(th) order hopping parameter expansion for the quark determinant. (orig.)

On Wilson bases in $L^2(\\mathbb{R}^d)$

DEFF Research Database (Denmark)

Bownik, Marcin; Sielemann Jakobsen, Mads; Lemvig, Jakob

2017-01-01

A Wilson system is a collection of finite linear combinations of time frequency shifts of a square integrable function. It is well known that, starting from a tight Gabor frame for $L^{2}(\\mathbb{R})$ with redundancy 2, one can construct an orthonormal Wilson basis for $L^2(\\mathbb{R})$ whose...... of redundancy $2^k$, where $k=1, 2, \\hdots, d$. These results generalize most of the known results about the existence of orthonormal Wilson bases....

Wilson's disease: Rapid diagnosis and differentiation of heterozygous and homozygous carriers with 64CuCl2

International Nuclear Information System (INIS)

Wesch, H.; Przuntek, H.; Feist, D.; Wuerzburg Univ.; Heidelberg Univ.

1980-01-01

In the modified radiocopper test, a constant amount of copper and not of radioactivity is injected, a difference being made between males and females. The rate of incorporation of 64 Cu into caeruloplasmin and urinary excretion of nuclides is measured. It is a method with low radiation exposure, providing a definite diagnosis after 30 hours. This was demonstrated in 27 homozygous patients, 30 parents and 33 siblings, and 25 controls: a clear-cut diagnosis was made in all untreated homozygous patients. In five of eight patients treated with D-penicillamine for several years, the values were in the range of heterozygotes, so that the test makes treatment control possible. The recognition of heterozygous carriers is interfered with by contraceptives and infections. The results in control subjects were all widely outside the range for patients with Wilson's disease. (orig.) [de

Taking Charge: Walter Sydney Adams and the Mount Wilson Observatory

Science.gov (United States)

Brashear, R.

2004-12-01

The growing preeminence of American observational astronomy in the first half of the 20th century is a well-known story and much credit is given to George Ellery Hale and his skill as an observatory-building entrepreneur. But a key figure who has yet to be discussed in great detail is Walter Sydney Adams (1876-1956), Hale's Assistant Director at Mount Wilson Observatory. Due to Hale's illnesses, Adams was Acting Director for much of Hale's tenure, and he became the second Director of Mount Wilson from 1923 to 1946. Behind his New England reserve Adams was instrumental in the growth of Mount Wilson and thus American astronomy in general. Adams was hand-picked by Hale to take charge of stellar spectroscopy work at Yerkes and Mount Wilson and the younger astronomer showed tremendous loyalty to Hale and Hale's vision throughout his career. As Adams assumed the leadership role at Mount Wilson he concentrated on making the observatory a place where researchers worked with great freedom but maintain a high level of cooperation. This paper will concentrate on Adams's early years and look at his growing relationship with Hale and how he came to be the central figure in the early history of Mount Wilson as both a solar and stellar observatory. His education, his years at Dartmouth and Yerkes (including his unfortunate encounter with epsilon Leonis), and his formative years on Mount Wilson are all important in learning how he shaped the direction of Mount Wilson and the development of American astronomy in the first half of the 20th century. This latter history cannot be complete until we bring Adams into better focus.

Is blinking of the eyes affected in extrapyramidal disorders? An interesting observation in a patient with Wilson disease.

Science.gov (United States)

Verma, Rajesh; Lalla, Rakesh; Patil, Tushar B

2012-11-27

Blinking of eye is a routine human activity which seldom attracts any attention of clinicians in health and disease. There is experimental evidence that blink rate is affected in extrapyramidal disorders affecting the balance of these neurotransmitters. However, no observations regarding blink rate in Wilson disease (WD) have been reported previously. We report a patient of WD with an increased spontaneous blink rate. A 24-year-old lady presented complaining of tremulousness of both upper limbs and head for 2 years, dysphagia and difficulty in speaking for 1.5 years and abnormal behaviour for last 1 year. We observed that her blink rate at rest was 32/min. Serum ceruloplasmin level was low (0.08 g/l). The patient was started on therapy with D-penicillamine, zinc sulphate, levodopa-carbidopa and trihexiphenidyl. At 1-month follow-up, patient's tremors were markedly decreased and blink rate at rest was decreased to 12/min.

Ebot, Wilson Atem

African Journals Online (AJOL)

Ebot, Wilson Atem. Vol 8-9, No 1 (1995) - Articles Language and socio-cultural change in Ejagham Abstract PDF. ISSN: 1016-0728. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use · Contact AJOL ...

Chromosome preference of disease genes and vectorization for the prediction of non-coding disease genes.

Science.gov (United States)

Peng, Hui; Lan, Chaowang; Liu, Yuansheng; Liu, Tao; Blumenstein, Michael; Li, Jinyan

2017-10-03

Disease-related protein-coding genes have been widely studied, but disease-related non-coding genes remain largely unknown. This work introduces a new vector to represent diseases, and applies the newly vectorized data for a positive-unlabeled learning algorithm to predict and rank disease-related long non-coding RNA (lncRNA) genes. This novel vector representation for diseases consists of two sub-vectors, one is composed of 45 elements, characterizing the information entropies of the disease genes distribution over 45 chromosome substructures. This idea is supported by our observation that some substructures (e.g., the chromosome 6 p-arm) are highly preferred by disease-related protein coding genes, while some (e.g., the 21 p-arm) are not favored at all. The second sub-vector is 30-dimensional, characterizing the distribution of disease gene enriched KEGG pathways in comparison with our manually created pathway groups. The second sub-vector complements with the first one to differentiate between various diseases. Our prediction method outperforms the state-of-the-art methods on benchmark datasets for prioritizing disease related lncRNA genes. The method also works well when only the sequence information of an lncRNA gene is known, or even when a given disease has no currently recognized long non-coding genes.

Acute putaminal necrosis and white matter demyelination in a child with subnormal copper metabolism in Wilson disease: MR imaging and spectroscopic findings

International Nuclear Information System (INIS)

Juan, Chun-Jung; Chung, Hsiao-Wen; Chen, Cheng-Yu.; Chin, Shy-Chy; Hsueh, Chun-Jen; Liu, Yi-Jui; Chu, Hsin; Zimmerman, Robert A.

2005-01-01

Wilson disease (WD) that manifests solely with acute and severe neurological damage in the absence of hepatic disease and Kayser-Fleischer ring of the cornea is rare and difficult to diagnose at the acute setting. This report describes unusual diffusion and proton spectroscopic magnetic resonance (MR) imaging findings in a 12-year-old boy with WD who presented with hemichorea and subnormal copper metabolism. The MR imaging findings of lactate accumulation, decrease of N-acerylaspartate/creatinine (NAA/Cr) ratio and markedly increased apparent diffusion coefficient (ADC) value of the asymmetrical edematous putaminal lesions in the early stage were suggestive of acute necrosis with anaerobic metabolism of glucose leading to poor clinical outcome at follow-up. (orig.)

Acute putaminal necrosis and white matter demyelination in a child with subnormal copper metabolism in Wilson disease: MR imaging and spectroscopic findings

Energy Technology Data Exchange (ETDEWEB)

Juan, Chun-Jung; Chung, Hsiao-Wen [National Taiwan University, Department of Electrical Engineering, Taipei (Taiwan); Tri-Service General Hospital, Department of Radiology, Taipei (Taiwan); Chen, Cheng-Yu.; Chin, Shy-Chy; Hsueh, Chun-Jen [Tri-Service General Hospital, Department of Radiology, Taipei (Taiwan); Liu, Yi-Jui [Feng Chia University, Department of Automatic Control Engineering, Taichung (Taiwan); Chu, Hsin [National Defense Medical Center, Department of Neurology, Taipei (Taiwan); Zimmerman, Robert A. [Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, Pennsylvania (United States)

2005-06-01

Wilson disease (WD) that manifests solely with acute and severe neurological damage in the absence of hepatic disease and Kayser-Fleischer ring of the cornea is rare and difficult to diagnose at the acute setting. This report describes unusual diffusion and proton spectroscopic magnetic resonance (MR) imaging findings in a 12-year-old boy with WD who presented with hemichorea and subnormal copper metabolism. The MR imaging findings of lactate accumulation, decrease of N-acerylaspartate/creatinine (NAA/Cr) ratio and markedly increased apparent diffusion coefficient (ADC) value of the asymmetrical edematous putaminal lesions in the early stage were suggestive of acute necrosis with anaerobic metabolism of glucose leading to poor clinical outcome at follow-up. (orig.)

Two-loop polygon Wilson loops in N = 4 SYM

International Nuclear Information System (INIS)

Anastasiou, C.; Brandhuber, A.; Heslop, P.; Spence, B.; Travaglini, G.; Khoze, V.V.

2009-01-01

We compute for the first time the two-loop corrections to arbitrary n-gon lightlike Wilson loops in N = 4 supersymmetric Yang-Mills theory, using efficient numerical methods. The calculation is motivated by the remarkable agreement between the finite part of planar six-point MHV amplitudes and hexagon Wilson loops which has been observed at two loops. At n = 6 we confirm that the ABDK/BDS ansatz must be corrected by adding a remainder function, which depends only on conformally invariant ratios of kinematic variables. We numerically compute remainder functions for n = 7,8 and verify dual conformal invariance. Furthermore, we study simple and multiple collinear limits of the Wilson loop remainder functions and demonstrate that they have precisely the form required by the collinear factorisation of the corresponding two-loop n-point amplitudes. The number of distinct diagram topologies contributing to the n-gon Wilson loops does not increase with n, and there is a fixed number of 'master integrals', which we have computed. Thus we have essentially computed general polygon Wilson loops, and if the correspondence with amplitudes continues to hold, all planar n-point two-loop MHV amplitudes in the N = 4 theory.

Wilson loops to 20th order numerical stochastic perturbation theory

Energy Technology Data Exchange (ETDEWEB)

Horsley, R. [Edinburgh Univ. (United Kingdom). School of Physics; Hotzel, G.; Perlt, H.; Schiller, A. [Leipzig Univ. (Germany). Inst. fuer Theoretische Physik; Ilgenfritz, E.M. [Humboldt-Universitaet, Berlin (Germany). Inst. fuer Physik; Joint Institute for Nuclear Research, VBLHEP, Dubna (Russian Federation); Millo, R.; Rakow, P.E.L. [Liverpool Univ. (Germany). Theoretical Physics Div.; Nakamura, Y. [RIKEN Advanced Institute for Computational Science, Kobe, Hyogo (Japan); Schierholz, G. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

2012-05-15

We calculate Wilson loops of various sizes up to 20 loops in SU(3) pure lattice gauge theory at different lattice sizes for Wilson gauge action using the technique of numerical stochastic perturbation theory. This allows us to investigate the perturbative series for various Wilson loops at high loop orders. We observe differences in the behavior of those series as function of the loop order. Up to n=20 we do not find evidence for the factorial growth of the expansion coefficients often assumed to characterize an asymptotic series. Based on the actually observed behavior we sum the series in a model parametrized by hypergeometric functions. Alternatively we estimate the total series in boosted perturbation theory using information from the first 14 loops. We introduce generalized ratios of Wilson loops of different sizes. Together with the corresponding Wilson loops from standard Monte Carlo measurements they enable us to assess their non-perturbative parts.

Zero Point Energy of Renormalized Wilson Loops

OpenAIRE

Hidaka, Yoshimasa; Pisarski, Robert D.

2009-01-01

The quark antiquark potential, and its associated zero point energy, can be extracted from lattice measurements of the Wilson loop. We discuss a unique prescription to renormalize the Wilson loop, for which the perturbative contribution to the zero point energy vanishes identically. A zero point energy can arise nonperturbatively, which we illustrate by considering effective string models. The nonperturbative contribution to the zero point energy vanishes in the Nambu model, but is nonzero wh...

The Legacy of G. Wilson Knight

Directory of Open Access Journals (Sweden)

Raw Laurence

2017-06-01

Full Text Available G. Wilson Knight (1897-1985 was one of the most influential Shakespearean critics of the mid-twentieth century. This piece surveys his work from 1930 until the early 1980s. Much affected by the First World War, he developed a style of criticism based on Christian principles of respect for other people and belief in an all-powerful God. Many of his most famous pieces (in THE WHEEL OF FIRE, for instance argue for human insignificance in an indifferent universe. It is up to all of us as individuals to develop methods of coping with this world. Wilson Knight’s ideas gained particular currency during the Second World War, when Britain’s very future seemed at risk due to the threat of Nazi invasion. Although much derided for his use of transcendent language—especially by his contemporary F. R. Leavis—Wilson Knight’s ideas seem to have acquired new significance in a globalized world, where individuals fight to main their identity in a technology-driven environment.

Ted Wilson passes on the torch

CERN Multimedia

2003-01-01

As part of the Laboratory's outreach programme, the CERN Accelerator School (CAS) brings together students and experienced physicists from all over the world with the aim of promoting the understanding of accelerator physics. As head of the School for 11 years, Ted Wilson became a CERN ambassador to the outside community. He retired in March, handing over the reigns of the CAS to Daniel Brandt. Ted Wilson and his assistant, Suzanne von Wartburg, during an EPAC meeting in 1994.The accelerator schools allowed some time for relaxation in the local surrounding for students as well as for the director of CAS.As a boy, Ted Wilson could have embarked on a career in pop music rather than physics, rubbing shoulders at secondary school in Liverpool with two of the future Beatles. But prefering classical music and answering the call of science, he took the more serious of the two paths, studying physics first at Oxford University then at the Rutherford Laboratory. After a year at CERN and four years at the Rutherford La...

Solar rotation measurements at Mount Wilson. Pt. 2

International Nuclear Information System (INIS)

Labonte, B.J.; Howard, R.; Carnegie Institution of Washington, Pasadena

1981-01-01

Possible sources of systematic error in solar Doppler rotational velocities are examined. Scattered light is shown to affect the Mount Wilson solar rotation results, but this effect is not enough to bring the spectroscopic results in coincidence with the sunspot rotation. Interference fringes at the spectrograph focus at Mount Wilson have in two intervals affected the rotation results. It has been possible to correlate this error with temperature and thus correct for it. A misalignment between the entrance and exit slits is a possible source of error, but for the Mount Wilson slit configuration the amplitude of this effect is negligibly small. Rapid scanning of the solar image also produces no measurable effect. (orig.)

Conformal blocks from Wilson lines with loop corrections

Science.gov (United States)

Hikida, Yasuaki; Uetoko, Takahiro

2018-04-01

We compute the conformal blocks of the Virasoro minimal model or its WN extension with large central charge from Wilson line networks in a Chern-Simons theory including loop corrections. In our previous work, we offered a prescription to regularize divergences from loops attached to Wilson lines. In this paper, we generalize our method with the prescription by dealing with more general operators for N =3 and apply it to the identity W3 block. We further compute general light-light blocks and heavy-light correlators for N =2 with the Wilson line method and compare the results with known ones obtained using a different prescription. We briefly discuss general W3 blocks.

August Wilson's Presentation of Interracial Movements in 1960s

Science.gov (United States)

Li, Yanghua

2018-01-01

August Wilson's "Two Trains Running" tells the life predicaments of the patrons at Memphis' restaurant in the 1960s. Though Wilson avoids addressing the interracial conflicts and movements on stage to eschew protesting and propaganda, they as social background could not be totally ignored in the play. The paper analyses Wilson's use of…

Presentación clínica, diagnóstico y evolución a largo plazo en 29 pacientes con enfermedad de Wilson Clinical presentation, diagnosis, and long-term outcome of 29 patients with Wilson's disease

Directory of Open Access Journals (Sweden)

J. L. Rodrigo Agudo

2008-08-01

Full Text Available Objetivo: analizar las características clínicas, el tratamiento y evolución de los pacientes diagnosticados de enfermedad de Wilson (EW en la región de Murcia. Pacientes y método: se realizó un análisis retrospectivo de las historias clínicas de los 29 pacientes (edad media ± DE, 20,3 ± 13,4 años con EW diagnosticados en los últimos 16 años. Resultados: el motivo de consulta más frecuente fue el descubrimiento de transaminasas elevadas, en casi la mitad de los pacientes, seguido de temblor o distonía en el 17% respectivamente. El anillo de Kayser-Fleischer se objetivó en 17 de los 29 (58,6% pacientes (100% de los pacientes con afectación neurológica pura y en el 35,3% de los pacientes con clínica hepática pura; p Objective: to analyze the clinical characteristics, treatment, and follow-up of a cohort of 29 patients with Wilson's disease (WD within the region of Murcia. Patients and method: we reviewed the medical records of 29 cases of WD (mean age, 20.3 ± 13.4 years diagnosed during the last 16 years. Results: the most frequent reason for consultation was upon discovering a high transaminase level in almost half the patients, followed by tremors or dystonia in 17% of patients, respectively. A Kayser-Fleischer ring was observed in 17/29 (58.6% of patients (100% of patients with pure neurological involvement and 35% of patients with pure clinical hepatic disease; p < 0.001. Blood copper levels not associated with ceruloplasmin as well as cupruria were notably superior in patients with neurological symptoms and in those with liver cirrhosis at the time of diagnosis. Patient clinical symptoms remained stable with D-penicillamine or trientine, or improved during the observation period, for 18 out of 29 patients (62%, while 11 out of 29 patients (38% got worse. Conclusions: in our region patients with WD are diagnosed at a younger age, and in most cases for hepatic disease. Patients with neurological disease o liver cirrhosis had

Operator product expansion on the lattice: analytic Wilson coefficients

Science.gov (United States)

Perlt, Holger

2006-12-01

We present first results for Wilson coefficients of operators up to first order in the covariant deriva- tives for the case of Wilson fermions. They are derived from the off-shell Compton scattering amplitude Wµν (a, p, q) of massless quarks with momentum p. The Wilson coefficients are clas- sified according to the transformation of the corresponding operators under the hypercubic group H(4). We give selected examples for a special choice of the momentum transfer q. All Wil- son coefficients are given in closed analytic form and in an expansion in powers of a up to first corrections.

Mining disease genes using integrated protein-protein interaction and gene-gene co-regulation information.

Science.gov (United States)

Li, Jin; Wang, Limei; Guo, Maozu; Zhang, Ruijie; Dai, Qiguo; Liu, Xiaoyan; Wang, Chunyu; Teng, Zhixia; Xuan, Ping; Zhang, Mingming

2015-01-01

In humans, despite the rapid increase in disease-associated gene discovery, a large proportion of disease-associated genes are still unknown. Many network-based approaches have been used to prioritize disease genes. Many networks, such as the protein-protein interaction (PPI), KEGG, and gene co-expression networks, have been used. Expression quantitative trait loci (eQTLs) have been successfully applied for the determination of genes associated with several diseases. In this study, we constructed an eQTL-based gene-gene co-regulation network (GGCRN) and used it to mine for disease genes. We adopted the random walk with restart (RWR) algorithm to mine for genes associated with Alzheimer disease. Compared to the Human Protein Reference Database (HPRD) PPI network alone, the integrated HPRD PPI and GGCRN networks provided faster convergence and revealed new disease-related genes. Therefore, using the RWR algorithm for integrated PPI and GGCRN is an effective method for disease-associated gene mining.

Density-dependent mass gain by Wilson's Warblers during stopover

Science.gov (United States)

Jeffrey F. Kelly; Linda S. DeLay; Deborah M. Finch

2002-01-01

The need restore energetic reserves at stopover sites constrains avian migration ecology. To describe that constraint, we examined relationships among mass gained by Wilson's Warblers (Wilsonia pusilla) during stopover, abundance of Wilson's Warblers (i.e. capture rate), and arthropod abundance during autumn migration. We found that amount...

Large Wilson loop averages from the Schwinger-Dyson equation

International Nuclear Information System (INIS)

Xue Shesheng

1987-01-01

Using Schwinger-Dyson equations for the large Wilson loop in abelian lattice gauge theories, we evaluate the vacuum expectation values of the Wilson loop of sizes 1x2, 2x2, 2x3, and so on, from which the string tension is extracted. (orig.)

Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes

Directory of Open Access Journals (Sweden)

Reverter Antonio

2008-09-01

Full Text Available Abstract Background The tissue specificity of gene expression has been linked to a number of significant outcomes including level of expression, and differential rates of polymorphism, evolution and disease association. Recent studies have also shown the importance of exploring differential gene connectivity and sequence conservation in the identification of disease-associated genes. However, no study relates gene interactions with tissue specificity and disease association. Methods We adopted an a priori approach making as few assumptions as possible to analyse the interplay among gene-gene interactions with tissue specificity and its subsequent likelihood of association with disease. We mined three large datasets comprising expression data drawn from massively parallel signature sequencing across 32 tissues, describing a set of 55,606 true positive interactions for 7,197 genes, and microarray expression results generated during the profiling of systemic inflammation, from which 126,543 interactions among 7,090 genes were reported. Results Amongst the myriad of complex relationships identified between expression, disease, connectivity and tissue specificity, some interesting patterns emerged. These include elevated rates of expression and network connectivity in housekeeping and disease-associated tissue-specific genes. We found that disease-associated genes are more likely to show tissue specific expression and most frequently interact with other disease genes. Using the thresholds defined in these observations, we develop a guilt-by-association algorithm and discover a group of 112 non-disease annotated genes that predominantly interact with disease-associated genes, impacting on disease outcomes. Conclusion We conclude that parameters such as tissue specificity and network connectivity can be used in combination to identify a group of genes, not previously confirmed as disease causing, that are involved in interactions with disease causing

Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

KAUST Repository

Alshahrani, Mona

2018-04-30

In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease\\'s (or patient\\'s) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

Norrie disease gene is distinct from the monoamine oxidase genes

OpenAIRE

Sims, Katherine B.; Ozelius, Laurie; Corey, Timothy; Rinehart, William B.; Liberfarb, Ruth; Haines, Jonathan; Chen, Wei Jane; Norio, Reijo; Sankila, Eeva; de la Chapelle, Albert; Murphy, Dennis L.; Gusella, James; Breakefield, Xandra O.

1989-01-01

The genes for MAO-A and MAO-B appear to be very close to the Norrie disease gene, on the basis of loss and /or disruption of the MAO genes and activities in atypical Norrie disease patients deleted for the DXS7 locus; linkage among the MAO genes, the Norrie disease gene, and the DXS7 locus; and mapping of all these loci to the chromosomal region Xp11. The present study provides evidence that the MAO genes are not disrupted in “classic” Norrie disease patients. Genomic DNA from these “nondelet...

Scaling properties of Wilson loops pierced by P-vortices

DEFF Research Database (Denmark)

Dunn, Patrick; Greensite, Jeffrey Paul

2012-01-01

P-vortices, in an SU(N) lattice gauge theory, are excitations on the center-projected Z(N) lattice. We study the ratio of expectation values of SU(2) Wilson loops, on the unprojected lattice, linked to a single P-vortex, to that of Wilson loops which are not linked to any P-vortices. When...

Evolutionary dynamics of human autoimmune disease genes and malfunctioned immunological genes

Directory of Open Access Journals (Sweden)

Podder Soumita

2012-01-01

Full Text Available Abstract Background One of the main issues of molecular evolution is to divulge the principles in dictating the evolutionary rate differences among various gene classes. Immunological genes have received considerable attention in evolutionary biology as candidates for local adaptation and for studying functionally important polymorphisms. The normal structure and function of immunological genes will be distorted when they experience mutations leading to immunological dysfunctions. Results Here, we examined the fundamental differences between the genes which on mutation give rise to autoimmune or other immune system related diseases and the immunological genes that do not cause any disease phenotypes. Although the disease genes examined are analogous to non-disease genes in product, expression, function, and pathway affiliation, a statistically significant decrease in evolutionary rate has been found in autoimmune disease genes relative to all other immune related diseases and non-disease genes. Possible ways of accumulation of mutation in the three steps of the central dogma (DNA-mRNA-Protein have been studied to trace the mutational effects predisposed to disease consequence and acquiring higher selection pressure. Principal Component Analysis and Multivariate Regression Analysis have established the predominant role of single nucleotide polymorphisms in guiding the evolutionary rate of immunological disease and non-disease genes followed by m-RNA abundance, paralogs number, fraction of phosphorylation residue, alternatively spliced exon, protein residue burial and protein disorder. Conclusions Our study provides an empirical insight into the etiology of autoimmune disease genes and other immunological diseases. The immediate utility of our study is to help in disease gene identification and may also help in medicinal improvement of immune related disease.

Gene therapy for ocular diseases.

Science.gov (United States)

Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

2011-05-01

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

Wilson loop's phase transition probed by non-local observable

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Hui-Ling Li

2018-04-01

Full Text Available In order to give further insights into the holographic Van der Waals phase transition, it would be of great interest to investigate the behavior of Wilson loop across the holographic phase transition for a higher dimensional hairy black hole. We offer a possibility to proceed with a numerical calculation in order to discussion on the hairy black hole's phase transition, and show that Wilson loop can serve as a probe to detect a phase structure of the black hole. Furthermore, for a first order phase transition, we calculate numerically the Maxwell's equal area construction; and for a second order phase transition, we also study the critical exponent in order to characterize the Wilson loop's phase transition.

Woodrow Wilson: Prophet of Peace. Teaching with Historic Places.

Science.gov (United States)

Goehner, Thomas B.

This lesson describes President Woodrow Wilson's struggle with and his ultimate failure at achieving lasting world peace through the League of Nations. The lesson focuses on November 23, 1923, the eve of the fifth anniversary of the Armistice that concluded World War I, when a frail and ill Wilson was ready to deliver a commemorative address by…

Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

KAUST Repository

AlShahrani, Mona; Hoehndorf, Robert

2018-01-01

In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease's (or patient's) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

Zero point energy of renormalized Wilson loops

International Nuclear Information System (INIS)

Hidaka, Yoshimasa; Pisarski, Robert D.

2009-01-01

The quark-antiquark potential, and its associated zero point energy, can be extracted from lattice measurements of the Wilson loop. We discuss a unique prescription to renormalize the Wilson loop, for which the perturbative contribution to the zero point energy vanishes identically. A zero point energy can arise nonperturbatively, which we illustrate by considering effective string models. The nonperturbative contribution to the zero point energy vanishes in the Nambu model, but is nonzero when terms for extrinsic curvature are included. At one loop order, the nonperturbative contribution to the zero point energy is negative, regardless of the sign of the extrinsic curvature term.

War, Medicine, and Cultural Diplomacy in the Americas: Frank Wilson and Brazilian cardiology.

Science.gov (United States)

Kropf, Simone P; Howell, Joel D

2017-10-01

American cultural diplomacy played a key role in the institutionalization of Brazilian cardiology. In 1942, Frank Wilson, an internationally recognized pioneer in electrocardiography, made an extended wartime visit to Rio de Janeiro and São Paulo. The visit was sponsored by the United States Department of State as part of Roosevelt's Good Neighbor Policy and brought Wilson together with a group of physicians who would establish the specialty of cardiology in Brazil. This US cultural and diplomatic initiative strengthened an academic network that was already evolving and would eventually prove to be of benefit to both sides. Latin American physicians began in the 1920s to visit Wilson's laboratory at the University of Michigan, where they established the relationships on which Wilson would build. While affiliation with the "Wilson school" advanced the cause of Brazilian cardiologists who sought to establish themselves as specialists, cooperation with Latin American physicians benefitted Wilson in his pursuit of wider recognition for his innovations in the use of electrocardiography (ECG). Wilson's identity as a scientific ambassador to Latin America helped in legitimating his approach to the clinical application of the ECG. A close examination of Wilson's relationship to Brazilian cardiology demonstrates the role played by science and medicine as a part of wartime cultural diplomacy, as well as the dynamics of the transnational circulation of scientific knowledge and practices. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Norrie disease gene is distinct from the monoamine oxidase genes.

Science.gov (United States)

Sims, K B; Ozelius, L; Corey, T; Rinehart, W B; Liberfarb, R; Haines, J; Chen, W J; Norio, R; Sankila, E; de la Chapelle, A

1989-09-01

The genes for MAO-A and MAO-B appear to be very close to the Norrie disease gene, on the basis of loss and/or disruption of the MAO genes and activities in atypical Norrie disease patients deleted for the DXS7 locus; linkage among the MAO genes, the Norrie disease gene, and the DXS7 locus; and mapping of all these loci to the chromosomal region Xp11. The present study provides evidence that the MAO genes are not disrupted in "classic" Norrie disease patients. Genomic DNA from these "nondeletion" Norrie disease patients did not show rearrangements at the MAOA or DXS7 loci. Normal levels of MAO-A activities, as well as normal amounts and size of the MAO-A mRNA, were observed in cultured skin fibroblasts from these patients, and MAO-B activity in their platelets was normal. Catecholamine metabolites evaluated in plasma and urine were in the control range. Thus, although some atypical Norrie disease patients lack both MAO-A and MAO-B activities, MAO does not appear to be an etiologic factor in classic Norrie disease.

Exact results for ABJ Wilson loops and open-closed duality

Energy Technology Data Exchange (ETDEWEB)

Hatsuda, Yasuyuki [Département de Physique Théorique et section de Mathématiques, Université de Genève,Genève, CH-1211 (Switzerland); Okuyama, Kazumi [Department of Physics, Shinshu University,Matsumoto 390-8621 (Japan)

2016-10-24

We find new exact relations between the partition function and vacuum expectation values (VEVs) of 1/2 BPS Wilson loops in ABJ theory, which allow us to predict the large N expansions of the 1/2 BPS Wilson loops from known results of the partition function. These relations are interpreted as an open-closed duality where the closed string background is shifted by the insertion of Wilson loops due to a back-reaction. Using the connection between ABJ theory and the topological string on local ℙ{sup 1}×ℙ{sup 1}, we explicitly write down non-trivial relations between open and closed string amplitudes.

Sextet Model with Wilson Fermions

DEFF Research Database (Denmark)

Hansen, Martin; Pica, Claudio

2017-01-01

We present new results from our ongoing study of the SU(3) sextet model with two flavors in the two-index symmetric representation of the gauge group. In the simulations use unimproved Wilson fermions to investigate the infrared properties of the model. We have previously presented results...

Wilson's disease: two treatment modalities. Correlations to pretreatment and posttreatment brain MRI

International Nuclear Information System (INIS)

Leiros da Costa, Maria do Desterro; Spitz, Mariana; Bacheschi, Luiz Alberto; Barbosa, Egberto Reis; Leite, Claudia Costa; Lucato, Leandro Tavares

2009-01-01

Brain magnetic resonance imaging (MRI) studies on Wilson's disease (WD) show lack of correlations between neurological and neuroimaging features. Long-term follow-up reports with sequential brain MRI in patients with neurological WD comparing different modalities of treatment are scarce. Eighteen patients with neurological WD underwent pretreatment and posttreatment brain MRI scans to evaluate the range of abnormalities and the evolution along these different periods. All patients underwent at least two MRI scans at different intervals, up to 11 years after the beginning of treatment. MRI findings were correlated with clinical picture, clinical severity, duration of neurological symptoms, and treatment with two different drugs. Patients were divided into two groups according to treatment: d-penicillamine (D-P), zinc (Zn), and Zn after the onset of severe intolerance to D-P. MRI scans before treatment showed, in all patients, hypersignal intensity lesions on T2- and proton-density-weighted images bilaterally and symmetrically at basal nuclei, thalamus, brain stem, cerebellum, brain cortex, and brain white matter. The most common neurological symptoms were: dysarthria, parkinsonism, dystonia, tremor, psychiatric disturbances, dysphagia, risus sardonicus, ataxia, chorea, and athetosis. From the neurological point of view, there was no difference on the evolution between the group treated exclusively with D-P and the one treated with Zn. Analysis of MRI scans with longer intervals after the beginning of treatment depicted a trend for neuroimaging worsening, without neurological correspondence, among patients treated with Zn. Neuroimaging pattern of evolution was more favorable for the group that received exclusively D-P. (orig.)

Gene Therapy for Parkinson's Disease

Directory of Open Access Journals (Sweden)

Rachel Denyer

2012-01-01

Full Text Available Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field.

Determination of low-energy constants of Wilson chiral perturbation theory

International Nuclear Information System (INIS)

Herdoiza, Gregorio; Univ. Autonoma de Madrid, Contoblanco; Univ. Autonoma de Madrid; Jansen, Karl; Univ. Cyprus, Nicosia; Michael, Chris; Ottnad, Konstantin; Urbach, Carsten; Univ. Bonn

2013-03-01

By matching Wilson twisted mass lattice QCD determinations of pseudoscalar meson masses to Wilson Chiral Perturbation Theory we determine the low-energy constants W 6 ' , W 8 ' and their linear combination c 2 . We explore the dependence of these low-energy constants on the choice of the lattice action and on the number of dynamical flavours.

Wilson loops in Kerr gravitation

International Nuclear Information System (INIS)

Bollini, C.G.; Giambiagi, J.J.; Tiomno, J.

1981-01-01

The ordered integrals for several paths in Kerr gravitation is computed in a compact form. When the path is closed its relation with the angular parallel displacement is discussed and the corresponding Wilson loop is calculated. The validity of Mandelstam relations for gauge fields is also explicitly verified. (Author) [pt

Robert Wilson's Invitation to Insanity.

Science.gov (United States)

Stephens, Judith L.

The plays of stage director Robert Wilson are devices presenting alternative modes of perception to theatre audiences accustomed to verbal/aural structures of experience. Uniting his interests in the arts and therapy, his plays create a theatrical event promoting empathy with the perceptions of the mentally or physically handicapped and…

Gene therapy for CNS diseases – Krabbe disease

Directory of Open Access Journals (Sweden)

Mohammad A. Rafi

2016-06-01

Full Text Available This is a brief report of the 19th Annual Meeting of the American Society of Gene and Cell Therapy that took place from May 4th through May 7th, 2016 in Washington, DC, USA. While the meeting provided many symposiums, lectures, and scientific sessions this report mainly focuses on one of the sessions on the "Gene Therapy for central nervous system (CNS Diseases" and specifically on the "Gene Therapy for the globoid cell leukodystrophy or Krabbe disease. Two presentations focused on this subject utilizing two animal models of this disease: mice and dog models. Different serotypes of adeno-associate viral vectors (AAV alone or in combination with bone marrow transplantations were used in these research projects. The Meeting of the ASGCT reflected continuous growth in the fields of gene and cell therapy and brighter forecast for efficient treatment options for variety of human diseases.

Kenneth G Wilson (1936–2013)

Indian Academy of Sciences (India)

The best reference for anyone interested in the development of Wilson's thinking in this period ... work on the critical point was a seminar in the Chemistry Department by his ... The basic theoretical tool used was the renormalization group.

Determination of low-energy constants of Wilson chiral perturbation theory

Energy Technology Data Exchange (ETDEWEB)

Herdoiza, Gregorio [Mainz Univ. (Germany). Inst fuer Kernphysik, PRISMA Cluster of Excellence; Univ. Autonoma de Madrid, Contoblanco (Spain). Dept. de Fisica Teorica; Univ. Autonoma de Madrid (Spain). Inst. de Fisica Teorica UAM/CSIC; Jansen, Karl [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC; Univ. Cyprus, Nicosia (Cyprus). Dept. of Physics; Michael, Chris [Liverpool Univ. (United Kingdom). Theoretical Physics Division; Ottnad, Konstantin; Urbach, Carsten [Bonn Univ. (Germany). Helmholtz-Institut fuer Strahlen und Kernphysik; Univ. Bonn (Germany). Bethe Center for Theoretical Physics; Collaboration: European Twisted Mass Collaboration

2013-03-15

By matching Wilson twisted mass lattice QCD determinations of pseudoscalar meson masses to Wilson Chiral Perturbation Theory we determine the low-energy constants W{sub 6}{sup '}, W{sub 8}{sup '} and their linear combination c{sub 2}. We explore the dependence of these low-energy constants on the choice of the lattice action and on the number of dynamical flavours.

Gene transfer therapy in vascular diseases.

Science.gov (United States)

McKay, M J; Gaballa, M A

2001-01-01

Somatic gene therapy of vascular diseases is a promising new field in modern medicine. Recent advancements in gene transfer technology have greatly evolved our understanding of the pathophysiologic role of candidate disease genes. With this knowledge, the expression of selective gene products provides the means to test the therapeutic use of gene therapy in a multitude of medical conditions. In addition, with the completion of genome sequencing programs, gene transfer can be used also to study the biologic function of novel genes in vivo. Novel genes are delivered to targeted tissue via several different vehicles. These vectors include adenoviruses, retroviruses, plasmids, plasmid/liposomes, and oligonucleotides. However, each one of these vectors has inherent limitations. Further investigations into developing delivery systems that not only allow for efficient, targeted gene transfer, but also are stable and nonimmunogenic, will optimize the clinical application of gene therapy in vascular diseases. This review further discusses the available mode of gene delivery and examines six major areas in vascular gene therapy, namely prevention of restenosis, thrombosis, hypertension, atherosclerosis, peripheral vascular disease in congestive heart failure, and ischemia. Although we highlight some of the recent advances in the use of gene therapy in treating vascular disease discovered primarily during the past two years, many excellent studies published during that period are not included in this review due to space limitations. The following is a selective review of practical uses of gene transfer therapy in vascular diseases. This review primarily covers work performed in the last 2 years. For earlier work, the reader may refer to several excellent review articles. For instance, Belalcazer et al. (6) reviewed general aspects of somatic gene therapy and the different vehicles used for the delivery of therapeutic genes. Gene therapy in restenosis and stimulation of

Towards a nonperturbative calculation of weak Hamiltonian Wilson coefficients

Science.gov (United States)

Bruno, Mattia; Lehner, Christoph; Soni, Amarjit; Rbc; Ukqcd Collaborations

2018-04-01

We propose a method to compute the Wilson coefficients of the weak effective Hamiltonian to all orders in the strong coupling constant using Lattice QCD simulations. We perform our calculations adopting an unphysically light weak boson mass of around 2 GeV. We demonstrate that systematic errors for the Wilson coefficients C1 and C2 , related to the current-current four-quark operators, can be controlled and present a path towards precise determinations in subsequent works.

Non-supersymmetric Wilson loop in N = 4 SYM and defect 1d CFT

Science.gov (United States)

Beccaria, Matteo; Giombi, Simone; Tseytlin, Arkady A.

2018-03-01

Following Polchinski and Sully (arXiv:1104.5077), we consider a generalized Wilson loop operator containing a constant parameter ζ in front of the scalar coupling term, so that ζ = 0 corresponds to the standard Wilson loop, while ζ = 1 to the locally supersymmetric one. We compute the expectation value of this operator for circular loop as a function of ζ to second order in the planar weak coupling expansion in N = 4 SYM theory. We then explain the relation of the expansion near the two conformal points ζ = 0 and ζ = 1 to the correlators of scalar operators inserted on the loop. We also discuss the AdS5 × S 5 string 1-loop correction to the strong-coupling expansion of the standard circular Wilson loop, as well as its generalization to the case of mixed boundary conditions on the five-sphere coordinates, corresponding to general ζ. From the point of view of the defect CFT1 defined on the Wilson line, the ζ-dependent term can be seen as a perturbation driving a RG flow from the standard Wilson loop in the UV to the supersymmetric Wilson loop in the IR. Both at weak and strong coupling we find that the logarithm of the expectation value of the standard Wilson loop for the circular contour is larger than that of the supersymmetric one, which appears to be in agreement with the 1d analog of the F-theorem.

Skein relations and Wilson loops in Chern-Simons gauge theory

International Nuclear Information System (INIS)

Horne, J.H.

1990-01-01

We derive the skein relations for the fundamental representations of SO(N), Sp(2n), SU(mvertical stroken), and OSp(mvertical stroke2n). These relations can be used recursively to calculate the expectation values of Wilson lines in three-dimensional Chern-Simons gauge theory with these gauge groups. A combination of braiding and tying of Wilson lines completely describes the skein relations. (orig.)

Constructing an integrated gene similarity network for the identification of disease genes.

Science.gov (United States)

Tian, Zhen; Guo, Maozu; Wang, Chunyu; Xing, LinLin; Wang, Lei; Zhang, Yin

2017-09-20

Discovering novel genes that are involved human diseases is a challenging task in biomedical research. In recent years, several computational approaches have been proposed to prioritize candidate disease genes. Most of these methods are mainly based on protein-protein interaction (PPI) networks. However, since these PPI networks contain false positives and only cover less half of known human genes, their reliability and coverage are very low. Therefore, it is highly necessary to fuse multiple genomic data to construct a credible gene similarity network and then infer disease genes on the whole genomic scale. We proposed a novel method, named RWRB, to infer causal genes of interested diseases. First, we construct five individual gene (protein) similarity networks based on multiple genomic data of human genes. Then, an integrated gene similarity network (IGSN) is reconstructed based on similarity network fusion (SNF) method. Finally, we employee the random walk with restart algorithm on the phenotype-gene bilayer network, which combines phenotype similarity network, IGSN as well as phenotype-gene association network, to prioritize candidate disease genes. We investigate the effectiveness of RWRB through leave-one-out cross-validation methods in inferring phenotype-gene relationships. Results show that RWRB is more accurate than state-of-the-art methods on most evaluation metrics. Further analysis shows that the success of RWRB is benefited from IGSN which has a wider coverage and higher reliability comparing with current PPI networks. Moreover, we conduct a comprehensive case study for Alzheimer's disease and predict some novel disease genes that supported by literature. RWRB is an effective and reliable algorithm in prioritizing candidate disease genes on the genomic scale. Software and supplementary information are available at http://nclab.hit.edu.cn/~tianzhen/RWRB/ .

A profusion of 1/2 BPS Wilson loops in N=4 Chern-Simons-matter theories

International Nuclear Information System (INIS)

Cooke, Michael; Drukker, Nadav; Trancanelli, Diego

2015-01-01

We initiate the study of 1/2 BPS Wilson loops in N=4 Chern-Simons-matter theories in three dimensions. We consider a circular or linear quiver with Chern-Simons levels k, −k and 0, and focus on loops preserving one of the two SU(2) subgroups of the R-symmetry. In the cases with no vanishing Chern-Simons levels, we find a pair of Wilson loops for each pair of adjacent nodes on the quiver connected by a hypermultiplet (nodes connected by twisted hypermultiplets have Wilson loops preserving another set of supercharges). We expect this classical pairwise degeneracy to be lifted by quantum corrections. In the case with nodes with vanishing Chern-Simons terms connected by twisted hypermultiplets, we find that the usual 1/4 BPS Wilson loops are automatically enlarged to 1/2 BPS, as happens also in 3-dimensional Yang-Mills theory. When the nodes with vanishing Chern-Simons levels are connected by untwisted hypermultiplets, we do not find any Wilson loops coupling to those nodes which are classically invariant. Rather, we find several loops whose supersymmetry variation, while non zero, vanishes in any correlation function, so is weakly zero. We expect only one linear combination of those Wilson loops to remain BPS when quantum corrections are included. We analyze the M-theory duals of those Wilson loops and comment on their degeneracy. We also show that these Wilson loops are cohomologically equivalent to certain 1/4 BPS Wilson loops whose expectation value can be evaluated by the appropriate localized matrix model.

Holography of Wilson-loop expectation values with local operator insertions

International Nuclear Information System (INIS)

Miwa, Akitsugu; Yoneya, Tamiaki

2006-01-01

We study the expectation values of Wilson-loop operators with the insertions of local operators Z J and Z-bar J for large J from the bulk viewpoint of AdS/CFT correspondence. Classical solutions of strings attached to such deformed Wilson loops at the conformal boundary are constructed and are applied to the computation of Wilson-loop expectation values. We argue that in order to have such solutions for general insertions at finite positions in the base spacetime of the gauge theory, it is crucial to interpret the holographic correspondence in the semi-classical picture as a tunneling phenomenon, as has been previously established for holographic computations of correlators of BMN operators. This also requires to use the Euclideanized AdS background and Euclidean super Yang-Mills theory

Wilson Martins: between the intelligentsia and the university (1951

Directory of Open Access Journals (Sweden)

Névio de Campos

2012-05-01

Full Text Available Abstract The purpose of this article is to analyze the presence of Ortega y Gasset in the Parana’s State group during the 1950s, especially his influence in the thinking of Wilson Martins, and to emphasize the debate on the ideas of the intellectual and the university. The article discusses about the contributions of this Parana’s thinker on the Parana’s university teaching constituting and organizing process, and emphasizes that the Wilson Martins’ role consisted in promoting the debate on the presence of the intellectual person in modern society, attributing the mission as guardian of the moral and herald of cultural renovation, without forgetting the Brazilian and European political-cultural context as the founding background to higher education. It bases itself on the speech entitled “The rebellion against intelligence and the mission of the university”, that occurred at the University of Parana in 1951, and on the work The History of Brazilian Intelligence, written by Wilson Martins.

Wilson fermions at finite temperature

International Nuclear Information System (INIS)

Creutz, M.

1996-01-01

The author conjectures on the phase structure expected for lattice gauge theory with two flavors of Wilson fermions, concentrating on large values of the hopping parameter. Numerous phases are expected, including the conventional confinement and deconfinement phases, as well as an Aoki phase with spontaneous breaking of flavor and parity and a large hopping phase corresponding to negative quark masses

Wilson Fermions with Four Fermion Interactions

DEFF Research Database (Denmark)

Rantaharju, Jarno; Drach, Vincent; Hietanen, Ari

2015-01-01

We present a lattice study of a four fermion theory, known as Nambu Jona-Lasinio (NJL) theory, via Wilson fermions. Four fermion interactions naturally occur in several extensions of the Standard Model as a low energy parameterisation of a more fundamental theory. In models of dynamical electroweak...

Wilson loops in superconformal Chern-Simons theory and fundamental strings in Anti-de Sitter supergravity dual

International Nuclear Information System (INIS)

Rey, Soo-Jong; Suyama, Takao; Yamaguchi, Satoshi

2009-01-01

We study Wilson loop operators in three-dimensional, N = 6 superconformal Chern-Simons theory dual to IIA superstring theory on AdS 4 x CP 3 . Novelty of Wilson loop operators in this theory is that, for a given contour, there are two linear combinations of Wilson loop transforming oppositely under time-reversal transformation. We show that one combination is holographically dual to IIA fundamental string, while orthogonal combination is set to zero. We gather supporting evidences from detailed comparative study of generalized time-reversal transformations in both D2-brane worldvolume and ABJM theories. We then classify supersymmetric Wilson loops and find at most 1/6 supersymmetry. We next study Wilson loop expectation value in planar perturbation theory. For circular Wilson loop, we find features remarkably parallel to circular Wilson loop in N = 4 super Yang-Mills theory in four dimensions. First, all odd loop diagrams vanish identically and even loops contribute nontrivial contributions. Second, quantum corrected gauge and scalar propagators take the same form as those of N = 4 super Yang-Mills theory. Combining these results, we propose that expectation value of circular Wilson loop is given by Wilson loop expectation value in pure Chern-Simons theory times zero-dimensional Gaussian matrix model whose variance is specified by an interpolating function of 't Hooft coupling. We suggest the function interpolates smoothly between weak and strong coupling regime, offering new test ground of the AdS/CFT correspondence.

On the duality-transformed Wilson loop operator

International Nuclear Information System (INIS)

Mizrachi, L.

1981-08-01

Duality transformation of the vacuum expectation value of the Wilson loop operator is performed in the radial gauge (xsub(μ)Asub(μ)sup(a)(x) = 0). It is found to be equal, up to a multiplicative constant, to , where O(c) is a line integral along the loop c (defining the Wilson loop operator) of a function of the dual field variables. In the weak coupling region self duality is recovered in the sense that the Lagrangian is local gauge invariant defined in terms of the dual gauge potentials but with g (the coupling constant) replaced by 1/g, and O(c) is simply the line integral of the dual gauge potentials. For large g, a strong coupling expansion is suggested (but the theory is not local gauge invariant). (author)

Kenneth G Wilson (1936–2013)

Indian Academy of Sciences (India)

perceptions of strongly interacting systems – either in particle physics or in condensed matter. The Nobel citation mentions the cryptic term 'renormalization group'. An article elsewhere in this issue ... young research student who had graduated from Harvard University in 1956 – Kenneth Wilson. Gell-Mann suggested that ...

Esclusa Wilson

Directory of Open Access Journals (Sweden)

Editorial, Equipo

1959-11-01

Full Text Available En la presa Wilson, construida sobre el río Tennessee, ya existía una esclusa y canal que permitía la navegación fluvial por el río. Este rio tiene un curso de difícil navegación en una extensión próxima a la presa, pero la construcción de canales y esclusas ha permitido mejorar estas vías navegables. Estos últimos años ha aumentado tanto la navegación, que la esclusa existente no bastaba para hacer frente al paso de tantas embarcaciones dedicadas al transporte de mercancías que, aún en competencia con él transporte por ferrocarril y carretera, ha llegado a un volumen anual de unos trece millones de toneladas.

Edwin B. Wilson and the rise of mathematical economics in America, 1920-1940

OpenAIRE

Carvajalino, Juan

2017-01-01

In the paper, Edwin B. Wilson's influence on the rise of mathematical economics in America between the 1920s and 1940s is explored. The focus is laid on showing how on the grounds of his foundational ideas about science Wilson worked at the organizational and educational fronts to modernize economics, at this at three levels. First, the paper shows the ways in which around 1930 Wilson was key, at the nationwide level, in the constitution of the first organized community of American mathematic...

Ranking candidate disease genes from gene expression and protein interaction: a Katz-centrality based approach.

Directory of Open Access Journals (Sweden)

Jing Zhao

Full Text Available Many diseases have complex genetic causes, where a set of alleles can affect the propensity of getting the disease. The identification of such disease genes is important to understand the mechanistic and evolutionary aspects of pathogenesis, improve diagnosis and treatment of the disease, and aid in drug discovery. Current genetic studies typically identify chromosomal regions associated specific diseases. But picking out an unknown disease gene from hundreds of candidates located on the same genomic interval is still challenging. In this study, we propose an approach to prioritize candidate genes by integrating data of gene expression level, protein-protein interaction strength and known disease genes. Our method is based only on two, simple, biologically motivated assumptions--that a gene is a good disease-gene candidate if it is differentially expressed in cases and controls, or that it is close to other disease-gene candidates in its protein interaction network. We tested our method on 40 diseases in 58 gene expression datasets of the NCBI Gene Expression Omnibus database. On these datasets our method is able to predict unknown disease genes as well as identifying pleiotropic genes involved in the physiological cellular processes of many diseases. Our study not only provides an effective algorithm for prioritizing candidate disease genes but is also a way to discover phenotypic interdependency, cooccurrence and shared pathophysiology between different disorders.

Exact results for Wilson loops in arbitrary representations

Energy Technology Data Exchange (ETDEWEB)

Fiol, Bartomeu; Torrents, Genís [Departament de Física Fonamental i Institut de Ciències del Cosmos, Universitat de Barcelona,Martí i Franquès 1, 08028 Barcelona, Catalonia (Spain)

2014-01-08

We compute the exact vacuum expectation value of 1/2 BPS circular Wilson loops of N=4 U(N) super Yang-Mills in arbitrary irreducible representations. By localization arguments, the computation reduces to evaluating certain integrals in a Gaussian matrix model, which we do using the method of orthogonal polynomials. Our results are particularly simple for Wilson loops in antisymmetric representations; in this case, we observe that the final answers admit an expansion where the coefficients are positive integers, and can be written in terms of sums over skew Young diagrams. As an application of our results, we use them to discuss the exact Bremsstrahlung functions associated to the corresponding heavy probes.

Republished review: Gene therapy for ocular diseases.

Science.gov (United States)

Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

2011-07-01

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

Evolutionary signatures amongst disease genes permit novel methods for gene prioritization and construction of informative gene-based networks.

Directory of Open Access Journals (Sweden)

Nolan Priedigkeit

2015-02-01

Full Text Available Genes involved in the same function tend to have similar evolutionary histories, in that their rates of evolution covary over time. This coevolutionary signature, termed Evolutionary Rate Covariation (ERC, is calculated using only gene sequences from a set of closely related species and has demonstrated potential as a computational tool for inferring functional relationships between genes. To further define applications of ERC, we first established that roughly 55% of genetic diseases posses an ERC signature between their contributing genes. At a false discovery rate of 5% we report 40 such diseases including cancers, developmental disorders and mitochondrial diseases. Given these coevolutionary signatures between disease genes, we then assessed ERC's ability to prioritize known disease genes out of a list of unrelated candidates. We found that in the presence of an ERC signature, the true disease gene is effectively prioritized to the top 6% of candidates on average. We then apply this strategy to a melanoma-associated region on chromosome 1 and identify MCL1 as a potential causative gene. Furthermore, to gain global insight into disease mechanisms, we used ERC to predict molecular connections between 310 nominally distinct diseases. The resulting "disease map" network associates several diseases with related pathogenic mechanisms and unveils many novel relationships between clinically distinct diseases, such as between Hirschsprung's disease and melanoma. Taken together, these results demonstrate the utility of molecular evolution as a gene discovery platform and show that evolutionary signatures can be used to build informative gene-based networks.

Baryon Regge trajectories from the area-law of Wilson loop

International Nuclear Information System (INIS)

Simonov, Yu.A.

1989-01-01

In the proper-time path integral representation of the three-quark Green function, baryon masses are calculated for large angular momenta L. Dynamics is given by vacuum background fields in the Wilson loop. Assuming an area law for large Wilson loops one obtains linear baryon Regge trajectories with the same slope as for mesons. For large L the baryon has an asymmetric structure of the quark-diquark type. Dynamic masses of the quark and diquark are generated, which grow with L. 8 refs

3-loop heavy flavor Wilson coefficients in deep-inelastic scattering

International Nuclear Information System (INIS)

Ablinger, J.; Hasselhuhn, A.; Schneider, C.; Manteuffel, A. von

2014-09-01

We present our most recent results on the calculation of the heavy flavor contributions to deep-inelastic scattering at 3-loop order in the large Q 2 limit, where the heavy flavor Wilson coefficients are known to factorize into light flavor Wilson coefficients and massive operator matrix elements. We describe the different techniques employed for the calculation and show the results in the case of the heavy flavor non-singlet and pure singlet contributions to the structure function F 2 (x,Q 2 ).

Arthropod prey of Wilson's Warblers in the understory of Douglas-fir forests

Science.gov (United States)

Hagar, J.C.; Dugger, K.M.; Starkey, E.E.

2007-01-01

Availability of food resources is an important factor in avian habitat selection. Food resources for terrestrial birds often are closely related to vegetation structure and composition. Identification of plant species important in supporting food resources may facilitate vegetation management to achieve objectives for providing bird habitat. We used fecal analysis to describe the diet of adult Wilson's Warblers (Wilsonia pusilla) that foraged in the understory of Douglas-fir (Pseudotsuga menziesii) forests in western Oregon during the breeding season. We sampled arthropods at the same sites where diet data were collected, and compared abundance and biomass of prey among seven common shrub species. Wilson's Warblers ate more caterpillars (Lepidoptera larvae), flies (Diptera), beetles (Coleoptera), and Homoptera than expected based on availability. Deciduous shrubs supported higher abundances of arthropod taxa and size classes used as prey by Wilson's Warblers than did evergreen shrubs. The development and maintenance of deciduous understory vegetation in conifer forests of the Pacific Northwest may be fundamental for conservation of food webs that support breeding Wilson's Warblers and other shrub-associated, insectivorous songbirds.

Open Wilson lines and generalized star product in noncommutative scalar field theories

International Nuclear Information System (INIS)

Kiem, Youngjai; Sato, Haru-Tada; Rey, Soo-Jong; Yee, Jung-Tay

2002-01-01

Open Wilson line operators and a generalized star product have been studied extensively in noncommutative gauge theories. We show that they also show up in noncommutative scalar field theories as universal structures. We first point out that the dipole picture of noncommutative geometry provides an intuitive argument for the robustness of the open Wilson lines and generalized star products therein. We calculate the one-loop effective action of noncommutative scalar field theory with a cubic self-interaction and show explicitly that the generalized star products arise in the nonplanar part. It is shown that, at the low-energy, large noncommutativity limit, the nonplanar part is expressible solely in terms of the scalar open Wilson line operator and descendants

Inductive matrix completion for predicting gene-disease associations.

Science.gov (United States)

Natarajan, Nagarajan; Dhillon, Inderjit S

2014-06-15

Most existing methods for predicting causal disease genes rely on specific type of evidence, and are therefore limited in terms of applicability. More often than not, the type of evidence available for diseases varies-for example, we may know linked genes, keywords associated with the disease obtained by mining text, or co-occurrence of disease symptoms in patients. Similarly, the type of evidence available for genes varies-for example, specific microarray probes convey information only for certain sets of genes. In this article, we apply a novel matrix-completion method called Inductive Matrix Completion to the problem of predicting gene-disease associations; it combines multiple types of evidence (features) for diseases and genes to learn latent factors that explain the observed gene-disease associations. We construct features from different biological sources such as microarray expression data and disease-related textual data. A crucial advantage of the method is that it is inductive; it can be applied to diseases not seen at training time, unlike traditional matrix-completion approaches and network-based inference methods that are transductive. Comparison with state-of-the-art methods on diseases from the Online Mendelian Inheritance in Man (OMIM) database shows that the proposed approach is substantially better-it has close to one-in-four chance of recovering a true association in the top 100 predictions, compared to the recently proposed Catapult method (second best) that has bigdata.ices.utexas.edu/project/gene-disease. © The Author 2014. Published by Oxford University Press.

Symmetries of Ginsparg-Wilson chiral fermions

International Nuclear Information System (INIS)

Mandula, Jeffrey E.

2009-01-01

The group structure of the variant chiral symmetry discovered by Luescher in the Ginsparg-Wilson description of lattice chiral fermions is analyzed. It is shown that the group contains an infinite number of linearly independent symmetry generators, and the Lie algebra is given explicitly. CP is an automorphism of this extended chiral group, and the CP transformation properties of the symmetry generators are found. The group has an infinite-parameter invariant subgroup, and the factor group, whose elements are its cosets, is isomorphic to the continuum chiral symmetry group. Features of the currents associated with these symmetries are discussed, including the fact that some different, noncommuting symmetry generators lead to the same Noether current. These are universal features of lattice chiral fermions based on the Ginsparg-Wilson relation; they occur in the overlap, domain-wall, and perfect-action formulations. In a solvable example, free overlap fermions, these noncanonical elements of lattice chiral symmetry are related to complex energy singularities that violate reflection positivity and impede continuation to Minkowski space.

3-loop heavy flavor Wilson coefficients in deep-inelastic scattering

Energy Technology Data Exchange (ETDEWEB)

Ablinger, J.; Hasselhuhn, A.; Schneider, C. [Johannes-Kepler-Univ. Linz (Austria). RISC; Behring, A.; Bluemlein, J.; Freitas, A. de; Raab, C.; Round, M. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Manteuffel, A. von [Mainz Univ. (Germany). PRISMA Cluster of Excellence; Wissbrock, F. [Johannes-Kepler-Univ. Linz (Austria). RISC; Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); IHES Institut des Hautes Etudes Scientifiques, Bures-sur-Yvette (France)

2014-09-15

We present our most recent results on the calculation of the heavy flavor contributions to deep-inelastic scattering at 3-loop order in the large Q{sup 2} limit, where the heavy flavor Wilson coefficients are known to factorize into light flavor Wilson coefficients and massive operator matrix elements. We describe the different techniques employed for the calculation and show the results in the case of the heavy flavor non-singlet and pure singlet contributions to the structure function F{sub 2}(x,Q{sup 2}).

Gene expression profiling in autoimmune diseases

DEFF Research Database (Denmark)

Bovin, Lone Frier; Brynskov, Jørn; Hegedüs, Laszlo

2007-01-01

A central issue in autoimmune disease is whether the underlying inflammation is a repeated stereotypical process or whether disease specific gene expression is involved. To shed light on this, we analysed whether genes previously found to be differentially regulated in rheumatoid arthritis (RA...

Topological susceptibility in lattice QCD with unimproved Wilson fermions

International Nuclear Information System (INIS)

Chowdhury, Abhishek; De, Asit K.; De Sarkar, Sangita; Harindranath, A.; Mondal, Santanu; Sarkar, Anwesa; Maiti, Jyotirmoy

2012-01-01

We address a long standing problem regarding topology in lattice simulations of QCD with unimproved Wilson fermions. Earlier attempt with unimproved Wilson fermions at β=5.6 to verify the suppression of topological susceptibility with decreasing quark mass (m q ) was unable to unambiguously confirm the suppression. We carry out systematic calculations for two degenerate flavours at two different lattice spacings (β=5.6 and 5.8). The effects of quark mass, lattice volume and the lattice spacing on the spanning of different topological sectors are presented. We unambiguously demonstrate the suppression of the topological susceptibility with decreasing quark mass, expected from chiral Ward identity and chiral perturbation theory.

The epsilon regime of chiral perturbation theory with Wilson-type fermions

Energy Technology Data Exchange (ETDEWEB)

Jansen, K. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC; Shindler, A. [Liverpool Univ. (United Kingdom). Theoretical Physics Division

2009-11-15

In this proceeding contribution we report on the ongoing effort to simulate Wilson-type fermions in the so called epsilon regime of chiral perturbation theory (cPT).We present results for the chiral condensate and the pseudoscalar decay constant obtained with Wilson twisted mass fermions employing two lattice spacings, two different physical volumes and several quark masses. With this set of simulations we make a first attempt to estimate the systematic uncertainties. (orig.)

The epsilon regime of chiral perturbation theory with Wilson-type fermions

International Nuclear Information System (INIS)

Jansen, K.; Shindler, A.

2009-11-01

In this proceeding contribution we report on the ongoing effort to simulate Wilson-type fermions in the so called epsilon regime of chiral perturbation theory (cPT).We present results for the chiral condensate and the pseudoscalar decay constant obtained with Wilson twisted mass fermions employing two lattice spacings, two different physical volumes and several quark masses. With this set of simulations we make a first attempt to estimate the systematic uncertainties. (orig.)

Genes and Disease: Prader-Willi Syndrome

Science.gov (United States)

... MD): National Center for Biotechnology Information (US); 1998-. Genes and Disease [Internet]. Show details National Center for ... 45K) PDF version of this title (3.8M) Gene sequence Genome view see gene locations Entrez Gene ...

Beyond the scope of Free-Wilson analysis: building interpretable QSAR models with machine learning algorithms.

Science.gov (United States)

Chen, Hongming; Carlsson, Lars; Eriksson, Mats; Varkonyi, Peter; Norinder, Ulf; Nilsson, Ingemar

2013-06-24

A novel methodology was developed to build Free-Wilson like local QSAR models by combining R-group signatures and the SVM algorithm. Unlike Free-Wilson analysis this method is able to make predictions for compounds with R-groups not present in a training set. Eleven public data sets were chosen as test cases for comparing the performance of our new method with several other traditional modeling strategies, including Free-Wilson analysis. Our results show that the R-group signature SVM models achieve better prediction accuracy compared with Free-Wilson analysis in general. Moreover, the predictions of R-group signature models are also comparable to the models using ECFP6 fingerprints and signatures for the whole compound. Most importantly, R-group contributions to the SVM model can be obtained by calculating the gradient for R-group signatures. For most of the studied data sets, a significant correlation with that of a corresponding Free-Wilson analysis is shown. These results suggest that the R-group contribution can be used to interpret bioactivity data and highlight that the R-group signature based SVM modeling method is as interpretable as Free-Wilson analysis. Hence the signature SVM model can be a useful modeling tool for any drug discovery project.

Wilson's disease: two treatment modalities. Correlations to pretreatment and posttreatment brain MRI

Energy Technology Data Exchange (ETDEWEB)

Leiros da Costa, Maria do Desterro [Federal University of Paraiba, Movement Disorders Unit, Paraiba (Brazil); Spitz, Mariana; Bacheschi, Luiz Alberto; Barbosa, Egberto Reis [University of Sao Paulo, Movement Disorders Unit, Sao Paulo (Brazil); Leite, Claudia Costa; Lucato, Leandro Tavares [University of Sao Paulo, Department of Radiology, Sao Paulo (Brazil)

2009-10-15

Brain magnetic resonance imaging (MRI) studies on Wilson's disease (WD) show lack of correlations between neurological and neuroimaging features. Long-term follow-up reports with sequential brain MRI in patients with neurological WD comparing different modalities of treatment are scarce. Eighteen patients with neurological WD underwent pretreatment and posttreatment brain MRI scans to evaluate the range of abnormalities and the evolution along these different periods. All patients underwent at least two MRI scans at different intervals, up to 11 years after the beginning of treatment. MRI findings were correlated with clinical picture, clinical severity, duration of neurological symptoms, and treatment with two different drugs. Patients were divided into two groups according to treatment: d-penicillamine (D-P), zinc (Zn), and Zn after the onset of severe intolerance to D-P. MRI scans before treatment showed, in all patients, hypersignal intensity lesions on T2- and proton-density-weighted images bilaterally and symmetrically at basal nuclei, thalamus, brain stem, cerebellum, brain cortex, and brain white matter. The most common neurological symptoms were: dysarthria, parkinsonism, dystonia, tremor, psychiatric disturbances, dysphagia, risus sardonicus, ataxia, chorea, and athetosis. From the neurological point of view, there was no difference on the evolution between the group treated exclusively with D-P and the one treated with Zn. Analysis of MRI scans with longer intervals after the beginning of treatment depicted a trend for neuroimaging worsening, without neurological correspondence, among patients treated with Zn. Neuroimaging pattern of evolution was more favorable for the group that received exclusively D-P. (orig.)

Wilson loops in 5d $\\mathcal{N}=1$ theories and S-duality arXiv

CERN Document Server

Assel, Benjamin

We study the action of S-duality on half-BPS Wilson loop operators in 5d $\\mathcal{N}=1$ theories. The duality is the statement that different massive deformations of a single 5d SCFT are described by different gauge theories, or equivalently that the SCFT points in parameter space of two gauge theories coincide. The pairs of dual theories that we study are realized by brane webs in type IIB string theory that are S-dual to each other. We focus on $SU(2)$ SQCD theories with $N_f \\le 4$ flavors, which are self-dual, and on $SU(3)$ SQCD theories, which are dual to $SU(2)^2$ quiver theories. From string theory engineering we predict that Wilson loops are mapped to dual Wilson loops under S-duality. We confirm the predictions with exact computations of Wilson loop VEVs, which we extract from the 5d half-index in the presence of auxiliary loop operators (also known as higher qq-characters) sourced by D3 branes placed in the brane webs. A special role is played by Wilson loops in tensor products of the (anti)fundam...

Nambu-Jona-Lasinio model with Wilson fermions

DEFF Research Database (Denmark)

Rantaharju, Jarno; Drach, Vincent; Pica, Claudio

2017-01-01

We present a lattice study of a Nambu-Jona-Lasinio (NJL) model using Wilson fermions. Four-fermion interactions are a natural part of several extensions of the Standard Model, appearing as a low-energy description of a more fundamental theory. In models of dynamical electroweak symmetry breaking...

The Observatory as Laboratory: Spectral Analysis at Mount Wilson Observatory

Science.gov (United States)

Brashear, Ronald

2018-01-01

This paper will discuss the seminal changes in astronomical research practices made at the Mount Wilson Observatory in the early twentieth century by George Ellery Hale and his staff. Hale’s desire to set the agenda for solar and stellar astronomical research is often described in terms of his new telescopes, primarily the solar tower observatories and the 60- and 100-inch telescopes on Mount Wilson. This paper will focus more on the ancillary but no less critical parts of Hale’s research mission: the establishment of associated “physical” laboratories as part of the observatory complex where observational spectral data could be quickly compared with spectra obtained using specialized laboratory equipment. Hale built a spectroscopic laboratory on the mountain and a more elaborate physical laboratory in Pasadena and staffed it with highly trained physicists, not classically trained astronomers. The success of Hale’s vision for an astronomical observatory quickly made the Carnegie Institution’s Mount Wilson Observatory one of the most important astrophysical research centers in the world.

Analysis of the robustness of network-based disease-gene prioritization methods reveals redundancy in the human interactome and functional diversity of disease-genes.

Directory of Open Access Journals (Sweden)

Emre Guney

Full Text Available Complex biological systems usually pose a trade-off between robustness and fragility where a small number of perturbations can substantially disrupt the system. Although biological systems are robust against changes in many external and internal conditions, even a single mutation can perturb the system substantially, giving rise to a pathophenotype. Recent advances in identifying and analyzing the sequential variations beneath human disorders help to comprehend a systemic view of the mechanisms underlying various disease phenotypes. Network-based disease-gene prioritization methods rank the relevance of genes in a disease under the hypothesis that genes whose proteins interact with each other tend to exhibit similar phenotypes. In this study, we have tested the robustness of several network-based disease-gene prioritization methods with respect to the perturbations of the system using various disease phenotypes from the Online Mendelian Inheritance in Man database. These perturbations have been introduced either in the protein-protein interaction network or in the set of known disease-gene associations. As the network-based disease-gene prioritization methods are based on the connectivity between known disease-gene associations, we have further used these methods to categorize the pathophenotypes with respect to the recoverability of hidden disease-genes. Our results have suggested that, in general, disease-genes are connected through multiple paths in the human interactome. Moreover, even when these paths are disturbed, network-based prioritization can reveal hidden disease-gene associations in some pathophenotypes such as breast cancer, cardiomyopathy, diabetes, leukemia, parkinson disease and obesity to a greater extend compared to the rest of the pathophenotypes tested in this study. Gene Ontology (GO analysis highlighted the role of functional diversity for such diseases.

Parton densities in quantum chromodynamics gauge invariance, path-dependence and Wilson lines

CERN Document Server

Cherednikov, Igor O

2016-01-01

The purpose of this book is to give a systematic pedagogical exposition of the quantitative analysis of Wilson lines and loops in quantum chromodynamics. Using techniques from the previous volume (Wilson Lines in Quantum Field Theory, 2014), ab initio techniques are developed and practical tools for their implementation presented. An emphasis is put on their renormalization and on implications on processes observable at experimental facilities.

Symmetries of Maldacena-Wilson loops from integrable string theory

International Nuclear Information System (INIS)

Muenkler, Hagen

2017-01-01

This thesis discusses hidden symmetries within N=4 supersymmetric Yang-Mills theory or its AdS/CFT dual, string theory in AdS 5 x S 5 . Here, we focus on the Maldacena-Wilson loop, which is a suitable object for this study since its vacuum expectation value is finite for smooth contours and the conjectured duality to scattering amplitudes provides a conceptual path to transfer its symmetries to other observables. Its strong-coupling description via minimal surfaces in AdS 5 allows to construct the symmetries from the integrability of the underlying classical string theory. This approach has been utilized before to derive a strong-coupling Yangian symmetry of the Maldacena-Wilson loop and describe equiareal deformations of minimal surfaces in AdS 3 . These two findings are connected and extended in the present thesis. In order to discuss the symmetries systematically, we first discuss the symmetry structure of the underlying string model. The discussion can be generalized to the discussion of generic symmetric space models. For these, we find that the symmetry which generates the equiareal deformations of minimal surfaces in AdS 3 has a central role in the symmetry structure of the model: It acts as a raising operator on the infinite tower of conserved charges, thus generating the spectral parameter, and can be employed to construct all symmetry variations from the global symmetry of the model. It is thus referred to as the master symmetry of symmetric space models. Additionally, the algebra of the symmetry variations and the conserved charges is worked out. For the concrete case of minimal surfaces in AdS 5 , we discuss the deformation of the four-cusp solution, which provides the dual description of the four-gluon scattering amplitude. This marks the first step toward transferring the master symmetry to scattering amplitudes. Moreover, we compute the master and Yangian symmetry variations of generic, smooth boundary curves. The results leads to a coupling

Symmetries of Maldacena-Wilson loops from integrable string theory

Energy Technology Data Exchange (ETDEWEB)

Muenkler, Hagen

2017-09-11

This thesis discusses hidden symmetries within N=4 supersymmetric Yang-Mills theory or its AdS/CFT dual, string theory in AdS{sub 5} x S{sup 5}. Here, we focus on the Maldacena-Wilson loop, which is a suitable object for this study since its vacuum expectation value is finite for smooth contours and the conjectured duality to scattering amplitudes provides a conceptual path to transfer its symmetries to other observables. Its strong-coupling description via minimal surfaces in AdS{sub 5} allows to construct the symmetries from the integrability of the underlying classical string theory. This approach has been utilized before to derive a strong-coupling Yangian symmetry of the Maldacena-Wilson loop and describe equiareal deformations of minimal surfaces in AdS{sub 3}. These two findings are connected and extended in the present thesis. In order to discuss the symmetries systematically, we first discuss the symmetry structure of the underlying string model. The discussion can be generalized to the discussion of generic symmetric space models. For these, we find that the symmetry which generates the equiareal deformations of minimal surfaces in AdS{sub 3} has a central role in the symmetry structure of the model: It acts as a raising operator on the infinite tower of conserved charges, thus generating the spectral parameter, and can be employed to construct all symmetry variations from the global symmetry of the model. It is thus referred to as the master symmetry of symmetric space models. Additionally, the algebra of the symmetry variations and the conserved charges is worked out. For the concrete case of minimal surfaces in AdS{sub 5}, we discuss the deformation of the four-cusp solution, which provides the dual description of the four-gluon scattering amplitude. This marks the first step toward transferring the master symmetry to scattering amplitudes. Moreover, we compute the master and Yangian symmetry variations of generic, smooth boundary curves. The results

Breeding habitat use by sympatric and allopatric populations of Wilson's Warblers and Yellow Warblers

Science.gov (United States)

Ruth, J.M.; Stanley, T.R.

2002-01-01

We studied Wilson's Warbler (Wilsonia pusilla) and Yellow Warbler (Dendroica petechia) habitat use in allopatric and sympatric populations in the Rocky Mountains of northern Colorado and southeastern Wyoming in order to better understand the different habitat needs and interactions of these two species. Foraging Wilson's Warblers and Yellow Warblers used very similar habitat, both selecting larger, more open shrubs. In spite of similar foraging habitat, comparisons of habitat use by the two species at the sympatric sites yielded no evidence of foraging habitat partitioning or exclusion. There was evidence of nesting habitat partitioning. Wilson's Warblers nested on the ground, with some evidence that they used smaller, more densely stemmed shrubs under which to nest. Yellow Warblers are shrub nesters and selected larger, more open shrubs in which to nest. Results provide no evidence that Yellow Warblers can be blamed for population declines in Wilson's Warblers.

Notes on winter feeding behavior and molt in Wilson's phalaropes

Science.gov (United States)

Burger, J.; Howe, M.

1975-01-01

Wilson's Phalaropes, Steganopus tricolor, migrate in late summer from the prairie regions of North America to their wintering grounds in the highlands of Peru and the inland and coastal waters of Chile, Bolivia, Paraguay, Uruguay, and Argentina (Holmes 1939, Meyer de Schauensee 1970). Reports on these birds from their wintering habitat are few. This paper describes numbers, feeding behavior, and molt of Wilson's Phalaropes wintering in a freshwater marsh in central Argentina. Fieldwork in Argentina was conducted by the senior author. The junior author analyzed molt patterns of birds collected there and added data he collected in North Dakota in 1968 and 1969.

Nonalcoholic Fatty Liver Disease & NASH

Science.gov (United States)

... Eating, Diet, & Nutrition Clinical Trials Wilson Disease Nonalcoholic Fatty Liver Disease & NASH View or Print All Sections Definition & Facts Nonalcoholic fatty liver disease (NAFLD) is a condition in which fat ...

Neural Inductive Matrix Completion for Predicting Disease-Gene Associations

KAUST Repository

Hou, Siqing

2018-05-21

In silico prioritization of undiscovered associations can help find causal genes of newly discovered diseases. Some existing methods are based on known associations, and side information of diseases and genes. We exploit the possibility of using a neural network model, Neural inductive matrix completion (NIMC), in disease-gene prediction. Comparing to the state-of-the-art inductive matrix completion method, using neural networks allows us to learn latent features from non-linear functions of input features. Previous methods use disease features only from mining text. Comparing to text mining, disease ontology is a more informative way of discovering correlation of dis- eases, from which we can calculate the similarities between diseases and help increase the performance of predicting disease-gene associations. We compare the proposed method with other state-of-the-art methods for pre- dicting associated genes for diseases from the Online Mendelian Inheritance in Man (OMIM) database. Results show that both new features and the proposed NIMC model can improve the chance of recovering an unknown associated gene in the top 100 predicted genes. Best results are obtained by using both the new features and the new model. Results also show the proposed method does better in predicting associated genes for newly discovered diseases.

DISEASES: text mining and data integration of disease-gene associations.

Science.gov (United States)

Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi; Binder, Janos X; Jensen, Lars Juhl

2015-03-01

Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition of human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should not stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases. The DISEASES resource is accessible through a web interface at http://diseases.jensenlab.org/, where the text-mining software and all associations are also freely available for download. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Wilson loops, instantons and quantum mechanics

International Nuclear Information System (INIS)

Schiereck, Marc

2014-05-01

In this thesis we examine two different problems. The first is the computation of vacuum expectation values of Wilson loop operators in ABJM theory, the other problem is finding the instanton series of the refined topological string on certain local Calabi-Yau geometries in the Nekrasov-Shatashvili limit. Based on the description of ABJM theory as a matrix model, it is possible to find a description of it in terms of an ideal Fermi gas with a non-trivial one-particle Hamiltonian. The vacuum-expectation-values of Wilson loop operators in ABJM theory correspond to averages of operators in the statistical-mechanical problem. Using the WKB expansion, it is possible to extract the full 1/N expansion of the vevs, up to exponentially small contributions, for arbitrary Chern-Simons coupling. We compute these vevs for the 1/6 and 1/2 BPS Wilson loops at any winding number. These can be written in terms of the Airy function. The expressions we found reproduce the low genus results previously obtained in the 't Hooft expansion. In another problem we use mirror symmetry, quantum geometry and modularity properties of elliptic curves to calculate the refined free energies, given in terms of an instanton sum, in the Nekrasov-Shatashvili limit on non-compact toric Calabi-Yau manifolds, based on del Pezzo surfaces. Quantum geometry here is to be understood as a quantum deformed version of rigid special geometry, which has its origin in the quantum mechanical behavior of branes in the topological string B-model. We argue that in the Seiberg-Witten picture only the Coulomb parameters lead to quantum corrections, while the mass parameters remain uncorrected. In certain cases we also compute the expansion of the free energies at the orbifold point and the conifold locus. We compute the quantum corrections order by order on ℎ by deriving second order differential operators, which act on the classical periods.

Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

Science.gov (United States)

Escott-Price, Valentina; Bellenguez, Céline; Wang, Li-San; Choi, Seung-Hoan; Harold, Denise; Jones, Lesley; Holmans, Peter; Gerrish, Amy; Vedernikov, Alexey; Richards, Alexander; DeStefano, Anita L; Lambert, Jean-Charles; Ibrahim-Verbaas, Carla A; Naj, Adam C; Sims, Rebecca; Jun, Gyungah; Bis, Joshua C; Beecham, Gary W; Grenier-Boley, Benjamin; Russo, Giancarlo; Thornton-Wells, Tricia A; Denning, Nicola; Smith, Albert V; Chouraki, Vincent; Thomas, Charlene; Ikram, M Arfan; Zelenika, Diana; Vardarajan, Badri N; Kamatani, Yoichiro; Lin, Chiao-Feng; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L; Vronskaya, Maria; Johnson, Andrew D; Ruiz, Agustin; Bihoreau, Marie-Thérèse; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Hanon, Olivier; Fitzpatrick, Annette L; Buxbaum, Joseph D; Campion, Dominique; Crane, Paul K; Baldwin, Clinton; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L; De Jager, Philip L; Deramecourt, Vincent; Johnston, Janet A; Evans, Denis; Lovestone, Simon; Letenneur, Luc; Hernández, Isabel; Rubinsztein, David C; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M; Fiévet, Nathalie; Huentelman, Matthew J; Gill, Michael; Brown, Kristelle; Kamboh, M Ilyas; Keller, Lina; Barberger-Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B; Myers, Amanda J; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Rogaeva, Ekaterina; Gallacher, John; George-Hyslop, Peter St; Clarimon, Jordi; Lleo, Alberto; Bayer, Anthony; Tsuang, Debby W; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petra; Collinge, John; Sorbi, Sandro; Garcia, Florentino Sanchez; Fox, Nick C; Hardy, John; Naranjo, Maria Candida Deniz; Bosco, Paolo; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Scarpini, Elio; Bonuccelli, Ubaldo; Mancuso, Michelangelo; Siciliano, Gabriele; Moebus, Susanne; Mecocci, Patrizia; Zompo, Maria Del; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Frank-García, Ana; Panza, Francesco; Solfrizzi, Vincenzo; Caffarra, Paolo; Nacmias, Benedetta; Perry, William; Mayhaus, Manuel; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M; Ingelsson, Martin; Beekly, Duane; Alvarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G; Coto, Eliecer; Hamilton-Nelson, Kara L; Gu, Wei; Razquin, Cristina; Pastor, Pau; Mateo, Ignacio; Owen, Michael J; Faber, Kelley M; Jonsson, Palmi V; Combarros, Onofre; O'Donovan, Michael C; Cantwell, Laura B; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H; Bennett, David A; Harris, Tamara B; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee F A G; Passmore, Peter; Montine, Thomas J; Bettens, Karolien; Rotter, Jerome I; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M; Kukull, Walter A; Hannequin, Didier; Powell, John F; Nalls, Michael A; Ritchie, Karen; Lunetta, Kathryn L; Kauwe, John S K; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R; Schmidt, Reinhold; Rujescu, Dan; Dartigues, Jean-François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M; Graff, Caroline; Psaty, Bruce M; Haines, Jonathan L; Lathrop, Mark; Pericak-Vance, Margaret A; Launer, Lenore J; Van Broeckhoven, Christine; Farrer, Lindsay A; van Duijn, Cornelia M; Ramirez, Alfredo; Seshadri, Sudha; Schellenberg, Gerard D; Amouyel, Philippe; Williams, Julie

2014-01-01

Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) which indexed novel susceptibility loci. The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Valentina Escott-Price

Full Text Available Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6 and 14 (IGHV1-67 p = 7.9×10-8 which indexed novel susceptibility loci.The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

Prioritization of candidate disease genes by topological similarity between disease and protein diffusion profiles.

Science.gov (United States)

Zhu, Jie; Qin, Yufang; Liu, Taigang; Wang, Jun; Zheng, Xiaoqi

2013-01-01

Identification of gene-phenotype relationships is a fundamental challenge in human health clinic. Based on the observation that genes causing the same or similar phenotypes tend to correlate with each other in the protein-protein interaction network, a lot of network-based approaches were proposed based on different underlying models. A recent comparative study showed that diffusion-based methods achieve the state-of-the-art predictive performance. In this paper, a new diffusion-based method was proposed to prioritize candidate disease genes. Diffusion profile of a disease was defined as the stationary distribution of candidate genes given a random walk with restart where similarities between phenotypes are incorporated. Then, candidate disease genes are prioritized by comparing their diffusion profiles with that of the disease. Finally, the effectiveness of our method was demonstrated through the leave-one-out cross-validation against control genes from artificial linkage intervals and randomly chosen genes. Comparative study showed that our method achieves improved performance compared to some classical diffusion-based methods. To further illustrate our method, we used our algorithm to predict new causing genes of 16 multifactorial diseases including Prostate cancer and Alzheimer's disease, and the top predictions were in good consistent with literature reports. Our study indicates that integration of multiple information sources, especially the phenotype similarity profile data, and introduction of global similarity measure between disease and gene diffusion profiles are helpful for prioritizing candidate disease genes. Programs and data are available upon request.

The Modern First Lady and Public Policy: From Edith Wilson through Hillary Rodham Clinton.

Science.gov (United States)

Black, Allida M.

2001-01-01

Discusses the role in and influence on public policy of twentieth century First Ladies including Edith Roosevelt, Helen Taft, Ellen Wilson, Edith Wilson, Florence Harding, Lou Henry Hoover, Eleanor Roosevelt, Jacqueline Kennedy, Lady Bird Johnson, Rosalynn Carter, Nancy Reagan, Barbara Bush, and Hillary Rodham Clinton. (CMK)

Exploring the potential relevance of human-specific genes to complex disease

Directory of Open Access Journals (Sweden)

Cooper David N

2011-01-01

Full Text Available Abstract Although human disease genes generally tend to be evolutionarily more ancient than non-disease genes, complex disease genes appear to be represented more frequently than Mendelian disease genes among genes of more recent evolutionary origin. It is therefore proposed that the analysis of human-specific genes might provide new insights into the genetics of complex disease. Cross-comparison with the Human Gene Mutation Database (http://www.hgmd.org revealed a number of examples of disease-causing and disease-associated mutations in putatively human-specific genes. A sizeable proportion of these were missense polymorphisms associated with complex disease. Since both human-specific genes and genes associated with complex disease have often experienced particularly rapid rates of evolutionary change, either due to weaker purifying selection or positive selection, it is proposed that a significant number of human-specific genes may play a role in complex disease.

Interference, heterogeneity and disease gene mapping

Energy Technology Data Exchange (ETDEWEB)

Keats, B. [Louisiana State Univ. Medical Center, New Orleans, LA (United States)

1996-12-31

The Human Genome Project has had a major impact on genetic research over the past five years. The number of mapped genes is now over 3,000 compared with approximately 1,600 in 1989 and only about 260 ten years before that. The realization that extensive variation could be detected in anonymous DNA segments greatly enhanced the potential for mapping by linkage analysis. Previously, linkage studies had depended on polymorphisms that could be detected in red blood cell antigens, proteins (revealed by electrophoresis and isoelectric focusing), and cytogenetic heteromorphisms. The identification of thousands of polymorphic DNA markers throughout the human genome has led to the construction of high density genetic linkage maps. These maps provide the data necessary to test hypotheses concerning differences in recombination rates and levels of interference. They are also important for disease gene mapping because the existence of these genes must be inferred from the phenotype. Showing linkage of a disease gene to a DNA marker is the first step towards isolating the disease gene, determining its protein product, and developing effective therapies. However, interpretation of results is not always straightforward. Factors such as etiological heterogeneity and undetected irregular segregation can lead to confusing linkage results and incorrect conclusions about the locations of disease genes. This paper will discuss these phenomena and present examples that illustrate the problems, as well as approaches to dealing with them. 23 refs., 3 figs., 3 tabs.

An Approach to Enforcing Clark-Wilson Model in Role-based Access Control Model

Institute of Scientific and Technical Information of China (English)

LIANGBin; SHIWenchang; SUNYufang; SUNBo

2004-01-01

Using one security model to enforce another is a prospective solution to multi-policy support. In this paper, an approach to the enforcing Clark-Wilson data integrity model in the Role-based access control (RBAC) model is proposed. An enforcement construction with great feasibility is presented. In this construction, a direct way to enforce the Clark-Wilson model is provided, the corresponding relations among users, transformation procedures, and constrained data items are strengthened; the concepts of task and subtask are introduced to enhance the support to least-privilege. The proposed approach widens the applicability of RBAC. The theoretical foundation for adopting Clark-Wilson model in a RBAC system with small cost is offered to meet the requirements of multi-policy support and policy flexibility.

Partially quenched lattice QCD with two degenerate dynamical light Wilson quarks

International Nuclear Information System (INIS)

De, Asit K.; Harindranath, A.; Maiti, Jyotirmoy

2006-01-01

We present our results of numerical studies of partially quenched latticed QCD with two degenerate flavors of dynamical quarks. Gauge configurations are generated with Wilson gauge action and tadpole improved Wilson fermions at β = 5.6 and K sea = 0.155, 0.156, 0.157 and 0.158. Suitably smeared gauge configurations are used to calculate the static interquark potential in order to set the physical scale. Mesonic propagators are calculated at above mentioned four different values of K val for each K sea . We present results for pion and rho masses. (author)

Extensions of the Wilson-Bappu effect among very luminous stars

International Nuclear Information System (INIS)

Stencel, R.E.

1978-01-01

Wilson and Bappu (1957) published their observational correlation of Msub(v) and the logarithm of the full width at half maximum of the CaII K-line central emission for G, K and M stars. The accuracy makes the approach valuable for late-type supergiants since other methods suffer from comparable errors. However, for F through M supergiants (Ia, O), circumstellar absorption obscures the chromospheric K-line core emission and excludes such objects from the Wilson-Bappu correlation. The author reports on a new class of emission lines in late-type giant and supergiant spectra that exhibit Msub(v) correlated widths, yet are detectable among the brightest stars. (Auth.)

SU(3) sextet model with Wilson fermions

DEFF Research Database (Denmark)

Hansen, Martin; Drach, Vincent; Pica, Claudio

2017-01-01

to be inside or very close to the lower boundary of the conformal window. We use the Wilson discretization for the fermions and map the phase structure of the lattice model. We study several spectral and gradient flow observables both in the bulk and the weak coupling phases. While in the bulk phase we find...

Improved quasi parton distribution through Wilson line renormalization

Energy Technology Data Exchange (ETDEWEB)

Chen, Jiunn-Wei [Department of Physics, Center for Theoretical Sciences, and Leung Center for Cosmology and Particle Astrophysics, National Taiwan University, Taipei, 106, Taiwan (China); Center for Theoretical Physics, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Ji, Xiangdong [INPAC, Department of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai, 200240 (China); Maryland Center for Fundamental Physics, Department of Physics, University of Maryland, College Park, MD 20742 (United States); Zhang, Jian-Hui, E-mail: jianhui.zhang@physik.uni-regensburg.de [Institut für Theoretische Physik, Universität Regensburg, D-93040 Regensburg (Germany)

2017-02-15

Recent developments showed that hadron light-cone parton distributions could be directly extracted from spacelike correlators, known as quasi parton distributions, in the large hadron momentum limit. Unlike the normal light-cone parton distribution, a quasi parton distribution contains ultraviolet (UV) power divergence associated with the Wilson line self energy. We show that to all orders in the coupling expansion, the power divergence can be removed by a “mass” counterterm in the auxiliary z-field formalism, in the same way as the renormalization of power divergence for an open Wilson line. After adding this counterterm, the quasi quark distribution is improved such that it contains at most logarithmic divergences. Based on a simple version of discretized gauge action, we present the one-loop matching kernel between the improved non-singlet quasi quark distribution with a lattice regulator and the corresponding quark distribution in dimensional regularization.

Improved quasi parton distribution through Wilson line renormalization

Directory of Open Access Journals (Sweden)

Jiunn-Wei Chen

2017-02-01

Full Text Available Recent developments showed that hadron light-cone parton distributions could be directly extracted from spacelike correlators, known as quasi parton distributions, in the large hadron momentum limit. Unlike the normal light-cone parton distribution, a quasi parton distribution contains ultraviolet (UV power divergence associated with the Wilson line self energy. We show that to all orders in the coupling expansion, the power divergence can be removed by a “mass” counterterm in the auxiliary z-field formalism, in the same way as the renormalization of power divergence for an open Wilson line. After adding this counterterm, the quasi quark distribution is improved such that it contains at most logarithmic divergences. Based on a simple version of discretized gauge action, we present the one-loop matching kernel between the improved non-singlet quasi quark distribution with a lattice regulator and the corresponding quark distribution in dimensional regularization.

Recent progress on the calculation of three-loop heavy flavor Wilson coefficients in deep-inelastic scattering

International Nuclear Information System (INIS)

Ablinger, J.; Hasselhuhn, A.; Schneider, C.; Behring, A.; Bluemlein, J.; Freitas, A. de; Raab, C.; Round, M.; Manteuffel, A. von

2014-07-01

We report on our latest results in the calculation of the three-loop heavy flavor contributions to the Wilson coefficients in deep-inelastic scattering in the asymptotic region Q 2 >>m 2 . We discuss the different methods used to compute the required operator matrix elements and the corresponding Feynman integrals. These methods very recently allowed us to obtain a series of new operator matrix elements and Wilson coefficients like the flavor non-singlet and pure singlet Wilson coefficients.

Olin C. Wilson (1909-1994)

Science.gov (United States)

Preston, George W.

1995-02-01

Congenial, fiercely independent, and firmly grounded in the virtues of experimental science, Olin Wilson was a canny practitioner of the art of the possible in observational astrophysics as it flourished in the middle of the 20th century. He enjoyed a long association with the Astronomical Society of the Pacific as a contributor to its Publications, as President of the Society, and as recipient of its Catherine Wolfe Bruce Medal. By the time he departed, stellar astrophysics had matured and had acquired new dimensions due to Olin's diligence and curiosity. (SECTION: Obituary)

Recent progress on the calculation of three-loop heavy flavor Wilson coefficients in deep-inelastic scattering

Energy Technology Data Exchange (ETDEWEB)

Ablinger, J.; Hasselhuhn, A.; Schneider, C. [Johannes Kepler Univ., Linz (Austria). Research Inst. for Symbolic Computation (RISC); Behring, A.; Bluemlein, J.; Freitas, A. de; Raab, C.; Round, M. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Manteuffel, A. von [Mainz Univ. (Germany). PRISMA Cluster of Excellence; Wissbrock, F. [Johannes Kepler Univ., Linz (Austria). Research Inst. for Symbolic Computation (RISC); Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); IHES Institut des Hautes Etudes Scientifiques, Bures-sur-Yvette (France)

2014-07-15

We report on our latest results in the calculation of the three-loop heavy flavor contributions to the Wilson coefficients in deep-inelastic scattering in the asymptotic region Q{sup 2}>>m{sup 2}. We discuss the different methods used to compute the required operator matrix elements and the corresponding Feynman integrals. These methods very recently allowed us to obtain a series of new operator matrix elements and Wilson coefficients like the flavor non-singlet and pure singlet Wilson coefficients.

The value-adding CFO: an interview with Disney's Gary Wilson. Interview by Geraldine E. Willigan.

Science.gov (United States)

Wilson, G

1990-01-01

Financing a company is more complex than ever-and more important to its economic success. The demands on a CFO are tremendous. Optimizing capital costs requires an unprecedented level of technical sophistication. Yet the best CFOs today are not mere technicians. They are also strategists and innovators. Gary Wilson exemplifies the new CFO. In his 5 years as executive vice president and CFO of the Walt Disney Company and his 12 years at Marriott Corporation, he has shown how the finance function can add value-not just account for it. How does a CFO create value for shareholders? "Just like all the great marketing and operating executives," Wilson says, "by being creative." To Wilson, being creative means rethinking assumptions and finding clever ways to achieve financial and strategic goals. Some of Wilson's innovative deal making-like the off-balance-sheet financing he used at Marriott-is well known. At Marriott, he discovered the power of separating the ownership of an asset from its control. Marriott's strength was in operations, yet the company had a great deal of money tied up in real estate. Growth would require even more investment in real estate. Wilson's solution was to sell the hotels-in effect, removing them and the debt used to finance them from the balance sheet-and contract to operate them. In this interview, Wilson gives his view of the role of finance in today's corporation and explains the thinking behind some of the successful deals he has engineered-including Disney's Silver Screen movie-making partnerships and Euro Disneyland.

Search for Activity in Comet-Asteroid Transition Object 107P/Wilson-Harrington

Science.gov (United States)

Khayat, Alain; Meech, K.; Pittichova, J.; Schorghofer, N.; Yang, B.; Sonnett, S.; Riesen, T.; Kleyna, J.; Kaluna, H.; Keane, J.

2010-10-01

Comet-asteroid transition object 107P/Wilson-Harrington was observed near its October 22, 2009 perihelion passage to search for activity. No activity was detected. Consequently, we place limits on possible dust production of 0.013 kg/s at 1.23 AU. Furthermore, the data was not sufficient to constrain a rotation period; however, it is clear that the rotation period is > 4hr. Our data is consistent with the observations of others (6.1 hr). Phase function fitting yielded a value of the phase coefficient beta= 0.0406 ± .0001 mag/deg, similar to C-type asteroids that have a linear phase curve at large phase angles. Thermal models for 107P/Wilson-Harrington show that the average loss rate of exposed crystalline ice at zero latitude is in the order of 0.3 meters/year. The derived high loss rate suggests that 107P/Wilson-Harrington is deprived of surface ice. Our observations and analysis confirm earlier findings that 107P/Wilson-Harrington is an example of the very few such objects discovered so far. Such study we made is a critical next step in understanding the life of dormant comets, and a window into the evolutionary end states of the lives of comets that become extinct. This work has been supported in part by AST-0807521 from the National Science Foundation.

A Gene Module-Based eQTL Analysis Prioritizing Disease Genes and Pathways in Kidney Cancer

Directory of Open Access Journals (Sweden)

Mary Qu Yang

Full Text Available Clear cell renal cell carcinoma (ccRCC is the most common and most aggressive form of renal cell cancer (RCC. The incidence of RCC has increased steadily in recent years. The pathogenesis of renal cell cancer remains poorly understood. Many of the tumor suppressor genes, oncogenes, and dysregulated pathways in ccRCC need to be revealed for improvement of the overall clinical outlook of the disease. Here, we developed a systems biology approach to prioritize the somatic mutated genes that lead to dysregulation of pathways in ccRCC. The method integrated multi-layer information to infer causative mutations and disease genes. First, we identified differential gene modules in ccRCC by coupling transcriptome and protein-protein interactions. Each of these modules consisted of interacting genes that were involved in similar biological processes and their combined expression alterations were significantly associated with disease type. Then, subsequent gene module-based eQTL analysis revealed somatic mutated genes that had driven the expression alterations of differential gene modules. Our study yielded a list of candidate disease genes, including several known ccRCC causative genes such as BAP1 and PBRM1, as well as novel genes such as NOD2, RRM1, CSRNP1, SLC4A2, TTLL1 and CNTN1. The differential gene modules and their driver genes revealed by our study provided a new perspective for understanding the molecular mechanisms underlying the disease. Moreover, we validated the results in independent ccRCC patient datasets. Our study provided a new method for prioritizing disease genes and pathways. Keywords: ccRCC, Causative mutation, Pathways, Protein-protein interaction, Gene module, eQTL

Wilson loops in very high order lattice perturbation theory

International Nuclear Information System (INIS)

Ilgenfritz, E.M.; Nakamura, Y.; Perlt, H.; Schiller, A.; Rakow, P.E.L.; Schierholz, G.; Regensburg Univ.

2009-10-01

We calculate Wilson loops of various sizes up to loop order n=20 for lattice sizes of L 4 (L=4,6,8,12) using the technique of Numerical Stochastic Perturbation Theory in quenched QCD. This allows to investigate the behaviour of the perturbative series at high orders. We discuss three models to estimate the perturbative series: a renormalon inspired fit, a heuristic fit based on an assumed power-law singularity and boosted perturbation theory. We have found differences in the behavior of the perturbative series for smaller and larger Wilson loops at moderate n. A factorial growth of the coefficients could not be confirmed up to n=20. From Monte Carlo measured plaquette data and our perturbative result we estimate a value of the gluon condensate left angle (α)/(π)GG right angle. (orig.)

Uncovering the triple omeron vertex from Wilson line formalism

International Nuclear Information System (INIS)

Chirilli, G. A.; Szymanowski, L.; Wallon, S.

2011-01-01

We compute the triple omeron vertex from the Wilson line formalism, including both planar and nonplanar contributions, and get perfect agreement with the result obtained in the Extended Generalized Logarithmic Approximation based on Reggeon calculus.

Biomedical Information Extraction: Mining Disease Associated Genes from Literature

Science.gov (United States)

Huang, Zhong

2014-01-01

Disease associated gene discovery is a critical step to realize the future of personalized medicine. However empirical and clinical validation of disease associated genes are time consuming and expensive. In silico discovery of disease associated genes from literature is therefore becoming the first essential step for biomarker discovery to…

Genetics Home Reference: Hirschsprung disease

Science.gov (United States)

... occur in combination with other conditions, such as Waardenburg syndrome , type IV; Mowat-Wilson syndrome ; or congenital central ... Disease MalaCards: hirschsprung disease 1 Orphanet: Hirschsprung disease Patient Support and Advocacy Resources (4 links) Bowel Group ...

"Mens Sana in Corpore Sano": Human Values in Thomas Wilson's "The Arte of Rhetorique."

Science.gov (United States)

Luehring, Janet

In 1553 the work that is touted as the first complete book written in English on rhetoric was published, Thomas Wilson's "Arte of Rhetorique." It became so popular it enjoyed eight printings within its century. Wilson was not a person to translate and read just for knowledge; he believed that knowledge should be imparted to the general…

Meson masses in electromagnetic fields with Wilson fermions

Science.gov (United States)

Bali, G. S.; Brandt, B. B.; Endrődi, G.; Gläßle, B.

2018-02-01

We determine the light meson spectrum in QCD in the presence of background magnetic fields using quenched Wilson fermions. Our continuum extrapolated results indicate a monotonous reduction of the connected neutral pion mass as the magnetic field grows. The vector meson mass is found to remain nonzero, a finding relevant for the conjectured ρ -meson condensation at strong magnetic fields. The continuum extrapolation was facilitated by adding a novel magnetic field-dependent improvement term to the additive quark mass renormalization. Without this term, sizable lattice artifacts that would deceptively indicate an unphysical rise of the connected neutral pion mass for strong magnetic fields are present. We also investigate the impact of these lattice artifacts on further observables like magnetic polarizabilities and discuss the magnetic field-induced mixing between ρ -mesons and pions. We also derive Ward-Takashi identities for QCD +QED both in the continuum formulation and for (order a -improved) Wilson fermions.

On strong-coupling correlation functions of circular Wilson loops and local operators

International Nuclear Information System (INIS)

Alday, Luis F; Tseytlin, Arkady A

2011-01-01

Motivated by the problem of understanding 3-point correlation functions of gauge-invariant operators in N=4 super Yang-Mills theory we consider correlators involving Wilson loops and a 'light' operator with fixed quantum numbers. At leading order in the strong-coupling expansion such correlators are given by the 'light' vertex operator evaluated on a semiclassical string world surface ending on the corresponding loops at the boundary of AdS 5 x S 5 . We study in detail the example of a correlator of two concentric circular Wilson loops and a dilaton vertex operator. The resulting expression is given by an integral of combinations of elliptic functions and can be computed analytically in some special limits. We also consider a generalization of the minimal surface ending on two circles to the case of non-zero angular momentum J in S 5 and discuss a special limit when one of the Wilson loops is effectively replaced by a 'heavy' operator with charge J. (paper)

Brain MRI and SPECT in the diagnosis of early neurological involvement in Wilson's disease

International Nuclear Information System (INIS)

Piga, Mario; Satta, Loredana; Serra, Alessandra; Loi, Gianluigi; Murru, Alessandra; Demelia, Luigi; Sias, Alessandro; Marrosu, Francesco

2008-01-01

To evaluate the impact of brain MRI and single-photon emission computed tomography (SPECT) in early detection of central nervous system abnormalities in patients affected by Wilson's disease (WD) with or without neurological involvement. Out of 25 consecutive WD patients, 13 showed hepatic involvement, ten hepatic and neurological manifestations, and twp hepatic, neurological, and psychiatric symptoms, including mainly movement disorders, major depression, and psychosis. Twenty-four healthy, age-gender matched subjects served as controls. All patients underwent brain MRI and 99m Tc-ethyl-cysteinate dimer (ECD) SPECT before starting specific therapy. Voxel-by-voxel analyses were performed using statistical parametric mapping to compare differences in 99m Tc-ECD brain uptake between the two groups. Brain MRI showed T2-weighted hyperintensities in seven patients (28%), six of whom were affected by hepatic and neurological forms. Brain perfusion SPECT showed pathological data in 19 patients (76%), revealing diffuse or focal hypoperfusion in superior frontal (Brodmann area (BA) 6), prefrontal (BA 9), parietal (BA 40), and occipital (BA 18, BA 39) cortices in temporal gyri (BA 37, BA 21) and in caudatus and putamen. Moreover, hepatic involvement was detected in nine subjects; eight presented both hepatic and neurological signs, while two exhibited WD-correlated hepatic, neurological, and psychiatric alterations. All but one patient with abnormal MRI matched with abnormal ECD SPECT. Pathologic MRI findings were obtained in six out of ten patients with hepatic and neurological involvement while abnormal ECD SPECT was revealed in eight patients. Both patients with hepatic, neurological, and psychiatric involvement displayed abnormal ECD SPECT and one displayed an altered MRI. These findings suggest that ECD SPECT might be useful in detecting early brain damage in WD, not only in the perspective of assessing and treating motor impairment but also in evaluating better the

Gene therapy for Stargardt disease associated with ABCA4 gene.

Science.gov (United States)

Han, Zongchao; Conley, Shannon M; Naash, Muna I

2014-01-01

Mutations in the photoreceptor-specific flippase ABCA4 lead to accumulation of the toxic bisretinoid A2E, resulting in atrophy of the retinal pigment epithelium (RPE) and death of the photoreceptor cells. Many blinding diseases are associated with these mutations including Stargardt's disease (STGD1), cone-rod dystrophy, retinitis pigmentosa (RP), and increased susceptibility to age-related macular degeneration. There are no curative treatments for any of these dsystrophies. While the monogenic nature of many of these conditions makes them amenable to treatment with gene therapy, the ABCA4 cDNA is 6.8 kb and is thus too large for the AAV vectors which have been most successful for other ocular genes. Here we review approaches to ABCA4 gene therapy including treatment with novel AAV vectors, lentiviral vectors, and non-viral compacted DNA nanoparticles. Lentiviral and compacted DNA nanoparticles in particular have a large capacity and have been successful in improving disease phenotypes in the Abca4 (-/-) murine model. Excitingly, two Phase I/IIa clinical trials are underway to treat patients with ABCA4-associated Startgardt's disease (STGD1). As a result of the development of these novel technologies, effective therapies for ABCA4-associated diseases may finally be within reach.

SPLPKG WFCMPR WFAPPX, Wilson-Fowler Spline Generator for Computer Aided Design And Manufacturing (CAD/CAM) Systems

International Nuclear Information System (INIS)

Fletcher, S.K.

2002-01-01

1 - Description of program or function: The three programs SPLPKG, WFCMPR, and WFAPPX provide the capability for interactively generating, comparing and approximating Wilson-Fowler Splines. The Wilson-Fowler spline is widely used in Computer Aided Design and Manufacturing (CAD/CAM) systems. It is favored for many applications because it produces a smooth, low curvature fit to planar data points. Program SPLPKG generates a Wilson-Fowler spline passing through given nodes (with given end conditions) and also generates a piecewise linear approximation to that spline within a user-defined tolerance. The program may be used to generate a 'desired' spline against which to compare other Splines generated by CAD/CAM systems. It may also be used to generate an acceptable approximation to a desired spline in the event that an acceptable spline cannot be generated by the receiving CAD/CAM system. SPLPKG writes an IGES file of points evaluated on the spline and/or a file containing the spline description. Program WFCMPR computes the maximum difference between two Wilson-Fowler Splines and may be used to verify the spline recomputed by a receiving system. It compares two Wilson-Fowler Splines with common nodes and reports the maximum distance between curves (measured perpendicular to segments) and the maximum difference of their tangents (or normals), both computed along the entire length of the Splines. Program WFAPPX computes the maximum difference between a Wilson- Fowler spline and a piecewise linear curve. It may be used to accept or reject a proposed approximation to a desired Wilson-Fowler spline, even if the origin of the approximation is unknown. The maximum deviation between these two curves, and the parameter value on the spline where it occurs are reported. 2 - Restrictions on the complexity of the problem - Maxima of: 1600 evaluation points (SPLPKG), 1000 evaluation points (WFAPPX), 1000 linear curve breakpoints (WFAPPX), 100 spline Nodes

Wilson loops en la correspondencia AdS/CFT

OpenAIRE

Aguilera Damia, Jeremías

2017-01-01

Esta tesis está abocada al estudio de operadores no locales e invariantes de gauge, denominados Wilson loops, tanto a través de técnicas propias de teoría de cuerdas como por medio de técnicas avanzadas en teorías de gauge.

Wilson and Gisvold's textbook of organic medicinal and pharmaceutical chemistry

National Research Council Canada - National Science Library

Wilson, Charles Owens; Beale, John Marlowe; Block, John H

2011-01-01

"For over half a century, Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry has served the discipline of medicinal chemistry for both graduate and undergraduate pharmacy...

Current status of gene therapy for motor neuron disease

Institute of Scientific and Technical Information of China (English)

Xingkai An; Rong Peng; Shanshan Zhao

2006-01-01

OBJECTIVE: Although the etiology and pathogenesis of motor neuron disease is still unknown, there are many hypotheses on motor neuron mitochondrion, cytoskeleton structure and functional injuries. Thus, gene therapy of motor neuron disease has become a hot topic to apply in viral vector, gene delivery and basic gene techniques.DATA SOURCES: The related articles published between January 2000 and October 2006 were searched in Medline database and ISl database by computer using the keywords "motor neuron disease, gene therapy", and the language is limited to English. Meanwhile, the related references of review were also searched by handiwork. STUDY SELECTION: Original articles and referred articles in review were chosen after first hearing, then the full text which had new ideas were found, and when refer to the similar study in the recent years were considered first.DATA EXTRACTION: Among the 92 related articles, 40 ones were accepted, and 52 were excluded because of repetitive study or reviews.DATA SYNTHESIS: The viral vectors of gene therapy for motor neuron disease include adenoviral, adeno-associated viral vectors, herpes simplex virus type 1 vectors and lentiviral vectors. The delivery of them can be achieved by direct injection into the brain, or by remote delivery after injection vectors into muscle or peripheral nerves, or by ex vivo gene transfer. The viral vectors of gene therapy for motor neuron disease have been successfully developed, but the gene delivery of them is hampered by some difficulties. The RNA interference and neuroprotection are the main technologies for gene-based therapy in motor neuron disease. CONCLUSION : The RNA interference for motor neuron disease has succeeded in animal models, and the neuroprotection also does. But, there are still a lot of questions for gene therapy in the clinical treatment of motor neuron disease.

Treating Duchenne Cardiomyopathy in the Mouse Model by Gene Repair

Science.gov (United States)

2017-08-01

Photoregulated Gene Expression for Spatiotemporal Control of Morphogenesis Time Commitments: 0 Supporting Agency: NSF Career Award, CBET-1151035...vector toolkit for human gene therapy. Mol Ther 2006, 14:316-327. 20. Gao G, Vandenberghe LH, Wilson JM: New recombinant serotypes of AAV vectors. Curr

Transformation of a Free-Wilson matrix into Fourier coefficients

Czech Academy of Sciences Publication Activity Database

Holík, M.; Halámek, Josef

2002-01-01

Roč. 20, - (2002), s. 422 - 428 ISSN 0931-8771 Institutional research plan: CEZ:AV0Z2065902 Keywords : Free-Wilson matrix * Fourier transform * multivariate regression Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 1.558, year: 2002

Lifebox | Wilson | Southern African Journal of Anaesthesia and ...

African Journals Online (AJOL)

Southern African Journal of Anaesthesia and Analgesia. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 18, No 1 (2012) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Lifebox. IH Wilson. Abstract.

Perturbation calculations with Wilson loop

International Nuclear Information System (INIS)

Peixoto Junior, L.B.

1984-01-01

We present perturbative calculations with the Wilson loop (WL). The dimensional regularization method is used with a special attention concerning to the problem of divergences in the WL expansion in second and fourth orders, in three and four dimensions. We show that the residue in the pole, in 4d, of the fourth order graphs contribution sum is important for the charge renormalization. We compute up to second order the exact expression of the WL, in three-dimensional gauge theories with topological mass as well as its assimptotic behaviour for small and large distances. the author [pt

Revisiting the dilatation operator of the Wilson-Fisher fixed point

Energy Technology Data Exchange (ETDEWEB)

Liendo, Pedro [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group

2017-01-15

We revisit the order ε dilatation operator of the Wilson-Fisher fixed point obtained by Kehrein, Pismak, and Wegner in light of recent results in conformal field theory. Our approach is algebraic and based only on symmetry principles. The starting point of our analysis is that the first correction to the dilatation operator is a conformal invariant, which implies that its form is fixed up to an infinite set of coefficients associated with the scaling dimensions of higher-spin currents. These coefficients can be fixed using well-known perturbative results, however, they were recently re-obtained using CFT arguments without relying on perturbation theory. Our analysis then implies that all order-ε scaling dimensions of the Wilson-Fisher fixed point can be fixed by symmetry.

Woodrow Wilson's hidden stroke of 1919: the impact of patient-physician confidentiality on United States foreign policy.

Science.gov (United States)

Menger, Richard P; Storey, Christopher M; Guthikonda, Bharat; Missios, Symeon; Nanda, Anil; Cooper, John M

2015-07-01

World War I catapulted the United States from traditional isolationism to international involvement in a major European conflict. Woodrow Wilson envisaged a permanent American imprint on democracy in world affairs through participation in the League of Nations. Amid these defining events, Wilson suffered a major ischemic stroke on October 2, 1919, which left him incapacitated. What was probably his fourth and most devastating stroke was diagnosed and treated by his friend and personal physician, Admiral Cary Grayson. Grayson, who had tremendous personal and professional loyalty to Wilson, kept the severity of the stroke hidden from Congress, the American people, and even the president himself. During a cabinet briefing, Grayson formally refused to sign a document of disability and was reluctant to address the subject of presidential succession. Wilson was essentially incapacitated and hemiplegic, yet he remained an active president and all messages were relayed directly through his wife, Edith. Patient-physician confidentiality superseded national security amid the backdrop of friendship and political power on the eve of a pivotal juncture in the history of American foreign policy. It was in part because of the absence of Woodrow Wilson's vocal and unwavering support that the United States did not join the League of Nations and distanced itself from the international stage. The League of Nations would later prove powerless without American support and was unable to thwart the rise and advance of Adolf Hitler. Only after World War II did the United States assume its global leadership role and realize Wilson's visionary, yet contentious, groundwork for a Pax Americana. The authors describe Woodrow Wilson's stroke, the historical implications of his health decline, and its impact on United States foreign policy.

Identification of human disease genes from interactome network using graphlet interaction.

Directory of Open Access Journals (Sweden)

Xiao-Dong Wang

Full Text Available Identifying genes related to human diseases, such as cancer and cardiovascular disease, etc., is an important task in biomedical research because of its applications in disease diagnosis and treatment. Interactome networks, especially protein-protein interaction networks, had been used to disease genes identification based on the hypothesis that strong candidate genes tend to closely relate to each other in some kinds of measure on the network. We proposed a new measure to analyze the relationship between network nodes which was called graphlet interaction. The graphlet interaction contained 28 different isomers. The results showed that the numbers of the graphlet interaction isomers between disease genes in interactome networks were significantly larger than random picked genes, while graphlet signatures were not. Then, we designed a new type of score, based on the network properties, to identify disease genes using graphlet interaction. The genes with higher scores were more likely to be disease genes, and all candidate genes were ranked according to their scores. Then the approach was evaluated by leave-one-out cross-validation. The precision of the current approach achieved 90% at about 10% recall, which was apparently higher than the previous three predominant algorithms, random walk, Endeavour and neighborhood based method. Finally, the approach was applied to predict new disease genes related to 4 common diseases, most of which were identified by other independent experimental researches. In conclusion, we demonstrate that the graphlet interaction is an effective tool to analyze the network properties of disease genes, and the scores calculated by graphlet interaction is more precise in identifying disease genes.

Identification of Human Disease Genes from Interactome Network Using Graphlet Interaction

Science.gov (United States)

Yang, Lun; Wei, Dong-Qing; Qi, Ying-Xin; Jiang, Zong-Lai

2014-01-01

Identifying genes related to human diseases, such as cancer and cardiovascular disease, etc., is an important task in biomedical research because of its applications in disease diagnosis and treatment. Interactome networks, especially protein-protein interaction networks, had been used to disease genes identification based on the hypothesis that strong candidate genes tend to closely relate to each other in some kinds of measure on the network. We proposed a new measure to analyze the relationship between network nodes which was called graphlet interaction. The graphlet interaction contained 28 different isomers. The results showed that the numbers of the graphlet interaction isomers between disease genes in interactome networks were significantly larger than random picked genes, while graphlet signatures were not. Then, we designed a new type of score, based on the network properties, to identify disease genes using graphlet interaction. The genes with higher scores were more likely to be disease genes, and all candidate genes were ranked according to their scores. Then the approach was evaluated by leave-one-out cross-validation. The precision of the current approach achieved 90% at about 10% recall, which was apparently higher than the previous three predominant algorithms, random walk, Endeavour and neighborhood based method. Finally, the approach was applied to predict new disease genes related to 4 common diseases, most of which were identified by other independent experimental researches. In conclusion, we demonstrate that the graphlet interaction is an effective tool to analyze the network properties of disease genes, and the scores calculated by graphlet interaction is more precise in identifying disease genes. PMID:24465923

beta. -Amyloid gene dosage in Alzheimer's disease

Energy Technology Data Exchange (ETDEWEB)

Murdoch, G H; Manuelidis, L; Kim, J H; Manuelidis, E E

1988-01-11

The 4-5 kd amyloid ..beta..-peptide is a major constituent of the characteristic amyloid plaque of Alzheimer's disease. It has been reported that some cases of sporatic Alzheimer's disease are associated with at least a partial duplication of chromosome 21 containing the gene corresponding to the 695 residue precursor of this peptide. To contribute to an understanding of the frequency to such a duplication event in the overall Alzheimer's population, the authors have determined the gene dosage of the ..beta..-amyloid gene in this collection of cases. All cases had a clinical diagnosis of Alzheimer's confirmed neuropathologically. Each Alzheimer's case had an apparent normal diploid ..beta..-amyloid gene dosage, while control Down's cases had the expected triploid dosage. Thus partial duplication of chromosome 21 may be a rare finding in Alzheimer's disease. Similar conclusions were just reported in several studies of the Harvard Alzheimer collection.

[Progress in research on pathogenic genes and gene therapy for inherited retinal diseases].

Science.gov (United States)

Zhu, Ling; Cao, Cong; Sun, Jiji; Gao, Tao; Liang, Xiaoyang; Nie, Zhipeng; Ji, Yanchun; Jiang, Pingping; Guan, Minxin

2017-02-10

Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.

Wilson's disease: {sup 31}P and {sup 1}H MR spectroscopy and clinical correlation

Energy Technology Data Exchange (ETDEWEB)

Sinha, Sanjib; Taly, A.B.; Prashanth, L.K. [National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neurology, Bangalore (India); Ravishankar, S.; Vasudev, M.K. [National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neuroimaging and Interventional Radiology, Bangalore (India)

2010-11-15

Proton ({sup 1}H) magnetic resonance spectroscopy (MRS) changes are noted in Wilson's disease (WD). However, there are no studies regarding membrane phospholipid abnormality using {sup 31}P MRS in these patients. We aimed to analyze the striatal spectroscopic abnormalities using {sup 31}P and {sup 1}H MRS in WD. Forty patients of WD (treated, 29; untreated,11) and 30 controls underwent routine MR image sequences and in vivo 2-D {sup 31}P and {sup 1}H MRS of basal ganglia using an image-selected technique on a 1.5-T MRI scanner. Statistical analysis was done using Student's t test. The mean durations of illness and treatment were 6.2 {+-} 7.4 and 4.8 {+-} 5.9 years, respectively. MRI images were abnormal in all the patients. {sup 1}H MRS revealed statistically significant reduction of N-acetyl aspartate (NAA)/choline (Cho) and NAA/creatine ratios in striatum ({sup 1}H MRS) of treated patients compared to controls. The mean values of phosphomonoesters (PME) (p < 0.0001), phosphodiesters (PDE) (p < 0.0001), and total phosphorus (TPh) (p < 0.0001) were elevated in patients compared to controls. Statistically significant elevated levels of ratio of PME/PDE (p = 0.05) observed in the striatum were noted in treated patients as compared to controls in the {sup 31}P MRS study. The duration of illness correlated well with increased PME/PDE [p < 0.001], PME/TPh [p < 0.05], and PDE/TPh [p < 0.05] and decreased NAA/Cho [p < 0.05] ratios. There was correlation of MRI score and reduced NAA/Cho ratio with disease severity. The PME/PDE ratio (right) was elevated in the treated group [p < 0.001] compared to untreated group. There is reduced breakdown and/or increased synthesis of membrane phospholipids and increased neuronal damage in basal ganglia in patients with WD. (orig.)

Discovering disease-associated genes in weighted protein-protein interaction networks

Science.gov (United States)

Cui, Ying; Cai, Meng; Stanley, H. Eugene

2018-04-01

Although there have been many network-based attempts to discover disease-associated genes, most of them have not taken edge weight - which quantifies their relative strength - into consideration. We use connection weights in a protein-protein interaction (PPI) network to locate disease-related genes. We analyze the topological properties of both weighted and unweighted PPI networks and design an improved random forest classifier to distinguish disease genes from non-disease genes. We use a cross-validation test to confirm that weighted networks are better able to discover disease-associated genes than unweighted networks, which indicates that including link weight in the analysis of network properties provides a better model of complex genotype-phenotype associations.

Speeding disease gene discovery by sequence based candidate prioritization

Directory of Open Access Journals (Sweden)

Porteous David J

2005-03-01

Full Text Available Abstract Background Regions of interest identified through genetic linkage studies regularly exceed 30 centimorgans in size and can contain hundreds of genes. Traditionally this number is reduced by matching functional annotation to knowledge of the disease or phenotype in question. However, here we show that disease genes share patterns of sequence-based features that can provide a good basis for automatic prioritization of candidates by machine learning. Results We examined a variety of sequence-based features and found that for many of them there are significant differences between the sets of genes known to be involved in human hereditary disease and those not known to be involved in disease. We have created an automatic classifier called PROSPECTR based on those features using the alternating decision tree algorithm which ranks genes in the order of likelihood of involvement in disease. On average, PROSPECTR enriches lists for disease genes two-fold 77% of the time, five-fold 37% of the time and twenty-fold 11% of the time. Conclusion PROSPECTR is a simple and effective way to identify genes involved in Mendelian and oligogenic disorders. It performs markedly better than the single existing sequence-based classifier on novel data. PROSPECTR could save investigators looking at large regions of interest time and effort by prioritizing positional candidate genes for mutation detection and case-control association studies.

A hybrid network-based method for the detection of disease-related genes

Science.gov (United States)

Cui, Ying; Cai, Meng; Dai, Yang; Stanley, H. Eugene

2018-02-01

Detecting disease-related genes is crucial in disease diagnosis and drug design. The accepted view is that neighbors of a disease-causing gene in a molecular network tend to cause the same or similar diseases, and network-based methods have been recently developed to identify novel hereditary disease-genes in available biomedical networks. Despite the steady increase in the discovery of disease-associated genes, there is still a large fraction of disease genes that remains under the tip of the iceberg. In this paper we exploit the topological properties of the protein-protein interaction (PPI) network to detect disease-related genes. We compute, analyze, and compare the topological properties of disease genes with non-disease genes in PPI networks. We also design an improved random forest classifier based on these network topological features, and a cross-validation test confirms that our method performs better than previous similar studies.

50 CFR 20.104 - Seasons, limits, and shooting hours for rails, woodcock, and common (Wilson's) snipe.

Science.gov (United States)

2010-10-01

... rails, woodcock, and common (Wilson's) snipe. 20.104 Section 20.104 Wildlife and Fisheries UNITED STATES... for rails, woodcock, and common (Wilson's) snipe. This section provides for the annual hunting of certain rails, woodcock, and snipe in the 48 contiguous United States. [44 FR 7148, Feb. 6, 1979...

AN EXPERIMENTAL ASSESSMENT OF THE PLATE HEAT EXCHANGER CHARACTERISTICS BY WILSON PLOT METHOD

Directory of Open Access Journals (Sweden)

Jan Opatřil

2016-10-01

Full Text Available An aim of this paper is suggestion of the evaluation method based on the experimental data and the Wilson plot method for the Plate Heat Exchangers (PHE. For the purpose of the project the new experimental loop was built for the testing of PHE to obtain the overhaul heat transfer coefficient and pressure drop between inlet and outlet of the fluid. The measurement were done for three different PHE with the performance range 30-100kW. The working fluid was water on both sides of the PHE. The differences are in number of pates as well as in extrusion profiles. The Wilson plot evaluation method was involved for the processing experimental data. To obtain more accurate correlations between the experimental data and theoretical results yield of the Wilson plot, the method was enhanced by the measured pressure drop involving. This approach could be useful for PHE designing software and for the manufacturing company.

Probing Wilson loops in N=4 Chern–Simons-matter theories at weak coupling

Directory of Open Access Journals (Sweden)

Luca Griguolo

2016-02-01

Full Text Available For three-dimensional N=4 super-Chern–Simons-matter theories associated to necklace quivers U(N0×U(N1×⋯U(N2r−1, we study at quantum level the two kinds of 1/2 BPS Wilson loop operators recently introduced in arXiv:1506.07614. We perform a two-loop evaluation and find the same result for the two kinds of operators, so moving to higher loops a possible quantum uplift of the classical degeneracy. We also compute the 1/4 BPS bosonic Wilson loop and discuss the quantum version of the cohomological equivalence between fermionic and bosonic Wilson loops. We compare the perturbative result with the Matrix Model prediction and find perfect matching, after identification and remotion of a suitable framing factor. Finally, we discuss the potential appearance of three-loop contributions that might break the classical degeneracy and briefly analyze possible implications on the BPS nature of these operators.

Parton densities in quantum chromodynamics. Gauge invariance, path-dependence, and Wilson lines

International Nuclear Information System (INIS)

Cherednikov, Igor O.

2017-01-01

The purpose of this book is to give a systematic pedagogical exposition of the quantitative analysis of Wilson lines and gauge-invariant correlation functions in quantum chromodynamics. Using techniques from the previous volume (Wilson Lines in Quantum Field Theory, 2014), an ab initio methodology is developed and practical tools for its implementation are presented. Emphasis is put on the implications of gauge invariance and path-dependence properties of transverse-momentum dependent parton density functions. The latter are associated with the QCD factorization approach to semi-inclusive hadronic processes, studied at currently operating and planned experimental facilities.

Parton densities in quantum chromodynamics. Gauge invariance, path-dependence, and Wilson lines

Energy Technology Data Exchange (ETDEWEB)

Cherednikov, Igor O. [Antwerpen Univ. (Belgium). Dept. Fysica; Veken, Frederik F. van der [CERN, Geneva (Switzerland)

2017-05-01

The purpose of this book is to give a systematic pedagogical exposition of the quantitative analysis of Wilson lines and gauge-invariant correlation functions in quantum chromodynamics. Using techniques from the previous volume (Wilson Lines in Quantum Field Theory, 2014), an ab initio methodology is developed and practical tools for its implementation are presented. Emphasis is put on the implications of gauge invariance and path-dependence properties of transverse-momentum dependent parton density functions. The latter are associated with the QCD factorization approach to semi-inclusive hadronic processes, studied at currently operating and planned experimental facilities.

New WZW D-branes from the algebra of Wilson loop operators

International Nuclear Information System (INIS)

Monnier, Samuel

2009-01-01

We investigate the algebra generated by the topological Wilson loop operators in WZW models. Wilson loops describe the nontrivial fixed points of the boundary renormalization group flows triggered by Kondo perturbations. Their enveloping algebra therefore encodes all the fixed points which can be reached by sequences of Kondo flows. This algebra is easily described in the case of SU(2), but displays a very rich structure for higher rank groups. In the latter case, its action on known D-branes creates a profusion of new and generically non-rational D-branes. We describe their symmetries and the geometry of their worldvolumes. We briefly explain how to extend these results to coset models.

Dream Recall Frequencies and Dream Content in Wilson's Disease with and without REM Sleep Behaviour Disorder: A Neurooneirologic Study.

Science.gov (United States)

Tribl, Gotthard G; Trindade, Mateus C; Schredl, Michael; Pires, Joana; Reinhard, Iris; Bittencourt, Thais; Lorenzi-Filho, Geraldo; Alves, Rosana Cardoso; de Andrade, Daniel Ciampi; Fonoff, Erich T; Bor-Seng-Shu, Edson; Machado, Alexandre A; Teixeira, Manoel J; Barbosa, Egberto R

2016-01-01

Objective. Violent dream content and its acting out during rapid eye movement sleep are considered distinctive for rapid eye movement sleep behaviour disorder (RBD). This study reports first quantitative data on dreaming in a cohort of patients with treated Wilson's disease (WD) and in patients with WD with RBD. Methods. Retrospective questionnaires on different dimensions of dreaming and a prospective two-week home dream diary with self-rating of emotions and blinded, categorical rating of content by an external judge. Results. WD patients showed a significantly lower dream word count and very few other differences in dream characteristics compared to age- and sex-matched healthy controls. Compared to WD patients without RBD, patients with WD and RBD reported significantly higher nightmare frequencies and more dreams with violent or aggressive content retrospectively; their prospectively collected dream reports contained significantly more negative emotions and aggression. Conclusions. The reduction in dream length might reflect specific cognitive deficits in WD. The lack of differences regarding dream content might be explained by the established successful WD treatment. RBD in WD had a strong impact on dreaming. In accordance with the current definition of RBD, violent, aggressive dream content seems to be a characteristic of RBD also in WD.

Toward precision holography with supersymmetric Wilson loops

Energy Technology Data Exchange (ETDEWEB)

Faraggi, Alberto [Instituto de Física, Pontificia Universidad Católica de Chile,Casilla 306, Santiago (Chile); Zayas, Leopoldo A. Pando [The Abdus Salam International Centre for Theoretical Physics,Strada Costiera 11, 34014 Trieste (Italy); Michigan Center for Theoretical Physics, Department of Physics,University of Michigan, Ann Arbor, MI 48109 (United States); Silva, Guillermo A. [Instituto de Física de La Plata - CONICET & Departamento de Física - UNLP,C.C. 67, 1900 La Plata (Argentina); Trancanelli, Diego [Institute of Physics, University of São Paulo,05314-970 São Paulo (Brazil)

2016-04-11

We consider certain 1/4 BPS Wilson loop operators in SU(N)N=4 supersymmetric Yang-Mills theory, whose expectation value can be computed exactly via supersymmetric localization. Holographically, these operators are mapped to fundamental strings in AdS{sub 5}×S{sup 5}. The string on-shell action reproduces the large N and large coupling limit of the gauge theory expectation value and, according to the AdS/CFT correspondence, there should also be a precise match between subleading corrections to these limits. We perform a test of such match at next-to-leading order in string theory, by deriving the spectrum of quantum fluctuations around the classical string solution and by computing the corresponding 1-loop effective action. We discuss in detail the supermultiplet structure of the fluctuations. To remove a possible source of ambiguity in the ghost zero mode measure, we compare the 1/4 BPS configuration with the 1/2 BPS one, dual to a circular Wilson loop. We find a discrepancy between the string theory result and the gauge theory prediction, confirming a previous result in the literature. We are able to track the modes from which this discrepancy originates, as well as the modes that by themselves would give the expected result.

BOOK REVIEW: Democracy and Political Life in Nigeria | Wilson ...

African Journals Online (AJOL)

In this review of Victor Dike's book - \\"Democracy and Political Life in Nigeria\\", Inam Wilson underscores the author's attempts to draw a connection between Nigeria's chequered political history and her present economic trajectory to explain why Nigeria is today facing numerous sociopolitical and economic challenges, ...

Parkinson's disease and mitochondrial gene variations

DEFF Research Database (Denmark)

Andalib, Sasan; Vafaee, Manouchehr Seyedi; Gjedde, Albert

2014-01-01

Parkinson's disease (PD) is a common disorder of the central nervous system in the elderly. The pathogenesis of PD is a complex process, with genetics as an important contributing factor. This factor may stem from mitochondrial gene variations and mutations as well as from nuclear gene variations...

Generating Gene Ontology-Disease Inferences to Explore Mechanisms of Human Disease at the Comparative Toxicogenomics Database.

Directory of Open Access Journals (Sweden)

Allan Peter Davis

Full Text Available Strategies for discovering common molecular events among disparate diseases hold promise for improving understanding of disease etiology and expanding treatment options. One technique is to leverage curated datasets found in the public domain. The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/ manually curates chemical-gene, chemical-disease, and gene-disease interactions from the scientific literature. The use of official gene symbols in CTD interactions enables this information to be combined with the Gene Ontology (GO file from NCBI Gene. By integrating these GO-gene annotations with CTD's gene-disease dataset, we produce 753,000 inferences between 15,700 GO terms and 4,200 diseases, providing opportunities to explore presumptive molecular underpinnings of diseases and identify biological similarities. Through a variety of applications, we demonstrate the utility of this novel resource. As a proof-of-concept, we first analyze known repositioned drugs (e.g., raloxifene and sildenafil and see that their target diseases have a greater degree of similarity when comparing GO terms vs. genes. Next, a computational analysis predicts seemingly non-intuitive diseases (e.g., stomach ulcers and atherosclerosis as being similar to bipolar disorder, and these are validated in the literature as reported co-diseases. Additionally, we leverage other CTD content to develop testable hypotheses about thalidomide-gene networks to treat seemingly disparate diseases. Finally, we illustrate how CTD tools can rank a series of drugs as potential candidates for repositioning against B-cell chronic lymphocytic leukemia and predict cisplatin and the small molecule inhibitor JQ1 as lead compounds. The CTD dataset is freely available for users to navigate pathologies within the context of extensive biological processes, molecular functions, and cellular components conferred by GO. This inference set should aid researchers, bioinformaticists, and

Lack of association of the Norrie disease gene with retinoschisis phenotype.

Science.gov (United States)

Shastry, B S; Hiraoka, M; Trese, M T

2000-01-01

It has been reported recently that mice carrying a disrupted Norrie disease gene produced alterations in the murine eye that are similar to congenital retinoschisis. Therefore, it was of interest to determine whether mutations in the Norrie disease gene can account for the disease in families with retinoschisis that do not carry mutations in the retinoschisis gene. The patient set comprised 5 cases of retinoschisis (1 familial and 4 sporadic), all unrelated to each other. Fundus examination of affected individuals showed foveal and peripheral schisis, and the visual acuity range was 20/40-20/60. Peripheral blood specimens were collected from affected and unaffected family members. DNA was extracted and amplified by polymerase chain reaction amplification of exons of the Norrie disease gene. The amplified products were sequenced by the dideoxy chain termination method. The data revealed no disease-specific sequence alterations in the Norrie disease gene. Although we cannot completely exclude the possibility of the Norrie disease gene as a candidate gene, the above results suggest that the structural and functional changes in the Norrie disease gene are not associated with clinically typical retinoschisis families that do not contain mutations in the coding regions and splice sites of the retinoschisis gene.

Wilson and Domainwall Kernels on Oakforest-PACS

Science.gov (United States)

Kanamori, Issaku; Matsufuru, Hideo

2018-03-01

We report the performance of Wilson and Domainwall Kernels on a new Intel Xeon Phi Knights Landing based machine named Oakforest-PACS, which is co-hosted by University of Tokyo and Tsukuba University and is currently fastest in Japan. This machine uses Intel Omni-Path for the internode network. We compare performance with several types of implementation including that makes use of the Grid library. The code is incorporated with the code set Bridge++.

Comments on ''Geomagnetic response to magnetic clouds'' by Robert M. Wilson; and reply

International Nuclear Information System (INIS)

Gonzalez, W.D.; Gonzalez, A.L.C.; Wilson, R.M.

1988-01-01

The paper 'Geomagnetic Response to Magnetic Clouds' by Wilson (1987) tried to show an association between geomagnetic storm intervals and the passage of interplanetary magnetic clouds at the Earth's magnetosphere. The association is shown through a superposed epoch analysis of the interplanetary magnetic field (IMF)-B Z component and the D st geomagnetic storm index for 19 cloud events occurring between 1973 and 1978. Two aspects of the magnetic cloud-storm relationship are challenged. The first concerns the northward-southward rotation of the IMF-B Z component which is known to exist but not accounted for in Wilson's article. The second concerns the magnitude of the storms associated with the passage of magnetic clouds. In a reply Wilson explains the distinction between N-turning and S-turning clouds of the 19 clouds studied 12 were southward and 7 northward turning. The average behaviour of both is similar, the differences being due to the different onset values of D st . The second problem is attributed to a misunderstanding of the meaning of the I-bars given in the original article. The original results of Wilson are reaffirmed. The comment on the reply suggests that the average peak D st value for S-N clouds is larger by 30% than for the N-S clouds and that the final intensity of the storm can be altered by the type of cloud involved (S-N) or (N-S). (U.K.)

Gene-Environment Interaction in Parkinson's Disease

DEFF Research Database (Denmark)

Chuang, Yu-Hsuan; Lill, Christina M; Lee, Pei-Chen

2016-01-01

BACKGROUND AND PURPOSE: Drinking caffeinated coffee has been reported to provide protection against Parkinson's disease (PD). Caffeine is an adenosine A2A receptor (encoded by the gene ADORA2A) antagonist that increases dopaminergic neurotransmission and Cytochrome P450 1A2 (gene: CYP1A2...

Mining biological databases for candidate disease genes

Science.gov (United States)

Braun, Terry A.; Scheetz, Todd; Webster, Gregg L.; Casavant, Thomas L.

2001-07-01

The publicly-funded effort to sequence the complete nucleotide sequence of the human genome, the Human Genome Project (HGP), has currently produced more than 93% of the 3 billion nucleotides of the human genome into a preliminary `draft' format. In addition, several valuable sources of information have been developed as direct and indirect results of the HGP. These include the sequencing of model organisms (rat, mouse, fly, and others), gene discovery projects (ESTs and full-length), and new technologies such as expression analysis and resources (micro-arrays or gene chips). These resources are invaluable for the researchers identifying the functional genes of the genome that transcribe and translate into the transcriptome and proteome, both of which potentially contain orders of magnitude more complexity than the genome itself. Preliminary analyses of this data identified approximately 30,000 - 40,000 human `genes.' However, the bulk of the effort still remains -- to identify the functional and structural elements contained within the transcriptome and proteome, and to associate function in the transcriptome and proteome to genes. A fortuitous consequence of the HGP is the existence of hundreds of databases containing biological information that may contain relevant data pertaining to the identification of disease-causing genes. The task of mining these databases for information on candidate genes is a commercial application of enormous potential. We are developing a system to acquire and mine data from specific databases to aid our efforts to identify disease genes. A high speed cluster of Linux of workstations is used to analyze sequence and perform distributed sequence alignments as part of our data mining and processing. This system has been used to mine GeneMap99 sequences within specific genomic intervals to identify potential candidate disease genes associated with Bardet-Biedle Syndrome (BBS).

Values in Higher Education. The Wilson Lecture Series.

Science.gov (United States)

Wilson, O. Meredith

The text of a lecture in the University of Arizona Wilson Lecture Series on values in higher education is presented, with responses by Richard H. Gallagher, Jeanne McRae McCarthy, and Raymond H. Thompson. The theme of the talk is that man is by evolution and by necessity a thinking animal, who now finds himself in a technologically dependent…

Wilson?s disease presenting as rapid eye movement sleep behavior disorder: a possible window to early treatment

Directory of Open Access Journals (Sweden)

Gotthard G. Tribl

2014-09-01

Full Text Available Objective To describe characteristics of REM sleep behavior disorder in Wilson’s disease. Method Questionnaire-based interviews (patients and relatives, neurological examinations, two-week prospective dream-diary, video-polysomnography, transcranial sonography, MRI. Results Four Wilson’s disease cases with REM sleep behavior disorder were described; three had REM sleep behavior disorder as initial symptom. All showed mesencephalic tegmental/tectal sonographic hyperechogenicities and two presented ponto-mesencephalic tegmental MRI hyperintensities. Conclusion This first description of REM sleep behavior disorder in Wilson’s disease in literature documents REM sleep behavior disorder as a possible presenting symptom of Wilson’s disease and adds further evidence to the parallelism of Parkinson’s disease and Wilson’s disease in phenotype and brainstem topography, which ought to be further studied. REM sleep behavior disorder has prognostic relevance for neurodegeneration in α-synucleinopathies. In Wilson’s disease, usefulness of early diagnosis and treatment are already well established. REM sleep behavior disorder in Wilson’s disease offers a possible theoretical model for potential early treatment in this extrapyramidal and brainstem paradigm syndrome, previewing the possibility of neuroprotective treatment for REM sleep behavior disorder in “pre-clinical” Parkinson’s disease.

Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease.

Science.gov (United States)

Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

2014-01-01

We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. http://rged.wall-eva.net. © The Author(s) 2014. Published by Oxford University Press.

Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease

Science.gov (United States)

Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

2014-01-01

We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Availability and implementation: Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. Database URL: http://rged.wall-eva.net PMID:25252782

Diet of Wilson's warblers and distribution of arthropod prey in the understory of Douglas-fir forests

Science.gov (United States)

Hagar, Joan C.; Dugger, Kate; Starkey, Edward E.

2007-01-01

Availability of food resources is an important factor in avian habitat selection. Food resources for terrestrial birds often are closely related to vegetation structure and composition. Identification of plant species important in supporting food resources may facilitate vegetation management to achieve objectives for providing bird habitat. We used fecal analysis to describe the diet of adult Wilson's Warblers (Wilsonia pusilla) that foraged in the understory of Douglas-fir (Pseudotsuga menziesii) forests in western Oregon during the breeding season. We sampled arthropods at the same sites where diet data were collected, and compared abundance and biomass of prey among seven common shrub species. Wilson's Warblers ate more caterpillars (Lepidoptera larvae), flies (Diptera), beetles (Coleoptera), and Homoptera than expected based on availability. Deciduous shrubs supported higher abundances of arthropod taxa and size classes used as prey by Wilson's Warblers than did evergreen shrubs. The development and maintenance of deciduous understory vegetation in conifer forests of the Pacific Northwest may be fundamental for conservation of food webs that support breeding Wilson's Warblers and other shrub-associated, insectivorous songbirds.

Ornamental “borderlands”: Elisabeth Wilson and Martin Heydrich’s historiographies of “primitive” ornament

Directory of Open Access Journals (Sweden)

Priyanka Basu

2015-06-01

Full Text Available This article examines texts by Elisabeth Wilson and Martin Heydrich written in 1914 at the University of Leipzig on the subject of ‘primitive’ ornament. Both synopsize the history and literature of this field from its beginnings in the nineteenth century to the time of their writing. This article considers how Wilson and Heydrich represent this history and how the field’s multidisciplinary practitioners perceived its pressing problems. Above all, Wilson and Heydrich set up a number of recurring oppositions between major approaches to ‘primitive’ art and ornament, between ‘materialist’ interpretation, allied with archaeology, symbolic interpretation practiced for the most part by ethnologists, and an ‘aesthetic’ approach, pursued by art theorists and focused on the psychological will of its creators. These issues and this configuration of approaches are further examined in one of August Schmarsow’s important essays on art history and ethnology.

MyGeneFriends: A Social Network Linking Genes, Genetic Diseases, and Researchers.

Science.gov (United States)

Allot, Alexis; Chennen, Kirsley; Nevers, Yannis; Poidevin, Laetitia; Kress, Arnaud; Ripp, Raymond; Thompson, Julie Dawn; Poch, Olivier; Lecompte, Odile

2017-06-16

The constant and massive increase of biological data offers unprecedented opportunities to decipher the function and evolution of genes and their roles in human diseases. However, the multiplicity of sources and flow of data mean that efficient access to useful information and knowledge production has become a major challenge. This challenge can be addressed by taking inspiration from Web 2.0 and particularly social networks, which are at the forefront of big data exploration and human-data interaction. MyGeneFriends is a Web platform inspired by social networks, devoted to genetic disease analysis, and organized around three types of proactive agents: genes, humans, and genetic diseases. The aim of this study was to improve exploration and exploitation of biological, postgenomic era big data. MyGeneFriends leverages conventions popularized by top social networks (Facebook, LinkedIn, etc), such as networks of friends, profile pages, friendship recommendations, affinity scores, news feeds, content recommendation, and data visualization. MyGeneFriends provides simple and intuitive interactions with data through evaluation and visualization of connections (friendships) between genes, humans, and diseases. The platform suggests new friends and publications and allows agents to follow the activity of their friends. It dynamically personalizes information depending on the user's specific interests and provides an efficient way to share information with collaborators. Furthermore, the user's behavior itself generates new information that constitutes an added value integrated in the network, which can be used to discover new connections between biological agents. We have developed MyGeneFriends, a Web platform leveraging conventions from popular social networks to redefine the relationship between humans and biological big data and improve human processing of biomedical data. MyGeneFriends is available at lbgi.fr/mygenefriends. ©Alexis Allot, Kirsley Chennen, Yannis

Parasitic copepods on Oligoplites spp. (Osteichthyes, Carangidae from the Brazilian coastal zone, with the redescription of Tuxophorus caligodes Wilson, 1908 (Siphonostomatoida, Tuxophoridae Copépodes parasitos de Oligoplites spp. (Osteichthyes, Carangidae da costa brasileira, com a redescrição de Tuxophorus caligodes Wilson, 1908 (Siphonostomatoida, Tuxophoridae

Directory of Open Access Journals (Sweden)

Ricardo Massato Takemoto

2002-05-01

Full Text Available Four species of caligid copepods, parasites of Oligoplites palometa (Cuvier, 1833, O. saurus (Bloch & Schneider, 1801 and O. saliens (Bloch, 1793 (Osteichthyes: Carangidae from the Sepetiba Bay, coast of the state of Rio de Janeiro, Brazil, are presented. New geographical and host records for Caligus robustus Bassett-Smith, 1898, C. rufimaculatus Wilson, 1905, C. bonito Wilson, 1905 and Metacaligus rufus (Wilson, 1908 are given. Caligus oligoplitisi Carvalho, 1954 is considered a new junior synonym of C. robustus. Fishes of the genus Oligoplites are new host records for this species of copepod. Redescription and illustration of Tuxophorus caligodes Wilson, 1908, collected on the body surface of Oligoplites saliens, O. palometa and O. saurus, are provided.Quatro espécies de copépodes caligídeos, parasitos de Oligoplites palometa (Cuvier, 1833, O. saurus (Bloch & Schneider, 1801 e O. saliens (Bloch, 1793 (Osteichthyes, Carangidae da Baia de Sepetiba, litoral do Estado do Rio de Janeiro, Brasil, são descritos. São apresentados o registro de novo hospedeiro e nova distribuição geográfica para Caligus robustus Bassett-Smith, 1898, C. rufimaculatus Wilson, 1905, C. bonito Wilson, 1905 e Metacaligus rufus (Wilson, 1908. Caligus oligoplitisi Carvalho, 1954, é considerado novo sinônimo júnior de C. robustus. Tuxophorus caligodes Wilson, 1908, coletado na superfície do corpo de Oligoplites saliens, O. palometa e O. saurus é redescrito e ilustrado. Peixes do gênero Oligoplites são novos hospedeiros para estas espécies de copépodes.

A history of altruism focusing on Darwin, Allee and E.O. Wilson.

Science.gov (United States)

Domondon, Andrew T

2013-06-01

The problem of altruism refers to the apparent difficulty in reconciling the existence of altruists, individuals who reduce their own fitness to increase the fitness of others, with natural selection. A historical and philosophical overview of solutions to this apparent contradiction is presented through a close reading of the key texts of Charles Darwin, Warder C. Allee and Edward O. Wilson. Following an analysis of Darwin's explanation for altruism, I examine the ideas of group selection and kin selection advanced by Allee and Wilson, respectively, Attention is also given to the philosophical implications each associated with their respective solutions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Wilson loops on three-manifolds and their M2-brane duals

International Nuclear Information System (INIS)

Farquet, Daniel; Sparks, James

2014-01-01

We compute the large N limit of Wilson loop expectation values for a broad class of N=2 supersymmetric gauge theories defined on a general class of background three-manifolds M_3, diffeomorphic to S"3. We find a simple closed formula which depends on the background geometry only through a certain supersymmetric Killing vector field. The supergravity dual of such a Wilson loop is an M2-brane wrapping the M-theory circle, together with a complex curve Σ_2 in a self-dual Einstein manifold M_4, whose conformal boundary is M_3. We show that the regularized action of this M2-brane also depends only on the supersymmetric Killing vector, precisely reproducing the large N field theory computation.

An extensive analysis of disease-gene associations using network integration and fast kernel-based gene prioritization methods

Science.gov (United States)

Valentini, Giorgio; Paccanaro, Alberto; Caniza, Horacio; Romero, Alfonso E.; Re, Matteo

2014-01-01

Objective In the context of “network medicine”, gene prioritization methods represent one of the main tools to discover candidate disease genes by exploiting the large amount of data covering different types of functional relationships between genes. Several works proposed to integrate multiple sources of data to improve disease gene prioritization, but to our knowledge no systematic studies focused on the quantitative evaluation of the impact of network integration on gene prioritization. In this paper, we aim at providing an extensive analysis of gene-disease associations not limited to genetic disorders, and a systematic comparison of different network integration methods for gene prioritization. Materials and methods We collected nine different functional networks representing different functional relationships between genes, and we combined them through both unweighted and weighted network integration methods. We then prioritized genes with respect to each of the considered 708 medical subject headings (MeSH) diseases by applying classical guilt-by-association, random walk and random walk with restart algorithms, and the recently proposed kernelized score functions. Results The results obtained with classical random walk algorithms and the best single network achieved an average area under the curve (AUC) across the 708 MeSH diseases of about 0.82, while kernelized score functions and network integration boosted the average AUC to about 0.89. Weighted integration, by exploiting the different “informativeness” embedded in different functional networks, outperforms unweighted integration at 0.01 significance level, according to the Wilcoxon signed rank sum test. For each MeSH disease we provide the top-ranked unannotated candidate genes, available for further bio-medical investigation. Conclusions Network integration is necessary to boost the performances of gene prioritization methods. Moreover the methods based on kernelized score functions can further

Disease candidate gene identification and prioritization using protein interaction networks

Directory of Open Access Journals (Sweden)

Aronow Bruce J

2009-02-01

Full Text Available Abstract Background Although most of the current disease candidate gene identification and prioritization methods depend on functional annotations, the coverage of the gene functional annotations is a limiting factor. In the current study, we describe a candidate gene prioritization method that is entirely based on protein-protein interaction network (PPIN analyses. Results For the first time, extended versions of the PageRank and HITS algorithms, and the K-Step Markov method are applied to prioritize disease candidate genes in a training-test schema. Using a list of known disease-related genes from our earlier study as a training set ("seeds", and the rest of the known genes as a test list, we perform large-scale cross validation to rank the candidate genes and also evaluate and compare the performance of our approach. Under appropriate settings – for example, a back probability of 0.3 for PageRank with Priors and HITS with Priors, and step size 6 for K-Step Markov method – the three methods achieved a comparable AUC value, suggesting a similar performance. Conclusion Even though network-based methods are generally not as effective as integrated functional annotation-based methods for disease candidate gene prioritization, in a one-to-one comparison, PPIN-based candidate gene prioritization performs better than all other gene features or annotations. Additionally, we demonstrate that methods used for studying both social and Web networks can be successfully used for disease candidate gene prioritization.

Tuning up an oldtimer: hybrid Monte Carlo with Wilson fermions

International Nuclear Information System (INIS)

Schilling, K.; Hannemann, V.; Lippert, T.; Noeckel, B.

1995-01-01

We show that BiCGStab inversion algorithm helps to speed up by 50% the computation of the fermionic force inside the Hybrid Monte Carlo (HMC) simulation of full QCD with Wilson fermions, in the chiral regime of small quark masses. ((orig.))

Perturbative evaluation of the Thermal Wilson Loop

International Nuclear Information System (INIS)

Gava, E.; Jengo, R.

1981-06-01

The Thermal Wilson Loop 0 sup(β) dtauA 0 (tau, x-vector)>, representing an order parameter for the gauge theory and expected to be zero in the confining phase, is perturbatively evaluated up to the O(g 4 ) included for an SU(N) pure Yang-Mills theory. This evaluation should be meaningful at high temperature, β → 0. Its behaviour is discussed and a possible need for non-perturbative instanton-like contributions is pointed out. (author)

Gene-wide analysis detects two new susceptibility genes for Alzheimer's Disease

OpenAIRE

Escott-Price, Valentina; Bellenguez, Céline; Wang, Li-San; Choi, Seung-Hoan; Harold, Denise; Jones, Lesley; Holmans, Peter Alan; Gerrish, Amy; Vedernikov, Alexey; Richards, Alexander; DeStefano, Anita L.; Lambert, Jean-Charles; Ibrahim-Verbaas, Carla A.; Naj, Adam C.; Sims, Rebecca

2014-01-01

PUBLISHED BACKGROUND: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over...

Tagging of resistance gene(s) to rhizomania disease in sugar beet ...

African Journals Online (AJOL)

The rhizomania disease is one of the most important diseases in Iran and some other parts of the world which potentially could play a role in decreasing sugar yield in fields. One approach to combat with this disease is the use of resistance varieties. This varieties have been identified which are having resistance genes to ...

Retinoschisislike alterations in the mouse eye caused by gene targeting of the Norrie disease gene.

Science.gov (United States)

Ruether, K; van de Pol, D; Jaissle, G; Berger, W; Tornow, R P; Zrenner, E

1997-03-01

To investigate the retinal function and morphology of mice carrying a replacement mutation in exon 2 of the Norrie disease gene. Recently, Norrie disease mutant mice have been generated using gene targeting technology. The mutation removes the 56 N-terminal amino acids of the Norrie gene product. Ganzfeld electroretinograms (ERGs) were obtained in five animals hemizygous or homozygous for the mutant gene and in three female animals heterozygous for the mutant gene. As controls, three males carrying the wild-type gene were examined. Electroretinogram testing included rod a- and b-wave V-log I functions, oscillatory potentials, and cone responses. The fundus morphology has been visualized by scanning laser ophthalmoscopy. Rod and cone ERG responses and fundus morphology were not significantly different among female heterozygotes and wild-type mice. In contrast, the hemizygous mice displayed a severe loss of ERG b-wave, leading to a negatively shaped scotopic ERG and a marked reduction of oscillatory potentials. The a-wave was normal at low intensities, and only with brighter flashes was there a moderate amplitude loss. Cone amplitudes were barely recordable in the gene-targeted males. Ophthalmoscopy revealed snowflakelike vitreal changes, retinoschisis, and pigment epithelium irregularities in hemizygotes and homozygotes, but no changes in female heterozygotes. The negatively shaped scotopic ERG in male mice with a Norrie disease gene mutation probably was caused by retinoschisis. Pigment epithelial changes and degenerations of the outer retina are relatively mild. These findings may be a clue to the embryonal retinoschisislike pathogenesis of Norrie disease in humans or it may indicate a different expression of the Norrie disease gene defect in mice compared to that in humans.

Multivariable biorthogonal continuous--discrete Wilson and Racah polynomials

International Nuclear Information System (INIS)

Tratnik, M.V.

1990-01-01

Several families of multivariable, biorthogonal, partly continuous and partly discrete, Wilson polynomials are presented. These yield limit cases that are purely continuous in some of the variables and purely discrete in the others, or purely discrete in all the variables. The latter are referred to as the multivariable biorthogonal Racah polynomials. Interesting further limit cases include the multivariable biorthogonal Hahn and dual Hahn polynomials

The SPINK gene family and celiac disease susceptibility

NARCIS (Netherlands)

Wapenaar, M.C.; Monsuur, A.J.; Poell, J.; Slot, R. van 't; Meijer, J.W.R.; Meijer, G.A.; Mulder, C.J.; Mearin, M.L.; Wijmenga, C.

2007-01-01

The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was

The SPINK gene family and celiac disease susceptibility

NARCIS (Netherlands)

Wapenaar, Martin C.; Monsuur, Alienke J.; Poell, Jos; Slot, Ruben Van 't; Meijer, Jos W. R.; Meijer, Gerrit A.; Mulder, Chris J.; Mearin, Maria Luisa; Wijmenga, Cisca

The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was

Wilson loops and its correlators with chiral operators in N = 2, 4 SCFT at large N

Science.gov (United States)

Sysoeva, E.

2018-03-01

In this paper we compute the vacuum expectation value of the Wilson loop and its correlators with chiral primary operators in N = 2, 4 superconformal U( N ) gauge theories at large N . After localization these quantities can be computed in terms of a deformed U( N ) matrix model. The Wilson loops we deal with are in the fundamental and symmetric representations.

Détermination expérimentale des paramètres de Wilson Experimental Dertermination of Wilson Parameters

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Monfort J.-P.

2006-11-01

Full Text Available La volabilité relative ait; =(yilxil(Y;lxi des constituants d'un mélange binaire a été mesurée à partir d'un nouveau dispositif expérimental, on reporte les données d'équilibre liquide-vapeur obtenues à 45'C de plusieurs binaires : toluène-acétoni-trile, benzène-acétonitrile et benzène-n-heptane. En ajustant à l'équation de Wilson les données expérimentales de «i/; de ces constituants ainsi que des volatilités relatives des constituants des mélanges d'hydrocarbures-alcools, obtenues dans un précédent travail, on calcule les paramètres énergétiques. La prédiction des points de bulle de mélanges binaires et ternaires obtenue à partir de ces paramètres est satisfaisante. La méthode expérimentale ainsi proposée convient particulièrement pour la sélection des solvant extractifs utilisés dans la distillation extractive. From a new expérimental method, relative volatilities aiti = (yilxil(yilxi for a binary mixture are obtained; vapor-liquid equilibrium data are presented for several systems, i.e. toluene-acétonitrile, benzene-acétonitrile and benzene-n-heptane at 45°C. The two adjustable energyparameters of thé Wilson équation, are obtained by adopting thé «,/j data for these binary mixtures and for alcohol-hydrocarbon mixtures previously studied. Theresults obtained in predicting bubble-pressure data for binary and ternary mixtures are consistent with experimental data.

Comments on correlation functions of large spin operators and null polygonal Wilson loops

Energy Technology Data Exchange (ETDEWEB)

Cardona, Carlos A., E-mail: cargicar@iafe.uba.ar [Instituto de Astronomia y Fisica del Espacio (CONICET-UBA), C.C. 67 - Suc. 28, 1428 Buenos Aires (Argentina); Physics Department, University of Buenos Aires, CONICET, Ciudad Universitaria, 1428 Buenos Aires (Argentina)

2013-02-11

We discuss the relation between correlation functions of twist-two large spin operators and expectation values of Wilson loops along light-like trajectories. After presenting some heuristic field theoretical arguments suggesting this relation, we compute the divergent part of the correlator in the limit of large 't Hooft coupling and large spins, using a semi-classical world-sheet which asymptotically looks like a GKP rotating string. We show this diverges as expected from the expectation value of a null Wilson loop, namely, as (ln{mu}{sup -2}){sup 2}, {mu} being a cut-off of the theory.

Comments on correlation functions of large spin operators and null polygonal Wilson loops

International Nuclear Information System (INIS)

Cardona, Carlos A.

2013-01-01

We discuss the relation between correlation functions of twist-two large spin operators and expectation values of Wilson loops along light-like trajectories. After presenting some heuristic field theoretical arguments suggesting this relation, we compute the divergent part of the correlator in the limit of large 't Hooft coupling and large spins, using a semi-classical world-sheet which asymptotically looks like a GKP rotating string. We show this diverges as expected from the expectation value of a null Wilson loop, namely, as (lnμ −2 ) 2 , μ being a cut-off of the theory.

Nucleon electromagnetic form factors with Wilson fermions

International Nuclear Information System (INIS)

Goeckeler, M.; Haegler, P.; Horsley, R.

2007-10-01

The nucleon electromagnetic form factors continue to be of major interest for experimentalists and phenomenologists alike. They provide important insights into the structure of nuclear matter. For a range of interesting momenta they can be calculated on the lattice. The limiting factor continues to be the value of the pion mass. We present the latest results of the QCDSF collaboration using gauge configurations with two dynamical, non-perturbatively improved Wilson fermions at pion masses as low as 350 MeV. (orig.)

Nucleon electromagnetic form factors with Wilson fermions

Energy Technology Data Exchange (ETDEWEB)

Goeckeler, M. [Regensburg Univ. (Germany). Inst. fuer Theoretische Physik; Haegler, P. [Technische Univ. Muenchen, Garching (Germany). Inst. fuer Theoretische Physik; Horsley, R. [Edinburgh Univ. (GB). School of Physics] (and others)

2007-10-15

The nucleon electromagnetic form factors continue to be of major interest for experimentalists and phenomenologists alike. They provide important insights into the structure of nuclear matter. For a range of interesting momenta they can be calculated on the lattice. The limiting factor continues to be the value of the pion mass. We present the latest results of the QCDSF collaboration using gauge configurations with two dynamical, non-perturbatively improved Wilson fermions at pion masses as low as 350 MeV. (orig.)

Gene editing as a promising approach for respiratory diseases.

Science.gov (United States)

Bai, Yichun; Liu, Yang; Su, Zhenlei; Ma, Yana; Ren, Chonghua; Zhao, Runzhen; Ji, Hong-Long

2018-03-01

Respiratory diseases, which are leading causes of mortality and morbidity in the world, are dysfunctions of the nasopharynx, the trachea, the bronchus, the lung and the pleural cavity. Symptoms of chronic respiratory diseases, such as cough, sneezing and difficulty breathing, may seriously affect the productivity, sleep quality and physical and mental well-being of patients, and patients with acute respiratory diseases may have difficulty breathing, anoxia and even life-threatening respiratory failure. Respiratory diseases are generally heterogeneous, with multifaceted causes including smoking, ageing, air pollution, infection and gene mutations. Clinically, a single pulmonary disease can exhibit more than one phenotype or coexist with multiple organ disorders. To correct abnormal function or repair injured respiratory tissues, one of the most promising techniques is to correct mutated genes by gene editing, as some gene mutations have been clearly demonstrated to be associated with genetic or heterogeneous respiratory diseases. Zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN) and clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) systems are three innovative gene editing technologies developed recently. In this short review, we have summarised the structure and operating principles of the ZFNs, TALENs and CRISPR/Cas9 systems and their preclinical and clinical applications in respiratory diseases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Age-dependent changes of cerebral copper metabolism in Atp7b -/- knockout mouse model of Wilson's disease by [64Cu]CuCl2-PET/CT.

Science.gov (United States)

Xie, Fang; Xi, Yin; Pascual, Juan M; Muzik, Otto; Peng, Fangyu

2017-06-01

Copper is a nutritional metal required for brain development and function. Wilson's disease (WD), or hepatolenticular degeneration, is an inherited human copper metabolism disorder caused by a mutation of the ATP7B gene. Many WD patients present with variable neurological and psychiatric symptoms, which may be related to neurodegeneration secondary to copper metabolism imbalance. The objective of this study was to explore the feasibility and use of copper-64 chloride ([ 64 C]CuCl 2 ) as a tracer for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD using an Atp7b -/- knockout mouse model of WD and positron emission tomography/computed tomography (PET/CT) imaging. Continuing from our recent study of biodistribution and radiation dosimetry of [ 64 C]CuCl 2 in Atp7b -/- knockout mice, PET quantitative analysis revealed low 64 Cu radioactivity in the brains of Atp7b -/- knockout mice at 7th weeks of age, compared with 64 Cu radioactivity in the brains of age- and gender-matched wild type C57BL/6 mice, at 24 h (h) post intravenous injection of [ 64 C]CuCl 2 as a tracer. Furthermore, age-dependent increase of 64 Cu radioactivity was detected in the brains of Atp7b -/- knockout mice from the 13th to 21th weeks of age, based on the data derived from a longitudinal [ 64 C]CuCl 2 -PET/CT study of Atp7b -/- knockout mice with orally administered [ 64 Cu]CuCl 2 as a tracer. The findings of this study support clinical use of [ 64 Cu]CuCl 2 -PET/CT imaging as a tool for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD patients presenting with variable neurological and psychiatric symptoms.

An extensive analysis of disease-gene associations using network integration and fast kernel-based gene prioritization methods.

Science.gov (United States)

Valentini, Giorgio; Paccanaro, Alberto; Caniza, Horacio; Romero, Alfonso E; Re, Matteo

2014-06-01

In the context of "network medicine", gene prioritization methods represent one of the main tools to discover candidate disease genes by exploiting the large amount of data covering different types of functional relationships between genes. Several works proposed to integrate multiple sources of data to improve disease gene prioritization, but to our knowledge no systematic studies focused on the quantitative evaluation of the impact of network integration on gene prioritization. In this paper, we aim at providing an extensive analysis of gene-disease associations not limited to genetic disorders, and a systematic comparison of different network integration methods for gene prioritization. We collected nine different functional networks representing different functional relationships between genes, and we combined them through both unweighted and weighted network integration methods. We then prioritized genes with respect to each of the considered 708 medical subject headings (MeSH) diseases by applying classical guilt-by-association, random walk and random walk with restart algorithms, and the recently proposed kernelized score functions. The results obtained with classical random walk algorithms and the best single network achieved an average area under the curve (AUC) across the 708 MeSH diseases of about 0.82, while kernelized score functions and network integration boosted the average AUC to about 0.89. Weighted integration, by exploiting the different "informativeness" embedded in different functional networks, outperforms unweighted integration at 0.01 significance level, according to the Wilcoxon signed rank sum test. For each MeSH disease we provide the top-ranked unannotated candidate genes, available for further bio-medical investigation. Network integration is necessary to boost the performances of gene prioritization methods. Moreover the methods based on kernelized score functions can further enhance disease gene ranking results, by adopting both

The "double panda" sign in Leigh disease.

Science.gov (United States)

Sonam, Kothari; Bindu, P S; Gayathri, Narayanappa; Khan, Nahid Akhtar; Govindaraju, C; Arvinda, Hanumanthapura R; Nagappa, Madhu; Sinha, Sanjib; Thangaraj, K; Taly, Arun B

2014-07-01

Although the "face of the giant panda" sign on magnetic resonance imaging (MRI) is traditionally considered to be characteristic of Wilson disease, it has also been reported in other metabolic disorders. This study describes the characteristic "giant panda" sign on MRI in a child with Leigh disease. The diagnosis was based on the history of neurological regression; examination findings of oculomotor abnormalities, hypotonia, and dystonia; raised serum lactate levels; and characteristic brain stem and basal ganglia signal changes on MRI. The midbrain and pontine tegmental signal changes were consistent with the "face of the giant panda and her cub" sign. In addition to Wilson disease, metabolic disorders such as Leigh disease should also be considered in the differential diagnosis of this rare imaging finding. © The Author(s) 2013.

Wilson line distributions in hot SU(2) gluodynamics

International Nuclear Information System (INIS)

Ilgenfritz, E.M.

1982-01-01

Monte-Carlo results concerning the order parameter related to confinement and its distribution from the point of view of the dilute instanton gas approximation are Discussed. Identified is a threshold effect in the Wilson line distribution with the onset of instantons and established is the relation between the temperature of instanton saturation and the confinement temperature. Some other details of our Monte-Carlo results are reported as well

Raising and Lowering Operators for Askey-Wilson Polynomials

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Siddhartha Sahi

2007-01-01

Full Text Available In this paper we describe two pairs of raising/lowering operators for Askey-Wilson polynomials, which result from constructions involving very different techniques. The first technique is quite elementary, and depends only on the ''classical'' properties of these polynomials, viz. the q-difference equation and the three term recurrence. The second technique is less elementary, and involves the one-variable version of the double affine Hecke algebra.

A maize resistance gene functions against bacterial streak disease in rice.

Science.gov (United States)

Zhao, Bingyu; Lin, Xinghua; Poland, Jesse; Trick, Harold; Leach, Jan; Hulbert, Scot

2005-10-25

Although cereal crops all belong to the grass family (Poacea), most of their diseases are specific to a particular species. Thus, a given cereal species is typically resistant to diseases of other grasses, and this nonhost resistance is generally stable. To determine the feasibility of transferring nonhost resistance genes (R genes) between distantly related grasses to control specific diseases, we identified a maize R gene that recognizes a rice pathogen, Xanthomonas oryzae pv. oryzicola, which causes bacterial streak disease. Bacterial streak is an important disease of rice in Asia, and no simply inherited sources of resistance have been identified in rice. Although X. o. pv. oryzicola does not cause disease on maize, we identified a maize gene, Rxo1, that conditions a resistance reaction to a diverse collection of pathogen strains. Surprisingly, Rxo1 also controls resistance to the unrelated pathogen Burkholderia andropogonis, which causes bacterial stripe of sorghum and maize. The same gene thus controls resistance reactions to both pathogens and nonpathogens of maize. Rxo1 has a nucleotide-binding site-leucine-rich repeat structure, similar to many previously identified R genes. Most importantly, Rxo1 functions after transfer as a transgene to rice, demonstrating the feasibility of nonhost R gene transfer between cereals and providing a valuable tool for controlling bacterial streak disease.

Network-based association of hypoxia-responsive genes with cardiovascular diseases

International Nuclear Information System (INIS)

Wang, Rui-Sheng; Oldham, William M; Loscalzo, Joseph

2014-01-01

Molecular oxygen is indispensable for cellular viability and function. Hypoxia is a stress condition in which oxygen demand exceeds supply. Low cellular oxygen content induces a number of molecular changes to activate regulatory pathways responsible for increasing the oxygen supply and optimizing cellular metabolism under limited oxygen conditions. Hypoxia plays critical roles in the pathobiology of many diseases, such as cancer, heart failure, myocardial ischemia, stroke, and chronic lung diseases. Although the complicated associations between hypoxia and cardiovascular (and cerebrovascular) diseases (CVD) have been recognized for some time, there are few studies that investigate their biological link from a systems biology perspective. In this study, we integrate hypoxia genes, CVD genes, and the human protein interactome in order to explore the relationship between hypoxia and cardiovascular diseases at a systems level. We show that hypoxia genes are much closer to CVD genes in the human protein interactome than that expected by chance. We also find that hypoxia genes play significant bridging roles in connecting different cardiovascular diseases. We construct a hypoxia-CVD bipartite network and find several interesting hypoxia-CVD modules with significant gene ontology similarity. Finally, we show that hypoxia genes tend to have more CVD interactors in the human interactome than in random networks of matching topology. Based on these observations, we can predict novel genes that may be associated with CVD. This network-based association study gives us a broad view of the relationships between hypoxia and cardiovascular diseases and provides new insights into the role of hypoxia in cardiovascular biology. (paper)

Understanding gene expression in coronary artery disease through ...

Indian Academy of Sciences (India)

Understanding gene expression in coronary artery disease through global profiling, network analysis and independent validation of key candidate genes. Prathima ... Table 2. Differentially expressed genes in CAD compared to age and gender matched controls. .... Regulation of nuclear pre-mRNA domain containing 1A.

IUE observations of the evolution of Comet Wilson (1986l) - comparison with P/Halley

International Nuclear Information System (INIS)

Roettger, E.E.; Feldman, P.D.; A'hearn, M.F.; Festou, M.C.; Mcfadden, L.A.

1989-01-01

IUE observations of Comet Wilson from September 1986 to November 1987, through perihelion, allow a comparison to be conducted between this 'new' comet and the highly evolved P/Halley, at comparable heliocentric distances. The temporal decreases of both OH and dust in Comet Wilson near perihelion were monotonic and slow, by contrast to Comet Halley's rapid fluctuations. Despite these differences, relative gas abundances were similar within a factor of about 2 for comparable heliocentric and geocentric distances; this indicates that P/Halley's in situ gas measurements may be typical of comets generally. 33 refs

Urban research in a hostile setting: Godfrey Wilson in Broken Hill, Northern Rhodesia, 1938-1940

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Karen Tranberg Hansen

Full Text Available Acknowledged for his pioneering urban anthropological research in Broken Hill through the publication of An Essay on the Economics of Detribalization in Northern Rhodesia (Parts I and II, 1940 and 1941, Godfrey Wilson's professional career was cut short by his death during World War II. The late 1990s transfer and cataloguing at the University of Cape Town of the Monica and Godfrey Wilson papers has made an enormously rich research archive accessible to the public. For the first time, Godfrey Wilson's notes from his fieldwork in Broken Hill enable us to examine his research project through his own observations. Based on a preliminary overview of these records and a tentative analysis of some of their contents, this article revisits the Broken Hill research project against the background of the published essay on the economics of detribalisation. Wilson's argument about temporary urbanisation is demonstrated through migration histories, information about length of stay in towns, and an analysis of the economics of urban livelihoods that focuses on wages including rations, household expenditures, and urban-rural transfers. But the published essay barely explains how in fact he conducted his field research. Although there are very few direct indications, we can infer some of his fieldwork practices and field methodology from notes that occasionally evoke an immediate sense of the trials and tribulations of everyday African life in Broken Hill in the early World War II years. How might experiences in the field have influenced Wilson's analysis? Overall, I discuss his work from two angles, first in the context of a time and place characterised by conflicting agendas, and secondly, in retrospect as the conceptual space and time of early World War II colonial Northern Rhodesia have yielded to different explanatory perspectives.

Norrie disease and MAO genes: nearest neighbors.

Science.gov (United States)

Chen, Z Y; Denney, R M; Breakefield, X O

1995-01-01

The Norrie disease and MAO genes are tandemly arranged in the p11.4-p11.3 region of the human X chromosome in the order tel-MAOA-MAOB-NDP-cent. This relationship is conserved in the mouse in the order tel-MAOB-MAOA-NDP-cent. The MAO genes appear to have arisen by tandem duplication of an ancestral MAO gene, but their positional relationship to NDP appears to be random. Distinctive X-linked syndromes have been described for mutations in the MAOA and NDP genes, and in addition, individuals have been identified with contiguous gene syndromes due to chromosomal deletions which encompass two or three of these genes. Loss of function of the NDP gene causes a syndrome of congenital blindness and progressive hearing loss, sometimes accompanied by signs of CNS dysfunction, including variable mental retardation and psychiatric symptoms. Other mutations in the NDP gene have been found to underlie another X-linked eye disease, exudative vitreo-retinopathy. An MAOA deficiency state has been described in one family to date, with features of altered amine and amine metabolite levels, low normal intelligence, apparent difficulty in impulse control and cardiovascular difficulty in affected males. A contiguous gene syndrome in which all three genes are lacking, as well as other as yet unidentified flanking genes, results in severe mental retardation, small stature, seizures and congenital blindness, as well as altered amine and amine metabolites. Issues that remain to be resolved are the function of the NDP gene product, the frequency and phenotype of the MAOA deficiency state, and the possible occurrence and phenotype of an MAOB deficiency state.

Disease gene characterization through large-scale co-expression analysis.

Directory of Open Access Journals (Sweden)

Allen Day

2009-12-01

Full Text Available In the post genome era, a major goal of biology is the identification of specific roles for individual genes. We report a new genomic tool for gene characterization, the UCLA Gene Expression Tool (UGET.Celsius, the largest co-normalized microarray dataset of Affymetrix based gene expression, was used to calculate the correlation between all possible gene pairs on all platforms, and generate stored indexes in a web searchable format. The size of Celsius makes UGET a powerful gene characterization tool. Using a small seed list of known cartilage-selective genes, UGET extended the list of known genes by identifying 32 new highly cartilage-selective genes. Of these, 7 of 10 tested were validated by qPCR including the novel cartilage-specific genes SDK2 and FLJ41170. In addition, we retrospectively tested UGET and other gene expression based prioritization tools to identify disease-causing genes within known linkage intervals. We first demonstrated this utility with UGET using genetically heterogeneous disorders such as Joubert syndrome, microcephaly, neuropsychiatric disorders and type 2 limb girdle muscular dystrophy (LGMD2 and then compared UGET to other gene expression based prioritization programs which use small but discrete and well annotated datasets. Finally, we observed a significantly higher gene correlation shared between genes in disease networks associated with similar complex or Mendelian disorders.UGET is an invaluable resource for a geneticist that permits the rapid inclusion of expression criteria from one to hundreds of genes in genomic intervals linked to disease. By using thousands of arrays UGET annotates and prioritizes genes better than other tools especially with rare tissue disorders or complex multi-tissue biological processes. This information can be critical in prioritization of candidate genes for sequence analysis.

Human gene therapy and imaging in neurological diseases

International Nuclear Information System (INIS)

Jacobs, Andreas H.; Winkler, Alexandra; Castro, Maria G.; Lowenstein, Pedro

2005-01-01

Molecular imaging aims to assess non-invasively disease-specific biological and molecular processes in animal models and humans in vivo. Apart from precise anatomical localisation and quantification, the most intriguing advantage of such imaging is the opportunity it provides to investigate the time course (dynamics) of disease-specific molecular events in the intact organism. Further, molecular imaging can be used to address basic scientific questions, e.g. transcriptional regulation, signal transduction or protein/protein interaction, and will be essential in developing treatment strategies based on gene therapy. Most importantly, molecular imaging is a key technology in translational research, helping to develop experimental protocols which may later be applied to human patients. Over the past 20 years, imaging based on positron emission tomography (PET) and magnetic resonance imaging (MRI) has been employed for the assessment and ''phenotyping'' of various neurological diseases, including cerebral ischaemia, neurodegeneration and brain gliomas. While in the past neuro-anatomical studies had to be performed post mortem, molecular imaging has ushered in the era of in vivo functional neuro-anatomy by allowing neuroscience to image structure, function, metabolism and molecular processes of the central nervous system in vivo in both health and disease. Recently, PET and MRI have been successfully utilised together in the non-invasive assessment of gene transfer and gene therapy in humans. To assess the efficiency of gene transfer, the same markers are being used in animals and humans, and have been applied for phenotyping human disease. Here, we review the imaging hallmarks of focal and disseminated neurological diseases, such as cerebral ischaemia, neurodegeneration and glioblastoma multiforme, as well as the attempts to translate gene therapy's experimental knowledge into clinical applications and the way in which this process is being promoted through the use of

Brain MRI and SPECT in the diagnosis of early neurological involvement in Wilson's disease

Energy Technology Data Exchange (ETDEWEB)

Piga, Mario; Satta, Loredana; Serra, Alessandra; Loi, Gianluigi [Policlinico Universitario, University of Cagliari, Nuclear Medicine, Department of Medical Science, Monserrato, Cagliari (Italy); Murru, Alessandra; Demelia, Luigi [Policlinico Universitario, University of Cagliari, Gastroenterology, Department of Medical Science, Monserrato, Cagliari (Italy); Sias, Alessandro [Policlinico Universitario, University of Cagliari, Radiology, Department of Medical Science, Monserrato, Cagliari (Italy); Marrosu, Francesco [Policlinico Universitario, University of Cagliari, Neurology, Department of Medical Science, Monserrato, Cagliari (Italy)

2008-04-15

To evaluate the impact of brain MRI and single-photon emission computed tomography (SPECT) in early detection of central nervous system abnormalities in patients affected by Wilson's disease (WD) with or without neurological involvement. Out of 25 consecutive WD patients, 13 showed hepatic involvement, ten hepatic and neurological manifestations, and twp hepatic, neurological, and psychiatric symptoms, including mainly movement disorders, major depression, and psychosis. Twenty-four healthy, age-gender matched subjects served as controls. All patients underwent brain MRI and {sup 99m}Tc-ethyl-cysteinate dimer (ECD) SPECT before starting specific therapy. Voxel-by-voxel analyses were performed using statistical parametric mapping to compare differences in {sup 99m}Tc-ECD brain uptake between the two groups. Brain MRI showed T2-weighted hyperintensities in seven patients (28%), six of whom were affected by hepatic and neurological forms. Brain perfusion SPECT showed pathological data in 19 patients (76%), revealing diffuse or focal hypoperfusion in superior frontal (Brodmann area (BA) 6), prefrontal (BA 9), parietal (BA 40), and occipital (BA 18, BA 39) cortices in temporal gyri (BA 37, BA 21) and in caudatus and putamen. Moreover, hepatic involvement was detected in nine subjects; eight presented both hepatic and neurological signs, while two exhibited WD-correlated hepatic, neurological, and psychiatric alterations. All but one patient with abnormal MRI matched with abnormal ECD SPECT. Pathologic MRI findings were obtained in six out of ten patients with hepatic and neurological involvement while abnormal ECD SPECT was revealed in eight patients. Both patients with hepatic, neurological, and psychiatric involvement displayed abnormal ECD SPECT and one displayed an altered MRI. These findings suggest that ECD SPECT might be useful in detecting early brain damage in WD, not only in the perspective of assessing and treating motor impairment but also in evaluating

Eugene Onegin the Cold War Monument: How Edmund Wilson Quarreled with Vladimir Nabokov

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Tim Conley

2014-01-01

Full Text Available The tale of how Edmund Wilson quarreled with Vladimir Nabokov over the latter’s 1964 translation of Eugene Onegin can be instructively read as a politically charged event, specifically a “high culture” allegory of the Cold War. Dissemination of anti-Communist ideals (often in liberal and literary guises was the mandate of the Congress for Cultural Freedom, whose funding and editorial initiatives included the publication of both pre-Revolution Russian literature and, more notoriously, the journal Encounter (1953-1990, where Nabokov’s fiery “Reply” to Wilson appeared. This essay outlines the propaganda value of the Onegin debate within and to Cold War mythology.

Mandelstam cuts and light-like Wilson loops in N=4 SUSY

Energy Technology Data Exchange (ETDEWEB)

Lipatov, L.N. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik; St. Petersburg Inst. of Nuclear Physics, Gatchina (Russian Federation); Prygarin, A. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik

2010-08-15

We perform an analytic continuation of the two-loop remainder function for the six-point planar MHV amplitude in N=4 SUSY, found by Goncharov, Spradlin, Vergu and Volovich from the light-like Wilson loop representation. The remainder function is continued into a physical region, where all but two energy invariants are negative. It turns out to be pure imaginary in the multi-Regge kinematics, which is in an agreement with the predictions based on the Steinmann relations for the Regge poles and Mandelstam cut contributions. The leading term reproduces correctly the expression calculated by one of the authors in the BFKL approach, while the subleading term presents a result, that was not yet found with the use of the unitarity techniques. This supports the applicability of the Wilson loop approach to the planar MHV amplitudes in N=4 SUSY. (orig.)

Mandelstam cuts and light-like Wilson loops in N=4 SUSY

International Nuclear Information System (INIS)

Lipatov, L.N.; Prygarin, A.

2010-08-01

We perform an analytic continuation of the two-loop remainder function for the six-point planar MHV amplitude in N=4 SUSY, found by Goncharov, Spradlin, Vergu and Volovich from the light-like Wilson loop representation. The remainder function is continued into a physical region, where all but two energy invariants are negative. It turns out to be pure imaginary in the multi-Regge kinematics, which is in an agreement with the predictions based on the Steinmann relations for the Regge poles and Mandelstam cut contributions. The leading term reproduces correctly the expression calculated by one of the authors in the BFKL approach, while the subleading term presents a result, that was not yet found with the use of the unitarity techniques. This supports the applicability of the Wilson loop approach to the planar MHV amplitudes in N=4 SUSY. (orig.)

Retinitis pigmentosa: genes and disease mechanisms.

Science.gov (United States)

Ferrari, Stefano; Di Iorio, Enzo; Barbaro, Vanessa; Ponzin, Diego; Sorrentino, Francesco S; Parmeggiani, Francesco

2011-06-01

Retinitis pigmentosa (RP) is a group of inherited disorders affecting 1 in 3000-7000 people and characterized by abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium of the retina which lead to progressive visual loss. RP can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. While usually limited to the eye, RP may also occur as part of a syndrome as in the Usher syndrome and Bardet-Biedl syndrome. Over 40 genes have been associated with RP so far, with the majority of them expressed in either the photoreceptors or the retinal pigment epithelium. The tremendous heterogeneity of the disease makes the genetics of RP complicated, thus rendering genotype-phenotype correlations not fully applicable yet. In addition to the multiplicity of mutations, in fact, different mutations in the same gene may cause different diseases. We will here review which genes are involved in the genesis of RP and how mutations can lead to retinal degeneration. In the future, a more thorough analysis of genetic and clinical data together with a better understanding of the genotype-phenotype correlation might allow to reveal important information with respect to the likelihood of disease development and choices of therapy.

How Hugh Hampton Young's treatment of President Woodrow Wilson's urinary retention and urosepsis affected the resolution of World War I.

Science.gov (United States)

Fogg, Ryan; Kutikov, Alexander; Uzzo, Robert G; Canter, Daniel

2011-09-01

President Woodrow Wilson was never able to gain ratification of the Treaty of Versailles, the peace accord to end World War I. Before he could convince the American people of the importance of ratification, Wilson suffered a stroke followed by life threatening urinary sepsis due to urinary retention, and was treated by the father of modern urology, Hugh Hampton Young. The effects of these health problems are examined in the context of their implications on international affairs. Biographical sources and primary documentation of Wilson's physicians were reviewed to determine the effect of Wilson's stroke on his voiding habits. Hugh Hampton Young's evaluation and decision making is examined in depth. In the fall of 1919 President Wilson was recovering from a stroke. Shortly after the stroke his preexisting voiding dysfunction progressed to urinary retention from which urinary sepsis developed. Hugh Hampton Young advised on Wilson's case and counseled patience over surgery. The President began voiding spontaneously and recovered from sepsis. The illness left him severely weakened and unable to mount an aggressive campaign to persuade the U.S. Senate of the importance of ratifying the Treaty of Versailles. His personal physician, Admiral Cary T. Grayson, stated that the President was mentally never the same after the sepsis. Wilson's voiding dysfunction contributed to his inability to win approval for the Treaty of Versailles and the League of Nations. As a result, the United States returned to a policy of isolationism and Europe plunged into 2 decades of upheaval, leading to World War II. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

SU(2) string tension from large Wilson loops

International Nuclear Information System (INIS)

Karsch, F.; Lang, C.B.

1984-01-01

We determine expectation values of Wilson loops and correlations of Polyakov loops on lattices of size 10 X 16 3 and 8 X 16 3 at β values 2.25 and 2.375. Utilizing a recently proposed method to reduce the variance of loop expectation values, we are able to measure loops up to 6 X 6. We find Λsub(L) = 0.0151 +- 0.0006√sub(K) at β = 2.375. (orig.)

Pontes e rupturas no fabular de Wilson Bueno

OpenAIRE

Furquim, Fulvia Maria Giaretta de Almeida

2008-01-01

O trabalho tem por objetivo analisar tres obras contemporaneas do escritor paranaense Wilson Bueno (1949- ), que fazem parte de um projeto literario, em que as personagens sao apresentadas de uma visao inicialmente plural, como se apenas uma delas pudesse ser a representacao do todo, para uma optica individualista, caracteristica de um sistema capitalista. Sao elas: Manual de Zoofilia (1991), Jardim Zoologico (1999) e Cachorrros do Ceu (2005). O escritor contemporaneo segue a tradicao dos bes...

Wilson flow and scale setting from lattice QCD

Energy Technology Data Exchange (ETDEWEB)

Bornyakov, V.G. [Institute for High Energy Physics, Protvino (Russian Federation); Institute of Theoretical and Experimental Physics, Moscow (Russian Federation); Far Eastern Federal Univ., Vladivostok (Russian Federation). School of Biomedicine; Horsley, R. [Edinburgh Univ. (United Kingdom). School of Physics and Astronomy; Hudspith, R. [York Univ., Toronto, ON (Canada). Dept. of Mathematics and Statistics; Collaboration: QCDSF-UKQCD Collaboration; and others

2015-08-15

We give a determination of the phenomenological value of the Wilson (or gradient) flow scales t{sub 0} and w{sub 0} for 2+1 flavours of dynamical quarks. The simulations are performed keeping the average quark mass constant, which allows the approach to the physical point to be made in a controlled manner. O(a) improved clover fermions are used and together with four lattice spacings this allows the continuum extrapolation to be taken.

FocusHeuristics - expression-data-driven network optimization and disease gene prediction.

Science.gov (United States)

Ernst, Mathias; Du, Yang; Warsow, Gregor; Hamed, Mohamed; Endlich, Nicole; Endlich, Karlhans; Murua Escobar, Hugo; Sklarz, Lisa-Madeleine; Sender, Sina; Junghanß, Christian; Möller, Steffen; Fuellen, Georg; Struckmann, Stephan

2017-02-16

To identify genes contributing to disease phenotypes remains a challenge for bioinformatics. Static knowledge on biological networks is often combined with the dynamics observed in gene expression levels over disease development, to find markers for diagnostics and therapy, and also putative disease-modulatory drug targets and drugs. The basis of current methods ranges from a focus on expression-levels (Limma) to concentrating on network characteristics (PageRank, HITS/Authority Score), and both (DeMAND, Local Radiality). We present an integrative approach (the FocusHeuristics) that is thoroughly evaluated based on public expression data and molecular disease characteristics provided by DisGeNet. The FocusHeuristics combines three scores, i.e. the log fold change and another two, based on the sum and difference of log fold changes of genes/proteins linked in a network. A gene is kept when one of the scores to which it contributes is above a threshold. Our FocusHeuristics is both, a predictor for gene-disease-association and a bioinformatics method to reduce biological networks to their disease-relevant parts, by highlighting the dynamics observed in expression data. The FocusHeuristics is slightly, but significantly better than other methods by its more successful identification of disease-associated genes measured by AUC, and it delivers mechanistic explanations for its choice of genes.

GENE ARRAY ANALYSIS OF THE VENTRAL PROSTATE IN RATS EXPOSED TO EITHER VINCLOZOLIN OR PROCYMIDONE

Science.gov (United States)

GENE ARRAY ANALYSIS OF THE VENTRAL PROSTATE IN RATS EXPOSED TO EITHER VINCLOZOLIN OR PROCYMIDONE. MB Rosen, VS Wilson, JE Schmid, and LE Gray Jr. US EPA, ORD, NHEERL, RTP, NC.Vinclozolin (Vi) and procymidone (Pr) are antiandrogenic fungicides. While changes in gene expr...

[Wilson's principles--a base of modern teratology].

Science.gov (United States)

Burdan, Franciszek; Bełzek, Artur; Szumiło, Justyna; Dudka, Jarosław; Korobowicz, Agnieszka; Tokarska, Edyta; Klepacz, Lidia; Bełzek, Marta; Klepacz, Robert

2006-03-01

Wilson's principles were formulated after thalidomide tragedy. They become a fundamental for teratological studies with drugs and other factors that may disturb fetal development. It is postulated that susceptibility to teratogen depends on the genotype and developmental stage of the conceptus. Teratogenic agents act in specific manner on developing cells and tissues. The exposition depends on the agent's nature and availability. Manifestations of deviant development depends on the dosage and exposure frequency. In case of abnormal development the final manifestations include death of embryo or fetus, malformation, growth retardation and functional disorder.

Genetics of sputum gene expression in chronic obstructive pulmonary disease.

Directory of Open Access Journals (Sweden)

Weiliang Qiu

Full Text Available Previous expression quantitative trait loci (eQTL studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals. We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD patients to identify functional effects of known susceptibility genes and to find novel disease genes. By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs. The 3309 SNPs were tested for association with COPD in a genomewide association study (GWAS dataset, which included 2940 COPD cases and 1380 controls. Adjusting for 3309 tests (p<1.5e-5, the two SNPs which were significantly associated with COPD were located in two separate genes in a known COPD locus on chromosome 15: CHRNA5 and IREB2. Detailed analysis of chromosome 15 demonstrated additional eQTLs for IREB2 mapping to that gene. eQTL SNPs for CHRNA5 mapped to multiple linkage disequilibrium (LD bins. The eQTLs for IREB2 and CHRNA5 were not in LD. Seventy-four additional eQTL SNPs were associated with COPD at p<0.01. These were genotyped in two COPD populations, finding replicated associations with a SNP in PSORS1C1, in the HLA-C region on chromosome 6. Integrative analysis of GWAS and gene expression data from relevant tissue from diseased subjects has located potential functional variants in two known COPD genes and has identified a novel COPD susceptibility locus.

Genetics of Sputum Gene Expression in Chronic Obstructive Pulmonary Disease

Science.gov (United States)

Qiu, Weiliang; Cho, Michael H.; Riley, John H.; Anderson, Wayne H.; Singh, Dave; Bakke, Per; Gulsvik, Amund; Litonjua, Augusto A.; Lomas, David A.; Crapo, James D.; Beaty, Terri H.; Celli, Bartolome R.; Rennard, Stephen; Tal-Singer, Ruth; Fox, Steven M.; Silverman, Edwin K.; Hersh, Craig P.

2011-01-01

Previous expression quantitative trait loci (eQTL) studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals. We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD) patients to identify functional effects of known susceptibility genes and to find novel disease genes. By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP) data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs). The 3309 SNPs were tested for association with COPD in a genomewide association study (GWAS) dataset, which included 2940 COPD cases and 1380 controls. Adjusting for 3309 tests (p<1.5e-5), the two SNPs which were significantly associated with COPD were located in two separate genes in a known COPD locus on chromosome 15: CHRNA5 and IREB2. Detailed analysis of chromosome 15 demonstrated additional eQTLs for IREB2 mapping to that gene. eQTL SNPs for CHRNA5 mapped to multiple linkage disequilibrium (LD) bins. The eQTLs for IREB2 and CHRNA5 were not in LD. Seventy-four additional eQTL SNPs were associated with COPD at p<0.01. These were genotyped in two COPD populations, finding replicated associations with a SNP in PSORS1C1, in the HLA-C region on chromosome 6. Integrative analysis of GWAS and gene expression data from relevant tissue from diseased subjects has located potential functional variants in two known COPD genes and has identified a novel COPD susceptibility locus. PMID:21949713

Off-shell amplitudes as boundary integrals of analytically continued Wilson line slope

International Nuclear Information System (INIS)

Kotko, P.; Serino, M.; Staśto, A.M.

2016-01-01

One of the methods to calculate tree-level multi-gluon scattering amplitudes is to use the Berends-Giele recursion relation involving off-shell currents or off-shell amplitudes, if working in the light cone gauge. As shown in recent works using the light-front perturbation theory, solutions to these recursions naturally collapse into gauge invariant and gauge-dependent components, at least for some helicity configurations. In this work, we show that such structure is helicity independent and emerges from analytic properties of matrix elements of Wilson line operators, where the slope of the straight gauge path is shifted in a certain complex direction. This is similar to the procedure leading to the Britto-Cachazo-Feng-Witten (BCFW) recursion, however we apply a complex shift to the Wilson line slope instead of the external momenta. While in the original BCFW procedure the boundary integrals over the complex shift vanish for certain deformations, here they are non-zero and are equal to the off-shell amplitudes. The main result can thus be summarized as follows: we derive a decomposition of a helicity-fixed off-shell current into gauge invariant component given by a matrix element of a straight Wilson line plus a reminder given by a sum of products of gauge invariant and gauge dependent quantities. We give several examples realizing this relation, including the five-point next-to-MHV helicity configuration.

Wilson Disease

Science.gov (United States)

... helps the body digest fats and the fat-soluble vitamins A, D, E, and K. removing waste products ... pipes may pick up copper residue, but running water lowers the level to within ... use of vitamins and dietary supplements, with their health care provider. ...

Wilson Disease

Science.gov (United States)

... and inappropriate behavior, depression accompanied by suicidal thoughts, neurosis, or psychosis. WD is diagnosed with tests that ... and inappropriate behavior, depression accompanied by suicidal thoughts, neurosis, or psychosis. WD is diagnosed with tests that ...

Wilson disease

Science.gov (United States)

Symptoms may include: Abnormal posture of arms and legs Confusion or delirium Dementia Difficulty moving arms and legs, stiffness Difficulty walking (ataxia) Emotional or behavioral changes Enlargement of ...

Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease

NARCIS (Netherlands)

Robak, L.A.; Jansen, I.E.; Rooij, J van; Uitterlinden, A.G.; Kraaij, R.; Jankovic, J.; Heutink, P.; Shulman, J.M.; Bloem, B.; Post, B.; Scheffer, H.; Warrenburg, B.P.C. van de; et al.,

2017-01-01

Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. We examined whether a genetic burden of variants in other lysosomal storage disorder genes is more broadly associated with Parkinson's disease susceptibility. The

Gene prioritization for livestock diseases by data integration

DEFF Research Database (Denmark)

Jiang, Li; Sørensen, Peter; Thomsen, Bo Stjerne

2012-01-01

in bovine mastitis. Gene-associated phenome profile and transcriptome profile in response to Escherichia coli infection in the mammary gland were integrated to make a global inference of bovine genes involved in mastitis. The top ranked genes were highly enriched for pathways and biological processes...... underlying inflammation and immune responses, which supports the validity of our approach for identifying genes that are relevant to animal health and disease. These gene-associated phenotypes were used for a local prioritization of candidate genes located in a QTL affecting the susceptibility to mastitis...

Pleiotropic Effects of Variants in Dementia Genes in Parkinson Disease

Directory of Open Access Journals (Sweden)

Laura Ibanez

2018-04-01

Full Text Available Background: The prevalence of dementia in Parkinson disease (PD increases dramatically with advancing age, approaching 80% in patients who survive 20 years with the disease. Increasing evidence suggests clinical, pathological and genetic overlap between Alzheimer disease, dementia with Lewy bodies and frontotemporal dementia with PD. However, the contribution of the dementia-causing genes to PD risk, cognitive impairment and dementia in PD is not fully established.Objective: To assess the contribution of coding variants in Mendelian dementia-causing genes on the risk of developing PD and the effect on cognitive performance of PD patients.Methods: We analyzed the coding regions of the amyloid-beta precursor protein (APP, Presenilin 1 and 2 (PSEN1, PSEN2, and Granulin (GRN genes from 1,374 PD cases and 973 controls using pooled-DNA targeted sequence, human exome-chip and whole-exome sequencing (WES data by single variant and gene base (SKAT-O and burden tests analyses. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE or the Montreal Cognitive Assessment (MoCA. The effect of coding variants in dementia-causing genes on cognitive performance was tested by multiple regression analysis adjusting for gender, disease duration, age at dementia assessment, study site and APOE carrier status.Results: Known AD pathogenic mutations in the PSEN1 (p.A79V and PSEN2 (p.V148I genes were found in 0.3% of all PD patients. There was a significant burden of rare, likely damaging variants in the GRN and PSEN1 genes in PD patients when compared with frequencies in the European population from the ExAC database. Multiple regression analysis revealed that PD patients carrying rare variants in the APP, PSEN1, PSEN2, and GRN genes exhibit lower cognitive tests scores than non-carrier PD patients (p = 2.0 × 10−4, independent of age at PD diagnosis, age at evaluation, APOE status or recruitment site.Conclusions: Pathogenic mutations in

Gene-Environment Interactions in the Development of Complex Disease Phenotypes

Directory of Open Access Journals (Sweden)

Kenneth Olden

2008-03-01

Full Text Available The lack of knowledge about the earliest events in disease development is due to the multi-factorial nature of disease risk. This information gap is the consequence of the lack of appreciation for the fact that most diseases arise from the complex interactions between genes and the environment as a function of the age or stage of development of the individual. Whether an environmental exposure causes illness or not is dependent on the efficiency of the so-called “environmental response machinery” (i.e., the complex of metabolic pathways that can modulate response to environmental perturbations that one has inherited. Thus, elucidating the causes of most chronic diseases will require an understanding of both the genetic and environmental contribution to their etiology. Unfortunately, the exploration of the relationship between genes and the environment has been hampered in the past by the limited knowledge of the human genome, and by the inclination of scientists to study disease development using experimental models that consider exposure to a single environmental agent. Rarely in the past were interactions between multiple genes or between genes and environmental agents considered in studies of human disease etiology. The most critical issue is how to relate exposure-disease association studies to pathways and mechanisms. To understand how genes and environmental factors interact to perturb biological pathways to cause injury or disease, scientists will need tools with the capacity to monitor the global expression of thousands of genes, proteins and metabolites simultaneously. The generation of such data in multiple species can be used to identify conserved and functionally significant genes and pathways involved in geneenvironment interactions. Ultimately, it is this knowledge that will be used to guide agencies such as the U.S. Department of Health and Human Services in decisions regarding biomedical research funding

Local anomaly cancellation in heterotic E8 x E8 orbifold compactifications with Wilson line backgrounds

International Nuclear Information System (INIS)

Walter, M.G.A.

2004-02-01

We consider several examples of a special class of heterotic compactifications, i.e. heterotic E 8 x E 8 orbifolds with Wilson line backgrounds. By developing a local perspective we show that a brane world like picture emerges. As an important result we prove that the local massless spectrum at such a brane can always be traced back to the global spectrum of a (different) orbifold without Wilson lines. One particular implication of this result is that the use of (discrete) Wilson lines for the construction of phenomenologically interesting models has to be rethought. We show that stringy constraints render the brane spectra consistent. Using our local picture we are able to compute the local anomalies appearing at the different branes for our examples and show that they can all be cancelled by a local version of the Green-Schwarz mechanism at the same time. (orig.)

NDP gene mutations in 14 French families with Norrie disease.

Science.gov (United States)

Royer, Ghislaine; Hanein, Sylvain; Raclin, Valérie; Gigarel, Nadine; Rozet, Jean-Michel; Munnich, Arnold; Steffann, Julie; Dufier, Jean-Louis; Kaplan, Josseline; Bonnefont, Jean-Paul

2003-12-01

Norrie disease is a rare X-inked recessive condition characterized by congenital blindness and occasionally deafness and mental retardation in males. This disease has been ascribed to mutations in the NDP gene on chromosome Xp11.1. Previous investigations of the NDP gene have identified largely sixty disease-causing sequence variants. Here, we report on ten different NDP gene allelic variants in fourteen of a series of 21 families fulfilling inclusion criteria. Two alterations were intragenic deletions and eight were nucleotide substitutions or splicing variants, six of them being hitherto unreported, namely c.112C>T (p.Arg38Cys), c.129C>G (p.His43Gln), c.133G>A (p.Val45Met), c.268C>T (p.Arg90Cys), c.382T>C (p.Cys128Arg), c.23479-1G>C (unknown). No NDP gene sequence variant was found in seven of the 21 families. This observation raises the issue of misdiagnosis, phenocopies, or existence of other X-linked or autosomal genes, the mutations of which would mimic the Norrie disease phenotype. Copyright 2003 Wiley-Liss, Inc.

Wilson cycle passive margins: Control of orogenic inheritance on continental breakup

DEFF Research Database (Denmark)

Petersen, Kenni D.; Schiffer, Christian

2016-01-01

Abstract Rifts and passive margins often develop along old suture zones where colliding continents merged during earlier phases of the Wilson cycle. For example, the North Atlantic formed after continental break-up along sutures formed during the Caledonian and Variscan orogenies. Even though suc...

LGscore: A method to identify disease-related genes using biological literature and Google data.

Science.gov (United States)

Kim, Jeongwoo; Kim, Hyunjin; Yoon, Youngmi; Park, Sanghyun

2015-04-01

Since the genome project in 1990s, a number of studies associated with genes have been conducted and researchers have confirmed that genes are involved in disease. For this reason, the identification of the relationships between diseases and genes is important in biology. We propose a method called LGscore, which identifies disease-related genes using Google data and literature data. To implement this method, first, we construct a disease-related gene network using text-mining results. We then extract gene-gene interactions based on co-occurrences in abstract data obtained from PubMed, and calculate the weights of edges in the gene network by means of Z-scoring. The weights contain two values: the frequency and the Google search results. The frequency value is extracted from literature data, and the Google search result is obtained using Google. We assign a score to each gene through a network analysis. We assume that genes with a large number of links and numerous Google search results and frequency values are more likely to be involved in disease. For validation, we investigated the top 20 inferred genes for five different diseases using answer sets. The answer sets comprised six databases that contain information on disease-gene relationships. We identified a significant number of disease-related genes as well as candidate genes for Alzheimer's disease, diabetes, colon cancer, lung cancer, and prostate cancer. Our method was up to 40% more accurate than existing methods. Copyright © 2015 Elsevier Inc. All rights reserved.

A maize resistance gene functions against bacterial streak disease in rice

OpenAIRE

Zhao, Bingyu; Lin, Xinghua; Poland, Jesse; Trick, Harold; Leach, Jan; Hulbert, Scot

2005-01-01

Although cereal crops all belong to the grass family (Poacea), most of their diseases are specific to a particular species. Thus, a given cereal species is typically resistant to diseases of other grasses, and this nonhost resistance is generally stable. To determine the feasibility of transferring nonhost resistance genes (R genes) between distantly related grasses to control specific diseases, we identified a maize R gene that recognizes a rice pathogen, Xanthomonas oryzae pv. oryzicola, wh...

Non-Abelian Stokes theorem for the Wilson loop operator in an arbitrary representation and its implication to quark confinement

Science.gov (United States)

Matsudo, Ryutaro; Kondo, Kei-Ichi

2015-12-01

We give a gauge-independent definition of magnetic monopoles in the S U (N ) Yang-Mills theory through the Wilson loop operator. For this purpose, we give an explicit proof of the Diakonov-Petrov version of the non-Abelian Stokes theorem for the Wilson loop operator in an arbitrary representation of the S U (N ) gauge group to derive a new form for the non-Abelian Stokes theorem. The new form is used to extract the magnetic-monopole contribution to the Wilson loop operator in a gauge-invariant way, which enables us to discuss confinement of quarks in any representation from the viewpoint of the dual superconductor vacuum.

Association between Polymorphisms in Antioxidant Genes and Inflammatory Bowel Disease.

Directory of Open Access Journals (Sweden)

Cristiana Costa Pereira

Full Text Available Inflammation is the driving force in inflammatory bowel disease (IBD and its link to oxidative stress and carcinogenesis has long been accepted. The antioxidant system of the intestinal mucosa in IBD is compromised resulting in increased oxidative injury. This defective antioxidant system may be the result of genetic variants in antioxidant genes, which can represent susceptibility factors for IBD, namely Crohn's disease (CD and ulcerative colitis (UC. Single nucleotide polymorphisms (SNPs in the antioxidant genes SOD2 (rs4880 and GPX1 (rs1050450 were genotyped in a Portuguese population comprising 436 Crohn's disease and 367 ulcerative colitis patients, and 434 healthy controls. We found that the AA genotype in GPX1 is associated with ulcerative colitis (OR = 1.93, adjusted P-value = 0.037. Moreover, we found nominal significant associations between SOD2 and Crohn's disease susceptibility and disease subphenotypes but these did not withstand the correction for multiple testing. These findings indicate a possible link between disease phenotypes and antioxidant genes. These results suggest a potential role for antioxidant genes in IBD pathogenesis and should be considered in future association studies.

Gene expression profiling in autoimmune diseases: chronic inflammation or disease specific patterns?

DEFF Research Database (Denmark)

Bovin, Lone Frier; Brynskov, Jørn; Hegedüs, Laszlo

2007-01-01

) patients and healthy individuals were specific for the arthritic process or likewise altered in other chronic inflammatory diseases such as chronic autoimmune thyroiditis (Hashimoto's thyroiditis, HT) and inflammatory bowel disease (IBD). Using qPCR for 18 RA-discriminative genes, there were no significant...

New Genes and New Insights from Old Genes: Update on Alzheimer Disease

Science.gov (United States)

Ringman, John M.; Coppola, Giovanni

2013-01-01

Purpose of Review: This article discusses the current status of knowledge regarding the genetic basis of Alzheimer disease (AD) with a focus on clinically relevant aspects. Recent Findings: The genetic architecture of AD is complex, as it includes multiple susceptibility genes and likely nongenetic factors. Rare but highly penetrant autosomal dominant mutations explain a small minority of the cases but have allowed tremendous advances in understanding disease pathogenesis. The identification of a strong genetic risk factor, APOE, reshaped the field and introduced the notion of genetic risk for AD. More recently, large-scale genome-wide association studies are adding to the picture a number of common variants with very small effect sizes. Large-scale resequencing studies are expected to identify additional risk factors, including rare susceptibility variants and structural variation. Summary: Genetic assessment is currently of limited utility in clinical practice because of the low frequency (Mendelian mutations) or small effect size (common risk factors) of the currently known susceptibility genes. However, genetic studies are identifying with confidence a number of novel risk genes, and this will further our understanding of disease biology and possibly the identification of therapeutic targets. PMID:23558482

Light quark masses with Nf = 2 Wilson fermions

International Nuclear Information System (INIS)

Eicker, N.; Lippert, Th.; Orth, B.; Schilling, K.

2002-01-01

We present new data on the mass of the light and strange quarks from SESAM/TχL. The results were obtained on lattice-volumes of 16 3 x 32 and 24 3 x 40 points, with the possibility to investigate finite-size effects. Since the SESAM/TχL ensembles at β = 5.6 have been complemented by configurations with β = 5.5, moreover, we are now able to attempt the continuum extrapolation (CE) of the quark masses with standard Wilson fermions

DRUMS: a human disease related unique gene mutation search engine.

Science.gov (United States)

Li, Zuofeng; Liu, Xingnan; Wen, Jingran; Xu, Ye; Zhao, Xin; Li, Xuan; Liu, Lei; Zhang, Xiaoyan

2011-10-01

With the completion of the human genome project and the development of new methods for gene variant detection, the integration of mutation data and its phenotypic consequences has become more important than ever. Among all available resources, locus-specific databases (LSDBs) curate one or more specific genes' mutation data along with high-quality phenotypes. Although some genotype-phenotype data from LSDB have been integrated into central databases little effort has been made to integrate all these data by a search engine approach. In this work, we have developed disease related unique gene mutation search engine (DRUMS), a search engine for human disease related unique gene mutation as a convenient tool for biologists or physicians to retrieve gene variant and related phenotype information. Gene variant and phenotype information were stored in a gene-centred relational database. Moreover, the relationships between mutations and diseases were indexed by the uniform resource identifier from LSDB, or another central database. By querying DRUMS, users can access the most popular mutation databases under one interface. DRUMS could be treated as a domain specific search engine. By using web crawling, indexing, and searching technologies, it provides a competitively efficient interface for searching and retrieving mutation data and their relationships to diseases. The present system is freely accessible at http://www.scbit.org/glif/new/drums/index.html. © 2011 Wiley-Liss, Inc.

Role of T cell receptor delta gene in susceptibility to celiac disease.

Science.gov (United States)

Roschmann, E; Wienker, T F; Volk, B A

1996-02-01

There is a strong genetic influence on the susceptibility to celiac disease. Although in the vast majority of patients with celiac disease, the HLA-DQ(alpha1*0501, beta1*0201) heterodimer encoded by the alleles HLA-DQA1*0501 and HLA-DQB1*0201 seems to confer the primary disease susceptibility, it cannot be excluded that other genes contribute to disease susceptibility, as indicated by the difference in concordance rates between monozygotic twins and HLA identical siblings (70% vs. 30%). Obviously other genes involved in the genetic control of T cell mediated immune response could potentially influence susceptibility to celiac disease. The density of T cells using the gammadelta T cell receptor (TCR) is considerably increased in the jejunal epithelium of patients with celiac disease, an abnormality considered to be specific for celiac disease. This suggests an involvement of gammadelta T cells in the pathogenesis of the disease. To ascertain whether the TCR delta (TCRD) gene contributes to celiac disease susceptibility we carried out an association study and genetic linkage analysis using a highly polymorphic microsatellite marker at the TCRD locus on chromosome 14q11.2. The association study demonstrated no significant difference in allele frequencies of the TCRD gene marker between celiac disease patients and controls; accordingly, the relative risk estimates did not reach the level of statistical significance. In the linkage analysis, performed in 23 families, the logarithm of the odds (LOD) scores calculated for celiac disease versus the TCRD gene marker excluded linkage, suggesting that there is no determinant contributing to celiac disease status at or 5 cM distant to the analyzed TCRD gene marker. In conclusion, the results of the present study provide no evidence that the analyzed TCRD gene contributes substantially to celiac disease susceptibility.

Exponentiation for products of Wilson lines within the generating function approach

International Nuclear Information System (INIS)

Vladimirov, A.A.

2015-01-01

We present the generating function approach to the perturbative exponentiation of correlators of a product of Wilson lines and loops. The exponentiated expression is presented in closed form as an algebraic function of correlators of known operators, which can be seen as a generating function for web diagrams. The expression is naturally split onto two parts: the exponentiation kernel, which accumulates all non-trivial information about web diagrams, and the defect of exponentiation, which reconstructs the matrix exponent and is a function of the exponentiation kernel. The detailed comparison of the presented approach with existing approaches to exponentiation is presented as well. We also give examples of calculations within the generating function exponentiation, namely, we consider different configurations of light-like Wilson lines in the multi-gluon-exchange-webs (MGEW) approximation. Within this approximation the corresponding correlators can be calculated exactly at any order of perturbative expansion by only algebraic manipulations. The MGEW approximation shows violation of the dipole formula for infrared singularities at three-loop order.

A conditioning technique for matrix inversion for Wilson fermions

International Nuclear Information System (INIS)

DeGrand, T.A.

1988-01-01

I report a simple technique for conditioning conjugate gradient or conjugate residue matrix inversion as applied to the lattice gauge theory problem of computing the propagator of Wilson fermions. One form of the technique provides about a factor of three speedup over an unconditioned algorithm while running at the same speed as an unconditioned algorithm. I illustrate the method as it is applied to a conjugate residue algorithm. (orig.)

Abelian Chern-Simons theory as the strong large-mass limit of topologically massive abelian gauge theory: the Wilson loop

International Nuclear Information System (INIS)

Giavarini, G.; Martin, C.P.; Ruiz Ruiz, F.

1993-01-01

We show that the renormalized vacuum expectation value of the Wilson loop for topologically massive abelian gauge theory in bbfR 3 can be defined so that its large-mass limit be the renormalized vaccum expectation value of the Wilson loop for abelian Chern-Simons theory also in bbfR 3 . (orig.)

Wilson Loop and related strings for the instanton and their variational derivatives

International Nuclear Information System (INIS)

Bollini, C.G.; Giambiagi, J.J.; Tiomno, J.

1980-05-01

Ordered integrals along arcs (or circles) and segments for the instanton are computed. They are to obtain variational and partial derivatives for open an d closed strings. The D'Alembertian for wilson loops is also computed. (Author) [pt

Prioritizing chronic obstructive pulmonary disease (COPD) candidate genes in COPD-related networks.

Science.gov (United States)

Zhang, Yihua; Li, Wan; Feng, Yuyan; Guo, Shanshan; Zhao, Xilei; Wang, Yahui; He, Yuehan; He, Weiming; Chen, Lina

2017-11-28

Chronic obstructive pulmonary disease (COPD) is a multi-factor disease, which could be caused by many factors, including disturbances of metabolism and protein-protein interactions (PPIs). In this paper, a weighted COPD-related metabolic network and a weighted COPD-related PPI network were constructed base on COPD disease genes and functional information. Candidate genes in these weighted COPD-related networks were prioritized by making use of a gene prioritization method, respectively. Literature review and functional enrichment analysis of the top 100 genes in these two networks suggested the correlation of COPD and these genes. The performance of our gene prioritization method was superior to that of ToppGene and ToppNet for genes from the COPD-related metabolic network or the COPD-related PPI network after assessing using leave-one-out cross-validation, literature validation and functional enrichment analysis. The top-ranked genes prioritized from COPD-related metabolic and PPI networks could promote the better understanding about the molecular mechanism of this disease from different perspectives. The top 100 genes in COPD-related metabolic network or COPD-related PPI network might be potential markers for the diagnosis and treatment of COPD.

Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease.

Science.gov (United States)

Johnson, Michael R; Shkura, Kirill; Langley, Sarah R; Delahaye-Duriez, Andree; Srivastava, Prashant; Hill, W David; Rackham, Owen J L; Davies, Gail; Harris, Sarah E; Moreno-Moral, Aida; Rotival, Maxime; Speed, Doug; Petrovski, Slavé; Katz, Anaïs; Hayward, Caroline; Porteous, David J; Smith, Blair H; Padmanabhan, Sandosh; Hocking, Lynne J; Starr, John M; Liewald, David C; Visconti, Alessia; Falchi, Mario; Bottolo, Leonardo; Rossetti, Tiziana; Danis, Bénédicte; Mazzuferi, Manuela; Foerch, Patrik; Grote, Alexander; Helmstaedter, Christoph; Becker, Albert J; Kaminski, Rafal M; Deary, Ian J; Petretto, Enrico

2016-02-01

Genetic determinants of cognition are poorly characterized, and their relationship to genes that confer risk for neurodevelopmental disease is unclear. Here we performed a systems-level analysis of genome-wide gene expression data to infer gene-regulatory networks conserved across species and brain regions. Two of these networks, M1 and M3, showed replicable enrichment for common genetic variants underlying healthy human cognitive abilities, including memory. Using exome sequence data from 6,871 trios, we found that M3 genes were also enriched for mutations ascertained from patients with neurodevelopmental disease generally, and intellectual disability and epileptic encephalopathy in particular. M3 consists of 150 genes whose expression is tightly developmentally regulated, but which are collectively poorly annotated for known functional pathways. These results illustrate how systems-level analyses can reveal previously unappreciated relationships between neurodevelopmental disease-associated genes in the developed human brain, and provide empirical support for a convergent gene-regulatory network influencing cognition and neurodevelopmental disease.

String corrections to circular Wilson loop and anomalies

Science.gov (United States)

Cagnazzo, Alessandra; Medina-Rincon, Daniel; Zarembo, Konstantin

2018-02-01

We study string quantum corrections to the ratio of latitude and circular Wilson loops in N = 4 super-Yang-Mills theory at strong coupling. Conformal gauge for the corresponding minimal surface in AdS5 × S 5 is singular and we show that an IR anomaly associated with the divergence in the conformal factor removes previously reported discrepancy with the exact field-theory result. We also carefully check conformal anomaly cancellation and recalculate fluctuation determinants by directly evaluting phaseshifts for all the fluctuation modes.

Journal of Genetics | Indian Academy of Sciences

Indian Academy of Sciences (India)

Genetic analysis of 55 northern Vietnamese patients with Wilson disease: ..... with familial Norrie disease: bilateral blindness and leucocoria without other deficits ... A novel missense mutation of ADAR1gene in a Chinese family leading to ...

Segment-based Eyring-Wilson viscosity model for polymer solutions

International Nuclear Information System (INIS)

Sadeghi, Rahmat

2005-01-01

A theory-based model is presented for correlating viscosity of polymer solutions and is based on the segment-based Eyring mixture viscosity model as well as the segment-based Wilson model for describing deviations from ideality. The model has been applied to several polymer solutions and the results show that it is reliable both for correlation and prediction of the viscosity of polymer solutions at different molar masses and temperature of the polymer

Syndrome parkinsonien secondaire à une maladie de Wilson chez ...

African Journals Online (AJOL)

Nous apportons une observation d'un cas de la maladie de Wilson, révélé par un syndrome parkinsonien. Le diagnostic a reposé sur les troubles neuropsychiques, la présence de l'anneau cornéen de Kayser-Fleischer, et les troubles du métabolisme du cuivre. Le scanner cérébral était normal, et l'IRM cérébrale a montré ...

Corrections to the Banks-Casher relation with Wilson quarks

CERN Document Server

Necco, S

2013-01-01

The Banks-Casher relation links the spectral density of the Dirac operator with the existence of a chiral condensate and spontaneous breaking of chiral symmetry. This relation receives corrections from a finite value of the quark mass, a finite space-time volume and, if evaluated on a discrete lattice, from the finite value of the lattice spacing a. We present a status report of a determination of these corrections for Wilson quarks.

Spatial investigation of the elemental distribution in Wilson's disease liver after d-penicillamine treatment by LA-ICP-MS.

Science.gov (United States)

Hachmöller, Oliver; Zibert, Andree; Zischka, Hans; Sperling, Michael; Groba, Sara Reinartz; Grünewald, Inga; Wardelmann, Eva; Schmidt, Hartmut H-J; Karst, Uwe

2017-12-01

At present, the copper chelator d-penicillamine (DPA) is the first-line therapy of Wilson's disease (WD), which is characterized by an excessive copper overload. Lifelong DPA treatments aim to reduce the amount of detrimental excess copper retention in the liver and other organs. Although DPA shows beneficial effect in many patients, it may cause severe adverse effects. Despite several years of copper chelation therapy, discontinuation of DPA therapy can be linked to a rapidly progressing liver failure, indicating a high residual liver copper load. In order to investigate the spatial distribution of remaining copper and additional elements, such as zinc and iron, in rat and human liver samples after DPA treatment, a high resolution (spotsize of 10μm) laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging method was applied. Untreated LPP -/- rats, an established animal model for WD, appeared with a high overall copper concentration and a copper distribution of hotspots distributed over the liver tissue. In contrast, a low (>2-fold decreased) overall copper concentration was detected in liver of DPA treated animals. Importantly, however, copper distribution was highly inhomogeneous with lowest concentrations in direct proximity to blood vessels, as observed using novel zonal analysis. A human liver needle biopsy of a DPA treated WD patient substantiated the finding of an inhomogeneous copper deposition upon chelation therapy. In contrast, comparatively homogenous distributions of zinc and iron were observed. Our study indicates that a high resolution LA-ICP-MS analysis of liver samples is excellently suited to follow efficacy of chelator therapy in WD patients. Copyright © 2017 Elsevier GmbH. All rights reserved.

In Search of 'Birth Month Genes': Using Existing Data Repositories to Locate Genes Underlying Birth Month-Disease Relationships.

Science.gov (United States)

Boland, Mary Regina; Tatonetti, Nicholas P

2016-01-01

Prenatal and perinatal exposures vary seasonally (e.g., sunlight, allergens) and many diseases are linked with variance in exposure. Epidemiologists often measure these changes using birth month as a proxy for seasonal variance. Likewise, Genome-Wide Association Studies have associated or implicated these same diseases with many genes. Both disparate data types (epidemiological and genetic) can provide key insights into the underlying disease biology. We developed an algorithm that links 1) epidemiological data from birth month studies with 2) genetic data from published gene-disease association studies. Our framework uses existing data repositories - PubMed, DisGeNET and Gene Ontology - to produce a bipartite network that connects enriched seasonally varying biofactorss with birth month dependent diseases (BMDDs) through their overlapping developmental gene sets. As a proof-of-concept, we investigate 7 known BMDDs and highlight three important biological networks revealed by our algorithm and explore some interesting genetic mechanisms potentially responsible for the seasonal contribution to BMDDs.

Perturbative expansions from Monte Carlo simulations at weak coupling: Wilson loops and the static-quark self-energy

Science.gov (United States)

Trottier, H. D.; Shakespeare, N. H.; Lepage, G. P.; MacKenzie, P. B.

2002-05-01

Perturbative coefficients for Wilson loops and the static-quark self-energy are extracted from Monte Carlo simulations at weak coupling. The lattice volumes and couplings are chosen to ensure that the lattice momenta are all perturbative. Twisted boundary conditions are used to eliminate the effects of lattice zero modes and to suppress nonperturbative finite-volume effects due to Z(3) phases. Simulations of the Wilson gluon action are done with both periodic and twisted boundary conditions, and over a wide range of lattice volumes (from 34 to 164) and couplings (from β~9 to β~60). A high precision comparison is made between the simulation data and results from finite-volume lattice perturbation theory. The Monte Carlo results are shown to be in excellent agreement with perturbation theory through second order. New results for third-order coefficients for a number of Wilson loops and the static-quark self-energy are reported.

Gravity duals of half-BPS Wilson loops

International Nuclear Information System (INIS)

D'Hoker, Eric; Estes, John; Gutperle, Michael

2007-01-01

We explicitly construct the fully back-reacted half-BPS solutions in Type IIB supergravity which are dual to Wilson loops with 16 supersymmetries in N = 4 super Yang-Mills. In a first part, we use the methods of a companion paper to derive the exact general solution of the half-BPS equations on the space AdS 2 x S 2 x S 4 x Σ, with isometry group SO(2, 1) x SO(3) x SO(5) in terms of two locally harmonic functions on a Riemann surface Σ with boundary. These solutions, generally, have varying dilaton and axion, and non-vanishing 3-form fluxes. In a second part, we impose regularity and topology conditions. These non-singular solutions may be parametrized by a genus g ≥ 0 hyperelliptic surface Σ, all of whose branch points lie on the real line. Each genus g solution has only a single asymptotic AdS 5 x S 5 region, but exhibits g homology 3-spheres, and an extra g homology 5-spheres, carrying respectively RR 3-form and RR 5-form charges. For genus 0, we recover AdS 5 x S 5 with 3 free parameters, while for genus g ≥ 1, the solution has 2g+5 free parameters. The genus 1 case is studied in detail. Numerical analysis is used to show that the solutions are regular throughout the g = 1 parameter space. Collapse of a branch cut on Σ subtending either a homology 3-sphere or a homology 5-sphere is non-singular and yields the genus g-1 solution. This behavior is precisely expected of a proper dual to a Wilson loop in gauge theory

One-loop Wilson loops and the particle-interface potential in AdS/dCFT

Directory of Open Access Journals (Sweden)

Marius de Leeuw

2017-05-01

Full Text Available We initiate the calculation of quantum corrections to Wilson loops in a class of four-dimensional defect conformal field theories with vacuum expectation values based on N=4 super Yang–Mills theory. Concretely, we consider an infinite straight Wilson line, obtaining explicit results for the one-loop correction to its expectation value in the large-N limit. This allows us to extract the particle-interface potential of the theory. In a further double-scaling limit, we compare our results to those of a previous calculation in the dual string-theory set-up consisting of a D5-D3 probe-brane system with flux, and we find perfect agreement.

Frequency-dependent changes in the amplitude of low-frequency fluctuations in patients with Wilson's disease: a resting-state fMRI study.

Science.gov (United States)

Hu, Xiaopeng; Chen, Siyi; Huang, Chang-Bing; Qian, Yinfeng; Yu, Yongqiang

2017-06-01

To investigate the frequency-dependent changes in the amplitude of low-frequency fluctuations (ALFF) in patients with Wilson's disease (WD). Resting-state function magnetic resonance imaging (R-fMRI) were employed to measure the amplitude of ALFF in 28 patients with WD and 27 matched normal controls. Slow-5 (0.01-0.027 Hz) and slow-4 (0.027-0.073 Hz) frequency bands were analyzed. Apart from the observation of atrophy in the cerebellum, basal ganglia, occipital gyrus, frontal gyrus, precentral gyrus, and paracentral lobule, we also found widespread differences in ALFF of the two bands in the medial frontal gyrus, inferior temporal gyrus, insula, basal ganglia, hippocampus/parahippocampal gyrus, and thalamus bilaterally. Compared to normal controls, WD patients had increased ALFF in the posterior lobe of the cerebellum, inferior temporal gyrus, brain stem, basal ganglia, and decreased ALFF in the anterior lobe of the cerebellum and medial frontal gyrus. Specifically, we observed that the ALFF abnormalities in the cerebellum and middle frontal gyrus were greater in the slow-5 than in the slow-4 band. Correlation analysis showed consistently positive correlations between urinary copper excretion (Cu), serum ceruloplasmin (CP) and ALFFs in the cerebellum. Our study suggests the accumulation of copper profoundly impaired intrinsic brain activity and the impairments seem to be frequency-dependent. These results provide further insights into the understanding of the pathophysiology of WD.

College Board Response to "Harvard Educational Review" Article by Santelices and Wilson

Science.gov (United States)

College Board, 2010

2010-01-01

This is the College Board's response to a research article by Drs. Maria Veronica Santelices and Mark Wilson in the Harvard Educational Review, entitled "Unfair Treatment? The Case of Freedle, the SAT, and the Standardization Approach to Differential Item Functioning" (see EJ930622).

Web tools for the prioritization of candidate disease genes.

NARCIS (Netherlands)

Oti, M.O.; Ballouz, S.; Wouters, M.A.

2011-01-01

Despite increasing sequencing capacity, genetic disease investigation still frequently results in the identification of loci containing multiple candidate disease genes that need to be tested for involvement in the disease. This process can be expedited by prioritizing the candidates prior to

Integrated Analyses of Gene Expression Profiles Digs out Common Markers for Rheumatic Diseases

Science.gov (United States)

Wang, Lan; Wu, Long-Fei; Lu, Xin; Mo, Xing-Bo; Tang, Zai-Xiang; Lei, Shu-Feng; Deng, Fei-Yan

2015-01-01

Objective Rheumatic diseases have some common symptoms. Extensive gene expression studies, accumulated thus far, have successfully identified signature molecules for each rheumatic disease, individually. However, whether there exist shared factors across rheumatic diseases has yet to be tested. Methods We collected and utilized 6 public microarray datasets covering 4 types of representative rheumatic diseases including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and osteoarthritis. Then we detected overlaps of differentially expressed genes across datasets and performed a meta-analysis aiming at identifying common differentially expressed genes that discriminate between pathological cases and normal controls. To further gain insights into the functions of the identified common differentially expressed genes, we conducted gene ontology enrichment analysis and protein-protein interaction analysis. Results We identified a total of eight differentially expressed genes (TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, PRF1), each associated with at least 3 of the 4 studied rheumatic diseases. Meta-analysis warranted the significance of the eight genes and highlighted the general significance of four genes (CX3CR1, LY96, TLR5, and PRF1). Protein-protein interaction and gene ontology enrichment analyses indicated that the eight genes interact with each other to exert functions related to immune response and immune regulation. Conclusion The findings support that there exist common factors underlying rheumatic diseases. For rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and osteoarthritis diseases, those common factors include TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, and PRF1. In-depth studies on these common factors may provide keys to understanding the pathogenesis and developing intervention strategies for rheumatic diseases. PMID:26352601

Dysregulation of RNA Mediated Gene Expression in Motor Neuron Diseases.

Science.gov (United States)

Gonçalves, Inês do Carmo G; Rehorst, Wiebke A; Kye, Min Jeong

2016-01-01

Recent findings indicate an important role for RNA-mediated gene expression in motor neuron diseases, including ALS (amyotrophic lateral sclerosis) and SMA (spinal muscular atrophy). ALS, also known as Lou Gehrig's disease, is an adult-onset progressive neurodegenerative disorder, whereby SMA or "children's Lou Gehrig's disease" is considered a pediatric neurodevelopmental disorder. Despite the difference in genetic causes, both ALS and SMA share common phenotypes; dysfunction/loss of motor neurons that eventually leads to muscle weakness and atrophy. With advanced techniques in molecular genetics and cell biology, current data suggest that these two distinct motor neuron diseases share more than phenotypes; ALS and SMA have similar cellular pathological mechanisms including mitochondrial dysfunction, oxidative stress and dysregulation in RNA-mediated gene expression. Here, we will discuss the current findings on these two diseases with specific focus on RNA-mediated gene regulation including miRNA expression, pre-mRNA processing and RNA binding proteins.

Wilson Fermions and Axion Electrodynamics in Optical Lattices

International Nuclear Information System (INIS)

Bermudez, A.; Martin-Delgado, M. A.; Mazza, L.; Rizzi, M.; Goldman, N.; Lewenstein, M.

2010-01-01

We show that ultracold Fermi gases in optical superlattices can be used as quantum simulators of relativistic lattice fermions in 3+1 dimensions. By exploiting laser-assisted tunneling, we find an analogue of the so-called naive Dirac fermions, and thus provide a realization of the fermion doubling problem. Moreover, we show how to implement Wilson fermions, and discuss how their mass can be inverted by tuning the laser intensities. In this regime, our atomic gas corresponds to a phase of matter where Maxwell electrodynamics is replaced by axion electrodynamics: a 3D topological insulator.

Parallel tempering in full QCD with Wilson fermions

International Nuclear Information System (INIS)

Ilgenfritz, E.-M.; Kerler, W.; Mueller-Preussker, M.; Stueben, H.

2002-01-01

We study the performance of QCD simulations with dynamical Wilson fermions by combining the hybrid Monte Carlo algorithm with parallel tempering on 10 4 and 12 4 lattices. In order to compare tempered with standard simulations, covariance matrices between subensembles have to be formulated and evaluated using the general properties of autocorrelations of the parallel tempering algorithm. We find that rendering the hopping parameter κ dynamical does not lead to an essential improvement. We point out possible reasons for this observation and discuss more suitable ways of applying parallel tempering to QCD

Aldosterone synthase gene is not a major susceptibility gene for progression of chronic kidney disease in patients with autosomal dominant polycystic kidney disease

Directory of Open Access Journals (Sweden)

Gnanasambandan Ramanathan

2017-01-01

Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is the most common heritable kidney disease and is characterized by bilateral renal cysts. Hypertension is a frequent cause of chronic kidney disease (CKD and mortality in patients with ADPKD. The aldosterone synthase gene polymorphisms of the renin-angiotensin-aldosterone system have been extensively studied as hypertension candidate genes. The present study is aimed to investigate the potential modifier effect of CYP11B2 gene on the progression of CKD in ADPKD. One hundred and two ADPKD patients and 106 healthy controls were recruited based on Ravine inclusion and exclusion criteria. The three tag-SNPs within CYP11B2 gene (rs3802230, rs4543, and rs4544 were genotyped using FRET-based KASPar method. Cochran-Armitage trend test was used to assess the potential associations between these polymorphisms and CKD stages. Mantel- Haenszel stratified analysis was used to explore confounding and interaction effects of these polymorphisms. Of the three tag-SNPs genotyped, rs4544 polymorphism was monomorphic and rs3802230 deviated Hardy-Weinberg equilibrium. The CYP11B2 tag-SNPs did not show significant association with ADPKD or CKD. Further, these polymorphisms did not exhibit confounding effect on the relationship between CKD progression and hypertension. Our results suggest that aldosterone synthase gene is not a major susceptibility gene for progression of CKD in South Indian ADPKD patients.

Infrared singularities of fermion propagator and their connection with the Wilson loop

International Nuclear Information System (INIS)

Sissakyan, A.N.; Skachkov, N.B.; Shevchenko, O.Yu.

1987-01-01

The factorization of infrared singularities of gauge-invariant spinor propagator is proved in the framework of QED. It turns out that this infrared factor coincides with the Wilson loop and accumulates all the dependence on the form of the path of the initial Green function

The Development of Field Guides for Birding: Gwillim, Wilson, Audubon and Peterson.

Science.gov (United States)

Cameron, Teddy

2000-01-01

Discusses the increasing interest of the public in nature and art of the 18th and 19th centuries, and making watercolor painting a part of the curriculum. Focuses on the works and publishing of Gwillim, Wilson, Audubon, and Peterson. (Contains 12 references.) (YDS)

Probability-based collaborative filtering model for predicting gene-disease associations.

Science.gov (United States)

Zeng, Xiangxiang; Ding, Ningxiang; Rodríguez-Patón, Alfonso; Zou, Quan

2017-12-28

Accurately predicting pathogenic human genes has been challenging in recent research. Considering extensive gene-disease data verified by biological experiments, we can apply computational methods to perform accurate predictions with reduced time and expenses. We propose a probability-based collaborative filtering model (PCFM) to predict pathogenic human genes. Several kinds of data sets, containing data of humans and data of other nonhuman species, are integrated in our model. Firstly, on the basis of a typical latent factorization model, we propose model I with an average heterogeneous regularization. Secondly, we develop modified model II with personal heterogeneous regularization to enhance the accuracy of aforementioned models. In this model, vector space similarity or Pearson correlation coefficient metrics and data on related species are also used. We compared the results of PCFM with the results of four state-of-arts approaches. The results show that PCFM performs better than other advanced approaches. PCFM model can be leveraged for predictions of disease genes, especially for new human genes or diseases with no known relationships.

p.H1069Q mutation in ATP7B and biochemical parameters of copper metabolism and clinical manifestation of Wilson's disease.

Science.gov (United States)

Gromadzka, Graznya; Schmidt, Harmut H J; Genschel, Janine; Bochow, Bettina; Rodo, M; Tarnacka, Beatek; Litwin, Thomas; Chabik, Grzegorz; Członkowska, Anna

2006-02-01

We compared the effect of the p.H1069Q mutation and other non-p.H1069Q mutations in ATP7B on the phenotypic expression of Wilson's disease (WD), and assessed whether the clinical phenotype of WD in compound heterozygotes depends on the type of mutation coexisting with the p.H1069Q. One hundred forty-two patients with clinically, biochemically, and genetically diagnosed WD were studied. The mutational analysis of ATP7B was performed by direct sequencing. A total number of 26 mutations in ATP7B were identified. The p.His1069Gln was the most common mutation (allelic frequency: 72%). Seventy-three patients were homozygous for this mutation. Of compound heterozygotes, 37 had frameshift/nonsense mutation, and 20 had other missense mutation on one of their ATP7B alleles. Twelve patients had two non-p.H1069Q mutations. Patients homozygous for the p.H1069Q mutation had the less severe disturbances of copper metabolism and the latest presentation of first WD symptoms. The most severely disturbed copper metabolism and the earliest age at initial disease manifestation was noticed in non-p.H1069Q patients. In compound heterozygotes, the type of mutation coexisting with the p.H1069Q to a small extent influenced WD phenotype. The phenotype of WD varied considerably among patients with the same genotype. The p.H1069Q mutation is associated with late WD manifestation and with a mild disruption of copper metabolism. In compound heterozygotes, the phenotype of WD to a small extent depends on the type of mutation coexisting with the p.H1069Q. Besides genotype, additional modifying factors seem to determine WD manifestations. Copyright (c) 2005 Movement Disorder Society.

Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms

Directory of Open Access Journals (Sweden)

Joanna Balding

2004-01-01

Full Text Available THE mechanisms responsible for development of inflammatory bowel disease (IBD have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n=172 and healthy controls (n=389 for polymorphisms in genes encoding various cytokines (interleukin (IL-1β, IL-6, tumour necrosis factor (TNF, IL-10, IL-1 receptor antagonist. Association of these genotypes to disease incidence and pathophysiology was investigated. No strong association was found with occurrence of IBD. Variation was observed between the ulcerative colitis study group and the control population for the TNF-α-308 polymorphism (p=0.0135. There was also variation in the frequency of IL-6-174 and TNF-α-308 genotypes in the ulcerative colitis group compared with the Crohn's disease group (p=0.01. We concluded that polymorphisms in inflammatory genes are associated with variations in IBD phenotype and disease susceptibility. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently pathophysiology of IBD, or serve merely as markers in linkage disequilibrium with susceptibility genes remains unclear.

KMeyeDB: a graphical database of mutations in genes that cause eye diseases.

Science.gov (United States)

Kawamura, Takashi; Ohtsubo, Masafumi; Mitsuyama, Susumu; Ohno-Nakamura, Saho; Shimizu, Nobuyoshi; Minoshima, Shinsei

2010-06-01

KMeyeDB (http://mutview.dmb.med.keio.ac.jp/) is a database of human gene mutations that cause eye diseases. We have substantially enriched the amount of data in the database, which now contains information about the mutations of 167 human genes causing eye-related diseases including retinitis pigmentosa, cone-rod dystrophy, night blindness, Oguchi disease, Stargardt disease, macular degeneration, Leber congenital amaurosis, corneal dystrophy, cataract, glaucoma, retinoblastoma, Bardet-Biedl syndrome, and Usher syndrome. KMeyeDB is operated using the database software MutationView, which deals with various characters of mutations, gene structure, protein functional domains, and polymerase chain reaction (PCR) primers, as well as clinical data for each case. Users can access the database using an ordinary Internet browser with smooth user-interface, without user registration. The results are displayed on the graphical windows together with statistical calculations. All mutations and associated data have been collected from published articles. Careful data analysis with KMeyeDB revealed many interesting features regarding the mutations in 167 genes that cause 326 different types of eye diseases. Some genes are involved in multiple types of eye diseases, whereas several eye diseases are caused by different mutations in one gene.

Perturbative expansions from Monte Carlo simulations at weak coupling: Wilson loops and the static-quark self-energy

International Nuclear Information System (INIS)

Trottier, H.D.; Shakespeare, N.H.; Lepage, G.P.; Mackenzie, P.B.

2002-01-01

Perturbative coefficients for Wilson loops and the static-quark self-energy are extracted from Monte Carlo simulations at weak coupling. The lattice volumes and couplings are chosen to ensure that the lattice momenta are all perturbative. Twisted boundary conditions are used to eliminate the effects of lattice zero modes and to suppress nonperturbative finite-volume effects due to Z(3) phases. Simulations of the Wilson gluon action are done with both periodic and twisted boundary conditions, and over a wide range of lattice volumes (from 3 4 to 16 4 ) and couplings (from β≅9 to β≅60). A high precision comparison is made between the simulation data and results from finite-volume lattice perturbation theory. The Monte Carlo results are shown to be in excellent agreement with perturbation theory through second order. New results for third-order coefficients for a number of Wilson loops and the static-quark self-energy are reported

Standard model Wilson coefficients for c → ul{sup +}l{sup -} transitions at next-to-leading order

Energy Technology Data Exchange (ETDEWEB)

Boer, Stefan de [TU Dortmund (Germany); Mueller, Bastian; Seidel, Dirk [Uni Siegen (Germany)

2016-07-01

The standard theoretical framework to deal with exclusive, weak decays of heavy mesons is the so-called weak effective Hamiltonian. It involves the short-distance Wilson coefficients, which depend on the renormalization scale μ. For specific calculations one has to evolve the Wilson coefficients down from the electroweak scale μ{sub W} to the typical mass scale of the decay under consideration. This is done by solving a renormalization group equation for the effective operator basis. In this talk the results of a consistent two-step running of the c → ul{sup +}l{sup -} Wilson coefficients are presented. This running involves the intermediate scale μ{sub b} (with μ{sub W} > μ{sub b} > μ{sub c}) where the bottom quark is integrated out. All the matching coefficients and anomalous dimensions are taken to the required order by generalizing and extending results from b → s or s → d transitions available in the literature.

PTPN22 gene polymorphisms in autoimmune diseases with special reference to systemic lupus erythematosus disease susceptibility

Directory of Open Access Journals (Sweden)

Pradhan V

2010-01-01

Full Text Available Systemic lupus erythematosus (SLE is a prototype autoimmune disease. SLE is a result of one or more immune mechanisms, like autoantibody production, complement activation, multiple inflammation and immune complex deposition leading to organ tissue damage. SLE affected patients are susceptible to common and opportunistic infections. There are several reports suggesting that Mycobacterium tuberculosis infection precipitates SLE in patients from endemic areas. Genetic factors and environmental factors also play an important role in the overall susceptibility to SLE pathophysiology. Recently, protein tyrosine phosphatase, non-receptor type 22 (PTPN22 gene, has been found to be associated with several autoimmune diseases like SLE, Grave′s disease and Hashimoto thyroiditis. The missense R620W polymorphism, rs 2476601, in PTPN22 gene at the nucleotide 1858 in codon 620 (620Arg > Trp has been associated with autoimmune diseases. The PTPN22 locus is also found to be responsible for development of pulmonary tuberculosis in certain populations. The PTPN22 1858C/T gene locus will be ideal to look for SLE susceptibility to tuberculosis in the Indian population. In this review, we focus on human PTPN22 gene structure and function as well as the association of PTPN22 gene polymorphisms with SLE susceptibility

A brief history of Alzheimer's disease gene discovery.

Science.gov (United States)

Tanzi, Rudolph E

2013-01-01

The rich and colorful history of gene discovery in Alzheimer's disease (AD) over the past three decades is as complex and heterogeneous as the disease, itself. Twin and family studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases. The inheritance of AD exhibits a dichotomous pattern. On one hand, rare mutations inAPP, PSEN1, and PSEN2 are fully penetrant for early-onset (95%) late-onset AD. These four genes account for 30-50% of the inheritability of AD. Genome-wide association studies have recently led to the identification of additional highly confirmed AD candidate genes. Here, I review the past, present, and future of attempts to elucidate the complex and heterogeneous genetic underpinnings of AD along with some of the unique events that made these discoveries possible.

ABJM Wilson loops in arbitrary representations

Energy Technology Data Exchange (ETDEWEB)

Hatsuda, Yasuyuki [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group; Tokyo Institute of Technology (Japan). Dept. of Physics; Honda, Masazumi [High Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki (Japan); Moriyama, Sanefumi [Nagoya Univ. (Japan). Kobayashi Maskawa Inst. and Graduate School of Mathematics; Okuyama, Kazumi [Shinshu Univ., Matsumoto, Nagano (Japan). Dept. of Physics

2013-06-15

We study vacuum expectation values (VEVs) of circular half BPS Wilson loops in arbitrary representations in ABJM theory. We find that those in hook representations are reduced to elementary integrations thanks to the Fermi gas formalism, which are accessible from the numerical studies similar to the partition function in the previous studies. For non-hook representations, we show that the VEVs in the grand canonical formalism can be exactly expressed as determinants of those in the hook representations. Using these facts, we can study the instanton effects of the VEVs in various representations. Our results are consistent with the worldsheet instanton effects studied from the topological string and a prescription to include the membrane instanton effects by shifting the chemical potential, which has been successful for the partition function.

ABJM Wilson loops in arbitrary representations

International Nuclear Information System (INIS)

Hatsuda, Yasuyuki; Moriyama, Sanefumi; Okuyama, Kazumi

2013-06-01

We study vacuum expectation values (VEVs) of circular half BPS Wilson loops in arbitrary representations in ABJM theory. We find that those in hook representations are reduced to elementary integrations thanks to the Fermi gas formalism, which are accessible from the numerical studies similar to the partition function in the previous studies. For non-hook representations, we show that the VEVs in the grand canonical formalism can be exactly expressed as determinants of those in the hook representations. Using these facts, we can study the instanton effects of the VEVs in various representations. Our results are consistent with the worldsheet instanton effects studied from the topological string and a prescription to include the membrane instanton effects by shifting the chemical potential, which has been successful for the partition function.

Wilson loops in minimal surfaces

International Nuclear Information System (INIS)

Drukker, Nadav; Gross, David J.; Ooguri, Hirosi

1999-01-01

The AdS/CFT correspondence suggests that the Wilson loop of the large N gauge theory with N = 4 supersymmetry in 4 dimensions is described by a minimal surface in AdS 5 x S 5 . The authors examine various aspects of this proposal, comparing gauge theory expectations with computations of minimal surfaces. There is a distinguished class of loops, which the authors call BPS loops, whose expectation values are free from ultra-violet divergence. They formulate the loop equation for such loops. To the extent that they have checked, the minimal surface in AdS 5 x S 5 gives a solution of the equation. The authors also discuss the zig-zag symmetry of the loop operator. In the N = 4 gauge theory, they expect the zig-zag symmetry to hold when the loop does not couple the scalar fields in the supermultiplet. They will show how this is realized for the minimal surface

Wilson loops and minimal surfaces

International Nuclear Information System (INIS)

Drukker, Nadav; Gross, David J.; Ooguri, Hirosi

1999-01-01

The AdS-CFT correspondence suggests that the Wilson loop of the large N gauge theory with N=4 supersymmetry in four dimensions is described by a minimal surface in AdS 5 xS 5 . We examine various aspects of this proposal, comparing gauge theory expectations with computations of minimal surfaces. There is a distinguished class of loops, which we call BPS loops, whose expectation values are free from ultraviolet divergence. We formulate the loop equation for such loops. To the extent that we have checked, the minimal surface in AdS 5 xS 5 gives a solution of the equation. We also discuss the zigzag symmetry of the loop operator. In the N=4 gauge theory, we expect the zigzag symmetry to hold when the loop does not couple the scalar fields in the supermultiplet. We will show how this is realized for the minimal surface. (c) 1999 The American Physical Society

New results on the 3-loop heavy flavor Wilson coefficients in deep-inelastic scattering

Energy Technology Data Exchange (ETDEWEB)

Ablinger, Jakob; Schneider, Carsten [Johannes Kepler Univ., Linz (Austria). Research Inst. for Symbolic Computation; Bluemlein, Johannes; Freitas, Abilio de; Wissbrock, Fabian [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Hasselhuhn, Alexander [Johannes Kepler Univ., Linz (Austria). Research Inst. for Symbolic Computation; Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Klein, Sebastian [RWTH Aachen Univ. (Germany). Inst. fuer Theoretische Physik E

2013-01-02

We report on recent results obtained for the 3-loop heavy flavor Wilson coefficients in deepinelastic scattering (DIS) at general values of the Mellin variable N at larger scales of Q{sup 2}. These concern contributions to the gluonic ladder-topologies, the transition matrix elements in the variable flavor scheme of O(n{sub f}T{sup 2}{sub F}) and O(T{sup 2}{sub F}), and first results on higher 3-loop topologies. The knowledge of the heavy flavor Wilson coefficients at 3-loop order is of importance to extract the parton distribution functions and {alpha}{sub s}(M{sup 2}{sub Z}) in complete NNLO QCD analyses of the world precision data on the structure function F{sub 2}(x,Q{sup 2}).

BPS Wilson loops and Bremsstrahlung function in ABJ(M): a two loop analysis

Energy Technology Data Exchange (ETDEWEB)

Bianchi, Marco S. [Institut für Physik, Humboldt-Universität zu Berlin,Newtonstraße 15, 12489 Berlin (Germany); Griguolo, Luca [Dipartimento di Fisica e Scienze della Terra, Università di Parmaand INFN Gruppo Collegato di Parma,Viale G.P. Usberti 7/A, 43100 Parma (Italy); Leoni, Matias [Physics Department, FCEyN-UBA & IFIBA-CONICETCiudad Universitaria, Pabellón I, 1428, Buenos Aires (Argentina); Penati, Silvia [Dipartimento di Fisica, Università di Milano-Bicoccaand INFN, Sezione di Milano-Bicocca,Piazza della Scienza 3, I-20126 Milano (Italy); Seminara, Domenico [Dipartimento di Fisica, Università di Firenzeand INFN Sezione di Firenze,via G. Sansone 1, 50019 Sesto Fiorentino (Italy)

2014-06-19

We study a family of circular BPS Wilson loops in N=6 super Chern-Simons-matter theories, generalizing the usual 1/2-BPS circle. The scalar and fermionic couplings depend on two deformation parameters and these operators can be considered as the ABJ(M) counterpart of the DGRT latitudes defined in N=4 SYM. We perform a complete two-loop analysis of their vacuum expectation value, discuss the appearance of framing-like phases and propose a general relation with cohomologically equivalent bosonic operators. We make an all-loop proposal for computing the Bremsstrahlung function associated to the 1/2-BPS cusp in terms of these generalized Wilson loops. When applied to our two-loop result it reproduces the known expression. Finally, we comment on the generalization of this proposal to the bosonic 1/6-BPS case.

Current Experimental Studies of Gene Therapy in Parkinson's Disease

Directory of Open Access Journals (Sweden)

Jing-ya Lin

2017-05-01

Full Text Available Parkinson's disease (PD was characterized by late-onset, progressive dopamine neuron loss and movement disorders. The progresses of PD affected the neural function and integrity. To date, most researches had largely addressed the dopamine replacement therapies, but the appearance of L-dopa-induced dyskinesia hampered the use of the drug. And the mechanism of PD is so complicated that it's hard to solve the problem by just add drugs. Researchers began to focus on the genetic underpinnings of Parkinson's disease, searching for new method that may affect the neurodegeneration processes in it. In this paper, we reviewed current delivery methods used in gene therapies for PD, we also summarized the primary target of the gene therapy in the treatment of PD, such like neurotrophic factor (for regeneration, the synthesis of neurotransmitter (for prolong the duration of L-dopa, and the potential proteins that might be a target to modulate via gene therapy. Finally, we discussed RNA interference therapies used in Parkinson's disease, it might act as a new class of drug. We mainly focus on the efficiency and tooling features of different gene therapies in the treatment of PD.

Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids

Directory of Open Access Journals (Sweden)

Sathidpak Nantasanti

2015-11-01

Full Text Available The recent development of 3D-liver stem cell cultures (hepatic organoids opens up new avenues for gene and/or stem cell therapy to treat liver disease. To test safety and efficacy, a relevant large animal model is essential but not yet established. Because of its shared pathologies and disease pathways, the dog is considered the best model for human liver disease. Here we report the establishment of a long-term canine hepatic organoid culture allowing undifferentiated expansion of progenitor cells that can be differentiated toward functional hepatocytes. We show that cultures can be initiated from fresh and frozen liver tissues using Tru-Cut or fine-needle biopsies. The use of Wnt agonists proved important for canine organoid proliferation and inhibition of differentiation. Finally, we demonstrate that successful gene supplementation in hepatic organoids of COMMD1-deficient dogs restores function and can be an effective means to cure copper storage disease.

Influence of cusps and intersections on the Wilson loop in ν-dimensional space

International Nuclear Information System (INIS)

Bezerra, V.B.

1984-01-01

A discussion is given about the influence of cusps and intersections on the calculation of the Wilson loop in ν-dimensional space. In particular, for the two-dimensional case, it is shown that there are no divergences. (Author) [pt

G2D: a tool for mining genes associated with disease

OpenAIRE

Perez-Iratxeta, Carolina; Wjst, Matthias; Bork, Peer; Andrade, Miguel A

2005-01-01

Abstract Background Human inherited diseases can be associated by genetic linkage with one or more genomic regions. The availability of the complete sequence of the human genome allows examining those locations for an associated gene. We previously developed an algorithm to prioritize genes on a chromosomal region according to their possible relation to an inherited disease using a combination of data mining on biomedical databases and gene sequence analysis. Results We have implemented this ...

Prioritization of candidate disease genes by combining topological similarity and semantic similarity.

Science.gov (United States)

Liu, Bin; Jin, Min; Zeng, Pan

2015-10-01

The identification of gene-phenotype relationships is very important for the treatment of human diseases. Studies have shown that genes causing the same or similar phenotypes tend to interact with each other in a protein-protein interaction (PPI) network. Thus, many identification methods based on the PPI network model have achieved good results. However, in the PPI network, some interactions between the proteins encoded by candidate gene and the proteins encoded by known disease genes are very weak. Therefore, some studies have combined the PPI network with other genomic information and reported good predictive performances. However, we believe that the results could be further improved. In this paper, we propose a new method that uses the semantic similarity between the candidate gene and known disease genes to set the initial probability vector of a random walk with a restart algorithm in a human PPI network. The effectiveness of our method was demonstrated by leave-one-out cross-validation, and the experimental results indicated that our method outperformed other methods. Additionally, our method can predict new causative genes of multifactor diseases, including Parkinson's disease, breast cancer and obesity. The top predictions were good and consistent with the findings in the literature, which further illustrates the effectiveness of our method. Copyright © 2015 Elsevier Inc. All rights reserved.

Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease.

Science.gov (United States)

Chiba, Hirofumi; Kakuta, Yoichi; Kinouchi, Yoshitaka; Kawai, Yosuke; Watanabe, Kazuhiro; Nagao, Munenori; Naito, Takeo; Onodera, Motoyuki; Moroi, Rintaro; Kuroha, Masatake; Kanazawa, Yoshitake; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Negoro, Kenichi; Nagasaki, Masao; Unno, Michiaki; Shimosegawa, Tooru

2018-01-01

Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score ([Formula: see text]) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing [Formula: see text] >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of [Formula: see text] (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 ([Formula: see text] = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). We confirmed the existence of cis-regulated ASM around

Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease

Science.gov (United States)

Chiba, Hirofumi; Kakuta, Yoichi; Kinouchi, Yoshitaka; Kawai, Yosuke; Watanabe, Kazuhiro; Nagao, Munenori; Naito, Takeo; Onodera, Motoyuki; Moroi, Rintaro; Kuroha, Masatake; Kanazawa, Yoshitake; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Negoro, Kenichi; Nagasaki, Masao; Unno, Michiaki; Shimosegawa, Tooru

2018-01-01

Background Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. Methods CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score (ΔRAS¯) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing ΔRAS¯ >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. Results We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of ΔRAS¯ (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 (ΔRAS¯ = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). Conclusions We confirmed the existence of cis-regulated ASM around IBD

Cross disease analysis of co-functional microRNA pairs on a reconstructed network of disease-gene-microRNA tripartite.

Science.gov (United States)

Peng, Hui; Lan, Chaowang; Zheng, Yi; Hutvagner, Gyorgy; Tao, Dacheng; Li, Jinyan

2017-03-24

MicroRNAs always function cooperatively in their regulation of gene expression. Dysfunctions of these co-functional microRNAs can play significant roles in disease development. We are interested in those multi-disease associated co-functional microRNAs that regulate their common dysfunctional target genes cooperatively in the development of multiple diseases. The research is potentially useful for human disease studies at the transcriptional level and for the study of multi-purpose microRNA therapeutics. We designed a computational method to detect multi-disease associated co-functional microRNA pairs and conducted cross disease analysis on a reconstructed disease-gene-microRNA (DGR) tripartite network. The construction of the DGR tripartite network is by the integration of newly predicted disease-microRNA associations with those relationships of diseases, microRNAs and genes maintained by existing databases. The prediction method uses a set of reliable negative samples of disease-microRNA association and a pre-computed kernel matrix instead of kernel functions. From this reconstructed DGR tripartite network, multi-disease associated co-functional microRNA pairs are detected together with their common dysfunctional target genes and ranked by a novel scoring method. We also conducted proof-of-concept case studies on cancer-related co-functional microRNA pairs as well as on non-cancer disease-related microRNA pairs. With the prioritization of the co-functional microRNAs that relate to a series of diseases, we found that the co-function phenomenon is not unusual. We also confirmed that the regulation of the microRNAs for the development of cancers is more complex and have more unique properties than those of non-cancer diseases.

Local anomaly cancellation in heterotic E{sub 8} x E{sub 8} orbifold compactifications with Wilson line backgrounds

Energy Technology Data Exchange (ETDEWEB)

Walter, M.G.A.

2004-02-01

We consider several examples of a special class of heterotic compactifications, i.e. heterotic E{sub 8} x E{sub 8} orbifolds with Wilson line backgrounds. By developing a local perspective we show that a brane world like picture emerges. As an important result we prove that the local massless spectrum at such a brane can always be traced back to the global spectrum of a (different) orbifold without Wilson lines. One particular implication of this result is that the use of (discrete) Wilson lines for the construction of phenomenologically interesting models has to be rethought. We show that stringy constraints render the brane spectra consistent. Using our local picture we are able to compute the local anomalies appearing at the different branes for our examples and show that they can all be cancelled by a local version of the Green-Schwarz mechanism at the same time. (orig.)

Wilson Dslash Kernel From Lattice QCD Optimization

Energy Technology Data Exchange (ETDEWEB)

Joo, Balint [Jefferson Lab, Newport News, VA; Smelyanskiy, Mikhail [Parallel Computing Lab, Intel Corporation, California, USA; Kalamkar, Dhiraj D. [Parallel Computing Lab, Intel Corporation, India; Vaidyanathan, Karthikeyan [Parallel Computing Lab, Intel Corporation, India

2015-07-01

Lattice Quantum Chromodynamics (LQCD) is a numerical technique used for calculations in Theoretical Nuclear and High Energy Physics. LQCD is traditionally one of the first applications ported to many new high performance computing architectures and indeed LQCD practitioners have been known to design and build custom LQCD computers. Lattice QCD kernels are frequently used as benchmarks (e.g. 168.wupwise in the SPEC suite) and are generally well understood, and as such are ideal to illustrate several optimization techniques. In this chapter we will detail our work in optimizing the Wilson-Dslash kernels for Intel Xeon Phi, however, as we will show the technique gives excellent performance on regular Xeon Architecture as well.

Dual conformal transformations of smooth holographic Wilson loops

Energy Technology Data Exchange (ETDEWEB)

Dekel, Amit [Nordita, KTH Royal Institute of Technology and Stockholm University, Roslagstullsbacken 23, SE-106 91 Stockholm (Sweden)

2017-01-19

We study dual conformal transformations of minimal area surfaces in AdS{sub 5}×S{sup 5} corresponding to holographic smooth Wilson loops and some other related observables. To act with dual conformal transformations we map the string solutions to the dual space by means of T-duality, then we apply a conformal transformation and finally T-dualize back to the original space. The transformation maps between string solutions with different boundary contours. The boundary contours of the minimal surfaces are not mapped back to the AdS boundary, and the regularized area of the surface changes.

Lattice QCD at finite temperature with Wilson fermions

International Nuclear Information System (INIS)

Pinke, Christopher

2014-01-01

The subatomic world is governed by the strong interactions of quarks and gluons, described by Quantum Chromodynamics (QCD). Quarks experience confinement into colour-less objects, i.e. they can not be observed as free particles. Under extreme conditions such as high temperature or high density, this constraint softens and a transition to a phase where quarks and gluons are quasi-free particles (Quark-Gluon-Plasma) can occur. This environment resembles the conditions prevailing during the early stages of the universe shortly after the Big Bang. The phase diagram of QCD is under investigation in current and future collider experiments, for example at the Large Hadron Collider (LHC) or at the Facility for Antiproton and Ion Research (FAIR). Due to the strength of the strong interactions in the energy regime of interest, analytic methods can not be applied rigorously. The only tool to study QCD from first principles is given by simulations of its discretised version, Lattice QCD (LQCD). These simulations are in the high-performance computing area, hence, the numerical aspects of LQCD are a vital part in this field of research. In recent years, Graphic Processing Units (GPUs) have been incorporated in these simulations as they are a standard tool for general purpose calculations today. In the course of this thesis, the LQCD application CL 2 QCD has been developed, which allows for simulations on GPUs as well as on traditional CPUs, as it is based on OpenCL. CL 2 QCD constitutes the first application for Wilson type fermions in OpenCL. It provides excellent performance and has been applied in physics studies presented in this thesis. The investigation of the QCD phase diagram is hampered by the notorious sign-problem, which restricts current simulation algorithms to small values of the chemical potential. Theoretically, studying unphysical parameter ranges allows for constraints on the phase diagram. Of utmost importance is the clarification of the order of the finite

Gene targeting approaches to complex genetic diseases: atherosclerosis and essential hypertension.

OpenAIRE

Smithies, O; Maeda, N

1995-01-01

Gene targeting allows precise, predetermined changes to be made in a chosen gene in the mouse genome. To date, targeting has been used most often for generation of animals completely lacking the product of a gene of interest. The resulting "knockout" mice have confirmed some hypotheses, have upset others, but have rarely been uninformative. Models of several human genetic diseases have been produced by targeting--including Gaucher disease, cystic fibrosis, and the fragile X syndrome. These di...

Role of genes in oro-dental diseases

Directory of Open Access Journals (Sweden)

Kavitha B

2010-01-01

Full Text Available In oral cavity, the spectrum of diseases due to genetic alterations ranges from developmental disturbances of teeth to the pre-cancerous and cancerous lesions. Of late, significant progress has been made in the molecular analysis of tumors. With molecular genetic testing emerging as diagnostic, prognostic, and therapeutic approach, a review of genetic alterations ranging from the development of oro-facial structures to the tumors in the head and neck region are addressed in this article. The functional regulatory aspect of genes in relation to oro-facial structures are discussed separately, i.e., in relation to tooth genesis, tooth agenesis (non-syndromic, syndromic, tooth structural alterations, syndromic oro-facial defects, bone diseases, skin diseases (genodermatoses, and malignant tumors. In this literature, various genes involved in the development of the oro-facial structures and tooth in particular are discussed. The genetic basis of disorders in the tooth development (agenesis, hypodontia, tooth structural defects like amelogenesis imperfecta (AI, dentinogenesis imperfecta (DI, and oro-facial structural alterations (various syndromes are explained.

Polymorphisms in miRNA genes and their involvement in autoimmune diseases susceptibility.

Science.gov (United States)

Latini, Andrea; Ciccacci, Cinzia; Novelli, Giuseppe; Borgiani, Paola

2017-08-01

MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate the expression of multiple protein-encoding genes at the post-transcriptional level. MicroRNAs are involved in different pathways, such as cellular proliferation and differentiation, signal transduction and inflammation, and play crucial roles in the development of several diseases, such as cancer, diabetes, and cardiovascular diseases. They have recently been recognized to play a role also in the pathogenesis of autoimmune diseases. Although the majority of studies are focused on miRNA expression profiles investigation, a growing number of studies have been investigating the role of polymorphisms in miRNA genes in the autoimmune diseases development. Indeed, polymorphisms affecting the miRNA genes can modify the set of targets they regulate or the maturation efficiency. This review is aimed to give an overview about the available studies that have investigated the association of miRNA gene polymorphisms with the susceptibility to various autoimmune diseases and to their clinical phenotypes.

Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids

NARCIS (Netherlands)

Nantasanti, Sathidpak; Spee, Bart; Kruitwagen, Hedwig S.; Chen, Chen; Geijsen, Niels; Oosterhoff, Loes A.; van Wolferen, Monique E.; Pelaez, Nicolas; Fieten, Hille; Wubbolts, Richard W.; Grinwis, Guy C.; Chan, Jefferson; Huch, Meritxell; Vries, Robert R. G.; Clevers, Hans; de Bruin, Alain; Rothuizen, Jan; Penning, Louis C.; Schotanus, Baukje A.

2015-01-01

The recent development of 3D-liver stem cell cultures (hepatic organoids) opens up new avenues for gene and/or stem cell therapy to treat liver disease. To test safety and efficacy, a relevant large animal model is essential but not yet established. Because of its shared pathologies and disease

Life-threatening infectious diseases of childhood: single-gene inborn errors of immunity?

Science.gov (United States)

Alcaïs, Alexandre; Quintana-Murci, Lluis; Thaler, David S; Schurr, Erwin; Abel, Laurent; Casanova, Jean-Laurent

2010-12-01

The hypothesis that inborn errors of immunity underlie infectious diseases is gaining experimental support. However, the apparent modes of inheritance of predisposition or resistance differ considerably among diseases and among studies. A coherent genetic architecture of infectious diseases is lacking. We suggest here that life-threatening infectious diseases in childhood, occurring in the course of primary infection, result mostly from individually rare but collectively diverse single-gene variations of variable clinical penetrance, whereas the genetic component of predisposition to secondary or reactivation infections in adults is more complex. This model is consistent with (i) the high incidence of most infectious diseases in early childhood, followed by a steady decline; (ii) theoretical modeling of the impact of monogenic or polygenic predisposition on the incidence distribution of infectious diseases before reproductive age; (iii) available molecular evidence from both monogenic and complex genetics of infectious diseases in children and adults; (iv) current knowledge of immunity to primary and secondary or latent infections; (v) the state of the art in the clinical genetics of noninfectious pediatric and adult diseases; and (vi) evolutionary data for the genes underlying single-gene and complex disease risk. With the recent advent of new-generation deep resequencing, this model of single-gene variations underlying severe pediatric infectious diseases is experimentally testable. © 2010 New York Academy of Sciences.

Systematic identification of latent disease-gene associations from PubMed articles.

Science.gov (United States)

Zhang, Yuji; Shen, Feichen; Mojarad, Majid Rastegar; Li, Dingcheng; Liu, Sijia; Tao, Cui; Yu, Yue; Liu, Hongfang

2018-01-01

Recent scientific advances have accumulated a tremendous amount of biomedical knowledge providing novel insights into the relationship between molecular and cellular processes and diseases. Literature mining is one of the commonly used methods to retrieve and extract information from scientific publications for understanding these associations. However, due to large data volume and complicated associations with noises, the interpretability of such association data for semantic knowledge discovery is challenging. In this study, we describe an integrative computational framework aiming to expedite the discovery of latent disease mechanisms by dissecting 146,245 disease-gene associations from over 25 million of PubMed indexed articles. We take advantage of both Latent Dirichlet Allocation (LDA) modeling and network-based analysis for their capabilities of detecting latent associations and reducing noises for large volume data respectively. Our results demonstrate that (1) the LDA-based modeling is able to group similar diseases into disease topics; (2) the disease-specific association networks follow the scale-free network property; (3) certain subnetwork patterns were enriched in the disease-specific association networks; and (4) genes were enriched in topic-specific biological processes. Our approach offers promising opportunities for latent disease-gene knowledge discovery in biomedical research.

Chronic obstructive pulmonary disease candidate gene prioritization based on metabolic networks and functional information.

Directory of Open Access Journals (Sweden)

Xinyan Wang

Full Text Available Chronic obstructive pulmonary disease (COPD is a multi-factor disease, in which metabolic disturbances played important roles. In this paper, functional information was integrated into a COPD-related metabolic network to assess similarity between genes. Then a gene prioritization method was applied to the COPD-related metabolic network to prioritize COPD candidate genes. The gene prioritization method was superior to ToppGene and ToppNet in both literature validation and functional enrichment analysis. Top-ranked genes prioritized from the metabolic perspective with functional information could promote the better understanding about the molecular mechanism of this disease. Top 100 genes might be potential markers for diagnostic and effective therapies.

Wilson loops in the Higgs phase of large N field theories on the conifold

International Nuclear Information System (INIS)

Caceres, E.; Hernandez, R.

2000-04-01

We study the quark-antiquark interaction in the large N limit of the superconformal field theory on D-3branes at a Calabi-Yau conical singularity. We compute the Wilson loop in the AdS 5 x T 11 supergravity background for the SU(2N) x SU(2N) theory. We also calculate the Wilson loop for the Higgs phase where the gauge group is broken to SU(N) x SU(N) x SU D (N). This corresponds to a two center configuration with some of the branes at the singularity and the rest of them at a smooth point. The calculation exhibits the expected Coulomb dependence for the interaction. The angular distribution of the BPS states is different than the one for a spherical horizon. (author)

Copépodes parasitos de Oligoplites spp. (Osteichthyes, Carangidae) da costa brasileira, com a redescrição de Tuxophorus caligodes Wilson, 1908 (Siphonostomatoida, Tuxophoridae)

OpenAIRE

Takemoto, Ricardo Massato; Universidade Estadual de Matingá; Luque, José Luis; UFRRJ; Luque, José Luis; UFRRJ

2008-01-01

Four species of caligid copepods, parasites of Oligoplites palometa (Cuvier, 1833), O. saurus (Bloch & Schneider, 1801) and O. saliens (Bloch, 1793) (Osteichthyes: Carangidae) from the Sepetiba Bay, coast of the state of Rio de Janeiro, Brazil, are presented. New geographical and host records for Caligus robustus Bassett-Smith, 1898, C. rufimaculatus Wilson, 1905, C. bonito Wilson, 1905 and Metacaligus rufus (Wilson, 1908) are given. Caligus oligoplitisi Carvalho, 1954 is considered a new jun...

Comparative Transcriptomics to Identify Novel Genes and Pathways in Dinoflagellates

Science.gov (United States)

Ryan, D.

2016-02-01

The unarmored dinoflagellate Karenia brevis is among the most prominent harmful, bloom-forming phytoplankton species in the Gulf of Mexico. During blooms, the polyketides PbTx-1 and PbTx-2 (brevetoxins) are produced by K. brevis. Brevetoxins negatively impact human health and the Gulf shellfish harvest. However, the genes underlying brevetoxin synthesis are currently unknown. Because the K. brevis genome is extremely large ( 1 × 1011 base pairs long), and with a high proportion of repetitive, non-coding DNA, it has not been sequenced. In fact, large, repetitive genomes are common among the dinoflagellate group. High-throughput RNA sequencing technology enabled us to assemble Karenia transcriptomes de novo and investigate potential genes in the brevetoxin pathway through comparative transcriptomics. The brevetoxin profile varies among K. brevis clonal cultures. For example, well-documented Wilson-CCFWC268 typically produces 8-10 pg PbTx per cell, whereas SP1 produces differences in gene expression. Of the 85,000 transcripts in the K. brevis transcriptome, 4,600 transcripts, including novel unannotated orthologs and putative polyketide synthases (PKSs), were only expressed by brevetoxin-producing K. brevis and K. papilionacea, not K. mikimotoi. Examination of gene expression between the typical- and low-toxin Wilson clones identified about 3,500 genes with significantly different expression levels, including 2 putative PKSs. One of the 2 PKSs was only found in the brevetoxin-producing Karenia species. These transcriptomes could not have been characterized without high-throughput RNA sequencing.

Wilson polynomials/functions and intertwining operators for the generic quantum superintegrable system on the 2-sphere

Science.gov (United States)

Miller, W., Jr.; Li, Q.

2015-04-01

The Wilson and Racah polynomials can be characterized as basis functions for irreducible representations of the quadratic symmetry algebra of the quantum superintegrable system on the 2-sphere, HΨ = EΨ, with generic 3-parameter potential. Clearly, the polynomials are expansion coefficients for one eigenbasis of a symmetry operator L2 of H in terms of an eigenbasis of another symmetry operator L1, but the exact relationship appears not to have been made explicit. We work out the details of the expansion to show, explicitly, how the polynomials arise and how the principal properties of these functions: the measure, 3-term recurrence relation, 2nd order difference equation, duality of these relations, permutation symmetry, intertwining operators and an alternate derivation of Wilson functions - follow from the symmetry of this quantum system. This paper is an exercise to show that quantum mechancal concepts and recurrence relations for Gausian hypergeometrc functions alone suffice to explain these properties; we make no assumptions about the structure of Wilson polynomial/functions, but derive them from quantum principles. There is active interest in the relation between multivariable Wilson polynomials and the quantum superintegrable system on the n-sphere with generic potential, and these results should aid in the generalization. Contracting function space realizations of irreducible representations of this quadratic algebra to the other superintegrable systems one can obtain the full Askey scheme of orthogonal hypergeometric polynomials. All of these contractions of superintegrable systems with potential are uniquely induced by Wigner Lie algebra contractions of so(3, C) and e(2,C). All of the polynomials produced are interpretable as quantum expansion coefficients. It is important to extend this process to higher dimensions.

Wilson polynomials/functions and intertwining operators for the generic quantum superintegrable system on the 2-sphere

International Nuclear Information System (INIS)

Miller, W Jr; Li, Q

2015-01-01

The Wilson and Racah polynomials can be characterized as basis functions for irreducible representations of the quadratic symmetry algebra of the quantum superintegrable system on the 2-sphere, HΨ = EΨ, with generic 3-parameter potential. Clearly, the polynomials are expansion coefficients for one eigenbasis of a symmetry operator L 2 of H in terms of an eigenbasis of another symmetry operator L 1 , but the exact relationship appears not to have been made explicit. We work out the details of the expansion to show, explicitly, how the polynomials arise and how the principal properties of these functions: the measure, 3-term recurrence relation, 2nd order difference equation, duality of these relations, permutation symmetry, intertwining operators and an alternate derivation of Wilson functions - follow from the symmetry of this quantum system. This paper is an exercise to show that quantum mechancal concepts and recurrence relations for Gausian hypergeometrc functions alone suffice to explain these properties; we make no assumptions about the structure of Wilson polynomial/functions, but derive them from quantum principles. There is active interest in the relation between multivariable Wilson polynomials and the quantum superintegrable system on the n-sphere with generic potential, and these results should aid in the generalization. Contracting function space realizations of irreducible representations of this quadratic algebra to the other superintegrable systems one can obtain the full Askey scheme of orthogonal hypergeometric polynomials. All of these contractions of superintegrable systems with potential are uniquely induced by Wigner Lie algebra contractions of so(3, C) and e(2,C). All of the polynomials produced are interpretable as quantum expansion coefficients. It is important to extend this process to higher dimensions. (paper)

Network analysis of differential expression for the identification of disease-causing genes.

Directory of Open Access Journals (Sweden)

Daniela Nitsch

Full Text Available Genetic studies (in particular linkage and association studies identify chromosomal regions involved in a disease or phenotype of interest, but those regions often contain many candidate genes, only a few of which can be followed-up for biological validation. Recently, computational methods to identify (prioritize the most promising candidates within a region have been proposed, but they are usually not applicable to cases where little is known about the phenotype (no or few confirmed disease genes, fragmentary understanding of the biological cascades involved. We seek to overcome this limitation by replacing knowledge about the biological process by experimental data on differential gene expression between affected and healthy individuals. Considering the problem from the perspective of a gene/protein network, we assess a candidate gene by considering the level of differential expression in its neighborhood under the assumption that strong candidates will tend to be surrounded by differentially expressed neighbors. We define a notion of soft neighborhood where each gene is given a contributing weight, which decreases with the distance from the candidate gene on the protein network. To account for multiple paths between genes, we define the distance using the Laplacian exponential diffusion kernel. We score candidates by aggregating the differential expression of neighbors weighted as a function of distance. Through a randomization procedure, we rank candidates by p-values. We illustrate our approach on four monogenic diseases and successfully prioritize the known disease causing genes.

Insights into Wilson's Warbler migration from analyses of hydrogen stable-isotope ratios

Science.gov (United States)

Jeffrey F. Kelly; Viorel Atudorei; Zachary D. Sharp; Deborah M. Finch

2002-01-01

Our ability to link the breeding locations of individual passerines to migration stopover sites and wintering locations is limited. Stable isotopes of hydrogen contained in bird feathers have recently shown potential in this regard. We measured hydrogen stable-isotope ratios (deltaD) of feathers from breeding, migrating, and wintering Wilson's Warblers. Analyses...

A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes

DEFF Research Database (Denmark)

Hansen, Kasper Lage; Hansen, Niclas Tue; Karlberg, Erik, Olof, Linnart

2008-01-01

to be overexpressed in the normal tissues where defects cause pathology. In contrast, cancer genes and complexes were not overexpressed in the tissues from which the tumors emanate. We specifically identified a complex involved in XY sex reversal that is testis-specific and down-regulated in ovaries. We also......Heritable diseases are caused by germ-line mutations that, despite tissuewide presence, often lead to tissue-specific pathology. Here, we make a systematic analysis of the link between tissue-specific gene expression and pathological manifestations in many human diseases and cancers. Diseases were...

Renormalisation constants of quark bilinears in lattice QCD with four dynamical Wilson quarks

NARCIS (Netherlands)

Blossier, B.; Brinet, M.; Carrasco, N.; Dimopoulos, P.; Du, X.; Frezzotti, R.; Gimenez, V.; Herdoiza, G.; Jansen, K.; Lubicz, V.; Palao, D.; Pallante, E.; Pene, O.; Petrov, K.; Reker, S.; Rossi, G. C.; Sanfilippo, F.; Scorzato, L.; Simula, S.; Urbach, C.

2011-01-01

We present preliminary results of the non-perturbative computation of the RI-MOM renormalisation constants in a mass-independent scheme for the action with Iwasaki glue and four dynamical Wilson quarks employed by ETMC. Our project requires dedicated gauge ensembles with four degenerate sea quark

LncRNAs: emerging players in gene regulation and disease ...

Indian Academy of Sciences (India)

and Glavac 2013), accounting for about 20,000 protein coding ... general information on lncRNAs' feature (Da Sacco et al. 2012). ..... mal cells, stabilized Zeb2 intron encompasses an internal ..... cially growth-control genes and cell mobility-induced genes ..... RNAs in development and disease of the central nervous system.

Vitamin D receptor gene variants in Parkinson's disease patients ...

African Journals Online (AJOL)

Background: Vitamin D plays an important role in neurodegenerative disorders as a crucial neuro-immunomodulator. Accumulating data provide evidences that vitamin D receptor (VDR) gene is a candidate gene for susceptibility to Parkinson's disease (PD). Aim: To find out whether the risk of the development of sporadic ...

Expression of novel Alzheimer's disease risk genes in control and Alzheimer's disease brains.

Directory of Open Access Journals (Sweden)

Celeste M Karch

Full Text Available Late onset Alzheimer's disease (LOAD etiology is influenced by complex interactions between genetic and environmental risk factors. Large-scale genome wide association studies (GWAS for LOAD have identified 10 novel risk genes: ABCA7, BIN1, CD2AP, CD33, CLU, CR1, EPHA1, MS4A6A, MS4A6E, and PICALM. We sought to measure the influence of GWAS single nucleotide polymorphisms (SNPs and gene expression levels on clinical and pathological measures of AD in brain tissue from the parietal lobe of AD cases and age-matched, cognitively normal controls. We found that ABCA7, CD33, and CR1 expression levels were associated with clinical dementia rating (CDR, with higher expression being associated with more advanced cognitive decline. BIN1 expression levels were associated with disease progression, where higher expression was associated with a delayed age at onset. CD33, CLU, and CR1 expression levels were associated with disease status, where elevated expression levels were associated with AD. Additionally, MS4A6A expression levels were associated with Braak tangle and Braak plaque scores, with elevated expression levels being associated with more advanced brain pathology. We failed to detect an association between GWAS SNPs and gene expression levels in our brain series. The minor allele of rs3764650 in ABCA7 is associated with age at onset and disease duration, and the minor allele of rs670139 in MS4A6E was associated with Braak tangle and Braak plaque score. These findings suggest that expression of some GWAS genes, namely ABCA7, BIN1, CD33, CLU, CR1 and the MS4A family, are altered in AD brains.

Gene therapy and angiogenesis in patients with coronary artery disease

DEFF Research Database (Denmark)

Kastrup, Jens

2010-01-01

-blind placebo-controlled trials could not confirm the initial high efficacy of either the growth factor protein or the gene therapy approaches observed in earlier small trials. The clinical studies so far have all been without any gene-related serious adverse events. Future trials will focus on whether...... an improvement in clinical results can be obtained with a cocktail of growth factors or by a combination of gene and stem cell therapy in patients with severe coronary artery disease, which cannot be treated effectively with current treatment strategies....... of VEGF and FGF in patients with coronary artery disease. The initial small and unblinded studies with either recombinant growth factor proteins or genes encoding growth factors were encouraging, demonstrating both clinical improvement and evidence of angiogenesis. However, subsequent larger double...

Exploring matrix factorization techniques for significant genes identification of Alzheimer’s disease microarray gene expression data

Directory of Open Access Journals (Sweden)

Hu Xiaohua

2011-07-01

Full Text Available Abstract Background The wide use of high-throughput DNA microarray technology provide an increasingly detailed view of human transcriptome from hundreds to thousands of genes. Although biomedical researchers typically design microarray experiments to explore specific biological contexts, the relationships between genes are hard to identified because they are complex and noisy high-dimensional data and are often hindered by low statistical power. The main challenge now is to extract valuable biological information from the colossal amount of data to gain insight into biological processes and the mechanisms of human disease. To overcome the challenge requires mathematical and computational methods that are versatile enough to capture the underlying biological features and simple enough to be applied efficiently to large datasets. Methods Unsupervised machine learning approaches provide new and efficient analysis of gene expression profiles. In our study, two unsupervised knowledge-based matrix factorization methods, independent component analysis (ICA and nonnegative matrix factorization (NMF are integrated to identify significant genes and related pathways in microarray gene expression dataset of Alzheimer’s disease. The advantage of these two approaches is they can be performed as a biclustering method by which genes and conditions can be clustered simultaneously. Furthermore, they can group genes into different categories for identifying related diagnostic pathways and regulatory networks. The difference between these two method lies in ICA assume statistical independence of the expression modes, while NMF need positivity constrains to generate localized gene expression profiles. Results In our work, we performed FastICA and non-smooth NMF methods on DNA microarray gene expression data of Alzheimer’s disease respectively. The simulation results shows that both of the methods can clearly classify severe AD samples from control samples, and

Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.

Directory of Open Access Journals (Sweden)

Maria Victoria Fernández

2017-11-01

Full Text Available Alzheimer disease (AD, Frontotemporal lobar degeneration (FTD, Amyotrophic lateral sclerosis (ALS and Parkinson disease (PD have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations.

[From gene to disease: from the ABCA4 gene to Stargardt disease, cone-rod dystrophy and retinitis pigmentosa

NARCIS (Netherlands)

Cremers, F.P.M.; Maugeri, A.; Klevering, B.J.; Hoefsloot, L.H.; Hoyng, C.B.

2002-01-01

Autosomal recessive Stargardt disease is caused by mutations in the ABCA4 gene. Mutations in ABCA4 are also found in two-thirds of cases with autosomal recessive cone-rod dystrophy, and a small fraction of patients with autosomal recessive retinitis pigmentosa. Patients with autosomal recessive

Defining the Human Macula Transcriptome and Candidate Retinal Disease Genes UsingEyeSAGE

Science.gov (United States)

Rickman, Catherine Bowes; Ebright, Jessica N.; Zavodni, Zachary J.; Yu, Ling; Wang, Tianyuan; Daiger, Stephen P.; Wistow, Graeme; Boon, Kathy; Hauser, Michael A.

2009-01-01

Purpose To develop large-scale, high-throughput annotation of the human macula transcriptome and to identify and prioritize candidate genes for inherited retinal dystrophies, based on ocular-expression profiles using serial analysis of gene expression (SAGE). Methods Two human retina and two retinal pigment epithelium (RPE)/choroid SAGE libraries made from matched macula or midperipheral retina and adjacent RPE/choroid of morphologically normal 28- to 66-year-old donors and a human central retina longSAGE library made from 41- to 66-year-old donors were generated. Their transcription profiles were entered into a relational database, EyeSAGE, including microarray expression profiles of retina and publicly available normal human tissue SAGE libraries. EyeSAGE was used to identify retina- and RPE-specific and -associated genes, and candidate genes for retina and RPE disease loci. Differential and/or cell-type specific expression was validated by quantitative and single-cell RT-PCR. Results Cone photoreceptor-associated gene expression was elevated in the macula transcription profiles. Analysis of the longSAGE retina tags enhanced tag-to-gene mapping and revealed alternatively spliced genes. Analysis of candidate gene expression tables for the identified Bardet-Biedl syndrome disease gene (BBS5) in the BBS5 disease region table yielded BBS5 as the top candidate. Compelling candidates for inherited retina diseases were identified. Conclusions The EyeSAGE database, combining three different gene-profiling platforms including the authors’ multidonor-derived retina/RPE SAGE libraries and existing single-donor retina/RPE libraries, is a powerful resource for definition of the retina and RPE transcriptomes. It can be used to identify retina-specific genes, including alternatively spliced transcripts and to prioritize candidate genes within mapped retinal disease regions. PMID:16723438

Recursion relations for multi-gluon off-shell amplitudes on the light-front and Wilson lines

Directory of Open Access Journals (Sweden)

C. Cruz-Santiago

2015-06-01

Full Text Available We analyze the off-shell scattering amplitudes in the framework of the light-front perturbation theory. It is shown that the previously derived recursion relation between tree level off-shell amplitudes in this formalism actually resums whole classes of graphs into a Wilson line. More precisely, we establish a correspondence between the light-front methods for the computation of the off-shell amplitudes and the approach which makes use of the matrix elements of straight infinite Wilson lines, which are manifestly gauge invariant objects. Furthermore, since it is needed to explicitly verify the gauge invariance of light-front amplitudes, it is demonstrated that the Ward identities in this framework need additional instantaneous terms in the light-front graphs.

Adaptive Multigrid Algorithm for the Lattice Wilson-Dirac Operator

International Nuclear Information System (INIS)

Babich, R.; Brower, R. C.; Rebbi, C.; Brannick, J.; Clark, M. A.; Manteuffel, T. A.; McCormick, S. F.; Osborn, J. C.

2010-01-01

We present an adaptive multigrid solver for application to the non-Hermitian Wilson-Dirac system of QCD. The key components leading to the success of our proposed algorithm are the use of an adaptive projection onto coarse grids that preserves the near null space of the system matrix together with a simplified form of the correction based on the so-called γ 5 -Hermitian symmetry of the Dirac operator. We demonstrate that the algorithm nearly eliminates critical slowing down in the chiral limit and that it has weak dependence on the lattice volume.

Critical behavior of the Schwinger model with Wilson fermions

International Nuclear Information System (INIS)

Azcoiti, V.; Laliena, V.

1995-09-01

A detailed analysis, in the framework of the MFA approach, of the critical behaviour of the lattice Schwinger model with Wilson fermions on lattices up to 24 2 , through the study of the Lee-Yang zeros and the specific heat, is presented. Compelling evidence is found for a critical line ending at k= 0.25 at large β. Finite size scaling analysis on lattices 8 2 , 12 2 , 16 2 , 20 2 and 24 2 indicates a continuous transition. The hyper scaling relation is verified in the explored β region

B-physics with N{sub f}=2 Wilson fermions

Energy Technology Data Exchange (ETDEWEB)

Bernardoni, F.; Simma, H.; Sommer, R. [John von Neumann-Institut fuer Computing NIC/DESY, Zeuthen (Germany)] [and others

2013-09-15

We report the final results of the ALPHA collaboration for some B-physics observables: f{sub B}, f{sub B{sub s}} and m{sub b}. We employ CLS configurations with 2 flavors of O(a) improved Wilson fermions in the sea and pion masses ranging down to 190 MeV. The b-quark is treated in HQET to order 1/m{sub b}. The renormalization, the matching and the improvement were performed non-perturbatively, and three lattice spacings reaching a=0.048 fm are used in the continuum extrapolation.

Molecular detection of disease resistance genes to powdery mildew ...

African Journals Online (AJOL)

A study was conducted to detect the presence of disease resistance genes to infection of wheat powdery mildew (Blumeria graminis f. sp. tritici) in selected wheat cultivars from China using molecular markers. Genomic DNA of sixty cultivars was extracted and tested for the presence of selected prominent resistance genes to ...

Supergravity couplings to Noncommutative Branes, Open Wilson Lines and Generalised Star Products

International Nuclear Information System (INIS)

Das, S.R.; Trivedi, S.P.

2001-01-01

Noncommutative gauge theories can be constructed from ordinary U(∞) gauge theories in lower dimensions. Using this construction we identify the operators on noncommutative D-branes which couple to linearized supergravity backgrounds, from a knowledge of such couplings to lower dimensional D-branes with no B field. These operators belong to a class of gauge invariant observables involving open Wilson lines. Assuming a DBI form of the coupling we show, to second order in the gauge potential but to all orders of the noncommutativity parameter, that our proposal agrees with the operator obtained in terms of ordinary gauge fields by considering brane actions in backgrounds and then using the Seiberg-Witten map to rewrite this in terms of noncommutative gauge fields. Our result clarify why a certain commutative but non-associative 'generalized star product' appears both in the expansion of the open Wilson line, as well as in string amplitude computations of open string-closed string couplings. We outline how our procedure can be used to obtain operators in the noncommutative theory which are holographically dual to supergravity modes. (author)

Topology, the Wilson flow and the HMC algorithm

CERN Document Server

Luscher, Martin

2010-01-01

An old and apparently persistent problem in numerical lattice QCD is that the simulations tend to get trapped in a sector of fixed topological charge when the lattice spacing is taken to zero. The effect sets in very rapidly and may invalidate the simulation results in certain cases. In this talk, the issue is discussed using the Wilson flow as a tool. The flow has a simple scaling behaviour and allows one to understand how exactly the topological sectors emerge in the continuum limit. Further studies however suggest that the observed slowdown of the simulations at small lattice spacings is only partly caused by the emergence of the sectors.

A computational method based on the integration of heterogeneous networks for predicting disease-gene associations.

Directory of Open Access Journals (Sweden)

Xingli Guo

Full Text Available The identification of disease-causing genes is a fundamental challenge in human health and of great importance in improving medical care, and provides a better understanding of gene functions. Recent computational approaches based on the interactions among human proteins and disease similarities have shown their power in tackling the issue. In this paper, a novel systematic and global method that integrates two heterogeneous networks for prioritizing candidate disease-causing genes is provided, based on the observation that genes causing the same or similar diseases tend to lie close to one another in a network of protein-protein interactions. In this method, the association score function between a query disease and a candidate gene is defined as the weighted sum of all the association scores between similar diseases and neighbouring genes. Moreover, the topological correlation of these two heterogeneous networks can be incorporated into the definition of the score function, and finally an iterative algorithm is designed for this issue. This method was tested with 10-fold cross-validation on all 1,126 diseases that have at least a known causal gene, and it ranked the correct gene as one of the top ten in 622 of all the 1,428 cases, significantly outperforming a state-of-the-art method called PRINCE. The results brought about by this method were applied to study three multi-factorial disorders: breast cancer, Alzheimer disease and diabetes mellitus type 2, and some suggestions of novel causal genes and candidate disease-causing subnetworks were provided for further investigation.

Identifying noncoding risk variants using disease-relevant gene regulatory networks.

Science.gov (United States)

Gao, Long; Uzun, Yasin; Gao, Peng; He, Bing; Ma, Xiaoke; Wang, Jiahui; Han, Shizhong; Tan, Kai

2018-02-16

Identifying noncoding risk variants remains a challenging task. Because noncoding variants exert their effects in the context of a gene regulatory network (GRN), we hypothesize that explicit use of disease-relevant GRNs can significantly improve the inference accuracy of noncoding risk variants. We describe Annotation of Regulatory Variants using Integrated Networks (ARVIN), a general computational framework for predicting causal noncoding variants. It employs a set of novel regulatory network-based features, combined with sequence-based features to infer noncoding risk variants. Using known causal variants in gene promoters and enhancers in a number of diseases, we show ARVIN outperforms state-of-the-art methods that use sequence-based features alone. Additional experimental validation using reporter assay further demonstrates the accuracy of ARVIN. Application of ARVIN to seven autoimmune diseases provides a holistic view of the gene subnetwork perturbed by the combinatorial action of the entire set of risk noncoding mutations.

Correlation between NFATC1 gene polymorphisms and congenital heart disease in children.

Science.gov (United States)

Li, C-L; Niu, L; Fu, M-Y; Tian, J; Wang, Q-W; An, X-J

2017-08-01

To analyze the links between NFATC1 gene polymorphism and congenital heart disease in children. In the present study, we selected 85 children patients with congenital heart disease who were hospitalized from February 2013 to February 2015 as research subjects (observation group), and 92 healthy subjects as control group. Restriction fragment length polymorphism (RFLP) was used for analysis of NFATC1 gene in samples from each group. The distribution of NFATC1 genotype and allele between the observation group (children with congenital heart disease) and the control group showed no significant difference (p >0.05), but AA, GG genotypes, and allele frequency between pathological samples of children with congenital heart disease and the control group displayed significant difference (p congenital heart disease in observation group also showed a difference, i.e., homozygote (AA, GG) ratio in children with severe congenital heart disease is relatively high. There is a correlation between NFATC1 genes and the incidence of congenital heart disease in children, and a correlation between different genotypes and allele frequency and the incidence of the disease.

Subtracting infrared renormalons from Wilson coefficients: Uniqueness and power dependences on ΛQCD

Science.gov (United States)

Mishima, Go; Sumino, Yukinari; Takaura, Hiromasa

2017-06-01

In the context of operator product expansion (OPE) and using the large-β0 approximation, we propose a method to define Wilson coefficients free from uncertainties due to IR renormalons. We first introduce a general observable X (Q2) with an explicit IR cutoff, and then we extract a genuine UV contribution XUV as a cutoff-independent part. XUV includes power corrections ˜(ΛQCD2/Q2)n which are independent of renormalons. Using the integration-by-regions method, we observe that XUV coincides with the leading Wilson coefficient in OPE and also clarify that the power corrections originate from UV region. We examine scheme dependence of XUV and single out a specific scheme favorable in terms of analytical properties. Our method would be optimal with respect to systematicity, analyticity and stability. We test our formulation with the examples of the Adler function, QCD force between Q Q ¯, and R -ratio in e+e- collision.

Gene co-expression networks shed light into diseases of brain iron accumulation.

Science.gov (United States)

Bettencourt, Conceição; Forabosco, Paola; Wiethoff, Sarah; Heidari, Moones; Johnstone, Daniel M; Botía, Juan A; Collingwood, Joanna F; Hardy, John; Milward, Elizabeth A; Ryten, Mina; Houlden, Henry

2016-03-01

Aberrant brain iron deposition is observed in both common and rare neurodegenerative disorders, including those categorized as Neurodegeneration with Brain Iron Accumulation (NBIA), which are characterized by focal iron accumulation in the basal ganglia. Two NBIA genes are directly involved in iron metabolism, but whether other NBIA-related genes also regulate iron homeostasis in the human brain, and whether aberrant iron deposition contributes to neurodegenerative processes remains largely unknown. This study aims to expand our understanding of these iron overload diseases and identify relationships between known NBIA genes and their main interacting partners by using a systems biology approach. We used whole-transcriptome gene expression data from human brain samples originating from 101 neuropathologically normal individuals (10 brain regions) to generate weighted gene co-expression networks and cluster the 10 known NBIA genes in an unsupervised manner. We investigated NBIA-enriched networks for relevant cell types and pathways, and whether they are disrupted by iron loading in NBIA diseased tissue and in an in vivo mouse model. We identified two basal ganglia gene co-expression modules significantly enriched for NBIA genes, which resemble neuronal and oligodendrocytic signatures. These NBIA gene networks are enriched for iron-related genes, and implicate synapse and lipid metabolism related pathways. Our data also indicates that these networks are disrupted by excessive brain iron loading. We identified multiple cell types in the origin of NBIA disorders. We also found unforeseen links between NBIA networks and iron-related processes, and demonstrate convergent pathways connecting NBIAs and phenotypically overlapping diseases. Our results are of further relevance for these diseases by providing candidates for new causative genes and possible points for therapeutic intervention. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Metastable states and quasicycles in a stochastic Wilson-Cowan model of neuronal population dynamics

KAUST Repository

Bressloff, Paul C.

2010-01-01

We analyze a stochastic model of neuronal population dynamics with intrinsic noise. In the thermodynamic limit N→∞, where N determines the size of each population, the dynamics is described by deterministic Wilson-Cowan equations. On the other hand

78 FR 73559 - Moose-Wilson Corridor Comprehensive Management Plan, Environmental Impact Statement, Grand Teton...

Science.gov (United States)

2013-12-06

...-Wilson Corridor Comprehensive Management Plan, Environmental Impact Statement, Grand Teton National Park... is preparing a Comprehensive Management Plan and Environmental Impact Statement (EIS) for the Moose...; (2) distinguish the corridor's fundamental and other important resources and values; (3) clearly...

DDMGD: the database of text-mined associations between genes methylated in diseases from different species

KAUST Repository

Raies, A. B.

2014-11-14

Gathering information about associations between methylated genes and diseases is important for diseases diagnosis and treatment decisions. Recent advancements in epigenetics research allow for large-scale discoveries of associations of genes methylated in diseases in different species. Searching manually for such information is not easy, as it is scattered across a large number of electronic publications and repositories. Therefore, we developed DDMGD database (http://www.cbrc.kaust.edu.sa/ddmgd/) to provide a comprehensive repository of information related to genes methylated in diseases that can be found through text mining. DDMGD\\'s scope is not limited to a particular group of genes, diseases or species. Using the text mining system DEMGD we developed earlier and additional post-processing, we extracted associations of genes methylated in different diseases from PubMed Central articles and PubMed abstracts. The accuracy of extracted associations is 82% as estimated on 2500 hand-curated entries. DDMGD provides a user-friendly interface facilitating retrieval of these associations ranked according to confidence scores. Submission of new associations to DDMGD is provided. A comparison analysis of DDMGD with several other databases focused on genes methylated in diseases shows that DDMGD is comprehensive and includes most of the recent information on genes methylated in diseases.

Recent results on the 3-loop heavy flavor Wilson coefficients in deep-inelastic scattering

Energy Technology Data Exchange (ETDEWEB)

Bluemlein, J.; Freitas A. de; Raab, C.; Wissbrock, F. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Ablinger, J.; Hasselhuhn, A.; Round, M.; Schneider, C. [Johannes Kepler Univ., Linz (Austria). Research Inst. for Symbolic Computation; Manteuffel, A. von [Mainz Univ. (Germany). PRISMA Cluster of Excellence; Mainz Univ. (Germany). Inst. fuer Physik

2013-07-15

We report on recent progress in the calculation of the 3-loop massive Wilson coefficients in deep-inelastic scattering at general values of N for neutral and charged current reactions in the asymptotic region Q{sup 2}>>m{sup 2}.

The Wilson loop expectation values in 2-and 3-dimensional SU(2) LGT

International Nuclear Information System (INIS)

Li Zhibing; Zheng Weihong; Guo Shuohong

1989-01-01

An improved Monte Carlo scheme is applied to the computation of expectation values of nxm Wilson loops in both 2-and 3-dimensional SU(2) lattice gauge theories. The results are compared with those simulated by the discrete group Y 120 and the exact results in two dimensions

Systems Pharmacology-Based Approach of Connecting Disease Genes in Genome-Wide Association Studies with Traditional Chinese Medicine.

Science.gov (United States)

Kim, Jihye; Yoo, Minjae; Shin, Jimin; Kim, Hyunmin; Kang, Jaewoo; Tan, Aik Choon

2018-01-01

Traditional Chinese medicine (TCM) originated in ancient China has been practiced over thousands of years for treating various symptoms and diseases. However, the molecular mechanisms of TCM in treating these diseases remain unknown. In this study, we employ a systems pharmacology-based approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. We studied 102 TCM components and their target genes by analyzing microarray gene expression experiments. We constructed disease-gene networks from 2558 GWAS studies. We applied a systems pharmacology approach to prioritize disease-target genes. Using this bioinformatics approach, we analyzed 14,713 GWAS disease-TCM-target gene pairs and identified 115 disease-gene pairs with q value < 0.2. We validated several of these GWAS disease-TCM-target gene pairs with literature evidence, demonstrating that this computational approach could reveal novel indications for TCM. We also develop TCM-Disease web application to facilitate the traditional Chinese medicine drug repurposing efforts. Systems pharmacology is a promising approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. The computational approaches described in this study could be easily expandable to other disease-gene network analysis.

Digital Gene Expression Analysis to Screen Disease Resistance-Relevant Genes from Leaves of Herbaceous Peony (Paeonia lactiflora Pall. Infected by Botrytis cinerea.

Directory of Open Access Journals (Sweden)

Saijie Gong

Full Text Available Herbaceous peony (Paeonia lactiflora Pall. is a well-known traditional flower in China and is widely used for landscaping and garden greening due to its high ornamental value. However, disease spots usually appear after the flowering of the plant and may result in the withering of the plant in severe cases. This study examined the disease incidence in an herbaceous peony field in the Yangzhou region, Jiangsu Province. Based on morphological characteristics and molecular data, the disease in this area was identified as a gray mold caused by Botrytis cinerea. Based on previously obtained transcriptome data, eight libraries generated from two herbaceous peony cultivars 'Zifengyu' and 'Dafugui' with different susceptibilities to the disease were then analyzed using digital gene expression profiling (DGE. Thousands of differentially expressed genes (DEGs were screened by comparing the eight samples, and these genes were annotated using the Gene ontology (GO and Kyoto encyclopedia of genes and genomes (KEGG database. The pathways related to plant-pathogen interaction, secondary metabolism synthesis and antioxidant system were concentrated, and 51, 76, and 13 disease resistance-relevant candidate genes were identified, respectively. The expression patterns of these candidate genes differed between the two cultivars: their expression of the disease-resistant cultivar 'Zifengyu' sharply increased during the early stages of infection, while it was relatively subdued in the disease-sensitive cultivar 'Dafugui'. A selection of ten candidate genes was evaluated by quantitative real-time PCR (qRT-PCR to validate the DGE data. These results revealed the transcriptional changes that took place during the interaction of herbaceous peony with B. cinerea, providing insight into the molecular mechanisms of host resistance to gray mold.

[Treatable diseases of the nervous system with cataract formation].

Science.gov (United States)

Baumgartner, R W; Waespe, W

1993-02-01

The detection of a cataract in combination with a neurological deficit may provide the physician with important diagnostic help. But a minority of underlying diseases (angiokeratoma corporis diffusum, cerebrotendinous xanthomatosis, diabetes mellitus, galactosemia, hypocalcemia, Refsum's disease, Wilson's disease; Charles Bonnet syndrome; relapsing Perichondritis; adverse effects of medication and intoxications) can be treated causally. Therefore they are summed up and discussed in this paper.

Targeted delivery of genes to endothelial cells and cell- and gene-based therapy in pulmonary vascular diseases.

Science.gov (United States)

Suen, Colin M; Mei, Shirley H J; Kugathasan, Lakshmi; Stewart, Duncan J

2013-10-01

Pulmonary arterial hypertension (PAH) is a devastating disease that, despite significant advances in medical therapies over the last several decades, continues to have an extremely poor prognosis. Gene therapy is a method to deliver therapeutic genes to replace defective or mutant genes or supplement existing cellular processes to modify disease. Over the last few decades, several viral and nonviral methods of gene therapy have been developed for preclinical PAH studies with varying degrees of efficacy. However, these gene delivery methods face challenges of immunogenicity, low transduction rates, and nonspecific targeting which have limited their translation to clinical studies. More recently, the emergence of regenerative approaches using stem and progenitor cells such as endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) have offered a new approach to gene therapy. Cell-based gene therapy is an approach that augments the therapeutic potential of EPCs and MSCs and may deliver on the promise of reversal of established PAH. These new regenerative approaches have shown tremendous potential in preclinical studies; however, large, rigorously designed clinical studies will be necessary to evaluate clinical efficacy and safety. © 2013 American Physiological Society. Compr Physiol 3:1749-1779, 2013.

Two Alzheimer’s disease risk genes increase entorhinal cortex volume in young adults

Directory of Open Access Journals (Sweden)

Amanda Marie Dibattista

2014-10-01

Full Text Available Alzheimer’s disease (AD risk genes alter brain structure and function decades before disease onset. Apolipoprotein E (APOE is the strongest known genetic risk factor for Alzheimer’s disease, and a related gene, apolipoprotein J (APOJ, also affects disease risk. However, the extent to which these genes affect brain structure in young adults remains unclear. Here, we report that AD risk alleles of these two genes, APOE-ε4 and APOJ-C, cumulatively alter brain volume in young adults. Using voxel-based morphometry in 57 individuals, we examined the entorhinal cortex, one of the earliest brain regions affected in AD pathogenesis. APOE-ε4 carriers exhibited higher right entorhinal cortex volume compared to non-carriers. Interestingly, APOJ-C risk genotype was associated with higher bilateral entorhinal cortex volume in non-APOE-ε4 carriers. To determine the combined disease risk of APOE and APOJ status per subject, we used cumulative odds ratios as regressors for volumetric measurements. Higher disease risk corresponded to greater right entorhinal cortex volume. These results suggest that, years before disease onset, two key AD genetic risk factors may exert influence on the structure of a brain region where AD pathogenesis takes root.

DDMGD: the database of text-mined associations between genes methylated in diseases from different species.

Science.gov (United States)

Bin Raies, Arwa; Mansour, Hicham; Incitti, Roberto; Bajic, Vladimir B

2015-01-01

Gathering information about associations between methylated genes and diseases is important for diseases diagnosis and treatment decisions. Recent advancements in epigenetics research allow for large-scale discoveries of associations of genes methylated in diseases in different species. Searching manually for such information is not easy, as it is scattered across a large number of electronic publications and repositories. Therefore, we developed DDMGD database (http://www.cbrc.kaust.edu.sa/ddmgd/) to provide a comprehensive repository of information related to genes methylated in diseases that can be found through text mining. DDMGD's scope is not limited to a particular group of genes, diseases or species. Using the text mining system DEMGD we developed earlier and additional post-processing, we extracted associations of genes methylated in different diseases from PubMed Central articles and PubMed abstracts. The accuracy of extracted associations is 82% as estimated on 2500 hand-curated entries. DDMGD provides a user-friendly interface facilitating retrieval of these associations ranked according to confidence scores. Submission of new associations to DDMGD is provided. A comparison analysis of DDMGD with several other databases focused on genes methylated in diseases shows that DDMGD is comprehensive and includes most of the recent information on genes methylated in diseases. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Asymptomatic rheumatic heart disease in South African schoolchildren

African Journals Online (AJOL)

[8] The WHF criteria, which represent the only evidence-based standardised guideline for the .... in high and low risk Australian children. Circulation 2014 ... Wilson J, Jungner G. Principles and practice of screening for disease. Arch Intern Med ...

Tissue-specific functional networks for prioritizing phenotype and disease genes.

Directory of Open Access Journals (Sweden)

Yuanfang Guan

Full Text Available Integrated analyses of functional genomics data have enormous potential for identifying phenotype-associated genes. Tissue-specificity is an important aspect of many genetic diseases, reflecting the potentially different roles of proteins and pathways in diverse cell lineages. Accounting for tissue specificity in global integration of functional genomics data is challenging, as "functionality" and "functional relationships" are often not resolved for specific tissue types. We address this challenge by generating tissue-specific functional networks, which can effectively represent the diversity of protein function for more accurate identification of phenotype-associated genes in the laboratory mouse. Specifically, we created 107 tissue-specific functional relationship networks through integration of genomic data utilizing knowledge of tissue-specific gene expression patterns. Cross-network comparison revealed significantly changed genes enriched for functions related to specific tissue development. We then utilized these tissue-specific networks to predict genes associated with different phenotypes. Our results demonstrate that prediction performance is significantly improved through using the tissue-specific networks as compared to the global functional network. We used a testis-specific functional relationship network to predict genes associated with male fertility and spermatogenesis phenotypes, and experimentally confirmed one top prediction, Mbyl1. We then focused on a less-common genetic disease, ataxia, and identified candidates uniquely predicted by the cerebellum network, which are supported by both literature and experimental evidence. Our systems-level, tissue-specific scheme advances over traditional global integration and analyses and establishes a prototype to address the tissue-specific effects of genetic perturbations, diseases and drugs.

Daily survival rate and habitat characteristics of nests of Wilson's Plover

Science.gov (United States)

Zinsser, Elizabeth; Sanders, Felicia J.; Gerard, Patrick D.; Jodice, Patrick G.R.

2017-01-01

We assessed habitat characteristics and measured daily survival rate of 72 nests of Charadrius wilsonia (Wilson's Plover) during 2012 and 2013 on South Island and Sand Island on the central coast of South Carolina. At both study areas, nest sites were located at slightly higher elevations (i.e., small platforms of sand) relative to randomly selected nearby unused sites, and nests at each study area also appeared to be situated to enhance crypsis and/or vigilance. Daily survival rate (DSR) of nests ranged from 0.969 to 0.988 among study sites and years, and the probability of nest survival ranged from 0.405 to 0.764. Flooding and predation were the most common causes of nest failure at both sites. At South Island, DSR was most strongly related to maximum tide height, which suggests that flooding and overwash may be common causes of nest loss for Wilson's Plovers at these study sites. The difference in model results between the 2 nearby study sites may be partially due to more-frequent flooding at Sand Island because of some underlying yet unmeasured physiographic feature. Remaining data gaps for the species include regional assessments of nest and chick survival and habitat requirements during chick rearing.

Evaluation of the norrie disease gene in a family with incontinentia pigmenti.

Science.gov (United States)

Shastry, B S; Trese, M T

2000-01-01

Incontinentia pigmenti (IP) is an ectodermal multisystem disorder which can affect dental, ocular, cardiac and neurologic structures. The ocular changes of IP can have a very similar appearance to the retinal detachment of X-linked familial exudative vitreoretinopathy, which has been shown to be caused by the mutations in the Norrie disease gene. Therefore, it is of interest to determine whether similar mutations in the gene can account for the retinal pathology in patients with IP. To test our hypothesis, we have analyzed the entire Norrie disease gene for a family with IP, by single strand conformational polymorphism followed by DNA sequencing. The sequencing data revealed no disease-specific sequence alterations. These data suggest that ocular findings of IP are perhaps associated with different genes and there is no direct relationship between the genotype and phenotype. Copyright 2000 S. Karger AG, Basel

Widespread and highly persistent gene transfer to the CNS by retrovirus vector in utero: implication for gene therapy to Krabbe disease.

Science.gov (United States)

Shen, Jin-Song; Meng, Xing-Li; Yokoo, Takashi; Sakurai, Ken; Watabe, Kazuhiko; Ohashi, Toya; Eto, Yoshikatsu

2005-05-01

Brain-directed prenatal gene therapy may benefit some lysosomal storage diseases that affect the central nervous system (CNS) before birth. Our previous study showed that intrauterine introduction of recombinant adenoviruses into cerebral ventricles results in efficient gene transfer to the CNS in the mouse. However, transgene expression decreased with time due to the non-integrative property of adenoviral vectors. In this study, in order to obtain permanent gene transduction, we investigated the feasibility of retrovirus-mediated in utero gene transduction. Concentrated retrovirus encoding the LacZ gene was injected into the cerebral ventricles of the embryos of normal and twitcher mice (a murine model of Krabbe disease) at embryonic day 12. The distribution and maintenance of the transgene expression in the recipient brain were analyzed histochemically, biochemically and by the quantitative polymerase chain reaction method pre- and postnatally. Efficient and highly persistent gene transduction to the brain was achieved both in normal and the twitcher mouse. Transduced neurons, astrocytes and oligodendrocytes were distributed throughout the brain. The transduced LacZ gene, its transcript and protein expression in the brain were maintained for 14 months without decrement. In addition, gene transduction to multiple tissues other than the brain was also detected at low levels. This study suggests that brain-directed in utero gene transfer using retrovirus vector may be beneficial to the treatment of lysosomal storage diseases with severe brain damage early in life, such as Krabbe disease. Copyright (c) 2005 John Wiley & Sons, Ltd.

Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease.

Directory of Open Access Journals (Sweden)

Peter R Sinnaeve

Full Text Available Systemic and local inflammation plays a prominent role in the pathogenesis of atherosclerotic coronary artery disease, but the relationship of whole blood gene expression changes with coronary disease remains unclear. We have investigated whether gene expression patterns in peripheral blood correlate with the severity of coronary disease and whether these patterns correlate with the extent of atherosclerosis in the vascular wall. Patients were selected according to their coronary artery disease index (CADi, a validated angiographical measure of the extent of coronary atherosclerosis that correlates with outcome. RNA was extracted from blood of 120 patients with at least a stenosis greater than 50% (CADi > or = 23 and from 121 controls without evidence of coronary stenosis (CADi = 0. 160 individual genes were found to correlate with CADi (rho > 0.2, P<0.003. Prominent differential expression was observed especially in genes involved in cell growth, apoptosis and inflammation. Using these 160 genes, a partial least squares multivariate regression model resulted in a highly predictive model (r(2 = 0.776, P<0.0001. The expression pattern of these 160 genes in aortic tissue also predicted the severity of atherosclerosis in human aortas, showing that peripheral blood gene expression associated with coronary atherosclerosis mirrors gene expression changes in atherosclerotic arteries. In conclusion, the simultaneous expression pattern of 160 genes in whole blood correlates with the severity of coronary artery disease and mirrors expression changes in the atherosclerotic vascular wall.

Imaging the impact of genes on Parkinson's disease

DEFF Research Database (Denmark)

van der Vegt, J P M; van Nuenen, B F L; Bloem, B R

2009-01-01

by the discovery of mutations in single genes that can cause autosomal dominant (alpha-synuclein (SNCA)) and leucine rich repeat kinase 2 (LRRK2) gene) or recessive (Parkin, PTEN-induced putative kinase 1 (PINK1), DJ-1, and ATP13A2 gene) forms of PD. Here, we review how structural and functional neuroimaging...... of individuals carrying a mutation in one of the PD genes has offered a unique avenue of research into the pathogenesis of PD. In symptomatic mutation carriers (i.e. those with overt disease), brain mapping can help to link the molecular pathogenesis of PD more directly with functional and structural changes...... monogenic forms of PD, common polymorphisms in genes that influence mono-aminergic signaling or synaptic plasticity may have modifying effects on distinct aspects of PD. We also discuss how functional and structural neuroimaging can be used to better characterize these genotype-phenotype correlations....

The Reflection Effect on the Eclipsing Binary by the Wilson and Devinney's Model and Russell and Merrill's Model

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Seong Hee Choea

1992-06-01

Full Text Available The reflection effect on three types of eclipsing binaries has been analyzed Wilson and Devinney's model and Russell and Merrill's model. The reflection effect was displayed on the theoretical light curves for the various conditions using the Wilson and Devinney's light curve program. Two models were compared after the rectifing the theoretical light curves including the reflection effect with the Russell and Merrill's method. The result shows that two models have an agreement on the reflection effect just in cases of the small difference in temperature and albedo between two stars in the system.

Discovering hidden relationships between renal diseases and regulated genes through 3D network visualizations

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Bhavnani Suresh K

2010-11-01

Full Text Available Abstract Background In a recent study, two-dimensional (2D network layouts were used to visualize and quantitatively analyze the relationship between chronic renal diseases and regulated genes. The results revealed complex relationships between disease type, gene specificity, and gene regulation type, which led to important insights about the underlying biological pathways. Here we describe an attempt to extend our understanding of these complex relationships by reanalyzing the data using three-dimensional (3D network layouts, displayed through 2D and 3D viewing methods. Findings The 3D network layout (displayed through the 3D viewing method revealed that genes implicated in many diseases (non-specific genes tended to be predominantly down-regulated, whereas genes regulated in a few diseases (disease-specific genes tended to be up-regulated. This new global relationship was quantitatively validated through comparison to 1000 random permutations of networks of the same size and distribution. Our new finding appeared to be the result of using specific features of the 3D viewing method to analyze the 3D renal network. Conclusions The global relationship between gene regulation and gene specificity is the first clue from human studies that there exist common mechanisms across several renal diseases, which suggest hypotheses for the underlying mechanisms. Furthermore, the study suggests hypotheses for why the 3D visualization helped to make salient a new regularity that was difficult to detect in 2D. Future research that tests these hypotheses should enable a more systematic understanding of when and how to use 3D network visualizations to reveal complex regularities in biological networks.

Genomic analysis of primordial dwarfism reveals novel disease genes.

Science.gov (United States)

Shaheen, Ranad; Faqeih, Eissa; Ansari, Shinu; Abdel-Salam, Ghada; Al-Hassnan, Zuhair N; Al-Shidi, Tarfa; Alomar, Rana; Sogaty, Sameera; Alkuraya, Fowzan S

2014-02-01

Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in defining clinical subgroups. In this study, we present the results of clinical and genomic characterization of 16 new patients in whom a broad definition of PD was used (e.g., 3M syndrome was included). We report a novel PD syndrome with distinct facies in two unrelated patients, each with a different homozygous truncating mutation in CRIPT. Our analysis also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance. PD is extremely heterogeneous genetically and clinically, and genomic tools are often required to reach a molecular diagnosis.