gebhart/patrepeval huggingface dataset:
Treating the full spectrum of dementia with memantine (2003)

An increasing number of elderly people result in increased social and economical impact of dementia, particularly its most common form Alzheimer's disease (AD). Dementia itself consists of a wide spectrum of disease, ranging from the mild cognitive impairment that progresses through several clinical milestones to advanced dementia. Drugs available at the moment on the market are approved for the treatment of mild to moderate dementia and their symptomatic effect is based on cholinergic substitution. However, the largest amount of costs utilised for dementia is institutional care for severely affected patients. At this stage of the disease both vascular and degenerative mechanisms contribute to the clinical expression of the disease. Recent clinical trials with the antiglutamatergic drug memantine have shown that cognitive benefit could be observed in patients with vascular dementia and reduced care dependence in those with moderately severe to severe form of the disease. The later findings are results from the M-BEST study, which is briefly rewieved here with some of the epidemiological, socioeconomical and clinical implications of such therapy.
A Machine Vision Method for Automated Alignment of Fundus Imaging Systems (2010)

Image acquisition and processing of pupil images can be used to align fundus imaging systems rapidly, accurately, and with minimal operator intervention.
Transcription switches for protoxylem and metaxylem vessel formation (2005)

Land plants evolved xylem vessels to conduct water and nutrients, and to support the plant. Microarray analysis with a newly established Arabidopsis in vitro xylem vessel element formation system and promoter analysis revealed the possible involvement of some plant-specific NAC-domain transcription factors in xylem formation. VASCULAR-RELATED NAC-DOMAIN6 (VND6) and VND7 can induce transdifferentiation of various cells into metaxylem- and protoxylem-like vessel elements, respectively, in Arabidopsis and poplar. A dominant repression of VND6 and VND7 specifically inhibits metaxylem and protoxylem vessel formation in roots, respectively. These findings suggest that these genes are transcription switches for plant metaxylem and protoxylem vessel formation.
Linkage analysis between schizophrenia and the Darierʼs disease region on 12q (1996)

There have been reports of an association between Darier's disease, an autosomal dominant genodermatosis, and psychiatric illness. Recently the gene causing Darier's disease has been mapped to an area on 12q, between D12S58 and D12S84. The findings of linkage analysis of 4 markers in the Darier's disease region on 12q in five families segregating schizophrenia are presented. They fail to support close linkage between schizophrenia and the Darier's disease region on 12q.
Effects of B and C on the ordering of L1-CoPt thin films (2001)

We have investigated the effects of B and C on the ordering of L10-CoPt films and confirmed the following quite different role between B and C in CoPt. A small amount of B considerably decreases the temperature for ordering and is interstitially incorporated into L10-CoPt along its c axis due to the large negative heat of solutions with Co and Pt. X-ray photoelectron spectroscopy analyses have revealed that B atoms combine with Co and Pt. In contrast, C is not incorporated into the CoPt lattice due to its positive heat of solution, resulting in no decrease in the ordering temperature. The present results reveal that CoPt films containing a small amount of B are promising for high density recording media.
Conjugation of poly-L-lysine to albumin and horseradish peroxidase: a novel method of enhancing the cellular uptake of proteins. (1978)

The carbodiimide-catalyzed conjugation of a 6700 molecular weight fragment of poly-L-lysine to radiolabeled human serum albumin or to horseradish peroxidase enhances the membrane transport of each protein into cultured mouse fibroblasts approximately 11- and 200-fold, respectively. At least 50% of the peroxidase activity remained after conjugation. Trypsinization and carbamylation of the two conjugates demonstrates that the enhancement of their cellular uptake is related to their poly-L-lysine content. Simple addition to the medium of comparable amounts of free poly-L-lysine has no effect on the transport of either native protein. Addition of poly-L-ornithine (molecular weight 200,000) at 3-30 microgram/ml, a condition known to cause enhancement of 125I-labeled human serum albumin uptake by mouse sarcoma cells, has no visible effect on the cellular uptake of native horseradish peroxidase. The intracellular localization of the enzyme-poly-L-lysine conjugate can be demonstrated cytochemically by either light or transmission electron microscopy. A concentration of conjugate that increases the uptake more than 200-fold does not cause any detectable morphological change suggestive of cell toxicity. Furthermore, because poly-L-lysine is an excellent substrate for intracellular proteolytic enzymes, it can be expected to be broken down and reutilized in the cell.
Polyethylene-based water-equivalent phantom material for X-ray dosimetry at tube voltages from 10 to 100 kV (1985)

A water-equivalent plastic material RW-1, in the form of thin foils as well as of thicker sheets, has been produced by melting powdered polyethylene together with CaCO3 and MgO. The mixture has been developed in a three-step procedure, starting with provisional mixtures and using data from their measured attenuation curves to determine the final composition. The attenuation curves of RW-1 and of water, as well as their backscatter factors, are in excellent agreement for x-ray tube voltages from 10 to 100 kV.
Characterization of the Stress Response of a Bioluminescent Biological Sensor in Batch and Continuous Cultures (1996)

The effects of temperature, growth stage, and inducer (ethanol) concentration on the kinetics and magnitude of the stress response were investigated by using an Escherichia coli strain with the grpE heat shock promoter fused to the Vibrio fischeri lux genes. When stressed, the cells responded by changing the level of specific light emission, which was measured both on- and off-line. These measurements were used to characterize and optimize the sensitivity of the construct by determining the conditions at which the culture exhibited maximum specific bioluminescence and minimum response time to ethanol induction in batch cultivation. The results of the batch study were then applied to continuous cultivation, and the effect of dilution rate was determined. These results are of considerable interest in the development of an on-line biological sensor system for the detection and toxicity assessment of chemical pollutants.
Gateway-Compatible Yeast One-Hybrid Screens (2006)

INTRODUCTIONProtein-DNA interactions (PDIs) between transcription factors (TFs) and their target genes form the backbone of transcription regulatory networks. Such PDIs can be identified with either a TF or a gene as a starting point. The Gateway-compatible yeast one-hybrid (Y1H) system provides a high-throughput, gene-centered method for the identification of interactions between a "DNA bait" (e.g., cis-regulatory DNA elements or gene promoters) and "protein preys" (e.g., TFs). The Y1H system is a genetic system to detect PDIs based on selection of reporter gene expression in yeast. DNA baits are fused by Gateway cloning to two reporter genes, HIS3 and lacZ, and the resulting DNA bait::reporter constructs are subsequently integrated into the genome of the host yeast strain. After integration, baits are examined for self-activation (i.e., their ability to drive reporter gene expression in the absence of an exogenous prey protein). Subsequently, each DNA bait is screened for interacting proteins by transforming a library of preys into the corresponding Y1H DNA bait yeast strain. Preys are hybrid proteins composed of a protein from the organism of interest and a heterologous transcription activation domain. When a prey protein binds to the DNA bait, the heterologous activation domain activates reporter gene expression. Thus, physical interactions between both repressors and activators and their DNA targets can be identified.
The Presence of the V617F Mutation Is Associated with Higher Haemoglobin, Older Age and an Increased Risk of Thrombosis in Essential Thrombocythemia. (2005)

Abstract The acquired single nucleotide valine to phenylalanine mutation (V617F) in the JAK2 tyrosine kinase is reported at variable frequencies in patients with the Philadelphia negative myeloproliferative disorders. As yet it is unclear whether its presence has an impact upon the clinical phenotype, complications or prognosis of these conditions. We have screened 87 patients under our care with myeloproliferative diseases (28 Polcythemia Vera [PV], 50 Essential Thrombocythemia [ET] and 9 Idiopathic Myelofibrosis[IMF]) using a modification of previously reported allele specific PCR on whole blood DNA (Baxter,E.J et al 2005Lancet, 365, 1054–1061) and then correlated these results with clinical data. Overall there were 50 females and 37 males with a median age of 57.4 years (range 11–92) and median follow-up of 61.4 months (1–313). V617F was detected in 26 (93%) patients with PV, 26 (52%) ET and 2 (22%) IMF. Further analysis was performed to correlate V617F status with clinical features in the patients with ET. No survival data is presented for these patients due to the inherent bias in the analysis of fresh rather than archived samples. This will be performed in a prospective manner. However, one of the V617F positive ET patients subsequently died from AML, interestingly remaining heterozygous for this mutation. When comparing ET patients with detectable V617F against those without the mutation, the following significant differences were identified at the time of diagnosis: an older age (median 49.5 vs 39.3 years, p=0.04), higher haemoglobin (median 14 vs 13g/dl, p=0.03) and documented thrombotic events (11/26 vs 2/24, p=0.01). There were no significant differences in gender, platelet count at diagnosis or duration of follow-up. Overall thrombotic events were also more frequent in V617F positive patients (16/26 vs 7/24, p=0.02). There was no difference in thrombotic events following diagnosis (5/26 vs 5/24) or in the type of thromboses (microvasular, arterial or venous). Advanced age is a well established risk factor for thrombosis in ET, hence it is possible that V617F was associated with thrombosis as a consequence of the older age of our ET patients. Multivariate analysis was limited by small patient numbers and failed to demonstrate a significant predictive impact of either age or V617F mutation upon thrombosis. Ongoing studies will hopefully provide larger numbers for further analysis.
Regulation of Mesothelial Cell Mitogenesis by Antisense Oligonucleotides for the Urokinase Receptor (1995)

The association of urokinase-type plasminogen activator (uPA) with its receptor (uPAR) influences various biologic functions, including cell migration, angiogenesis, differentiation, and wound healing. Expression of uPAR at the mesothelial surface could, therefore, influence cellular responses in the pleural space. We found that a line of cultured human mesothelial cells (MeT5A) expressed specific and saturable binding sites for uPA that increased on stimulation with PMA. Ligand blotting studies showed that the mesothelial receptor is a 50 kD protein similar to that in other cell lines. Binding of active and intact, but not amino terminal or low molecular weight fragment, uPA to mesothelial cells enhanced DNA synthesis and cell proliferation, and antibodies against either the active site of uPA or uPAR abrogated this effect. We reasoned that regulation of uPAR expression could control uPA-induced mitogenesis and tested this hypothesis with antisense oligonucleotides complementary to uPAR mRNA. Phosphorothioate-modified antisense oligonucleotides inhibited uPA-mediated mesothelial cell proliferation in a concentration-dependent manner. These effects were associated with decreased binding of 125I-uPA and reduced expression of the uPAR gene product. The results indicate that uPAR is involved in signal transduction pathways that control uPA-mediated mesothelial cell proliferation, a process implicated in the pathogenesis of mesothelial inflammation and pleural neoplasia. Antisense oligonucleotides to uPAR suppress mesothelial cell mitogenesis in vitro and offer a potential means of regulating the process in vivo.
Non-HFE Hemochromatosis (2005)

The term "non-HFE hemochromatosis" (non-HFE HC) refers to several phenotypically similar but genetically distinct forms of hereditary hemochromatosis affecting individuals without pathogenic mutations of HFE. The involved genes are, sinsu strictu, transferrin receptor 2 (TfR2), hemojuvelin (HJV), and hepcidin (HAMP). Non-HFE HC share common pathogenic and clinical features with HFE HC. However, depending on the role of the affected gene in iron trafficking, the clinical onset may be earlier and phenotypic expressivity more severe than classic HC. Other forms of hereditary iron overload have distinct pathogenesis and phenotype. The most prevalent of these forms is "ferroportin disease," characterized by autosomal dominant trait, predominant reticuloendothelial cell iron overload, and mild organ damage. Non-HFE HC gene products, while responsible for rarer cases of HC as compared with HFE, are much more central than HFE in human iron homeostasis and understanding their function will greatly advance our comprehension of iron trafficking in health and disease.
Identification of a genomic fragment of Mycobacterium tuberculosis responsible for in vivo growth advantage. (1993)

The purpose of this work was to develop a system to identify virulence determinants of M. tuberculosis by genetic complementation. The ability to grow in mouse spleen and/or lung was defined as a potential phenotype for virulence. Enrichment for growing recombinant clones from a pool of H37Ra transformants containing the integrating pYUB178::H37Rv cosmid library was accomplished by in vivo selection. A molecular strategy was devised to isolate and clone the 25-kb H37Rv genomic fragment ivg that conferred in vivo growth advantage to H37Ra. This study is a first step toward understanding the genetics of virulence in M. tuberculosis. A detailed description of these experiments has been submitted for publication in Infection and Immunity.
Detection of enterohaemorrhagic Escherichia coli O157:H7 in minced beef using immunomagnetic separation. (1996)

Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 has been recently recognized as a human pathogen associated with haemorrhagic colitis and haemolytic uraemic syndrome. Most outbreaks of haemorrhagic colitis resulted from the consumption of undercooked minced beef or raw milk. Dairy cattle have been identified as a reservoir of EHEC O157: H7. In this study E. coli O157 specific antibody, coated on magnetic beads, was used to concentrate and release EHEC O157:H7 from meat samples. A survey of retail fresh minced beef and hamburger samples using this procedure revealed that 3 (5%) of 58 beef samples were positive for EHEC O157:H7. Two of the strains produced both VT1 and VT2 verotoxins, and one produced only VT2. Immunomagnetic separation is a sensitive and simple technique for the isolation of E. coli O157 from food, and could be useful for a further elucidation of the epidemiology of this organism. The relatively high prevalence of EHEC O157:H7 in beef samples may constitute a risk for public health. Thus, a suitable epidemiologic control and effective methods of prevention should be applied.
Gene Co-Expression Modules as Clinically Relevant Hallmarks of Breast Cancer Diversity (2014)

Co-expression modules are groups of genes with highly correlated expression patterns. In cancer, differences in module activity potentially represent the heterogeneity of phenotypes important in carcinogenesis, progression, or treatment response. To find gene expression modules active in breast cancer subpopulations, we assembled 72 breast cancer-related gene expression datasets containing ∼5,700 samples altogether. Per dataset, we identified genes with bimodal expression and used mixture-model clustering to ultimately define 11 modules of genes that are consistently co-regulated across multiple datasets. Functionally, these modules reflected estrogen signaling, development/differentiation, immune signaling, histone modification, ERBB2 signaling, the extracellular matrix (ECM) and stroma, and cell proliferation. The Tcell/Bcell immune modules appeared tumor-extrinsic, with coherent expression in tumors but not cell lines; whereas most other modules, interferon and ECM included, appeared intrinsic. Only four of the eleven modules were represented in the PAM50 intrinsic subtype classifier and other well-established prognostic signatures; although the immune modules were highly correlated to previously published immune signatures. As expected, the proliferation module was highly associated with decreased recurrence-free survival (RFS). Interestingly, the immune modules appeared associated with RFS even after adjustment for receptor subtype and proliferation; and in a multivariate analysis, the combination of Tcell/Bcell immune module down-regulation and proliferation module upregulation strongly associated with decreased RFS. Immune modules are unusual in that their upregulation is associated with a good prognosis without chemotherapy and a good response to chemotherapy, suggesting the paradox of high immune patients who respond to chemotherapy but would do well without it. Other findings concern the ECM/stromal modules, which despite common themes were associated with different sites of metastasis, possibly relating to the "seed and soil" hypothesis of cancer dissemination. Overall, co-expression modules provide a high-level functional view of breast cancer that complements the "cancer hallmarks" and may form the basis for improved predictors and treatments.
Sequence and expression of a novel GABAA receptor α subunit (1989)

Cloned cDNA encoding the bovine alpha 4 subunit of the GABAA receptor has been isolated. The predicted 51 amino acid long mature protein contains an exceptionally long intracellular domain and shares 53-56% sequence similarity to the previously characterized alpha 1, alpha 2 and alpha 3 subunits. Co-expression of alpha 4 and beta 1 in Xenopus oocytes resulted in the formation of GABA-gated chloride channels with expected pharmacology, although no benzodiazepine potentiation was observed. Northern analysis indicates that a 4 kb alpha 4 mRNA is expressed in the calf cerebellum, cortex and hippocampus but is barely detectable in the rat brain.
Distribution of a Vitamin B1 Destructive Enzyme in Fish (1943)

use of the described procedure permits easy determination of the presence of a vitamin B1 destructive enzyme in fish tissues. The distribution of this enzyme in 31 species of fish in the Great Lakes region has been studied and its occurrence is rather common. On the other hand, our results with 9 species of saltwater fish all proved negative.
SERINE β-LACTAMASES AND PENICILLIN-BINDING PROTEINS (1991)

peer reviewed
A buffer allocation scheme for ATM networks: complete sharing based on virtual partition (1995)

Buffer allocation to provide an efficient and fair use of the available buffer spaces is critically important for ATM networks. A complete sharing with virtual partition (CSVP) strategy for buffer management at a multiplexer or an output port of an output buffered switch is proposed and analyzed. The total buffer space is partitioned based on the relative traffic loads (measured or estimated). Virtual partition allows a newly arriving cell belonging to an oversubscribed type to occupy the spare space of an undersubscribed type, and to be overwritten when necessary. Using a fluid flow approach, a set of partial differential equations with a triangular stability region is established to characterize the dynamics of a system supporting two traffic flows. Under a buffer full condition, the system behavior is described by a set of non-homogeneous ordinary differential equations. The cell loss probability for each traffic type is obtained by solving the ordinary differential equations. Numerical examples indicate that by appropriately selecting the partitions, the CSVP method may be used to provide differential cell loss rate requirements by the different traffic types.
Formulation Of Controlled Release Matrix Tablets Of Isosorbide Dinitrate (2001)

Different retardant polymers Including Carbopol 934P, HydroxyPropyl Methyl Cellulose (HPMC) (Methocel K4M) and Eudragit NE30D, RL30D and RS30D as release controlling materials were evaluated. The drug release medium consisted of hydrochloric acid buffer, pH-1.2, for the first two hours and phosphate buffer, pH-6.8, for the remaining period of time during the experiments. The influence of variables including polymer type, drug: polymer ratio, tablet filler type and tablet hardness on isosorbide dinitrate (ISDN) release profile was discussed. From the retardant polymers investigated, Eudragit NE30D exhibited proper release characteristics. The pattern of drug release from formulation prepared from Eudragit NE30D was shown to correspond to the Higuchi equation. According to the equation, Mt/Mu=k.tn, lSDN release mechanism from Eudragit NE30D matrix tablets (40 mg) was based on non-Fickian-Diffusion process. It was also realized that, matrix preparation was a suitable method for the formulation of ISDN-CR tablets.
Reactions of a 4‐(trifluoromethyl)thiazole dianion (1991)

Abstract Treatment of 2‐trifluoroacetamido‐4‐(trifluoromethyl)thiazole with two equivalents of n ‐butyllithium at ‐78° produced the thiazole dianion 5 in situ , which reacted preferentially at the 5‐position with a variety of electrophiles. These electrophiles include: an aldehyde, ketone, chloroformate, acid chloride, phosphorus oxychloride, silicon chloride, and disulfide. Dianion 5 also combined with dibromodifluoromethane at ‐98° to give the corresponding 5‐(bromodifluoromethyl)thiazole 7 , which is an unusual reaction for an aromatic or heteroaromatic system. Compound 7 was converted to a 4,5‐ bis ‐(trifluoromethyl)thiazole 8 using tetrabutylammonium fluoride.
Endothelial cells interact with the core protein of basement membrane perlecan through beta 1 and beta 3 integrins: an adhesion modulated by glycosaminoglycan. (1992)

Aortic endothelial cells adhere to the core protein of murine perlecan, a heparan sulfate proteoglycan present in endothelial basement membrane. We found that cell adhesion was partially inhibited by beta 1 integrin-specific mAb and almost completely blocked by a mixture of beta 1 and alpha v beta 3 antibodies. Furthermore, adhesion was partially inhibited by a synthetic peptide containing the perlecan domain III sequence LPASFRGDKVTSY (c-RGD) as well as by GRGDSP, but not by GRGESP. Both antibodies contributed to the inhibition of cell adhesion to immobilized c-RGD whereas only beta 1-specific antibody blocked residual cell adhesion to proteoglycan core in the presence of maximally inhibiting concentrations of soluble RGD peptide. A fraction of endothelial surface-labeled detergent lysate bound to a core affinity column and 147-, 116-, and 85-kD proteins were eluted with NaCl and EDTA. Polyclonal anti-beta 1 and anti-beta 3 integrin antibodies immunoprecipitated 116/147 and 85/147 kD surface-labeled complexes, respectively. Cell adhesion to perlecan was low compared to perlecan core, and cell adhesion to core, but not to immobilized c-RGD, was selectively inhibited by soluble heparin and heparan sulfates. This inhibition by heparin was also observed with laminin and fibronectin and, in the case of perlecan, was found to be independent of heparin binding to substrate. These data support the hypothesis that endothelial cells interact with the core protein of perlecan through beta 1 and beta 3 integrins, that this binding is partially RGD-independent, and that this interaction is selectively sensitive to a cell-mediated effect of heparin/heparan sulfates which may act as regulatory ligands.