gebhart/patrepeval huggingface dataset:
ATM germline heterozygosity does not play a role in chronic lymphocytic leukemia initiation but influences rapid disease progression through loss of the remaining ATM allele (2011)

Ataxia telangiectasia patients, with constitutional bi-allelic ATM mutations, have a marked risk of lymphoid tumors and ATM mutation carriers have a smaller risk of cancer. Sporadic ATM mutations occur in 10-20% of chronic lymphocytic leukemia and are often associated with chromosome 11q deletions which cause loss of an ATM allele. The role of constitutional ATM mutations in the pathogenesis of chronic lymphocytic leukemia is unknown. Here we investigated the frequency of constitutional ATM mutations in either of two chronic lymphocytic leukemia cohorts, those with and without a chromosome 11q deletion. We found that in comparison to controls, constitutional pathogenic ATM mutations were increased in patients with chromosome 11q deletions (6 of 140 vs. 0 of 281, P = 0.001) but not in those without 11q deletions (2 of 178 vs. 0 of 281, P = 0.15). These results suggest that ATM germline heterozygosity does not play a role in chronic lymphocytic leukemia initiation but rather influences rapid disease progression through ATM loss.
Irreversible inhibition of serine proteases by peptide derivatives of (.alpha.-aminoalkyl)phosphonate diphenyl esters (1991)

Peptidyl derivatives of diphenyl (alpha-aminoalkyl)phosphonates have been synthesized and are effective and specific inhibitors of serine proteases at low concentrations. Z-PheP(OPh)2 irreversibly reacts with chymotrypsin (kobsd/[I] = 1200 M-1 s-1) and does not react with two elastases. The best inhibitor for most chymotrypsin-like enzymes including bovine chymotrypsin, cathepsin G, and rat mast cell protease II is the tripeptide Suc-Val-Pro-PheP(OPh)2 which corresponds to the sequence of an excellent p-nitroanilide substrate for several chymases. The valine derivative Z-ValP(OPh)2 is specific for elastases and reacts with human leukocyte elastase (HLE, 280 M-1 s-1) but not with chymotrypsin. The tripeptide Boc-Val-Pro-ValP(OPh)2, which has a sequence found in a good trifluoromethyl ketone inhibitor of HLE, is the best inhibitor for HLE (kobsd/[I] = 27,000 M-1 s-1) and porcine pancreatic elastase (PPE, kobsd/[I] = 11,000 M-1 s-1). The rates of inactivation of chymotrypsin by MeO-Suc-Ala-Ala-Pro-PheP(OPh)2 and PPE and HLE by MeO-Suc-Ala-Ala-Pro-ValP(OPh)2 were decreased 2-5-fold in the presence of the corresponding substrate, which demonstrates active site involvement. Only one of two diastereomers of Suc-Val-Pro-PheP(OPh)2 reacts with chymotrypsin (146,000 M-1 s-1), and the enzyme-inhibitor complex had one broad signal at 25.98 ppm in the 31P NMR spectrum corresponding to the Ser-195 phosphonate ester. Phosphonylated serine proteases are extremely stable since the half-time for reactivation was greater than 48 h for the inhibited elastases and 7.5-26 h for chymotrypsin.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunotoxin treatment targeted to the high-molecular-weight melanoma—associated antigen prolonging the survival of immunodeficient rats with invasive intracranial human glioblastoma multiforme (2004)

Targeted treatment of highly invasive GBMs proved effective, and these results emphasize the clinical relevance of this antigen as a target molecule for immunotoxin treatment of human GBMs.
Intravenous Lidocaine Attenuates Acute Lung Injury Induced by Hydrochloric Acid Aspiration in Rabbits (1998)

Intravenous lidocaine started before and immediately after acid instillation attenuated the acute lung injury, in part by inhibiting the sequestration and activation of neutrophils.
Curcumin-induced apoptosis in ovarian carcinoma cells is p53-independent and involves p38 mitogen-activated protein kinase activation and downregulation of Bcl-2 and survivin expression and Akt signaling (2009)

New cytotoxic agents are urgently needed for the treatment of advanced ovarian cancer because of the poor long-term response of this disease to conventional chemotherapy. Curcumin, obtained from the rhizome of Curcuma longa, has potent anticancer activity; however, the mechanism of curcumin-induced cytotoxicity in ovarian cancer cells remains a mystery. In this study we show that curcumin exhibited time- and dose-dependent cytotoxicity against monolayer cultures of ovarian carcinoma cell lines with differing p53 status (wild-type p53: HEY, OVCA429; mutant p53: OCC1; null p53: SKOV3). In addition, p53 knockdown or p53 inhibition did not diminish curcumin killing of HEY cells, confirming p53-independent cytotoxicity. Curcumin also killed OVCA429, and SKOV3 cells grown as multicellular spheroids. Nuclear condensation and fragmentation, as well as DNA fragmentation and poly (ADP-ribose) polymerase-1 cleavage in curcumin-treated HEY cells, indicated cell death by apoptosis. Procaspase-3, procaspase-8, and procaspase-9 cleavage, in addition to cytochrome c release and Bid cleavage into truncated Bid, revealed that curcumin activated both the extrinsic and intrinsic pathways of apoptosis. Bax expression was unchanged but Bcl-2, survivin, phosphorylated Akt (on serine 473), and total Akt were downregulated in curcumin-treated HEY cells. Curcumin also activated p38 mitogen-activated protein kinase (MAPK) without altering extracellular signal-regulated kinase 1/2 activity. We conclude that p53-independent curcumin-induced apoptosis in ovarian carcinoma cells involves p38 MAPK activation, ablation of prosurvival Akt signaling, and reduced expression of the antiapoptotic proteins Bcl-2 and survivin. These data provide a mechanistic rationale for the potential use of curcumin in the treatment of ovarian cancer.
Conjugal Transfer of Plasmid-Borne Multiple Antibiotic Resistance in Streptococcus faecalis var. zymogenes (1974)

A strain of Streptococcus faecalis var. zymogenes, designated JH1, had high-level resistance to the antibiotics streptomycin, kanamycin, neomycin, erythromycin, and tetracycline. These resistances were lost en bloc from approximately 0.1% of cells grown in nutrient broth at 45 C. The frequency of resistance loss was not increased by growth in the presence of the "curing" agents acriflavine or acridine orange, but after prolonged storage in nutrient agar 17% of cells became antibiotic sensitive. Covalently closed circular deoxyribonucleic acid (DNA) molecules were isolated from the parental strain and from antibiotic-sensitive segregants by using cesium chloride-ethidium bromide gradients. DNA molecular species were identified by using neutral sucrose gradients. Strain JH1 contained two covalently closed circular DNA species of molecular weights 50 x 10(6) and 38 x 10(6). An antibiotic-sensitive segregant, strain JH1-9, had lost the larger molecular species. A second sensitive segregant, strain JH1-5, had also lost the larger molecular species but a new molecular species of approximate molecular weight 6 x 10(6) was present. The antibiotic resistances that were curable from the parental strain were transferred to antibiotic-sensitive strains of S. faecalis and to strain JH1-9, during mixed incubation in nutrient broth at 37 C. Data to be described are interpreted to suggest that the transfer is by a conjugal mechanism. Analysis of the plasmid species in recipient clones showed that all had received the plasmid of molecular weight 50 x 10(6). Strain JH1-5 was not a good recipient. Analysis of one successful recipient clone of JH1-5 revealed that it had gained the 50 x 10(6) molecular weight plasmid but lost the 6 x 10(6) molecular weight species. These data are interpreted to mean that the multiple antibiotic resistance is borne by a transferable plasmid of 50 x 10(6) molecular weight, and that in clone JH1-5 this plasmid suffered a large deletion leaving only a 6 x 10(6) remnant which was incompatible with the complete replicon.
Assembly of adeno-associated virus type 2 capsids in vitro. (1997)

Capsid proteins VP1, VP2 and VP3 of adeno-associated virus type 2 (AAV-2) were separately expressed by recombinant baculoviruses, purified under denaturing conditions and renatured in the presence of 0.5 M arginine, followed by dialysis against buffers of physiological ionic strength. At a protein concentration of 0.05 mg/ml, the three capsid proteins predominantly formed monomers and, to a lesser extent, oligomers, as determined by sedimentation analysis. Oligomerization increased at higher protein concentrations. The capsid protein oligomers consisted of globular, non-capsid-like structures, as detected by electron microscopy. Addition of a HeLa cell extract significantly stimulated oligomerization of the capsid proteins, probably due to interactions with HeLa cell proteins. Characterization of structures sedimenting around 60S by immunoprecipitation and electron microscopy showed that, in addition to other aggregates, empty capsid-like structures were formed in vitro. The identity of these structures as empty AAV capsids was verified by immunoelectron microscopy. Analysis of capsid formation in HeLa cells by transfection of VP expression constructs allowing separate expression of VP1, VP2 and VP3 showed that they were able to form capsids, although with a reduced efficiency as compared to VP proteins expressed from the wt cap gene. This finding suggests that the mutations introduced to allow separate capsid protein expression reduced the efficiency of capsid assembly in vivo and might also explain the reduced recovery of empty capsids employing the in vitro assembly procedure.
Antidepressant effects of augmentative transcranial magnetic stimulation (2007)

The data do not support previous reports from smaller samples indicating an augmenting or accelerating antidepressant effect of rTMS. Further exploration of the possible efficacy of other stimulation protocols or within selected sub-populations of patients is necessary.
Plasma Levels of Cholesteryl Ester Transfer Protein and the Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women (2004)

Elevated CETP levels are associated with an increasing risk of future CAD in apparently healthy individuals, but only in those with high triglyceride levels.
The Therapeutic Realizations Scale—Revised (TRS-R): Psychometric characteristics and relationship to treatment process and outcome (2000)

Therapeutic realizations are one of five universal, session-level change processes explicated in the Generic Model of Psychotherapy. Realizations refer to session impacts, the moment-to-moment accomplishments that patients experience within sessions. This study establishes the psychometric characteristics and factor structure of a modified patient-rated measure of session-level effects, the Therapeutic Realization Scale-Revised (TRS-R). In addition, it shows the relationship of the TRS-R to treatment process and outcome from the perspective of both patients and therapists. The findings provide support for the TRS-R as a reliable and valid, multidimensional index of session-level treatment effects.
A Comparative Study of Technics for the Detection of Antibodies to Native Deoxyribonucleic Acid (1977)

Antibodies to native DNA have been assessed by three separate radioimmunoassay methods: the Millipore filter technic, the Farr ammonium sulfate precipitation test, and a commercially available kit method. Although each method was found to be reliably reproducible, the different units by which results are expressed made comparison difficult because of the technical variations inherent in each test. The correlation between tests was, however, high. To allow for interlaboratory standardization, it is suggested that the assay method used be clearly specified. Results are best expressed in terms of mg of DNA bound per deciliter of test serum. It appears that the centrally standardized radioimmunoassay kit is the most convenient method by which these antibodies can be measured in routine laboratories.
Three-dimensional histoculture: origins and applications in cancer research. (1991)

The ability to grow cells in monolayer culture has afforded investigators the opportunity to study many aspects of cancer cell biology under carefully controlled conditions. Nonetheless, an important factor that has often been overlooked is that cells in this configuration undergo a loss of structural integrity that may significantly alter their functional properties. Three-dimensional histoculture represents a useful alternative approach to monolayer culture because it preserves the native architecture of cells while still allowing ease of experimental manipulation. This review discusses the origins of three-dimensional cultures, the potential application of these cultures to assays of tumor cell metastasis and drug sensitivity, and the evidence from gene expression studies that these cultures may be more realistic tumor models than cell monolayers.
A Short Pulse of IL-4 Delivered by DCs Electroporated With Modified mRNA Can Both Prevent and Treat Autoimmune Diabetes in NOD Mice (2010)

Bone marrow-derived dendritic cells (DCs) are cells of the immune system that have been used as a tool to boost, modulate, or dampen immune responses. In the context of autoimmunity, DCs can be modified to express immunoregulatory products encoded by transgenes, and used therapeutically in adoptive cellular therapy. DCs that were lentivirally transduced (lt) to express interleukin 4 (IL-4) can significantly delay or prevent the onset of autoimmune diabetes in nonobese diabetic (NOD) mice. However, modifying cells using viral vectors carries the dual risk of oncogenicity or immunogenicity. This study demonstrates that NOD DCs, electroporated with "translationally enhanced" IL-4 mRNA (eDC/IL-4), can be equally efficient therapeutically, despite the reduced amount and shorter duration of IL-4 secretion. Moreover, a single injection of eDC/IL-4 in NOD mice shortly after the onset of hyperglycemia was able to maintain stable glycemia for up to several months in a significant fraction of treated mice. Treatment with eDC/IL-4 boosted regulatory T (Tregs) cell functions and modulated T helper responses to reduce pathogenicity. Thus, treatment with DCs, electroporated with modified IL-4 mRNA to express IL-4 for up to 24 hours, constitutes a viable cellular therapy approach for the regulation of autoimmune diabetes, as a preferred alternative to the use of viral vectors.
Acetabular Cartilage Delamination in Femoroacetabular Impingement (2009)

There should be a high level of suspicion for articular cartilage delamination in men and in patients with primarily cam-type femoroacetabular impingement. Acetabular overcoverage may be protective against delamination. Preoperative high-quality magnetic resonance arthrograms should be carefully analyzed for evidence of delamination in this patient population.
Optimal Brain Damage (1989)

We have used information-theoretic ideas to derive a class of practical and nearly optimal schemes for adapting the size of a neural network. By removing unimportant weights from a network, several improvements can be expected: better generalization, fewer training examples required, and improved speed of learning and/or classification. The basic idea is to use second-derivative information to make a tradeoff between network complexity and training set error. Experiments confirm the usefulness of the methods on a real-world application. 1 INTRODUCTION Most successful applications of neural network learning to real-world problems have been achieved using highly structured networks of rather large size [for example (Waibel, 1989; LeCun et al., 1990)]. As applications become more complex, the networks will presumably become even larger and more structured. Design tools and techniques for comparing different architectures and minimizing the network size will be needed. More impor...
OR-1, a member of the nuclear receptor superfamily that interacts with the 9-cis-retinoic acid receptor. (1995)

We have cloned a member of the nuclear receptor superfamily. The cDNA was isolated from a rat liver library and encodes a protein of 446 aa with a predicted mass of 50 kDa. This clone (OR-1) shows no striking homology to any known member of the steroid/thyroid hormone receptor superfamily. The most related receptor is the ecdysone receptor and the highest homologies represent < 10% in the amino-terminal domain, between 15-37% in the carboxyl-terminal domain and 50-62% in the DNA binding domain. The expression of OR-1 appears to be widespread in both fetal and adult rat tissues. Potential DNA response elements composed of a direct repeat of the hexameric motif AGGTCA spaced by 0-6 nt were tested in gel shift experiments. OR-1 was shown to interact with the 9-cis-retinoic acid receptor (retinoid X receptor, RXR) and the OR-1/RXR complex to bind to a direct repeat spaced by 4 nt (DR4). In transfection experiments, OR-1 appears to activate RXR-mediated function through the DR4. Therefore OR-1 might modulate 9-cis-retinoic acid signaling by interacting with RXR.
Simplified backside-contact solar cells (1990)

Experimental and modeling results for a family of simplified backside-contact designs are presented. This simplification hinges upon the demonstration of a self-aligned metalization technique as well as an optimization of heavily doped, compensated regions in the solar cell. The resulting devices can be fabricated without mask alignment and require as few as one mask. A 10.5 cm/sup 2/ one-sun cell that achieves 21.9% efficiency is presented as an example of the potential for these device designs. Prospective performance for concentrator cells of this type is also discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Molecular Aspects of Picornavirus Infection and Detection (1989)

Molecular biology of viral replication Virion structure and cell surface interactions Genetic determinants of viral disease and application to diagnosis
Prader-Willi Syndrome and Growth Hormone Deficiency (2014)

Prader-Willi syndrome (PWS) is a rare multisystem genetic disorder demonstrating great variability with changing clinical features during patient's life. It is characterized by severe hypotonia with poor sucking and feeding difficulties in early infancy, followed by excessive eating and gradual development of morbid obesity in later infancy or early childhood. The phenotype is most probably due to hypothalamic dysfunction which is also responsible for growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies, central adrenal insufficiency and hypogonadism. The multidimensional problems of patients with PWS can be managed with multidisciplinary approach. Reduced GH secretion, low peak GH response to stimulation, decreased spontaneous GH secretion and low serum IGF-1 levels in PWS patients have been documented in many studies. GH therapy has multiple beneficial effects on growth and body composition, motor and mental development in PWS patients. The recommended dosage for GH is 0.5-1 mg/m2/day. GH therapy should not be started in the presence of obstructive sleep apnea syndrome, adenotonsillar hypertrophy, severe obesity and diabetes mellitus. GH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental and life-style measures.
Cytochrome P450 Metabolism of Betel Quid‐Derived Compounds: Implications for the Development of Prevention Strategies for Oral and Pharyngeal Cancers (2013)

Betel quid (BQ) products, with or without tobacco, have been classified by the International Agency for Research on Cancer (IARC) as group I human carcinogens that are associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. There are estimated 600 million BQ users worldwide. In Taiwan alone there are 2 million habitual users (approximately 10% of the population). Oral and pharyngeal cancers result from interactions between genes and environmental factors (BQ exposure). Cytochrome p450 (CYP) families are implicated in the metabolic activation of BQ- and areca nut-specific nitrosamines. In this review, we summarize the current knowledge base regarding CYP genetic variants and related oral disorders. In clinical applications, we focus on cancers of the oral cavity and pharynx and OPMDs associated with CYP gene polymorphisms, including CYP1A1, CYP2A6, CYP2E1, and CYP26B1. Our discussion of CYP polymorphisms provides insight into the importance of screening tests in OPMDs patients for the prevention of oral and pharyngeal cancers. Future studies will establish a strong foundation for the development of chemoprevention strategies, polymorphism-based clinical diagnostic tools (e.g., specific single-nucleotide polymorphism (SNP) "barcodes"), and effective treatments for BQ-related oral disorders.
The Receptor for Advanced Glycation End Products Is Induced by the Glycation Products Themselves and Tumor Necrosis Factor-α through Nuclear Factor-κB, and by 17β-Estradiol through Sp-1 in Human Vascular Endothelial Cells (2000)

The binding of advanced glycation end products (AGE) to the receptor for AGE (RAGE) is known to deteriorate various cell functions and is implicated in the pathogenesis of diabetic vascular complications. Here we show that AGE, tumor necrosis factor-alpha (TNF-alpha), and 17beta-estradiol (E(2)) up-regulated RAGE mRNA and protein levels in human microvascular endothelial cells and ECV304 cells, with the mRNA stability being essentially invariant. Transient transfection experiments with human RAGE promoter-luciferase chimeras revealed that the region from nucleotide number -751 to -629 and the region from -239 to -89 in the RAGE 5'-flanking sequence exhibited the AGE/TNF-alpha and E(2) responsiveness, respectively. Site-directed mutation of an nuclear factor-kappaB (NF-kappaB) site at -671 or of Sp-1 sites at -189 and -172 residing in those regions resulted in an abrogation of the AGE/TNF-alpha- or E(2)-mediated transcriptional activation. Electrophoretic mobility shift assays revealed that ECV304 cell nuclear extracts contained factors which retarded the NF-kappaB and Sp-1 elements, and that the DNA-protein complexes were supershifted by anti-p65/p50 NF-kappaB and anti-Sp-1/estrogen receptor alpha antibodies, respectively. These results suggest that AGE, TNF-alpha, and E(2) can activate the RAGE gene through NF-kappaB and Sp-1, causing enhanced AGE-RAGE interactions, which would lead to an exacerbation of diabetic microvasculopathy.
Machine Translation and the Disruption of Foreign Language Learning Activities (2015)

This study examines the question of how language teachers in a highly technology-friendly university environment view machine translation and the implications that this has for the personal learning environments of students. It brings an activity-theory perspective to the question, examining the ways that the introduction of new tools can disrupt the relationship between different elements in an activity system. This perspective opens up for an investigation of the ways that new tools have the potential to fundamentally alter traditional learning activities. In questionnaires and group discussions, respondents showed general agreement that although use of machine translation by students could be considered cheating, students are bound to use it anyway, and suggested that teachers focus on the kinds of skills students would need when using machine translation and design assignments and exams to practice and assess these skills. The results of the empirical study are used to reflect upon questions of what the roles of teachers and students are in a context where many of the skills that a person needs to be able to interact in a foreign language increasingly can be outsourced to laptops and smartphones.