gebhart/patrepeval huggingface dataset:
Carbon nanotube interconnects: a process solution (2004)

The susceptibility of common interconnect metals to electromigration at current densities of 10/sup 6/ A/cm/sup 2/ or greater has been a concern. The ITRS Roadmap emphasizes interconnect technology as a critical element and calls for innovative material and process solutions. This talk will present the potential of carbon nanotubes (CNTs) as interconnects and a processing scheme to integrate them in device fabrication.
Predictors of First Recurrence of Clostridium difficile Infection: Implications for Initial Management (2012)

Symptomatic recurrence of Clostridium difficile infection (CDI) occurs in approximately 20% of patients and is challenging to treat. Identifying those at high risk could allow targeted initial management and improve outcomes. Adult toxin enzyme immunoassay-positive CDI cases in a population of approximately 600,000 persons from September 2006 through December 2010 were combined with epidemiological/clinical data. The cumulative incidence of recurrence ≥ 14 days after the diagnosis and/or onset of first-ever CDI was estimated, treating death without recurrence as a competing risk, and predictors were identified from cause-specific proportional hazards regression models. A total of 1678 adults alive 14 days after their first CDI were included; median age was 77 years, and 1191 (78%) were inpatients. Of these, 363 (22%) experienced a recurrence ≥ 14 days after their first CDI, and 594 (35%) died without recurrence through March 2011. Recurrence risk was independently and significantly higher among patients admitted as emergencies, with previous gastrointestinal ward admission(s), last discharged 4-12 weeks before first diagnosis, and with CDI diagnosed at admission. Recurrence risk also increased with increasing age, previous total hours admitted, and C-reactive protein level at first CDI (all P < .05). The 4-month recurrence risk increased by approximately 5% (absolute) for every 1-point increase in a risk score based on these factors. Risk factors, including increasing age, initial disease severity, and hospital exposure, predict CDI recurrence and identify patients likely to benefit from enhanced initial CDI treatment.
Methotrexate polyglutamate concentrations are not associated with disease control in rheumatoid arthritis patients receiving long‐term methotrexate therapy (2010)

In contrast to other studies, the results of the present study did not show a relationship between the MTXGlu(n) concentration and reduced disease activity in patients with RA who were receiving long-term MTX therapy. However, disease activity was influenced by the RBC folate level, which may be a more important factor than MTXGlu(n) concentrations for disease control. In accordance with the findings of previous studies, we were unable to show a relationship between MTXGlu(n) concentrations and adverse effects. Prospective studies will be important to determine whether there is a role for measuring MTXGlu(n) concentrations in patients receiving long-term treatment with MTX.
T Cells Engineered with a Cytomegalovirus-Specific Chimeric Immunoreceptor (2010)

Cytomegalovirus (CMV) infection in patients receiving hematopoietic stem cell transplants (HSCT) is associated with morbidity and mortality. Adoptive T cell immunotherapy has been used to treat viral reactivation but is hardly feasible in high-risk constellations of CMV-positive HSCT patients and CMV-negative stem cell donors. We endowed human effector T cells with a chimeric immunoreceptor (cIR) directed against CMV glycoprotein B. These cIR-engineered primary T cells mediated antiviral effector functions such as cytokine production and cytolysis. This first description of cIR-redirected CMV-specific T cells opens up a new perspective for HLA-independent immunotherapy of CMV infection in high-risk patients.
Carnitine acetyltransferase activity in the human brain and its microvessels is decreased in Alzheimer's disease (1992)

L-Carnitine and acetyl-L-carnitine facilitate mitochondrial beta-oxidation of fatty acids. In the brain, they may also have a role in acetylcholine synthesis. Carnitine acetyltransferase catalyzes the interchange between L-carnitine and acetyl-L-carnitine. Recently, acetyl-L-carnitine was reported to have a beneficial effect in patients with Alzheimer's disease. We therefore assessed carnitine acetyl-transferase activity in selected brain regions and in isolated cerebral microvessels obtained at autopsy from patients with Alzheimer's disease and from age-matched control subjects. We found a 25 to 40% decrease in carnitine acetyltransferase activity in patients with Alzheimer's disease, which attained statistical significance in most brain regions and in cerebral microvessels. These findings document another neurochemical abnormality in patients with Alzheimer's disease and provide a rationale for the use of acetyl-L-carnitine in the treatment of patients with Alzheimer's disease.
Interfering with Apoptosis: Ca 2+ -Binding Protein ALG-2 and Alzheimer's Disease Gene ALG-3 (1996)

Two apoptosis-linked genes, named ALG-2 and ALG-3, were identified by means of a functional selection strategy. ALG-2 codes for a Ca(2+)-binding protein required for T cell receptor-, Fas-, and glucocorticoid-induced cell death. ALG-3, a partial complementary DNA that is homologous to the familial Alzheimer's disease gene STM2, rescues a T cell hybridoma from T cell receptor- and Fas-induced apoptosis. These findings suggest that ALG-2 may mediate Ca(2+)-regulated signals along the death pathway and that cell death may play a role in Alzheimer's disease.
Concomitant Activation of the JAK/STAT, PI3K/AKT, and ERK Signaling Is Involved in Leptin-Mediated Promotion of Invasion and Migration of Hepatocellular Carcinoma Cells (2007)

Various epidemiologic studies have shown that obesity is associated with hepatocellular carcinoma. Leptin, the key player in the regulation of energy balance and body weight control, also acts as a growth factor on certain organs in both normal and disease states. It is plausible that leptin acts to promote hepatocellular carcinogenesis directly affecting malignant properties of liver cancer cells. However, a direct role for leptin in hepatocellular carcinoma has not been shown. In this study, we analyzed the role of leptin and the mechanism(s) underlying its action in hepatocellular carcinoma cells, which express both short and long isoforms of leptin receptors. Treatment with leptin resulted in increased proliferation of both HepG2 and Huh7 cells and involves activation of signal transducers and activators of transcription 3 (STAT3), AKT, and extracellular signal-regulated kinase (ERK) signaling pathways. Leptin-induced phosphorylation of ERK and AKT was dependent on Janus-activated kinase (JAK)/STAT activation. Intriguingly, we also found that leptin potently induces invasion of hepatocellular carcinoma cells in Matrigel invasion and electric cell-substrate impedance-sensing assays. Leptin-stimulated invasion was effectively blocked by pharmacologic inhibitors of JAK/STAT and, to a lesser extent, by ERK and phosphatidylinositol 3-kinase (PI3K) inhibition. Importantly, leptin also induced the migration of both HepG2 and Huh7 cells on fibronectin matrix. Inhibition of JAK/STAT, ERK, and PI3K activation using pharmacologic inhibitors effectively blocked leptin-induced migration of HepG2 and Huh7 cells. Taken together, these data indicate that leptin promotes hepatocellular carcinoma growth, invasiveness, and migration and implicate the JAK/STAT pathway as a critical mediator of leptin action. Our findings have potential clinical implications for hepatocellular carcinoma progression in obese patients.
The Ultradian Rhythm of Alternating Cerebral Hemispheric Activity (1993)

This review covers cognitive and electroencephalographic studies of the ultradian rhythm of alternating cerebral hemispheric activity found in humans and animals. This endogenous alternation of right and left dominance ranges in periodicity from about 25 to 300 min with peaks between 90-200 min during waking and around 100 min during sleep. Studies of lateralized EEG activity during sleep are reported as correlates of the REM-NREM sleep cycle. Studies of lateralized ultradian rhythms of EEG during wakefulness reveal a correlation between hemispheric dominance and the nasal cycle. The rhythm of cerebral dominance has also been identified with tests of lateralized cognitive performance using left and right hemisphere dependent tasks. Awakening from REM or NREM sleep is associated with different effects on left or right hemispheric dominance. This rhythm plays an important role in cognitive performance, memory processes, visual perception, levels of arousal and performance, mood, and individual and social behavior.
Rituximab The First Monoclonal Antibody Approved for the Treatment of Lymphoma (2000)

Rituximab, a genetically engineered monoclonal chimeric antibody, targets the CD20 antigen expressed on B cells. It was approved by the US Food and Drug Administration on November 26, 1997, for the indication of relapsed or refractory, CD20-positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma (LG/F NHL), and by the European Agency for the Evaluation of Medicinal Products on June 2, 1998, for therapy of patients with Stage III/IV, follicular, chemoresistant or relapsed NHL. Eight Phase II or II clinical trials in LG/F NHL patients have been completed: five single-agent studies and three combination studies. Rituximab has a favorable safety profile: most adverse events (AEs) are Grade 1 or 2, and the frequency of AEs decrease with subsequent infusions. AEs in the combination studies are consistent with those seen with individual agents. For evaluable patients in the single-agent studies, overall response rates (ORR) ranged from 40% to 60%, median duration of response (DR) ranged from 5.9 to 15.0+ months, and median time to progression (TTP) ranged from 8.1 to 19.4+ months. For evaluable patients in the combination studies, the ORR ranged from 45% to 100%, median DR ranged from 11.7+ to 39.1+ months, and median TTP ranged from 12.9+ to 40.5+ months. Studies in intermediate- and high-grade NHL are ongoing. Long-term development plans include evaluating the safety and efficacy of rituximab in various types of lymphoma and in combination with other lymphoma regimens. Future studies may explore ways to increase rituximab efficacy by upregulating CD20 or increasing effector function with different cytokines.
Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders (2002)

Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic disorders compiled to support research and education in human genomics and the practice of clinical genetics. Started by Dr Victor A. McKusick as the definitive reference Mendelian Inheritance in Man, OMIM (www.ncbi.nlm.nih.gov/omim) is now distributed electronically by the National Center for Biotechnology Information (NCBI), where it is integrated with the Entrez suite of databases. Derived from the biomedical literature, OMIM is written and edited at Johns Hopkins University with input from scientists and physicians around the world. Each OMIM entry has a full-text summary of a genetically determined phenotype and/or gene and has numerous links to other genetic databases such as DNA and protein sequence, PubMed references, general and locus-specific mutation databases, approved gene nomenclature, and the highly detailed mapviewer, as well as patient support groups and many others. OMIM is an easy and straightforward portal to the burgeoning information in human genetics.
HYBRIDIZATION BETWEENESCHERICHIA COLIAND SHIGELLA (1957)

Luria explored the question of bacterial hybridization only briefly, but established that these two types of intestinal bacteria
 could mate and produce hybrids possessing characteristics of each. This had implications for laboratory diagnosis, raising
 the possibility that a hybrid possessing Shigella's pathogenic qualities could test as an E. coli, or vice-versa.
Low‐level laser irradiation (LLLI) promotes proliferation of mesenchymal and cardiac stem cells in culture (2007)

The present study clearly demonstrates the ability of LLLI to promote proliferation of MSCs and CSCs in vitro. These results may have an important impact on regenerative medicine.
Improved measurement of androgen receptors in human breast cancer. (1989)

Molybdate-stabilized androgen receptors have been quantitated in cytosols derived from 1026 malignant breast tumors including all new cases of primary breast cancer reported in the western region of Norway during the 3-year period 1985-1987. A simple single point saturation assay using the synthetic labeled ligand methyltrienolone was evaluated for this purpose. This approach also allowed the simultaneous determination of estrogen and progesterone receptor from the same cytosol preparation. The cytosol content of albumin was also recorded in order to control for dilution by extracellular proteins. Androgen receptor was the sex hormone receptor most frequently found both in primary and secondary breast cancer. In primary tumors 84.9% (723 of 852) showed a cytosol concentration higher than 10 fmol/mg protein compared to 71.2 and 67.1% for estrogen and progesterone receptors, respectively. This incidence is about 2 times higher than previously reported for androgen receptors in the literature and may be due to the stabilizing effects of molybdate and a serine protease inhibitor on the recovery of active binding sites in cytosol. Cytosol concentration of androgen receptor is generally lower than that of the other sex hormone receptors; the average level was 65.5 fmol/mg cytosol protein compared to 86.8 and 84.7 for estrogen and progesterone receptors, respectively. Both incidence and cytosol concentrations were lower for all sex hormone receptors in soft tissue metastasis than in the primary tumor. This decrease is not likely to be due to differences in tumor cellularity since metastatic tumors appear to be more cellular as judged from a lower cytosol content of extracellular proteins (albumin). No significant differences were observed in any parameter investigated between different metastatic sites (skin, lymph nodes). Androgen receptor levels were strongly correlated to estrogen and progesterone receptor concentration in both primary and secondary cancers. Cytosol androgen receptor concentration increases with age. This increase is more significant in metastatic than in primary tumors. Evidently, tumor cellularity is a confounding factor in primary tumors since tumor cytosols from younger patients showed a higher content of extracellular proteins. Receptor levels in lymph node metastasis did not exhibit age dependence. This may suggest that locally produced factors rather than circulating levels of sex steroids modulate tumor receptor expression. In metastatic tissues androgen receptors are present with twice the frequency of progesterone receptors and one in four of these tumors express androgen receptor as their sole sex hormone receptor. This supports the view that some of the beneficial effects of high dose progestin treatment of advanced breast cancer are mediated through the androgen receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
Converting a broad matrix metalloproteinase family inhibitor into a specific inhibitor of MMP ‐9 and MMP ‐14 (2018)

MMP-14 and MMP-9 are two well-established cancer targets for which no specific clinically relevant inhibitor is available. Using a powerful combination of computational design and yeast surface display technology, we engineered such an inhibitor starting from a nonspecific MMP inhibitor, N-TIMP2. The engineered purified N-TIMP2 variants showed enhanced specificity toward MMP-14 and MMP-9 relative to a panel of off-target MMPs. MMP-specific N-TIMP2 sequence signatures were obtained that could be understood from the structural perspective of MMP/N-TIMP2 interactions. Our MMP-9 inhibitor exhibited 1000-fold preference for MMP-9 vs. MMP-14, which is likely to translate into significant differences under physiological conditions. Our results provide new insights regarding evolution of promiscuous proteins and optimization strategies for design of inhibitors with single-target specificities.
Challenges and recent advances in MOF–polymer composite membranes for gas separation (2016)

This review summarizes the recent progress in the fabrication of MOF-polymer membranes including the challenges, difficulties and corresponding solutions.
Desensitization of G-protein-coupled Receptors (1999)

Agonist-induced phosphorylation of G-protein-coupled receptors has been shown to facilitate the desensitization processes, such as receptor internalization, decreased efficiency of coupling to G-proteins, or decreased ligand affinity. The lowered affinity may be an intrinsic property of the phosphorylated receptor or it may be the result of altered interactions between the modified receptor and downstream components such as G-proteins or arrestins. To address this issue, we purified cAR1, the major chemoattractant receptor of Dictyostelium discoideum by a strategy that is independent of the ligand binding capacity of the receptor. To our knowledge, this represents the first successful purification of a chemoattractant receptor. The hexyl-histidine-tagged receptor was solubilized from a highly enriched plasma membrane preparation and purified by Ni2+-chelating chromatography. The protocol offers a simple way to purify 100-500 micrograms of a G-protein coupled receptor that can be targeted to the plasma membrane of D. discoideum. The Kd value for the purified cAR1 was about 200 nM, consistent with that of receptors that are not coupled to G-proteins in intact cells. In contrast, the affinity of phosphorylated cAR1, purified from desensitized cells, was about three times lower. Treatment of the phosphorylated receptor with protein phosphatases caused dephosphorylation and parallel restoration of higher affinity. We propose that ligand-induced phosphorylation of G-protein-coupled receptors causes a decrease in intrinsic affinity and may be useful in maintaining the receptor's sensitivity at high agonist levels. This affinity decrease may precede other processes such as receptor internalization or uncoupling from G-proteins.
Rate of development of mutation at codon 215 of HIV‐1 reverse transcriptase and its predictive factors at the time of initiation of zidovudine therapy (1996)

The objective of the present study was to determine the rate of development of mutation at codon 215 of HIV-1 reverse transcriptase and to identify baseline characteristics associated with this mutation following initiation of zidovudine therapy. To achieve such a purpose, 80 HIV-1-infected patients starting zidovudine therapy have been submitted to clinical, immunological and virological monitoring at entry and every 12 weeks. The critical end point of the study was time to development of mutation at codon 215. The association of key baseline characteristics (CD4+ counts, clinical stage, HIV-1 p24 antigen, CD8+ counts, serum beta 2-microglobulin and virus phenotype) with the mutation at codon 215 was also investigated. A total of 38 subjects (48%) developed mutation at codon 215 during follow-up. The estimated Kaplan-Meier probability of remaining with wild genotype at 24, 48 and 96 weeks (96% CI) was 0.82 (0.73-0.90), 0.70 (0.60-0.80) and 0.53 (0.41-0.66) respectively. Univariate analysis showed that time to the development of mutation at codon 215 was positively associated with baseline p24 positivity, C clinical stage, low CD4+ count and high beta 2-microglobulin level. Only p24 antigenaemia and CD4+ count remained significantly independent predictive factors for the development of mutation at codon 215 in the Cox proportional hazard stepwise regression analysis [risk ratio (95% CI): 3.67 (1.75-7.70), P = 0.0007; 2.89 (1.17-6.72), P = 0.0073 respectively]. Thus, a continuous emergence of mutation at codon 215 was observed and HIV-1 p24 antigenaemia should be considered an independent predictor for faster development of zidovudine resistance.
Onivyde for the therapy of multiple solid tumors (2016)

Drug delivery system based on nanobiotechnology can improve the pharmacokinetics and therapeutic index of chemotherapeutic agents, which has revolutionized tumor therapy. Onivyde, also known as MM-398 or PEP02, is a nanoliposomal formulation of irinotecan which has demonstrated encouraging anticancer activity across a broad range of malignancies, including pancreatic cancer, esophago-gastric cancer, and colorectal cancer. This up-to-date review not only focuses on the structure, pharmacokinetics, and pharmacogenetics of Onivyde but also summarizes clinical trials and recommends Onivyde for patients with advanced solid tumors.
Health related quality of life outcomes after total hip and knee arthroplasties in a community based population. (2000)

Large improvements were reported for pain and function after joint arthroplasties, while small to moderate changes were seen in other areas related to quality of life. Patients with hip arthroplasties showed greater improvement in pain and function and were more satisfied with their outcomes than patients with knee arthroplasties. Although pain and function show large improvements, bodily pain and physical function were less than the values reported in the general population.
α-Conotoxin BuIA, a Novel Peptide from Conus bullatus, Distinguishes among Neuronal Nicotinic Acetylcholine Receptors (2004)

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels. Alpha subunits, together with beta 2 and/or beta 4 subunits, form ligand-binding sites at alpha/beta subunit interfaces. Predatory marine snails of the genus Conus are a rich source of nAChR-targeted peptides. Using conserved features of the alpha-conotoxin signal sequence and 3'-untranslated sequence region, we have cloned a novel gene from the fish-eating snail, Conus bullatus; the gene codes for a previously unreported alpha-conotoxin with unusual 4/4 spacing of amino acids in the two disulfide loops. Chemical synthesis of the predicted mature toxin was performed. The resulting peptide, alpha-conotoxin BuIA, was tested on cloned nAChRs expressed in Xenopus oocytes. The peptide potently blocks numerous rat nAChR subtypes, with highest potency for alpha 3- and chimeric alpha 6-containing nAChRs; BuIA blocks alpha 6/alpha 3 beta 2 nAChRs with a 40,000-fold lower IC(50) than alpha 4 beta 2 nAChRs. The kinetics of toxin unblock are dependent on the beta subunit. nAChRs with a beta 4 subunit have very slow off-times, compared with the corresponding beta 2 subunit-containing nAChR. In each instance, rat alpha x beta 4 may be distinguished from rat alpha x beta 2 by the large difference in time to recover from toxin block. Similar results are obtained when comparing mouse alpha 3 beta 2 to mouse alpha 3 beta 4, and human alpha 3 beta2 to human alpha 3 beta 4, indicating that the beta subunit dependence extends across species. Thus, alpha-conotoxin BuIA also represents a novel probe for distinguishing between beta 2- and beta 4-containing nAChRs.
Cloning of the toxin gene from Pasteurella multocida and its role in atrophic rhinitis (1990)

The gene for the osteolytic toxin of Pasteurella multocida has been cloned into a plasmid vector and expressed off its own promoter in Escherichia coli. Particular restriction endonucleases failed to cut the gene and regions flanking it, suggesting an A + T base ratio significantly greater than the remaining genome of P. multocida. Cloned toxin was indistinguishable from the native toxin with respect to molecular mass, antigenicity and toxicity in different tests. A single intraperitoneal injection of toxin purified from the recombinant E. coli reproduced in gnotobiotic pigs the pathological changes characteristic of atrophic rhinitis. The recombinant E. coli produced at least 10 times as much toxin as P. multocida.