gebhart/patrepeval huggingface dataset:
Enzymatic Characterization of Human Immunodeficiency Virus Type 1 Reverse Transcriptase Resistant to Multiple 2′,3′-Dideoxynucleoside 5′-Triphosphates (1995)

A set of five mutations (A62V, V75I, F77L, F116Y, and Q151M) in the polymerase domain of reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1), which confers on the virus a reduced sensitivity to multiple therapeutic dideoxynucleosides (ddNs), has been identified. In this study, we defined the biochemical properties of RT with such mutations by using site-directed mutagenesis, overproduction of recombinant RTs, and steady-state kinetic analyses. A single mutation, Q151M, which developed first among the five mutations in patients receiving therapy, most profoundly reduced the sensitivity of RT to multiple ddN 5'-triphosphate (ddNTPs). Addition of other mutations to Q151M further reduced the sensitivity of RT to ddNTPs. RT with the five mutations proved to be resistant by 65-fold to 3'-azido-2',3'-dideoxythymidine 5'-triphosphate (AZTTP), 12-fold to ddCTP, 8.8-fold to ddATP, and 3.3-fold to 2',3'-dideoxyguanosine 5'-triphosphate (ddGTP), compared with wild-type RT (RTwt). Steady-state kinetic studies revealed comparable catalytic efficiency (kcat/Km) of RTs carrying combined mutations as compared with that of RTwt (< 3-fold), although a marked difference was noted in inhibition constants (Ki) (e.g. Ki of a mutant RT carrying the five mutations was 62-fold higher for AZTTP than that of RTwt). Thus, we conclude that the alteration of RT's substrate recognition, caused by these mutations, accounts for the observed multi-ddN resistance of HIV-1. The features of multi-ddNTP-resistant RTs should provide insights into the molecular mechanism of RT discriminating ddNTPs from natural substrates.
Prognostic Importance of the Standardized Uptake Value on 18F-Fluoro-2-Deoxy-Glucose–Positron Emission Tomography Scan in Non–Small-Cell Lung Cancer: An Analysis of 125 Cases (1999)

We conclude that the FDG uptake in primary NSCLC on PET has an important prognostic value and could be complementary to other well-known factors in the decision on adjuvant treatment protocols.
Structure of Hybrid Backbone Methylphosphonate DNA Heteroduplexes:  Effect of R and S Stereochemistry, (2001)

Methyl phosphonate oligonucleotides have been used as antisense and antigene agents. Substitution of a methyl group for oxygen in the phosphate ester backbone introduces a new chiral center. Significant differences in physical properties and hybridization abilities are observed between the R(p) and S(p) diastereomers. Chirally pure methylphosphonate deoxyribooligonucleotides were synthesized, and the solution structures of duplexes formed between a single strand heptanucleotide methylphosphonate, d(Cp(Me)Cp(Me)Ap(Me)Ap(Me)Ap(Me)Cp(Me)A), hybridized to a complementary octanucleotide, d(TpGpTpTpTpGpGpC), were studied by NMR spectroscopy. Stereochemistry at the methylphosphonate center for the heptanucleotide was either RpRpRpRpRpRp (R(p) stereoisomer) or RpRpRpSpRpRp (S(p) stereoisomer, although only one of the six methylphosphonate centers has the S(p) stereochemistry). The results show that the methylphosphonate strands in the heteroduplexes exhibit increased dynamics relative to the DNA strand. Substitution of one chiral center from R(p) to S(p) has a profound effect on the hybridization ability of the methylphosphonate strand. Sugars in the phosphodiester strand exhibit C(2)(') endo sugar puckering while the sugars in the methyl phosphonate strand exhibit an intermediate C(4)(') endo puckering. Bases are well stacked on each other throughout the duplex. The hybridization of the methylphosphonate strand does not perturb the structure of the complementary DNA strand in the hetero duplexes. The sugar residue 5' to the S(p) chiral center shows A-form sugar puckering, with a C(3)(')-endo conformation. Minor groove width in the R(p) stereoisomer is considerably wider, particularly at the R(p) vs S(p) site and is attributed to either steric interactions across the minor groove or poorer metal ion coordination within the minor groove.
Sutureless Anastomosis of the Small Intestine and the Colon in Pigs Using an Absorbable Intraluminal Stent and Fibrin Glue (1995)

A new sutureless anastomosis technique employing a sliding absorbable intraluminal nontoxic stent (SAINT) and fibrin glue with limited (minutes) stump margin pressure is described. Fifty-one (27 small intestine, 24 colon) SAINT anastomoses were performed in 31 Landrace pigs (25-35 kg). Controls consisted of 48 (26 small intestine, 22 colon) continuous single-layer submucosal anastomoses in 26 pigs. SAINTs, which dissolve in about 30-60 min, were formed from heated sucrose and water poured into handcrafted aluminum molds. Follow-up from 7 to 540 days showed no stenosis or anastomotic imperfections in the latter part of the experiment after the SAINT production and surgical techniques were improved. The SAINT group had fewer site adhesions, faster healing, less foreign body reaction, and fewer lymphocytes than the control group. Initial results indicate that the SAINT-fibrin glue procedure may be an effective sutureless anastomotic method from the duodenum to the sigmoid colon.
Ii Chain Controls the Transport of Major Histocompatibility Complex Class II Molecules to and from Lysosomes (1997)

Major histocompatibility complex class II molecules are synthesized as a nonameric complex consisting of three alpha beta dimers associated with a trimer of invariant (Ii) chains. After exiting the TGN, a targeting signal in the Ii chain cytoplasmic domain directs the complex to endosomes where Ii chain is proteolytically processed and removed, allowing class II molecules to bind antigenic peptides before reaching the cell surface. Ii chain dissociation and peptide binding are thought to occur in one or more postendosomal sites related either to endosomes (designated CIIV) or to lysosomes (designated MIIC). We now find that in addition to initially targeting alpha beta dimers to endosomes, Ii chain regulates the subsequent transport of class II molecules. Under normal conditions, murine A20 B cells transport all of their newly synthesized class II I-A(b) alpha beta dimers to the plasma membrane with little if any reaching lysosomal compartments. Inhibition of Ii processing by the cysteine/serine protease inhibitor leupeptin, however, blocked transport to the cell surface and caused a dramatic but selective accumulation of I-A(b) class II molecules in lysosomes. In leupeptin, I-A(b) dimers formed stable complexes with a 10-kD NH2-terminal Ii chain fragment (Ii-p10), normally a transient intermediate in Ii chain processing. Upon removal of leupeptin, Ii-p10 was degraded and released, I-A(b) dimers bound antigenic peptides, and the peptide-loaded dimers were transported slowly from lysosomes to the plasma membrane. Our results suggest that alterations in the rate or efficiency of Ii chain processing can alter the postendosomal sorting of class II molecules, resulting in the increased accumulation of alpha beta dimers in lysosome-like MIIC. Thus, simple differences in Ii chain processing may account for the highly variable amounts of class II found in lysosomal compartments of different cell types or at different developmental stages.
Intranasal Dexmedetomidine as a Sedative Premedication for Patients Undergoing Suspension Laryngoscopy: A Randomized Double-Blind Study (2016)

ClinicalTrials.gov NCT 02108171.
Three-Dimensional Structures of the Free and Antigen-Bound Fab from Monoclonal Antilysozyme Antibody HyHEL-63, (2000)

Antigen-antibody complexes provide useful models for studying the structure and energetics of protein-protein interactions. We report the cloning, bacterial expression, and crystallization of the antigen-binding fragment (Fab) of the anti-hen egg white lysozyme (HEL) antibody HyHEL-63 in both free and antigen-bound forms. The three-dimensional structure of Fab HyHEL-63 complexed with HEL was determined to 2.0 A resolution, while the structure of the unbound antibody was determined in two crystal forms, to 1.8 and 2.1 A resolution. In the complex, 19 HyHEL-63 residues from all six complementarity-determining regions (CDRs) of the antibody contact 21 HEL residues from three discontinuous polypeptide segments of the antigen. The interface also includes 11 bound water molecules, 3 of which are completely buried in the complex. Comparison of the structures of free and bound Fab HyHEL-63 reveals that several of the ordered water molecules in the free antibody-combining site are retained and that additional waters are added upon complex formation. The interface waters serve to increase shape and chemical complementarity by filling cavities between the interacting surfaces and by contributing to the hydrogen bonding network linking the antigen and antibody. Complementarity is further enhanced by small (<3 A) movements in the polypeptide backbones of certain antibody CDR loops, by rearrangements of side chains in the interface, and by a slight shift in the relative orientation of the V(L) and V(H) domains. The combining site residues of complexed Fab HyHEL-63 exhibit reduced temperature factors compared with those of the free Fab, suggesting a loss in conformational entropy upon binding. To probe the relative contribution of individual antigen residues to complex stabilization, single alanine substitutions were introduced in the epitope of HEL recognized by HyHEL-63, and their effects on antibody affinity were measured using surface plasmon resonance. In agreement with the crystal structure, HEL residues at the center of the interface that are buried in the complex contribute most to the binding energetics (DeltaG(mutant) - DeltaG(wild type) > 3.0 kcal/mol), whereas the apparent contributions of solvent-accessible residues at the periphery are much less pronounced (<1.5 kcal/mol). In the latter case, the mutations may be partially compensated by local rearrangements in solvent structure that help preserve shape complementarity and the interface hydrogen bonding network.
Breath holding spells in 91 children and response to treatment with iron (1999)

To evaluate the prognosis of breath holding spells (BHS) after iron treatment, 91 children (56 boys, 35 girls) aged between 6 months and 40 months (median, 17) were followed prospectively for a median of 45 months (range, 6-89). In 49 of the children, the frequency of BHS was less than 10 each month, in 22 it was 10-30 each month, and in 20 more than 30 each month. The spells were cyanotic in 60 children. All patients were evaluated initially and during follow up for haematological indices. Electroencephalographic and electrocardiographic abnormalities were also recorded. Sixty three patients were found to have iron deficiency anaemia and were treated with iron (6 mg/kg/day) for three months. Other patients were not given any treatment. After three months, there was a significant difference for correction of cyanotic spells between children who had been treated with iron and those who had not (84.1% v 21.4%). During further follow up, febrile convulsions occurred in 10 children (six were on iron treatment initially). It appears that treating iron deficiency anaemia is effective in reducing the frequency of BHS.
Effects of Dicer and Argonaute down-regulation on mRNA levels in human HEK293 cells (2006)

RNA interference and the microRNA (miRNA) pathway can induce sequence-specific mRNA degradation and/or translational repression. The human genome encodes hundreds of miRNAs that can post-transcriptionally repress thousands of genes. Using reporter constructs, we observed that degradation of mRNAs bearing sites imperfectly complementary to the endogenous let-7 miRNA is considerably stronger in human HEK293 than HeLa cells. The degradation did not result from the Ago2-mediated endonucleolytic cleavage but it was Dicer- and Ago2-dependent. We used this feature of HEK293 to address the size of a pool of transcripts regulated by RNA silencing in a single cell type. We generated HEK293 cell lines depleted of Dicer or individual Ago proteins. The cell lines were used for microarray analyses to obtain a comprehensive picture of RNA silencing. The 3'-untranslated region sequences of a few hundred transcripts that were commonly up-regulated upon Ago2 and Dicer knock-downs showed a significant enrichment of putative miRNA-binding sites. The up-regulation upon Ago2 and Dicer knock-downs was moderate and we found no evidence, at the mRNA level, for activation of silenced genes. Taken together, our data suggest that, independent of the effect on translation, miRNAs affect levels of a few hundred mRNAs in HEK293 cells.
In-vitro potency of azithromycin against Gram-negative bacilli is method-dependent (1991)

Journal Article In-vitro potency of azithromycin against Gram-negative bacilli is method-dependent Get access ARTHUR L. BARRY, ARTHUR L. BARRY aThe Clinical Microbiology InstituteP.O. Box 947, Tualatin, Oregon 97062 Search for other works by this author on: Oxford Academic PubMed Google Scholar PETER C. FUCHS PETER C. FUCHS bSt. Vincent Hospital and Medical Center PortlandOregon. USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, Volume 28, Issue 4, October 1991, Pages 607–610, https://doi.org/10.1093/jac/28.4.607 Published: 01 October 1991
Gratings on porous silicon structures for sensing applications (2009)

We investigate the use of gratings on porous silicon structures for sensing applications. Examples of two classes of systems are studied: grating-coupled waveguide biosensors, and diffraction-based biosensors.
The epidemiology of estrogen replacement therapy and Alzheimer's disease (1997)

The burden of Alzheimer's disease (AD) falls more heavily on women than men. It is hypothesized that plummeting levels of circulating estrogens after the menopause increase a woman's risk for this disorder and, conversely, that estrogen replacement therapy may lower the risk for dementia due to AD. A number of estrogenic properties support the biological credibility of this hypothesis. Estrogen interacts with neurotrophins and neurotransmitter systems relevant to AD and in some model systems estrogen modulates synaptic plasticity. Effects on beta-amyloid and apolipoprotein E may be especially germane to putative effects. Estrogen also may blunt neurotoxic consequences of the stress response mediated by the hypothalamic-pituitary-adrenal axis, augment cerebral glucose utilization, and enhance cerebral blood flow. Clinical studies of postmenopausal women suggest beneficial estrogen effects on specific cognitive skills, and small preliminary trials of estrogen replacement in women with AD support claims of clinical meaningful efficacy. Consistent with the estrogen hypothesis, cross-sectional studies imply that postmenopausal estrogen use could be associated with a lower risk for AD. Several recent epidemiologic studies in which information on estrogen replacement therapy was collected prospectively further support this contention, with a dose-response relation evident in some reports. Because estrogen users tend to differ from nonusers in a number of lifestyle characteristics, convincing demonstration of putative protective effects could best some from randomized, placebo-controlled, primary intervention trials. For the present, however, the issue of estrogen efficacy in lowering a woman's risk for AD remains unsettled.
Multipath execution (1998)

Article Free Access Share on Multipath execution: opportunities and limits Authors: Pritpal S. Ahuja Depts. of Computer Science, Princeton University, Princeton, New Jersey Depts. of Computer Science, Princeton University, Princeton, New JerseyView Profile , Kevin Skadron Depts. of Computer Science, Princeton University, Princeton, New Jersey Depts. of Computer Science, Princeton University, Princeton, New JerseyView Profile , Margaret Martonosi Depts. of Electrical Engineering, Princeton University, Princeton, New Jersey Depts. of Electrical Engineering, Princeton University, Princeton, New JerseyView Profile , Douglas W. Clark Depts. of Computer Science, Princeton University, Princeton, New Jersey Depts. of Computer Science, Princeton University, Princeton, New JerseyView Profile Authors Info & Claims ICS '98: Proceedings of the 12th international conference on SupercomputingJuly 1998 Pages 101–108https://doi.org/10.1145/277830.277854Online:13 July 1998Publication History 32citation410DownloadsMetricsTotal Citations32Total Downloads410Last 12 Months9Last 6 weeks2 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Phase III Trial of Ursodeoxycholic Acid To Prevent Colorectal Adenoma Recurrence (2005)

UDCA treatment was associated with a non-statistically significant reduction in total colorectal adenoma recurrence but with a statistically significant 39% reduction in recurrence of adenomas with high-grade dysplasia. Because severely dysplastic lesions have a high risk of progression to invasive colorectal carcinoma, this finding indicates that future chemoprevention trials of UDCA in individuals with such lesions should be considered.
L-type amino acid transporter 1 (LAT1) expression in malignant pleural mesothelioma. (2011)

L-Type amino acid transporter 1 (LAT1) is known to be highly expressed in various human neoplasms. However, little is known about how LAT1 is expressed in malignant pleural mesothelioma (MPM). Twenty-one patients were included in this study. Tumor sections were stained by immunohistochemistry for LAT1, glucose transporter 1 (GLUT1), GLUT3, hypoxia inducible factor-1α (HIF-1α), hexokinase I, vascular endothelial growth factor (VEGF), microvessel density (MVD) by determination of CD34, epidermal growth factor receptor (EGFR), phosphatase and tensin analog (PTEN), p-AKT, p-manmalian target of rapamycin (mTOR), p-S6K, p53 and BCL-2. LAT1 was overexpressed in approximately 50% of the patients with MPM. LAT1 expression was closely correlated with CD98, hypoxic markers, the mTOR pathway, Ki-67 and p53. The overexpression of LAT1 was closely associated with poor outcome in patients with MPM. LAT1 is closely associated with tumor development and progression in patients with MPM.
Globular Adiponectin Protected ob/ob Mice from Diabetes and ApoE-deficient Mice from Atherosclerosis (2003)

The adipocyte-derived hormone adiponectin has been shown to play important roles in the regulation of energy homeostasis and insulin sensitivity. In this study, we analyzed globular domain adiponectin (gAd) transgenic (Tg) mice crossed with leptin-deficient ob/ob or apoE-deficient mice. Interestingly, despite an unexpected similar body weight, gAd Tg ob/ob mice showed amelioration of insulin resistance and beta-cell degranulation as well as diabetes, indicating that globular adiponectin and leptin appeared to have both distinct and overlapping functions. Amelioration of diabetes and insulin resistance was associated with increased expression of molecules involved in fatty acid oxidation such as acyl-CoA oxidase, and molecules involved in energy dissipation such as uncoupling proteins 2 and 3 and increased fatty acid oxidation in skeletal muscle of gAd Tg ob/ob mice. Moreover, despite similar plasma glucose and lipid levels on an apoE-deficient background, gAd Tg apoE-deficient mice showed amelioration of atherosclerosis, which was associated with decreased expression of class A scavenger receptor and tumor necrosis factor alpha. This is the first demonstration that globular adiponectin can protect against atherosclerosis in vivo. In conclusion, replenishment of globular adiponectin may provide a novel treatment modality for both type 2 diabetes and atherosclerosis.
Toward Improving Caenorhabditis elegans Phenome Mapping With an ORFeome-Based RNAi Library (2004)

The recently completed Caenorhabditis elegans genome sequence allows application of high-throughput (HT) approaches for phenotypic analyses using RNA interference (RNAi). As large phenotypic data sets become available, "phenoclustering" strategies can be used to begin understanding the complex molecular networks involved in development and other biological processes. The current HT-RNAi resources represent a great asset for phenotypic profiling but are limited by lack of flexibility. For instance, existing resources do not take advantage of the latest improvements in RNAi technology, such as inducible hairpin RNAi. Here we show that a C. elegans ORFeome resource, generated with the Gateway cloning system, can be used as a starting point to generate alternative HT-RNAi resources with enhanced flexibility. The versatility inherent to the Gateway system suggests that additional HT-RNAi libraries can now be readily generated to perform gene knockdowns under various conditions, increasing the possibilities for phenome mapping in C. elegans.
PARP-2, A Novel Mammalian DNA Damage-dependent Poly(ADP-ribose) Polymerase (1999)

Poly(ADP-ribosylation) is a post-translational modification of nuclear proteins in response to DNA damage that activates the base excision repair machinery. Poly(ADP-ribose) polymerase which we will now call PARP-1, has been the only known enzyme of this type for over 30 years. Here, we describe a cDNA encoding a 62-kDa protein that shares considerable homology with the catalytic domain of PARP-1 and also contains a basic DNA-binding domain. We propose to call this enzyme poly(ADP-ribose) polymerase 2 (PARP-2). The PARP-2 gene maps to chromosome 14C1 and 14q11.2 in mouse and human, respectively. Purified recombinant mouse PARP-2 is a damaged DNA-binding protein in vitro and catalyzes the formation of poly(ADP-ribose) polymers in a DNA-dependent manner. PARP-2 displays automodification properties similar to PARP-1. The protein is localized in the nucleus in vivo and may account for the residual poly(ADP-ribose) synthesis observed in PARP-1-deficient cells, treated with alkylating agents or hydrogen peroxide.