gebhart/patrepeval huggingface dataset:
Identification of a gene signature in cell cycle pathway for breast cancer prognosis using gene expression profiling data (2008)

Taken together, the gene expression signature model we developed from well defined pathways is not only a consistently powerful prognosticator but also mechanistically linked to cancer biology. Our approach provides an alternative to the current methodology of identifying gene expression markers for cancer prognosis and drug responses using the whole genome gene expression data.
Theoretically Determined Three-Dimensional Structures for Amphipathic Segments of the HIV-1 gp41 Envelope Protein (1989)

Three-dimensional computer models for two segments of the C terminus of gp41, the transmembrane AIDS envelope protein, which may form amphipathic alpha-helices, have been generated using structure prediction techniques combined with energy minimization and molecular dynamics simulations. Regions gp41(772-790) and gp41(828-848) of the HXB2 strain of HIV-1 display extraordinarily high hydrophobic moment maxima as alpha-helices and when in an antiparallel conformation exhibit charge complementarity, implying that they may bind with each other and associate with the membrane. The feasibility of this hypothesis was tested in a series of computer simulations of these peptides, extended by several residues to include additional charge pairing. Beginning with a trial structure in the form of antiparallel alpha-helices of segments 770-794 and 824-856, systematic axial rotations and displacements were used to generate alternative initial states. Molecular dynamics simulations with alpha-helical torsional restraints yielded several approximately cylindrical dimeric structures highly stabilized by numerous salt links and other hydrogen bonds. This suggests that these two regions may fold back on each other in antiparallel fashion to form a loop in the tertiary structure over residues 770-856, with the loop closed by membrane-associated amphipathic alpha-helices with charged sides facing each other. We speculate that such structures could aggregate to form channels or otherwise destabilize the membrane, thereby contributing to the cytopathic effects of the gp120-gp41 complex.
An Endoluminal Sleeve Induces Substantial Weight Loss and Normalizes Glucose Homeostasis in Rats with Diet‐Induced Obesity (2008)

To investigate the contributions of two surgical gut manipulations-exclusion of the proximal intestine from alimentary flow and exposure of the jejunum to partially digested nutrients-to body weight regulation and metabolism, we have developed a rat model of an investigational device, the endoluminal sleeve (ELS). The ELS is a 10 cm, nutrient-impermeable, flexible tube designed for endoluminal implantation. ELS devices were surgically implanted in the duodenal bulb of rats with diet-induced obesity. Body weight, food intake, stool caloric content, and glucose homeostasis were subsequently evaluated. ELS-implanted rats demonstrated a 20% reduction of body weight compared to sham-operated (SO) controls. ELS-treated animals consumed an average of 27% fewer kcal/day than SO, and there was no evidence of malabsorption. ELS treatment improved fasting glycemia and glucose tolerance after oral and intraperitoneal (IP) administration. ELS treatment enhanced insulin sensitivity, as demonstrated by decreased fasting and glucose-stimulated insulin levels and confirmed by calculation of homeostasis model assessment of insulin resistance (IR). These data suggest that selective bypass of the proximal intestine by ELS, with enhanced delivery of partially digested nutrients to the jejunum, mimics many of the effects of Roux-en-Y gastric bypass (RYGB) on body weight and glucose metabolism. Thus, ELS implantation may be an effective treatment for obesity and diabetes. Since the ELS device is amenable to endoscopic placement, it may offer a valuable alternative to more invasive surgical approaches in selected patients with obesity and its metabolic complications.
Characterization of human immunodeficiency virus type 1 Pr55gag membrane association in a cell-free system: requirement for a C-terminal domain. (1994)

Association of the human immunodeficiency virus type 1 (HIV-1) gag polyprotein precursor with cellular membranes is necessary for assembly of virions. We used in vitro synthesized HIV-1 gag to study its association with isolated cellular membranes. Rabbit reticulocyte lysates programmed with HIV-1 gag mRNA incorporated [35S]methionine and [3H]myristate into two predominant species of 55 kDa and 40 kDa. Radioimmunoprecipitation with HIV-1-specific antibodies suggested that the 55-kDa protein represented the polyprotein precursor (Pr55gag), while the 40-kDa protein was a mixture of N- or C-terminal truncations of the gag precursor. The Pr55gag protein bound to cellular membranes, while the 40-kDa mixed protein species did not. Membrane binding studies with C terminus-truncated and point mutants revealed that the seven-amino acid sequence located between the two Cys-His arrays in the nucleocapsid region was necessary for stable association to occur. Therefore, we propose that signals in addition to myristate are required for the membrane association of HIV-1 gag proteins and that these signals include a domain in the nucleocapsid protein.
Phosphorylation of hepatitis C virus nonstructural protein 5A modulates its protein interactions and viral RNA replication (2004)

The study of the hepatitis C virus (HCV) has been hindered by the lack of in vitro model systems. The recent development of HCV subgenomic RNA replicons has permitted the study of viral RNA replication in cell culture; however, the requirements for efficient replication of replicons in this system are poorly understood. Many viral isolates do not function as replicons and most require conserved changes, termed adaptive mutations, to replicate efficiently. In this report, we focus on the HCV nonstructural protein 5A (NS5A), a frequent locus for adaptive mutation. We found the interaction between NS5A and human vesicle-associated membrane protein-associated protein A (hVAP-A), a cellular target N-ethylmaleimide-sensitive factor attachment protein receptor, to be required for efficient RNA replication: NS5A mutations that blocked interaction with hVAP-A strongly reduced HCV RNA replication. Further analyses revealed an inverse correlation between NS5A phosphorylation and hVAP-A interaction. A subset of the previously identified adaptive mutations suppressed NS5A hyperphosphorylation and promoted hVAP-A binding. Our results support a model in which NS5A hyperphosphorylation disrupts interaction with hVAP-A and negatively regulates viral RNA replication, suggesting that replicon-adaptive mutations act by preventing the phosphorylation-dependent dissociation of the RNA replication complex.
Increase of GKLF messenger RNA and protein expression during progression of breast cancer. (2000)

Genetic alterations found in carcinomas can alter specific regulatory pathways and provide a selective growth advantage by activation of transforming oncogenes. A subset of these genes, including wild-type alleles of GLI or c-MYC, and activated alleles of RAS or beta-catenin, exhibit transforming activity when expressed in diploid epithelial RK3E cells in vitro. By in vitro transformation of these cells, the zinc finger protein GKLF/KLF-4 was recently identified as a novel oncogene. Although GKLF is normally expressed in superficial, differentiating epithelial cells of the skin, oral mucosa, and gut, expression is consistently up-regulated in dysplastic epithelium and in squamous cell carcinoma of the oral cavity. In the current study, we used in situ hybridization, Northern blot analysis, and immunohistochemistry to detect GKLF at various stages of tumor progression in the breast, prostate, and colon. Overall, expression of GKLF mRNA was detected by in situ hybridization in 21 of 31 cases (68%) of carcinoma of the breast. Low-level expression of GKLF mRNA was observed in morphologically normal (uninvolved) breast epithelium adjacent to tumor cells. Increased expression was observed in neoplastic cells compared with adjacent uninvolved epithelium for 14 of 19 cases examined (74%). Ductal carcinoma in situ exhibited similar expression as invasive carcinoma, suggesting that GKLF is activated prior to invasion through the basement membrane. Expression as determined by Northern blot was increased in most breast tumor cell lines and in immortalized human mammary epithelial cells when these were compared with finite-life span human mammary epithelial cells. Alteration of GKLF expression was confirmed by the use of a novel monoclonal antibody that detected the protein in normal and neoplastic tissues in a distribution consistent with localization of the mRNA. In contrast to most breast tumors, expression of GKLF in tumor cells of colorectal or prostatic carcinomas was reduced or unaltered compared with normal epithelium. The results demonstrate that GKLF expression in epithelial compartments is altered in a tissue-type specific fashion during tumor progression, and suggest that increased expression of GKLF mRNA and protein may contribute to the malignant phenotype of breast tumors.
Association of genetic polymorphism of glutathione S-transferase (GSTM1, GSTT1, GSTP1) with bladder cancer susceptibility (2011)

The glutathione-S-transferases (GSTs) comprise a class of enzymes that detoxify carcinogenic compounds by conjugating glutathione to facilitate their removal. Polymorphisms in GSTM1, GSTT1, and GSTP1 genes have been related to risk for bladder cancer. Studies focusing on GSTs gene variants relationship with the risk of bladder cancer have produced conflicting and inconsistent results. We examine the association between genetic polymorphism of glutathione S-transferase P1, GSTM1, GSTT1 genes and development of bladder transitional cell carcinoma (TCC). The study population consisted of 166 histologically confirmed male bladder TCC cases and 332 healthy male controls. Genotyping was done using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method and also investigated combined gene interactions. The GSTP1 Val/Val genotype was significantly associated with bladder cancer (OR = 4.32, 95% CI: 2.64-6.34), whereas the association observed for GSTM1 null (OR = 1.32, 95% CI: 0.82-2.62; P = 0.67) and GSTT1 null genotype (OR = 1.18, 95% CI: 0.79-1.67; P = 0.74) did not reach statistical significance. There was a significant multiple interaction between GSTM1, GSTT1, and GSTP1 genotypes in risk of bladder cancer (P for interaction = 0.02). The risk associated with the concurrent presence of GSTM1 positive and GSTP1 Ile/Val or Val/Val (OR = 3.71, 95% CI: 2.34-5.54) and GSTT1 positive and GSTP1 Ile/Val or Val/Val (OR = 2.66, 95% CI: 1.54-4.72) was statistically significant. Patients carrying GSTP1 Val/Val genotype were at increased risk for developing high-grade (OR = 7.68, 95% CI: 4.73-19.25) and muscle invasive (OR = 10.67, 95% CI: 6.34-21.75) bladder cancer. High risk for bladder TCC also was observed with respect to combined GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 4.76, 95% CI: 2.68-18.72) and GSTM1 null/GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 6.42, 95% CI: 4.76-14.72) genotype variant. This study suggests that the GSTP1 polymorphism and its combination with GSTM1, and GSTT1 may be associated with bladder cancer susceptibility in the Iranian population. Further confirmation in large population-based studies is needed.
An analytical method for the 3D-location estimation of circular features for an active-vision system (2002)

A closed-form analytical solution to the circular-feature problem, which arose in the context of a 3-D object recognition system, is presented. Compared to previous methods, it is mathematically simpler, provides a solution for the case in which there does not exist a priori knowledge concerning the radius of a marker, and can be extended and applied to general quadratic surfaces. In addition, the method is clearer from a geometrical viewpoint. The method was applied to a set of circles, located on a calibration plate, whose locations were known with respect to a reference frame. The camera was calibrated prior to the application of the method. Since various distortion factors had to be compensated in order to obtain accurate estimates of the parameters of the imaged circle, an ellipse, with respect to the camera's image frame, a sequential compensation procedure was applied to the input grey-level image. Experimental results showing the validity of the method are reported.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
BC-PDS: Protecting Privacy and Self-Sovereignty through BlockChains for OpenPDS (2017)

In the Big Data era, personal metadata may will become a new type of corporate asset, however there have already been a growing public concern about user's privacy mined from metadata. In this paper we address the problem of implementing the self-sovereignty of personal metadata on the existing OpenPDS/SafeAnswers framework according to the Windhover Principle. In order to do that, we propose a new framework, called BlocakChain-based Personal Data Store (BCPDS), to realize two basic properties: notary and autonomy. This framework, firstly introduces the BlockChain as a notary, into OpenPDS/SafeAnswers for secure storage of personal meta-data instead of the original database. Next, we present an AutoNomybased Access Control (ANAC) to improve the SafeAnswers module, where ANAC is a new mechanism that enforces access based on the relationship among all authorized users and metadata's owner. In addition, we also propose General Access Structure (GAS) and threshold secret sharing scheme in BlockChain as an implementation method for our BC-PDS framework.
Insights into a Key Developmental Switch and Its Importance for Efficient Plant Breeding (2000)

Sexual reproduction of plants starts with the formation of gametes and a 2-fold reduction in the number of chromosomes (ploidy) of these cells. Fertilization, the union of sperm and egg cell restores the ploidy level to its normal value again. During the formation of pollen grains, the structures
Encapsulation of bacteria and viruses in electrospun nanofibres (2006)

Bacteria and viruses were encapsulated in electrospun polymer nanofibres. The bacteria and viruses were suspended in a solution of poly(vinyl alcohol) (PVA) in water and subjected to an electrostatic field of the order of 1 kV cm−1. Encapsulated bacteria in this work, (Escherichia coli, Staphylococcus albus) and bacterial viruses (T7, T4, λ) managed to survive the electrospinning process while maintaining their viability at fairly high levels. Subsequently the bacteria and viruses remain viable during three months at −20 and −55 °C without a further decrease in number. The present results demonstrate the potential of the electrospinning process for the encapsulation and immobilization of living biological material.
Effect of smokeless tobacco (snus) on smoking and public health in Sweden (2003)

Snus availability in Sweden appears to have contributed to the unusually low rates of smoking among Swedish men by helping them transfer to a notably less harmful form of nicotine dependence.
Design and analysis of an image transfer system using microlens arrays (1994)

Efficient large-aperture lens elements are required for 3-D integral imaging and display systems. A systematic evaluation of the spatial resolution capabilities of microlens optical combinations and the synthesis of a large-aperture objective lens by a segmented lens form is reported. It is shown that by employing an optical combination comprising macrolens arrays in conjunction with microlens focusing screens a suitable transmission element, which retains the required angular and lateral resolution, can be constructed. The advantage of using segmented lenses is their capacity to produce spatially inverted, scaled images suitable for direct orthoscopic capture. The analysis of spatial resolution presented by various authors is examined and evaluated by comparison with collated evidence.
Molybdenum Nitride Complexes with Ph3SiO Ligands Are Exceedingly Practical and Tolerant Precatalysts for Alkyne Metathesis and Efficient Nitrogen Transfer Agents (2009)

The molybdenum nitride complex [(Ph(3)SiO)(3)Mo[triple bond]N] (10), which can be conveniently prepared in situ from readily available [(Me(3)SiO)(2)((Me(3)Si)(2)N)Mo[triple bond]N] (9) and Ph(3)SiOH, and the pyridine adduct of 10, [(pyridine)(Ph(3)SiO)(3)Mo[triple bond]N] (11), exhibit excellent catalytic activity in alkyne metathesis reactions of all kinds. Adduct 11 is sufficiently stable to be weighed in air and is therefore much easier to use than any of the established, structurally defined alkyne metathesis precatalysts known to date. This new system is compatible with a host of functional groups, including esters, amides, alkenes, carbamates, ethers, silyl ethers, sulfonates, thioethers, THP acetals, glycosides, ketones, enoates, thiophenes, pyridines, thiazoles, and nitro groups, and even accepts protected propargyl alcohols as substrates. It has been used for the preparation of key intermediates for bioactive natural products, such as gallicynoic acid I, homoepilachnene, epothilone A, cruentaren A, and a fully synthetic latrunculin analogue. However, 9 and 11 react with aldehydes and acid chlorides to give the corresponding nitrile derivatives.
Cervical papillomaviruses segregate within morphologically distinct precancerous lesions (1985)

We combined molecular hybridization and histological analysis of 58 biopsy samples from the uterine cervix to correlate the presence of certain strains of human papillomaviruses (HPVs) with specific pathological changes. HPV sequences were frequently detected (85%) in biopsies that contained a broad spectrum of precancerous changes. The presence of HPV 16 correlated strongly with precancers that exhibited morphological aberrations commonly found in invasive carcinomas and precancers that have a high risk of progression. This association underscores the potential importance of HPV type 16 in the genesis of genital cancers and emphasizes the value of histological analysis for detecting potentially oncogenic HPVs.
Characterizing the mu-conotoxin binding site on voltage-sensitive sodium channels with toxin analogs and channel mutations. (1995)

The three-dimensional organization of the domains of the rat skeletal muscle sodium channel subtype 1 (rSkM1) and the toxin-channel interaction surface have been explored by a complementary mutagenesis approach. This method involves probing mutant channels with analogs of the peptide toxin, mu-conotoxin (mu-CTX), for which the tertiary structure has been determined. mu-CTX has an overall net charge of +5. The blocking of Na+ currents of rSkM1 expressed in Xenopus oocytes by mu-CTX analogs in which negative charge had been removed by Asn substitution for Asp or positive charge had been decreased by Gln substitution for Arg or Lys was studied; the mu-CTX analogs exhibited decreased blocking potencies of up to 228-fold compared with an IC50 = 51.4 +/- 2.2 nM for native mu-CTX on wild-type rSkM1. Mutations at Arg 13 of mu-CTX were the most critical in decreasing potency and at Lys9 were the least critical. Charge alone, however, was not the essential factor in some toxin substitutions: the IC50 value for Asp12Asn showed little change while that for Asp12Glu was increased approximately 100-fold due to a change in conformation (revealed by NMR measurements of the toxin in solution). Focusing on the sites in the channel which might be involved in toxin binding, mutations were introduced involving substitutions at more than a dozen mostly anionic sites in putative extracellular residues of rSkM1. The toxin binding results indicate: firstly, many channel mutations at anionic sidechains on the putative extracellular surface of mu-CTX-sensitive channels, thought to be possible sites of interaction with toxin, have been shown to have no effect on toxin binding. Secondly, one channel mutation, rSkM1/Tyr401Cys, (in the loop between S5 and S6 of Domain 1), affected mu-CTX potency causing a 3.7-fold increase in IC50 value. The ratio of toxin blocking potencies was not significantly different when wild-type and the mutant (Tyr401Cys) rSkM1 channels were studied with two toxin analogs, Arg19Gln and Arg13Gln, in contrast to all other toxin derivatives examined. Since Tyr401 is known to be in the channel pore, these results suggest that either or both of the Arg residues at positions 13 and 19 of mu-CTX interact(s) with residue Tyr401 of rSkM1 and, therefore, indicate that mu-CTX extends into the pore region of the channel.
NiagaraCQ (2000)

Continuous queries are persistent queries that allow users to receive new results when they become available. While continuous query systems can transform a passive web into an active environment, they need to be able to support millions of queries due to the scale of the Internet. No existing systems have achieved this level of scalability. NiagaraCQ addresses this problem by grouping continuous queries based on the observation that many web queries share similar structures. Grouped queries can share the common computation, tend to fit in memory and can reduce the I/O cost significantly. Furthermore, grouping on selection predicates can eliminate a large number of unnecessary query invocations. Our grouping technique is distinguished from previous group optimization approaches in the following ways. First, we use an incremental group optimization strategy with dynamic re-grouping. New queries are added to existing query groups, without having to regroup already installed queries. Second, we use a query-split scheme that requires minimal changes to a general-purpose query engine. Third, NiagaraCQ groups both change-based and timer-based queries in a uniform way. To insure that NiagaraCQ is scalable, we have also employed other techniques including incremental evaluation of continuous queries, use of both pull and push models for detecting heterogeneous data source changes, and memory caching. This paper presents the design of NiagaraCQ system and gives some experimental results on the system's performance and scalability.
Carbapenemase-producing Klebsiella pneumoniae in Brooklyn, NY: molecular epidemiology and in vitro activity of polymyxin B and other agents (2005)

Multiresistant K. pneumoniae with bla(KPC) are present in multiple hospitals in New York City. The most consistently active agents in vitro were tigecycline and polymyxin B, particularly when the latter was combined with rifampicin. The clinical efficacy of these agents remains to be determined.
Integrating acoustic echo cancellation with adaptive beamforming microphone arrays (1999)

In hands-free and untethered man–machine speed communication, acoustic echo control (AEC) is widely acknowledged as a critical issue determining, e.g., the quality of a full-duplex dialogue, or the speech recognition performance of voice control applications. In comparison to single microphones, microphone arrays (MAs) allow for an improved acoustic front-end by increased spatial selectivity and the flexibility to track moving sources. It is argued that in most cases, however, this will not suffice to eliminate the need for AEC. The most effective solution to AEC is provided by echo cancellation systems, which model the acoustic echo path from the source to the receiver by an adaptive digital filter. While the echo path for a time-invariant MA can be modeled by a single adaptive filter, adaptive beamforming MAs require a time-variant filter capable of tracking the change of the beamforming characteristic instantaneously or, alternatively, one echo canceller for each sensor of the array. Given the considerable computational load for acoustic echo cancelers, a concept is proposed here that limits the beamforming to several fixed beams and foresees one echo canceler for each beam. In addition to computational efficiency, this system provides synergies enhancing the control of the acoustic echo canceler as well as source finding for beamforming.