gebhart/patrepeval huggingface dataset:
Doublecortin mutations cluster in evolutionarily conserved functional domains (2000)

Mutations in the X-linked gene doublecortin ( DCX ) result in lissencephaly in males or subcortical laminar heterotopia ('double cortex') in females. Various types of mutation were identified and the sequence differences included nonsense, splice site and missense mutations throughout the gene. Recently, we and others have demonstrated that DCX interacts and stabilizes microtubules. Here, we performed a detailed sequence analysis of DCX and DCX-like proteins from various organisms and defined an evolutionarily conserved Doublecortin (DC) domain. The domain typically appears in the N-terminus of proteins and consists of two tandemly repeated 80 amino acid regions. In the large majority of patients, missense mutations in DCX fall within the conserved regions. We hypothesized that these repeats may be important for microtubule binding. We expressed DCX or DCLK (KIAA0369) repeats in vitro and in vivo. Our results suggest that the first repeat binds tubulin but not microtubules and enhances microtubule polymerization. To study the functional consequences of DCX mutations, we overexpressed seven of the reported mutations in COS7 cells and examined their effect on the microtubule cytoskeleton. The results demonstrate that some of the mutations disrupt microtubules. The most severe effect was observed with a tyrosine to histidine mutation at amino acid 125 (Y125H). Produced as a recombinant protein, this mutation disrupts microtubules in vitro at high molar concentration. The positions of the different mutations are discussed according to the evolutionarily defined DC-repeat motif. The results from this study emphasize the importance of DCX-microtubule interaction during normal and abnormal brain development.
Interactions of retinol with binding proteins: studies with rat cellular retinol-binding protein and with rat retinol-binding protein (1991)

The interactions of retinol with rat cellular retinol-binding protein (CRBP) and with rat serum retinol-binding protein (RBP) were studied. The equilibrium dissociation constants of the two retinol-protein complexes (Kd) were found to be 13 x 10(-9) and 20 x 10(-9) M for CRBP and for RBP, respectively. The kinetic parameters governing the interactions of retinol with the two binding proteins were also studied. It was found that although the equilibrium dissociation constants of the two retinol-protein complexes were similar, retinol interacted with CRBP 3-5-fold faster than with RBP; the rate constants for dissociation of retinol from CRBP and from RBP (koff) were 0.57 and 0.18 min-1, respectively. The rate constants for association of retinol with the two proteins (kon) were calculated from the expression: Kd = koff/kon. The kon's for retinol associating with CRBP and with RBP were found to be 4.4 x 10(7) and 0.9 x 10(7) M-1 min-1, respectively. The data suggest that the initial events of uptake of retinol by cells are not rate-limiting for this process and that the rate of uptake is probably determined by the rate of metabolism of this ligand. The data indicate further that the distribution of retinol between RBP in blood and CRBP in cytosol is at equilibrium and that intracellular levels of retinol are regulated by the levels of CRBP.
Devices for the Treatment of Obesity: Will Understanding the Physiology of Satiety Unravel New Targets for Intervention? (2008)

The rise in the prevalence of obesity in the last few decades and its growing impact on health has driven the scientific community to investigate the physiological basis of energy homeostasis and mechanisms of satiety, and seek targets for intervention against this burgeoning epidemic. Recent findings highlight the role of gut-derived, hormonal signals in the regulation of satiety. These hormones act together with the dense and intricate enteric nervous system to coordinate and regulate gastrointestinal satiety signals, motility, and digestive processes. Bariatric surgical approaches attempt to take advantage of these mechanisms to facilitate early satiety and weight loss. Some of these procedures, by altering the anatomical structure of the upper gastrointestinal tract, also modify the hormonal response to food. Similarly, devices such as volume-occupying elements and nerve stimulators attempt to alter the gastrointestinal milieu in a manner that will ultimately lead to long-term weight loss. Novel surgical, endoscopic, and device-oriented methodologies seem to be promising approaches to treat obesity, yet further research is needed to appreciate their long-term effect.
Clustering via Concave Minimization (1996)

The problem of assigning m points in the n-dimensional real space R n to k clusters is formulated as that of determining k centers in R n such that the sum of distances of each point to the nearest center is minimized. If a polyhedral distance is used, the problem can be formulated as that of minimizing a piecewise-linear concave function on a polyhedral set which is shown to be equivalent to a bilinear program: minimizing a bilinear function on a polyhedral set. A fast finite k-Median Algorithm consisting of solving few linear programs in closed form leads to a stationary point of the bilinear program. Computational testing on a number of realworld databases was carried out. On the Wisconsin Diagnostic Breast Cancer (WDBC) database, k-Median training set correctness was comparable to that of the k-Mean Algorithm, however its testing set correctness was better. Additionally, on the Wisconsin Prognostic Breast Cancer (WPBC) database, distinct and clinically important survival curv...
Noble and Coinage Metal Nanowires by Electrochemical Step Edge Decoration (2002)

A general method is described for the electrodeposition of long (>500 μm) nanowires composed of noble or coinage metals including nickel, copper, silver, and gold. Nanowires of these metals, with diameters in the range from 60 to 750 nm, were obtained by electrochemical step edge decoration (ESED), the selective electrodeposition of metal at step edges. Nanowire growth by ESED was accomplished on highly oriented pyrolytic graphite surfaces by applying three voltage pulses in succession: An oxidizing “activation” pulse, a large amplitude, reducing “nucleation” pulse, and a small amplitude reducing “growth” pulse. The activation pulse potential was optimized to oxidize step edges on the graphite surface just prior to deposition. The nucleation pulse had an overpotential for metal deposition of between −150 and −500 mV and a duration of 5−100 ms. The growth pulse had a small deposition overpotential of less than −100 mV. Nanowire growth was characterized by a time-independent deposition current, and consequently, the nanowire radius was proportional to the square root of the deposition time in accordance with the expected growth law.
Effect of different levels of omega-3 and omega-6 fatty acids on azoxymethane-induced colon carcinogenesis in F344 rats. (1988)

The effect of various levels of dietary Menhaden fish oil containing omega-3 fatty acids plus corn oil containing omega-6 fatty acids fed during the postinitiation phase of colon carcinogenesis was studied in male F344 rats. Starting at 5 weeks of age, groups of animals were fed the 5% corn oil (5% CO) diet. At 7 weeks of age, all animals except the vehicle-treated controls were administered s.c. injections of azoxymethane (15 mg/kg body wt/week for 2 weeks). 4 days after carcinogen or vehicle treatment, groups of animals were transferred to experimental diets containing 4% Menhaden oil + 1% corn oil (4% MO + 1% CO), 23.5% corn oil (23.5% CO), 17.6% corn oil + 5.9% Menhaden oil (17.6% CO + 5.9% MO), 11.8% corn oil + 11.8% Menhaden oil (11.8% CO + 11.8% MO), or 5.9% corn oil + 17.6% Menhaden oil (5.9% CO + 17.6% MO) and fed these diets until termination of the experiment at Week 38 after carcinogen treatment. An additional group consuming a 5% CO diet was continued on these diets. Colon mucosal ornithine decarboxylase activity and microsomal fatty acid composition of colon mucosa were measured in vehicle-treated animals fed experimental diets for 14 weeks. Fatty acids were also analyzed in the microsomal fraction of colon tumors at termination of the experiment. The body weights of animals fed various experimental diets were comparable. Feeding of high fat diets containing 17.6% CO + 5.9% MO, 11.8% CO + 11.8% MO, or 5.9% CO + 17.6% MO significantly inhibited the incidence (percentage of animals with tumors) of colon adenocarcinomas compared to that of 23.5% CO diet. However, the multiplicity (number of tumors/rat) of colon adenocarcinomas was significantly inhibited only in groups fed the 5.9% CO + 17.6% MO compared to those fed the 23.5% CO diet. The incidence and multiplicity of adenocarcinomas were greater in animals fed the 23.5% CO diet compared to those fed the 5% CO diet. Colonic mucosal ornithine decarboxylase activity was lower in animals fed the 11.8% CO + 11.8% MO, 5.9% CO + 17.6% MO, 5% CO, and 4% MO + 1% CO diets compared to the levels in animals fed the 23.5% CO diet. The increasing levels of Menhaden oil in the diet significantly increased the omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid and decreased the omega-6 fatty acids such as linoleic acid, linolenic acid, and arachidonic acid in microsomal fractions from colonic mucosa and tumors.
Innovative, precise, and descriptive terms for group crisis support services: a United Nations initiative. (2007)

Terminology borrowed from other disciplines for use in crisis intervention is inadvertently open to misinterpretation and misrepresentation. Misconceptions about terminology are most common when terms are transmitted across social, cultural, national, language, and attitudinal boundaries. Critical Incident Stress Management, which is a subset of crisis intervention, encountered that exact problem with three of its terms: demobilization, defusing, and Critical Incident Stress Debriefing. Several flawed studies based on misinterpretations of the meaning of these terms have appeared in the literature. The studies may have stimulated some practitioners of crisis intervention to incorrectly conclude that those interventions were ineffective. Professionals within the Critical Incident Stress Management Unit of the Department of Safety and Security of the United Nations suggested alternative and augmented terminology to reduce the potential for further misinterpretations of Critical Incident Stress Management procedures.
Nowcasting, business cycle dating and the interpretation of new information when real time data are available (2008)

A canonical model is described which reflects the real time informational context of&#13;\ndecision-making. Comparisons are drawn with ‘conventional’ models that incorrectly omit&#13;\nmarket-informed insights on future macroeconomic conditions and inappropriately incorporate&#13;\ninformation that was not available at the time. It is argued that conventional&#13;\nmodels are misspecified and misinterpret news. However, neither diagnostic tests applied&#13;\nto the conventional models nor typical impulse response analysis will be able to expose&#13;\nthese deficiencies clearly. This is demonstrated through an analysis of quarterly US data&#13;\n1968q4-2006q1. However, estimated real time models considerably improve out-of-sample&#13;\nforecasting performance, provide more accurate ‘nowcasts’ of the current state of the&#13;\nmacroeconomy and provide more timely indicators of the business cycle. The point is illustrated&#13;\nthrough an analysis of the US recessions of 1990q3—1991q2 and 2001q1—2001q4
Methylation and intratumoural heterogeneity of 14-3-3 σ in oral cancer (2007)

14-3-3 sigma has been a major G2/M checkpoint control gene and has demonstrated that its inactivation in various cancers occurs mostly by epigenetic hypermethylation, not by genetic change. This study investigated the methylation status and expression of the 14-3-3 sigma gene in 46 oral squamous cell carcinomas by methylation-specific polymerase chain reaction, reverse transcriptase-polymerase chain reaction, Western blotting and immunohistochemistry. Exons of the p53 gene were examined for mutations by sequencing analysis and CyclinD1 by immunohistochemistry. Methylation of the 14-3-3 sigma gene was detected in 13% (6/46) of the oral tumours, but not in corresponding adjacent non-malignant and normal gingival tissues. Intratumoural heterogeneity was found in the tumour tissues including three 14-3-3 sigma-methylated samples. Methylation of 14-3-3 sigma was detected in 3 SCC with p53 mutations and 3 with wild-type p53. Our major findings are: (a) methylation of 14-3-3 gene promoter is a rare event in oral cancer; (b) it is not always associated with 14-3-3 protein levels and there is no clear relationship between its methylation and p53 mutation; (c) loss of 14-3-3 sigma expression is associated with reduced CyclinD1 gene expression.
CD8-Mediated Protection against Ebola Virus Infection Is Perforin Dependent (2005)

CD8 T cells have been shown to play an important role in the clearance and protection against fatal Ebola virus infection. In this study, we examined the mechanisms by which CD8 T cells mediate this protection. Our data demonstrate that all normal mice infected s.c. with a mouse-adapted Ebola virus survived the infection, as did 100% of mice deficient in Fas and 90% of those deficient in IFN-gamma. In contrast, perforin-deficient mice uniformly died after s.c. challenge. Perforin-deficient mice failed to clear viral infection even though they developed normal levels of neutralizing anti-Ebola Abs and 5- to 10-fold higher levels of IFN-gamma than control mice. Using MHC class I tetramers, we have also shown that perforin-deficient mice have 2- to 4-fold higher numbers of Ebola-specific CD8s than control mice. These findings suggest that the clearance of Ebola virus is perforin-dependent and provide an additional example showing that this basic immunologic mechanism is not limited to the clearance of noncytopathic viruses.
Immunoaffinity Purification of Plasma Membrane with Secondary Antibody Superparamagnetic Beads for Proteomic Analysis (2006)

Plasma membrane (PM) has very important roles in cell-cell interaction and signal transduction, and it has been extensively targeted for drug design. A major prerequisite for the analysis of PM proteome is the preparation of PM with high purity. Density gradient centrifugation has been commonly employed to isolate PM, but it often occurred with contamination of internal membrane. Here we describe a method for plasma membrane purification using second antibody superparamagnetic beads that combines subcellular fractionation and immunoisolation strategies. Four methods of immunoaffinity were compared, and the variation of crude plasma membrane (CPM), superparamagnetic beads, and antibodies was studied. The optimized method and the number of CPM, beads, and antibodies suitable for proteome analysis were obtained. The PM of mouse liver was enriched 3-fold in comparison with the density gradient centrifugation method, and contamination from mitochondria was reduced 2-fold. The PM protein bands were extracted and trypsin-digested, and the resulting peptides were resolved and characterized by MALDI-TOF-TOF and ESI-Q-TOF, respectively. Mascot software was used to analyze the data against IPI-mouse protein database. Nonredundant proteins (248) were identified, of which 67% are PM or PM-related proteins. No endoplasmic reticulum (ER) or nuclear proteins were identified according to the GO annotation in the optimized method. Our protocol represents a simple, economic, and reproducible tool for the proteomic characterization of liver plasma membrane.
Mobile Gene Cassettes and Integrons: Moving Antibiotic Resistance Genes in Gram‐Negative Bacteria (2007)

In Gram-negative pathogens, multiple antibiotic resistance is common and many of the known resistance genes are contained in mobile gene cassettes. Cassettes can be integrated into or deleted from their receptor elements, the integrons, or infrequently may be integrated at other locations via site-specific recombination catalysed by an integron-encoded recombinase. As a consequence, arrays of several different antibiotic resistance genes can be created. Over 40 gene cassettes and three distinct classes of integrons have been identified to date. Cassette-associated genes conferring resistance to beta-lactams, aminoglycosides, trimethoprim, chloramphenicol, streptothricin and quaternary ammonium compounds used as antiseptics and disinfectants have been found. In addition, most members of the commonest family of integrons (class 1) include a sulfonamide resistance determinant in the backbone structure. Integrons are themselves translocatable, though most are defective transposon derivatives. Integron movement allows transfer of the cassette-associated resistance genes from one replicon to another or into another active transposon which facilitates spread of integrons that are transposition defective. Horizontal transfer of the resistance genes can be achieved when an integron containing one or more such genes is incorporated into a broad-host-range plasmid. Likewise, single cassettes integrated at secondary sites in a broad-host-range plasmid can also move across species boundaries.
Galactosylation does not prevent the rapid clearance of long-term, 4°C-stored platelets (2007)

Cold storage of platelets for transfusion is desirable to extend platelet storage times and to prevent bacterial growth. However, the rapid clearance of cold-stored platelets prevents their use. A novel method for preventing the rapid clearance of cold-stored platelets has previously been developed in a murine model. Cold storage induces the clustering and recognition of exposed beta-N-acetylglucosamine (betaGlcNAc) on platelet surfaces. Glycosylation of betaGlcNAc residues with uridine 5'-diphosphogalactose (UDP-galactose) results in the normal survival of short-term (2 h) 0 degrees C-stored murine platelets. Based on this finding, we developed a similar glycosylation process by adding UDP-galactose to human apheresis platelets. A phase 1 clinical trial was conducted transfusing radiolabeled autologous apheresis platelets stored for 48 hours at 4 degrees C with or without pretreatment with UDP-galactose. In contrast to the murine study, galactosylation of human platelets did not prevent the accelerated platelet clearance routinely observed after 4 degrees C storage. We next developed a murine model of platelet storage for 48 hours at 4 degrees C and showed that UDP-galactose treatment of murine platelets also did not prevent their rapid clearance, in agreement with the human platelet study. We conclude that different mechanisms of clearance may exist for short- and long-term cold-stored platelets.
Dendritic cells (I): Biological functions. (2001)

Dendritic cells (DCs) are potent antigen presenting cells (APCs) that possess the ability to stimulate naïve T cells. They comprise a system of leukocytes widely distributed in all tissues, especially in those that provide an environmental interface. DCs posses a heterogeneous haemopoietic lineage, in that subsets from different tissues have been shown to posses a differential morphology, phenotype and function. The ability to stimulate naïve T cell proliferation appears to be shared between these various DC subsets. It has been suggested that the so-called myeloid and lymphoid-derived subsets of DCs perform specific stimulatory or tolerogenic function, respectively. DCs are derived from bone marrow progenitors and circulate in the blood as immature precursors prior to migration into peripheral tissues. Within different tissues, DCs differentiate and become active in the taking up and processing of antigens (Ags), and their subsequent presentation on the cell surface linked to major histocompatibility (MHC) molecules. Upon appropriate stimulation, DCs undergo further maturation and migrate to secondary lymphoid tissues where they present Ag to T cells and induce an immune response. DCs are receiving increasing scientific and clinical interest due to their key role in anti-cancer host responses and potential use as biological adjuvants in tumour vaccines, as well as their involvement in the immunobiology of tolerance and autoimmunity.
A critical contemplation on the role of heat shock proteins in transfer of antigenic peptides during antigen presentation. (1994)

Evidence is presented to demonstrate that HSPs mediate transfer of antigenic peptides during antigen presentation by MHC class I-restricted T cells. Transfer of peptides through HSP-chaperones is preferred over direct diffusion of peptides to their destinations because of our belief that few molecular phenomena within cells occur in liquid-phase and there is little evidence for the presence of free peptides in the cell. Further, chaperoning of peptides by HSPs is likely to: (i) shield peptides from their ultimate degradation to single amino acids by cytosolic proteases, (ii) minimize the chances of fortuitous and unproductive coupling with other proteins, (iii) help achieve higher local peptide concentrations than might be possible by passive diffusion, and (iv) obtain a mechanism for the process of transfer to be regulated or modulated. The evidence in support of an involvement of HSPs in transfer of peptides is critically discussed. The theme that HSPs are functional fore-runners of the MHC molecules, first proposed by us (Srivastava and Heike, 1991), is further developed.
Remote Near-IR Spectroscopy over an Optical Fiber with a Modified FT Spectrometer (1988)

A Fourier transform (FT) spectrometer was configured to measure near-infrared (near-IR) transmission spectra using 80 meters of a 206-μm optical fiber. The single-beam signal-to-noise ratio (S/N) was evaluated for the remote-sensing spectrometer for both Ge and InSb detectors. The instrumental performance was compared with that of the conventional FT spectrometer. The optical attenuation of several different fibers was measured and their possible use as transmission sensors was evaluated. Some advantages and implications of combining an FT spectrometer with optical-fiber sensor measurements are discussed.
O-Glycosylation Regulates LNCaP Prostate Cancer Cell Susceptibility to Apoptosis Induced by Galectin-1 (2007)

Resistance to apoptosis is a critical feature of neoplastic cells. Galectin-1 is an endogenous carbohydrate-binding protein that induces death of leukemia and lymphoma cells, breast cancer cells, and the LNCaP prostate cancer cell line, but not other prostate cancer cell lines. To understand the mechanism of galectin-1 sensitivity of LNCaP cells compared with other prostate cancer cells, we characterized glycan ligands that are important for conferring galectin-1 sensitivity in these cells, and analyzed expression of glycosyltransferase genes in galectin-1-sensitive, prostate-specific antigen-positive (PSA(+)) LNCaP cells compared with a galectin-1-resistant PSA(-) LNCaP subclone. We identified one glycosyltransferase, core 2 N-acetylglucosaminyltransferase, which is down-regulated in galectin-1-resistant PSA(-) LNCaP cells compared with galectin-1-sensitive PSA(+) LNCaP cells. Intriguingly, this is the same glycosyltransferase required for galectin-1 susceptibility of T lymphoma cells, indicating that similar O-glycan ligands on different polypeptide backbones may be common death trigger receptors recognized by galectin-1 on different types of cancer cells. Blocking O-glycan elongation by expressing alpha2,3-sialyltransferase 1 rendered LNCaP cells resistant to galectin-1, showing that specific O-glycans are critical for galectin-1 susceptibility. Loss of galectin-1 susceptibility and synthesis of endogenous galectin-1 has been proposed to promote tumor evasion of immune attack; we found that galectin-1-expressing prostate cancer cells killed bound T cells, whereas LNCaP cells that do not express galectin-1 did not kill T cells. Resistance to galectin-1-induced apoptosis may directly contribute to the survival of prostate cancer cells as well as promote immune evasion by the tumor.