gebhart/patrepeval huggingface dataset:
The Suppressor of fused gene encodes a novel PEST protein involved in Drosophila segment polarity establishment. (1995)

Suppressor of fused, Su(fu), was identified as a semi-dominant suppressor of the putative serine/threonine kinase encoded by the segment polarity gene fused in Drosophila melanogaster. The amorphic Su(fu) mutation is viable, shows a maternal effect and displays no phenotype by itself. Su(fu) mutations are often found associated to karmoisin (kar) mutations but two complementation groups can be clearly identified. By using a differential hybridization screening method, we have cloned the Su(fu) region and identified chromosomal rearrangements associated with Su(fu) mutations. Two classes of cDNAs with similar developmental patterns, including a maternal contribution, are detectable in the region. Transformation experiments clearly assigned the Su(fu)+ function to one of these transcription units while the other one can be most likely assigned to the kar+ function. Surprisingly the 5' end of the kar RNA mapped within the 3' untranslated region of the Su(fu) transcribed sequence. The Su(fu) gene encodes a 53-kD protein, which contains a PEST sequence and shows no significant homologies with known proteins. Genetic analysis shows that proper development requires a fine tuning of the genetic doses of fu and Su(fu) both maternally and zygotically. These results, together with previous genetic and molecular data, suggest that fused and Suppressor of fused could act through a competitive posttraductionnal modification of a common target in the hedgehog signaling pathway.
FimH Antagonists: Structure–Activity and Structure–Property Relationships for Biphenyl α‐D‐Mannopyranosides (2012)

Urinary tract infections (UTIs) are caused primarily by uropathogenic Escherichia coli (UPEC), which encode filamentous surface-adhesive organelles called type 1 pili. FimH is located at the tips of these pili. The initial attachment of UPEC to host cells is mediated by the interaction of the carbohydrate recognition domain (CRD) of FimH with oligomannosides on urothelial cells. Blocking these lectins with carbohydrates or analogues thereof prevents bacterial adhesion to host cells and therefore offers a potential therapeutic approach for prevention and/or treatment of UTIs. Although numerous FimH antagonists have been developed so far, few of them meet the requirement for clinical application due to poor pharmacokinetics. Additionally, the binding mode of an antagonist to the CRD of FimH can switch from an in-docking mode to an out-docking mode, depending on the structure of the antagonist. In this communication, biphenyl α-D-mannosides were modified to improve their binding affinity, to explore their binding mode, and to optimize their pharmacokinetic properties. The inhibitory potential of the FimH antagonists was measured in a cell-free competitive binding assay, a cell-based flow cytometry assay, and by isothermal titration calorimetry. Furthermore, pharmacokinetic properties such as log D, solubility, and membrane permeation were analyzed. As a result, a structure-activity and structure-property relationships were established for a series of biphenyl α-D-mannosides.
Demo Abstract: A BeepBeep Ranging System on Mobile Phones (2007)

The demo, BeepBeep, shows a high-accuracy acousticbased ranging system without relaying on any pre-planned infrastructure or inter-device time synchronization. Moreover, the BeepBeep is a pure software-based solution and readily applicable to many low-cost sensor platforms and to most commercial-off-the-shelf mobile devices. Our demo using two common cell phones shows that BeepBeep can achieve average two centimeters accuracy within a range of more than ten meters.
CXCR4 Is a Major Chemokine Receptor on Glioma Cells and Mediates Their Survival (2002)

Chemokines were described originally in the context of providing migrational cues for leukocytes. They are now known to have broader activities, including those that favor tumor growth. We addressed whether and which chemokines may be important promoters of the growth of the incurable brain neoplasm, malignant gliomas. Analyses of 16 human glioma lines for the expression of chemokine receptors belonging to the CXCR and CCR series revealed low to negligible levels of all receptors, with the exception of CXCR4 that was expressed by 13 of 16 lines. All six resected human glioma specimens showed similarly high CXCR4 expression. The CXCR4 on glioma lines is a signaling receptor in that its agonist, stromal cell-derived factor-1 (SDF-1; CXCL12), produced rapid phosphorylation of mitogen-activated protein kinases. Furthermore, SDF-1 induced the phosphorylation of Akt (protein kinase B), a kinase associated with survival, and prevented the apoptosis of glioma cells when serum was withdrawn from the culture medium. SDF-1 also mediated glioma chemotaxis, in accordance with this better known role of chemokines. We conclude that glioma cells express a predominant chemokine receptor, CXCR4, and that this functions to regulate survival in part through activating pathways such as Akt.
Pegylated Interferon-α2a Inhibits Proliferation of Human Liver Cancer Cells In Vitro and In Vivo (2013)

Although in vitro anti-proliferative effects of PEG-IFN-α2a were relatively weak, PEG-IFN-α2a induced strong anti-tumor effects on HCC cells in vivo. The data suggest potential clinical application of PEG-IFN-α2a for the prevention and treatment of HCC.
Antiferromagnetically coupled perpendicular recording media (2003)

We demonstrate that the Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction can be used to improve the stability of perpendicular recording media. Both the nucleation field and the coercivity in the perpendicular direction increase due to the antiferromagnetic coupling (AFC). Analogous to longitudinal AFC media, it is observed that the magnetization of the stabilization layer slowly relaxes to the antiparallel state. This relaxation is primarily driven by the demagnetizing fields in the stabilization layer and hence becomes slower with increasing bit density.
Synthesis of bromoallene under conditions of phase-transfer catalysis (1986)

A new method was developed for the production of bromoallene by the dehydrobromination of 1,2,3-tribromopropane under the conditions of phase-transfer catalysis. It was shown that the bromoallene is produced as a result of the isomerization of the initially formed propargyl bromide. During the dehydrohalogenation of 2-bromo-3-chloro-1-propene, bromoallene, i.e., the product from rearrangement with participation of the bromine atom, is formed in addition to propargyl chloride and chloroallene.
Frequent and Simultaneous Epigenetic Inactivation of TP53 Pathway Genes in Acute Lymphoblastic Leukemia (2011)

Aberrant DNA methylation is one of the most frequent alterations in patients with Acute Lymphoblastic Leukemia (ALL). Using methylation bead arrays we analyzed the methylation status of 807 genes implicated in cancer in a group of ALL samples at diagnosis (n = 48). We found that 154 genes were methylated in more than 10% of ALL samples. Interestingly, the expression of 13 genes implicated in the TP53 pathway was downregulated by hypermethylation. Direct or indirect activation of TP53 pathway with 5-aza-2'-deoxycitidine, Curcumin or Nutlin-3 induced an increase in apoptosis of ALL cells. The results obtained with the initial group of 48 patients was validated retrospectively in a second cohort of 200 newly diagnosed ALL patients. Methylation of at least 1 of the 13 genes implicated in the TP53 pathway was observed in 78% of the patients, which significantly correlated with a higher relapse (p = 0.001) and mortality (p<0.001) rate being an independent prognostic factor for disease-free survival (DFS) (p = 0.006) and overall survival (OS) (p = 0.005) in the multivariate analysis. All these findings indicate that TP53 pathway is altered by epigenetic mechanisms in the majority of ALL patients and correlates with prognosis. Treatments with compounds that may reverse the epigenetic abnormalities or activate directly the p53 pathway represent a new therapeutic alternative for patients with ALL.
Instability and Triangulation of the Action Potential Predict Serious Proarrhythmia, but Action Potential Duration Prolongation Is Antiarrhythmic (2001)

Lengthening of APD without instability or triangulation is not proarrhythmic but rather antiarrhythmic.
Minimally invasive approaches to prostate cancer: a review of the current literature. (2007)

The use of minimally invasive techniques has revolutionized the surgical treatment of prostate cancer. Pure LRP has been shown to be feasible and reproducible. However, it has a steep learning curve and is difficult to learn. In contrast, RALP is easier to learn and is now the surgical treatment of choice in most centers of excellence in the United States. The superior optics with respect to visualization and magnification translates into a procedure that is equivalent, if not superior, with respect to perioperative parameters, oncologic outcomes, and functional outcomes to its open counterpart.
Neural and Behavioural Plasticity (1991)

Abstract A great deal is now known about the cellular changes that take place in neural circuits and, over the past twenty years, the chick has proved to be an invaluable model for work on memory formation. The prior experience of the chick is controllable in a way that is impossible to match in any other vertebrate, and the pharmacology and phases of memory formation are better established. In addition, the anatomy of the chick brain is now well established, allowing valuable comparisons with animal models. This book reviews all the main aspects of work on learning and plasticity in behaviour and neural mechanisms in the chick, together with related topics such as the development of behaviour and lateralization of function. It is an authoritative reference for researchers who wish to use the chick or to draw on the relevant literature. The aim is to introduce a wider audience to the chick as an experimental model, and to describe the way in which it has been used in the investigation of learning and plasticity at every level, from the behavioural to the molecular.
Site-directed mutagenesis using thermostable enzymes. (1995)

The two-primer method for site-directed mutagenesis facilitates the mutation of targets in double-stranded DNA. We have encountered difficulties using the original method for the mutagenesis of DNA cloned into pBluescript vectors, which is possibly due to the presence of regions of secondary structure that cannot be efficiently copied by the enzymes used. We report a modification of the two-primer method using the thermostable VentR DNA polymerase and Thermus aquaticus ligase, allowing an increase in reaction temperatures. The modified method is functional with the pBluescript family of vectors.
High-performance immunoaffinity chromatography and chemiluminescent detection in the automation of a parathyroid hormone sandwich immunoassay (1991)

An automated sandwich immunoassay was developed based on high-performance immunoaffinity chromatography and chemiluminescent detection, using the determination of parathyroid hormone (PTH) in plasma as a model system. In this method, injections of plasma and acridinium ester-labeled anti-(1-34 PTH) antibodies were made onto a column containing immobilized anti-(44-68 PTH) antibodies. Upon elution, PTH and its associated labeled antibody were combined with an alkaline peroxide postcolumn reagent, and the resulting light production was measured. Factors considered in optimizing this system included the column's dissociation properties, the rate of light production in the postcolumn reactor, and the use of sequential vs simultaneous injection of sample and labeled antibody. The final system developed required 6 min per plasma injection, following a 1-h incubation of sample with labeled antibody. The response was linear over 2-3 orders of magnitude and the lower limit of detection for a 66-microL plasma sample was only 16 amol, or 2.4 x 10(-13) M. Overall, this method had a precision and response similar to those of manual PTH methods but required 24-fold less time to perform. By using different immobilized and labeled antibodies, this method could easily be adapted for use with other analytes.
Investigating the role of proinflammatory CD16+ monocytes in the pathogenesis of inflammatory bowel disease (2010)

Infiltrating monocytes and macrophages contribute to the initiation and perpetuation of mucosal inflammation characteristic for human inflammatory bowel disease (IBD). Peripheral blood monocytes expressing the low-affinity Fcgamma receptor CD16 have been identified previously as a major proinflammatory cell population, based on their unique cytokine secretion profile. However, the contribution of these cells to the pathogenesis of inflammatory bowel disease remains to be elucidated. Thus, in this study we investigated whether the peripheral CD16(+) monocyte count correlates with common IBD disease parameters, and whether these cells infiltrate the intestinal mucosa under inflammatory conditions. We observed that CD16(+) peripheral blood monocytes are increased significantly in active Crohn's disease, particularly in patients with high Crohn's disease activity index and colonic involvement. Furthermore, we found that CD16(+) cells are a major contributor to the inflammatory infiltrate in Crohn's disease mucosa, although their spontaneous migration through primary human intestinal endothelial cells is limited. Our data suggest that lamina propria, but not peripheral blood, CD16(+) monocytes are a crucial proinflammatory cell population in IBD, and a potential target for anti-inflammatory therapy.
A monoclonal antibody against the platelet fibrinogen receptor contains a sequence that mimics a receptor recognition domain in fibrinogen (1989)

The binding of fibrinogen to its platelet receptor, the glycoprotein IIb-IIIa complex, is mediated, in part, by an Arg-Gly-Asp (RGD) sequence within the fibrinogen A alpha chain. PAC1 is an IgM-kappa murine monoclonal antibody that binds to the platelet fibrinogen receptor, and its binding is inhibited by both fibrinogen and RGD-containing peptides. To identify the regions of PAC1 that interact with the fibrinogen receptor, we determined the mRNA sequences of PAC1 immunoglobulin heavy and light chain variable regions. Five out of the six complementarity-determining regions (CDRs) of PAC1 had entirely germline sequences with no regions of similarity to fibrinogen. However, CDR3 of the PAC1 heavy chain (H-CDR3) was very large and unique due to the insertion of a novel D region segment. H-CDR3 contained a sequence, Arg-Tyr-Asp (RYD), that, if present in the proper conformation, might behave like the RGD sequence in fibrinogen. A 21-residue synthetic peptide encompassing the H-CDR3 region inhibited fibrinogen-dependent platelet aggregation as well as the binding of PAC1 (Ki = 10 microM) and fibrinogen (Ki = 5 microM) to activated platelets. The RYD region of H-CDR3 appeared to be central to its function, because substitution of the tyrosine with glycine increased the inhibitory potency of the peptide by 10-fold, while replacing the tyrosine with D-alanine or inverting the RYD sequence sharply reduced the inhibitory potency. Thus, the linear sequence, RYD, within H-CDR3 of PAC1 appears to mimic the RGD receptor recognition sequence in fibrinogen. This type of immunologic approach could be useful in studying the structural basis of other receptor-ligand interactions.
Pathophysiology of Infections After Internal Fixation of Fractures (2000)

Infection complicating internal fixation of fractures is a serious complication that is difficult to treat. Whenever metallic devices are implanted in vivo, successful biointegration requires that host cells colonize the highly reactive implant surface. Bacteria such as staphylococci can also become adherent to metallic or polymeric implants and will compete with host cells for colonization of the implant surface. Once adherent, these bacteria form a biofilm and undergo phenotypic changes that make them resistant to the normal host immune response as well as to antibiotics. Furthermore, metallic implants themselves cause specific deficits in the function of the local immune system that may render the host response to infection inadequate. Any associated soft-tissue injury causes even greater impairment of local immune function. Despite the potentially detrimental impact of internal fixation, fracture stability is of paramount importance in achieving fracture union and in preventing infection. It has been demonstrated in animal models that contaminated fractures without internal fixation develop clinical infection more commonly than similar fractures treated with internal fixation at the time of colonization. Because of the potential for infection whenever internal fixation is utilized, appropriate prophylactic antibiotic coverage for staphylococci and Gram-negative organisms should be provided. Open wounds and severely damaged soft tissues require aggressive management so that a viable soft-tissue envelope is maintained around the implant. Host factors such as smoking and malnourishment should be corrected. Early diagnosis and aggressive treatment of implant-related infection with antibiotics, debridement, and maintenance of stable internal fixation are essential to successful treatment.
Characterization of Interpolyelectrolyte Complexes between Double-Stranded DNA and Polylysine Comb-Type Copolymers Having Hydrophilic Side Chains (1998)

The polyionic interaction between DNA and polycations grafted with hydrophilic dextran side chains was evaluated. The comb-type copolymers, poly(L-lysine)-graft-dextran, were successfully prepared by employing a reductive amination reaction between epsilon-amino groups of poly(L-lysine) (PLL) and the reductive ends of dextran (Dex). A coupling efficacy on the order of 70% was obtained regardless of intrinsic philicities of the solvents used, either aqueous buffer or DMSO. The resulting graft copolymers, which varied in the degree of grafting and the length of hydrophilic side chains, formed a soluble complex with DNA. They also affected the melting behavior of double-stranded DNA (dsDNA) in different ways. Copolymers having a high degree of grafting thermally stabilized dsDNA without affecting its reversible transition between single-stranded and double-stranded forms. However, copolymers with a low degree of grafting or with a high degree of grafting of short dextran chains impeded the reversibility of this transition. Furthermore, highly grafted copolymers also accelerated the hybridization of DNA strands in a low-ionic strength medium. It is of particular note that these copolymers scarcely altered circular dichroismic signals of dsDNA even when the copolymers were added in excess. This suggested that the copolymer interacted with dsDNA without affecting its native structure or physicochemical properties. Finally, the copolymer even formed a stable complex with a short oligonucleotide (20 bases). We, therefore, concluded that, by regulating the degree of grafting and the molecular weight of grafted side chains, it would be possible to design novel different graft copolymers capable of acting as carriers of functional genes to target cells or tissue.
Cell surface localization and density of the tumor-associated variant of the epidermal growth factor receptor, EGFRvIII. (1997)

The potential of therapeutic targeting of tumor cell surface epidermal growth factor receptors (EGFRs) by modified ligands or specific antibodies has been limited by the normal tissue distribution of the receptor. The identification and characterization of a variant of this receptor, EGFRvIII, which is not expressed in normal tissues but has been described in gliomas, non-small cell lung carcinomas, and breast carcinomas, has provided a highly specific, internalizing target for antibody-mediated approaches. To determine the feasibility of immunotargeting EGFRvIII, we have assessed the qualitative distribution and quantitative expression at both the population and cellular levels of EGFRvIII in 21 biopsy samples of human gliomas by indirect analytical and quantitative flow cytometry and by immunohistochemical assay of frozen and formalin-fixed tissue. Consistent with previous reports, 50% of gliomas tested (1 of 2 anaplastic astrocytomas, 7 of 12 glioblastoma multiforme, and 2 of 6 oligodendrogliomas) expressed EGFRvIII, as determined by a minimum of 2 separate assays. Minimum estimates of the proportion of positive tumor cells in these populations ranged from 37-86%; in four of five cases in which quantitation of the EGFRvIII density/cell was performed, values of 2.7-6.8 x 10(5) were obtained with monoclonal antibody (mAb) L8A4 (EGFRvIII specific), levels consistent with successful in vivo immunotargeting. Confocal microscopic analysis confirmed that the subcellular localization of EGFRvIII was identical to that described for EGFR: predominant cell membrane expression, with some perinuclear distribution suggestive of localization to the Golgi region. Neither EGFR nor EGFRvIII was found within the nucleus. This study establishes for the first time that approximately 50% of human glioma biopsies contain cell populations expressing a sufficient number of membrane-expressed EGFRvIIIs to mediate specific anti-EGFRvIII mAb localization. Coupled with previous demonstrations of the rapid internalization of specific mAb-EGFRvIII complexes and the susceptibility of the targeted cells to isotope or toxin-mediated cytotoxicity, this study establishes the validity of targeting EGFRvIII for therapy of mutant receptor-positive gliomas, breast carcinomas, and non-small cell lung carcinomas.
A robust CMA adaptive array for multiple narrowband sources (2003)

A new version of the CMA/LMS adaptive array (constant modulus algorithm with the least-mean-square algorithm) that recovers both the arrival angles and the signals from multiple narrowband sources is presented. The algorithm operates in two stages, to resolve problems of imperfect cancellation found in single-stage multiple-emitter CMA algorithms. An orthogonalized CMA loop finds and adapts the beamforming weights in each direction: a new LMS cocanceller (LMSCC) loop finds and adapts the steering vectors in each direction. Interference-cancellation results from a real-time hardware implementation of the algorithm with a VHF antenna array are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Incorporating Gene Significance in the Impact Analysis of Signaling Pathways (2012)

Identification of the most impacted signaling pathways in a given condition is a crucial step in understanding the underlying biological mechanism. An impact analysis that is able to take in consideration the structure of a given signaling pathway was proposed to measure the impact on each pathway given a list of differentially expressed (DE) genes and their fold changes. Here, we investigated the utility of incorporating the individual gene significance in the impact analysis of signaling pathways. We propose two alternative models to incorporate the individual gene p-values and compare their performance over a pool of 24 datasets. In addition, the two new models offer the ability to work with the entire set of gene expression measurements, thus eliminating the need to select differentially expressed genes.