gebhart/patrepeval huggingface dataset:
Impaired Long-Term Potentiation, Spatial Learning, and Hippocampal Development in fyn Mutant Mice (1992)

Mice with mutations in four nonreceptor tyrosine kinase genes, fyn, src, yes, and abl, were used to study the role of these kinases in long-term potentiation (LTP) and in the relation of LTP to spatial learning and memory. All four kinases were expressed in the hippocampus. Mutations in src, yes, and abl did not interfere with either the induction or the maintenance of LTP. However, in fyn mutants, LTP was blunted even though synaptic transmission and two short-term forms of synaptic plasticity, paired-pulse facilitation and post-tetanic potentiation, were normal. In parallel with the blunting of LTP, fyn mutants showed impaired spatial learning, consistent with a functional link between LTP and learning. Although fyn is expressed at mature synapses, its lack of expression during development resulted in an increased number of granule cells in the dentate gyrus and of pyramidal cells in the CA3 region. Thus, a common tyrosine kinase pathway may regulate the growth of neurons in the developing hippocampus and the strength of synaptic plasticity in the mature hippocampus.
Metastasis‐associated 5T4 antigen disrupts cell‐cell contacts and induces cellular motility in epithelial cells (1996)

The 5T4 antigen is defined by a monoclonal antibody (MAb) specific for human trophoblast. It is also expressed by many types of tumour cell and has been associated with metastasis and poor clinical outcome in a number of cancers. This pattern of expression is consistent with a mechanistic involvement of 5T4 molecules in the spread of cancer cells. The 5T4 antigen is a transmembrane glycoprotein with a 310 amino acid extracellular domain and a 44 amino acid cytoplasmic domain. Transfection of full-length 5T4 cDNA into epithelial cells alters cell-cell contacts and cellular motility. Thus, in 5T4-transfected CL-SI murine mammary cells, 5T4 expression is associated with dendritic morphology, accompanied by abrogation of actin/cadherin-containing contacts and increased motility. In transfected MDCK canine kidney epithelial cells, 5T4 over-expression also results in increased motility, but disruption of cell-cell contacts, either by culturing cells in low calcium medium or by addition of HGF/SF, is needed. The effects of 5T4 expression on morphology and motility are separable since cells transfected with a truncated form of 5T4 cDNA in which the cytoplasmic domain is deleted reveal that the latter is necessary to abrogate actin/cadherin-containing contacts but does not influence the effects on motility. Thus, 5T4 molecules can deliver signals through both the extracellular and intracellular domains, and the resultant effects are consistent with a role for 5T4 molecules in invasion processes. © 1996 Wiley-Liss, Inc.
P59, an hsp 90-binding protein. Cloning and sequencing of its cDNA and preparation of a peptide-directed polyclonal antibody. (1992)

The primary sequence of the rabbit liver cDNA coding for protein p59 has been determined. The protein binds to the 90-kDa heat shock protein (hsp 90) and is associated with it, including when hsp 90 participates in hetero-oligomeric complexes of untransformed mammalian steroid receptors that sediment at 8-10 S. The cloned cDNA codes for an open reading frame of 458 amino acids defining a yet unknown protein. However, 55% amino acid homology to peptidyl-prolyl isomerase is found between amino acids 41 and 137, suggesting rotamase activity for p59, which speculatively may apply to bound hsp 90 and thus be implied in the intracellular trafficking of hetero-oligomeric forms of steroid hormone receptors. A polyclonal antibody derived from the COOH-terminal peptide 441-458 demonstrates a good affinity for rabbit, rat, and human "p59" protein. It interacts with at least one epitope, available in 8-10 S untransformed steroid receptor complexes and different from that recognized by the monoclonal antibody KN382/EC-1.
Trapping of Bead-Based Reagents within Microfluidic Systems:  On-Chip Solid-Phase Extraction and Electrochromatography (1999)

A 330-pL chromatographic bed was fabricated on a glass substrate as part of an electroosmotically pumped microfluidic system. Two weirs within a sample channel formed a cavity in which octadecylsilane (ODS) coated silica beads (1.5-4 microns diameter) were trapped. ODS beads were mobilized into and out of the cavity using electroosmotic flow through a bead-introduction channel which accessed the cavity. This procedure allowed the beads in the cavity to be repeatedly exchanged. A 1 nM solution of a nonpolar analyte (BODIPY 493/503) in buffer was loaded onto the beads for different lengths of time using an electroosmotic flow of 1.2 nL/s. The material retained on the ODS phase was then eluted by electroosmotic flow of acetonitrile with a concentration enhancement of up to 500 times. Capillary electrochromatography was conducted using a similar device. BODIPY and fluorescein were loaded onto a 200-micron-long chromatographic bed and then separated in an isocratic CEC run with an acetonitrile/buffer mobile phase. Complete separation was achieved in less than 20 s with a 2-micron plate height.
Oxide-nitride-oxide antifuse reliability (2002)

Compact, low-resistance oxide-nitride-oxide (ONO) antifuses are studied for time-dependent dielectric breakdown (TDDB), program disturb, programmed antifuse resistance stability, and effective screen. ONO antifuses are superior to oxide antifuses. No ONO antifuse failures were observed in 1.8 million accelerated burn-in device-hours accumulated on 1108 product units. This is in agreement with the 1/E field acceleration model.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
One face of a transmembrane helix is crucial in mechanosensitive channel gating (1998)

MscL is a mechanosensitive channel in bacteria that responds directly to membrane tension by opening a large conductance pore. To determine functionally important residues within this molecule, we have randomly mutagenized mscL, expressed the genes in living bacteria, and screened for gain-of-function mutants with hampered growth. Expression of these genes caused leakage of cytoplasmic solutes on little or no hypo-osmotic stress. In excised patches, the mutant channels gated at membrane tensions that are less than that required for the gating of the wild-type MscL. Hence, the data suggest that the slowed or no-growth phenotype is caused by solute loss because of inappropriate gating of the channel. Most of the mutations mapped to the first transmembrane domain. When this domain is modeled as an alpha-helix, the most severe mutations are substitutions of smaller amino acids (three glycines and one valine) on one facet, suggesting an important role for this structure in MS channel gating.
Investor Expectations and Fundamentals: Disappointment Ahead? (2000)

The average annual return of the S&P 500 since 1994 has exceeded 25 percent. Confidence is high and investors are looking forward to continued above-average returns. The authors of this Economic Commentary attempt to reconcile investors' expectations with a decline in the equity premium, using a standard approach to stock-price valuation.
Targeted therapy for malignant melanoma (1994)

Malignant melanoma is a tumor that offers unique possibilities for approaches to targeted therapy by virtue of the pigment biosynthesis pathway. Such approaches may seek to use the incorporation of toxic intermediates or to use the natural transcriptional control of genes coding for enzymes involved in melanin formation to regulate gene therapy. In this paper, we describe how the 5'-flanking sequences of the genes for tyrosinase or tyrosinase-related protein 1 can be used to drive expression of complementary DNA, coding for immunity-stimulating proteins or for drug-activating enzymes, specifically in melanoma cells. The combination of the tissue specificity resulting from these techniques, coupled with innovative delivery systems, should provide the maximum available therapeutic index and lead to the design of new treatments with limited side effects.
Dehydroepiandrosterone Activates Mutant Androgen Receptors Expressed in the Androgen-Dependent Human Prostate Cancer Xenograft CWR22 and LNCaP Cells (1997)

An androgen receptor (AR) gene mutation identified in the androgen-dependent human prostate cancer xenograft, CWR22, changed codon 874 in the ligand-binding domain (exon H) from CAT for histidine to TAT for tyrosine and abolished a restriction site for the endonuclease SfaNI. SfaNI digestion of AR exon H DNA from normal but not from prostate cancer tissue indicated H874Y is a somatic mutation that occurred before the initial tumor transplant. CWR22, an epithelial cell tumor, expresses a 9.6-kb AR mRNA similar in size to the AR mRNA in human benign prostatic hyperplasia. AR protein is present in cell nuclei by immunostaining as in other androgen-responsive tissues. Transcriptional activity of recombinant H874Y transiently expressed in CV1 cells in the presence of testosterone or dihydrotestosterone was similar to that of wild type AR. With dihydrotestosterone at a near physiological concentration (0.01 nM), H874Y and wild type AR induced 2-fold greater luciferase activity than did the LNCaP mutant AR T877A. The adrenal androgen, dehydroepiandrosterone (10 and 100 nM) with H874Y stimulated a 3- to 8-fold greater response than with wild type AR and at 100 nM the response was similar with the LNCaP mutant. H874Y, like the LNCaP cell mutant, was more responsive to estradiol and progesterone than was wild type AR. The antiandrogen hydroxyflutamide (10 nM) had greater agonist activity (4- to 7-fold) with both mutant ARs than with wild type AR. AR mutations that alter ligand specificity may influence tumor progression subsequent to androgen withdrawal by making the AR more responsive to adrenal androgens or antiandrogens.
Novel Non-Peptide Fibrinogen Receptor Antagonists. 1. Synthesis and Glycoprotein IIb-IIIa Antagonistic Activities of 1,3,4-Trisubstituted 2-Oxopiperazine Derivatives Incorporating Side-Chain Functions of the RGDF Peptide (1998)

Based on the lead tetrapeptide RGDF, two possible non-peptide glycoprotein (GP) IIb-IIIa antagonists possessing an (S)-2-oxopiperazine-3-acetic acid moiety as a scaffold incorporating the indispensable Asp fragment were prepared, and (S)-4-[[trans-[4-(guanidinomethyl)-cyclohexyl]carbonyl]glycyl]-2- oxopiperazine-1,3-diacetic acid, 1a, was identified as a potential lead. A series of 3-substituted 2-oxopiperazine-1-acetic acids bearing the Arg-Gly equivalent at the 4-position were prepared and evaluated for their ability to prevent platelet aggregation and for their binding affinity for the GP IIb-IIIa receptor purified from human HEL cells. (S)-4-[(4-Amidinobenzoyl)glycyl]-3-[(methoxycarbonyl)methyl]- 2-oxopiperazine-1-acetic acid, 9 (TAK-029), inhibited in vitro human platelet aggregation with an IC50 value of 0.03 microM and GP IIb-IIIa-fibrinogen binding with an IC50 value of 0.49 nM. The [4-(2-aminoethyl)benzoyl]glycyl derivative 26 showed activity comparable to that of 9 (IC50 = 0.093 microM, guinea pig platelet aggregation assay). Compound 9 dose-dependently inhibited ex vivo platelet aggregation in guinea pigs (0.03 and 0.1 mg/kg, i.v.), and long-lasting inhibition of platelet aggregation was observed upon oral administration of 9 (3 mg/kg) to guinea pigs. On the other hand, the activity of 26 disappeared within 1 h after a dose of 1 mg/kg (i.v.). Compound 9 may therefore be useful in the clinical treatment of arterial thrombotic diseases.
Targeting the Raf/MEK/ERK pathway with small-molecule inhibitors. (2008)

Mutations occur in some cancer cells and result in elevated expression or constitutive activation of various growth factor receptors. The Raf/MEK/ERK pathway is often activated by mutations in these growth factor receptors. This pathway is regulated by upstream Ras, which is mutated in 20 to 30% of human cancers. B-Raf is also activated by mutation, especially in melanoma and thyroid cancers. Many of the events elicited by the Raf/MEK/ERK pathway have direct effects on survival and proliferative pathways. Aberrant regulation of the Raf/MEK/ERK pathway can contribute to uncontrolled cell growth and lead to malignant transformation. The effective targeting of this pathway may result in the suppression of cell growth, and death of malignant cells. This review focuses on targeting the Raf/MEK/ERK pathway with small-molecule inhibitors for the treatment of cancer.
Hexahedral shell mesh construction via volumetric polycube map (2010)

Shells are three-dimensional structures. One dimension, the thickness, is much smaller than the other two dimensions. Shell structures can be widely found in many real-world objects. This paper presents a method to construct a layered hexahedral mesh for shell objects. Given a closed 2-manifold and the user-specified thickness, we construct the shell space using the distance field and then parameterize the shell space to a polycube domain. The volume parameterization induces the hexahedral tessellation in the object shell space. As a result, the constructed mesh is an all-hexahedral mesh in which most of the vertices are regular, i.e., the valence is 6 for interior vertices and 5 for boundary vertices. The mesh also has a layered structure that all layers have exactly the same tessellation. We prove our parameterization is guaranteed to be bijective. As a result, the constructed hexahedral mesh is free of degeneracy, such as self-intersection, flip-over, etc. We also show that the iso-parametric line (in the thickness dimension) is orthogonal to the other two isoparametric lines. We demonstrate the efficacy of our method upon models of various topology.
The Role of Glial Cells in Drug Abuse (2009)

Neuronal dysfunction in the prefrontal cortex, limbic structures, nucleus accumbens and ventral tegmental area is considered to underlie the general physiopathological mechanisms for substance use disorders. Glutamatergic, dopaminergic and opioidoergic neuronal mechanisms in those brain areas have been targeted in the development of pharmacotherapies for drug abuse and dependence. However, despite the pivotal role of neurons in the mechanisms of addiction, these cells are not the only cell type in charge of sustaining and regulating neurotransmission. Glial cells, particularly astrocytes, play essential roles in the regulation of glutamatergic neurotransmission, neurotransmitter metabolism, and supply of energy substrates for synaptic transmission. In addition, astrocytes are markedly affected by exposure to ethanol and other substances of abuse. These features of astrocytes suggest that alterations in the function of astrocytes and other glial cells in reward circuits may contribute to drug addiction. Recent research has shown that the control of glutamate uptake and the release of neurotrophic factors by astrocytes influences behaviors of addiction and may play modulatory roles in psychostimulant, opiate, and alcohol abuse. Less is known about the contributions of microglia and oligodendrocytes to drug abuse, although, given the ability of these cells to produce growth factors and cytokines in response to alterations in synaptic transmission, further research should better define their role in drug addiction. The available knowledge on the involvement of glial cells in addictive behaviors suggests that regulation of glutamate transport and neurotrophins may constitute new avenues for the treatment of drug addiction.
A Novel Putative Tyrosine Kinase Receptor Encoded by the eph Gene (1987)

Growth factors and their receptors are involved in the regulation of cell proliferation and also play a key role in oncogenesis. In this study, a novel putative kinase receptor gene, termed eph, has been identified and characterized by molecular cloning. Its primary structure is similar to that of tyrosine kinase receptors thus far cloned and includes a cysteine-rich region in the extracellular domain. However, other features of the sequence distinguish the eph gene product from known receptors with tyrosine kinase activity. Thus the eph protein may define a new class of these molecules. The eph gene is overexpressed in several human carcinomas, suggesting that this gene may be involved in the neoplastic process of some tumors.
Biochemical Characterization of a Prokaryotic Phenylalanine Ammonia Lyase (2005)

The committed biosynthetic reaction to benzoyl-coenzyme A in the marine bacterium "Streptomyces maritimus" is carried out by the novel prokaryotic phenylalanine ammonia lyase (PAL) EncP, which converts the primary amino acid L-phenylalanine to trans-cinnamic acid. Recombinant EncP is specific for L-phenylalanine and shares many biochemical features with eukaryotic PALs, which are substantially larger proteins by approximately 200 amino acid residues.
Physical Exercise Improves Glucose Metabolism in Lifestyle-Related Diseases (2003)

The beneficial effects of physical exercise on the decreased insulin sensitivity caused by detrimental lifestyle were reviewed based on experimental evidences. In epidemiological studies, disease prevention has been considered at three levels: primary (avoiding the occurrence of disease), secondary (early detection and reversal), and tertiary (prevention or delay of complications). The major purpose of physical exercise for primary prevention and treatment of lifestyle-related diseases is to improve insulin sensitivity. It is known that, during physical exercise, glucose uptake by the working muscles rises 7 to 20 times over the basal level, depending on the intensity of the work performed. However, intense exercise provokes the release of insulin-counter regulatory hormones such as glucagons and catecholamines, which ultimately cause a reduction in the insulin action. Continued physical training improves the reduced peripheral tissue sensitivity to insulin in impaired glucose tolerance and Type II diabetes, along with regularization of abnormal lipid metabolism. Furthermore, combination of salt intake restriction and physical training ameliorates hypertension. In practical terms, before diabetic patients undertake any program of physical exercise, various medical examinations are needed to determine whether they have good glycemic control and are without progressive complications. Because the effect of exercise that is manifested in improved insulin sensitivity decreases within 3 days after exercise and is no longer apparent after 1 week, a continued program is needed. For a safety practice, moderate- or low-intensity exercise is preferable. In conclusion, we have found sufficient evidences that support the theory that, combined with other forms of therapy, mild exercise training increases insulin action despite no influence on body mass index or maximal oxygen uptake. Along with evident benefits in health promotion, moderate-intensity exercise might play an important role in facilitating treatment of various diseases.
A 2D Barcode-Based Mobile Payment System (2009)

Mobile payment is very important and critical solution for mobile commerce. A user-friendly mobile payment solution is strongly needed to support mobile users to conduct secure and reliable payment transactions using mobile devices. This paper presents an innovative mobile payment system based on 2-dimensional (2D) barcodes for mobile users to improve mobile user experience in mobile payment.Unlike other existing mobile payment systems, the proposed payment solution provides distinct advantages to support buy-and-sale products and services based on 2D barcodes.This system uses one standard 2D barcode (DataMatrix) as an example to demonstrate how to deal with underlying mobile business workflow, mobile transactions and security issues. The paper discusses system architecture, design and implementation of the proposed mobile payment solution, as well as 2D barcode based security solutions. In addition, this paper also presents some application examples of the system.
Buffeting Analysis of a 700 m Steel Cable-Stayed Bridge for the Design of Pylon Foundation (2004)

A buffeting analysis is carried out to evaluate the effect of aerodynamic turbulences on the design of the pylon foundation of a 700 m steel cable-stayed bridge. Both completed and in construction structures are investigated in evaluating the along-bridge-axis bending moment at the tower leg and caisson. Based on current investigations, expected aerodynamic member forces are found to reach several times compared to gust-factored static wind results. The maximum bending moment in construction particularly exceeds a design value invoking to find out a measure for suppressing wind-induced vibrations. This study examined a possibility of using buffeting cables as one of feasible measures leaving couple of open questions in details.
A new bicortical tibial fixation technique in anterior cruciate ligament reconstruction with quadruple hamstring graft (2000)

We report a prospective series of 101 patients receiving a four-strand semitendinosus-gracilis autograft for anterior cruciate ligament reconstruction using a new bicortical tibial fixation technique with bioabsorbable interference screws. Patients (average age 32 years) were operated on between November 1997 and Mai 1998, and follow-up was at least 12 months postoperatively. The evaluation consisted of history, clinical examination, IKDC score, Cincinnati Knee Score, KT-1000 testing, standardized radiography and magnetic resonance imaging. One hundred patients were available for follow-up. There were two traumatic reruptures 6 and 11 months postoperatively. By IKDC score 87 patients were in groups A and B, 12 in group C, and 2 with a rerupture in group D. Mean Cincinnati Knee Score was 82 (range 46-100), KT-1000 manual maximum at follow-up showed an average difference of 1.7 mm between the sides. Full extension was rapidly achieved in all cases, and flexion averaged 135 degrees . Considering the enlargement caused by the bioabsorbable interference screws, the incidence of tunnel widening was 6.6% on the femoral side and 1.7% on the tibial side. Tunnel widening did not affect the clinical results. Three patients experienced an effusion after more than 6 months postoperatively. There was one infection, which settled without functional impairment after early arthroscopic lavage and intravenous antibiotics. Otherwise no complications occurred. The described technique for anterior cruciate ligament reconstruction combines the advantage of anatomical graft position with sufficient graft fixation. A short intra-articular graft construct with a strong tendon to bone interface was created. Clinically, 87% of patients had a normal or nearly normal IKDC score at follow-up. Magnetic resonance imaging revealed a considerable increase in tunnel area caused by the insertion of the interference screws. On the other hand, the development of a "fibrous interzone" between the graft and the bone tunnel was prevented in most cases. At short-term follow-up the bicortical tibial fixation proved to be efficient even with an aggressive rehabilitation program.
Anaphylactic shock: mechanisms and treatment. (1995)

This paper reviews the mechanisms of anaphylactic shock in terms of the immunoglobulin and non-immunoglobulin triggering events, and the cellular events based on the rise in intracellular cyclic AMP and calcium that release preformed granule-associated mediators and the rapidly formed, newly synthesized mediators predominantly based on arachidonic acid metabolism. These primary mediators recruit other cells with the release of secondary mediators that either potentiate or ultimately curtail the anaphylactic reaction. The roles of these mediators in the various causes of cardiovascular collapse are examined. The treatment of anaphylactic shock involves oxygen, adrenaline and fluids. The importance and safety of intravenous adrenaline are discussed. Combined H1 and H2 blocking antihistamines and steroids have a limited role. Glucagon and other adrenergic drugs are occasionally used, and several new experimental drugs are being developed.