gebhart/patrepeval huggingface dataset:
Biomarker Discovery in Low-Grade Breast Cancer Using Isobaric Stable Isotope Tags and Two-Dimensional Liquid Chromatography-Tandem Mass Spectrometry (iTRAQ-2DLC-MS/MS) Based Quantitative Proteomic Analysis (2008)

The present pilot study constitutes a proof-of-principle in the use of a quantitative LC-MS/MS based proteomic method for the comparative analysis of representative low-grade breast primary tumor tissues with and without metastases and metastasis in lymph node relative to the nonmetastatic tumor type. The study method incorporated iTRAQ stable isotope labeling, two-dimensional liquid chromatography, nanoelectrospray ionization and high resolution tandem mass spectrometry using the hybrid QqTOF platform (iTRAQ-2DLC-MS/MS). The principal aims of this study were (1) to define the protein spectrum obtainable using this approach, and (2) to highlight potential candidates for verification and validation studies focused on biomarkers involved in metastatic processes in breast cancer. The study resulted in the reproducible identification of 605 nonredundant proteins (p < or = 0.05). A quantitative comparison revealed 3/3 proteins with significantly increased/decreased level in metastatic primary tumor and 13/6 proteins with increased/decreased level in lymph node metastasis compared to nonmetastatic primary tumor (p < 0.01). Changes in selected differentially expressed proteins were verified with qRT-PCR. Although our pilot scale study does not warrant general biological conclusions, the synergic regulation of some proteins with related function (e.g., heme binding proteins, proteins of energetic metabolism, interferon induced proteins, proteins with adhesive function) determined in our sample set reflects the ability of our method in providing biologically meaningful data. The main conclusion from this pilot study was that our quantitative proteomic method constitutes a novel way of analyzing cancerous breast tissue biopsy samples that can be extended as part of a larger scale biomarker discovery program.
Can Your Eyes Tell Me How You Think? A Gaze Directed Estimation of the Mental Activity (2013)

We investigate the possibility of estimating the cognitive process used by a person when addressing a mental challenge by following the Eye Accessing Cue (EAC) model from the Neuro-Linguistic Programming (NLP) theory [1]. This model, showed in figure 1, describes the eyemovements that are not used for visual tasks (non visual movements) and suggests that the direction of gaze, in such a case, can be an indicator for the internal representational system used by a person facing a given query. The actual EAC is thought to be identified by distinguishing between the relative position of the iris and the eye socket (lid edge). Our approach is to determine the four limits of the eye socket: the inner and outer corners, the upper and lower lids and the iris center and to subsequently analyze the identified region. The entire method flowchart is presented in figure 2. The schematics of the method used for independently looking for the position of each eye landmark is described in figure 3. Given the face square position by Viola-Jones algorithm [4] and the eye centers given by the method from [3], we fuse information related to position, normalized luminance, template matching and shape constraining. For position and luminance, we construct priors over the training database, while for template matching we describe a patch by concatenation of integral and edge projections on horizontal and vertical directions. The score of how likely is a patch to be centered on the true landmark position is given by a Multi Layer Perceptron. For the shape constrain, inspired by the CLM [2], we construct the probability density function in the eigenspace of the shapes in the training set. By ordering the landmarks according to a prior confidence (e.g. eye outer corners are more reliable than upper and lower eye boundaries) and by keeping all points fixed with the exception of the current least reliable, we build the likelihood of various current landmark positions. This information is fused with previous stages and we iteratively improve the landmark position. The final landmark position is taken as the weighted center of mass of the convex combination between initial stages and shape likelihood. To study the specific of the gaze direction we introduce Eye-Chimera database, which comprises 1172 frontal face images, grouped according to the 7 gaze directions, with a set of 5 points marked for each eye: the iris center and 4 points delimiting the bounding box. Recognizing individual EACs. The recognition of the EAC case (gaze direction) is done by identifying the position of the iris center inside the eye socket complemented by the information of the interior of the eye delimited shape. The interior of the eye quadrilateral shape is described by the integral projections normalized to 32 samples. For the actual recognition we have trained a random forrest to take as input the EAC feature (landmarks positions and integral features). We consider two types of recognition situations: three cases (looking
Familial dopa-responsive cervical dystonia (2006)

The authors present four cases from two unrelated families with young-onset predominant cervical dystonia with a dramatic sustained response to levodopa. Onset age was 12 years (range 9 to 15). Additional symptoms included postural hand tremor and laryngeal dystonia. Genetic testing for GTP cyclohydrolase I, tyrosine hydroxylase, and sepiapterin reductase was negative. These cases may represent new forms of dopa-responsive dystonia. Levodopa is advisable in all patients with young-onset cervical dystonia.
Fibroblast growth factor receptor signaling affects development and function of dopamine neurons – inhibition results in a schizophrenia‐like syndrome in transgenic mice (2006)

Developing and mature midbrain dopamine (DA) neurons express fibroblast growth factor (FGF) receptor-1 (FGFR1). To determine the role of FGFR1 signaling in the development of DA neurons, we generated transgenic mice expressing a dominant negative mutant [FGFR1(TK-)] from the catecholaminergic, neuron-specific tyrosine hydroxylase (TH) gene promoter. In homozygous th(tk-)/th(tk-) mice, significant reductions in the size of TH-immunoreactive neurons were found in the substantia nigra compacta (SNc) and the ventral tegmental area (VTA) at postnatal days 0 and 360. Newborn th(tk-)/th(tk-) mice had a reduced density of DA neurons in both SNc and VTA, and the changes in SNc were maintained into adulthood. The reduced density of DA transporter in the striatum further demonstrated an impaired development of the nigro-striatal DA system. Paradoxically, the th(tk-)/th(tk-) mice had increased levels of DA, homovanilic acid and 3-methoxytyramine in the striatum, indicative of excessive DA transmission. These structural and biochemical changes in DA neurons are similar to those reported in human patients with schizophrenia and, furthermore, these th(tk-)/th(tk-) mice displayed an impaired prepulse inhibition that was reversed by a DA receptor antagonist. Thus, this study establishes a new developmental model for a schizophrenia-like disorder in which the inhibition of FGF signaling leads to alterations in DA neurons and DA-mediated behavior.
Is Chlamydia pneumoniae Infection Associated With Stroke in Children With Sickle Cell Disease? (2004)

Stroke in children with SCD does not seem to be associated with C pneumoniae infection in our population.
Characterization of Self‐Assembling of Glucose Dehydrogenase in Mono‐ and Multilayers on Gold Electrodes (2004)

Abstract Glucose dehydrogenase (GDH) was assembled electrostatically onto QCM‐gold electrodes by their sequential deposition with anionic polyelectrolytes such as PSS and PASA. For the layer‐by‐layer arrangements both the microgravimetric and the electrochemical sensor signal were followed. Increasing amounts of GDH were deposited by stepwise formation of alternating layers of GDH and PSS or PASA. The mass increase was about 1.88 μg/cm 2 for one GDH/PASA bilayer and 2.4 μg/cm 2 for a GDH/PSS bilayer. The addition of phenolic compounds resulted in an oxidation current, which could be catalytically increased by the GDH catalysed reaction in the presence of glucose. The system functions as glucose sensor when quinones are present in nonlimiting amount. The amperometric response was already diffusion limited when a single layer of GDH was adsorbed. The sensor sensitivity increased by a factor of 10 when MSA was used instead of MUA as initial electrode modifier.
Creation of a mouse expressing defective human factor IX (2004)

The majority of cases of human hemophilia B are the result of missense mutations in the coagulation factor IX gene and defective circulating factor IX is detectable in most patients. The available mouse factor IX knockout models of hemophilia B (FIXKO mouse) reproduce the bleeding phenotype of human hemophilia B, but because the models produce no factor IX they fail to reproduce the dominant human phenotype. We have created a human factor IX mouse model of hemophilia B (R333Q-hFIX mouse) by homologous recombination in embryonic stem cells. The mouse expresses no mouse factor IX, but instead expresses a missense mutant human factor IX from the mouse FIX promoter. Mutant human factor IX mRNA transcript and circulating human factor IX are detectable throughout development, but factor IX activity is less than 1% and the mouse exhibits the hemophilic phenotype. When R333Q-hFIX mice were challenged by intramuscular injection of adeno-associated virus expressing human factor IX, factor IX expression without the development of antibodies was observed. In contrast, given the same treatment, FIXKO mice consistently develop antibodies. Our R333Q-hFIX mice strain will complement the FIXKO mice for studying factor IX circulating kinetics and gene therapy.
A Gene Homologous to Human Endogenous Retrovirus Overexpressed in Childhood Acute Lymphoblastic Leukemia (2004)

To clarify the mechanism of progression and acquired drug resistance of leukemia, we searched for an overexpressed gene in drug-resistant leukemia cells and identified an approximately 5-kb transcript by using the subtraction method. The nucleotide sequence of the gene was highly homologous to those of human endogenous retrovirus (HERV) transcripts. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that the gene was overexpressed in cells from 6 childhood acute lymphoblastic leukemia patients (60%) but not in bone marrow cells at remission. Peripheral blood mononuclear cells from normal controls (n=11) and bone marrow cells from non-leukemia patients (n=13) did not express the gene. These findings indicate that the gene may play a role in leukemogenesis and may be a novel leukemia marker. Further studies on the functional role of the gene are needed.
Comparative Efficacy of Positron Emission Tomography with FDG and Computed Tomographic Scanning in Preoperative Staging of Non-Small Cell Lung Cancer (1999)

PET-FDG is a reliable method for preoperative staging of patients with lung cancer and would help to optimize management of these patients. Accurate lymph node staging of lung cancer may be ideally performed by simultaneous review of PET and CT scans.
SAbPred: a structure-based antibody prediction server (2016)

SAbPred is a server that makes predictions of the properties of antibodies focusing on their structures. Antibody informatics tools can help improve our understanding of immune responses to disease and aid in the design and engineering of therapeutic molecules. SAbPred is a single platform containing multiple applications which can: number and align sequences; automatically generate antibody variable fragment homology models; annotate such models with estimated accuracy alongside sequence and structural properties including potential developability issues; predict paratope residues; and predict epitope patches on protein antigens. The server is available at http://opig.stats.ox.ac.uk/webapps/sabpred.
Interaction of plasminogen and fibrin in plasminogen activation. (1990)

Glu1-, Lys77-, miniplasminogens, kringle 1-3, kringle 1-5A, and kringle 1-5R were able to bind with fibrin, while microplasminogen and kringle 4 did not bind significantly. Kringle 1-5A, but not kringle 1-3, effectively inhibited the binding of Glu1-, Lys77-, and miniplasminogens with fibrin. Miniplasminogen also inhibited the binding of Glu1-plasminogen with fibrin. The binding of kringle 1-3 with fibrin was blocked by mini- or Glu1-plasminogen. It is therefore evident that there are two fibrin-binding domains in plasminogen and that the one in kringle 5 is of higher affinity than that in kringle 1-3. CNBr cleavage products of fibrinogen effectively enhanced the activation of Glu1-, Lys77-, or miniplasminogens, but not microplasminogen, by tissue-type plasminogen activator. Kringle 1-5, but not kringle 1-3, dose-dependently inhibited the enhancement by fibrinogen degradation products of Glu1-plasminogen activation by the activator. Lysine and epsilon-aminocaproic acid could inhibit the binding of plasminogens and plasminogen derivatives with fibrin and block the enhancement effect of fibrinogen degradation products on plasminogen activation. The data clearly illustrate that the binding of plasminogen with fibrin, mainly determined by kringle 5, is essential for effective activation by tissue-type plasminogen activator. However, the presence of kringle 1-4 in the plasminogen molecule is required for the full enhancing effect since the kcat/Km of miniplasminogen activation in the presence of fibrinogen degradation products was 8.2 microM-1 min-1 which is significantly less than 52.0 microM-1 min-1 of Glu1-plasminogen.
Development of questionnaires to measure patient preferences for intranasal corticosteroids in patients with allergic rhinitis (2005)

B-20.
Functional acetylcholine receptor from Torpedo marmorata in planar membranes. (1980)

Planar bilayer membranes containing functional acetylcholine receptor were formed from vesicles of Torpedo marmorata electric organ without extracting the acetylcholine receptor from its native environment. Native vesicles were transformed into monolayers which subsequently were apposed into planar bilayers. In the absence of agonists the membrane conductance was similar to that of lipid bilayers. Addition of carbamoylcholine or succinylcholine caused increased membrane conductance and this could be competitively inhibited by d-tubocurarine and suppressed by alpha-bungarotoxin. The amplitude of the conductance response was proportional to the number of alpha-bungarotoxin binding sites in the bilayers. Asymmetric membranes could be formed with the ligand binding sites on only one membrane surface. Desensitization of acetylcholine receptor was evident from equilibrium and kinetic data of the carbamoylcholine-activated conductance. Carbamoylcholine-induced membrane permeability was about 7 times higher for K+ and Na+ ions than for Cl-. At low levels of conductance, single-channel fluctuations of 20-25 pS in conductance and 1.3-msec lifetime were resolved in physiological saline containing carbamoylcholine. The ratio of observed channels to alpha-bungarotoxin sites present showed that a significant fraction of acetylcholine receptor in the membrane was functional. The quantitative aspects of the cation channel, the desensitization, and the ligand binding properties were in close agreement with established values. This transformation of natural acetylcholine receptor vesicles to planar bilayers conserves the essential properties of the in vivo receptor.
Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy (2017)

Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (T<sub>SCM</sub>) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8<sup>+</sup> T<sub>SCM</sub> cells can be generated in vitro from naive CD8<sup>+</sup> T cells via Wnt signalling; however, methods do not yet exist for inducing T<sub>SCM</sub> cells from activated or memory T cells. Here, we show a strategy for generating T<sub>SCM</sub>-like cells in vitro (iT<sub>SCM</sub> cells) from activated CD4<sup>+</sup> and CD8<sup>+</sup> T cells in mice and humans by coculturing with stromal cells that express a Notch ligand. iT<sub>SCM</sub> cells lose PD-1 and CTLA-4 expression, and produce a large number of tumour-specific effector cells after restimulation. This method could therefore be used to generate antigen-specific effector T cells for adoptive immunotherapy.
Asparagine-linked protein glycosylation: from eukaryotic to prokaryotic systems (2006)

Asparagine-linked protein glycosylation is a prevalent protein modification reaction in eukaryotic systems. This process involves the co-translational transfer of a pre-assembled tetradecasaccharide from a dolichyl-pyrophosphate donor to the asparagine side chain of nascent proteins at the endoplasmic reticulum (ER) membrane. Recently, the first such system of N-linked glycosylation was discovered in the Gram-negative bacterium, Campylobacter jejuni. Glycosylation in this organism involves the transfer of a heptasaccharide from an undecaprenyl-pyrophosphate donor to the asparagine side chain of proteins at the bacterial periplasmic membrane. Here we provide a detailed comparison of the machinery involved in the N-linked glycosylation systems of eukaryotic organisms, exemplified by the yeast Saccharomyces cerevisiae, with that of the bacterial system in C. jejuni. The two systems display significant similarities and the relative simplicity of the bacterial glycosylation process could provide a model system that can be used to decipher the complex eukaryotic glycosylation machinery.
Learning Deep Embeddings with Histogram Loss (2016)

We suggest a loss for learning deep embeddings. The new loss does not introduce parameters that need to be tuned and results in very good embeddings across a range of datasets and problems. The loss is computed by estimating two distribution of similarities for positive (matching) and negative (non-matching) sample pairs, and then computing the probability of a positive pair to have a lower similarity score than a negative pair based on the estimated similarity distributions. We show that such operations can be performed in a simple and piecewise-differentiable manner using 1D histograms with soft assignment operations. This makes the proposed loss suitable for learning deep embeddings using stochastic optimization. In the experiments, the new loss performs favourably compared to recently proposed alternatives.
Conformationally defined neurotransmitter analogs. Selective inhibition of glutamate uptake by one pyrrolidine-2,4-dicarboxylate diastereomer (1991)

In order to determine the conformational requirements for binding of L-glutamate to the proteins involved in the process of neurotransmission, rigid analogues containing an embedded glutamate moiety have been prepared. These "conformer mimics", the pyrrolidine-2,4-dicarboxylates 4, 7, 11, and 14, were synthesized from commercially available trans-4-hydroxy-L-proline and cis-4-hydroxy-D-proline, and then were tested for their ability to inhibit the high-affinity transport of [3H]-L-glutamate into synaptosomes and to block the binding of radioligands to the NMDA (N-methyl-D-aspartate), KA (kainate), and QA (quisqualate) glutamate neurotransmitter receptor sites. While none of the four analogues binds effectively to the excitatory receptors, the L-trans-isomer 7 is a potent and selective competitive inhibitor of L-glutamate transport. These results delineate a specific structural/conformational preference for binding to the uptake system that is distinct from that required for binding to the NMDA, KA, and QA receptors.
Antibody Capture Immunoassay Detection of Japanese Encephalitis Virus Immunoglobulin M and G Antibodies in Cerebrospinal Fluid (1982)

Immunoglobulin M (IgM) and IgG antibodies to Japanese encephalitis virus (JEV) were detected in acute-phase cerebrospinal fluid (CSF) specimens from patients with acute encephalitis by using a solid-phase radioimmunoassay of the antibody capture type. Of 12 patients with JEV infections subsequently proven by hemagglutination inhibition serology, 11 had JEV IgM antibodies, as measured by antibody capture radioimmunoassay, in the first CSF specimen (geometric mean titer, 1:2,500) compared with 0 of 8 patients with acute encephalitis proven not to be due to JEV. Specific IgM anti-JEV activity (units per microgram) was greater in CSF than in parallel serum specimens in all 11 positive cases by more than fourfold on the average (range, 1.4 to 13). Among seven patients with broadly reactive hemagglutination inhibition seroresponses typical of persons previously exposed to other flaviviruses, six had high levels of JEV IgG antibodies (as measured by antibody capture radioimmunoassay) in their acute-phase CSF (geometric mean titer, 1:26,000), whereas in five patients experiencing their first flavivirus infection, JEV IgG antibodies measured by antibody capture radio-immunoassay were either absent (one patient) or weakly reactive (four patients; geometric mean titer, 1:3,200). Specific IgG anti-JEV activity was greater in CSF than in parallel serum specimens in eight of the nine positive cases measured (range, 1.3- to 24-fold). The antibody capture solid-phase immunoassay approach is well suited for detecting specific antibody activity in CSF.
The effect of cyclosporine, total lymphoid irradiation, and cobra venom factor on hyperacute rejection. (1987)

Transplantation into sensitized recipients is contraindicated due to the potential for hyperacute rejection. In order to study the mechanism of hyperacute rejection and the role of immunosuppression in the face of presensitization, we evaluated the effect of total lymphoid irradiation, cyclosporine, and cobra venom factor, alone and in combination, on hyperacute rejection of heterotopic rat heart allografts. Lewis rats were sensitized to strongly RT-1-incompatible ACI rats by three successive skin grafts. Heart allografts were then performed, and survived for a mean period of 15.7 +/- 7.4 hours. Neither preoperative treatment of hypersensitized rats with total lymphoid irradiation alone nor with cyclosporine (5 mg/kg/day) resulted in a prolongation of survival (20.4 +/- 16.6 hours and 35.6 +/- 6.2 hours, respectively). However, complement depletion using cobra venom factor significantly prolonged mean graft survival time to 114.4 +/- 31.0 hours (p less than 0.05). Cyclosporine (10 mg/kg/day) also significantly prolonged survival to 149 +/- 29 hours (p less than 0.01), but did not lower the antibody or complement levels. The addition of total lymphoid irradiation or cyclosporine to treatment with cobra venom factor did not result in longer survival than cobra venom factor alone. In conclusion, cobra venom factor and cyclosporine delay but do not prevent hyperacute rejection, while total lymphoid irradiation has no observable effect on hyperacute rejection.
Direct in situ reverse transcriptase-polymerase chain reaction (2001)

In situ hybridization has been used for localization of specific nucleic acid sequences at the cellular level despite providing relatively low-detection sensitivity. In situ reverse transcriptase-polymerase chain reactions (RT-PCR) enhance sensitivity and thus enable localization of low-abundance mRNA in a cell. However, the available methods are fraught with problems of nonspecific amplifications as a result of mispriming and/or amplification from partially digested residual genomic DNA in tissue. Herein, we demonstrate that nonspecific background amplification can be eliminated by pretreatment of samples with restriction enzymes before DNase I digestion. Primers tagged with a far-red shifted fluorescent dye such as Cy5 in PCR reactions allow identification of target mRNA by fluorescence microscopy. These novel modifications lead to increased specificity and rapid in situ detection of cellular mRNA and thus may be used for pathological diagnosis.