gebhart/patrepeval huggingface dataset:
Real-Time Travel Path Prediction Using GPS-Enabled Mobile Phones (2008)

This paper presents an algorithm to predict an individual’s real-time travel path and destination using data from a Global Positioning System (GPS) enabled mobile phone. The algorithm uses spatially-aware, geometric representations of a user’s historical trip data in its comparisons thus eliminating the need for taxing calculations. This technique also promotes scalability through the use of enterprise spatial database systems. Multiple modes of transportation are supported since the algorithm does not rely on road network information. This Path Prediction algorithm can enable a variety of services such as real-time localized traffic incident reporting, location-based advertising, and live traffic management.
A Heuristic Method for Assigning a False-discovery Rate for Protein Identifications from Mascot Database Search Results (2005)

MS/MS and database searching has emerged as a valuable technology for rapidly analyzing protein expression, localization, and post-translational modifications. The probability-based search engine Mascot has found widespread use as a tool to correlate tandem mass spectra with peptides in a sequence database. Although the Mascot scoring algorithm provides a probability-based model for peptide identification, the independent peptide scores do not correlate with the significance of the proteins to which they match. Herein, we describe a heuristic method for organizing proteins identified at a specified false-discovery rate using Mascot-matched peptides. We call this method PROVALT, and it uses peptide matches from a random database to calculate false-discovery rates for protein identifications and reduces a complex list of peptide matches to a nonredundant list of homologous protein groups. This method was evaluated using Mascot-identified peptides from a Trypanosoma cruzi epimastigote whole-cell lysate, which was separated by multidimensional LC and analyzed by MS/MS. PROVALT was then compared with the two traditional methods of protein identification when using Mascot, the single peptide score and cumulative protein score methods, and was shown to be superior to both in regards to the number of proteins identified and the inclusion of lower scoring nonrandom peptide matches.
Review: Mammalian peptidoglycan recognition proteins (PGRPs) in innate immunity (2010)

Peptidoglycan recognition proteins (PGRPs or PGLYRPs) are innate immunity proteins that are conserved from insects to mammals, recognize bacterial peptidoglycan, and function in antibacterial immunity and inflammation. Mammals have four PGRPs - PGLYRP1, PGLYRP2, PGLYRP3, and PGLYRP4. They are secreted proteins expressed in polymorphonuclear leukocytes (PGLYRP1), liver (PGLYRP2), or on body surfaces, mucous membranes, and in secretions (saliva, sweat) (PGLYRP3 and PGLYRP4). All PGRPs recognize bacterial peptidoglycan. Three PGRPs, PGLYRP1, PGLYRP3, and PGLYRP4 are directly bactericidal for both Gram-positive and Gram-negative bacteria and have no enzymatic activity, whereas PGLYRP2 is an N-acetylmuramoyl-L-alanine amidase that hydrolyzes bacterial cell wall peptidoglycan. Peptidoglycan recognition proteins influence host- pathogen interactions not only through their antibacterial or peptidoglycan-hydrolytic properties, but also through their pro-inflammatory and anti-inflammatory properties that are independent of their hydrolytic and antibacterial activities. The PGRPs likely play a role both in antibacterial defenses and several inflammatory diseases. They modulate local inflammatory responses in tissues (such as arthritic joints) and there is evidence for association of PGRPs with inflammatory diseases, such as psoriasis.
Prospects For Stem Cell Transplantation in the Treatment of Hepatic Disease (2010)

Stem cell therapy has the potential to provide a valuable adjunct to the management of hepatic disease. Preclinical studies have demonstrated a range of endogenous repair processes that can be exploited through stem cell therapy. Initial translational studies have been encouraging and have suggested improved liver function in advanced chronic liver disease and enhanced liver regeneration after portal vein embolization. This article reviews the potential for stem cell therapies to enhance hepatic regeneration in acute and chronic hepatic disease and is based on a MEDLINE and PubMed search for English language articles investigating mechanisms of hepatic regeneration and delivery of cell therapies. Two main mechanisms of potential stem cell therapy delivery have emerged: (1) a direct contribution to the functional hepatocyte population with embryonic, induced pluripotent, or adult stem cells and (2) the promotion of endogenous regenerative processes with bone marrow-derived stem cells. Bioartificial hepatic support systems may be proven to be an effective method of using ex vivo differentiated hepatocytes and be indicated as a bridging therapy to definitive surgery in acute liver failure. The administration of bone marrow-derived stem cells may enhance liver regeneration in chronic liver disease after portal vein embolization and could facilitate regeneration after partial hepatic resection. Ultimately, the most appropriate hepatic disease targets for stem cell therapies will become apparent as mechanisms of stem involvement in hepatic regeneration are further elucidated.
An autopsy case of autosomal-recessive juvenile parkinsonism with a homozygous exon 4 deletion in theparkin gene (2000)

We report the neuropathologic and genetic features of a 70-year-old man with autosomal-recessive juvenile parkinsonism (AR-JP). At the age of 32 years, he developed a dystonic gait, followed by hand tremor, rigidity, bradykinesia, and impaired postural reflex. Levodopa was effective in ameliorating these symptoms. Pathologic examination of autopsy specimens from this patient revealed loss of pigmented neurons and gliosis in the substantia nigra pars compacta (SNPC), being most pronounced in the medial and ventrolateral regions, and locus ceruleus (LC). The melanin content of the remaining SNPC neurons was low. This feature was less marked in the LC. There were no Lewy bodies, as confirmed by immunostaining for alpha-synuclein. An additional, significant finding in this patient was neuronal loss and fibrillary gliosis in the substantia nigra pars reticulata; this feature has not been reported previously in AR-JP. Gene analysis revealed that this autopsied patient and his siblings had the parkin gene mutation (homozygous exon 4 deletion) that is responsible for the disease.
Removal of Amphipathic Epitopes from Genetically Engineered Antibodies: Production of Modified Immunoglobulins with Reduced Immunogenicity (2000)

Several approaches have been developed to reduce the human immune response to nonhuman antibodies. However, chimeric antibodies and humanized antibodies often have decreased binding affinity. We described a new approach for reducing the immunogenicity of chimeric antibodies while maintaining the affinity. This approach seeks to prevent the recognition of murine immunogenic peptides from the antibody variable region by human lymphocytes. Putative immunogenic epitopes in the variable region are identified and subjected to site directed mutagenesis to make them human and/or to break the amphipathic motifs. The R3 antibody, which blocks the epidermal growth factor (EGF) receptor, was used as a model system to test this approach. Four segments containing possible amphipathic epitopes were found in the heavy variable domain using the program AMPHI. Six amino acids within two of these segments were substituted by the corresponding residues from a homologous human sequence. No mutations were made in the murine light variable domain. Experiments in monkeys suggested that the "detope" R3 antibody was less immunogenic than its chimeric analogue. A search for possible amphipathic epitopes in the Kabat database revealed the presence of conserved patterns in the different families of variable region sequences, suggesting that the proposed method may be of general applicability.
Antigen‐presenting cells pulsed with unfractionated tumor‐derived peptides are potent tumor vaccines (1997)

Vaccination with peptides isolated from tumor cells circumvents the need for identifying specific tumor rejection antigens and extends the use of active immunotherapy to the majority of cancers where specific tumor antigens have not yet been identified. In this study, we examined the efficacy of tumor vaccines composed of unfractionated tumor peptides presented by antigen-presenting cells (APC) to induce cytotoxic T lymphocyte (CTL) responses and tumor immunity. RMA-S cells pulsed with peptides isolated from ovalbumin (OVA)-expressing tumor cells were highly effective at inducing primary, OVA-specific CTL responses in vitro and priming CTL responses in vivo. In addition, tumor peptide-pulsed RMA-S cells induced protective immunity in mice when challenged with OVA-expressing tumor cells. To enhance the clinical relevance of these studies, cells pulsed with tumor peptides were evaluated in the poorly immunogenic, B16/F10.9 melanoma post-surgical metastasis model. Treatment of tumor-bearing mice with peptide-pulsed RMA-S cells or with adherent splenocytes (enriched for professional APC) caused a significant reduction in lung metastases. The antimetastatic effect of peptide-pulsed splenocytes could be further enhanced by pretreating the cells with antisense oligonucleotides directed against the TAP-2 gene which was previously shown to increase the density of specific peptide/MHC class I complexes and thereby improve the APC function of the treated cells (Nair et el., J. Immunol. 1996. 156: 1772). This study suggests that APC loaded with unfractionated peptides derived from poorly immunogenic, highly metastatic tumor cells may represent a potent form of tumor vaccine.
Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease (2015)

The incidence of autoimmune diseases is increasing along with the expansion of industrial food processing and food additive consumption. The intestinal epithelial barrier, with its intercellular tight junction, controls the equilibrium between tolerance and immunity to non-self-antigens. As a result, particular attention is being placed on the role of tight junction dysfunction in the pathogenesis of AD. Tight junction leakage is enhanced by many luminal components, commonly used industrial food additives being some of them. Glucose, salt, emulsifiers, organic solvents, gluten, microbial transglutaminase, and nanoparticles are extensively and increasingly used by the food industry, claim the manufacturers, to improve the qualities of food. However, all of the aforementioned additives increase intestinal permeability by breaching the integrity of tight junction paracellular transfer. In fact, tight junction dysfunction is common in multiple autoimmune diseases and the central part played by the tight junction in autoimmune diseases pathogenesis is extensively described. It is hypothesized that commonly used industrial food additives abrogate human epithelial barrier function, thus, increasing intestinal permeability through the opened tight junction, resulting in entry of foreign immunogenic antigens and activation of the autoimmune cascade. Future research on food additives exposure-intestinal permeability-autoimmunity interplay will enhance our knowledge of the common mechanisms associated with autoimmune progression.
Evaluation of Clinical and Immunogenetic Risk Factors for the Development of Hepatotoxicity during Antituberculosis Treatment (2002)

Though several risk factors for the development of hepatotoxicity due to antituberculosis drugs have been suggested, involvement of genetic factors is not fully established. We have studied the major histocompatibility complex (MHC) class II alleles and clinical risk factors for the development of hepatotoxicity in 346 North Indian patients with tuberculosis undergoing antituberculosis treatment. Of these, 56 patients developed drug-induced hepatotoxicity (DIH group), whereas the remaining 290 patients did not (non-DIH group). The DIH group was comparatively older, had lower pretreatment serum albumin, and a higher frequency of moderately/far advanced disease radiographically than the latter. Further, patients with high alcohol intake had threefold higher odds of developing hepatotoxicity. In multivariate logistic regression analysis, older age (odds ratio [OR] 1.2), moderately/far advanced disease (OR 2.0), serum albumin < 3.5 g/dl (OR 2.3), absence of HLA-DQA1*0102 (OR 4.0), and presence of HLA-DQB1*0201 (OR 1.9) were independent risk factors for DIH. Our results suggest that the risk of hepatotoxicity from antituberculosis drugs is influenced by clinical and genetic factors.
Modeling of penalties on chains of optical amplifiers with equalizing filters (2000)

A mathematical model for the calculation of optical signal-to-noise ratio (SNR) on cascades of erbium doped fiber amplifiers (EDFA's) with interposed equalizing filters in the fiber spans is presented. The model enables to simulate different types of cascade, whether the filters are placed after each amplifier or after any group of amplifiers. Criteria for the design of the optimal filter are presented for a typical configuration. The relation between preemphasis and penalty on SNR is studied, and for the first time to our knowledge it is shown that some asymmetry may arise when using in line optical filters. A study of the sensitivity of penalty at receiver toward preemphasis at transmitter based on the model is presented.
Trafficking of tail-anchored proteins: transport from the endoplasmic reticulum to the plasma membrane and sorting between surface domains in polarised epithelial cells (2002)

Tail-anchored (TA) proteins, which are defined by an N-terminal cytosolic region and a C-terminal transmembrane domain (TMD), provide useful models for studying the role of the TMD in sorting within the exo-endocytic system. Previous work has shown that a short TMD is required to keep ER-resident TA proteins from escaping to downstream compartments of the secretory pathway. To investigate the role of the TMD in TA protein sorting, we used model constructs, which consisted of GFP linked at its C-terminus to the tail region of cytochrome b(5) with TMDs of differing length or hydrophobicity. Expression of these constructs in CV-1 cells demonstrated that the feature determining exit from the ER is hydrophobicity and that if exit occurs, at least a part of the protein reaches the cell surface. To investigate which pathway to the surface is followed by plasma-membrane-directed TA constructs, we expressed the TA constructs in polarised Madin Darby Canine Kidney (MDCK) cells. The constructs with 22 and 25 residue TMDs were localised basolaterally, but addition at the C-terminus of a 20-residue peptide containing an N-glycosylation site resulted in glycosylation-dependent relocation of approximately 50% of the protein to the apical surface. This result suggests that TA proteins may reach the basolateral surface without a signal or that our constructs contain a weak basolateral determinant that is recessive to the apical information carried by the glycan. To assess the effect of the TMDs of endogenous TA proteins, GFP was linked to the tails of syntaxin 3 and 4, which localise to the apical and basolateral surface, respectively, of MDCK cells. The two GFP fusion proteins showed a different surface distribution, which is consistent with a role for the two syntaxin TMDs in polarised sorting.
Production of a monoclonal antibody-methotrexate conjugate utilizing dextran T-40 and its biologic activity. (1984)

Methotrexate (MTX), a folate antagonist and anticancer agent, was linked covalently to murine monoclonal anti-HLA IgG1 antibody (H-1) with the use of dextran T-40 as a multivalent carrier. As determined spectrophotometrically, the conjugate was composed of 9.20 mol MTX per 1 mol antibody. Of the substituted MTX, 46.3% (4.30 mol MTX per 1 mol antibody) exhibited inhibitory activity on dihydrofolate reductase. The MTX conjugated to H-1 [MTX-(H-l)] showed significantly stronger cytotoxicity against HLA-bearing cells than cells lacking HLA (p less than 0.001) in cultivation after a 2-hour exposure to the drugs. In the same experiment, free MTX showed equivalent cytotoxicity to cells both bearing and lacking HLA. When cells were cultivated for 3 days with the drugs, MTX-(H-l) also showed significantly stronger cytotoxicity than free MTX or MTX-control IgG conjugate against HLA-bearing cells (p less than 0.001), and the MTX-(H-l), MTX-control IgG, and free MTX showed equivalent cytotoxicity to cells lacking HLA. Our results indicate that the MTX-(H-l) conjugate binds to the cell surface antigen by its antibody action and exerts greater MTX cytotoxicity than free MTX in vitro.
Cabazitaxel: A Novel Drug for Hormone-Refractory Prostate Cancer (2013)

Cabazitaxel has recently been approved by FDA for the treatment of docetaxel resistant hormone-refractory prostate cancer. It has been developed by Sanofi-Aventis under the trade name of Jevtana. It is given in combination with prednisone/prednisolone and has passed the clinical trial over well-known drug mitoxantrone. This drug is a microtubule depolymerization inhibitor, which can penetrate blood brain barrier (BBB). The FDA granted fast track designation to this drug in November 2009 and thereafter, new drug application submission was done in March 2010. Priority review to this drug was granted in April 2010 and finally in July 2010 it was approved by FDA. It is available in the form of injection in the dose of 60 mg/1.5 mL, which should be diluted prior to its use by the diluents supplied along with the injection. It is a second-line drug and has proven to be effective in patients experiencing docetaxel based treatment failure.
3D-QSAR Study of Combretastatin A-4 Analogs Based on Molecular Docking (2011)

Combretastatin A-4 (CA-4), its analogues and their excellent antitumoral and antivascular activities, have attracted considerable interest of medicinal chemists. In this article, a docking simulation was used to identify molecules having the same binding mode as the lead compound, and 3D-QSAR models had been built by using CoMFA based on docking. As a result, these studies indicated that the QSAR models were statistically significant with high predictabilities (CoMFA model, q2 = 0.786, r2 = 0.988). Our models may offer help to better comprehend the structure-activity relationships for this class of compounds and also facilitate the design of novel inhibitors with good chemical diversity.
Basic and Clinical Studies of Glucocorticosteroid Receptors in Lymphoid Malignancies (1996)

Glucocorticosteroids, including prednisone and dexamethasone, are among the most effective agents employed in the treatment of lymphoid malignancies. The efficacy of glucocorticoids in these malignancies is based on their ability to induce programmed cell death, or apoptosis, of immature lymphocytes (see Chapter 18, this volume). Biochemical and molecular studies indicate that glucocorticoid-induced lymphocytolysis is mediated through the glucocorticoid receptor and involves regulation of gene expression, although genes that mediate the lethal effect of glucocorticoids are unidentified.
Astrocyte-derived TGF-beta 2 and NGF differentially regulate neural recognition molecule expression by cultured astrocytes. (1991)

Because of the importance of neural recognition molecules expressed by glial cells to mediate interactions with neurons, growth factors and cytokines known to be functional during morphogenesis and in diseases of the nervous system were studied for their effects on recognition molecule expression by cultured immature and mature astrocytes from several brain regions. In cultures of immature astrocytes, transforming growth factors-beta 1 (TGF-beta 1) and -beta 2 (TGF-beta 2) and nerve growth factor (NGF) increased expression of the neural adhesion molecule L1, leading to a glia-mediated L1-specific increase in neurite outgrowth of dorsal root ganglion neurons on the astrocyte substrate. L1 expression induced by TGF-beta was inhibited by addition of antibodies to NGF, suggesting that TGF-beta influences L1 expression by modulating production of NGF by astrocytes. TGF-beta 1 and -beta 2 decreased expression of N-CAM by immature astrocytes. Since N-CAM expression was not affected by NGF and antibodies to NGF did not abolish the TGF-beta-induced decrease in N-CAM expression, NGF did not appear to be the mediator for regulating expression of N-CAM. Expression of the adhesion molecule on glia (AMOG) was not affected by any factor. NGF and TGF-beta 2 in latent form, but not TGF-beta 1 were found in the culture supernatants. Addition of interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), platelet-derived growth factor (PDGF), or basic fibroblast growth factor (bFGF) to the cultures did not change recognition molecule expression. REcognition molecule expression by mature astrocytes was not found to be modified by any of the factors tested. In view of the observation that levels of L1 and N-CAM expression correlated with the presence of TGF-beta 2 and NGF in the culture supernatants of immature astrocytes, an autocrine regulatory mechanism for recognition molecule expression by these cells is suggested to play a crucial role in regulation of neuron-glia interactions.
Long-Distance Axonal Regeneration in the Transected Adult Rat Spinal Cord Is Promoted by Olfactory Ensheathing Glia Transplants (1998)

The lack of axonal regeneration in the injured adult mammalian spinal cord leads to permanent functional impairment. To induce axonal regeneration in the transected adult rat spinal cord, we have used the axonal growth-promoting properties of adult olfactory bulb ensheathing glia (EG). Schwann cell (SC)-filled guidance channels were grafted to bridge both cord stumps, and suspensions of pure (98%) Hoechst-labeled EG were stereotaxically injected into the midline of both stumps, 1 mm from the edges of the channel. In EG-transplanted animals, numerous neurofilament-, GAP-43-, anti-calcitonin gene-related peptide (CGRP)-, and serotonin-immunoreactive fibers traversed the glial scars formed at both cord-graft interfaces. Supraspinal serotonergic axons crossed the transection gap through connective tissue bridges formed on the exterior of the channels, avoiding the channel interior. Strikingly, after crossing the distal glial scar, these fibers elongated in white and periaqueductal gray matter, reaching the farthest distance analyzed (1.5 cm). Tracer-labeled axons present in SC grafts were found to extend across the distal interface and up to 800 microm beyond in the distal cord. Long-distance regeneration (at least 2.5 cm) of injured ascending propriospinal axons was observed in the rostral spinal cord. Transplanted EG migrated longitudinally and laterally from the injection sites, reaching the farthest distance analyzed (1.5 cm). They moved through white matter tracts, gray matter, and glial scars, overcoming the inhibitory nature of the CNS environment, and invaded SC and connective tissue bridges and the dorsal and ventral roots adjacent to the transection site. Transplanted EG and regenerating axons were found in the same locations. Because EG seem to provide injured spinal axons with appropriate factors for long-distance elongation, these cells offer new possibilities for treatment of CNS conditions that require axonal regeneration.