gebhart/patrepeval huggingface dataset:
Heparanase affects adhesive and tumorigenic potential of human glioma cells. (2003)

Heparanase is an endo-beta-glucuronidase responsible for the cleavage of heparan sulfate, participating in extracellular matrix degradation and remodeling. Traditionally, heparanase activity was well correlated with the metastatic potential of a large number of tumor-derived cell types. More recently, heparanase up-regulation was detected in essentially all human tumors examined, correlating, in some cases, with poor postoperative survival and increased tumor vascularity. The role of heparanase in primary tumor progression is, however, poorly understood. Here, we overexpressed the human heparanase gene in a human glioma cell line, U87. We found that heparanase overexpression induces cell invasion, as might be expected. Surprisingly, elevated heparanase expression levels correlated with decreased proliferation rates and increased cell spreading and formation of a tight monolayer rather than large cell aggregates. This phenotypic appearance was accompanied by beta1-integrin activation, FAK and Akt phosphorylation, and Rac activation. In a xenograft tumor model, relatively moderate heparanase expression levels significantly enhanced tumor development and tumor vascularity, whereas high heparanase expression levels inhibited tumor growth. These results indicate that heparanase activates signal transduction pathways and, depending on its expression levels, may modulate tumor progression.
THE GENETICS AND MOLECULAR BIOLOGY OF THE SYNAPTONEMAL COMPLEX (2004)

▪ Abstract The synaptonemal complex (SC) is a protein lattice that resembles railroad tracks and connects paired homologous chromosomes in most meiotic systems. The two side rails of the SC, known as lateral elements (LEs), are connected by proteins known as transverse filaments. The LEs are derived from the axial elements of the chromosomes and play important roles in chromosome condensation, pairing, transverse filament assembly, and prohibiting double-strand breaks (DSBs) from entering into recombination pathways that involve sister chromatids. The proteins that make up the transverse filaments of the SC also play a much earlier role in committing a subset of DSBs into a recombination pathway, which results in the production of reciprocal meiotic crossovers. Sites of crossover commitment can be observed as locations where the SC initiates and as immunostaining foci for a set of proteins required for the processing of DSBs to mature crossovers. In most (but not all) organisms it is the establishment of sites marking such crossover-committed DSBs that facilitates completion of synapsis (full-length extension of the SC). The function of the mature full-length SC may involve both the completion of meiotic recombination at the DNA level and the exchange of the axial elements of the two chromatids involved in the crossover. However, the demonstration that the sites of crossover formation are designated prior to SC formation, and the finding that these sites display interference, argues against a role of the mature SC in mediating the process of interference. Finally, in at least some organisms, modifications of the SC alone are sufficient to ensure meiotic chromosome segregation in the complete absence of meiotic recombination.
Cisplatin Alters Antitumor Immunity and Synergizes with PD-1/PD-L1 Inhibition in Head and Neck Squamous Cell Carcinoma (2017)

Head and neck squamous cell carcinoma (HNSCC) has been treated for decades with cisplatin chemotherapy, and anti-PD-1 immunotherapy has recently been approved for the treatment of this disease. However, preclinical studies of how antitumor immunity in HNSCC is affected by cisplatin alone or in combination with immunotherapies are lacking. Here, we show that sublethal doses of cisplatin may enhance antigen presentation and T-cell killing <i>in vitro</i>, though cisplatin also upregulates tumor cell expression of PD-L1 and may impair T-cell function at higher doses. In a syngeneic mouse model of HNSCC, concurrent use of cisplatin and anti-PD-L1/PD-1 delayed tumor growth and enhanced survival without significantly reducing the number or function of tumor-infiltrating immune cells or increasing cisplatin-induced toxicities. These results suggest that moderate doses of cisplatin may enhance antitumor immunity by mechanisms other than direct tumor cell killing, which may be further enhanced by anti-PD-L1/PD-1 therapy. <i>Cancer Immunol Res; 5(12); 1141-51. ©2017 AACR</i>.
Effect of elevated CO2on phosphorus nutrition of phosphate-deficientArabidopsis thaliana(L.) Heynh under different nitrogen forms (2012)

Phosphorus (P) nutrition is always a key issue regarding plants responses to elevated CO(2). Yet it is unclear of how elevated CO(2) affects P uptake under different nitrogen (N) forms. This study investigated the influence of elevated CO(2) (800 µl l(-1)) on P uptake and utilization by Arabidopsis grown in pH-buffered phosphate (P)-deficient (0.5 µM) hydroponic culture supplying with 2mM nitrate (NO(3)(-)) or ammonium (NH(4)(+)). After 7 d treatment, elevated CO(2) enhanced the biomass production of both NO(3)(-)- and NH(4) (+)-fed plants but decreased the P amount absorbed per weight of roots and the P concentration in the shoots of plants supplied with NH(4)(+). In comparison, elevated CO(2) increased the amount of P absorbed per weight of roots, as well as the P concentration in plants and alleviated P deficiency-induced symptoms of plants supplied with NO(3)(-). Elevated CO(2) also increased the root/shoot ratio, total root surface area, and acid phosphatase activity, and enhanced the expression of genes or transcriptional factors involving in P uptake, allocation and remobilization in P deficient plants. Furthermore, elevated CO(2) increased the nitric oxide (NO) level in roots of NO(3)(-)-fed plants but decreased it in NH(4)(+)-fed plants. NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) inhibited plant P acquisition by roots under elevated CO(2). Considering all of these findings, this study concluded that a combination of elevated CO(2) and NO(3)(-) nutrition can induce a set of plant adaptive strategies to improve P status from P-deficient soluble sources and that NO may be a signalling molecule that controls these processes.
On-Line Random Naive Bayes for Tracking (2010)

Randomized learning methods (i.e., Forests or Ferns) have shown excellent capabilities for various computer vision applications. However, it was shown that the tree structure in Forests can be replaced by even simpler structures, e.g., Random Naive Bayes classifiers, yielding similar performance. The goal of this paper is to benefit from these findings to develop an efficient on-line learner. Based on the principals of on-line Random Forests, we adapt the Random Naive Bayes classifier to the on-line domain. For that purpose, we propose to use on-line histograms as weak learners, which yield much better performance than simple decision stumps. Experimentally we show, that the approach is applicable to incremental learning on machine learning datasets. Additionally, we propose to use an IIR filtering-like forgetting function for the weak learners to enable adaptivity and evaluate our classifier on the task of tracking by detection.
Immunochemical analysis of intact M protein secreted from cell wall-less streptococci (1981)

M protein is a major virulence factor of group A streptococci, which provides these organisms with protection against phagocytosis in the absence of specific antibody. To gain insight into the nature of the native M-protein molecule, type 12 M protein was isolated and purified from the extracellular supernatants of a group A streptococcal L form and stabilized protoplasts. The intact purified M protein from both sources had a molecular weight of 58,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This is in contrast to the 32,0000-dalton molecule isolated from the parent type 12 organism by using a nonionic detergent. The purified secretory M protein removed opsonic antibodies from type 12 rabbit immune serum, as demonstrated by a bactericidal assay. Therefore, it appears that either previous nondestructive methods of M-protein isolation have not removed intact M protein from cell walls or part of the molecule is fragmented during its association with cell walls.
STAT3 Expression, Molecular Features, Inflammation Patterns, and Prognosis in a Database of 724 Colorectal Cancers (2011)

STAT3 activation in colorectal cancer is associated with adverse clinical outcome, supporting its potential roles as a prognostic biomarker and a chemoprevention and/or therapeutic target.
Identification of Protein Tyrosine Phosphatases and Dual-Specificity Phosphatases in Mammalian Spermatozoa and Their Role in Sperm Motility and Protein Tyrosine Phosphorylation1 (2009)

Protein tyrosine kinases have important roles in spermatozoa; however, little is known about the presence and regulation in these cells of their counterparts in signaling, namely, protein tyrosine phosphatases (PTPs) and dual-specificity phosphatases (DSPs). The objectives of the present study were to identify PTPs and DSPs in boar, stallion, and dog spermatozoa; to characterize their subcellular distribution; and to investigate the roles of tyrosine phosphatases in maintenance of protein tyrosine phosphorylation level and in sperm motility. Using Western blotting with specific antibodies in boar and stallion sperm lysates, we unequivocally identified two PTPs (PTPRB and PTPN11) and two DSPs (DUSP3 and DUSP4). In dog sperm lysates, only PTPN11, DUSP3, and DUSP4 were detected. In all these species, we did not detect the specific signal with anti-PTPRC (CD45), CDKN3, DUSP1, DUSP2, DUSP6, DUSP9, PTPN1, PTPN3, PTPN6, PTPN7, PTPN13, PTPRA, PTPRG, PTPRJ, PTPRK, or PTPRZ antibodies. Positive matches were further investigated by indirect immunofluorescence and confocal microscopy. Results showed that PTPRB was associated with the plasma membrane in the head and tail of boar and stallion spermatozoa. In agreement with Western blotting results, PTPRB antibodies did not show immunoreactivity in dog sperm analyzed by immunofluorescence. In the three species, DUSP4 was mainly found in the tail of spermatozoa, with little or no immunoreactivity in the head. PTPN11 was mainly located in the postacrosomal region in the head, whereas DUSP3 immunoreactivity was extended within the acrosome. PTPN11 and DUSP3 showed immunoreactivity in the tail that was restricted to the midpiece. Finally, we incubated boar, stallion, and dog spermatozoa with pervanadate and sodium orthovanadate, two PTP inhibitors, and analyzed overall protein tyrosine phosphorylation and assessed sperm motility. Sodium orthovanadate and pervanadate showed concentration-dependent inhibition of sperm motility that was rapid and reversible. Pervanadate also increased tyrosine phosphorylation of different proteins in capacitated and noncapacitated spermatozoa. Results showed that the phosphatases PTPN11, DUSP4, and DUSP3 are present in boar, stallion, and dog spermatozoa. PTPRB is also present in boar and stallion spermatozoa but was not detected in dog. The subcellular distribution of the identified phosphatases is diverse, suggesting that they likely have specific roles in sperm. Finally, PTP activity has a positive role in the regulation of motility and is involved in protein tyrosine phosphorylation in mammalian sperm.
Raman Spectroscopy of Hydrogen Molecules in Crystalline Silicon (1998)

We report on a Raman spectroscopy study of float-zone crystalline silicon after exposure to a hydrogen plasma. New lines measured at 3601 and $2622\mathrm{cm}{}^{\ensuremath{-}1}$ are attributed to vibrational excitations of ${\mathrm{H}}_{2}$ and ${\mathrm{D}}_{2}$ molecules, respectively, positioned at the tetrahedral interstitial site within the Si lattice. These results correct a recent identification of molecular hydrogen in Si and confirm recent calculations that the vibrational frequency of the ${\mathrm{H}}_{2}$ molecule in Si will be reduced by several hundred wave numbers from the known value for the ${\mathrm{H}}_{2}$ molecule in the gas state.
Single-Tube Genotyping without Oligonucleotide Probes (1999)

We report the development of a self-contained (homogeneous), single-tube assay for the genotyping of single-nucleotide polymorphisms (SNPs), which does not rely on fluorescent oligonucleotide probes. The method, which we call Tm-shift genotyping, combines allele-specific PCR with the discrimination between amplification products by their melting temperatures (Tm). Two distinct forward primers, each of which contains a 3'-terminal base that corresponds to one of the two SNP allelic variants, are combined with a common reverse primer in a single-tube reaction. A GC-tail is attached to one of the forward allele-specific primers to increase the Tm of the amplification product from the corresponding allele. PCR amplification, Tm analysis, and allele determination of genomic template DNA are carried out on a fluorescence-detecting thermocycler with a dye that fluoresces when bound to dsDNA. We demonstrate the accuracy and reliability of Tm-shift genotyping on 100 samples typed for two SNPs, and recommend it both as a simple and inexpensive diagnostic tool for genotyping medically relevant SNPs and as a high-throughput SNP genotyping method for gene mapping.
Translocation of Jellyfish Green Fluorescent Protein via the Tat System of Escherichia coli and Change of Its Periplasmic Localization in Response to Osmotic Up-shock (2001)

The bacterial twin arginine translocation (Tat) pathway is capable of exporting cofactor-containing enzymes into the periplasm. To assess the capacity of the Tat pathway to export heterologous proteins and to gain information about the property of the periplasm, we fused the twin arginine signal peptide of the trimethylamine N-oxide reductase to the jellyfish green fluorescent protein (GFP). Unlike the Sec pathway, the Tat system successfully exported correctly folded GFP into the periplasm of Escherichia coli. Interestingly, GFP appeared as a halo in most cells and occasionally showed a polar localization in wild type strains. When subjected to a mild osmotic up-shock, GFP relocalized very quickly at the two poles of the cells. The conversion from the halo structure to a periplasmic gathering at particular locations was also observed with spherical cells of the DeltarodA-pbpA mutant or of the wild type strain treated with lysozyme. Therefore, the periplasm is not a uniform compartment and the polarization of GFP is unlikely to be caused by simple invagination of the cytoplasmic membrane at the poles. Moreover, the polar gathering of GFP is reversible; the reversion was accelerated by glucose and inhibited by azide and carbonyl cyanide m-chlorophenylhydrazone, indicating an active adaptation of the bacteria to the osmolarity in the medium. These results strongly suggest a relocalization of periplasmic substances in response to environmental changes. The polar area might be the preferential zone where bacteria sense the change in the environment.
Wafer scale photonic-die attachment (2002)

A new low cost manufacturing system has been established for the attachment of photonic dies such as lasers and photodetectors. This system is based on wafer scale photonic-die bonding technology-WSPD, recently developed at AMP. WSPD technology combines the passive alignment of optical elements on a silicon or glass wafer board, and fluxless local soldering technology. The approach provides the capability of low cost, high volume (speed), high precision die attachment for hybrid integration of optoelectronic device packaging.
Purification and biologic characterization of plasma-derived megakaryocyte growth and development factor (1995)

The isolation and cloning of the ligand for the cytokine receptor, Mpl, have been recently described. In this report we present details of the purification of this novel cytokine (megakaryocyte growth and development factor [MGDF]) from aplastic canine plasma. Two forms of canine MGDF, with apparent molecular weights of 25 kD and 31 kD and sharing a common N-terminal amino acid sequence, were isolated. The sole contaminant detected in purified 25-kD or 31-kD MGDF was canine Ig. Canine MGDF is characterized as a human megakaryocyte colony-stimulating factor that acts synergistically with human recombinant stem cell factor but not interleukin-3. MGDF also appears to be physiologically regulated in response to platelet demand. In canine and murine models, serum levels of MGDF activity peak during the thrombocytopenic periods after irradiation, 5-fluorouracil, or antiplatelet antisera injections. These data indicate that the megakaryocyte-stimulating activity that accumulates in plasma in response to platelet losses is a novel cytokine that functions through an interaction with the Mpl cytokine receptor.
The prognostic impact of minimal residual disease in patients with chronic lymphocytic leukemia requiring first-line therapy (2014)

A proportion of patients with chronic lymphocytic leukemia achieve a minimal residual disease negative status after therapy. We retrospectively evaluated the impact of minimal residual disease on the outcome of 255 consecutive patients receiving any front-line therapy in the context of a detailed prognostic evaluation, including assessment of IGHV, TP53, NOTCH1 and SF3B1 mutations. The median follow-up was 73 months (range, 2-202) from disease evaluation. The median treatment-free survival durations for patients achieving a complete response without or with minimal residual disease, a partial response and no response were 76, 40, 11 and 11 months, respectively (P<0.001). Multivariate analysis revealed that three variables had a significant impact on treatment-free survival: minimal residual disease (P<0.001), IGHV status (P<0.001) and β2-microglobulin levels (P=0.012). With regards to overall survival, factors predictive of an unfavorable outcome were minimal residual disease positivity (P=0.014), together with advanced age (P<0.001), unmutated IGHV status (P=0.001), TP53 mutations (P<0.001) and elevated levels of β2-microglobulin (P=0.003). In conclusion, for patients requiring front-line therapy, achievement of minimal residual disease negativity is associated with significantly prolonged treatment-free and overall survival irrespective of other prognostic markers or treatment administered.
The Biology of Monocytes and Dendritic Cells: Contribution to HIV Pathogenesis (2018)

Myeloid cells such as monocytes, dendritic cells (DC) and macrophages (MΦ) are key components of the innate immune system contributing to the maintenance of tissue homeostasis and the development/resolution of immune responses to pathogens. Monocytes and DC, circulating in the blood or infiltrating various lymphoid and non-lymphoid tissues, are derived from distinct bone marrow precursors and are typically short lived. Conversely, recent studies revealed that subsets of tissue resident MΦ are long-lived as they originate from embryonic/fetal precursors that have the ability to self-renew during the life of an individual. Pathogens such as the human immunodeficiency virus type 1 (HIV-1) highjack the functions of myeloid cells for viral replication (e.g., MΦ) or distal dissemination and cell-to-cell transmission (e.g., DC). Although the long-term persistence of HIV reservoirs in CD4+ T-cells during viral suppressive antiretroviral therapy (ART) is well documented, the ability of myeloid cells to harbor replication competent viral reservoirs is still a matter of debate. This review summarizes the current knowledge on the biology of monocytes and DC during homeostasis and in the context of HIV-1 infection and highlights the importance of future studies on long-lived resident MΦ to HIV persistence in ART-treated patients.
A Quantitative Proteomics Design for Systematic Identification of Protease Cleavage Events (2010)

We present here a novel proteomics design for systematic identification of protease cleavage events by quantitative N-terminal proteomics, circumventing the need for time-consuming manual validation. We bypass the singleton detection problem of protease-generated neo-N-terminal peptides by introducing differential isotopic proteome labeling such that these substrate reporter peptides are readily distinguished from all other N-terminal peptides. Our approach was validated using the canonical human caspase-3 protease and further applied to mouse cathepsin D and E substrate processing in a mouse dendritic cell proteome, identifying the largest set of protein protease substrates ever reported and gaining novel insight into substrate specificity differences of these cathepsins.
Regulation of Apoptosis by a Prostate-Specific and Prostate Cancer-Associated Noncoding Gene, PCGEM1 (2006)

PCGEM1 is a prostate tissue-specific, and prostate cancer-associated noncoding RNA (ncRNA) gene. Previous results revealed a significant association of elevated PCGEM1 expression levels in prostate cancer cells of African-American patients, whose mortality rate is the highest among prostate cancer patients. Functional study of PCGEM1 demonstrated a marked increase in colony formation in LNCaP prostate cancer cells and NIH3T3 mouse fibroblast cells. This study demonstrates that PCGEM1 overexpression in LNCaP cell culture model results in the inhibition of apoptosis induced by doxorubicin (DOX). Induction of p53 and p21(Waf1/Cip1) by DOX were delayed in LNCaP cells stably overexpressing PCGEM1 (LNCaP-PCGEM1 cells) compared to control LNCaP cells. The protein levels of cleaved caspase 7, and cleaved PARP were attenuated in DOXtreated LNCaP-PCGEM1 cells compared to control LNCaP cells. Similar results were observed in LNCaP cells transiently overexpressing PCGEM1. The inhibition of PARP cleavage by PCGEM1 overexpression was also observed in LNCaP-PCGEM1 cells incubated with etoposide and sodium selenite. Fluorescence-Activated Cell Sorter Annexin-V analysis revealed significantly lower percentage of apoptotic cells in DOX-treated LNCaP-PCGEM1 cells compared to control LNCaP cells. The attenuation of apoptic response appears to be androgen dependent in this experimental model, as androgen-independent variants of LNCaP cells did not exhibit this response. In summary, this study provides new insights into cell biologic functions and novel features of an ncRNA. Further, these data unravel biological mechanisms of cell growth/cell survival-associated functions of this ncRNA in a widely used prostate cancer cell culture model.
High fidelity DNA synthesis by theThermus aquaticusDNA polymerase (1990)

We demonstrate that despite lacking a 3'----5' proofreading exonuclease, the Thermus aquaticus (Taq) DNA polymerase can catalyze highly accurate DNA synthesis in vitro. Under defined reaction conditions, the error rate per nucleotide polymerized at 70 degrees C can be as low as 10(-5) for base substitution errors and 10(-6) for frameshift errors. The frequency of mutations produced during a single round of DNA synthesis of the lac Z alpha gene by Taq polymerase responds to changes in dNTP concentration, pH, and the concentration of MgCl2 relative to the total concentration of deoxynucleotide triphosphates present in the reaction. Both base substitution and frameshift error rates of less than 1/100,000 were observed at pH 5-6 (70 degrees C) or when MgCl2 and deoxynucleotide triphosphates were present at equimolar concentrations. These high fidelity reaction conditions for DNA synthesis by the Taq polymerase may be useful for specialized uses of DNA amplified by the polymerase chain reaction.