gebhart/patrepeval huggingface dataset:
Curcumin inhibits colon cancer malignant progression and promotes T cell killing by regulating miR‐206 expression (2023)

Colon cancer is a great threat to human health. Curcumin, as a traditional Chinese medicine extract with anti-tumor and anti-inflammatory effects, can affect the development of diverse human diseases including cancer. The aim of this research was to probe the mechanism by which curcumin regulates colon cancer progression. Colon cancer cells were processed with graded concentrations of curcumin. The proliferation and apoptosis of the treated cells were determined by MTT, colony formation assay and flow cytometry. Expression of signaling pathway-related proteins and programmed death-ligand 1 (PD-L1) was measured by western blotting. The effect of curcumin on tumor cell growth was verified through T cell-mediated killing and ELISA assays. The relationship between target gene expression and the survival rate of colon cancer patients was analyzed by a survival curve. Curcumin treatment restrained proliferation and accelerated apoptosis of colon cancer cells. It elevated miR-206 expression, which in turn affected colon cancer cell function. miR-206 enhanced colon cancer cell apoptosis and inhibited PD-L1 expression; thus, curcumin enhanced the killing effect of T cells on tumor cells by suppressing PD-L1 through inhibiting the JAK/STAT3 pathway. Patients with high expression of miR-206 had better survival rates than those with low expression. Curcumin can regulate miR-206 expression and inhibit the malignant behavior of colon cancer cells and enhance T cell killing through the JAK/STAT3 pathway.
Gastrin-amidating enzyme in the porcine pituitary and antrum. Characterization of molecular forms and substrate specificity. (1991)

As is the case with many other peptide hormones of the brain and intestine, the formation of biologically active gastrin from a glycine-extended processing intermediate occurs via the action of a peptidylglycyl alpha-amidating monooxygenase (PAM). The observation that gastrin exists primarily as unamidated precursors in the pituitary but as amidated gastrin in the antrum prompted this study to examine whether the amidating enzymes in the two organs were different in their characteristics. Amidating activity was quantified by measuring the conversion of glycine-extended tridecagastrin (G13-Gly) to amidated tridecagastrin and glycine-extended hexapancreatic polypeptide (PP6-Gly) to amidated hexapancreatic polypeptide by radio-immunoassay. Two molecular forms of amidating activity were identified in both the porcine antrum and pituitary. The first, PAM-A, had an apparent Mr of 51,000 and a net negative charge at pH 7.0, whereas PAM-B was smaller (Mr approximately 30,000) and had a net positive charge at pH 7.0. Both molecular forms were similar in their cofactor requirements (copper, ascorbic acid, and catalase) and pH optima in the antrum and pituitary. The Km was significantly lower and the Vmax higher for PP6-Gly than for G13-Gly in the pituitary and antrum. These data suggest that although there is no difference between antral and pituitary PAM, the selective affinity of PAM for certain substrates may provide a mechanism for the differential amidation of different hormones within a given tissue or cell.
Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a phase II double-blinded, randomized, dose-escalating trial (2002)

CDP870 is effective, was very well tolerated in this small study, and has an extended duration of action following one or more intravenous doses.
A Single Tyrosine Residue in the Membrane-proximal Domain of the Granulocyte-Macrophage Colony-stimulating Factor, Interleukin (IL)-3, and IL-5 Receptor Common β-Chain Is Necessary and Sufficient for High Affinity Binding and Signaling by All Three Ligands (1996)

The beta-chain of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and interleukin-5 (IL-5) receptors functions as a communal receptor subunit and is often referred to as beta common (betac). Analogous to other shared receptor subunits including gp130 and the IL-2R gamma chain, betac mediates high affinity binding and signal transduction of all of its ligands. It is not clear, however, how these common receptor subunits can recognize several ligands and indeed whether they exhibit a common binding pocket to accomplish this. We have performed molecular modeling of betac based on the known structures of the growth hormone and prolactin receptors and targeted the putative F'-G' loop for mutagenesis. Substitution of this whole predicted loop region with alanines completely abrogated high affinity binding of GM-CSF, IL-3, and IL-5. Individual alanine substitutions across the loop revealed that a single residue, Tyr421, is critical for high affinity binding of GM-CSF, IL-3, and IL-5, whereas alanine substitution of adjacent residues has little or no effect on high affinity binding. Significantly, reintroducing Tyr421 into the polyalanine-substituted mutant restored high affinity ligand binding of GM-CSF, IL-3, and IL-5, indicating that within this region the tyrosine residue alone is sufficient for high affinity ligand interaction. Functional studies measuring STAT5 activation revealed that alanine substitution of Tyr421 severely impaired the ability of betac to signal. These results show for the first time that a single residue in a shared receptor subunit acts as a binding determinant for different ligands and may have implications for other receptor systems where communal receptor subunits exhibit hydrophobic residues in their putative F'-G' loops. These results also raise the possibility that a single compound targeted to this region may simultaneously inhibit the binding and function of multiple cytokines.
Small‐Molecule End‐Groups of Linear Polymer Determine Cell‐type Gene‐Delivery Efficacy (2009)

End-modified polymers are promising for the nonviral delivery of genes to cancer cells, immune cells, and human stem cells and point to polymer end-groups as regulators for cell-type specificity. A library of polymers has been synthesized and, although some polymers are strong transfection agents overall, for each cell type, a particular polymer is most effective.
High-efficiency solution-processed perovskite solar cells with millimeter-scale grains (2015)

State-of-the-art photovoltaics use high-purity, large-area, wafer-scale single-crystalline semiconductors grown by sophisticated, high-temperature crystal growth processes. We demonstrate a solution-based hot-casting technique to grow continuous, pinhole-free thin films of organometallic perovskites with millimeter-scale crystalline grains. We fabricated planar solar cells with efficiencies approaching 18%, with little cell-to-cell variability. The devices show hysteresis-free photovoltaic response, which had been a fundamental bottleneck for the stable operation of perovskite devices. Characterization and modeling attribute the improved performance to reduced bulk defects and improved charge carrier mobility in large-grain devices. We anticipate that this technique will lead the field toward synthesis of wafer-scale crystalline perovskites, necessary for the fabrication of high-efficiency solar cells, and will be applicable to several other material systems plagued by polydispersity, defects, and grain boundary recombination in solution-processed thin films.
VLSI implementation issues of TURBO decoder design for wireless applications (2003)

Finite precision effects on the performance of TURBO decoders have been analyzed and the optimal word lengths of variables have been determined considering tradeoffs between the performance and the hardware cost. It is shown that the performance degradation from the infinite precision is negligible if 4 bits are used for received bits and 6 bits for the extrinsic information. The state metrics normalization method suitable for TURBO decoders is also discussed. This method requires small amount of hardware and its speed does not depend on the number of states. Furthermore, we propose novel power-down techniques, which can achieve very high power-down efficiency without performance or latency degradation at the expense of negligible hardware overhead.
Expression and Function of the Chemokine Receptors CXCR1 and CXCR2 in Sepsis (1999)

Neutrophils (polymorphonuclear neutrophils; PMN) and a redundant system of chemotactic cytokines (chemokines) have been implicated in the pathogenesis of the acute respiratory distress syndrome in patients with sepsis. PMN express two cell surface receptors for the CXC chemokines, CXCR1 and CXCR2. We investigated the expression and function of these receptors in patients with severe sepsis. Compared with normal donors, CXCR2 surface expression was down-regulated by 50% on PMN from septic patients (p < 0.005), while CXCR1 expression persisted. In vitro migratory responses to the CXCR1 ligand, IL-8, were similar in PMN from septic patients and normal donors. By contrast, the migratory response to the CXCR2 ligands, epithelial cell-derived neutrophil activator (ENA-78) and the growth-related oncogene proteins, was markedly suppressed in PMN from septic patients (p < 0.05). Ab specific for CXCR1 blocked in vitro migration of PMN from septic patients to IL-8 (p < 0.05), but not to FMLP. Thus, functionally significant down-regulation of CXCR2 occurs on PMN in septic patients. We conclude that in a complex milieu of multiple CXC chemokines, CXCR1 functions as the single dominant CXC chemokine receptor in patients with sepsis. These observations offer a potential strategy for attenuating adverse inflammation in sepsis while preserving host defenses mediated by bacteria-derived peptides such as FMLP.
Cyclooxygenase 2- and prostaglandin E(2) receptor EP(2)-dependent angiogenesis in Apc(Delta716) mouse intestinal polyps. (2002)

To investigate angiogenesis during intestinal polyp development, we determined the microvessel density (MVD) in polyps of Apc knockout (Apc(Delta716)) mice, a model for human familial adenomatous polyposis. We scored MVD also in several compound mutants carrying Apc(Delta716), namely, mice with an additional mutation in Smad4, in which the polyps progress into invasive adenocarcinomas; mice with a cyclooxygenase (COX)-2 gene (Ptgs2) mutation, in which adenoma growth is suppressed; and mice with prostaglandin E(2) EP receptor gene mutations. In both simple Apc(Delta716) and compound Apc(Delta716) Smad4 mutants, MVD increased in a polyp size-dependent manner only in the polyps expanded beyond a threshold of about 1 mm in diameter. These results indicate that tumor angiogenesis is stimulated only after tumors grow to a certain size, and this angiogenic switch is common to both benign adenomas and malignant adenocarcinomas. In Apc(Delta716) polyposis attenuated by the COX-2 gene mutation, in contrast, MVD did not increase even in polyps larger than 1 mm. The same phenomenon was observed in the compound mutant mice with Apc(Delta716) and the EP(2) receptor gene mutations, but not in other EP compound mutants. We also immunohistochemically studied COX-2 and angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor. Interestingly, expression of these proteins was also increased in polyps larger than 1 mm. These results suggest that, in both benign and malignant mouse intestinal tumors, stromal expression of COX-2 results in elevated prostaglandin E(2) levels that stimulate cell surface receptor EP(2), followed by induction of vascular endothelial growth factor that causes tumor angiogenesis.
A dynamic QoS control based on optimistic processor reservation (2002)

The paper proposes a dynamic QOS control scheme using a processor reservation system. In our scheme, a system allocates processor capacity for each application, then the application increases or decreases the current resource usage by using a feedback mechanism. This scheme allows the application to reserve resources optimistically. This means that a system can allocate all processor resources to respective applications every time. Our approach makes it easy to build a continuous media application with a dynamic QOS control scheme, and allocates processor capacity very efficiently without unexpected degradation of a media stream's quality.
Inhibition of vascular smooth muscle cell proliferation by ribozymes that cleave c-myb mRNA. (1996)

Proliferation of injured smooth muscle cells contributes to the reocclusion or restenosis of coronary arteries that often occurs following angioplasty procedures. We have identified and optimized nuclease-resistant ribozymes that efficiently cleave c-myb RNA. Three ribozymes targeting different sites in the c-myb mRNA were synthesized chemically and delivered to rat aortic smooth muscle cells with cationic lipids; all three inhibited serum-stimulated cell proliferation significantly. RNA molecules with two base substitutions in the catalytic core that render the ribozyme catalytically inactive had little effect on smooth muscle cell proliferation. Ribozymes with scrambled binding arm sequences also failed to affect cell cycle progression of vascular smooth muscle cells. Furthermore, inhibition of rat smooth muscle cell proliferation correlated with a reduction in intact c-myb mRNA. Efficacy of the chemically-modified ribozyme was compared directly to phosphorothioate antisense oligodeoxynucleotides targeting the same site in the c-myb RNA; the ribozyme had superior efficacy and showed greater specificity than the antisense molecules. Exogenously delivered ribozymes also inhibited porcine and human smooth muscle cell proliferation effectively. Ribozymes targeting c-myb or other regulators of smooth muscle cell proliferation may represent novel therapeutics for the treatment of restenosis after coronary angioplasty.
Isolation and Characterization of Umbilical Cord Blood-Derived Multipotent Stem Cells Arising from Adherent CD45+/CD34+ Cell Subset. (2005)

Abstract Introduction: Using a cell separation medium (PrepaCyte-MLPC, BioE, Inc.) and plastic adherence, umbilical cord blood (UCB)-derived multipotent stem cells were isolated, expanded, and characterized. These stem cells, termed multi-lineage progenitor cells (MLPCs), are the only such cell type from any source demonstrated to be CD45+/CD34+ upon initial isolation. Methods: PrepaCyte-MLPC, an antibody-based cell separation medium, is added to an UCB unit (American Red Cross Cord Blood Program). Following homo- and heterophilic aggregation of undesired cell populations and subsequent sedimentation to gravity, the supernatant containing stem cells is expressed. After overnight incubation in a T-flask in MSCGM (Cambrex, Inc.), non-adherent cells are washed, leaving adherent cells to expand in culture. As MLPC colonies are observed, cells are further enriched by detachment (PBS/0.1% EGTA) and transfer to a new T-flask. Results: MLPCs were isolated and expanded from 3 of 10 UCB units. Cells were initially positive for CD45, CD34, CD133, SSEA-3, SSEA-4, and several MSC markers. Several days into culture, expression of HSC/ESC markers was lost. MSC marker expression was maintained; cells remain positive for CD9, CD13, CD29, CD44, CD73, CD90, and CD105. These MLPC lines have been cultured through at least 16 passages with no apparent impact on expansion or differentiation potential. Cell lines have been successfully differentiated into cell types representative of each embryonic layer (i.e., adipocytes, osteocytes, myocytes, hepatocytes, and endothelial and neural cells). Additional experiments and limited-dilution cloning are underway, and further studies (cytogentic/molecular and animal teratoma studies) are planned. Conclusions: UCB-derived MLPCs were isolated as a rare population of adherent, initially CD45+/CD34+ cells with lymphoid morphology. Following successful expansion in culture, multi-potency was demonstrated. MLPCs may serve a role in bone marrow transplantation (for malignant and non-malignant disease) and regenerative medicine; clinical studies are in an early phase of development.
A full fill-factor CCD imager with integrated signal processors (1990)

A (64*64) imager that combines simple charge-domain analog signal processors in a parallel, pipelined architecture to realize an integrated signal processor that performs a simple edge detection algorithm in real time is described. With a serial output clock rate of 10 MHz, the signal processor is capable of 1000-frames/s operation. This signal-processing capability is implemented with standard CMOS technology without decreasing the fill factor of the imager, without significantly increasing power dissipation, and with only a 15 % increase in chip area. As a column of image pixel data is shifted simultaneously, local interactions between neighboring column elements are directly performed in parallel. As row values are sequentially clocked through the processor local interactions between neighboring row elements are similarly performed by delay elements. This architecture is able to implement efficiently linear convolutions that are separable and recursively defined. It is also suitable for certain types of nonlinear filtering operations that perform image segmentation a basic machine vision task.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Pro-neurotrophins secreted from retinal ganglion cell axons are necessary for ephrinA-p75NTR-mediated axon guidance (2010)

This indicates that retinal cells secrete proneurotrophins, inducing the ephrinA-p75NTR interaction and enabling repellent axon guidance. The antagonistic functions of proBDNF and BDNF raise the possibility that topographic branching is controlled by local control of processing of proneurotrophins.
Dendrimers: From Design to Application—A Progress Report (1999)

A unique combination of a clearly defined particle structure and a very highly functionalized surface is offered by the topical dendrimers. Many groups work on this unusual molecular architecture to develop new applications. The most advanced progress in this respect is an MRI contrast agent based on dendrimers (see schematic representation) that facilitate the visualization of bloodstreams.
Phase I and II studies of the combination of recombinant human interferon-gamma and 5-fluorouracil in patients with advanced colorectal carcinoma. (1989)

Based on the in vitro and in vivo data suggesting synergistic cytolysis by the combination of 5-fluorouracil and interferon-gamma against a variety of malignant cell lines including a human colon carcinoma cell line (HT-29), we initiated studies in patients with advanced colon or rectal carcinoma. Forty-six patients received 5-fluorouracil as an intravenous injection on days 1-5 and recombinant human interferon-gamma as an intramuscular injection on days 1-14, followed by a rest period of 14 days; courses were repeated every 28 days. In the phase I study, cohorts of two patients received a stepwise dose level increase to achieve the maximum tolerated dose (MTD), at which a total of six patients were studied. The dose levels constituting the MTD were as follows: 5-fluorouracil (500 g/m2/day) and recombinant gamma-interferon (0.5 mg/m2/day). Four patients achieved a partial response in the phase I study. In the phase II study, 30 patients received therapy at the MTD. Among 29 evaluable patients in the phase II study, two patients achieved a partial response. Common toxicities included malaise, fever, anorexia, nausea and vomiting, and diarrhea. Transient severe myelosuppression was common but did not result in significant morbidity. Our data suggest that the combination of 5-fluorouracil and recombinant gamma-interferon did not have the same antitumor effect in patients as it had in the preclinical experiments.
Role of DNA Ligase in the Illegitimate Recombination That Generates λbio-Transducing Phages in Escherichia coli (2001)

We studied the role of DNA ligase in illegitimate recombination in Escherichia coli. A temperature-sensitive mutation in the lig gene reduced the frequency with which lambdabio-transducing phages were generated to 10-14% of that of wild type under UV irradiation. Reintroduction of the lig gene into this mutant restored the frequency of recombinant phage generation to that of wild type. Furthermore, overexpression of DNA ligase enhanced illegitimate recombination by 10-fold with or without UV irradiation. In addition, when DNA ligase was present in only limited amounts, UV-induced or spontaneous illegitimate recombination occurred exclusively at hotspot sites that have relatively long sequences of homology (9 or 13 bp). However, when DNA ligase was overexpressed, most of the illegitimate recombination took place at non-hotspot sites having only short sequences of homology (<4 bp). Thus, the level of ligase activity affects the frequency of illegitimate recombination, the length of sequence homology at the recombination sites, and the preference for recombination at hotspots, at least after UV irradiation. These observations support our hypothesis that the illegitimate recombination that generates lambdabio-transducing phages is mediated by the DNA break-and-join mechanism.
Serial Intravascular Ultrasound Assessment of the Efficacy of Intracoronary γ-Radiation Therapy for Preventing Recurrence in Very Long, Diffuse, In-Stent Restenosis Lesions (2001)

- Serial IVUS analysis shows that gamma-irradiation reduces recurrent in-stent neointimal hyperplasia in long, diffuse ISR lesions; however, it is even more effective when given at a higher dose.
The Pathophysiology of IgA Nephropathy (2011)

Here we discuss recent advances in understanding the biochemical, immunologic, and genetic pathogenesis of IgA nephropathy, the most common primary glomerulonephritis. Current data indicate that at least four processes contribute to development of IgA nephropathy. Patients with IgA nephropathy often have a genetically determined increase in circulating levels of IgA1 with galactose-deficient O-glycans in the hinge-region (Hit 1). This glycosylation aberrancy is, however, not sufficient to induce renal injury. Synthesis and binding of antibodies directed against galactose-deficient IgA1 are required for formation of immune complexes that accumulate in the glomerular mesangium (Hits 2 and 3). These immune complexes activate mesangial cells, inducing proliferation and secretion of extracellular matrix, cytokines, and chemokines, which result in renal injury (Hit 4). Recent genome-wide association studies identify five distinct susceptibility loci--in the MHC on chromosome 6p21, the complement factor H locus on chromosome 1q32, and in a cluster of genes on chromosome 22q22--that potentially influence these processes and contain candidate mediators of disease. The significant variation in prevalence of risk alleles among different populations may also explain some of the sizable geographic variation in disease prevalence. Elucidation of the pathogenesis of IgA nephropathy provides an opportunity to develop disease-specific therapies.