gebhart/patrepeval huggingface dataset:
Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor (2002)

We investigated the role of the CXCR4 chemokine receptor in development of the mouse hippocampus. CXCR4 mRNA is expressed at sites of neuronal and progenitor cell migration in the hippocampus at late embryonic and early postnatal ages. mRNA for stromal cell-derived factor 1 (SDF-1), the only known ligand for the CXCR4 receptor, is expressed close to these migration sites, in the meninges investing the hippocampal primordium and the primordium itself. In mice engineered to lack the CXCR4 receptor, the morphology of the hippocampal dentate gyrus (DG) is dramatically altered. Gene expression markers for DG granule neurons and bromodeoxyuridine labeling of dividing cells revealed an underlying defect in the stream of postmitotic cells and secondary dentate progenitor cells that migrate toward and form the DG. In the absence of CXCR4, the number of dividing cells in the migratory stream and in the DG itself is reduced, and neurons appear to differentiate prematurely before reaching their target. Our findings indicate a role for the SDF-1/CXCR4 chemokine signaling system in DG morphogenesis. Finally, the DG is unusual as a site of adult neurogenesis. We find that both CXCR4 and SDF-1 are expressed in the adult DG, suggesting an ongoing role in DG morphogenesis.
c‐myc amplification is an independent prognostic factor in postmenopausal breast cancer (1992)

The c-myc proto-oncogene was analyzed in 311 cases of primary breast cancer, in 8% of which it was found to be amplified, usually at moderately increased copy number (2-5 copies). The adjacent pvt gene was co-amplified with c-myc in all tumors analyzed. C-myc amplification was significantly correlated to a high S-phase fraction and to amplification of the c-erbB-2 proto-oncogene. Weak relationships were found between c-myc amplification and the presence of lymph-node metastasis, advanced stage, DNA non-diploidy and premenopausal status, but not tumor size, estrogen receptor or progesterone receptor status, or int-2 amplification. C-myc amplification, and especially a high gene copy number (greater than 5 copies), was significantly related to early recurrence and death in breast cancer, a relationship seen in both the lymph-node-negative and node-positive subcategories. A particularly strong correlation with poor clinical outcome was seen in postmenopausal patients (p greater than 0.0005), an association which persisted in multivariate survival analysis. We conclude that the activation of c-myc is indeed associated with rapidly growing and progressive breast cancer. Gene amplification, on the other hand, is relatively infrequent and occurs mostly at low copy number, implying that tumors are heterogeneous with respect to cell clones harboring c-myc amplification. An immunohistochemical assessment would more accurately illustrate the importance of c-myc activation in human breast cancer. However, the obvious instability of the c-myc transcript and translate suggests that c-myc is not a suitable prognostic marker for routine purposes.
Electrostatic Spraying:  A Novel Technique for Preparation of Polymer Coatings on Electrodes (1996)

A liquid flow emerging from a tip or a thin tube under the influence of a strong electric field will, due to charging of the dielectric liquid, break up into small droplets. Thus, if a polymer material is dissolved in the liquid, this electrodeposition technique can be utilized for producing polymer coatings on electrodes. The method was applied for in situ formation of ultrathin (∼3000 Å) cellulose acetate (CA) phase inversion membranes on glassy carbon electrodes. The purpose of the membrane was to protect the electrode surface from fouling by macromolecular species. The spraying liquid consisted of CA, acetone, and aqueous magnesium perchlorate as pore former, and the spraying voltage was 14 kV. Profilometric measurements showed that the thickness of the spray-cast membranes was much more uniform than that of similar membranes formed by solvent casting. By using cadmium and lead as test analytes and differential pulse anodic stripping voltammetry as detection method, it was found that the membranes prepared by spray casting offered better protection against interference from poly(ethylene glycol) (PEG) 6000 than those prepared by solvent casting. Also, the interference from PEG 2000 was significantly reduced. Experimental details of the electrostatic spraying technique are given.
Effect of Recombinant α1-Antitrypsin Fc-Fused (AAT-Fc) Protein on the Inhibition of Inflammatory Cytokine Production and Streptozotocin-Induced Diabetes (2013)

α1-Antitrypsin (AAT) is a member of the serine proteinase inhibitor family that impedes the enzymatic activity of serine proteinases, including human neutrophil elastase, cathepsin G and neutrophil proteinase 3. Here, we expressed recombinant AAT by fusing the intact AAT gene to the constant region of IgG1 to generate soluble recombinant AAT-Fc protein. The recombinant AAT-Fc protein was produced in Chinese hamster ovary (CHO) cells and purified using mini-protein A affinity chromatography. Recombinant AAT-Fc protein was tested for antiinflammatory function and AAT-Fc sufficiently suppressed tumor necrosis factor (TNF)-α-induced interleukin (IL)-6 in human peripheral blood mononuclear cells (PBMCs) and inhibited cytokine-induced TNFα by different cytokines in mouse macrophage Raw 264.7 cells. However, AAT-Fc failed to suppress lipopolysaccharide-induced cytokine production in both PBMCs and macrophages. In addition, our data showed that AAT-Fc blocks the development of hyperglycemia in a streptozotocin-induced mouse model of diabetes. Interestingly, we also found that plasma-derived AAT specifically inhibited the enzymatic activity of elastase but that AAT-Fc had no inhibitory effect on elastase activity.
Regulation of Immune Responses by Prostaglandin E2 (2011)

PGE(2), an essential homeostatic factor, is also a key mediator of immunopathology in chronic infections and cancer. The impact of PGE(2) reflects the balance between its cyclooxygenase 2-regulated synthesis and 15-hydroxyprostaglandin dehydrogenase-driven degradation and the pattern of expression of PGE(2) receptors. PGE(2) enhances its own production but suppresses acute inflammatory mediators, resulting in its predominance at late/chronic stages of immunity. PGE(2) supports activation of dendritic cells but suppresses their ability to attract naive, memory, and effector T cells. PGE(2) selectively suppresses effector functions of macrophages and neutrophils and the Th1-, CTL-, and NK cell-mediated type 1 immunity, but it promotes Th2, Th17, and regulatory T cell responses. PGE(2) modulates chemokine production, inhibiting the attraction of proinflammatory cells while enhancing local accumulation of regulatory T cells cells and myeloid-derived suppressor cells. Targeting the production, degradation, and responsiveness to PGE(2) provides tools to modulate the patterns of immunity in a wide range of diseases, from autoimmunity to cancer.
CC chemokines induce the generation of killer cells from CD56+ cells (1996)

We describe here that members of the CC chemokines exhibit biological activities other than chemotaxis. Macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, monocyte chemoattractant protein-1 and RANTES, but not interleukin (IL)-8, induce the generation of cytolytic cells, designated here as CHAK (CC chemokine-activated killer) cells to distinguish them from IL-2-activated (LAK) cells. Like IL-2, CC chemokines can induce the proliferation and activation of killer cells. While incubating CC chemokines with CD4+ or CD8+ cells did not generate CHAK activity, all CC chemokines were capable of inducing CHAK activity upon incubating with CD56+ cells, suggesting that the primary effectors are NK cells. However, the presence of other cell types, such as CD4+ or CD8+, are necessary to induce the proliferation of CD56+ cells. Confirming the involvement of T cell-derived factors in inducing the proliferation of these cells, anti-IL-2 and anti-interferon-gamma, but not anti-IL-1 beta, anti-tumor necrosis factor-alpha, anti-IL-8, or anti-granulocyte/monocyte-colony-stimulating factor inhibited RANTES-induced proliferation of nylon wool column-nonadherent cells. Our results may have important clinical applications for the utilization of CHAK cells in the treatment of cancer and immunodeficient patients.
Generalized just-in-time trace compilation using a parallel task farm in a dynamic binary translator (2011)

Dynamic Binary Translation (DBT) is the key technology behind cross-platform virtualization and allows software compiled for one Instruction Set Architecture (ISA) to be executed on a processor supporting a different ISA. Under the hood, DBT is typically implemented using Just-In-Time (JIT) compilation of frequently executed program regions, also called traces . The main challenge is translating frequently executed program regions as fast as possible into highly efficient native code. As time for JIT compilation adds to the overall execution time, the JIT compiler is often decoupled and operates in a separate thread independent from the main simulation loop to reduce the overhead of JIT compilation. In this paper we present two innovative contributions. The first contribution is a generalized trace compilation approach that considers all frequently executed paths in a program for JIT compilation, as opposed to previous approaches where trace compilation is restricted to paths through loops. The second contribution reduces JIT compilation cost by compiling several hot traces in a concurrent task farm. Altogether we combine generalized light-weight tracing, large translation units, parallel JIT compilation and dynamic work scheduling to ensure timely and efficient processing of hot traces. We have evaluated our industry-strength, LLVM-based parallel DBT implementing the ARCompact ISA against three benchmark suites (EEMBC, BioPerf and SPEC CPU2006) and demonstrate speedups of up to 2.08 on a standard quad-core Intel Xeon machine. Across short- and long-running benchmarks our scheme is robust and never results in a slowdown. In fact, using four processors total execution time can be reduced by on average 11.5% over state-of-the-art decoupled, parallel (or asynchronous ) JIT compilation.
beta-Amyloid toxicity in organotypic hippocampal cultures: protection by EUK-8, a synthetic catalytic free radical scavenger. (1996)

Oxygen free radicals have been proposed to mediate amyloid peptide (beta-AP)-induced neurotoxicity. To test this hypothesis, we evaluated the effects of EUK-8, a synthetic catalytic superoxide and hydrogen peroxide scavenger, on neuronal injury produced by beta-AP in organotypic hippocampal slice cultures. Cultures of equivalent postnatal day 35 (defined as mature) and 14 (defined as immature) were exposed to various concentrations of beta-AP (1-42 or 1-40) in the absence or presence of 25 microM EUK-8 for up to 72 hours. Neuronal injury was assessed by lactate dehydrogenase release and semiquantitative analysis of propidium iodide uptake at various times after the initiation of beta-AP exposure. Free radical production was inferred from the relative increase in dichlorofluorescein fluorescence, and the degree of lipid peroxidation was determined by assaying thiobarbituric acid-reactive substances. Treatment of mature cultures with beta-AP (50-250 microg/ml) in serum-free conditions resulted in a reproducible pattern of damage, causing a time-dependent increase in neuronal injury accompanied with formation of reactive oxygen species. However, immature cultures were entirely resistant to beta-AP-induced neurotoxicity and also demonstrated no dichlorofluorescein fluorescence or increased lipid peroxidation after beta-AP treatment. Moreover, mature slices exposed to beta-AP in the presence of 25 microM EUK-8 were significantly protected from beta-AP-induced neurotoxicity. EUK-8 also completely blocked beta-AP-induced free radical accumulation and lipid peroxidation. These results not only support a role for oxygen free radicals in beta-AP toxicity but also highlight the therapeutic potential of synthetic radical scavengers in Alzheimer disease.
A benchmark of hemoglobin blocking during library preparation for mRNA-Sequencing of human blood samples (2020)

RNA-Sequencing (RNA-Seq) of peripheral blood can be a valuable source of information for investigating the status and mechanism of diseases. However, blood contains 50-80% unwanted hemoglobin (Hb) transcripts. Lexogen's QuantSeq mRNA-Seq-Kit for Illumina RNA-Seq features a 'Globin Block' (GB) module that depletes Hb cDNAs during library preparation. Here, we aimed to assess GB's effectiveness and checked for technical biases attributable to GB. Using whole blood total RNA samples of 91 healthy individuals, we sequenced 91 pairs of GB and non-blocked samples (noGB) on Illumina HiSeq2500 and 8 pairs of GB/noGB technical replicates on HiSeq4000. GB reduced the fraction of Hb transcripts from 43% (s.d. 14%) to 8.0% (s.d. 4.3%). From GB samples we detected 1,397 more expressed genes at approximately 11 million reads per RNA-isolate. Enrichment and differential expression analyses did not reveal significant differences for GB and noGB samples with respect to molecular function. In contrast to results from studies that have examined the performance of GB during RNA isolation, we were able to assign GB to corresponding noGB samples (from multiple sequencing runs on HiSeq2500) with at least 89.8% accuracy from the complete correlation matrix of all GB/GB, noGB/noGB and GB/noGB pairs. However, the use of different sequencers (HiSeq2500 vs HiSeq4000) impaired assignment of technical replicates, whereas assignment of GB to corresponding noGB samples worked perfectly when sequencing on one lane on HiSeq4000. Lexogen's GB RNA-Seq module is a valuable addition during mRNA-Seq library preparation which works even with low amounts of input total RNA (50 ng per sample). GB facilitated the detection of low abundant transcripts and yielded more non-hemoglobin reads, while preserving biological information. We observed that differences in sequencing run and platform have a far greater effect on technical variation than the use of GB.
Phase I trial of the chimeric anti-GD2 monoclonal antibody ch14.18 in patients with malignant melanoma (1992)

The chimeric monoclonal anti-GD2 antibody ch14.18 is made up of the variable region of the murine anti-GD2 antibody 14.18 (or its IgG2a switch variant 14G2a) and the constant region of human IgG1k. Ch14.18 mediates antibody dependent cytotoxicity and complement dependent lysis in vitro. In a phase I trial, 13 patients with metastatic melanoma received ch14.18 as a single dose of 5-100 mg. Therapy was associated with an infusion-related abdominal/pelvic pain syndrome, which required intravenous morphine for control. The pharmacokinetics of ch14.18 best fit a two-compartment model with a T1/2 alpha of 24 +/- 1 hr and a T1/2 beta of 181 +/- 73 hr. Eight of 13 patients developed a weak-modest antibody response directed at the variable region of ch14.18. Clinical antitumor responses were not observed at the doses employed in this study. However, patients receiving greater than 45 mg of ch14.18 had antibody detectable on tumor cells analyzed by fluorescent activated cell sorter. Further modification of the therapeutic regime employing larger doses and frequent administration of ch14.18 are planned.
Improvements in the Assessment of Bacterial Viability and Killing (2007)

Clinicians must maintain the principle of patient autonomy, ensure the viability of an appropriate informed consent process and facilitate surrogate judgment. An interdisciplinary team-based approach is required, and, in some cases, assisted by formal ethics consultations in vexing situations.
Tracking human face features in thermal images for respiration monitoring (2010)

A method has been developed to track a region related to respiration process in thermal images. The respiration region of interest (ROI) consisted of the skin area around the tip of the nose. The method was then used as part of a non-contact respiration rate monitoring that determined the skin temperature changes caused by respiration. The ROI was located by the first determining the relevant salient features of the human face physiology. These features were the warmest and coldest facial points. The tracking method was tested on thermal video images containing no head movements, small random and regular head movements. The method proved valuable for tracking the ROI in all these head movement types. It was also possible to use this tracking method to monitor respiration rate involving a number of head movement types. Currently, more investigations are underway to improve the tracking method so that it can track the ROI in cases larger head movements.
A simple and efficient estimator for hyperbolic location (1994)

An effective technique in locating a source based on intersections of hyperbolic curves defined by the time differences of arrival of a signal received at a number of sensors is proposed. The approach is noniterative and gives an explicit solution. It is an approximate realization of the maximum-likelihood estimator and is shown to attain the Cramer-Rao lower bound near the small error region. Comparisons of performance with existing techniques of beamformer, spherical-interpolation, divide and conquer, and iterative Taylor-series methods are made. The proposed technique performs significantly better than spherical-interpolation, and has a higher noise threshold than divide and conquer before performance breaks away from the Cramer-Rao lower bound. It provides an explicit solution form that is not available in the beamforming and Taylor-series methods. Computational complexity is comparable to spherical-interpolation but substantially less than the Taylor-series method.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mitochondrial Iron Metabolism and Sideroblastic Anemia (2009)

Sideroblastic anemias are a heterogeneous group of disorders, characterized by mitochondrial iron overload in developing red blood cells. The unifying characteristic of all sideroblastic anemias is the ring sideroblast, which is a pathological erythroid precursor containing excessive deposits of non-heme iron in mitochondria with perinuclear distribution creating a ring appearance. Sideroblastic anemias may be hereditary or acquired. Hereditary sideroblastic anemias are caused by defects in genes present on the X chromosome (mutations in the ALAS2, ABCB7, or GRLX5 gene), genes on autosomal chromosomes, or mitochondrial genes. Acquired sideroblastic anemias are either primary (refractory anemia with ring sideroblasts, RARS, representing one subtype of the myelodysplastic syndrome) or secondary due to some drugs, toxins, copper deficiency, or chronic neoplastic disease. The pathogenesis of mitochondrial iron loading in developing erythroblasts is diverse. Ring sideroblasts can develop as a result of a heme synthesis defect in erythroblasts (ALAS2 mutations), a defect in iron-sulfur cluster assembly, iron-sulfur protein precursor release from mitochondria (ABCB7 mutations), or by a defect in intracellular iron metabolism in erythroid cells (e.g. RARS).
Glucagon-Like Peptide (GLP)-1(9-36)Amide-Mediated Cytoprotection Is Blocked by Exendin(9-39) Yet Does Not Require the Known GLP-1 Receptor (2010)

The widely expressed dipeptidyl peptidase-4 enzyme rapidly cleaves the gut hormone glucagon-like peptide-1 [GLP-1(7-36)amide] at the N terminus to generate GLP-1(9-36)amide. Both intact GLP-1(7-36)amide and GLP-1(9-36)amide exert cardioprotective actions in rodent hearts; however, the mechanisms underlying the actions of GLP-1(9-36)amide remain poorly understood. We used mass spectrometry of coronary effluents to demonstrate that isolated mouse hearts rapidly convert infused GLP-1(7-36)amide to GLP-1(9-36)amide. After ischemia-reperfusion (I/R) injury of isolated mouse hearts, administration of GLP-1(9-36)amide or exendin-4 improved functional recovery and reduced infarct size. The direct actions of these peptides were studied in cultured neonatal mouse cardiomyocytes. Both GLP-1(9-36)amide and exendin-4 increased levels of cAMP and phosphorylation of ERK1/2 and the phosphoinositide 3-kinase target protein kinase B/Akt. In I/R injury models in vitro, both peptides improved mouse cardiomyocyte viability and reduced lactate dehydrogenase release and caspase-3 activation. These effects were attenuated by inhibitors of ERK1/2 and phosphoinositide 3-kinase. Unexpectedly, the cardioprotective actions of GLP-1(9-36)amide were blocked by exendin(9-39) yet preserved in Glp1r(-/-) cardiomyocytes. Furthermore, GLP-1(9-36)amide, but not exendin-4, improved the survival of human aortic endothelial cells undergoing I/R injury, actions sensitive to the nitric oxide synthase inhibitor, N(G)-nitro-l-arginine methyl ester (L-NAME). In summary, our findings demonstrate separate actions for GLP-1(9-36)amide vs. the GLP-1R agonist exendin-4 and reveal the existence of a GLP-1(9-36)amide-responsive, exendin(9-39)-sensitive, cardioprotective signaling pathway distinct from that associated with the classical GLP-1 receptor.
Competitive queue policies for differentiated services (2002)

We consider the setting of a network providing differentiated services. As is often the case in differentiated services, we assume the packets are tagged as either being high- or low-priority packets. Outgoing links in the network are serviced by a single FIFO queue. Our model gives a benefit of /spl alpha//spl ges/1 to each high-priority packet and a benefit of 1 to each low-priority packet. A queue policy controls which of the arriving packets are dropped and which enter the queue. Once a packet enters the queue it is eventually sent. The aim of a queue policy is to maximize the sum of the benefits of all the packets it delivers. We analyze and compare different queue policies for this problem using the competitive analysis approach, where the benefit of the online policy is compared to the benefit of an optimal offline policy. We derive both upper and lower bounds for the policies we consider, and in most cases our bounds are tight. We believe that competitive analysis gives important insight into the performance of these simple queuing policies.