gebhart/patrepeval huggingface dataset:
Prolyl hydroxylase 2 inactivation enhances glycogen storage and promotes excessive neutrophilic responses (2017)

Fully activated innate immune cells are required for effective responses to infection, but their prompt deactivation and removal are essential for limiting tissue damage. Here, we have identified a critical role for the prolyl hydroxylase enzyme Phd2 in maintaining the balance between appropriate, predominantly neutrophil-mediated pathogen clearance and resolution of the innate immune response. We demonstrate that myeloid-specific loss of Phd2 resulted in an exaggerated inflammatory response to Streptococcus pneumonia, with increases in neutrophil motility, functional capacity, and survival. These enhanced neutrophil responses were dependent upon increases in glycolytic flux and glycogen stores. Systemic administration of a HIF-prolyl hydroxylase inhibitor replicated the Phd2-deficient phenotype of delayed inflammation resolution. Together, these data identify Phd2 as the dominant HIF-hydroxylase in neutrophils under normoxic conditions and link intrinsic regulation of glycolysis and glycogen stores to the resolution of neutrophil-mediated inflammatory responses. These results demonstrate the therapeutic potential of targeting metabolic pathways in the treatment of inflammatory disease.
Estimation of the sub-criticality of the sodium-cooled fast reactor Monju using the modified neutron source multiplication method (2012)

The Modified Neutron Source Method (MNSM) is applied to the Monju reactor. This static method to estimate sub-criticality has already given good results on commercial Pressurized Water Reactors. The MNSM consists both in the extraction of the fundamental mode seen by a detector to avoid the effect of higher modes near sources, and the correction of flux distortion effects due to control rod movement. Among Monju's particularities that have a big influence on MNSM factors are: the presence of two californium sources and the position of the detector which is located far from the core outside of the reactor vessel. The importance of spontaneous fission and ({alpha}, n) reactions which have increased during the shutdown period of 15 years will also be discussed. The relative position of detectors and sources deeply affect the correction factors in some regions. In order to evaluate the detector count rate, an analytical propagation has been conducted from the reactor vessel. For two subcritical states, an estimation of the reactivity has been made and compared to experimental data obtained in the restart experiments at Monju (2010). (authors)
Middle of Line (MOL) Process Investigation in Ring Oscillator failure (2020)

Ring Oscillators (ROs) are used for yield learning during the research phase of a CMO technology. We performed cross-sections and showed that the open and short defects are in the middle of line (MOL) gate structures. The defects which are related to MOL or prior processes, as well as the design and density, will be discussed in the paper.
Amifostine and autologous hematopoietic stem cell support of escalating-dose melphalan: A phase I study (2004)

This study was conducted to define a new maximum tolerated dose and the dose-limiting toxicity (DLT) of melphalan and autologous hematopoietic stem cell transplantation (AHSCT) when used with the cytoprotective agent amifostine. Fifty-eight patients with various types of malignancy who were ineligible for higher-priority AHSCT protocols were entered on a phase I study of escalating doses of melphalan beginning at 220 mg/m(2) and advancing by 20 mg/m(2) increments in planned cohorts of 4 to 8 patients until severe regimen-related toxicity (RRT) was encountered. In all patients, amifostine 740 mg/m(2) was given on 2 occasions before the first melphalan dose (ie, 24 hours before and again 15 minutes before). AHSCT was given 24 hours after the first melphalan dose. Melphalan was given in doses up to and including 300 mg/m(2). Hematologic depression was profound, although it was rapidly and equally reversible at all melphalan doses. Although mucosal RRT was substantial, it was not the DLT, and some patients given the highest melphalan doses (ie, 300 mg/m(2)) did not develop mucosal RRT. The DLT was not clearly defined. Cardiac toxicity in the form of atrial fibrillation occurred in 3 of 36 patients treated with melphalan doses >/=280 mg/m(2) and was deemed fatal in 1 patient given melphalan 300 mg/m(2). (Another patient with a known cardiomyopathy was given melphalan 220 mg/m(2) and died as a result of heart failure but did not have atrial fibrillation.) Another patient given melphalan 300 mg/m(2) died of hepatic necrosis. The maximum tolerated dose of melphalan in this setting was thus considered to be 280 mg/m(2), and 27 patients were given this dose without severe RRT. Moreover, 38 patients were evaluable for delayed toxicity related to RRT; none was noted. Tumor responses have been noted at all melphalan doses and in all diagnostic groups, and 21 patients are alive at median day +1121 (range, day +136 to day +1923), including 16 without evidence of disease progression at median day +1075 (range, day +509 to day +1638). Amifostine and AHSCT permit the safe use of melphalan 280 mg/m(2), an apparent increase over the dose of melphalan that can be safely administered with AHSCT but without amifostine. Further studies are needed not only to confirm these findings, but also to define the antitumor efficacy of this regimen. Finally, it may be possible to evaluate additional methods of further dose escalation of melphalan in this setting.
Model-based Conformance Testing of Security Properties (2013)

Modern systems need to comply to large and complex security policies that need to enforced at runtime. This runtime enforcement needs to happen on different levels, e.g., ranging from high level access control models to firewall rules. We present an approach for the modular specification of security policies (e.g., access control policies, firewall policies). Based on this formal model, i.e, the specification, we discuss a model-based test case generation approach that can be used for both testing the correctness of the security infrastructure as well as the conformance of its configuration to a high-level security policy.
Effects of IL‐4 and IL‐13 on total and allergen specific IgE production by cultured PBMC from allergic patients determined with recombinant pollen allergens (1995)

Our results indicate that the peripheral blood of allergic individuals contains long lived allergen specific B cells which have already switched to IgE production and which are not sensitive to IL-4 and IL-13 treatment. These results may have implications on attempts to use cytokines or cytokine antagonists in therapy of Type I allergy.
Protein kinase C-dependent and -independent pathways of proto-oncogene induction in human astrocytoma cells. (1987)

We compared the abilities of the muscarinic agonist carbachol, epidermal growth factor (EGF), and phorbol 12-myristate 13-acetate (PMA) to induce proto-oncogene mRNA accumulation and other cellular responses in normal and protein kinase C-deficient 1321-N1 human astrocytoma cells. PMA, carbachol, and EGF all stimulated rapid accumulation of mRNA for the proto-oncogenes c-fos and c-myc in the normal cells; in the protein kinase C-deficient cells, carbachol and EGF, but not PMA, retained this effect, which was not mimicked by the calcium ionophore A23187. Both carbachol and PMA activated protein kinase C in these cells, as evidenced by the stimulated phosphorylation of an acidic Mr 80,000 protein kinase C substrate protein with phosphoamino acid and peptide map identity. This response was mimicked by several other neurotransmitters in these cells, including epinephrine, histamine, oxotremorine, and serotonin, and was abolished in cells made protein kinase C-deficient by preincubation with high concentrations of PMA. Both PMA and carbachol promoted the phosphorylation of the ribosomal protein S6 and activated an S6 protein kinase in the normal but not in the protein kinase C-deficient cells. EGF, in contrast, did not appear to activate protein kinase C, but promoted the phosphorylation of S6 and activation of the S6 kinase in both normal and protein kinase C-deficient cells. We conclude that, in 1321-N1 cells, induction of c-fos and c-myc mRNA can occur through a protein kinase C-dependent pathway and one or more independent pathways, exemplified by the responses to carbachol and EGF in the protein kinase C-deficient cells.
Ex Vivo Expansion of CD34+CD90+CD49f+ Hematopoietic Stem and Progenitor Cells from Non-Enriched Umbilical Cord Blood with Azole Compounds (2018)

Umbilical cord blood (UCB) transplants in adults have slower hematopoietic recovery compared to bone marrow (BM) or peripheral blood (PB) stem cells mainly due to low number of total nucleated cells and hematopoietic stem and progenitor cells (HSPC). As such in this study, we aimed to perform ex vivo expansion of UCB HSPC from non-enriched mononucleated cells (MNC) using novel azole-based small molecules. Freshly-thawed UCB-MNC were cultured in expansion medium supplemented with small molecules and basal cytokine cocktail. The effects of the expansion protocol were measured based on in vitro and in vivo assays. The proprietary library of >50 small molecules were developed using structure-activity-relationship studies of SB203580, a known p38-MAPK inhibitor. A particular analog, C7, resulted in 1,554.1 ± 27.8-fold increase of absolute viable CD45<sup>+</sup> CD34<sup>+</sup> CD38<sup>-</sup> CD45RA<sup>-</sup> progenitors which was at least 3.7-fold higher than control cultures (p < .001). In depth phenotypic analysis revealed >600-fold expansion of CD34<sup>+</sup> /CD90<sup>+</sup> /CD49f<sup>+</sup> rare HSPCs coupled with significant (p < .01) increase of functional colonies from C7 treated cells. Transplantation of C7 expanded UCB grafts to immunodeficient mice resulted in significantly (p < .001) higher engraftment of human CD45<sup>+</sup> and CD45<sup>+</sup> CD34<sup>+</sup> cells in the PB and BM by day 21 compared to non-expanded and cytokine expanded grafts. The C7 expanded grafts maintained long-term human multilineage chimerism in the BM of primary recipients with sustained human CD45 cell engraftment in secondary recipients. In conclusion, a small molecule, C7, could allow for clinical development of expanded UCB grafts without pre-culture stem cell enrichment that maintains in vitro and in vivo functionality. Stem Cells Translational Medicine 2018;7:376-393.
Parametric Direction Estimation from Antenna Array Data Based on Calibration Information (1994)

In antenna array signal processing we are often concerned with accurate determination of signal parameters from array measurements. To obtain accurate direction estimates, knowledge of the array response is required. Most estimation techniques are sensitive to errors in the array response model. Thus, reliable array calibration schemes are of great importance. In practice, calibration is done by measuring the array response when only one emitter is present and the signal parameters of which are allowed to vary in a known way. Herein, methods for generating an array model from noise corrupted calibration vectors is developed. The performance of the technique is examined on data collected from a full-scale antenna array in the 870 MHz region.
Metabolic and behavioral effects of high-dose, exogenous testosterone in healthy men. (1994)

In addition to their use as replacement therapy for hypogonadal males, androgens, particularly testosterone (T), are being explored as potential hormonal male contraceptive agents, alone or in combination with other compounds. Androgens have regulatory effects on a variety of physiological systems in addition to gonadotropin secretion and spermatogenesis. Therefore, as hormonal contraceptive regiments that alter serum T levels are explored, it is important to evaluate their effects on these aspects of normal male physiology. The effects of exogenous T on suppression of spermatogenesis in 19 healthy men were recently compared, using a T dosage of 200 mg im/week for 20 weeks. Before treatment, the men were evaluated during a 3-month pretreatment period, and after treatment, they were followed for 4-6 months or until their sperm counts normalized. Because of the lack of information regarding the effects of exogenous T on nonreproductive physiology, we examined the effects of high-dose T on plasma lipids, calcium metabolism, and sexual behavior in our subjects. Mean serum T and estradiol levels increased significantly during the treatment period. Plasma high-density lipoprotein (HDL) cholesterol levels decreased significantly within the first month and remained suppressed during the duration of T administration. At the end of the treatment period, mean plasma HDL cholesterol had decreased by 13 +/- 2% (P < 0.05); plasma levels of HDL2, HDL3, and apoprotein AI also decreased significantly; mean levels of low density lipoprotein cholesterol and triglycerides were unchanged. After 1 month of the recovery period, plasma HDL levels had returned to the baseline range. Serum calcium levels decreased slightly during treatment; this decrease was statistically significant. Urinary calcium excretion did not change. Mean levels of serum intact PTH increased by 84 +/- 17% (P < 0.05) during T administration; in contrast, 25-hydroxyvitamin D levels decreased by 16 +/- 4% (P < 0.05), and 1,25-dihydroxyvitamin D levels did not change significantly. All markers of calcium metabolism returned to baseline during the posttreatment period. Little change was found in self-reported sexual and aggressive behaviors during the study. There was a trend toward increased arousal and spontaneous erections during T administration, but this did not reach statistical significance. Frequency of sexual intercourse, masturbation, and kissing and fondling did not change, nor was the subjects' satisfaction in their relationships affected by T administration. Mean body weight increased by 4.0 +/- 0.5 kg. Approximately half the men noted mild acne. Body weight and acne symptoms returned to baseline during the recovery period.(ABSTRACT TRUNCATED AT 400 WORDS)
Antiseizure Activity of Novel γ-Aminobutyric Acid (A) Receptor Subtype-Selective Benzodiazepine Analogues in Mice and Rat Models (2009)

The antiseizure activity of benzodiazepines (BDZs) 1-5 in mice and rats as animal models is described. These BDZs have selective efficacy for alpha2beta3gamma2 and alpha3beta3gamma2 GABA(A)-receptors. Significant anticonvulsant activity with little or no motor impairment and therapeutic indexes (TI) of 2.8-44 (mice, ip) were observed for compounds 2-4 in the subcutaneous metrazole seizure (scMET) test. In rats, orally (po) the TI was >5 to 105. These compounds represent novel leads in the search for anticonvulsants devoid of sedative, ataxic, and amnestic side effects.
Geometric Analysis and Decomposition of Normal and Hypertensive Human Right Ventricle From Diagnostic Medical Imaging (2011)

Pulmonary hypertension (PH) is a cardio-pulmonary illness which affects all ages and racial populations, and induces significant changes to right ventricle (RV) shape and function. As such, the functional state of the RV is commonly thought to be a major determinant of symptoms and survival rates for PH. However, there has been little success to-date to identify clinically obtainable metrics of RV shape and deformation as a means to detect the onset and progression of PH. This difficulty is heightened by the complexity of RV shapes, which continues to confound basic and clinical scientists.
Validity index-based vigilance test in adaptive resonance theory neural networks (2017)

One of the distinguishing features of Adaptive Resonance Theory (ART) is that it relies on a second similarity check, called a vigilance test, to accept or reject a sample into a given category. Generic unsupervised versions of ART rely on a single layer vigilance test, whereas their supervised counterparts possess a second layer test based on classification errors that trigger a match tracking procedure regulated by an inter-ART block. This work uses a second layer vigilance test based on validity indices. A new sample is accepted into a category if its match function surpasses the vigilance test of both layers: the standard first check is based on minimum similarity, and the second check analyses whether setting that sample as belonging to the winner category results in an improvement of the current data partition according to the chosen validity index used as a cost function. Namely, if the new clustering state is superior to the previous one, then learning is allowed for the winning category. Otherwise, the algorithm proceeds as usual in ART implementations. Thus, this local greedy heuristic uses the validity index as a reinforcement signal, looking at the immediate reward to guide the learning of the ART categories without an additional external optimizer algorithm. A sweep analysis of the first layer vigilance parameter was performed and experiments indicate that the presented approach outperforms the standard Fuzzy ART neural network when samples are randomly presented. When samples are presented in a predefined order, Fuzzy ART obtains the best peak performance, however the modified approach was less sensitive to parameter variations.
High-Throughput Screening of Mouse Gene Knockouts Identifies Established and Novel High Body Fat Phenotypes (2021)

These data support the finding of high body fat in 43 independent external published and/or IMPC KO lines. A novel obese phenotype was identified in 29 additional KO lines, with 27 still lacking the external confirmation now provided for <i>Ksr2</i> and <i>G2e3</i> KO mice. Undoubtedly, many mammalian obesity genes remain to be identified and characterized.
Expression of galectin-3 and MMP-9 in endometrial adenocarcinoma (2008)

Objective This study evaluated the expression of galectin-3 and MMP-9 in normal,atypical hyperplastic,and endometrial adenocarcinoma.To explore the relationship between the expression of galectin-3,MMP-9 and the genesis and development of endometrial adenocarcinoma.Methods To investigate the expressions of galectin-3 and MMP-9 using immunohistochemistry in normal proliferative endometrium (NE,n=10),atypical hyperplasia (AH,n=14),endometrial adenocarcinoma (EC,n=70).The relation between their expression and clinical-pathological characteristics was evaluated.Results The positive percentage of immunostaining of galectin-3 and MMP-9 was increased significantly from NE to AH and EC (P0.05).Expression of galectin-3 was significantly correlated with tumor grade,there was significant statistical increase between G1 to G3 (P0.05).But there was no significant difference among different clinical-pathological stages,muscle invasions and lymphatic metastasis of endometrial carcinoma (P0.05).Expression ofMMP-9wassignificantly correlated with tumor grade and myometrial invasion of endometrial carcinoma (P0.05),but no significant difference among clinical-pathological staging and lymphatic metastasis was found (P0.05).Conclusion This study shows that galectin-3 and MMP-9 were closely associated with tumor genesis and pathobiological behaviors,and provides further evidence for diagnosis and prognosis of endometrial adenocarcinoma.
N-MethylmorpholineN-Oxide (2001)

[7529-22-8] C5H11NO2 (MW 117.17) (used as a co-oxidant with OsO42 and ruthenates;3 acts a mild oxidizing agent4) Alternate Name: NMO. Physical Data: mp 75–76 °C (as monohydrate) Solubility: sol water, acetone, alcohol, ether. Form Supplied in: colorless deliquescent crystals; available commercially. Purification: crystallize from ethanol. Handling, Storage, and Precautions: refrigerate; hygroscopic; irritant; handle in a fume hood using gloves; avoid skin contact and inhalation; in case of contact, rinse immediately with water.
Phosphatidylcholine passes through lateral tight junctions for paracellular transport to the apical side of the polarized intestinal tumor cell-line CaCo2 (2016)

Phosphatidylcholine (PC) is the most abundant phospholipid in intestinal mucus, indicative of a specific transport system across the mucosal epithelium to the intestinal lumen. To elucidate this transport mechanism, we employed a transwell tissue culture system with polarized CaCo2 cells. It was shown that PC could not substantially be internalized by the cells. However, after basal application of increasing PC concentrations, an apical transport of 47.1±6.3nmolh(-1)mMPC(-1) was observed. Equilibrium distribution studies with PC applied in equal concentrations to the basal and apical compartments showed a 1.5-fold accumulation on the expense of basal PC. Disruption of tight junctions (TJ) by acetaldehyde or PPARγ inhibitors or by treatment with siRNA to TJ proteins suppressed paracellular transport by at least 50%. Transport was specific for the choline containing the phospholipids PC, lysoPC and sphingomyelin. We showed that translocation is driven by an electrochemical gradient generated by apical accumulation of Cl(-) and HCO3(-) through CFTR. Pretreatment with siRNA to mucin 3 which anchors in the apical plasma membrane of mucosal cells inhibited the final step of luminal PC secretion. PC accumulates in intestinal mucus using a paracellular, apically directed transport route across TJs.
Adult hematopoietic stem cells lacking Hif-1α self-renew normally (2016)

The hematopoietic stem cell (HSC) pool is maintained under hypoxic conditions within the bone marrow microenvironment. Cellular responses to hypoxia are largely mediated by the hypoxia-inducible factors, Hif-1 and Hif-2. The oxygen-regulated α subunits of Hif-1 and Hif-2 (namely, Hif-1α and Hif-2α) form dimers with their stably expressed β subunits and control the transcription of downstream hypoxia-responsive genes to facilitate adaptation to low oxygen tension. An initial study concluded that Hif-1α is essential for HSC maintenance, whereby Hif-1α-deficient HSCs lost their ability to self-renew in serial transplantation assays. In another study, we demonstrated that Hif-2α is dispensable for cell-autonomous HSC maintenance, both under steady-state conditions and following transplantation. Given these unexpected findings, we set out to revisit the role of Hif-1α in cell-autonomous HSC functions. Here we demonstrate that inducible acute deletion of Hif-1α has no impact on HSC survival. Notably, unstressed HSCs lacking Hif-1α efficiently self-renew and sustain long-term multilineage hematopoiesis upon serial transplantation. Finally, Hif-1α-deficient HSCs recover normally after hematopoietic injury induced by serial administration of 5-fluorouracil. We therefore conclude that despite the hypoxic nature of the bone marrow microenvironment, Hif-1α is dispensable for cell-autonomous HSC maintenance.
Self Heat‐Shock Protein (hsp60) Peptide Serves in a Conjugate Vaccine against a Lethal Pneumococcal Infection (1999)

Healthy persons manifest a high frequency of T cells reactive to epitopes of the self 60-kDa heat-shock protein (hsp60) molecule. It was reasoned that a self hsp60 peptide, p458m, might provide T cell help for a response to the T independent capsular polysaccharide of Streptococcus pneumoniae type 4 (PS4). The conjugate vaccine (PS4-p458m) induced resistance to challenge with >300,000 times the minimal lethal dose of pneumococci. PS4 conjugated to other immunogenic carriers (tetanus toxoid, a pneumolysin peptide, and others) or a commercial pneumococcal vaccine were far less effective. The effectiveness of the PS4-p458m conjugate was associated with an increased IgG1 antibody response to PS4, with long-term memory, and with T cell responses to the p458m peptide. Thus, T cell reactivity to a self epitope in a conjugate vaccine can be mobilized to induce help for resistance to a lethal infection.