gebhart/patrepeval huggingface dataset:
Theoretical density functional theory studies on interactions of small biologically active molecules with isolated heme group (2007)

We present ab-initio density functional theory studies on the interactions of small biologically active molecules, namely NO, CO, O(2), H(2)O, and NO(2) (-) with the full-size heme group. Our results show that the small molecule-iron bond is the strongest in carbonyl and the weakest in nitrite system. Trans influence induced by NO binding to the five-coordinate heme complex is shown. Nitric oxide in the resulting complex might be described as NO(-). The differences among the small ligands of XO type (CO, NO, O(2)), and their distant chemical behavior from H(2)O and NO(2) (-) ligands in binding to the Fe(II) ion, are shown. Moreover, the role of the heme ring as a reservoir of electrons in the studied complexes is invoked. The analysis of the parameters defining the iron-histidine bond indicates that this bond is longer and weaker in nitrosyl and carbonyl complexes than in the other systems. Our findings support the proposed mechanism of soluble guanylate cyclase (sGC) activation and suggest that the first step of sGC activation by CO may be the same as during the activation by NO. Obtained results are then compared with the data concerning smaller model of the heme, the porphyrin complexes, available in the literature.
Proteases and cytokines as mediators of interactions between cancer and stromal cells in tumours (2016)

Proteolytic enzymes are highly relevant in different processes of cancer progression. Their interplay with other signalling molecules such as cytokines represents important regulation of multicellular cross-talk. In this review, we discuss protease regulation mechanisms of cytokine signalling in various types of cancer. Additionally, we highlight the reverse whereby cytokines have an impact on protease expression in an autocrine and paracrine manner, representing complex feedback mechanisms among multiple members of these two protein families. The relevance of the protease-cytokine axis is illustrated in glioblastoma, where interactions between normal mesenchymal stem cells and cancer cells play an important role in this very malignant form of brain cancer.
Assessment of Public Health Affected by Municipal Piped Water Supply in Old Dhaka, Bangladesh (2015)

This study was performed to assess the local public health impacts caused from the consumption of the municipal water supply in the study area. A field survey was conducted in Bangladesh National Hospital to get a statistical overview of the water borne health hazards’ incidence rates among the dwellers of Sutrapur Thana. The study found that about 40% of all the patients in the hospital got admitted due to different types of water borne diseases. The most common water borne diseases observed were: diarrhea (about 40.7%), typhoid (about 32.3%), dysentery (about 6.6%) and hepatitis A (about 10.5%). Children were found to be the most vulnerable to these diseases. About 70% of the total water borne disease incidences was children. On the other hand, the incidence rate was highest (58.9%) in the wet season (June), whereas it was lowest (17.9%) in the dry season (January). However, when respondents from local community were asked to give their perception on the safety of the supplied water, 100% claimed that the water was unsafe for drinking purpose.
The insulin-like growth factor system in chronic kidney disease: Pathophysiology and therapeutic opportunities (2012)

The growth hormone-insulin-like growth factor-insulin-like growth factor binding protein (GH-IGF-IGFBP) axis plays a critical role in the maintenance of normal renal function and the pathogenesis and progression of chronic kidney disease (CKD). Serum IGF-I and IGFBPs are altered with different stages of CKD, the speed of onset, the amount of proteinuria, and the potential of remission. Recent studies demonstrate that growth failure in children with CKD is due to a relative GH insensitivity and functional IGF deficiency. The functional IGF deficiency in CKD results from either IGF resistance due to increased circulating levels of IGFBPs or IGF deficiency due to increased urinary excretion of serum IGF-IGFBP complexes. In addition, not only GH and IGFs in circulation, but locally produced IGFs, the high-affinity IGFBPs, and low-affinity insulin-like growth factor binding protein-related proteins (IGFBP-rPs) may also affect the kidney. With respect to diabetic kidney disease, there is growing evidence suggesting that GH, IGF-I, and IGFBPs are involved in the pathogenesis of diabetic nephropathy (DN). Thus, prevention of GH action by blockade either at the receptor level or along its signal transduction pathway offers the potential for effective therapeutic opportunities. Similarly, interrupting IGF-I and IGFBP actions also may offer a way to inhibit the development or progression of DN. Furthermore, it is well accepted that the systemic inflammatory response is a key player for progression of CKD, and how to prevent and treat this response is currently of great interest. Recent studies demonstrate existence of IGF-independent actions of high-affinity and low-affinity-IGFBPs, in particular, antiinflammatory action of IGFBP-3 and profibrotic action of IGFBP-rP2/CTGF. These findings reinforce the concept in support of the clinical significance of the IGF-independent action of IGFBPs in the assessment of pathophysiology of kidney disease and its therapeutic potential for CKD. Further understanding of GH-IGF-IGFBP etiopathophysiology in CKD may lead to the development of therapeutic strategies for this devastating disease. It would hold promise to use of GH, somatostatin analogs, IGFs, IGF agonists, GHR and insulin-like growth factor-I receptor (IGF-IR) antagonists, IGFBP displacer, and IGFBP antagonists as well as a combination treatment as therapeutic agents for CKD.
Drug discovery targeting Chk1 and Chk2 kinases. (2003)

The DNA damage response includes not only checkpoint and apoptosis, but also direct activation of DNA repair networks. Downstream in the DNA damage response pathway are Chk1, an essential checkpoint kinase, and Chk2, which plays a critical role in p53-dependent apoptosis. Chk1 inhibition is expected to lead to chemosensitization of tumors, while Chk2 inhibition could protect normal sensitive tissues from some chemotherapeutic agents. Drugs targeting Chk1 and Chk2 have the potential to significantly improve the therapeutic window of DNA damaging agents available in the clinic.
Application of the CFU-GM Assay to Predict Acute Drug-Induced Neutropenia: An International Blind Trial to Validate a Prediction Model for the Maximum Tolerated Dose (MTD) of Myelosuppressive Xenobiotics (2003)

In a previous study of prevalidation, a standard operating procedure (SOP) for two independent in vitro tests (human and mouse) had been developed, to evaluate the potential hematotoxicity of xenobiotics from their direct and the adverse effects on granulocyte-macrophages (CFU-GM). A predictive model to calculate the human maximum tolerated dose (MTD) was set up, by adjusting a mouse-derived MTD for the differential interspecies sensitivity. In this paper, we describe an international blind trial designed to apply this model to the clinical neutropenia, by testing 20 drugs, including 14 antineoplastics (Cytosar-U, 5-Fluorouracil, Myleran, Thioguanine, Fludarabine, Bleomycin, Methotrexate, Gemcitabine, Carmustine, Etoposide, Teniposide, Cytoxan, Taxol, Adriamycin); two antivirals (Retrovir, Zovirax,); three drugs for other therapeutic indications (Cyclosporin, Thorazine, Indocin); and one pesticide (Lindane). The results confirmed that the SOP developed generates reproducible IC90 values with both human and murine GM-CFU. For 10 drugs (Adriamycin, Bleomycin, Etoposide, Fludarabine, 5-Fluorouracil, Myleran, Taxol, Teniposide, Thioguanine, and Thorazine), IC90 values were found within the range of the actual drug doses tested (defined as the actual IC90). For the other 10 drugs (Carmustine, Cyclosporin, Cytosar-U, Cytoxan, Gemcitabine, Indocin, Lindane, Methotrexate, Retrovir, and Zovirax) extrapolation on the regression curve out of the range of the actual doses tested was required to derive IC90 values (extrapolated IC90). The model correctly predicted the human MTD for 10 drugs out of 10 that had "actual IC90 values" and 7 drugs out of 10 for those having only an extrapolated IC90. Two of the incorrect predictions (Gemcitabine and Zovirax) were within 6-fold of the correct MTD, instead of the 4-fold range required by the model, whereas the prediction with Cytosar-U was approximately 10-fold in error. A possible explanation for the failure in the prediction of these three drugs, which are pyrimidine analogs, is discussed. We concluded that our model correctly predicted the human MTD for 20 drugs out of 23, since the other three drugs (Topotecan, PZA, and Flavopiridol) were tested in the prevalidation study. The high percentage of predicitivity (87%), as well as the reproducibility of the SOP testing, confirm that the model can be considered scientifically validated in this study, suggesting promising applications to other areas of research in developing validated hematotoxicological in vitro methods.
BER sensitivity of OFDM systems to carrier frequency offset and Wiener phase noise (1995)

In this contribution the transmission of M-PSK and M-QAM modulated orthogonal frequency division multiplexed (OFDM) signals over an additive white Gaussian noise (AWGN) channel is considered. The degradation of the bit error rate (BER), caused by the presence of carrier frequency offset and carrier phase noise is analytically evaluated. It is shown that for a given BER degradation, the values of the frequency offset and the linewidth of the carrier generator that are allowed for OFDM are orders of magnitude smaller than for single carrier systems carrying the same bit rate.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
An immortalized rat liver stellate cell line (HSC-T6): a new cell model for the study of retinoid metabolism in vitro (2000)

Hepatocytes and hepatic stellate cells play important roles in retinoid storage and metabolism. Hepatocytes process postprandial retinyl esters and are responsible for secretion of retinol bound to retinol-binding protein (RBP) to maintain plasma retinol levels. Stellate cells are the body's major cellular storage sites for retinoid. We have characterized and utilized an immortalized rat stellate cell line, HSC-T6 cells, to facilitate study of the cellular aspects of hepatic retinoid processing. For comparison, we also carried out parallel studies in Hepa-1 hepatocytes. Like activated primary stellate cells, HSC-T6 express myogenic and neural crest cytoskeletal filaments. HSC-T6 cells take up and esterify retinol in a time- and concentration-dependent manner. Supplementation of HSC-T6 culture medium with free fatty acids (up to 300 micrometer) does not affect retinol uptake but does enhance retinol esterification up to 10-fold. RT-PCR analysis indicates that HSC-T6 cells express all 6 retinoid nuclear receptors (RARalpha, -beta, -gamma, and RXRalpha, -beta, -gamma) and like primary stellate cells, HSC-T6 stellate cells express cellular retinol-binding protein, type I (CRBP) but fail to express either retinol-binding protein (RBP) or transthyretin (TTR). Addition of retinol (10(-8)-10(-5) m) or all-trans-retinoic acid (10(-10)-10(-6) m) rapidly up-regulates CRBP expression. Using RAR-specific agonists and antagonists and an RXR-specific agonist, we show that members of the RAR-receptor family modulate HSC-T6 CRBP expression.Thus, HSC-T6 cells display the same retinoid-related phenotype as primary stellate cells in culture and will be a useful tool for study of hepatic retinoid storage and metabolism.
Crystallization Behavior of Poly(ethylene terephthalate) Blended with Hyperbranched Polymers:  The Effect of Terminal Groups and Composition of Hyperbranched Polymers (2000)

The effects of terminal groups and composition of hyperbranched polymers (HBPs) on the crystallization behavior of poly(ethylene terephthalate) (PET) in HBP/PET blends were investigated using in situ FT-IR spectroscopy and differential scanning calorimetry. Hyperbranched aliphatic polyester was synthesized from an AB2 type monomer and a B3 type core. The hydroxyl terminal groups of the HBP were transformed into acetate and benzoate groups by organic synthetic methods. The effects of the HBPs were compared with those of linear polyester (LPE) synthesized from an AB type monomer and a B2 type core. A small amount of HBP with hydroxyl groups could greatly reduce the relative crystallinity of PET through hydrogen bonds. HBP with acetate groups showed effects similar to those of LPE. As the composition of LPE was increased, the relative crystallinity of PET was slightly decreased. On the contrary, HBP with benzoate groups played the role of nucleating agent in the blends with PET. The crystallization rate of PET was highest in the blend with 12 wt % HBP. Dynamic viscosity measurements were performed to investigate the role of the HBPs as processing aids.
Contents Vol. 107, 2004 (2004)

A role for the MutL homologue MLH2 in controlling heteroduplex formation and
Downregulation of c-kit Expression in Human Endothelial Cells by Inflammatory Stimuli (1997)

In recent studies we have shown that the expression of stem cell factor (SCF ) in human endothelial cells is regulated by inflammatory processes. Gram-negative bacteria, interleukin-1 (IL-1), and lipopolysaccharide were able to upregulate the expression of SCF in human umbilical vein endothelial cells (HUVEC) (Blood 83:2836, 1994). Interestingly enough c-kit, the receptor of SCF, is coexpressed on HUVEC, suggesting an autoregulatory mechanism. To investigate the relation of c-kit and inflammatory processes we stimulated HUVEC with IL-1α and we established an in vitro model of inflammation. Binding experiments with 125I-SCF were performed to study the c-kit receptor expression on HUVEC. Scatchard analysis revealed both high-affinity receptors (Kd ≈0.36 nmol/L) and low-affinity receptors (Kd ≈2.9 nmol/L). Exposure to IL-1α led to a significant 50% reduction of c-kit high-affinity receptors, whereas the number of low-affinity receptors was not affected, in comparison to a control group of untreated HUVEC. Furthermore, using Northern blot analysis we studied the regulation c-kit mRNA expression in HUVEC after stimulation with IL-1α. Kinetic experiments showed a time-dependent downregulation of c-kit specific transcripts. In addition, we cocultured HUVEC with diverse bacterial strains. Experiments were performed over time with 1 × 106 bacteria/mL. Our data showed that, in contrary to the previously reported upregulation of SCF mRNA expression, stimulation with Yersinia enterocolitica or with Neisseria meningitidis led to a significant time-dependent downregulation of c-kit mRNA within 3 hours. These data indicate that inflammatory stimuli such as IL-1 or living bacteria activate a mechanism that downregulates c-kit receptor expression in human endothelial cells during the state of inflammation.
R-spondin1 plays an essential role in ovarian development through positively regulating Wnt-4 signaling (2008)

In mammals, female development has traditionally been considered a default process in the absence of the testis-determining gene, Sry. Recently, it has been documented that the gene for R-spondin1 (RSPO1), a novel class of soluble activator for Wnt/beta-catenin signaling, is mutated in two Italian families with female-to-male (XX) sex reversal. To elucidate the role of Rspo1 as a candidate female-determining gene in a mouse model, we generated Rspo1-null (Rspo1(-/-)) mice and found that Rspo1(-/-) XX mice displayed masculinized features including pseudohermaphroditism in genital ducts, depletion of fetal oocytes, male-specific coelomic vessel formation and ectopic testosterone production in the ovaries. Thus, although Rspo1 is required to fully suppress the male differentiation program and to maintain germ cell survival during the development of XX gonads, the loss of its activity has proved to be insufficient to cause complete XX sex reversal in mice. Interestingly, these partial sex-reversed phenotypes of Rspo1(-/-) XX mice recapitulated those of previously described Wnt-4(-/-) XX mice. In accordance with this finding, the expression of Wnt-4 and its downstream genes was deregulated in early Rspo1(-/-) XX gonads, suggesting that Rspo1 may participate in suppressing the male pathway in the absence of Sry and maintaining oocyte survival through positively regulating Wnt-4 signaling.
Cycloheximide resistance in yeast: the gene and its portein (1983)

Mutations in the yeast gene CYH2 can lead to resistance to cycloheximide, an inhibitor of eukaryotic protein synthesis. The gene product of CYH2 is ribosomal protein L29, a component of the 60S ribosomal subunit. We have cloned the wild-type and resistance alleles of CYH2 and determined their nucleotide sequence. Transcription of CYH2 appears to initiate and terminate at multiple sites, as judged by S1 nuclease analysis. The gene is transcribed into an RNA molecule of about 1082 nucleotides, containing an intervening sequence of 510 nucleotides. The splice junction of the intron resides within a codon near the 5' end of the gene. In confirmation of peptide analysis by Stocklein et al. (1) we find that resistance to cycloheximide is due to a transversion mutation resulting in the replacement of a glutamine by glutamic acid in position 37 of L29.
Autologous Bone Marrow Transplantation (1989)

Results with autologous marrow transplantation can be improved through systematically developed, carefully designed clinical trials that may be facilitated by collaborative research. Studies should focus on disease-directed drug combinations, several courses of high-dose therapy, treatment at a time of lower tumor burden, and reducing toxicity with hematopoietic growth factors.
Decreased N-acetyl-aspartate/choline ratio and increased lactate in the frontal lobe of patients with Huntington's disease: a proton magnetic resonance spectroscopy study. (1997)

The finding of lactate peaks supports the hypothesis that disturbed cerebral energy metabolism contributes to the pathogenesis of Huntington's disease.
Submicrometer precision biometry of the anterior segment of the human eye. (1997)

The dual-beam partial coherence interferometry enables fast, noninvasive, submicrometer precision biometry of the anterior segment of the eye. The precision of determining the anterior chamber depth and the lens thickness is more than one order of magnitude better than that of the currently used ultrasound and optical techniques, and it can be improved by a factor of 5 by using cycloplegia.
Evolved GANs for generating pareto set approximations (2018)

In machine learning, generative models are used to create data samples that mimic the characteristics of the training data. Generative adversarial networks (GANs) are neural-network based generator models that have shown their capacity to produce realistic samples in different domains. In this paper we propose a neuro-evolutionary approach for evolving deep GAN architectures together with the loss function and generator-discriminator synchronization parameters. We also propose the problem of Pareto set (PS) approximation as a suitable benchmark to evaluate the quality of neural-network based generators in terms of the accuracy of the solutions they generate. The covering of the Pareto front (PF) by the generated solutions is used as an indicator of the mode-collapsing behavior of GANs. We show that it is possible to evolve GANs that generate good PS approximations. Our method scales to up to 784 variables and that it is capable to create architecture transferable across dimensions and functions.
Seven ways that HetNets are a cellular paradigm shift (2013)

Imagine a world with more base stations than cell phones: this is where cellular technology is headed in 10-20 years. This mega-trend requires many fundamental differences in visualizing, modeling, analyzing, simulating, and designing cellular networks vs. the current textbook approach. In this article, the most important shifts are distilled down to seven key factors, with the implications described and new models and techniques proposed for some, while others are ripe areas for future exploration.
Altered lipid content inhibits autophagic vesicular fusion (2010)

The autophagic/lysosomal system includes a variety of vesicular compartments that undergo dynamic fusion events. However, the characteristics and factors modulating these interactions remain, for the most part, unknown. To gain insights on the properties that govern lysosomal fusion events, we have established an in vitro fusion assay using different lysosomal/autophagic compartments isolated from mouse liver. We have found that autophagosome/lysosome fusion is a temperature-dependent process (fusion increment of 0.2+/-0.01%/degrees C), which requires ATP (1-3 mM), GTP (1-2 mM), Ca(2+) (0.2-2 mM), and an acidic lysosomal pH (pH 5.2). Furthermore, changes in membrane lipid composition, induced either in vitro, by treatment with 25 mM methyl-beta-cyclodextrin, or in vivo, by subjecting animals to a high-fat-diet challenge (60% kcal in fat) reduce autophagosome/lysosome fusion up to 70% of that observed in untreated fractions or from animals under a normal regular diet. These findings reveal a novel role for lipids in autophagic fusion and provide a mechanism for the reduced macroautophagic rates observed during exposure to a chronic lipid challenge. Changes in the intracellular lipid content (i.e., metabolic disorders) may thus have pronounced effects on the fusion step of macroautophagy and affect the overall activity of this intracellular proteolytic pathway.
Geometry-Contrastive GAN for Facial Expression Transfer (2018)

In this paper, we propose a Geometry-Contrastive Generative Adversarial Network (GC-GAN) for transferring continuous emotions across different subjects. Given an input face with certain emotion and a target facial expression from another subject, GC-GAN can generate an identity-preserving face with the target expression. Geometry information is introduced into cGANs as continuous conditions to guide the generation of facial expressions. In order to handle the misalignment across different subjects or emotions, contrastive learning is used to transform geometry manifold into an embedded semantic manifold of facial expressions. Therefore, the embedded geometry is injected into the latent space of GANs and control the emotion generation effectively. Experimental results demonstrate that our proposed method can be applied in facial expression transfer even there exist big differences in facial shapes and expressions between different subjects.