gebhart/patrepeval huggingface dataset:
Functional characterization and chromosomal localization of a cloned taurine transporter from human placenta (1994)

A cDNA clone highly related to the rat brain taurine transporter has been isolated from a human placental cDNA library. Transfection of this cDNA into HeLa cells results in a marked elevation of taurine transport activity. The activity of the cDNA-induced transporter is dependent on the presence of Na+ as well as Cl-. The Na+/Cl-/taurine stoichiometry for the cloned transporter is 2:1:1. The transporter is specific for taurine and other beta-amino acids, including beta-alanine, and exhibits high affinity for taurine (Michaelis-Menten constant approximately 6 microM). The clone consists of a coding region 1863 bp long (including the termination codon), flanked by a 376 bp-long 5' non-coding region and a 625 bp-long 3' non-coding region. The nucleotide sequence of the coding region predicts a 620-amino acid protein with a calculated M(r) of 69,853. Northern-blot analysis of poly(A)+ RNA from several human tissues indicates a complex expression pattern differing across tissues. The principal transcript, 6.9 kb in size, is expressed abundantly in placenta and skeletal muscle, at intermediate levels in heart, brain, lung, kidney and pancreas and at low levels in liver. Cultured human cell lines derived from placenta (JAR and BeWo), intestine (HT-29), cervix (HeLa) and retinal pigment epithelium (HRPE), which are known to possess Na(+)- and Cl(-)-coupled taurine transport activity, also contain the 6.9 kb transcript. Somatic cell hybrid and in situ hybridization studies indicate that the cloned taurine transporter is localized to human chromosome 3 p24-->p26.
MicroRNA Regulation of Immune Cell Development and Function (2010)

Abstract Abstract SCI-31 The NF-kappa B pathway is a central mediator of inflammation and plays an important role in myeloid cell development. During activation of macrophages by LPS, three microRNAs (miRNAs) were initially identified as being upregulated in an NF-kappa B dependent manner. Subsequent efforts to characterize two of these miRNAs, namely miR-155 and miR-146a, have revealed important roles not only in inflammation but also in hematopoietic development. Curiously, these two miRNAs seem to play opposing roles in promoting immune cell and progenitor proliferation, and the phenotypes induced in gain and loss-of-function contexts will be discussed in detail. Specifically, miR-155 overexpression and miR-146a deficiency lead to myeloid proliferations with pathologic consequences. These differential roles are largely explained by the targets of these microRNAs, which include signal transduction regulators: SHIP1 and SOCS1 in the case of miR-155, and TRAF6 and IRAK1 in the case of miR-146a. The roles of these miRNAs as effector and feedback regulator of the NF-kappa B pathway, respectively, will be discussed in the context of myeloid development. More broadly, these studies, as well as studies of miRNAs in B-cell development, have revealed that understanding miRNA roles in these processes will illuminate new aspects of biology and pathology. For example, the regulation of hematopoietic development by these miRNAs has revealed important interconnections between pathways that previously may have been considered disparate. Moreover, these studies have begun to underscore the importance of identifying specific targets of a miRNA in a given physiologic or pathologic context. Disclosures: No relevant conflicts of interest to declare.
Release of histamine from rat mast cells by the complement peptides C3a and C5a. (1975)

Suspensions of rat mast cells were used to study the histamine-releasing actions of anaphylatoxins C3A and C5a in vitro. The peptides, derived from human or porcine complement proteins C3 and C5, were less potent than 48/80 but more potent than bradykinin in stimulating release of histamine from mast cells. The pattern of release resembled that of the anaphylactic release action, e.g. release was limited to less than 30 per cent of the cell histamine, the reaction was calcium-dependent and was potentiated by phosphatidyl serine. When C3a and C5a were added together to mast cell suspensions, the amount of histamine released was additive. Similarly, release by either peptide combined with bradykinin was additive. Histamine-releasing activity (as well as smooth muscle-stimulating activity) was abolished when the peptides were treated with pancreatic carboxy-peptidase B. Active or inactive peptides were bound by mast cells and addition of active C3a in combination with the inactive, des-arginine derivative, C3ai, resulted in partial inhibition of histamine release.
Alcoholic fermentation by ‘non‐fermentative’ yeasts (1986)

All type strains of 'non-fermentative' yeasts, available in the culture collection of the Centraalbureau voor Schimmelcultures, were reinvestigated for their capacity to ferment glucose in the classical Durham tube test. Although visible gas production was absent, nearly all strains produced significant amounts of ethanol under the test conditions. Under conditions of oxygen-limited growth, even strong alcoholic fermentation may occur in a number of yeasts hitherto considered as non-fermentative. Thus, shake-flask cultures of Hansenula nonfermentans and Candida silvae fermented more than half of the available sugar to ethanol. It is concluded that the taxonomic test for fermentation capacity, which relies on detection of gas formation in Durham tubes, is not reliable for a physiological classification of yeasts as fermentative and non-fermentative species.
Regulated Production of a Peroxisome Proliferator-activated Receptor-γ Ligand during an Early Phase of Adipocyte Differentiation in 3T3-L1 Adipocytes (2004)

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear hormone receptor that is critical for adipogenesis and insulin sensitivity. Ligands for PPARgamma include some polyunsaturated fatty acids and prostanoids and the synthetic high affinity antidiabetic agents thiazolidinediones. However, the identity of a biologically relevant endogenous PPARgamma ligand is unknown, and limited insight exists into the factors that may regulate production of endogenous PPARgamma ligands during adipocyte development. To address this question, we created a line of 3T3-L1 preadipocytes that carry a beta-galactosidase-based PPARgamma ligand-sensing vector system. In this system, induction of adipogenesis resulted in elevated beta-galactosidase activity that signifies activation of PPARgamma via its ligand-binding domain (LBD) and suggests generation and/or accumulation of a ligand moiety. The putative endogenous ligand appeared early in adipogenesis in response to increases in cAMP, accumulated in the medium, and dissipated later in adipogenesis. Organically extracted and high pressure liquid chromatography-fractionated conditioned media from differentiating cells, but not from mature adipocytes, were enriched in this activity. One or more components within the organic extract activated PPARgamma through interaction with its LBD, induced lipid accumulation in 3T3-L1 cells as efficiently as the differentiation mixture, and competed for binding of rosiglitazone to the LBD of PPARgamma. The active species appears to be different from other PPARgamma ligands identified previously. Our findings suggest that a novel biologically relevant PPARgamma ligand is transiently produced in 3T3-L1 cells during adipogenesis.
Analytical Validation of Multiplex Biomarker Assay to Stratify Colorectal Cancer into Molecular Subtypes (2019)

Previously, we classified colorectal cancers (CRCs) into five CRCAssigner (CRCA) subtypes with different prognoses and potential treatment responses, later consolidated into four consensus molecular subtypes (CMS). Here we demonstrate the analytical development and validation of a custom NanoString nCounter platform-based biomarker assay (NanoCRCA) to stratify CRCs into subtypes. To reduce costs, we switched from the standard nCounter protocol to a custom modified protocol. The assay included a reduced 38-gene panel that was selected using an in-house machine-learning pipeline. We applied NanoCRCA to 413 samples from 355 CRC patients. From the fresh frozen samples (n = 237), a subset had matched microarray/RNAseq profiles (n = 47) or formalin-fixed paraffin-embedded (FFPE) samples (n = 58). We also analyzed a further 118 FFPE samples. We compared the assay results with the CMS classifier, different platforms (microarrays/RNAseq) and gene-set classifiers (38 and the original 786 genes). The standard and modified protocols showed high correlation (> 0.88) for gene expression. Technical replicates were highly correlated (> 0.96). NanoCRCA classified fresh frozen and FFPE samples into all five CRCA subtypes with consistent classification of selected matched fresh frozen/FFPE samples. We demonstrate high and significant subtype concordance across protocols (100%), gene sets (95%), platforms (87%) and with CMS subtypes (75%) when evaluated across multiple datasets. Overall, our NanoCRCA assay with further validation may facilitate prospective validation of CRC subtypes in clinical trials and beyond.
Terfenadine (seldane®): A new drug for restoring sensitivity to multidrug resistant cancer cells (1993)

In our efforts to identify clinically effective drugs for reversing multidrug resistance (MDR) mediated by P-glycoprotein, we tested terfenadine for anti-MDR activity because it appeared to sensitize a patient to doxorubicin and because it met structural requirements defined for this activity. Terfenadine sensitized MCF-7/ADR human breast cancer cells and L1210/VMDRC.06 murine leukemia cells to doxorubicin. At concentrations < or = 10 microM, terfenadine decreased the IC50 to doxorubicin by up to 25-fold against MCF-7/ADR cells and completely restored sensitivity to L1210/VMDRC.06 cells. The drug had no effect on the sensitive, parental cell lines and enhanced activity of other drugs affected by the MDR phenotype. Terfenadine was as potent as trans-flupenthixol, one of the most active modulators of MDR. The mechanism of action of terfenadine appeared to be due to inhibition of the function of P-glycoprotein since it augmented the accumulation of doxorubicin and inhibited the efflux of rhodamine 123 from MDR lines but had no effect on drug accumulation or efflux in sensitive cells. Terfenadine displaced azidopine from P-glycoprotein, but at concentrations higher than expected based on its overall potency. Since terfenadine is clinically available, has numerous structural derivatives available for study, and has a relatively low toxicity profile, this drug and drugs of its class should be evaluated for future clinical trials.
Theory of optical gain in ideal GaN heterostructure lasers (1995)

We present gain calculations for ideal bulk GaN and 100 Å GaN quantum well laser structures. We show that due to the large electron and hole effective masses in GaN, the room-temperature material gain characteristics of a 100 Å quantum well are a little different from those of bulk GaN up to a gain level of 1000 cm−1, and that the transparency and threshold carrier density is approximately 2.5 times that in an equivalent GaAs structure, with the radiative current density being of order eight times larger. Comparing the unstrained zinc blende and wurtzite crystal structures, we predict improved gain characteristics in the wurtzite case. The introduction of compressive strain, e.g., through pseudomorphic growth between unstrained AlGaN barriers, will benefit both crystal structures, with wurtzite remaining better than zinc blende for mismatch up to about 1.5%. Finally, we note that the gain characteristics would be further improved if it were possible to grow tensile-strained zinc blende layers.
Aligned Gold Nanorods in Silica Made by Ion Irradiation of Core–Shell Colloidal Particles (2004)

Colloidal particles with a 14 nm diameter Au core surrounded by a 72 nm thick silica shell have been irradiated with 30 MeV heavy ions. The shell deforms into an oblate ellipsoid, while the core becomes rod‐shaped (aspect ratio up to 9) with the major axis along the beam. Optical extinction measurements show evidence for split plasmon bands, characteristic for anisotropic metal nanoparticles.
Activation of cAMP Signaling Interferes with Stress-Induced p53 Accumulation in ALL-Derived Cells by Promoting the Interaction between p53 and HDM2 (2011)

The tumor suppressor p53 provides an important barrier to the initiation and maintenance of cancers. As a consequence, p53 function must be inactivated for a tumor to develop. This is achieved by mutation in approximately 50% of cases and probably by functional inactivation in the remaining cases. We have previously shown that the second messenger cAMP can inhibit DNA damage-induced wild-type p53 accumulation in acute lymphoblastic leukemia cells, leading to a profound reduction of their apoptotic response. In the present article, we provide a mechanistic insight into the regulation of p53 levels by cAMP. We show that increased levels of cAMP augment the binding of p53 to its negative regulator HDM2, overriding the DNA damage-induced dissociation of p53 from HDM2. This results in maintained levels of p53 ubiquitination and proteasomal degradation, which in turn counteracts the DNA damage-induced stabilization of the p53 protein. The apoptosis inhibitory effect of cAMP is further shown to depend on this effect on p53 levels. These findings potentially implicate deregulation of cAMP signaling as a candidate mechanism used by transformed cells to quench the p53 response while retaining wild-type p53.
DNA sequencing and multiplex STR analysis on plastic microfluidic devices (2006)

The ability of plastic microfluidic devices with separation channel lengths of 6, 10 or 18 cm to perform high-quality and high-performance ssDNA analysis was evaluated. Specifically, four-color DNA sequencing separation of a terminator sequencing standard using replaceable, urea-denaturing linear polyacrylamide (LPA) solution as a sieving matrix, yielded read lengths of 410 bases in 15 min with base calling accuracy of 99.2% on a 6-cm device, and 640 bases in 35 min with accuracy of 98.0% on a 18-cm device. A two-color sizing analysis of four-locus (CSF1PO, TPOX, TH01, vWA) short tandem repeats (STRs) allelic ladder on a 10-cm device indicated a mean SD of +/- 0.08 base pairs (bp) between runs, and single bp resolution of spiked TH01 allele 9.3 (198 bp) from TH01 allele 10 (199 bp) of the CTTv ladder with R = 0.81. A four-color multiplex sizing analysis of three different AmpFlSTR allelic ladders consisting of nine loci (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820) and gender alleles (Amelogenin) on a 10-cm device had a mean SD of +/- 0.15 bp between runs for sizing three loci, i.e., FGA, D18S51 and D3S818; alleles differing by 2 bp in size were resolved with resolutions close to baseline. This work demonstrates that plastic microfluidic devices are capable of quality sequencing and STR sizing comparable to that of glass devices of similar separation lengths.
Scandinavian Journal of Gastroenterology: A New Millennium (2000)

Mitogen-activated protein kinases (MAPKs) and heat shock proteins (Hsps) are ubiquitous proteins that function in both normal and stress-related pathophysiological states of the cell. Recent advances in the study of such Hsps and their interaction with signaling kinase cascades, including the cloning of new members, has helped to define their physiological roles in various tissues. In the pancreas, three major MAPKs, ERKs, JNKs, and p38, have been demonstrated. While intracellular signals involved in the ERK cascade have been most extensively investigated, only a few upstream regulators and downstream effector proteins of the JNKs and p38 MAPK are known in the pancreas. Similarly, a number of Hsps have been identified in pancreas, including Hsp27, Hsp60, and Hsp70. Although the activation of various MAPKs and the induction of Hsp expression have clearly been demonstrated following experimental exposure of rodent pancreas to stress conditions, it remains to be determined whether Hsps have a protective or detrimental effect during acute pancreatitis or at the onset of pancreatic carcinoma. This review will summarize current knowledge of the regulation and function of stress-activated kinases and stress proteins in the pancreas.
The augmentation of tumor‐specific immunity by virus help. II. Enhanced induction of cytotoxic T lymphocyte and antibody responses to tumor antigens by vaccinia virus‐reactive helper T cells (1984)

The present study investigates the role of vaccinia virus-reactive helper T cells in causing enhanced induction of syngeneic tumor immunity. Vaccinia virus-reactive helper T cell activity capable of inducing the augmented generation of cytotoxic T lymphocyte (CTL) or antibody responses was generated in C3H/HeN mice by inoculating i.p. live virus. Immunization of these mice with vaccinia virus-infected syngeneic X5563 plasmacytoma or MH134 hapatoma cells led to augmented induction of immune resistance against the challenge with corresponding viable tumor cells when compared with the incidence of resistance observed in control mice not primed to vaccinia virus. In vitro cytotoxicity tests utilizing spleen cells and serum from mice which resulted in the augmented tumor resistance by virus help have revealed that spleen cells from C3H/HeN mice immune to the X5563 plasmacytoma exhibited appreciable anti-X5563 CTL activity, whereas serum from these mice failed to display any antibody response. In contrast, MH134-immune mice exhibited potent anti-MH134 antibody, but not CTL responses. Such an anti-tumor CTL or antibody response augmented by vaccinia virus-reactive helper T cells was found to be tumor specific. These results are discussed in the context of (a) the functional diversity of tumor antigens, and (b) mechanisms of virus help that are involved in various forms of augmented induction of syngeneic tumor immunity.
Ultralow-threshold-current-density quantum dot lasers using the dots-in-a-well (DWELL) structure (2000)

Quantum dots laser diodes using the dots-in-a-well (DWELL) structure (InAs dots in an InGaAs quantum wells) have exhibited significant recent progress. With a single InAs dot layer in In<SUB>0.15</SUB>Ga<SUB>0.85</SUB>As quantum well, threshold current densities are as low as 26 A cm<SUP>-2</SUP> at 1.25 micrometer. Quantum dot laser threshold current densities are now lower than any other reported semiconductor laser. In this work, the threshold current density is reduced to 16 A cm<SUP>-2</SUP> by HR coatings on the same device. Further investigation of performance reveals that use of multiple DWELL stacks improves the modal gain and internal quantum efficiency. It is suggested that carrier heating out of the quantum dots limits the T<SUB>O</SUB> value of these DWELL lasers.
Acute renal failure is NOT an “acute renal success”—a clinical study on the renal oxygen supply/demand relationship in acute kidney injury (2010)

Renal oxygenation is severely impaired in acute kidney injury after cardiac surgery, despite the decrease in glomerular filtration and tubular workload. This was caused by a combination of renal vasoconstriction and tubular sodium resorption at a high oxygen demand.
Neural Photo Editing with Introspective Adversarial Networks (2016)

The increasingly photorealistic sample quality of generative image models suggests their feasibility in applications beyond image generation. We present the Neural Photo Editor, an interface that leverages the power of generative neural networks to make large, semantically coherent changes to existing images. To tackle the challenge of achieving accurate reconstructions without loss of feature quality, we introduce the Introspective Adversarial Network, a novel hybridization of the VAE and GAN. Our model efficiently captures long-range dependencies through use of a computational block based on weight-shared dilated convolutions, and improves generalization performance with Orthogonal Regularization, a novel weight regularization method. We validate our contributions on CelebA, SVHN, and CIFAR-100, and produce samples and reconstructions with high visual fidelity.
Módulo para acelerar el diseño de engranajes cónicos de dientes rectos y helicoidales (2019)

En el trabajo se exponen los resultados obtenidos en el desarrollo de un módulo para acelerar el diseño de engranajes cónicos de dientes rectos y helicoidales,para una aplicación de diseño asistido por computadoras (por el termino en inglés “Computer Aided Desing” o “CAD” por sus siglas) basada en tecnologías de código abierto. Debido al constante bloqueo económico ejercido por los Estados Unidos hace más de medio siglo hacia Cuba, software propietario como Catia, Solid Edge, Solid Works y Autodesk Inventor, entre otros, cuentan con aceleradores diseño que automatizan la construcción y cálculo de estructuras y piezas mecánicas complejas, estas herramientas no se pueden utilizar de forma institucional debido a que al país se le prohíbe acceder a todo tipo de sistema que se considere de alta tecnología, existen otras herramientas de código abierto como FreeCad o LibreCad, pero estas no cuentan con aceleradores de diseños que optimicen el trabajo, la solución que se presenta es un módulo realizado con tecnologías de código abierto a partir de la un conjunto de técnicas de Open Cascade y como marco de trabajo Qt, que modele y calcule engranajes cónicos de dientes rectos y helicoidales, para solucionar problemas de la industria cubana.
Similar Elimination Rates of Glucagon-Like Peptide-1 in Obese Type 2 Diabetic Patients and Healthy Subjects (2003)

We have previously shown that type 2 diabetic patients have decreased plasma concentrations of glucagon-like peptide 1 (GLP-1) compared with healthy subjects after ingestion of a standard mixed meal. This decrease could be caused by differences in the metabolism of GLP-1. The objective of this study was to examine the pharmacokinetics of GLP-1 in healthy subjects and type 2 diabetic patients after iv bolus doses ranging from 2.5-25 nmol/subject. Bolus injections iv of 2.5, 5, 15, and 25 nmol of GLP-1 and a meal test were performed in six type 2 diabetic patients [age, mean (range): 56 (48-67) yr; body mass index: 31.2 (27.0-37.7) kg/m(2); fasting plasma glucose: 11.9 (8.3-14.3) mmol/liter; hemoglobin A(1C): 9.6 (7.0-12.5)%]. For comparison, six matched healthy subjects were examined. Peak plasma GLP-1 concentrations increased linearly with increasing doses of GLP-1 and were similar for type 2 diabetic patients and healthy subjects. The peak concentrations of total GLP-1 (C-terminal) after 2.5, 5, 15, and 25 nmol of GLP-1 were 357 +/- 56, 647 +/- 141, 1978 +/- 276, 3435 +/- 331 pmol/liter in the type 2 diabetic patients and 315 +/- 37, 676 +/- 64, 1848 +/- 146, 3168 +/- 358 pmol/liter, respectively, in the healthy subjects (not statistically significant). Peak concentrations of the intact GLP-1 peptide (N-terminal) were: 69 +/- 17, 156 +/- 44, 703 +/- 77, and 1070 +/- 117 pmol/liter in the type 2 diabetic patients and 75 +/- 14, 160 +/- 40, 664 +/- 79, 974 +/- 87 in the healthy subjects (not statistically significant). GLP-1 was eliminated rapidly with clearances of intact GLP-1 after 2.5, 5, 15, and 25 nmol of GLP-1 amounting to: 9.0 +/- 5.0, 8.1 +/- 6.0, 4.0 +/- 1.0, 4.0 +/- 1.0 liter/min in type 2 diabetic patients and 8.4 +/- 4.2, 7.6 +/- 4.5, 5.0 +/- 2.0, 5.0 +/- 1.0 liter/min in healthy subjects. The volume of distribution ranged from 9-26 liters per subject. No significant differences were found between healthy subjects and type 2 diabetic subjects. We conclude that elimination of GLP-1 is the same in obese type 2 diabetic patients and matched healthy subjects. The impaired incretin response seen after ingestion of a standard breakfast meal must therefore be caused by a decreased secretion of GLP-1 in type 2 diabetic patients.