gebhart/patrepeval huggingface dataset:
Stable knockdown of CFTR establishes a role for the channel in P2Y receptor‐stimulated anion secretion (2005)

P2Y receptor regulation of anion secretion was investigated in porcine endometrial gland (PEG) epithelial cells. P2Y2, P2Y4, and P2Y6 receptors were detected in monolayers of PEG cells and immunocytochemistry indicated that P2Y4 receptors were located in the apical membrane. Apical membrane current measurements showed that Ca2+-dependent and PKC-dependent Cl- channels were activated following treatment with uridine triphosphate (UTP) (5 microM). Current-voltage relationships comparing calcium-dependent and PKC-dependent UTP responses under biionic conditions showed significant differences in selectivity between Cl-)and I- for the PKC-dependent conductance (P(I)/P(Cl) = 0.76), but not for Ca2+-dependent conductance (PI/P(Cl) = 1.02). The I-/Cl- permeability ratio for the PKC-dependent conductance was identical to that measured for 8-cpt cAMP. Furthermore, PKC stimulation using phorbol 12-myristate 13-acetate (PMA) activated an apical membrane Cl- conductance that was blocked by the CFTR selective inhibitor, CFTRinh-172. CFTR silencing, accomplished by stable expression of small hairpin RNAs (shRNA), blocked the PKC-activated conductance associated with UTP stimulation and provided definitive evidence of a role for CFTR in anion secretion. CFTR activation increased the initial magnitude of Cl- secretion, and provided a more sustained secretory response compared to conditions where only Ca2+-activated Cl- channels were activated by UTP. Measurements of [cAMP]i following UTP and PMA stimulation were not significantly different than untreated controls. Thus, these results demonstrate that UTP and PMA activation of CFTR occurs independently of increases in intracellular cAMP and extend the findings of earlier studies of CFTR regulation by PKC in Xenopus oocytes to a mammalian anion secreting epithelium.
RT‐PCR detection of fibronectin EDA+ and EDB+ mRNA isoforms: Molecular markers for hepatocellular carcinoma (1994)

Alternative splicing of fibronectin pre-mRNA has been shown to be independently regulated at the EDA and EDB regions in a tissue and developmental stage-specific manner. In this study, RT-PCR approaches were developed for the detection of EDA and EDB FN mRNA isoforms in hepatocarcinoma cells (SK-Hep-I) grown in vitro and in human liver biopsies. While EDA+ and EDB+ isoforms were not present in control adult liver, they were detectable in the hepatocarcinoma cells and in fetal liver. The RT-PCR analysis, extended to biopsies of malignant and non-malignant hepatic tissues, showed that FN mRNAs containing the EDA and EDB sequences were present in the 14 hepatocellular carcinomas (HCCs) tested but absent in the non-tumorous liver tissues (i.e., normal parenchyma, non-specific reactive and chronic hepatitis, steatosis). The EDB+ FN mRNA isoforms were also detected in 3 cases of benign neoplasm (hepatocellular adenoma, HCA, I; nodular focal hyperplasia, NFH, 2), while the EDA+ was only detectable in I of the 2 cases of NFH. In addition, both EDA+ and EDB+ isoforms were expressed in 5 out of 9 cirrhotic livers surrounding the tumors. This molecular analysis, which can also be performed on small liver biopsies (2 mg), may therefore be a useful additional tool in the diagnosis of HCC.
Endovascular vs Open Abdominal Aortic Aneurysm Repair (1999)

Patients undergoing OAAA and EAAA repair had similar cardiac event rates and mortality. In patients undergoing EAAA repair, history of congestive heart failure and Q wave on electrocardiogram were predictors of cardiac events.
Physics of ultrasonic surgery using tissue fragmentation (2002)

The mechanism of interaction for the ultrasonic surgical aspirator is poorly understood. A model for the primary mechanism for tissue fragmentation is presented. This involves the horn-tip impact and other mechanical forces, operating in combination with hydrodynamic forces applied to the tissue on the forward stroke in each cycle. No evidence of cavitation in tissue was observed.
Catalytic and Allosteric Properties of Glycerol Kinase from Escherichia coli (1973)

Abstract Catalytic and allosteric properties of the normal and of a genetically altered glycerol kinase from Escherichia coli were examined. Normal glycerol kinase exhibited Michaelis-Menten kinetics for glycerol with an apparent Km of 10 µm. Gel filtration studies indicated that, at saturation, 3.7 moles of [14C]glycerol bound per mole of enzyme, and a dissociation constant of 10 µm was determined by ultrafiltration. The response of reaction velocity to MgATP concentration was not hyperbolic, and double reciprocal plots displayed downward curvature, indicating two apparent Km values of 80 to 100 µm and 400 to 500 µm. The unusual MgATP kinetic data were obtained by two different assay procedures, were observed throughout the course of purification, were the same for different enzyme preparations, and were unchanged by aging of the enzyme. Product inhibition studies suggested an ordered mechanism for the enzyme, with glycerol as the first substrate to bind. Fructose 1,6-bisphosphate was a noncompetitive inhibitor with respect to both substrates. The response of reaction velocity to fructose 1,6-bisphosphate concentration was slightly sigmoid, maximum inhibition was about 80%, and double reciprocal plots of fractional inhibition against inhibitor concentration indicated an apparent Ki of 0.5 mm. Gel filtration studies showed that, at saturation, 3.5 moles of [14C]fructose 1,6-bisphosphate bound per mole of enzyme, with a dissociation constant of 0.06 mm determined by ultrafiltration. Inhibition by fructose 1,6-bisphosphate was greatly reduced by high pH, high ionic strength, or 0.2 m guanidine hydrochloride, some of which also stimulated enzyme activity. Under such conditions, [14C]fructose 1,6-bisphosphate still bound to the enzyme. A genetically desensitized glycerol kinase was purified to apparent homogeneity. It had a specific activity twice that of the normal enzyme, but was identical in size, charge, and subunit composition. Although the mutant enzyme still bound [14C]fructose 1,6-bisphosphate, it was totally insensitive to inhibition. The mutant enzyme also displayed a nonhyperbolic response to MgATP. Both the normal and mutant glycerol kinases were markedly stabilized against heat inactivation by glycerol, but not by fructose 1,6-bisphosphate. In the absence of specific ligands, about 12 sulfhydryl groups per molecule of enzyme reacted with 5,5'-dithiobis(nitro-2-benzoic acid). In the presence of glycerol, only two sulfhydryl groups per molecule reacted with the reagent, while fructose 1,6-bisphosphate had no effect. These results are discussed in terms of the subunit structure of the enzyme and in terms of the mechanism of fructose 1,6-bisphosphate inhibition of glycerol kinase.
Escherichia coli‐based cell‐free synthesis of virus‐like particles (2007)

Virus-like particles (VLP) have received considerable attention for vaccine, drug delivery, gene therapy and material science applications. Although the number of unique VLP and their applications are rapidly growing, the positive impact of VLP applications is limited by the current diverse, expensive, and typically low-yielding production technologies available. These technologies, when scaled, often result in structurally and compositionally inconsistent products. We present Escherichia coli-based cell-free protein synthesis as a production technology to overcome many of the limitations of current VLP production processes. Using this technique, the MS2 bacteriophage coat protein VLP was produced at a yield 14 times the best published production yield. Also, a C-terminally truncated Hepatitis B core protein VLP was produced at similarly high yields (6 x 10(13) VLP/mL). These VLP were found to have comparable characteristics to those produced in vivo. The scalability of this technology was tested without loss in production yields. To our knowledge, this is the first time a prokaryote-based in vitro transcription/translation system has generated a virus-like particle.
CXC Chemokines Bind to Unique Sets of Selectivity Determinants That Can Function Independently and Are Broadly Distributed on Multiple Domains of Human Interleukin-8 Receptor B (1996)

Human interleukin-8 receptors A (IL-8RA) and B (IL-8RB) are seven-transmembrane domain (TMD) neutrophil chemokine receptors with similar sequences (77% amino acid identity) and similar G protein selectivity, but markedly different selectivity for CXC chemokines. IL-8RB is selective for IL-8, growth-related oncogene alpha (GRO alpha) and neutrophil-activating peptide-2 (NAP-2), whereas IL-8RA is selective only for IL-8. To identify selectivity determinants, we made eight chimeric receptors exchanging: 1) the three main regions of sequence divergence between IL-8RA and IL-8RB (the N-terminal segment before TMD1, the region from TMD4 to the end of the second extracellular (e2) loop, and the C-terminal tail), and 2) the N-terminal segment of CC chemokine receptor 1, which does not bind CXC chemokines. Chimeras were tested by direct 125I-IL-8, 125I-GRO alpha, and 125I-NAP-2 binding, heterologous competition binding, and calcium flux assays using human embryonic kidney 293 cells stably transfected with receptor DNAs. The following results were obtained: 1) chimeric receptors had binding sites for IL-8, GRO alpha and NAP-2 distinct from those on IL-8RA and IL-8RB; 2) IL-8, GRO alpha and NAP-2 bound to overlapping but distinct sites that mapped differentially to multiple domains on IL-8RB; 3) high affinity radioligand binding and high agonist potency were separable functions for IL-8, GRO alpha and NAP-2, suggesting that the determinants of high affinity binding may not be critical for receptor activation; and 4) determinants of GRO alpha and NAP-2 selectivity were found in both the N-terminal segment before TMD1 and the region from TMD4 to the end of the e2 loop of IL-8RB, and functioned independently of each other. Stated reciprocally, the N-terminal segment of IL-8RA was not a dominant selectivity determinant. These data suggest that both narrow and broad spectrum chemokine antagonists can be developed to block functions mediated by IL-8RB.
Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes. (1986)

The growth and differentiation of B cells to immunoglobulin (Ig)-secreting cells is regulated by a variety of soluble factors. This study presents data that support a role for transforming growth factor (TGF)-beta in this regulatory process. B lymphocytes were shown to have high-affinity receptors for TGF-beta that were increased fivefold to sixfold after in vitro activation. The addition of picogram quantities of TGF-beta to B cell cultures suppressed factor-dependent, interleukin 2 (IL 2) B cell proliferation and markedly suppressed factor-dependent (IL 2 or B cell differentiation factor) B cell Ig secretion. In contrast, the constitutive IgG production by an Epstein Barr virus-transformed B cell line was not modified by the presence of TGF-beta in culture. This cell line was found to lack high-affinity TGF-beta receptors. The degree of inhibition of B cell proliferation observed in in vitro cultures was found to be dependent not only on the concentration of TGF-beta added but also on the concentration of the growth stimulatory substance (IL 2) present. By increasing the IL 2 concentrations in culture, the inhibition of proliferation induced by TGF-beta could be partially overcome. In contrast, the inhibition of Ig secretion induced by TGF-beta could not be overcome by a higher concentration of stimulatory factor, demonstrating that the suppression of B cell differentiation by TGF-beta is not due solely to its effects on proliferation. Furthermore, it was demonstrated that B lymphocytes secrete TGF-beta. Unactivated tonsillar B cells had detectable amounts of TGF-beta mRNA on Northern blot analysis, and B cell activation with Staphylococcus aureus Cowan (SAC) resulted in a twofold to threefold increase in TGF-beta mRNA. Supernatants conditioned by unactivated B cells had small amounts of TGF-beta, SAC activation of the B cells resulted in a sixfold to sevenfold increase in the amount of TGF-beta present in the supernatants. Thus, B lymphocytes synthesize and secrete TGF-beta and express receptors for TGF-beta. The addition of exogenous TGF-beta to cultures of stimulated B cells inhibits subsequent proliferation and Ig secretion. TGF-beta may function as an autocrine growth inhibitor that limits B lymphocyte proliferation and ultimate differentiation.
Evidence for divergence of restriction fragment length polymorphism patterns following in vivo replication of porcine reproductive and respiratory syndrome virus (1999)

RFLP patterns distinguish the vaccine and field strains of PRRSV; however, as the vaccine virus spreads among a swine population, the RFLP pattern can change to a related intermediate pattern. A glycine at residue 151 of open reading frame 5 is another marker for the vaccine virus; this glycine is rapidly lost and eventually replaced with arginine as the vaccine virus replicates in pigs.
Hemispherical Rasterization for Self-Shadowing of Dynamic Objects (2004)

We present a method for interactive rendering of dynamic models with self-shadows due to time-varying, lowfrequency lighting environments. In contrast to previous techniques, the method is not limited to static or preanimated models. Our main contribution is a hemispherical rasterizer, which rapidly computes visibility by rendering blocker geometry into a 2D occlusion mask with correct occluder fusion. The response of an object to the lighting is found by integrating the visibility function at each of the vertices against the spherical harmonic functions and the BRDF. This yields transfer coefficients that are then multiplied by the lighting coefficients to obtain the final, shadowed exitant radiance. No precomputation is necessary and memory requirements are modest. The method supports both diffuse and glossy BRDFs.
cycloSal-2‘,3‘-dideoxy-2‘,3‘-didehydrothymidine Monophosphate (cycloSal-d4TMP):  Synthesis and Antiviral Evaluation of a New d4TMP Delivery System (1998)

The synthesis, hydrolysis, and antiviral evaluation of novel, lipophilic cycloSal-d4TMP derivatives 3a-h of the anti-HIV dideoxynucleoside 2',3'-dideoxy-2',3'-didehydrothymidine (d4T, 1) are reported. This pro-nucleotide concept has been designed to deliver d4TMP (2) by selective chemical hydrolysis. All compounds 3a-h were synthesized using phosphorus(III) chemistry in good yields and in somewhat lower yields using phosphorus(V) chemistry starting from substituted salicyl alcohols 6a-h. The phosphotriesters 3 were obtained without stereochemical preference with respect to the configuration at the phosphorus center as 1:1 diastereomeric mixtures. However, a few of the triesters 3 could be separated into the diastereomers by means of semipreparative HPLC. In a 1-octanol/phosphate buffer mixture, all compounds 3 exhibited 9-100-fold higher lipophilicity as judged from their Pa values as compared to d4T (1). Furthermore, in hydrolysis studies 3 decomposed under mild aqueous basic conditions releasing solely d4TMP (2) and the diols 6 following the designed tandem reaction sequence. A correlation of the electronic properties introduced by the substituents and the half-lives of triesters 3 was observed. Thus, by varying the substituent, the half-lives of 3 could be adjusted over a wide range of compounds still delivering d4TMP (2) selectively. Phosphotriesters 3 exhibited considerable activity against HIV-1 and HIV-2 in wild-type human T-lymphocyte (CEM/O) cells as well as mutant thymidine kinase-deficient (CEM/TK-) cells. Surprisingly, we observed a 3-80-fold difference in antiviral activity between the two diastereomers. Our data clearly prove that the cycloSal-d4TMPs deliver exclusively the nucleotide d4TMP not only under simulated hydrolysis conditions but also under cellular conditions and thus fulfill the thymidine kinase-bypass premise. Therefore, the cycloSal-nucleotide concept is the first reported pro-nucleotide system that delivers the dideoxynucleotide by a pH-driven, chemically activated, tandem reaction without the requirement of an enzymatic contribution.
Chemosensitivity prediction by transcriptional profiling (2001)

In an effort to develop a genomics-based approach to the prediction of drug response, we have developed an algorithm for classification of cell line chemosensitivity based on gene expression profiles alone. Using oligonucleotide microarrays, the expression levels of 6,817 genes were measured in a panel of 60 human cancer cell lines (the NCI-60) for which the chemosensitivity profiles of thousands of chemical compounds have been determined. We sought to determine whether the gene expression signatures of untreated cells were sufficient for the prediction of chemosensitivity. Gene expression-based classifiers of sensitivity or resistance for 232 compounds were generated and then evaluated on independent sets of data. The classifiers were designed to be independent of the cells' tissue of origin. The accuracy of chemosensitivity prediction was considerably better than would be expected by chance. Eighty-eight of 232 expression-based classifiers performed accurately (with P < 0.05) on an independent test set, whereas only 12 of the 232 would be expected to do so by chance. These results suggest that at least for a subset of compounds genomic approaches to chemosensitivity prediction are feasible.
A narrowband approach to efficient PCS spectrum sharing through decentralized DCA access policies (1997)

This article addresses spectrum sharing and open access for personal communications services (PCS). Traditional regulation has allocated electromagnetic spectrum through fragmentation into mutually exclusive frequency blocks. Block allocation schemes produce trunking inefficiencies in the use of multiple narrowband RF channels. Broadband allocation schemes such as code division multiple access (CDMA) can accommodate multiple users on a single RF channel. Due to the near-far problem, the only way competing CDMA operators could share common spectrum is through collocation of cell sites, which hinders market mechanisms. An alternative approach is narrowband spectrum sharing through a decentralized dynamic channel assignment (DCA) approach, such as autonomous reuse partitioning (ARP). Multiple-operator DCA allocation schemes for low-tier PCS systems have been proposed in some countries. Under such an approach, competing operators use a common air interface to share the available spectrum. Open access can improve opportunities for competition in the provision of PCS. Other things being equal, a multi-operator DCA system outperforms that achievable by multiple carriers under a traditional fragmented spectrum, even for overlapping networks and unequal traffic loads. In this article we use a discrete event simulation to explore the spectrum efficiency implications of adopting a narrowband decentralized DCA/ARP spectrum-sharing policy. We explore as well regulatory measures so operators will deploy infrastructure instead of appropriating channels from competitors.
[Metastatic colorectal cancer: new therapeutics]. (2000)

The best combination between DNA interaction drugs based on potentiation of DNA damage induced by thymidylate synthetase inhibitors and inhibition of DNA repair by DNA interactions remains to be evaluated.
Development of a novel noninvasive adhesive patch test for the evaluation of pigmented lesions of the skin (2014)

Our data suggest that mRNA molecular signatures can serve as a highly useful noninvasive method of differentiating melanoma from nevi and decrease the number of unnecessary biopsies.
Chorioallantoic membrane for in vivo investigation of tissue‐engineered construct biocompatibility (2012)

Abstract In tissue engineering approach, the scaffold plays a key role for a suitable outcome of cell‐scaffold interactions and for the success of tissue healing and regeneration. As a consequence, the characterization of scaffold properties and the in vivo evaluation of tissue responses and effects result to be essential in the development of suitable implantable device. Among the in vivo methods, the chick embryo chorioallantoic membrane (CAM) assay represents a rather simple and cost‐effective procedure to study the biocompatibility responses of graft materials. CAM is indeed characterized by low experiment costs, simplicity, relative speed in obtaining the expected results, limited ethical concern, no need of high‐level technical skill, and the absence of a mature immune system, resulting in an inexpensive, simple, and practical method to evaluate and characterize tissue‐engineered constructs. The results till now obtained suggest that CAM assay can be used as a pre‐screening assay, before in vivo animal studies, to determine whether the scaffold is liable to cause an adverse reaction and to evaluate its future enhancement of existing materials for tissue engineering. A review of the more recent results related to the use of CAM for in vivo biomaterial property evaluation is herein reported. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Sleep and delirium in unsedated patients in the intensive care unit (2015)

The objective signs of sleep were absent in all but one PSG, so even though patients were not sedated, sleep could not be quantified. Even in patients without delirium, sleep could only be quantified in one of four patients. Paroxystic activity is frequent in unsedated patients, unresponsive to voice, but the implication is unknown.
Lower levels of nucleoside triphosphate in the basal ganglia of depressed subjects: a phosphorous-31 magnetic resonance spectroscopy study (1997)

The low level of beta-nucleoside triphosphate is consistent with an abnormality of high-energy phosphate metabolism in the basal ganglia of subjects with major depression.
Developing a New Methodology for Improved Value Engineering Practices (2010)

Value engineering (VE) has been widely practiced in government and the design, construction, and manufacturing industries for decades and becomes a compulsory part in the development of many projects. However, several problems hinder the wider use of VE practices and many evidences indicate the overall public opinion on VE is highly controversial. The writers conducted several real case studies to identify weaknesses of existing VE practices. After identifying the desired features, a new methodology for improved VE practices is presented which integrates the knowledge management system, theory of inventive problem-solving, widely used techniques for dealing with complex decisions and a prompt and succinct performance measurement methodology. Our work attempts to overcome shortcomings of traditional VE practices and make it more efficient, more measurable, and more recognized.
Tetrahydrofuransäuren – eine neue Klasse von Verbindungen des Humanstoffwechsels (1984)

Abstract Im Humanurin wird die bisher als Naturstoff unbekannte Tetrahydro‐2,5‐furandiessigsäure (3,6‐Epoxyoctandisäure) ( 1a ) in täglichen Mengen von etwa 3–5 mg ausgeschieden. Höhere Homologe 2a, 3a, 4a und 5a werden ebenfalls gefunden, sie kommen aber nur in Spuren vor.