gebhart/patrepeval huggingface dataset:
Role of the adenovirus E1B 19,000-dalton tumor antigen in regulating early gene expression (1988)

Mutations in the adenovirus gene encoding the E1B 19-kilodalton protein (the 19K protein) result in pleiotropic phenotypes that affect the host cell and virus growth. Examination of viral gene expression in HeLa cells infected with E1B 19K mutant viruses revealed synthesis and accumulation of E1A proteins to higher steady-state levels than those proteins synthesized during infection with the wild-type virus. As a consequence of elevated E1A levels, another early gene product, the 72K DNA-binding protein, accumulated earlier in mutant-infected cells. In a 12S E1A cDNA virus background, E1B 19K gene mutations had a more profound effect. Larger amounts of the 12S E1A product were present in E1B mutant-infected cells. A deletion mutation that eliminated expression of the 19K protein was also responsible for a 200-fold increased plaque-forming efficiency of the 12S cDNA virus in HeLa cells and an increased rate of virus production. Therefore, the E1B 19K tumor antigen may function to down-regulate virus replication by repressing E1A-dependent gene transcription. Eliminating expression of the E1A 13S and 12S gene products by substitution of an E1A 9S cDNA gene, however, uncovered a stimulatory effect of the E1B 19K protein on early gene expression and virus replication. An E1A 9S virus with a wild-type gene encoding the E1B 19K protein displayed increased early gene transcription, synthesized more 72K DNA-binding protein, and replicated more efficiently than an E1A 9S virus containing a mutation that eliminated expression of the 19K protein. Therefore, the E1B 19K protein has both positive and negative effects on early gene expression and virus replication. In the presence of functional E1A gene products, the 19K protein repressed E1A-dependent gene expression, but in the absence of E1A, the 19K protein stimulated viral gene expression and DNA synthesis. This raises the possibility that the E1B 19K protein functions to repress transcription by modifying the activity of the E1A proteins. Independent of E1A, however, the E1B 19K protein can increase viral gene expression and DNA synthesis, which then leads to increased virus replication.
A role for fast rhythmic bursting neurons in cortical gamma oscillations in vitro (2004)

Basic cellular and network mechanisms underlying gamma frequency oscillations (30-80 Hz) have been well characterized in the hippocampus and associated structures. In these regions, gamma rhythms are seen as an emergent property of networks of principal cells and fast-spiking interneurons. In contrast, in the neocortex a number of elegant studies have shown that specific types of principal neuron exist that are capable of generating powerful gamma frequency outputs on the basis of their intrinsic conductances alone. These fast rhythmic bursting (FRB) neurons (sometimes referred to as "chattering" cells) are activated by sensory stimuli and generate multiple action potentials per gamma period. Here, we demonstrate that FRB neurons may function by providing a large-scale input to an axon plexus consisting of gap-junctionally connected axons from both FRB neurons and their anatomically similar counterparts regular spiking neurons. The resulting network gamma oscillation shares all of the properties of gamma oscillations generated in the hippocampus but with the additional critical dependence on multiple spiking in FRB cells.
Phase I Trial of 40-kd Branched Pegylated Interferon Alfa-2a for Patients With Advanced Renal Cell Carcinoma (2001)

PEG-IFN is a modified form of IFNalpha2a with distinct pharmacokinetic advantages and immunomodulatory and antitumor activity for patients with advanced RCC. A dose of 450 microg/wk by subcutaneous administration was determined as a suitable dose for further study. PEG-IFN is more convenient to administer than IFNalpha and has potential for increased efficacy, less toxicity, or both. The efficacy and toxicity of PEG-IFN will be further assessed in clinical trials and compared with IFNalpha.
Physiologically-Regulated Expression Vectors for Gene Therapy (2011)

Gene-replacement gene therapy has been under development for a number of years. In spite of the large amount of research invested into developing gene therapy for the treatment of recessive genetic disorders only a limited number of patients world-wide have received the benefits. In addition, several high profile adverse events in gene therapy trials have lead to an increasing awareness of the challenges facing gene therapy treatments before they become established in the clinic. This has necessitated the development of novel advances in gene therapy vector design and delivery. This chapter will focus on the development of gene expression vectors incorporating native genomic regulatory elements that ensure transgene expression is physiologically relevant. Three main advances will be discussed here in detail; the use of whole genomic DNA loci to ensure physiologically-regulated transgene expression; development of viral vectors based on the herpes simplex virus type 1 for delivery of whole genomic DNA loci; and the development of genomic mini-gene vectors that contain native regulatory regions for the physiologically-regulated expression of cDNA mini-genes. The principal aim of gene-replacement gene therapy is to complement the loss of function of an endogenous gene by supplying an exogenous ‘working’ copy in trans. The conventional approach to this is to supply a wild-type cDNA copy of the gene in a small vector in which transgene expression is controlled by a strong heterologous promoter, such as the immediate early promoter of cytomegalovirus (pCMV). The advantage of this approach is that the vectors are easy to use, have high levels of transgene expression, and fit easily into most viral delivery systems such as lentivirus and adenovirus. However, expression from these vectors is characteristically short-term and wide-spread with no tissue specificity or temporal regulation. One alternative to heterologous expression vectors for gene therapy is to utilise native genomic DNA regulatory elements to ensure gene expression that is both spatially and temporally regulated. A highly effective means of achieving gene expression that is physiologically-regulated is through the use of whole genomic loci which contain all introns, exons and regulatory regions in the correct genomic context. Expression from whole genomic loci has been proven to recapitulate endogenous expression. In the context of gene therapy, delivery of whole genomic loci using bacterial artificial chromosomes (BAC) has been shown to be an effective means of complementing gene deficiencies. Delivery of BAC vectors carrying complete loci encoding, for example, the genes for the human low density lipoprotein receptor (LDLR), the Friedreich's ataxia (FRDA) frataxin protein (FXN),
Single-Step Azide Introduction in Proteins via an Aqueous Diazo Transfer (2008)

The controlled introduction of azides in proteins provides targetable handles for selective protein manipulation. We present here an efficient diazo transfer protocol that can be applied in an aqueous solution, leading to the facile introduction of azides in the side chains of lysine residues and at the N-terminus of enzymes, e.g. horseradish peroxidase (HRP) and the red fluorescent protein DsRed. The effective introduction of azides was verified by mass spectrometry, after which the azido-proteins were used in Cu(I)-catalyzed [3 + 2] cycloaddition reactions. Azido-HRP retained its catalytic activity after conjugation of a small molecule. This modified protein could also be successfully immobilized on the surface of an acetylene-covered polymersome. Azido-DsRed was coupled to an acetylene-bearing protein allowing it to act as a fluorescent label, demonstrating the wide applicability of the diazo transfer procedure.
BAY-43-9006 Bayer/Onyx. (2003)

Bayer and Onyx are developing BAY-43-9006, an oral cytostatic Raf kinase inhibitor for the potential treatment of colorectal and breast cancers, hepatocellular carcinoma and non-small-cell lung cancer, in addition to acute myelogenous leukemia, myelodysplastic syndrome and other cancers. A US IND was filed in May 2000 and by February 2003 BAY-43-9006 was in phase II trials, with phase III trials expected to begin later in 2003.
The TT8 Gene Encodes a Basic Helix-Loop-Helix Domain Protein Required for Expression of DFR and BAN Genes in Arabidopsis Siliques (2000)

The TRANSPARENT TESTA8 (TT8) locus is involved in the regulation of flavonoid biosynthesis in Arabidopsis. The tt8-3 allele was isolated from a T-DNA-mutagenized Arabidopsis collection and found to be tagged by an integrative molecule, thus permitting the cloning and sequencing of the TT8 gene. TT8 identity was confirmed by complementation of tt8-3 and sequence analysis of an additional allele. The TT8 gene encodes a protein that displays a basic helix-loop-helix at its C terminus and represents an Arabidopsis ortholog of the maize R transcription factors. The TT8 transcript is present in developing siliques and in young seedlings. The TT8 protein is required for normal expression of two flavonoid late biosynthetic genes, namely, DIHYDROFLAVONOL 4-REDUCTASE (DFR) and BANYULS (BAN), in Arabidopsis siliques. Interestingly, TRANSPARENT TESTA GLABRA1 (TTG1) and TT2 genes also control the expression of DFR and BAN genes. Our results suggest that the TT8, TTG1, and TT2 proteins may interact to control flavonoid metabolism in the Arabidopsis seed coat.
In vivotelomere dynamics of human hematopoietic stem cells (1997)

Aging in vivo and cell division in vitro are associated with telomere shortening. Several lines of evidence suggest that telomere length may be a good predictor of the long term replicative capacity of cells. To investigate the natural fate of chromosome telomeres of hematopoietic stem cells in vivo, we measured the telomere length of peripheral blood granulocytes from 11 fully engrafted bone marrow transplant recipients and from their respective donors. In 10 of 11 donor-recipient pairs, the telomere length was significantly reduced in the recipient and the extent of reduction correlated inversely with the number of nucleated cells infused. These data provide internally controlled in vivo evidence that, concomitantly with their proliferation, hematopoietic stem cells lose telomere length; it is possible that, as a result, their proliferative potential is reduced. These findings must be taken into account when developing new protocols in which few stem cells are used for bone marrow transplantation or for gene therapy.
Regulation of the Release of Coexisting Neurotransmitters (1988)

The joy of neurobiologists at the discovery of the coexistence of several neuroactive substances within the same neuron terminals can be compared with the delight of a man who has bought a radio he thought would only receive AM broadcasts, but who then discovers that it also gets all the FM stations. The discovery that the given neuronal network has the possibility of transmitting several different signals at the same time, at many of its syn­ apses, lends new dimensions to the workings of this network. The pace of morphological discovery of ever new examples of the coexistencel colocalization of two or more neuroactive substances in the same neuron is very high, producing several hundred new examples of coexistence phe­ nomena in the periphery and eNS (cf. 1-6). The work on the functional implications of the possibility of multiple signalling through the same syn­ apse-using several coexisting neurotransmitters-has been much slower. In this review, we discuss some important questions concerning the release of coexisting neurotransmitters and through these get some insight into the functional implications of coexistence. These questions are as follows: (a) Will a neuron at every one of its processes (dendrites and axon
Novel Approach to Characterization of Combined Pharmacodynamic Effects of Antimicrobial Agents (2004)

There is considerable need for new modeling approaches in the study of combined antimicrobial effects. Current methods based on the Loewe additivity and Bliss independence models are associated with implicit assumptions about the interacting system. To circumvent these limitations, we propose an alternative approach to the quantification of pharmacodynamic drug interaction (PDI). Pilot time-kill studies were performed with 10(8) CFU of Pseudomonas aeruginosa/ml at baseline with meropenem or tobramycin alone. The studies were repeated with 25 concentration combinations of meropenem (0 to 64 mg/liter) and tobramycin (0 to 32 mg/liter) in a five-by-five array. The data were modeled with a three-dimensional response surface using effect summation as the basis of null interaction. The interaction index (Ii) is defined as the ratio of the volumes under the planes (VUP) of the observed and expected surfaces: VUP(observed)/VUP(expected). Synergy and antagonism are defined as Ii values of <1 and >1, respectively. In all combinations, an enhanced killing effect was seen compared to that of either drug at the same concentration. The most significant synergism was observed between 1 and 5 mg/liter of meropenem and between 1 and 4 mg/liter of tobramycin; seven out of nine combinations had a >2-log drop compared to the more potent agent. The Ii was found to be 0.76 (95% confidence interval, 0.65 to 0.91) for the concentration ranges of the agents. The results corroborate previous data indicating that meropenem is synergistic with an aminoglycoside when used in combination against P. aeruginosa. Our parametric approach to quantifying PDI appears robust and warrants further investigations.
Highly transparent LCD using new scattering-type liquid crystal with field sequential color edge light (2017)

We have developed highly transparent color liquid crystal display (LCD) using newly developed scattering-type liquid crystal, which shows transparent state when voltage is not applied, with field sequential color (FSC) driving method without employing color filter and polarizer. Furthermore the light is directly introduced to the panel glass substrates from the edge of the substrates (not from back surface). At surface of the substrates, the light takes a total reflection and propagates through the substrate. On the other hand, when a voltage higher than a threshold voltage (Vth) is applied to liquid crystal (LC) layer, the light is scattered towards the viewers. This newly developed display has high transmittance (80 %), wide color gamut and fast response time.
Rituximab (anti-CD20) selectively modifies Bcl-xL and apoptosis protease activating factor-1 (Apaf-1) expression and sensitizes human non-Hodgkin's lymphoma B cell lines to paclitaxel-induced apoptosis. (2003)

The anti-CD20 monoclonal antibody rituximab (Rituxan, IDEC-C2B8) has shown promising results in the clinical treatment of a subset of patients with low grade or follicular non-Hodgkin's lymphoma (NHL). However, chemotherapy- and rituximab-refractory NHL patients may benefit from a regimen in which rituximab acts as a sensitizing agent. This study examined the apoptotic signaling mediated by rituximab on rituximab- and paclitaxel-resistant CD20(+) NHL B cell lines (Ramos, Raji, Daudi, and 2F7). Treatment with either rituximab (20 micro g/ml) or paclitaxel (0.1-1000 nM) inhibited viable cell recovery of NHL lines. Neither rituximab nor paclitaxel induced significant apoptosis, although the combination treatment resulted in synergy in apoptosis. Rituximab selectively down-regulated Bcl-xL and induced apoptosis protease activating factor 1 (Apaf-1) expressions in Ramos cells. Paclitaxel down-regulated the expression of Bcl-xL and inhibitor of apoptosis proteins (c-IAP-1) and up-regulated the expression of Bad and Apaf-1. The combination treatment resulted in the formation of truncated Bid, cytosolic accumulation of cytochrome c and second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low PI, activation of caspase-9, caspase-7, caspase-3, and cleavage of poly(ADP-ribose) polymerase. The findings identify two potential novel intracellular targets of rituximab-mediated signaling in Ramos NHL cells (i.e., Bcl-xL and Apaf-1). Further, the findings show that both rituximab and paclitaxel selectively modify the expression pattern of proteins involved in the apoptosis signal transduction pathway and, through functional complementation, the combination results in synergy in apoptosis. The potential therapeutic significance of these findings is discussed.
LEACHING OF METALS FROM WASTE PRINTED CIRCUIT BOARDS (WPCBs) USING SULFURIC AND NITRIC ACIDS (2014)

This study aims to understand the acid-leaching behavior of metals from 2 to 4 mm waste printed circuit boards (WPCBs) containing 22.0% ± 1.1 Cu, 6.7% ± 0.2 Ca, 0.68% ± 0.02 Sn, 0.59 ± 0.01 % Pb, 2.71% ± 0.08 Al, 0.22% ± 0.01 Fe, etc.. Copper leaching was increased for sulfuric acid concentrations up to 1.2 mol/L and hydrogen peroxide concentrations of 10.0 vol% for a pulp density of 100 g/L at 50°C over 4 h, whereas for the same concentrations of sulfuric acid and hydrogen peroxide copper leaching was decreased from 75.7 to 56.7% with an increase in pulp density from 25 to 125 g/L.Under the same optimum conditions and a 100 g/L pulp density, the leached copper concentration was 16.66 g/L (75.7%) and the concentrations of Pb, Al, Fe, and Ca were 0.1 g/L, 0.64 g/L, 0.13 g/L, 0.79g/L, respectively.Above 50°C and 500 rpm, the amount of leached copper decreased.With nitric acid, 98.3% copper leaching was obtained under the optimum conditions of 3 mol/L nitric acid and an agitation speed of 800 rpm at 60°C for 5 h at 25 g/L pulp density.Under optimum conditions and 100 g/L pulp density, the concentration of Cu in the leachate was 21.12 g/L (96%), and the concentrations of Pb, Al, Fe and Ca were 0.52 g/L, 0.91 g/L, 0.13 g/L, 1.70 g/L, respectively.At the same pulp density, nitric acid enabled better leaching of copper and other metals than sulfuric acid with 10.0 vol% hydrogen peroxide.The solid precipitates obtained in the leach liquors of PCBs included stannic oxide and calcium aluminum oxide in nitric acid and gypsum in sulfuric acid.
Increased Epidermal Growth Factor Receptor Gene Copy Number Detected by Fluorescence In Situ Hybridization Associates With Increased Sensitivity to Gefitinib in Patients With Bronchioloalveolar Carcinoma Subtypes: A Southwest Oncology Group Study (2005)

Increased EGFR gene copy number detected by FISH is associated with improved survival after gefitinib therapy in patients with advanced BAC, suggesting FISH methodology can be used to assess survival potential in patients treated with EGFR tyrosine kinase inhibitors.
Presumed consent for organ donation: a case against (2011)

The number of organ donors in the UK is approximately 13 per million population (PMP) per year and has been gradually reducing for most of the last decade. Attempts have been made by transplant surgeons to improve rates of transplantation by using more marginal donors, splitting livers for two recipients and the increasing use of deceased after-cardiac-death donors; the only success has been with the use of living related transplantation and this is largely confined to the recipients of kidneys. For the majority awaiting solid organ transplantation the number of donated organs remains the limiting factor in the number of transplants performed in the UK.

The UK donation rate is now one of the lowest in the developed world while the US consistently achieves organ donation rates of in excess of 25 PMP and Spain approximately 35 PMP. At the same time the need for solid organ transplantation is growing, with rises in the number of patients on the waiting lists of at least 8% per year. Evidence suggests that the UK population is supportive of organ donation, with 90% in favour during a UK survey carried out in 2003, and there are currently more than 16 million people signed up to the organ donor register.

The UK, however, was not always lagging behind and in 1989 organ donation rates in the UK were leading the world at 16 PMP but between 1989 and 2009 the rates of donation in the UK have declined while elsewhere in Europe and the rest of the world they have raced ahead.
TLR4 links innate immunity and fatty acid–induced insulin resistance (2006)

TLR4 is the receptor for LPS and plays a critical role in innate immunity. Stimulation of TLR4 activates proinflammatory pathways and induces cytokine expression in a variety of cell types. Inflammatory pathways are activated in tissues of obese animals and humans and play an important role in obesity-associated insulin resistance. Here we show that nutritional fatty acids, whose circulating levels are often increased in obesity, activate TLR4 signaling in adipocytes and macrophages and that the capacity of fatty acids to induce inflammatory signaling in adipose cells or tissue and macrophages is blunted in the absence of TLR4. Moreover, mice lacking TLR4 are substantially protected from the ability of systemic lipid infusion to (a) suppress insulin signaling in muscle and (b) reduce insulin-mediated changes in systemic glucose metabolism. Finally, female C57BL/6 mice lacking TLR4 have increased obesity but are partially protected against high fat diet-induced insulin resistance, possibly due to reduced inflammatory gene expression in liver and fat. Taken together, these data suggest that TLR4 is a molecular link among nutrition, lipids, and inflammation and that the innate immune system participates in the regulation of energy balance and insulin resistance in response to changes in the nutritional environment.
Integrated optical sensor in glass for optical coherence tomography (OCT) (2000)

The in vivo examination of tissue structures (e.g., human skin, eye retina) by optical coherence tomography is a powerful tool for pharmaceutical and medical research for the development of new drugs and new diagnostic methods. The parallel integration of eight Michelson interferometers including all reference light paths in one small glass chip is the basis of a compact sensor system with a high resolution, short measurement time, and a large penetration depth especially in almost opaque tissue such as the human skin. The interferometer array is fabricated with silver ion exchanged waveguides.
CH4 storage and CO2 capture in highly porous zirconium oxide based metal–organic frameworks (2012)

A series of porous Zr oxoclusters-based MOFs was computationally explored for their gas storage/capture performances. The highly porous UiO-67(Zr) and UiO-68(Zr) solids show exceptionally high CH(4) and CO(2) adsorption capacities under operating conditions that make these thermal, water and mechanical resistant materials very promising for physisorption-based processes.