gebhart/patrepeval huggingface dataset:
HIV-1 Regulatory/Accessory Genes: Keys to Unraveling Viral and Host Cell Biology (1998)

Human immunodeficiency virus type-1 (HIV-1) manipulates fundamental host cell processes in sophisticated ways to achieve optimum replicative efficiency. Recent studies have provided new details on the molecular interactions of HIV-1 with its host cell. For example, HIV-1 encodes a protein that regulates transcriptional elongation by interacting with a cellular cyclin-dependent kinase, another that activates the specific nuclear export of viral RNA, and several others that affect the intracellular trafficking of viral and host cell proteins. Detailed analysis of the interplay between these viral proteins and normal cellular activities has provided new insights into central questions of virology and host cell biology.
Laser Scribing of High-Performance and Flexible Graphene-Based Electrochemical Capacitors (2012)

Although electrochemical capacitors (ECs), also known as supercapacitors or ultracapacitors, charge and discharge faster than batteries, they are still limited by low energy densities and slow rate capabilities. We used a standard LightScribe DVD optical drive to do the direct laser reduction of graphite oxide films to graphene. The produced films are mechanically robust, show high electrical conductivity (1738 siemens per meter) and specific surface area (1520 square meters per gram), and can thus be used directly as EC electrodes without the need for binders or current collectors, as is the case for conventional ECs. Devices made with these electrodes exhibit ultrahigh energy density values in different electrolytes while maintaining the high power density and excellent cycle stability of ECs. Moreover, these ECs maintain excellent electrochemical attributes under high mechanical stress and thus hold promise for high-power, flexible electronics.
The clinical pharmacology of therapeutic monoclonal antibodies (2004)

Abstract Seventeen monoclonal antibodies are currently approved in the United States for therapeutic use in organ transplantation, percutaneous coronary intervention, prophylaxis of respiratory syncytial virus disease, rheumatoid arthritis, Crohn's disease, asthma, chronic lymphocytic leukemia, acute myeloid leukemia, non‐Hodgkin's lymphoma, breast cancer, and colorectal cancer. All approved antibodies are of the IgG class. Thirteen are unconjugated intact antibodies, three are intact immunoconjugates, and one is a Fab fragment. Three of the antibodies are murine, five are chimeric, eight are humanized, and one is a fully human antibody generated by phage display technology. The antigen target and the structural and binding characteristics of the antibody determine the antibody's mechanism of action, pharmacokinetics, safety, and immunogenicity. Antibodies act through multiple mechanisms that include functional modulation of the antigen, recruitment of ADCC and CDC, and delivery of radionuclide or toxin payloads to target cells. Antibody half‐life is usually governed by interaction with the FcRn receptor. In some cases, the antigen may act as a sink for antibody elimination. Safety profiles are determined by the pharmacology and tissue distribution of the target antigen, antibody isotype, the antibody payload, cytokine release, hypersensitivity reactions to xenogeneic protein, and immunogenicity. Fully human antibody technology may allow development of antibodies that have reduced risks of hypersensitivity reactions and immunogenicity, thereby enhancing safety and efficacy. The exquisite target specificity of antibodies, improvements in antibody engineering technology, and the wide availability of novel and validated therapeutic targets provide many current and future opportunities for the clinical development of therapeutic antibodies. Drug Dev. Res. 61:108–120, 2004. © 2004 Wiley‐Liss, Inc.
Differential Brain Metabolic Predictors of Response to Paroxetine in Obsessive-Compulsive Disorder Versus Major Depression (2003)

These findings suggest that, although both OCD and major depressive disorder respond to SRIs, the two syndromes have different neurobiological substrates for response. Elevated activity in the right caudate may be a marker of responsiveness to antiobsessional treatment, while lower right amygdala activity and higher midline prefrontal activity may be required for response of depressive symptoms to treatment.
Enzyme-BasedNANDandNORLogic Gates with Modular Design (2009)

The logic gates NAND/NOR were mimicked by enzyme biocatalyzed reactions activated by sucrose, maltose and phosphate. The subunits performing AND/OR Boolean logic operations were designed using maltose phosphorylase and cooperative work of invertase/amyloglucosidase, respectively. Glucose produced as the output signal from the AND/OR subunits was applied as the input signal for the INVERTER gate composed of alcohol dehydrogenase, glucose oxidase, microperoxidase-11, ethanol and NAD(+), which generated the final output in the form of NADH inverting the logic signal from 0 to 1 or from 1 to 0. The final output signal was amplified by a self-promoting biocatalytic system. In order to fulfill the Boolean properties of associativity and commutativity in logic networks, the final NADH output signal was converted to the initial signals of maltose and phosphate, thus allowing assembling of the same standard units in concatenated sequences. The designed modular approach, signal amplification and conversion processes open the way toward complex logic networks composed of standard elements resembling electronic integrated circuitries.
A novel resource allocation scheme for ad hoc radio local area networks (2002)

A new resource allocation scheme suitable for the high bit rate radio LAN was developed. The scheme is an adaptive one which allocates a portion of the available bandwidth only to those users who are active. The scheme is given the name Linked cluster Graph theoretic Multiple Access (LGMA). The scheme places the nodes of an ad hoc network in different groups and dynamically divides the total network capacity between the groups. In order to evaluate the performance of the scheme, the probability of having i groups sharing the total capacity should be computed. This is done by computing the event probabilities p(M/sub k/=j) which correspond to the probability of having j active nodes in the network. Computing the probabilities P(M/sub k/=j) is a lengthy and tedious process. Thus, an approximate method for deriving the probabilities p(M/sub k/=j) has been developed. The network performance for different configurations of an ad hoc network using the LGMA scheme has been studied and the results have shown that the performance does not vary significantly for different configurations.
Knowledge of colorectal cancer screening guidelines and intention to obtain screening among nonadherent Filipino, Hmong, and Korean Americans (2018)

CRC screening intention among nonadherent Filipino, Hmong, and Korean Americans was low. Targeting knowledge of CRC screening guidelines may be effective strategies for increasing CRC screening intention among nonadherent Asian Americans. Cancer 2018;124:1560-7. © 2018 American Cancer Society.
α4‐β2 and other nicotinic acetylcholine receptor subtypes as targets of psychoactive and addictive drugs (1992)

1. Xenopus oocytes were injected with various muscle and neuronal nicotinic acetylcholine receptor (ACh receptor, cholinoceptor) subunit RNA combinations and their pharmacological properties studied using two-electrode voltage clamp. The functional expression of one of these combinations, rat alpha 4-2 beta 2, has not been previously described. The alpha 4-2 mRNA is a splicing variant transcribed from the alpha 4 gene. In the experiments reported here, the alpha 4-2 beta 2 subtype was functionally indistinguishable from the alpha 4-1 beta 2 subtype. 2. For each subtype, the relative potency of nicotine compared with acetylcholine was obtained by estimating the relative concentration of nicotine which would elicit the same current response as 0.1 microM Ach. The ratios of these concentrations (nicotine: ACh) for the mouse muscle ACh receptor-(alpha 1 beta 1 gamma delta) was 96.1:1. In contrast, the ratios for the rat neuronal subtypes were: alpha 2 beta 2, 1.01:1; alpha 3 beta 2, 2.01:1; alpha 4 beta 2, 0.76:1 and alpha 4-2 beta 2, 0.76:1. The much greater relative nicotine sensitivity of the neuronal subtypes as compared with muscle receptors illustrates their potential to mediate the psychoactive and addictive effects of nicotine. However, it does not appear that the differences in relative nicotinic sensitivity among the neuronal receptors themselves can be used as a simple discriminative tool in neuronal tissue. 3. The slopes of the log dose-log response curves at low ACh concentrations were all greater than 1 but less than 2, suggesting that at least two agonist binding sites mediate the functional response of each hetero-oligomer. 4. The response of all the neuronal subtypes to ACh could be inhibited by the psychoactive drugs mecamylamine, amitriptyline, phencyclidine, trifluoperazine and promethazine. With the exception of the very potent antagonist, mecamylamine, the degree of block of the peak current to ACh produced by 10 microM concentrations of these drugs was remarkably similar (around 50%). 5. The degree of inhibition produced when the antipsychotic drug, trifluoperazine, was co-applied with ACh increased as the duration of application increased. Such an effect was not observed with promethazine, a related phenothiazine derivative which does not have antipsychotic actions.
Identification of a cAMP response element within the glucose- 6-phosphatase hydrolytic subunit gene promoter which is involved in the transcriptional regulation by cAMP and glucocorticoids in H4IIE hepatoma cells (1999)

The expression of a luciferase reporter gene under the control of the human glucose 6-phosphatase gene promoter was stimulated by both dexamethasone and dibutyryl cAMP in H4IIE hepatoma cells. A cis-active element located between nucleotides -161 and -152 in the glucose 6-phosphatase gene promoter was identified and found to be necessary for both basal reporter-gene expression and induction of expression by both dibutyryl cAMP and dexamethasone. Nucleotides -161 to -152 were functionally replaced by the consensus sequence for a cAMP response element. An antibody against the cAMP response element-binding protein caused a supershift in gel-electrophoretic-mobility-shift assays using an oligonucleotide probe representing the glucose 6-phosphatase gene promoter from nucleotides -161 to -152. These results strongly indicate that in H4IIE cells the glucose 6-phosphatase gene-promoter sequence from -161 to -152 is a cAMP response element which is important for the regulation of transcription of the glucose 6-phosphatase gene by both cAMP and glucocorticoids.
Cigarette Smoke Causes Acute Fluctuations in the Cyclic GMP Content of the Isolated Intact Lung (1984)

The injection of a single bolus of the gas phase of cigarette smoke into the airway of an isolated, perfused and ventilated, canine lung preparation resulted in a sevenfold increase in lung cyclic GMP content by 2 s after exposure. Recovery of control levels occurred by 2 min after injection. Repeated smoke exposures of the same lung resulted in similar increases. These results indicate that cigarette smoke may activate lung guanylate cyclase when delivered through the airway and suggest that lung cyclic GMP levels may fluctuate acutely during smoking.
US Prevalence And Predictors Of Informal Caregiving For Dementia (2015)

In 2010, 5.5 million US adults ages seventy and older received informal care, including 3.6 million with cognitive impairment or probable dementia. Adults with probable dementia received 171 hours of monthly informal care, versus 89 hours for cognitively impaired adults without dementia and 66 hours for cognitively normal adults.
Expression of heat shock proteins (HSP27, HSP60, HSP70, HSP90, GRP78, GRP94) in hepatitis B virus-related hepatocellular carcinomas and dysplastic nodules (2005)

The expressions of HSPs are commonly up-regulated in HBV-related HCCs and GRP78 might play an important role in the stepwise progression of HBV-related hepatocarcinogenesis. GRP78, GRP94, and HSP90 may be important prognostic markers of HBV-related HCC, strongly suggesting vascular invasion and intrahepatic metastasis.
Topoisomerase II-reactive chemotherapeutic drugs induce apoptosis in thymocytes. (1991)

The effects of topoisomerase II-reactive epipodophyllotoxins etoposide and teniposide as well as amsacrine on the viability of thymocytes in primary culture has been examined. All three drugs were shown to produce DNA cleavage detectable by resolving isolated DNA by pulsed field agarose gel electrophoresis. The DNA cleavage was found to have two components. The first was due to the interaction of the drugs with topoisomerase II, whereas the second component was due to endonuclease cleavage caused by the drug-induced entry of the thymocytes into programmed cell death or apoptosis. This second component of the DNA cleavage was also detected in thymocytes undergoing apoptosis following exposure to the glucocorticoid analogue, dexamethasone. The effect of the drugs on programmed cell death is dependent upon new protein and RNA synthesis, indicating that topoisomerase II has a role in the very first stages of the process. These results are discussed in terms of the use of this class of topoisomerase II-reactive drugs in chemotherapy.
PSYCHOPATHOLOGIC DOMAINS AND INSIGHT IN SCHIZOPHRENIA (1998)

The earlier conceptualization of positive and negative symptom topologies for schizophrenia has given way to more complex models that propose three-and-four dimensions of psychopathology. These constructs may relate to neurobiologic heterogeneity and discrete symptom clusters have been shown to have distinct anatomical and cognitive correlates. Insight is an excellent example and the understanding of insight at psychopathologic and cognitive levels has facilitated new approaches to treatment and enhanced medication compliance.
Liquid crystal based electro-optic diffractive spectacle lenses and low operating voltage nematic liquid crystals (2005)

Diffractive optical elements in which discrete phase levels are used to approximate a continuous blaze profile offer the advantage over conventional refractive optics in that they are essentially planar structures and thus consume very little space. Furthermore, it has been shown that switchable diffractive elements can be fabricated using electro-optic materials such as inorganic electro-optic crystals and liquid crystals. In this work, liquid crystal diffractive lenses are investigated for their possible use as switchable spectacle lenses, an alternative to current bifocal and progressive lens technologies. In these lenses, discrete, rotationally symmetric electrodes are used to generate the stepped phase levels of a diffractive lens in a 5 micrometer layer of nematic liquid crystal. Near theoretical diffraction efficiencies are reported for both 2 and 4 phase level lenses and it is shown that the inter-electrode gap is a critical design parameter for achieving these values. For the 4 level lenses the near theoretical values are achieved by implementing a novel, multi-level electrode structure that eliminates the inter-electrode gap while maintaining electrical isolation between adjacent electrodes. Additionally, the results of a study aimed at reducing the operating voltages of nematic liquid crystal are also included. In this study, colorless molecular dopants with high dipole moments are added to commercial nematic liquid crystal mixtures for the purpose of increasing dielectric anisotropy, upon which the threshold voltage is inversely dependent. While a reduction in threshold voltage is observed it is determined that a reduction in order parameter is the cause. Quantum-chemical analysis of the dopant molecules indicate that the structures are too rigid for introduction into a liquid crystal host and a new, less rigid structure is proposed.
Peptide Ligands for Integrin .alpha.v.beta.3 Selected from Random Phage Display Libraries (1995)

The integrin alpha v beta 3 binds promiscuously to cell-adhesive proteins: vitronectin, fibronectin, and several others containing the RGD motif. We have explored molecular recognition by alpha v beta 3 through selection of ligands from large random libraries of peptides displayed on phage. Ligands bound by alpha beta 3 consisted primarily of RGD peptides; however, these peptides showed considerable heterogeneity with respect to the identities of amino acids flanking RGD. The tolerance of alpha v beta 3 for RGD peptides of diverse composition is consistent with its role in vivo as a versatile receptor for RGD-containing extracellular matrix proteins. Peptide ligands for alpha v beta 3 also included a novel binding sequence, identical to a tetrapeptide found in vitronectin, which is a candidate for a synergistic site in this adhesive protein that may act in concert with RGD to promote molecular recognition.
Electromagnetic determination of soil water content: Measurements in coaxial transmission lines (1980)

The dependence of the dielectric constant, at frequencies between 1 MHz and 1 GHz, on the volumetric water content is determined empirically in the laboratory. The effect of varying the texture, bulk density, temperature, and soluble salt content on this relationship was also determined. Time‐domain reflectometry (TDR) was used to measure the dielectric constant of a wide range of granular specimens placed in a coaxial transmission line. The water or salt solution was cycled continuously to or from the specimen, with minimal disturbance, through porous disks placed along the sides of the coaxial tube. Four mineral soils with a range of texture from sandy loam to clay were tested. An empirical relationship between the apparent dielectric constant K a and the volumetric water content θ v , which is independent of soil type, soil density, soil temperature, and soluble salt content, can be used to determine θ v , from air dry to water saturated, with an error of estimate of 0.013. Precision of θ v to within ±0.01 from K a can be obtained with a calibration for the particular granular material of interest. An organic soil, vermiculite, and two sizes of glass beads were also tested successfully. The empirical relationship determined here agrees very well with other experimenters' results, which use a wide range of electrical techniques over the frequency range of 20 MHz and 1 GHz and widely varying soil types. The results of applying the TDR technique on parallel transmission lines in the field to measure θ v versus depth are encouraging.
Pharmacokinetics and safety of single doses of drisapersen in non-ambulant subjects with Duchenne muscular dystrophy: Results of a double-blind randomized clinical trial (2013)

Duchenne muscular dystrophy (DMD) is a progressive, lethal neuromuscular disorder caused by the absence of dystrophin protein due to mutations of the dystrophin gene. Drisapersen is a 2'-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA. This study assessed safety, tolerability, and pharmacokinetics of drisapersen after a single subcutaneous administration in non-ambulatory subjects. Eligible subjects were non-ambulant boys aged ⩾9years, in wheelchairs for ⩾1 to ⩽4years, with a diagnosis of DMD resulting from a mutation correctable by drisapersen treatment. Four dose cohorts were planned (3, 6, 9 and 12mg/kg), but study objectives were met with the 9mg/kg dose. Less than proportional increase in exposure was demonstrated over the 3-9mg/kg dose range, though post hoc analysis showed dose proportionality was more feasible over the 3-6mg/kg range. Single doses of drisapersen at 3 and 6mg/kg did not result in significant safety or tolerability concerns; however, at the 9mg/kg dose, pyrexia and transient elevations in inflammatory parameters were seen. The maximum tolerated dose of 6mg/kg drisapersen was identified for further characterization in multiple dose studies in the non-ambulant DMD population.
The role of phosphatidylinositol 3‐kinase in neural cell adhesion molecule‐mediated neuronal differentiation and survival (2003)

The neural cell adhesion molecule, NCAM, is known to stimulate neurite outgrowth from primary neurones and PC12 cells presumably through signalling pathways involving the fibroblast growth factor receptor (FGFR), protein kinase A (PKA), protein kinase C (PKC), the Ras-mitogen activated protein kinase (MAPK) pathway and an increase in intracellular Ca2+ levels. Stimulation of neurones with the synthetic NCAM-ligand, C3, induces neurite outgrowth through signalling pathways similar to the pathways activated through physiological, homophilic NCAM-stimulation. We present here data indicating that phosphatidylinositol 3-kinase (PI3K) is required for NCAM-mediated neurite outgrowth from PC12-E2 cells and from cerebellar and dopaminergic neurones in primary culture, and that the thr/ser kinase Akt/protein kinase B (PKB) is phosphorylated downstream of PI3K after stimulation with C3. Moreover, we present data indicating a survival-promoting effect of NCAM-stimulation by C3 on cerebellar and dopaminergic neurones induced to undergo apoptosis. This protective effect of C3 included an inhibition of both DNA-fragmentation and caspase-3 activation. The survival-promoting effect of NCAM-stimulation was also shown to be dependent on PI3K.
Functional, biochemical, and molecular investigations of renal kallikrein-kinin system in diabetic rats (1999)

A reduction of renal kallikrein has been found in non-insulin-treated diabetic individuals, suggesting that an impaired renal kallikrein-kinin system (KKS) contributes to the development of diabetic nephropathy. We analyzed relevant components of the renal KKS in non-insulin-treated streptozotocin (STZ)-induced diabetic rats. Twelve weeks after a single injection of STZ, rats were normotensive and displayed hyperglycemia, polyuria, proteinuria, and reduced glomerular filtration rate. Blood bradykinin (BK) levels and prekallikrein activity were significantly increased compared with controls. Renal kallikrein activity was reduced by 70%, whereas urinary BK levels were increased up to threefold. Renal kininases were decreased as indicated by a 3-fold reduction in renal angiotensin-converting enzyme activity and a 1.8-fold reduction in renal expression of neutral endopeptidase 24.11. Renal cortical expression of kininogen and B2 receptors was enhanced to 1.4 and 1. 8-fold, respectively. Our data suggest that increased urinary BK levels found in severely hyperglycemic STZ-diabetic rats are related to increased filtration of components of the plasma KKS and/or renal kininogen synthesis in combination with decreased renal kinin-degrading activity. Thus, despite reduced renal kallikrein synthesis, renal KKS is activated in the advanced stage of diabetic nephropathy.
Planar, time-optimal, rest-to-rest slewing maneuvers of flexible spacecraft (1989)

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