gebhart/patrepeval huggingface dataset:
INVITED REVIEW: DRINKING AND THE BRAIN: CURRENT EVIDENCE<xref ref-type="fn" rid="fn1"><sup>*</sup></xref> (1992)

There is no question, as accumulating evidence reveals, that alcohol in excess negatively affects the brain and neuropsychological functioning, both immediately and in the long-term. The important question for social drinkers, however, is whether moderate amounts of alcohol can have deleterious effects on the brain or performance in either the medium- or long-term. It has been proposed that there is a continuum of negative consequences with light drinkers at one end and chronic alcoholics at the other end. Three levels of study of this hypothesis are distinguished; behavioural, structural, and cellular. Research into effects at these three levels is reviewed both for alcoholics and for social drinkers. A further hypothesis relates to the possibility that cognitive functioning is impaired even after blood alcohol concentration has returned to zero. It is concluded that while neither the continuity hypothesis nor a 'hangover' hypothesis is supported by current evidence, considerably more research is needed.
Crystal Polymorphism in Chemical Process Development (2011)

Polymorphism in molecular crystals is a prevalent phenomenon and is of great interest to the pharmaceutical community. The solid-state form is a key quality attribute of a crystalline product. Inconsistencies in the solid phase produced during the manufacturing and storage of drug substances and drug products may have severe consequences. It is essential to understand the solid-state behavior of the drug and to judiciously select the optimal solid form for development. This review highlights the pervasiveness and relevance of polymorphism and describes solid form screening and selection processes. Moreover, case studies on controlling polymorphs from a chemical development perspective are provided.
Peptide inhibitor of pancreatic lipase selected by phage display using different elution strategies (2005)

Interference with fat hydrolysis results in the reduced use of ingested lipids. Inhibition of pancreatic lipase reduces the efficiency of fat absorption in the small intestine and thereby initiates modest long-term reduction in body weight. In an attempt to select peptides with affinity for the surface of pancreatic lipase and potential inhibitory activity, a random, cyclic heptapeptide phage-displayed library was used. Five independent selections, differing in elution step, were performed. In three selection protocols, a sequential elution strategy was applied in anticipation of improving the selection of high-affinity clones. Four heptapeptides with the highest affinity, seemingly for pancreatic lipase, were selected, synthesized, and characterized for their capacity to inhibit enzyme function. Although no clear consensus among the sequenced peptides was found, one of the selected peptides inhibited pancreatic lipase with an apparent inhibition constant of 16 muM.
Methods to monitor the quaternary structure of G protein‐coupled receptors (2005)

A wide range of approaches has been applied to examine the quaternary structure of G protein-coupled receptors, the basis of such protein-protein interactions and how such interactions might modulate the pharmacology and function of these receptors. These include co-immunoprecipitation, various adaptations of resonance energy transfer techniques, functional complementation studies and the analysis of ligand-binding data. Each of the available techniques has limitations that restrict interpretation of the data. However, taken together, they provide a coherent body of evidence indicating that many, if not all, G protein-coupled receptors exist and function as dimer/oligomers. Herein we assess the widely applied techniques and discuss the relative benefits and limitations of these approaches.
Assessment of silver and gold substrates for the detection of amphetamine sulfate by surface enhanced Raman scattering (SERS) (2002)

Methods of detection of amphetamine sulfate using surface enhanced Raman scattering (SERS) from colloidal suspensions and vapour deposited films of both silver and gold are compared. Different aggregating agents are required to produce effective SERS from silver and gold colloidal suspensions. Gold colloid and vapour deposited gold films give weaker scattering than the equivalent silver substrates when high concentrations of drug are analysed but they also give lower detection limits, suggesting a smaller surface enhancement but stronger surface adsorption. A 10(-5) mol dm(-3) solution (the final concentration after addition of colloid was 10(-6) mol dm(-3)) of amphetamine sulfate was detected from gold colloid with an RSD of 5.4%. 25 microl of the same solution could be detected on a roughened gold film. The intensities of the spectra varied across the film surface resulting in relatively high RSDs. The precision was improved by averaging the scattering from several points on the surface. An attempt to improve the detection limit and precision by concentrating a suspension of gold colloid and amphetamine sulfate in aluminium wells did not give effective quantitation. Thus, positive identification and semi-quantitative estimation of amphetamine sulfate can be made quickly and easily using SERS from suspended gold colloid with the appropriate aggregating agents.
Expansion of human embryonic stem cells in defined serum‐free medium devoid of animal‐derived products (2005)

Human embryonic stem cells (hESCs) can serve as an unlimited cell source for cellular transplantation and tissue engineering due to their prolonged proliferation capacity and their unique ability to differentiate into derivatives of all three-germ layers. In order to reliably and safely produce hESCs, use of reagents that are defined, qualified, and preferably derived from a non-animal source is desirable. Traditionally, mouse embryonic fibroblasts (MEFs) have been used as feeder cells to culture undifferentiated hESCs. We recently reported a scalable feeder-free culture system using medium conditioned by MEFs. The base and conditioned medium (CM) still contain unknown bovine and murine-derived components, respectively. In this study, we report the development of a hESC culture system that utilizes a commercially available serum-free medium (SFM) containing human sourced and recombinant proteins supplemented with recombinant growth factor(s) and does not require conditioning with feeder cells. In this system, which employs human laminin coated surface and high concentration of hbFGF, the hESCs maintained undifferentiated hESC morphology and had a twofold increase in expansion compared to hESCs grown in MEF-CM. The hESCs also expressed surface markers SSEA-4 and Tra-1-60 and maintained expression of hTERT, Oct4, and Cripto genes similar to cells cultured in MEF-CM. In addition, hESCs maintained in this culture system were able to differentiate in vitro and in vivo into cells of all three-germ layers. The cells maintained a normal karyotype after prolonged culture in SFM. In summary, this study demonstrates that the hESCs cultured in defined non-conditioned serum-free medium (NC-SFM) supplemented with growth factor(s) retain the characteristics and replicative potential of hESCs. The use of defined culture system with NC-SFM on human laminin simplifies scale-up and allows for reproducible generation of hESCs under defined and controlled conditions that would serve as a starting material for production of hESC derived cells for therapeutic use.
Structural requirements for peptidic antagonists of the corticotropin-releasing factor receptor (CRFR): Development of CRFR2β-selective antisauvagine-30 (1998)

Different truncated and conformationally constrained analogs of corticotropin-releasing factor (CRF) were synthesized on the basis of the amino acid sequences of human/rat CRF (h/rCRF), ovine CRF (oCRF), rat urocortin (rUcn), or sauvagine (Svg) and tested for their ability to displace [125I-Tyr0]oCRF or [125I-Tyr0]Svg from membrane homogenates of human embryonic kidney (HEK) 293 cells stably transfected with cDNA coding for rat CRF receptor, type 1 (rCRFR1), or mouse CRF receptor, type 2beta (mCRFR2beta). Furthermore, the potency of CRF antagonists to inhibit oCRF- or Svg-stimulated cAMP production of transfected HEK 293 cells expressing either rCRFR1 (HEK-rCRFR1 cells) or mCRFR2beta (HEK-mCRFR2beta cells) was determined. In comparison with astressin, which exhibited a similar affinity to rCRFR1 (Kd = 5.7 +/- 1.6 nM) and mCRFR2beta (Kd = 4.0 +/- 2.3 nM), [DPhe11,His12]Svg(11-40), [DLeu11]Svg(11-40), [DPhe11]Svg(11-40), and Svg(11-40) bound, respectively, with a 110-, 80-, 68-, and 54-fold higher affinity to mCRFR2beta than to rCRFR1. The truncated analogs of rUcn displayed modest preference (2- to 7-fold) for binding to mCRFR2beta. In agreement with the results of these binding experiments, [DPhe11, His12]Svg(11-40), named antisauvagine-30, was the most potent and selective ligand to suppress agonist-induced adenylate cyclase activity in HEK cells expressing mCRFR2beta.
Control of Stress-Dependent Cardiac Growth and Gene Expression by a MicroRNA (2007)

The heart responds to diverse forms of stress by hypertrophic growth accompanied by fibrosis and eventual diminution of contractility, which results from down-regulation of alpha-myosin heavy chain (alphaMHC) and up-regulation of betaMHC, the primary contractile proteins of the heart. We found that a cardiac-specific microRNA (miR-208) encoded by an intron of the alphaMHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of betaMHC in response to stress and hypothyroidism. Thus, the alphaMHC gene, in addition to encoding a major cardiac contractile protein, regulates cardiac growth and gene expression in response to stress and hormonal signaling through miR-208.
The Central Role of the Alternative Complement Pathway in Human Disease (2006)

The complement system is increasingly recognized as important in the pathogenesis of tissue injury in vivo following immune, ischemic, or infectious insults. Within the complement system, three pathways are capable of initiating the processes that result in C3 activation: classical, alternative, and lectin. Although the roles that proinflammatory peptides and complexes generated during complement activation play in mediating disease processes have been studied extensively, the relative contributions of the three activating pathways is less well understood. Herein we examine recent evidence that the alternative complement pathway plays a key and, in most instances, obligate role in generating proinflammatory complement activation products in vivo. In addition, we discuss new concepts regarding the mechanisms by which the alternative pathway is activated in vivo, as recent clinical findings and experimental results have provided evidence that continuous active control of this pathway is necessary to prevent unintended targeting and injury to self tissues.
Enhanced antitumour immunity by combined use of temozolomide and TAT‐survivin pulsed dendritic cells in a murine glioma (2007)

Although chemotherapy remains among the best treatment options for most cancers, adjuvant therapies such as dendritic cell (DC)-based immunotherapy have been added to treatment protocols to destroy residual tumour cells. Combination treatment with low-dose temozolomide (TMZ) chemotherapy followed by vaccination with TAT-survivin-pulsed DCs enhanced T-cell responses specific for survivin and improved survival rate, as compared with DC alone or TMZ alone. Moreover, antigen-specific immunity appears to be mediated by CD8(+) T cells, as determined by in vitro T-cell subset depletion. These studies demonstrated that a combination of low-dose TMZ chemotherapy and TAT-based DC immunotherapy may be a novel strategy for safe and effective treatment of malignant gliomas.
Maternal serum placental growth factor at 11 + 0 to 13 + 6 weeks of gestation in the prediction of pre‐eclampsia (2008)

Effective screening for PE can be provided by a combination of maternal characteristics and obstetric history, uterine artery PI and maternal serum PlGF at 11 + 0 to 13 + 6 weeks' gestation.
Three-dimensional structure of CdX (X=Se,Te) nanocrystals by total x-ray diffraction (2007)

The three-dimensional structure of oleic acid-capped CdSe and thiol-capped CdTe nanocrystals used as quantum dots has been determined by total synchrotron radiation x-ray diffraction and atomic pair distribution function analysis. Both CdSe and CdTe are found to exhibit the zinc-blende-type atomic ordering. It is only slightly distorted in CdSe implying the presence of nanosize domains and very heavily distorted in CdTe due to the presence of distinct core-shell regions. The results well demonstrate the great potential of the experimental approach and thus encourage its wider application in quantum dot research.
Plasma sheath model and ion energy distribution for all radio frequencies (1999)

The spatiotemporal structure of the sheath and the ion energy distribution (IED) at the electrode of a collisionless electropositive glow discharge were studied with a model that is valid for arbitrary radio frequencies (rf). The model is based on the work of P. A. Miller and M. E. Riley [J. Appl. Phys. 82, 3689 (1997)] and uses an effective electric field to which the heavy ions respond. Given the plasma density and electron temperature at the sheath edge, and the waveform of either the potential or total current across the sheath, the spatial and/or temporal profiles of the following quantities were obtained: sheath thickness and capacitance, electron and ion densities, potential, and individual components of the current. An analytic expression for the energy split of the IED function was also obtained. The product ωτi of applied radian frequency ω and ion transit time τi is a critical parameter for describing the sheath dynamics.
Enhancement of farnesyl diphosphate pool as direct precursor of sesquiterpenes through metabolic engineering of the mevalonate pathway in Saccharomyces cerevisiae (2010)

The mevalonate pathway in the yeast Saccharomyces cerevisiae was deregulated in order to enhance the intracellular pool of farnesyl diphosphate (FPP), the direct precursor for the biosynthesis of sesquiterpenes. Over-expression of the catalytic domain of HMG1, both from the genome and plasmid, resulted in higher production of cubebol, a plant originating sesquiterpene, and increased squalene accumulation. Down-regulation of ERG9 by replacing its native promoter with the regulatable MET3 promoter, enhanced cubebol titers but simultaneous over-expression of tHMG1 and repression of ERG9 did not further improve cubebol production. Furtheremore, the concentrations of squalene and ergosterol were measured in the engineered strains. Unexpectedly, significant accumulation of squalene and restoring the ergosterol biosynthesis were observed in the ERG9 repressed strains transformed with the plasmids harboring cubebol synthase gene. This could be explained by a toxicity effect of cubebol, possibly resulting in higher transcription levels for the genes under control of MET3 promoter, which could lead to accumulation of squalene and ergosterol.
Endotoxin Activity and Inflammatory Markers in the Airways of Young Patients with Cystic Fibrosis (2002)

Chronic endobronchial infection frequently caused by gram-negative organisms and an increased, neutrophil-dominated inflammation are characteristics of cystic fibrosis (CF). The present study examines endotoxin levels in bronchoalveolar lavage fluids of CF versus non-CF (N) control children, and correlates these with the inflammatory markers interleukin-8 and neutrophils. Fifty-five patients with CF and 56 patients without CF between the ages of 0.04 to 13.25 years were included. Infection, defined as a bacterial count above 50,000 cfu/ml, was present in 27 CF and 25 N patients. Endotoxin levels were not different between patients with and without CF (infected: 74.9 +/- 12.1 EU/ml versus 51.4 +/- 12.5 EU/ml, p = 0.16; noninfected: 5.9 +/- 4.8 EU/ml versus 11.1 +/- 4.3 EU/ml, p = 0.28). Endotoxin activity correlated to the number of gram-negative organisms in CF and N patients, and endotoxin activity per bacterial colony forming unit did not differ with various gram-negative species. Both interleukin-8 and neutrophils were positively correlated with endotoxin, but this slope was shifted toward higher levels of inflammation in CF patients. We conclude that it is unlikely that higher levels of endotoxin in the absence of viable bacteria explain the increased inflammatory response in CF.
Role of AhR in positive regulation of cell proliferation and survival (2016)

The aryl hydrocarbon receptor (AhR) is an important nuclear transcription factor that is best known for mediating toxic responses by adjusting numbers of metabolism-related enzymes, including CYP1A1 and CYP1B1. Previous findings have revealed that, in addition to negatively regulating cell proliferation and survival, AhR may also positively regulate these pathways. Here, we review these findings and summarize distinct mechanisms by which AhR promotes cell proliferation and survival, including modulation of receptor expression, growth factor signalling and apoptosis, regulating the cell cycle and promoting cytokine expression. This review will aid better understanding the role of AhR in positive regulation of cell proliferation and survival.
Accuracy of intraocular lens power calculation in paediatric cataract surgery (2001)

For the overall group IOL power calculation is satisfactory. In eyes with axial lengths less than 20 mm and in children less than 36 months of age larger errors can arise. This study demonstrates the need for an IOL formula specifically designed for paediatric use.
Design of a Compliant and Force Sensing Hand for a Humanoid Robot (2005)

Abstract : Robot manipulation tasks in unknown and unstructured environments can often be better addressed with hands that are capable of force-sensing and passive compliance. We describe the design of a compact four degree-of-freedom (DOF) hand that exhibits these properties. This hand is being developed for a new humanoid robot platform. Our hand contains four modular Force Sensing Compliant (FSC) actuators acting on three fingers. One actuator controls the spread between two fingers. Three actuators independently control the top knuckle of each finger. The lower knuckles of the finger are passively coupled to the top knuckle. We place a pair of torsion springs between the motor housing and the hand chassis. By measuring the deflection of these springs, we can determine the acting force of the actuator. The springs also provide compliance in the finger and protect the motor gearbox from high impact shocks. Our novel actuators, combined with embedded control electrics, allow for a compact and dexterous hand design that is well suited to humanoid manipulation research.
The adsorption and thermal decomposition of digermane on Ge(111) (1993)

We have used multiple internal reflection infrared spectroscopy to investigate the interaction of digermane with Ge(111) at temperatures between 104–600 K. Digermane predominantly adsorbs molecularly on the surface below 120 K, displaying a vibrational spectrum similar to that of condensed digermane. At temperatures between 120–150 K, digermane dissociates via Ge–Ge bond scission to form adsorbed GeH3. Chemisorbed germyl GeH3 has a distinct symmetric deformation vibration at ∼772 cm−1, compared to a value of 721 cm−1 for molecularly adsorbed Ge2H6. At 200 K, Ge2H6 adsorption produces surface GeH3, GeH2, and GeH species with stretching vibrations at 2063, 2023, and 1968 cm−1, respectively. The surface GeH2 species is also identified by a characteristic scissor mode at ∼830 cm−1. Adsorption at 300 and 400 K produces only GeH2 and GeH, with a much lower concentration of GeH2 at 400 K. The surface GeH2 and GeH species are also generated by the successive decomposition of GeH3 upon heating. All surface hydrogen desorbs at ∼600 K.
Use of GPR1, GPR15, and STRL33 as Coreceptors by Diverse Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus Envelope Proteins (1998)

Human and simian immunodeficiency viruses (HIV and SIV, respectively) use chemokine receptors as coreceptors along with CD4 to mediate viral entry. Several orphan receptors, including GPR1, GPR15, and STRL33, can also serve as coreceptors for a more limited number of HIV and SIV isolates. We investigated whether these orphan receptors could function as efficient coreceptors for a diverse group of HIV and SIV envelopes (Envs) in comparison with the principal coreceptors CCR5 and CXCR4. We found that a limited number of HIV-1 isolates could mediate inefficient cell-cell fusion with the orphan receptors relative to CCR5 and CXCR4; however, none of the orphan receptors tested could support pseudotype virus infection despite robust infection via CCR5 or CXCR4. All except one of the SIV Envs tested mediated some degree of cell-cell fusion and pseudotype infection, with target cells expressing at least one of these orphan receptors, although CCR5 proved to be the most efficient coreceptor for infection. Only one SIV Env protein, BK28, could mediate infection using GPR1 as a coreceptor, albeit much less efficiently than with CCR5. In addition, use of these coreceptors did not correlate with the published tropism of the SIV clones and was strictly CD4 dependent for both SIV and HIV. We also examined the expression of these molecules in cell lines and primary cells widely used for virus propagation and as targets for infection. All cells examined expressed STRL33, a more limited number expressed GPR15, and GPR1 was much more restricted in its expression pattern. Taken together, our results indicate that GPR15 and STRL33 are rarely used by HIV-1 but are more frequently used by SIV strains, although not in a manner that correlates with SIV tropism.
Otitis Media—Principles of Judicious Use of Antimicrobial Agents (1998)

Otitis media is the leading indication for outpatient antimicrobial use in the United States. Overdiagnosis of and unnecessary prescribing for this condition has contributed to the spread of antimicrobial resistance. A critical step in reducing unnecessary prescribing is to identify the subset of patients who are unlikely to benefit from antibiotics. Conscientiously distinguishing acute otitis media (AOM) from otitis media with effusion (OME), and deferring antibiotics for OME will accomplish this goal, and will avoid up to 8 million unnecessary courses of antibiotics annually. Criteria for defining these conditions are presented, as well as the evidence supporting deferring antibiotic treatment. Discussions of shortened courses of antibiotics for AOM and restricted indications for antimicrobial prophylaxis are also presented.