gebhart/patrepeval huggingface dataset:
Improved efficacy with targeted pharmacogenetic-guided treatment of patients with depression and anxiety: A randomized clinical trial demonstrating clinical utility (2017)

The objective of this study was to evaluate the effect of pharmacogenetics-guided treatment on patients diagnosed with depression and/or anxiety, in a diverse set of clinical settings, as compared to the standard of care. The trial design followed a prospective, randomized, subject- and rater-blinded approach enrolling 685 patients from clinical providers specializing in Psychiatry, Internal Medicine, Obstetrics & Gynecology, and Family Medicine. The NeuroIDgenetix<sup>®</sup> test uses a genetic variant panel of ten genes, along with concomitant medications, to make medication management recommendations based on gene-drug and drug-drug interactions for over 40 medications used in the treatment of depression and anxiety. Pharmacogenetic testing was performed at the initial screening visit and baseline patient assessments were determined using the 17-item Hamilton Rating Scale for Depression (HAM-D17) and the Hamilton Rating Scale for Anxiety (HAM-A). Following enrollment and randomization, pharmacogenetic results for subjects assigned to the experimental group were provided to physicians to guide treatment selection, while control subjects were treated according to the usual standard of care. HAM-D17 and HAM-A assessments were collected at 4 weeks, 8 weeks, and 12 weeks after baseline to assess the efficacy of therapeutic selection. In patients diagnosed with depression, response rates (p = 0.001; OR: 4.72 [1.93-11.52]) and remission rates (p = 0.02; OR: 3.54 [1.27-9.88]) were significantly higher in the pharmacogenetics-guided group as compared to the control group at 12 weeks. In addition, patients in the experimental group diagnosed with anxiety showed a meaningful improvement in HAM-A scores at both 8 and 12 weeks (p = 0.02 and 0.02, respectively), along with higher response rates (p = 0.04; OR: 1.76 [1.03-2.99]). From these results, we conclude that pharmacogenetic-guided medication selection significantly improves outcomes of patients diagnosed with depression or anxiety, in a variety of healthcare settings.
Activation of RNA polymerase II transcription by the specific DNA-binding protein LSF. Increased rate of binding of the basal promoter factor TFIIB. (1992)

While the components of the initiation complex at an RNA polymerase II basal promoter have been well characterized, few mechanistic studies have focused on how upstream DNA-binding, transcriptional activators influence protein assembly at the initiation site. Our analysis of basal transcription on both the simian virus 40 and adenovirus major late promoters demonstrates that two slow steps in initiation of transcription are the assembly of the general transcription factors TFIID and TFIIB onto the template DNA. On the simian virus 40 major late promoter, the rate of initiation complex formation is dramatically increased in the presence of the cellular transcriptional activator LSF. Direct analysis by band mobility shift assays demonstrates that LSF has no effect on the rate of binding, or the stability of TFIID on the promoter, predicting that LSF would not affect the template commitment step. Rather, kinetic analyses demonstrate that LSF reduces the lag in the rate of initiation complex formation attributable to the slow addition of TFIIB and suggest that LSF increases the rate of association of TFIIB with the committed template. In addition, LSF increases the total number of transcription complexes in long term assays, which is also consistent with LSF increasing the rate of association of TFIIB, where TFIIB is not saturating. These results indicate a mechanism for the activation of the initiation of RNA polymerase II transcription by one upstream activating protein, LSF. This mechanism may also be applicable to other activators that function in cases where limiting concentrations of TFIIB in the cell dictate slow binding of TFIIB.
κB-Ras Is a Nuclear-Cytoplasmic Small GTPase That Inhibits NF-κB Activation through the Suppression of Transcriptional Activation of p65/RelA (2010)

NF-κB is an important transcription factor involved in various biological responses, including inflammation, cell differentiation, and tumorigenesis. κB-Ras was identified as an IκB-interacting small GTPase and is reported to disturb cytokine-induced NF-κB activation. In this study, we established that κB-Ras is a novel type of nuclear-cytoplasmic small GTPase that mainly binds to GTP, and its localization seemed to be regulated by its GTP/GDP-binding state. Unexpectedly, the GDP-binding form of the κB-Ras mutant exhibited a more potent inhibitory effect on NF-κB activation, and this inhibitory effect seemed to be due to suppression of the transactivation of a p65/RelA NF-κB subunit. κB-Ras suppressed phosphorylation at serine 276 on the p65/RelA subunit, resulting in decreased interaction between p65/RelA and the transcriptional coactivator p300. Interestingly, the GDP-bound κB-Ras mutant exhibited higher interactive affinity with p65/RelA and inhibited the phosphorylation of p65/RelA more potently than wild-type κB-Ras. Taken together, these findings suggest that the GDP-bound form of κB-Ras in cytoplasm suppresses NF-κB activation by inhibiting its transcriptional activation.
Measurement of the roughness surface using the normalized autocorrelation function of the fields of the texture of speckle pattern (2012)

We present a new method of measure of the roughness based on the analysis of the texture of speckle pattern on the surface. Images of speckle pattern over the surface are captured by means of a simple configuration using a laser, beam expander, and a camera charge coupled device (CCD). Using the properties of the normalized covariance function that we obtain from the image of the speckle through the inverse Fourier transform, we relate the values of the normalized covariance function. We compare the results obtained with the results obtained with a confocal microscope. This method can be considered as a noncontact surface profiling method and is easy to implement and can be used during the manufacturing process.
Improved Power Production Efficiency of Hydrothermal Reservoirs Using Downhole Pumps (2011)

This study investigates the potential gains in power production of high temperature geothermal fields through the use of electric submersable pumps(ESP) in reservoirs currently being exploited using two phase flashing systems. The use of downhole pumps is predicted to have two benefits, the first being an increase in mass flow per well which could potentially reduce drilling costs. The second benefit the pumps can provide is the prevention of exergy loss to the flashing process which occurs under conventional two phase wellbore flow. It was predicted that the power consumed by the pump can be recovered at the power plant resulting in higher energy output for each wellbore drilled. In addition to increased power production the study investigates the economic benefits of increasing the mass flow from each well to determine if the pumps maintainence costs and power consumption could be offset to yield higher returns for plant owners. A brief summary of potential social and enviromental benefits for a closed loop approach is also discussed as the author predicts these may become of increasing importance in coming years.
A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant <i>Staphylococcus aureus</i> pandemic (2013)

The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant bacteria that are adapted to thrive in hospitalized patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with health care. The most rapidly spreading and tenacious health-care-associated clone in Europe currently is EMRSA-15, which was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. Using phylogenomic methods to analyze the genome sequences for 193 S. aureus isolates, we were able to show that the current pandemic population of EMRSA-15 descends from a health-care-associated MRSA epidemic that spread throughout England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 subclone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this subclone over the last 20 yr has grown four times faster than its progenitor. Using comparative genomic analysis we identified the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens.
A new sublingual formulation of apomorphine in the treatment of patients with Parkinson's disease (1996)

A new formulation of a sublingual tablet with 10 mg apomorphine was examined in 13 patients with Parkinson's disease. Vitamin C (250 mg) was added sublingually to lower the salivary pH. Four patients received sublingual apomorphine and nine received sublingual apomorphine as well as vitamin C. Subcutaneous apomorphine was given to all patients. The study was designed as a randomized three-way cross-over study. Tmax, Cmax, and bioavailability (F) were determined. Clinical efficacy was assessed by hand-tapping during 30 s, walking time over 25 m, and a 4-point tremor score. The mean Tmax after subcutaneous apomorphine was 14.5 +/- 1.9 min with a mean Cmax of 19.2 +/- 3.8 ng/ml. The mean clearance of all patients was 3.8 +/- 0.6 L/min. The mean Tmax after sublingual apomorphine was 61.1 +/- 6.9 min vs. 61.7 +/- 8.2 min with vitamin C. The mean Cmax was 7.4 +/- 1.0 ng/ml (- vitamin C) vs. 4.3 +/- 1.3 ng/ml (+ vitamin C). These data resulted consequently in a not significantly different mean bioavailability, varying from 17.6% (- vitamin C) to 6.1% (+ vitamin C). The latency of onset of clinical efficacy varied between 25.0 +/- 8.5 min (- vitamin C) and 26.0 +/- 5.3 min (+ vitamin C). The duration of effect was lower (not significantly) when vitamin C was added: 88.0 +/- 12.5 min (- vitamin C) vs. 61.0 +/- 11.9 min (+ vitamin C). These data show that 10 mg apomorphine sublingually was effective in 56% of the patients. The combination with vitamin C did not significantly change the latency of onset or duration of clinical efficacy. Sublingual apomorphine should be considered as an alternative in the treatment of "off"-periods in Parkinson's disease, in particular when patients have the capacity to anticipate their off-periods.
Dose‐Finding Based on Efficacy–Toxicity Trade‐Offs (2004)

We present an adaptive Bayesian method for dose-finding in phase I/II clinical trials based on trade-offs between the probabilities of treatment efficacy and toxicity. The method accommodates either trinary or bivariate binary outcomes, as well as efficacy probabilities that possibly are nonmonotone in dose. Doses are selected for successive patient cohorts based on a set of efficacy-toxicity trade-off contours that partition the two-dimensional outcome probability domain. Priors are established by solving for hyperparameters that optimize the fit of the model to elicited mean outcome probabilities. For trinary outcomes, the new algorithm is compared to the method of Thall and Russell (1998, Biometrics 54, 251-264) by application to a trial of rapid treatment for ischemic stroke. The bivariate binary outcome case is illustrated by a trial of graft-versus-host disease treatment in allogeneic bone marrow transplantation. Computer simulations show that, under a wide rage of dose-outcome scenarios, the new method has high probabilities of making correct decisions and treats most patients at doses with desirable efficacy-toxicity trade-offs.
The Microstructure of the “Flash Crash”: <i>Flow Toxicity, Liquidity Crashes, and the Probability of Informed Trading</i> (2011)

The “flash crash” of May 6, 2010, was the second-largest point swing (1,010.14 points) and the biggest one-day point decline (998.5 points) in the history of the Dow Jones Industrial Average. For a few minutes, $1 trillion in market value vanished. In this article, the authors argue that the flash crash was the result of the new dynamics at play in the current market structure. They highlight the role played by order toxicity in affecting liquidity provision, and they show that a measure of this toxicity, the volume synchronized probability of informed trading (VPIN), captures the increasing toxicity of the order flow in the hours and days prior to collapse. Because the flash crash might have been avoided had liquidity providers remained in the marketplace, a solution is proposed in the form of a “VPIN contract” that would allow liquidity providers to dynamically monitor and manage their risks. <bold>TOPICS:</bold> <ext-link>Financial crises and financial market history</ext-link>, <ext-link>exchanges/markets/clearinghouses</ext-link>, <ext-link>in markets</ext-link>
Sexuality and body image following treatment for early‐stage vulvar cancer: a qualitative study (2014)

Findings from this study indicated that the majority of women experienced little to no long-term disruption to sexuality and body image following conservative treatment for early-stage vulvar cancer. Intimacy and relationship status were more closely linked to women's sexual satisfaction than physical arousal. Factors contributing to women experiencing negative emotions were radical vulvar excision, multiple vulvar procedures and/or the development of lymphoedema.
The role of oak pollen in hay fever consultations in general practice and the factors influencing patients' decisions to consult. (1996)

The consistency of the relationship between oak pollen and the early peak of hay fever over the years examined suggests that oak pollen is a major cause of hay fever symptoms.
FMR study on spin-sprayed Ni-Zn-Co ferrite films with high permeability usable for GHz noise suppressors (2005)

We previously revealed that spin sprayed Ni-Zn ferrite films had a weak in-plane uniaxial magnetic anisotropy induced parallel to the liquid flow direction during the spin spraying. Adding a small amount of Co to the films, we made the uniaxial magnetic anisotropy definitely strong. The imaginary part of the complex permeability (/spl mu/=/spl mu/'-j/spl mu/'') of the Co-containing films measured in the remanence state exhibited a dual step-like dispersion. In order to reveal the influence of magnetic anisotropy of the films on the magnetic resonance, we deposited, in this study, films #1 (Ni/sub 0.17/Zn/sub 0.22/Fe/sub 2.61/O/sub 4/) and #2 (Ni/sub 0.19/Zn/sub 0.20/Co/sub 0.03/Fe/sub 2.58/O/sub 4/) by spin spray ferrite plating at 90/spl deg/C. The imaginary permeability in the remanence state of the film #1 (which exhibited no definite in-plane magnetic anisotropy) had a maximum at about 450 MHz, which increased with increasing external dc magnetic field, H/sub dc/ in the range of 1-3 GHz to give a similar spectrum to that of the film #2. The resonance field, H/sub R/ of the film #2 under H/sub dc/ of 1-2 kOe, which was strong enough to saturate the magnetization, exhibited a prominent in-plane angular dependence, while H/sub R/ of the film #1 exhibited a very weak angular dependence. The difference between the maximum and the minimum values of H/sub R/ for the film #2 was about 60 Oe. This means that the film #2 consists of two regions, one with a crystalline anisotropy field having an in-plane isotropic distribution due to the cubic spinel structure, and the other with an induced uniaxial anisotropy field, H/sub k/ of about 60 Oe. Assigning H/sub k/ of 60 Oe, we calculated the natural resonance frequency, f/sub r/ as 1.6 GHz. This value approximately coincided with that of the higher frequency step of /spl mu/'' for the film #2 in the remanence state. This suggests that the magnetic loss in the remanence state for the films like #2 (which exhibit prominent uniaxial anisotropy induced in film plane) is ascribed to the two regions described above.
Tolerance and Contact Sensitivity to DNFB in Mice. II. Specific in Vitro Stimulation with a Hapten, 2,4-Dinitrobenzene Sulfonic Acid (DNB·SO3Na) (1974)

Summary A hapten, 2,4-dinitrobenzene sulfonic acidsodium salt (DNB·SO3Na), a tolerogen, was shown to stimulate (in vitro) specifically lymph node or spleen cells from mice contact-sensitized to DNFB. This stimulation could be carried out in the absence of added serum. Cells from normal and from tolerant mice were not stimulated by DNB·SO3Na.
Two alpha-chain hemoglobin variants, Hb Broussais and Hb Cemenelum, characterized by cation-exchange HPLC, isoelectric focusing, and peptide sequencing (1995)

We here report the characteristics of two rare alpha-chain hemoglobin (Hb) variants. The variants were found during quantification of HbA1c by cation-exchange HPLC with the Diamat glycohemoglobin analyzer. They were further characterized by isoelectric focusing and PolyCAT A cation-exchange chromatography. The structure of the abnormal Hbs was established by amino acid analysis after separation of the globin chains by reversed-phase chromatography, digestion with trypsin, separation of the peptides by reversed-phase chromatography, and amino acid sequencing. These studies showed that the two variants were Hb Broussais [alpha 90 (FG2)Lys-->Asn] and Hb Cemenelum [alpha 92 (FG4)Arg-->Trp].
Targeting copper in cancer therapy: ‘Copper That Cancer’ (2015)

Copper is an essential micronutrient involved in fundamental life processes that are conserved throughout all forms of life. The ability of copper to catalyze oxidation-reduction (redox) reactions, which can inadvertently lead to the production of reactive oxygen species (ROS), necessitates the tight homeostatic regulation of copper within the body. Many cancer types exhibit increased intratumoral copper and/or altered systemic copper distribution. The realization that copper serves as a limiting factor for multiple aspects of tumor progression, including growth, angiogenesis and metastasis, has prompted the development of copper-specific chelators as therapies to inhibit these processes. Another therapeutic approach utilizes specific ionophores that deliver copper to cells to increase intracellular copper levels. The therapeutic window between normal and cancerous cells when intracellular copper is forcibly increased, is the premise for the development of copper-ionophores endowed with anticancer properties. Also under investigation is the use of copper to replace platinum in coordination complexes currently used as mainstream chemotherapies. In comparison to platinum-based drugs, these promising copper coordination complexes may be more potent anticancer agents, with reduced toxicity toward normal cells and they may potentially circumvent the chemoresistance associated with recurrent platinum treatment. In addition, cancerous cells can adapt their copper homeostatic mechanisms to acquire resistance to conventional platinum-based drugs and certain copper coordination complexes can re-sensitize cancer cells to these drugs. This review will outline the biological importance of copper and copper homeostasis in mammalian cells, followed by a discussion of our current understanding of copper dysregulation in cancer, and the recent therapeutic advances using copper coordination complexes as anticancer agents.
Privacy and Security in E-Learning (2007)

For a variety of advantages, universities and other organizations are resorting to e-learning to provide instruction online. While many advances have been made in the mechanics of providing online instruction, the needs for privacy and security have to-date been largely ignored. This chapter examines privacy and security issues associated with e-learning. It presents the basic principles behind privacy practices and legislation. It investigates the more popular e-learning standards to determine their provisions and limitations for privacy and security. Privacy requirements for e-learning systems are explored with respect to the “privacy principles.” The capabilities of a number of existing privacy enhancing technologies, including methods for network privacy, policy-based privacy/security management, and trust systems, are reviewed and assessed.
Docosahexaenoic Acid (DHA) and Docosapentaenoic Acid (DPAn‐6) Algal Oils Reduce Inflammatory Mediators in Human Peripheral Mononuclear Cells In Vitro and Paw Edema In Vivo (2010)

The anti-inflammatory activity associated with fish oil has been ascribed to the long-chain polyunsaturated fatty acids (LC-PUFA), predominantly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Here we examined the anti-inflammatory effects of two DHA-rich algal oils, which contain little EPA, and determined the contribution of the constituent fatty acids, particularly DHA and docosapentaenoic acid (DPAn-6). In vitro, lipopolysaccharide (LPS)-stimulated Interleukin-1 beta (IL-1beta) and Tumor Necrosis Factor-alpha (TNF-alpha) secretion in human peripheral blood mononuclear cells (PBMC) was inhibited with apparent relative potencies of DPAn-6 (most potent) > DHA > EPA. In addition, DPAn-6 decreased intracellular levels of cyclooxygenase-2 (COX-2) and was a potent inhibitor of pro-inflammatory prostaglandin E2 (PGE2) production. DHA/DPAn-6-rich DHA-S (DHA-S) algal oil was more effective at reducing edema in rats than DHA-rich DHA-T (DHA-T), suggesting that DPAn-6 has anti-inflammatory properties. Further in vivo analyses demonstrated that feeding DPAn-6 alone, provided as an ethyl ester, reduced paw edema to an extent approaching that of indomethacin and enhanced the anti-inflammatory activity of DHA when given in combination. Together, these results demonstrate that DPAn-6 has anti-inflammatory activity and enhances the effect of DHA in vitro and in vivo. Thus, DHA-S algal oil may have potential for use in anti-inflammatory applications.
Digital Supply Chain Transformation toward Blockchain Integration (2017)

Digital supply chain integration is becoming \ increasingly dynamic. Access to customer demand \ needs to be shared effectively, and product and service \ deliveries must be tracked to provide visibility in the \ supply chain. Business process integration is based on \ standards and reference architectures, which should \ offer end-to-end integration of product data. \ Companies operating in supply chains establish \ process and data integration through the specialized \ intermediate companies, whose role is to establish \ interoperability by mapping and integrating companyspecific \ data for various organizations and systems. \ This has typically caused high integration costs, and \ diffusion is slow. This paper investigates the \ requirements and functionalities of supply chain \ integration. Cloud integration can be expected to offer \ a cost-effective business model for interoperable \ digital supply chains. We explain how supply chain \ integration through the blockchain technology can \ achieve disruptive transformation in digital supply \ chains and networks.