gebhart/patrepeval huggingface dataset:
Statins: novel additions to the dermatologic arsenal? (2004)

Abstract: The 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors (statins), atorvastatin, cerivastatin, fluvastatin, pravastatin, lovastatin and simvastatin, reduce atherogenesis and cardiovascular morbidity. Besides, there is growing evidence that statins have immunomodulatory activities. Statins downregulate the expression of adhesion molecules, intercellular adhesion molecule‐1 (ICAM‐1), monocyte chemotactic protein‐1 (MAC‐1) and lymphocyte function‐associated antigen‐1 (LFA‐1), on leucocytes and endothelial cells and, through binding to LFA‐1, interfere with ICAM‐1–LFA‐1 interaction, which is crucial for activation of lymphocytes by antigen‐presenting cells, ingress of leucocytes into the inflammation sites and immunologic cytotoxicity. Statins inhibit the inducible expression of major histocompatibility complex class II in several cell types including macrophages and downregulate the expression of T‐helper‐1 (Th1) chemokine receptors on T cells, leading further to inhibition of activation of lymphocytes and their infiltration into the inflammation sites. Statins block the induction of inducible nitric oxide synthase and the expression of several proinflammatory cytokines such as tumour necrosis factor‐α and interferon‐γ in macrophages and possess antioxidant effects. These agents inhibit the proliferation of immunocytes and the activation of natural killer cells. Regarding the above facts and in view of their safety and inexpensiveness, statins may prove invaluable in the treatment of a multiplicity of dermatologic disorders, especially those characterized by ingress of activated leucocytes into the skin, such as alopecia areata, vitiligo, lichen planus, subacute cutaneous lupus erythematosus, erythema multiforme, psoriasis, bullous pemphigoid, systemic sclerosis, mycosis fungoides, toxic epidermal necrolysis and Behcet's disease.
Caffeine Suppresses Amyloid-β Levels in Plasma and Brain of Alzheimer's Disease Transgenic Mice (2009)

Recent epidemiologic studies suggest that caffeine may be protective against Alzheimer's disease (AD). Supportive of this premise, our previous studies have shown that moderate caffeine administration protects/restores cognitive function and suppresses brain amyloid-beta (Abeta) production in AD transgenic mice. In the present study, we report that acute caffeine administration to both young adult and aged AD transgenic mice rapidly reduces Abeta levels in both brain interstitial fluid and plasma without affecting Abeta elimination. Long-term oral caffeine treatment to aged AD mice provided not only sustained reductions in plasma Abeta, but also decreases in both soluble and deposited Abeta in hippocampus and cortex. Irrespective of caffeine treatment, plasma Abeta levels did not correlate with brain Abeta levels or with cognitive performance in individual aged AD mice. Although higher plasma caffeine levels were strongly associated with lower plasma Abeta1-40 levels in aged AD mice, plasma caffeine levels were also not linked to cognitive performance. Plasma caffeine and theophylline levels were tightly correlated, both being associated with reduced inflammatory cytokine levels in hippocampus. Our conclusion is two-fold: first, that both plasma and brain Abeta levels are reduced by acute or chronic caffeine administration in several AD transgenic lines and ages, indicating a therapeutic value of caffeine against AD; and second, that plasma Abeta levels are not an accurate index of brain Abeta levels/deposition or cognitive performance in aged AD mice.
Treatment of Bipolar I Disorder in an Adolescent with Olanzapine (2000)

Bipolar I disorder is estimated to affect 0.6% of adolescents. Lithium, sodium valproate, carbamazapine, and adjunctive treatment with benzodiazapines and antipsychotics have been used to treat bipolar I disorders. We report a case of a 17-year-old adolescent male with bipolar I disorder who responded favorably to the treatment with the atypical antipsychotic olanzapine. We hypothesize that olanzapine's broad affinity for both dopaminergic and serotonergic receptors may be related to the beneficial therapeutic outcome.
A 5-GHz wireless LAN transmitter with integrated tunable high-Q RF filter (2008)

A tunable high-Q RF filter suitable for wireless transmitters has been implemented in standard CMOS technology. Two stagger-tuned Q-enhanced resonators form a filter that can be tuned across frequency and bandwidth. A 5.145-GHz filter with 200-MHz bandwidth and 0.8-dB of ripple is demonstrated in an 802.11a sliding-IF transmitter. The transmitter provides spectral mask and EVM-compliant output power of -8.26 dBm for a 54-Mb/s OFDM signal. At lower output power, an EVM of -32.3 dB is achieved.
Preclinical MRI and NMR Biomarkers of Alzheimer's Disease: Concepts and Applications (2008)

Alzheimer's disease is an important social and economic issue for our societies. The development of therapeutics against this severe dementia requires assessing the effects of new drugs in animal models thanks to dedicated biomarkers. This review first overviews Alzheimer's disease and its models as well as the concept of biomarkers. It then focuses on MRI and NMR biomarkers of Alzheimer's disease in animals. Anatomical markers such as atrophy and angiography are useful to phenotype newly developed models of Alzheimer's disease, even if the alterations in these animals are not as severe as in humans. Amyloid plaques imaging is a promising marker of the pathology in animals, and is a rapidly evolving field of MRI. Functional methods such as perfusion and diffusion imaging or spectroscopy are able to detect alterations in transgenic mice mimicking Alzheimer and also to show similar alterations than in humans. They can thus be good translational markers of the disease. Manganese-Enhanced MRI shows a reduction of neuronal transportation in transgenic models of Alzheimer and it allows monitoring improvements induced by treatments of the disease. It is thus a promising biomarker of the pathology in animals.
Activation of Dendritic Cells That Cross-Present Tumor-Derived Antigen Licenses CD8+ CTL to Cause Tumor Eradication (2004)

The fate of naive CD8(+) T cells is determined by the environment in which they encounter MHC class I presented peptide Ags. The manner in which tumor Ags are presented is a longstanding matter of debate. Ag presentation might be mediated by tumor cells in tumor draining lymph nodes or via cross-presentation by professional APC. Either pathway is insufficient to elicit protective antitumor immunity. We now demonstrate using a syngeneic mouse tumor model, expressing an Ag derived from the early region 1A of human adenovirus type 5, that the inadequate nature of the antitumor CTL response is not due to direct Ag presentation by the tumor cells, but results from presentation of tumor-derived Ag by nonactivated CD11c(+) APC. Although this event results in division of naive CTL in tumor draining lymph nodes, it does not establish a productive immune response. Treatment of tumor-bearing mice with dendritic cell-stimulating agonistic anti-CD40 mAb resulted in systemic efflux of CTL with robust effector function capable to eradicate established tumors. For efficacy of anti-CD40 treatment, CD40 ligation of host APC is required because adoptive transfer of CD40-proficient tumor-specific TCR transgenic CTL into CD40-deficient tumor-bearing mice did not lead to productive antitumor immunity after CD40 triggering in vivo. CpG and detoxified LPS (MPL) acted similarly as agonistic anti-CD40 mAb with respect to CD8(+) CTL efflux and tumor eradication. Together these results indicate that dendritic cells, depending on their activation state, orchestrate the outcome of CTL-mediated immunity against tumors, leading either to an ineffective immune response or potent antitumor immunity.
Effects of mutating putative two-component systems on biofilm formation by Streptococcus mutans UA159 (2001)

Streptococcus mutans has at least six pairs of open reading frames that are homologous to bacterial two-component regulatory systems. Putative response regulators from five out of six of these pairs were successfully mutated by insertion of a kanamycin resistance marker and the effects of inactivation of the genes on the ability of the cells to form biofilms in an in vitro model were assessed. Disruption of the response regulators of four systems had no effect on biofilm formation, whereas disruption of one response regulator caused a substantial decrease in biofilm formation as compared to the wild-type S. mutans.
Characterization of Methionine Export in Corynebacterium glutamicum (2005)

Corynebacterium glutamicum is known for its effective excretion of amino acids under particular metabolic conditions. Concomitant activities of uptake and excretion systems would create an energy-wasting futile cycle; amino acid export systems are therefore tightly regulated. We have used a DNA microarray approach to identify genes for membrane proteins which are overexpressed under conditions of elevated cytoplasmic concentrations of methionine. One of these genes was brnF, coding for the larger subunit of BrnFE, a previously identified two-component isoleucine export system. By deletion, complementation, and overexpression of the brnFE genes in a C. glutamicum strain, in which the two uptake systems for methionine were inactivated, we identified BrnFE as being responsible for methionine export. In the presence of both substrates in the cytoplasm, BrnFE was found to transport isoleucine and methionine at similar rates. The expression of the brnFE gene cluster depends on an Lrp-type transcription factor and was shown to be strongly induced by increasing cytoplasmic methionine concentration. Methionine was a better inducer than isoleucine, indicating that methionine rather than isoleucine might be the native substrate of BrnFE. When the synthesis of BrnFE was blocked by chloramphenicol, fast methionine export was still observed, but only at greatly increased cytoplasmic levels of this amino acid. This indicates the presence of at least one other methionine export system, presumably with low affinity but high capacity. Under conditions where cytoplasmic methionine does not exceed a concentration of 50 mM, BrnFE is the dominant export system for this amino acid.
Supportive angiogenic and osteogenic differentiation of mesenchymal stromal cells and endothelial cells in monolayer and co-cultures (2016)

Sites of implantation with compromised biology may be unable to achieve the required level of angiogenic and osteogenic regeneration. The specific function and contribution of different cell types to the formation of prevascularized, osteogenic networks in co-culture remains unclear. To determine how bone marrow-derived mesenchymal stromal cells (BMSCs) and endothelial cells (ECs) contribute to cellular proangiogenic differentiation, we analysed the differentiation of BMSCs and ECs in standardized monolayer, Transwell and co-cultures. BMSCs were derived from the iliac bone marrow of five patients, characterized and differentiated in standardized monolayers, permeable Transwells and co-cultures with human umbilical vein ECs (HUVECs). The expression levels of CD31, von Willebrand factor, osteonectin (ON) and Runx2 were assessed by quantitative reverse transcriptase polymerase chain reaction. The protein expression of alkaline phosphatase, ON and CD31 was demonstrated via histochemical and immunofluorescence analysis. The results showed that BMSCs and HUVECs were able to retain their lineage-specific osteogenic and angiogenic differentiation in direct and indirect co-cultures. In addition, BMSCs demonstrated a supportive expression of angiogenic function in co-culture, while HUVEC was able to improve the expression of osteogenic marker molecules in BMSCs.
Effect of Hypotension and Carbon Dioxide Changes in an Improved Genuine Closed Cranial Window Rat Model (2004)

The genuine closed cranial window model, in which the thinned parietal bone constitutes the covering of the preparation, has contributed to a better understanding of the pathophysiological mechanisms in migraine. In its present form, only measurements of the middle meningeal artery (MMA) are performed. The aim of this study was, in addition, to measure pial artery/arteriole (PA) diameter and cortical cerebral blood flux in the same cranial window. The model was evaluated by studying the effects of hypotension and changes in arterial carbon dioxide pressure (PaCO2), because these parameters might influence the interpretation of pharmacological experiments. Out of 23 successful experiments it was possible to measure all three parameters in 19 animals. In four, PA diameter could not be measured, while MMA diameter and local cortical cerebral blood flux (LCBF(Flux)) always could. Haemorrhage-induced hypotension (-64+/-0.8 mmHg) caused an increase of MMA diameter of 11.8+/-8.4%, PA diameter of 61.2+/-7.7% and a decrease in LCBF(Flux) of -36.4+/-2.5%. The decrease in blood pressure did not significantly change the MMA (P=0.38); however, the PA diameter and the LCBF(Flux) were affected (P<0.001). All three parameters were sensitive to hypo- and hypercapnia. In conclusion, we have shown that not only MMA but also PA diameter and LCBF(Flux) can be measured in the same cranial window. Tight control of PaCO2 is essential in pharmacological experiments. If test substances possess hypotensive actions, it may be difficult to interpret whether the PA dilation is caused by the induced hypotension per se or is a direct pharmacological action or a combination. In contrast, the MMA does not autoregulate and MMA diameter changes in pharmacological studies may exclusively be due to direct pharmacological effects.
Catalytic conversion of glycerol and sugar alcohols to value-added products (2006)

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.
Allergic rhinitis and asthma: inflammation in a one-airway condition (2006)

Inflammation is a key feature of both allergic rhinitis and asthma. There are therefore potential benefits for application of anti-inflammatory strategies that target both these anatomic sites.
Site-specific Tyrosine Phosphorylation of IκBα Negatively Regulates Its Inducible Phosphorylation and Degradation (1996)

The transcription factor NF-kappaB is retained in the cytoplasm by its interaction with the inhibitory subunit known as IkappaB. Signal-induced serine phosphorylation and subsequent ubiquitination of IkappaBalpha target it for degradation by the 26 S proteasome. Recently, pervanadate, a protein-tyrosine phosphatase inhibitor, was shown to block the degradation of IkappaBalpha, thus inhibiting NF-kappaB activation. We investigated the mechanism by which pervanadate inhibits the degradation of IkappaBalpha. Western blot analysis of IkappaBalpha from tumor necrosis factor-treated cells revealed a slower migrating IkappaBalpha species that was subsequently degraded. However, pervanadate-treated cells also revealed a slower migrating species of IkappaBalpha that appeared in a time- and dose-dependent manner and was not degraded by tumor necrosis factor. The slower migrating species of IkappaBalpha from pervanadate-treated cells was tyrosine-phosphorylated as revealed by cross-reactivity with anti-phosphotyrosine antibodies, by the ability of the specific tyrosine phosphatase PTP1B to dephosphorylate it, and by phosphoamino acid analysis of IkappaBalpha immunoprecipitated from 32P-labeled cells. By site-specific mutagenesis and deletion analysis, we identified Tyr-42 on IkappaBalpha as the phosphoacceptor site. Furthermore, in an in vitro reconstitution system, tyrosine-phosphorylated IkappaBalpha was protected from degradation. Our results demonstrate that inducible phosphorylation and degradation of IkappaBalpha are negatively regulated by phosphorylation at Tyr-42, thus preventing NF-kappaB activation.
CHEMISTRY OF OPIOID PEPTIDES (1983)

Journal Article CHEMISTRY OF OPIOID PEPTIDES Get access J S MORLEY, DSc J S MORLEY, DSc Pain Relief Foundation Walton HospitalLiverpool Search for other works by this author on: Oxford Academic PubMed Google Scholar British Medical Bulletin, Volume 39, Issue 1, 1983, Pages 5–10, https://doi.org/10.1093/oxfordjournals.bmb.a071790 Published: 01 March 1983
Molecular and Cultural Analysis of the Microflora Associated with Endodontic Infections (2002)

Cultural studies have indicated that a subset of the oral microflora is responsible for endodontic infections. Approximately 50% of oral bacteria are unculturable, so it is likely that currently unknown bacteria are present in such infections. In this study, cultural and molecular analyses were performed on the microflora in aspirate samples collected from 5 infected root canals. 16S rDNA sequences from 261 isolates and 624 clones were identified by comparison with database sequences. Sixty-five taxa were identified, of which 26 were found by the molecular method alone. A mean of 20.2 taxa was found in each sample. A new species of Dialister was the only organism present in all 5 samples. Twenty-seven novel taxa were detected, 18 of which belonged to the phylum Firmicutes and 8 to Bacteroidetes. Culture-independent, molecular analysis has revealed a more diverse microflora associated with endodontic infections than that revealed by cultural methods alone.
The Timing of Pediatric Immunization and the Risk of Insulin-Dependent Diabetes Mellitus (1997)

From the Division of Infectious Diseases, LDS Hospital and University of Utah School of Medicine (DCC), Salt Lake City, Utah; and Classen Immunotherapies, Inc. (JBC), Baltimore, Maryland Address for correspondence: John Barthelow Classen, M.D., M.B.A., Classen Immunotherapies, Inc., 6517 Montrose Avenue, Baltimore, MD 21212 (Fax: 410-377-8526; E-mail: [email protected])
Nucleation and Crystal Growth of Organic–Inorganic Lead Halide Perovskites under Different Relative Humidity (2015)

Organic-inorganic lead halide perovskite compounds are very promising materials for high-efficiency perovskite solar cells. But how to fabricate high-quality perovksite films under controlled humidity conditions is still an important issue due to their sensitivity to moisture. In this study, we investigated the influence of ambient humidity on crystallization and surface morphology of one-step spin-coated perovskite films, as well as the performance of solar cells based on these perovskite films. On the basis of experimental analyses and thin film growth theory, we conclude that the influence of ambient humidity on nucleation at spin-coating stage is quite different from that on crystal growth at annealing stage. At the spin-coating stage, high nucleation density induced by high supersaturation prefers to appear under anhydrous circumstances, resulting in layer growth and high coverage of perovskite films. But at the annealing stage, the modest supersaturation benefits formation of perovskite films with good crystallinity. The films spin-coated under low relative humidity (RH) followed by annealing under high RH show an increase of crystallinity and improved performance of devices. Therefore, a mechanism of fast nucleation followed by modest crystal growth (high supersaturation at spin-coating stage and modest supersaturation at annealing stage) is suggested in the formation of high-quality perovskite films.
Retrospective Review of 707 Cases of Spinal Cord Stimulation: Indications and Complications (2010)

Appropriate patient selection and minimizing complications are critical for successful spinal cord stimulation (SCS) therapy in managing intractable pain. We thus reviewed electronic medical records of 707 consecutive cases of patients who received SCS therapy in the Cleveland Clinic from 2000 to 2005 with an emphasis on indications and complications. SCS was used to treat complex regional pain syndrome (CRPS) (345 cases), failed back surgery syndrome (235 cases), peripheral vascular disease (20 cases), visceral pain in the chest, abdomen, and pelvis (37 cases), and peripheral neuropathy (70 cases). CRPS and failed back surgery syndrome accounted for 82% of the cases. The implant-to-trial ratio was 75% on average, with the highest for CRPS type 2 (83%) and the lowest for peripheral vascular diseases (65%). The only documented complication associated with SCS trials was lead migration in 5 of 707 patients (0.7%). There were no permanent neurological deficits or deaths as a result of SCS implant or its complications. Hardware-related complications were common (38%) and included lead migration (22.6%), lead connection failure (9.5%), and lead breakage (6%). Revisions or replacements were required in these cases. Biologically related complications included pain at the generator site (12%) and clinical infection (4.5%; 2.5% with positive culture). The rates of infection varied among the different diagnoses with the highest in failed back surgery syndrome (6.3%). Patients with diabetes had an infection rate of 9%, over the 4% in non-diabetics. Infections were managed successfully with explantation and antibiotic therapy without permanent sequela.
Methods for authenticating cell lines. (1992)

Methods for authentication of cell lines include tests for microbial contamination, verification of the species of origin, documentation of particular characteristics or functions and the absolute identification of individual cell lines. Experience indicates that mycoplasma contamination is still a serious problem in the cell culture field, with estimates on frequencies of infection varying from 10% upwards. The utilization of pre-screened reagents and antibiotic-free cultivation, plus the application of improved procedures, such as fluorescent dyes and molecular probes for detection, provide effective means to avoid mycoplasma infection and facilitate control. Viral contamination is perhaps more problematic, especially where no overt cytopathic effect results. The potential exists for the introduction of viruses from the cell culture technician or reagents used. Representative problem viruses are listed with standard procedures for screening. Detailed studies on animal cell cross contaminations have been performed and published. The frequency of detection of problem culture varied from 17-36% in studies performed in the USA. Both interspecies and intraspecies contaminations have been involved. Awareness of the potential for this problem plus the application of several characterization procedures are key factors for control. For example, fluorescent antibody staining, iso-enzyme analysis, cytogenetic evaluation and DNA finger-printing using molecular probes are needed for quality assurance on seed stocks. The critical importance of generating well-characterized reference cell stocks for use over the years is emphasized.
The Best of Both Worlds: Combining Recent Advances in Neural Machine Translation (2018)

Mia Xu Chen, Orhan Firat, Ankur Bapna, Melvin Johnson, Wolfgang Macherey, George Foster, Llion Jones, Mike Schuster, Noam Shazeer, Niki Parmar, Ashish Vaswani, Jakob Uszkoreit, Lukasz Kaiser, Zhifeng Chen, Yonghui Wu, Macduff Hughes. Proceedings of the 56th Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers). 2018.