gebhart/patrepeval huggingface dataset:
Flash X-ray Microscopy (1979)

Soft x-ray contact microscopy, utilizing single-shot exposures of approximately 60 nanoseconds duration in polymethyl methacrylate, has been realized with a resolution of 300 angstroms. The radiation spectrum is intense in the "window" between 23 and 44 angstroms where water is transparent compared to biological materials, and therefore permits viewing of wet samples.
Schottky-barrier height of a Ti-W alloy onn-type andp-type Si (1986)

Impurity effects on Schottky barriers have been investigated using a concentrated Ti-W alloy for barrier-height measurements on both n-type and p-type Si(100). The measurements were performed in the temperature range 175--295 K using forward current-voltage characteristics. Silicide-formation reaction was monitored by Rutherford backscattering spectroscopy, Auger-electron spectroscopy, and glancing-angle x-ray diffraction. The results showed that Ti dominates the barrier height, and that W does not play any role in barrier formation. The interdiffusion of Ti and Si dominated the reaction between the alloy and Si at the interface. For both the metal and the reacted silicide phase the n- and p-type barrier heights were found to decrease with increasing temperature with the sum equal, within the experimental accuracy, to the indirect energy gap of Si in the range of temperature measured. These results indicate that the temperature dependence of the barrier heights is mainly due to that of the indirect energy gap in Si.
Step-tunable (100 GHz) hybrid laser based on Verniereffect between Fabry-Perotcavity and sampled fibre Bragg grating (1999)

Frequency step-tunability is demonstrated in a hybrid fibre grating external cavity laser for the first time. This new configuration uses an in-fibre sampled Bragg grating as the frequency selective element which allows the laser to be step-tuned by 100 GHz from 1551.09 to 1556.66 nm.
Respiratory Syncytial Virus Predisposes Mice to Augmented Allergic Airway Responses Via IL-13-Mediated Mechanisms (2001)

The development of severe childhood asthma may be influenced by several factors including environmental and infectious stimuli. The causal relationship between infectious viral responses, such as respiratory syncytial virus (RSV), and severe asthma during early childhood is unclear. In these studies, the ability for an initial RSV infection to exacerbate and promote a more severe asthmatic-type response was investigated by combining established murine models of disease. We examined the ability of RSV to induce exacerbation of allergic disease over a relatively long period, leading to development of severe airway responses including airway inflammation and hyperreactivity. The preferential production of IL-13 during a primary RSV infection appears to play a critical role for the exacerbation of cockroach allergen-induced disease. The depletion of IL-13 during RSV infections inhibited the exacerbation and acceleration of severe allergen-induced airway hyperreactivity. This was indicated by decreases in airway hyperreactivity and changes in lung chemokine production. These data suggest that the airway responses during asthma can be greatly affected by a previous RSV infection, even when infection occurs before allergen sensitization. Overall, infection of the airways with RSV can induce an IL-13-dependent change in airway function and promotes an environment that contributes to the development of severe allergic asthmatic responses.
Low-overhead design of soft-error-tolerant scan flip-flops with enhanced-scan capability (2006)

With technology scaling, soft error resilience is becoming a major concern in circuit design. This paper presents a class of low-overhead flip-flops suitable for soft error detection and correction. The proposed design reuses logic elements typically available in a standard-cell implementation of a flip-flop to reduce hardware overhead. We demonstrate that the proposed flip-flops are also suitable for enhanced scan based delay fault testing, which allows arbitrary two-pattern test application for the best combinational path testability. The proposed flip-flops show an average power reduction of 16% and area improvement of 17% compared to the best alternative techniques with no additional delay overhead.
The causal link between human papillomavirus and invasive cervical cancer: A population‐based case‐control study in colombia and spain (1992)

To evaluate the association between human papillomavirus (HPV) and cervical cancer, we performed a population-based case-control study in Columbia and Spain, the former country having an incidence rate of cervical cancer about 8 times higher than the latter. It included 436 cases of histologically confirmed invasive cervical cancer and 387 randomly selected population controls. Information on demographic variables, sexual behaviour and other risk factors was obtained by interview. HPV-DNA was measured in cervical-swab specimens with 3 hybridization assays: ViraPap, Southern hybridization (SH) and polymerase chain reaction (PCR). The presence of HPV-DNA and detection of types 16, 18, 31, 33 and 35 were strongly associated with cervical cancer in each country regardless of the assay used. For both countries combined the adjusted odds ratios and 95% confidence intervals were: ViraPap OR = 25.9 (10.0-66.7); SH OR = 6.8 (3.4-13.4); and PCR OR = 28.8 (15.7-52.6). HPV-16 was the most common type detected in both cases and controls. Our results indicate that there is a very strong association between HPV 16, 18, 31, 33 and 35 and invasive cervical cancer and that this association is probably causal.
Acidic and basic fibroblast growth factors are present in glioblastoma multiforme. (1991)

Immunohistochemistry was performed on paraffin sections from human glioblastoma multiforme and normal brain tissue. Acidic fibroblast growth factor (FGF) was abundantly present in astrocytes from all glioblastomas studied. Basic FGF was found in the matrix surrounding proliferating blood vessels in most of the glioblastomas. In contrast, astrocytes from normal brain did not contain acidic FGF, and perivascular matrix staining was not demonstrated for basic FGF in the normal brain. Both growth factors could be demonstrated in neurons, Purkinje cells, capillary endothelium, and arterial walls in the normal brain. This study implicates both growth factors in the pathogenesis of malignant glioma. Both may be significant mediators of angiogenesis in glioblastoma.
Polarization Restricts Hepatitis C Virus Entry into HepG2 Hepatoma Cells (2009)

The primary reservoir for hepatitis C virus (HCV) replication is believed to be hepatocytes, which are highly polarized with tight junctions (TJ) separating their basolateral and apical domains. HepG2 cells develop polarity over time, resulting in the formation and remodeling of bile canalicular (BC) structures. HepG2 cells expressing CD81 provide a model system to study the effects of hepatic polarity on HCV infection. We found an inverse association between HepG2-CD81 polarization and HCV pseudoparticle entry. As HepG2 cells polarize, discrete pools of claudin-1 (CLDN1) at the TJ and basal/lateral membranes develop, consistent with the pattern of receptor staining observed in liver tissue. The TJ and nonjunctional pools of CLDN1 show an altered association with CD81 and localization in response to the PKA antagonist Rp-8-Br-cyclic AMPs (cAMPs). Rp-8-Br-cAMPs reduced CLDN1 expression at the basal membrane and inhibited HCV infection, supporting a model where the nonjunctional pools of CLDN1 have a role in HCV entry. Treatment of HepG2 cells with proinflammatory cytokines, tumor necrosis factor alpha and gamma interferon, perturbed TJ integrity but had minimal effect(s) on cellular polarity and HCV infection, suggesting that TJ integrity does not limit HCV entry into polarized HepG2 cells. In contrast, activation of PKC with phorbol ester reduced TJ integrity, ablated HepG2 polarity, and stimulated HCV entry. Overall, these data show that complex hepatocyte-like polarity alters CLDN1 localization and limits HCV entry, suggesting that agents which disrupt hepatocyte polarity may promote HCV infection and transmission within the liver.
Overexpression of ETS2 in human esophageal squamous cell carcinoma (2003)

The results suggested that ETS2 overexpressed in paired human ESCC tissue samples at both mRNA and protein levels and may be associated with the tumorigenesis of esophagus.
Culture conditions profoundly impact phenotype in BEAS‐2B, a human pulmonary epithelial model (2014)

BEAS-2B, an immortalized, human lung epithelial cell line, has been used to model pulmonary epithelial function for over 30 years. The BEAS-2B phenotype can be modulated by culture conditions that include the presence or absence of fetal bovine serum (FBS). The popularity of BEAS-2B as a model of arsenic toxicology, and the common use of BEAS-2B cultured both with and without FBS, led us to investigate the impact of FBS on BEAS-2B in the context of arsenic toxicology. Comparison of genome-wide gene expression in BEAS-2B cultured with or without FBS revealed altered expression in several biological pathways, including those related to carcinogenesis and energy metabolism. Real-time measurements of oxygen consumption and glycolysis in BEAS-2B demonstrated that FBS culture conditions were associated with a 1.4-fold increase in total glycolytic capacity, a 1.9-fold increase in basal respiration, a 2.0-fold increase in oxygen consumed for ATP production and a 2.8-fold increase in maximal respiration, compared with BEAS-2B cultured without FBS. Comparisons of the transcriptome changes in BEAS-2B resulting from FBS exposure to the transcriptome changes resulting from exposure to 1 μM sodium arsenite revealed that mRNA levels of 43% of the arsenite-modulated genes were also modulated by FBS. Cytotoxicity studies revealed that BEAS-2B cells exposed to 5% FBS for 8 weeks were almost 5 times more sensitive to arsenite cytotoxicity than non-FBS-exposed BEAS-2B cells. Phenotype changes induced in BEAS-2B by FBS suggest that culture conditions should be carefully considered when using BEAS-2B as an experimental model of arsenic toxicity.
In vivo evaluation of CYP1A2, CYP2A6, NAT‐2 and xanthine oxidase activities in a Greek population sample by the RP‐HPLC monitoring of caffeine metabolic ratios (2007)

A RP-HPLC method was developed for the assessment of caffeine and its metabolites in urine and was used for the evaluation of the CYP1A2, CYP2A6, xanthine oxidase (XO) and N-acetyl-transferase-2 (NAT-2) in vivo activities in 44 Greek volunteers (21 men, 23 women). Spot urine samples were analyzed 6 h after 200 mg caffeine consumption, following a 30 h methylxantine-free diet. The major urinary caffeine metabolites are 1-methyluric acid (1U), 5-acetylamino-6-formylamino-3-methyluracil (AFMU), 1-methylxanthine (1X), 1,7-dimethyluric acid (17U) and 1,7-dimethylxanthine (17X). CYP1A2, CYP2A6, XO and NAT-2 activities were estimated from the metabolic ratios (AFMU + 1U + 1X)/17U, 17U/17X, 1U/(1X + 1U) and AFMU/(AFMU + 1U + 1X), respectively. Metabolites and internal standard were extracted with chloroform/isopropanol (85:15, v/v) and separated on a C18 column by an isocratic HPLC system using a two-step elution with manual switch from solvent A (0.1% acetic acid-methanol-acetonitrile, 92:4:5 v/v) to solvent B (0.1% acetic acid-methanol, 60:40, v/v), and detected at 280 nm. The method exhibited adequate metabolite separation (resolution factors >1.48), accuracy (94.1-106.3%) and intraday and interday precision <8.02 and <8.78%, respectively (n = 6). Smoking affected only CYP1A2, whereas gender had no effect in any enzyme activity. NAT-2 exhibited bimodal distribution, 63.6% of volunteers being slow acetylators. The developed RP-HPLC method was fully validated and successfully applied for the evaluation of CYP1A2, CYP2A6, XO and NAT-2 activities.
Aspects of first‐order differential microphone arrays in the presence of sensor imperfections (2002)

Abstract Array processing for broadband signals like speech is not a trivial task. Most sensor arrangements and the related beamforming algorithms show strong frequency dependent characteristics. Differential microphone arrays promise frequency independent high directional gain with compact arrangements. However, this type of microphone array has also the problem that even small deviations in microphone properties can cause severe degradation of the array's performance. Especially at low frequencies the achievable gain is limited by the influence of sensor mismatch and sensor noise.In this contribution the performance of first‐order differential arrays is examined and important parameters such as array response and directivity index are thoroughly studied. The frequency dependence of these parameters is investigated in order to derive limits for a favorable frequency range. First, the performance of the array is examined for ideal sensors. Then, two different models for sensor mismatch are introduced to describe the degradation of the array's performance. In addition, solutions for sensor calibration and experimental results with real microphones are presented.
Cocrystal or Salt:  Does It Really Matter? (2007)

A structural analysis of over 80 salts and cocrystals synthesized from equimolar amounts of carboxylic acids and N-heterocycles demonstrates that salt formation as a result of proton transfer from the acid to the base frequently (11/24; 45%) results in a lattice with an unpredictable chemical (solvate) or stoichiometric composition. However, if no proton transfer takes place and the result is a molecular cocrystal, a crystal lattice with an unexpected chemical content or stoichiometry is much less likely (3/61; 5%). These results indicate that the process of converting a neutral carboxylic acid into a carboxylate anion can have important structural consequences that make structure prediction and targeted supramolecular synthesis of salts much more difficult than of cocrystals. Consequently, cocrystals may offer new opportunities for producing a greater diversity of solid forms of drug substances that exhibit the appropriate balance of critical properties for development into a viable and effective drug product.
Impact of Influenza B Lineage-Level Mismatch Between Trivalent Seasonal Influenza Vaccines and Circulating Viruses, 1999–2012 (2014)

The population-level impact of lineage-level mismatch between the vaccine and circulating strains of influenza B viruses is substantial, especially among children and adolescents. The results provide strong support for the inclusion of both influenza B lineages in seasonal influenza vaccines.
Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase (2007)

A small population of plasmacytoid DCs (pDCs) in mouse tumor-draining LNs can express the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO). We show that these IDO+ pDCs directly activate resting CD4+CD25+Foxp3+ Tregs for potent suppressor activity. In vivo, Tregs isolated from tumor-draining LNs were constitutively activated and suppressed antigen-specific T cells immediately ex vivo. In vitro, IDO+ pDCs from tumor-draining LNs rapidly activated resting Tregs from non-tumor-bearing hosts without the need for mitogen or exogenous anti-CD3 crosslinking. Treg activation by IDO+ pDCs was MHC restricted, required an intact amino acid-responsive GCN2 pathway in the Tregs, and was prevented by CTLA4 blockade. Tregs activated by IDO markedly upregulated programmed cell death 1 ligand 1 (PD-L1) and PD-L2 expression on target DCs, and the ability of Tregs to suppress target T cell proliferation was abrogated by antibodies against the programmed cell death 1/PD-L (PD-1/PD-L) pathway. In contrast, Tregs activated by anti-CD3 crosslinking did not cause upregulation of PD-Ls, and suppression by these cells was unaffected by blocking the PD-1/PD-L pathway. Tregs isolated from tumor-draining LNs in vivo showed potent PD-1/PD-L-mediated suppression, which was selectively lost when tumors were grown in IDO-deficient hosts. We hypothesize that IDO+ pDCs create a profoundly suppressive microenvironment within tumor-draining LNs via constitutive activation of Tregs.
Nanoporous Gold Films Created Using Templates Formed from Self‐Assembled Structures of Inorganic–Block Copolymer Micelles (2003)

A multistep procedure for creating nanohole‐patterned gold films (see Figure) is presented. The steps include the self‐assembly of metal‐loaded polystyrene‐ block ‐poly(2‐vinylpyridine) micelles on GaAs substrates, hydrogen gas plasma treatment, directional reactive ion etching, and gold sputtering. The size and separation of holes resemble that of the gold cluster pattern.
Structural Characterization of Proline-rich Tyrosine Kinase 2 (PYK2) Reveals a Unique (DFG-out) Conformation and Enables Inhibitor Design (2009)

Proline-rich tyrosine kinase 2 (PYK2) is a cytoplasmic, non-receptor tyrosine kinase implicated in multiple signaling pathways. It is a negative regulator of osteogenesis and considered a viable drug target for osteoporosis treatment. The high-resolution structures of the human PYK2 kinase domain with different inhibitor complexes establish the conventional bilobal kinase architecture and show the conformational variability of the DFG loop. The basis for the lack of selectivity for the classical kinase inhibitor, PF-431396, within the FAK family is explained by our structural analyses. Importantly, the novel DFG-out conformation with two diarylurea inhibitors (BIRB796, PF-4618433) reveals a distinct subclass of non-receptor tyrosine kinases identifiable by the gatekeeper Met-502 and the unique hinge loop conformation of Leu-504. This is the first example of a leucine residue in the hinge loop that blocks the ATP binding site in the DFG-out conformation. Our structural, biophysical, and pharmacological studies suggest that the unique features of the DFG motif, including Leu-504 hinge-loop variability, can be exploited for the development of selective protein kinase inhibitors.
In vitro co-cultures of human gut bacterial species as predicted from co-occurrence network analysis (2018)

Network analysis of large metagenomic datasets generated by current sequencing technologies can reveal significant co-occurrence patterns between microbial species of a biological community. These patterns can be analyzed in terms of pairwise combinations between all species comprising a community. Here, we construct a co-occurrence network for abundant microbial species encompassing the three dominant phyla found in human gut. This was followed by an in vitro evaluation of the predicted microbe-microbe co-occurrences, where we chose species pairs Bifidobacterium adolescentis and Bacteroides thetaiotaomicron, as well as Faecalibacterium prausnitzii and Roseburia inulinivorans as model organisms for our study. We then delineate the outcome of the co-cultures when equal distributions of resources were provided. The growth behavior of the co-culture was found to be dependent on the types of microbial species present, their specific metabolic activities, and resulting changes in the culture environment. Through this reductionist approach and using novel in vitro combinations of microbial species under anaerobic conditions, the results of this work will aid in the understanding and design of synthetic community formulations.
Acetazolamide in Bipolar Affective Disorders (1994)

Acetazolamide is a carbonic anhydrase inhibitor used for a variety of purposes, including adjunctively in the management of various types of epilepsy. A previous study on its psychotropic effects suggested the possibility of efficacy in atypical psychotic states, especially those characterized by cyclicity. In the present investigation, 16 patients with refractory affective symptomatology were treated with acetazolamide in a prospective open trial after exhaustive trials with antidepressants, lithium, carbamazepine, divalproex, and other anticonvulsants. Seven of the 16 (44%) responded positively, in some cases dramatically, for as long as 2 years. Analysis revealed that all of the responders were either in a depressive phase or in a rapid-cycling phase of a bipolar illness and that all had experienced partial positive response to at least one other anticonvulsant and were being maintained on anti-convulsant therapy when the response occurred. Salient theoretical issues are explored.
Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates (2015)

Novel therapies that specifically target activation and expansion of pathogenic immune cell subsets responsible for autoimmune attacks are needed to confer long-term remission. Pathogenic cells in autoimmunity include memory T lymphocytes that are long-lived and present rapid recall effector functions with reduced activation requirements. Whereas the CD28 costimulation pathway predominantly controls priming of naive T cells and hence generation of adaptive memory cells, the roles of CD28 costimulation on established memory T lymphocytes and the recall of memory responses remain controversial. In contrast to CD80/86 antagonists (CTLA4-Ig), selective CD28 antagonists blunt T cell costimulation while sparing CTLA-4 and PD-L1-dependent coinhibitory signals. Using a new selective CD28 antagonist, we showed that Ag-specific reactivation of human memory T lymphocytes was prevented. Selective CD28 blockade controlled both cellular and humoral memory recall in nonhuman primates and induced long-term Ag-specific unresponsiveness in a memory T cell-mediated inflammatory skin model. No modification of memory T lymphocytes subsets or numbers was observed in the periphery, and importantly no significant reactivation of quiescent viruses was noticed. These findings indicate that pathogenic memory T cell responses are controlled by both CD28 and CTLA-4/PD-L1 cosignals in vivo and that selectively targeting CD28 would help to promote remission of autoimmune diseases and control chronic inflammation.
Synthesis and protein-tyrosine kinase inhibitory activities of flavonoid analogs (1991)

Treatment of o-hydroxyacetophenones 2a-e with excess lithium bis(trimethylsilyl)amide followed by dialkyl carbonates gave alkyl 3-(2-hydroxyaryl)-3-oxopropanoates 3a-e. The latter substances were transformed through the reaction of their magnesium chelates with benzoyl chlorides into a series of 3-(alkoxycarbonyl)-2-arylflavones, which were subsequently elaborated into a variety of flavonoids. These compounds were tested for their abilities to inhibit the in vitro protein-tyrosine kinase activity of p56lck, an enzyme which is thought to play a key role in mediating signal transduction from the CD4 receptor during lymphocyte activation. All of the active compounds had either an amino or a hydroxyl substituent at the 4'-position of the 2-aryl ring. The most active substance prepared in this study is compound 17c, which is approximately 1 order of magnitude more potent than the natural product quercetin (1). Compound 17c was a competitive inhibitor of p56lck with respect to ATP and was highly selective for the inhibition of protein-tyrosine over protein-serine/threonine kinases.