gebhart/patrepeval huggingface dataset:
Uninfected Bystander Cells Impact the Measurement of HIV-Specific Antibody-Dependent Cellular Cytotoxicity Responses (2018)

The conformation of the HIV-1 envelope glycoprotein (Env) substantially impacts antibody recognition and antibody-dependent cellular cytotoxicity (ADCC) responses. In the absence of the CD4 receptor at the cell surface, primary Envs sample a "closed" conformation that occludes CD4-induced (CD4i) epitopes. The virus controls CD4 expression through the actions of Nef and Vpu accessory proteins, thus protecting infected cells from ADCC responses. However, gp120 shed from infected cells can bind to CD4 present on uninfected bystander cells, sensitizing them to ADCC mediated by CD4i antibodies (Abs). Therefore, we hypothesized that these bystander cells could impact the interpretation of ADCC measurements. To investigate this, we evaluated the ability of antibodies to CD4i epitopes and broadly neutralizing Abs (bNAbs) to mediate ADCC measured by five ADCC assays commonly used in the field. Our results indicate that the uninfected bystander cells coated with gp120 are efficiently recognized by the CD4i ligands but not the bNabs. Consequently, the uninfected bystander cells substantially affect <i>in vitro</i> measurements made with ADCC assays that fail to identify responses against infected versus uninfected cells. Moreover, using an mRNA flow technique that detects productively infected cells, we found that the vast majority of HIV-1-infected cells in <i>in vitro</i> cultures or <i>ex vivo</i> samples from HIV-1-infected individuals are CD4 negative and therefore do not expose significant levels of CD4i epitopes. Altogether, our results indicate that ADCC assays unable to differentiate responses against infected versus uninfected cells overestimate responses mediated by CD4i ligands.<b>IMPORTANCE</b> Emerging evidence supports a role for antibody-dependent cellular cytotoxicity (ADCC) in protection against HIV-1 transmission and disease progression. However, there are conflicting reports regarding the ability of nonneutralizing antibodies targeting CD4-inducible (CD4i) Env epitopes to mediate ADCC. Here, we performed a side-by-side comparison of different methods currently being used in the field to measure ADCC responses to HIV-1. We found that assays which are unable to differentiate virus-infected from uninfected cells greatly overestimate ADCC responses mediated by antibodies to CD4i epitopes and underestimate responses mediated by broadly neutralizing antibodies (bNAbs). Our results strongly argue for the use of assays that measure ADCC against HIV-1-infected cells expressing physiologically relevant conformations of Env to evaluate correlates of protection in vaccine trials.
Trait components provide tools to dissect the genetic susceptibility of migraine (2006)

The commonly used "end diagnosis" phenotype that is adopted in linkage and association studies of complex traits is likely to represent an oversimplified model of the genetic background of a disease. This is also likely to be the case for common types of migraine, for which no convincingly associated genetic variants have been reported. In headache disorders, most genetic studies have used end diagnoses of the International Headache Society (IHS) classification as phenotypes. Here, we introduce an alternative strategy; we use trait components-individual clinical symptoms of migraine-to determine affection status in genomewide linkage analyses of migraine-affected families. We identified linkage between several traits and markers on chromosome 4q24 (highest LOD score under locus heterogeneity [HLOD] 4.52), a locus we previously reported to be linked to the end diagnosis migraine with aura. The pulsation trait identified a novel locus on 17p13 (HLOD 4.65). Additionally, a trait combination phenotype (IHS full criteria) revealed a locus on 18q12 (HLOD 3.29), and the age at onset trait revealed a locus on 4q28 (HLOD 2.99). Furthermore, suggestive or nearly suggestive evidence of linkage to four additional loci was observed with the traits phonophobia (10q22) and aggravation by physical exercise (12q21, 15q14, and Xp21), and, interestingly, these loci have been linked to migraine in previous studies. Our findings suggest that the use of symptom components of migraine instead of the end diagnosis provides a useful tool in stratifying the sample for genetic studies.
In Silico Affinity Profiling of Neuroactive Polyphenols for Post-Traumatic Calpain Inactivation: A Molecular Docking and Atomistic Simulation Sensitivity Analysis (2014)

Calcium-activated nonlysosomal neutral proteases, calpains, are believed to be early mediators of neuronal damage associated with neuron death and axonal degeneration after traumatic neural injuries. In this study, a library of biologically active small molecular weight calpain inhibitors was used for model validation and inhibition site recognition. Subsequently, two natural neuroactive polyphenols, curcumin and quercetin, were tested for their sensitivity and activity towards calpain's proteolytic sequence and compared with the known calpain inhibitors via detailed molecular mechanics (MM), molecular dynamics (MD), and docking simulations. The MM and MD energy profiles (SJA6017 < AK275 < AK295 < PD151746 < quercetin < leupeptin < PD150606 < curcumin < ALLN < ALLM < MDL-28170 < calpeptin) and the docking analysis (AK275 < AK295 < PD151746 < ALLN < PD150606 < curcumin < leupeptin < quercetin < calpeptin < SJA6017 < MDL-28170 < ALLM) demonstrated that polyphenols conferred comparable calpain inhibition profiling. The modeling paradigm used in this study provides the first detailed account of corroboration of enzyme inhibition efficacy of calpain inhibitors and the respective calpain-calpain inhibitor molecular complexes' energetic landscape and in addition stimulates the polyphenol bioactive paradigm for post-SCI intervention with implications reaching to experimental in vitro, in cyto, and in vivo studies.
Efficient, broad-band holographic axilens doublets for IR sources (1993)

Recently, there has been rapid progress in developing semiconductor lasers as lowcost and compact monochromatic light sources for many applications.
Characterization of the locus encoding the [Ni-Fe] sulfhydrogenase from the archaeon Pyrococcus furiosus: evidence for a relationship to bacterial sulfite reductases (1995)

The hydBGDA genes, which encode the four subunits beta, gamma, delta and alpha of the [Ni-Fe] hydrogenase from the archaeon Pyrococcus furiosus, have been isolated and sequenced using a PCR/IPCR-based strategy. From the sequence analysis it appears that the four structural genes are tightly linked and organized in a single transcription unit. The hydD and hydA gene products are related to the small and the large subunits of several archaeal and eubacterial [Ni-Fe] hydrogenases with an overall degree of sequence relatedness ranging from 35% to 50% (identity + similarity). In particular, the amino acid sequence motifs involved in the accommodation of nickel and iron-sulfur clusters are conserved. In addition, the database search revealed that the hydB and hydG gene products are homologous to the asrA- and asrB-encoded subunits of the sulfite reductase enzyme from Salmonella typhimurium. This is particularly interesting in view of the recent finding that the P. furiosus hydrogenase appears to be a bifunctional enzyme endowed with both proton- and sulfur-reducing activities.
Phosphorylation by cAMP-Dependent Protein Kinase Causes a Conformational Change in the R Domain of the Cystic Fibrosis Transmembrane Conductance Regulator (1994)

Individuals with cystic fibrosis have a defect in the CFTR protein, a chloride channel regulated by cAMP-dependent protein kinase (PKA). The majority of the phosphorylation sites of PKA are located in the R domain of CFTR. It has been postulated that this domain may act as a gate for the chloride channel. Of the many possible mechanisms whereby the R domain could gate the channel, including interdomain interactions, charge distribution, or conformational change, we investigated the possibility that phosphorylation leads to conformational changes in the R domain. To test this hypothesis, a protocol for purification of human R domain peptide synthesized in a bacterial expression system was developed. Purified R domain was phosphorylated by PKA, and CD spectra were obtained. As a result of phosphorylation by PKA, a significant spectral change, indicative of a reduction in the alpha-helical content, was found. CD spectra of the R domain of a shark homologue of CFTR indicated similar changes in conformation as a result of phosphorylation by PKA. In contrast, phosphorylation of the human R domain by PKC, which has only a small influence on CFTR channel activity, failed to elicit CD spectral changes, indicating no conformational change comparable to those induced by PKA phosphorylation. These observations provide the first structural characterization of the R domain and suggest that the gating of the CFTR chloride channel by PKA may involve a conformational change in the R domain.
Digitalisation as a driver of industrial renewal – perception and qualitative evidence from the USA (2019)

Firms that are capable, undertake strategic renewal to ensure and reinforce a sustainable competitive advantage. Digitalisation is a major technological change; a strategic renewal that can deliver such an advantage. In this article, we adopt the theories of path dependence and strategic renewal to analyse the implementation and utilisation of digitalisation in the USA manufacturing industry based on qualitative interview data collected among policymakers, researchers and manufacturers. The analysis identified and described five US strengths (i.e. technology leaders, innovative tolerant culture, technology agnostic, market driven, speed) contributing industrial renewal through digitalisation, and five US weaknesses (i.e. technology driven, disorganised convergence, not part of the cultural identity, competitive not collaborative, short term perspective) inhibiting it. The strengths and weaknesses were further considered as they pertain to individuals, businesses and national policy. The study highlighted the systemic nature of the identified strengths and weaknesses, and suggested that in addition to policymakers, also research community and businesses should further strengthen what is already strong in the innovation system to indirectly mitigate the weaknesses.
Effects of quantum well recombination losses on the internal differential efficiency of multi-quantum-well lasers (2002)

Non-uniform carrier distribution in InGaAsP-InP multi-quantum-well (MQW) laser diodes is found to cause QW recombination losses to increase with rising injection current above threshold. These losses can have a larger effect on the internal differential efficiency than carrier leakage.
Changes in the Plasma Hanp Level During Long-Term Salt Loading in Patients with Essential Hypertension (1988)

Serial changes in the plasma hANP (human atrial natriuretic peptide) level in patients with essential hypertension were determined during high salt intake for two weeks after salt restriction for 5 days. The mean plasma hANP level decreased during salt depletion for 5 days from 60 +/- 10 pg/ml to 39 +/- 8 pg/ml. During high salt intake (20 g NaCl/day) for two weeks, the plasma hANP level increased gradually to a maximum of 71 +/- 16 pg/ml on day 7 and then decreased to 54 +/- 9 pg/ml on day 14. The plasma levels of renin activity, aldosterone and noradrenaline decreased during salt repletion. Changes in the plasma hANP level were correlated positively with those of urinary sodium excretion and negatively with those of plasma renin activity on days 7 and 14 of salt repletion. Change in the plasma hANP level correlated with that in the mean blood pressure on day 14, but not day 7 of salt repletion. These findings indicate that the plasma hANP level is closely related to sodium intake in patients with essential hypertension.
Enantioselective Construction of Quaternary Stereogenic Centers by the Addition of an Acyl Anion Equivalent to 1,3-Dienes (2020)

We report the enantioselective formation of quaternary stereogenic centers by the intermolecular addition of malononitrile, an acyl anion equivalent, and related pronucleophiles to several 1,3-disubstituted acyclic 1,3-dienes in the presence of a Pd-PHOX catalyst. Products are obtained in up to 88% yield and 99:1 er and in most cases are formed as a single regioisomer. The products' malononitrile unit undergoes oxidative functionalization to afford β,γ-unsaturated carbonyls bearing internal olefins and α-quaternary stereogenic centers.
High Ion/Ioff and low subthreshold slope planar-type InGaAs tunnel field effect transistors with Zn-diffused source junctions (2015)

We have demonstrated the operation of high on-off current ratio (Ion/Ioff) and low subthreshold slope planar-type InGaAs tunnel field effect transistors (TFETs) with Zn-diffused source junctions. The solid-phase Zn diffusion process has been shown to form defect-less p+/n source junctions with steep profiles because of the inherent nature of Zn diffusion into InGaAs, which has significantly improved the TFET performance. The devices presented in this paper have exhibited a record low subthreshold slope of 64 mV/dec for planar-type III-V TFETs and a large Ion/Ioff ratio of more than 106 at the same time.
Device effects of various Zr/Ti ratios of PZT thin-films prepared by sol-gel method (1992)

Abstract PZT, PbZrxTI1−xO3, thin-films with various Zr/Ti ratios, 100/0 (lead zirconate) to 0/100 (lead titanate), were prepared by the sol-gel method. Basic electric properties, dielectric constant, tan σ, P-E hysteresis curve, switching properties were measured respectively as a function of composition. Dielectric constant indicated a specific peak value (∼1100) around the morphotropic phase boundary between tetragonal and rhombohedral phase. Satisfactory low-voltage saturated hysteresis curves were observed for the compositions of PZT(90/10) through PZT(20/80). The remanent polarization and the coercive field increased as the titanium content decreased. The result of X-ray measurement showed that the lattice constants of thin-Film PZT are different from bulk ceramics for compatible compositionsS. The boundary, on which the c/a ratio must be 1 (rhombohedral phase), was slightly shifted to PbTiO3 side. This distortion in crystal structure is considered to be due to the thin-film effect, which the lattice mismatch between the platinum substrate and the PZT layer, restricted the ions to position into proper cites.
Progress in multi-trigger resists for EUV lithography (Conference Presentation) (2018)

Recent tool and source advances make the introduction of EUV lithography into high volume manufacturing in the very near future inevitable. Whilst traditional chemically amplified resists will likely support the initial insertion, a wide range of materials options are being examined for future nodes, aiming to identify a photoresist that simultaneously meets the resolution, line edge roughness and sensitivity requirement. However, this issue represents a fundamental trade-off in lithography (the RLS triangle) and it is difficult to overcome. For instance, addition of quenchers in chemically amplified resists reduces the acid diffusion length and increases the resolution of the patterned features, but decreases the sensitivity, and impacts on material stochastics affecting the line edge roughness. In this study we present results obtained with Irresistible Materials’ Multi Trigger Resist. The multi trigger concept enables high sensitivity patterning but also incorporates a quenching behaviour into the chemistry to improve resolution. The standard material consists of a base molecule – EX2, a crosslinker and a PAG. EUV light generates photoacids, as with a traditional chemically amplified resist, but the response of the resist matrix implements a logic-type function. Where two resist molecules are activated by two acids, in close proximity to each other, then the resist molecules will react catalytically and release both acids. When a resist molecule encounters a single acid in isolation then it will hold on to the acid, without itself reacting, thus removing the acid from the reaction. This behaviour allows a high sensitivity response at a certain dose threshold but turns the resist response off much more quickly (as a 2nd order reaction) as the dose decreases, leading to sharper lines and lower line width roughness. We present results where the molecular structure was modified to create enhanced versions of the standard resin. This will offer higher cross-linking capability and better mechanical strength to reduce the LER, wiggling and defects, and thus ultimately higher resolution. We present the lithography performance of the MTR2 resist series which shows 16nm half pitch lines patterned with a dose of 38mJ/cm2, giving a LER of 3.7 nm when patterned using an NXE3300. We also present a new resist formulation using a crosslinker with a high opacity non-metallic atom attached, which has patterned 13nm lines at the Paul Scherrer Institute (14nm half pitch) and also 13nm lines on the MET tool at Berkeley (20nm half pitch) with an LER of 4.24nm. We also present the lithographic performance of the MTR3 resist series which is 10% faster than the MTR2 series when patterning with EUV lithography at PSI, and has achieved a 2.95nm LER at 16nm half pitch, and 3.80nm LER at 14nm half pitch at PSI. Performance across various process conditions is also discussed, including process conditions to reduce wiggling and improve LER.
Anion...π, lone pair...π, and F...F interactions in nucleobase derivatives (2011)

systematic errors and how to correct the problems with the way least squares refinement is currently undertaken.
Learning to diagnose by doing (2018)

Abstract: "This paper is a study on the process of evolution of a novice to an expert in a diagnostic context. In this paper, we have chosen an abstract example of a diagnostic problem. The results in this article are based on a longitudinal study of a single subject. The empirical base is a protocol of the subject as he solved this problem until he mastered the most sophisticated strategy. Based on an analysis of the protocol, we have identified four different strategies that were used by the subject to solve the given set of problems. These strategies vary in their efficiency of diagnosis and in their modes of reasoniing. We also identify the different operators that were used by the subject to transform one strategy into a more efficient one. The learning process has been implemented as a computer simulation. Finally, we discuss the hypotheses that are suggested by this experiment and the implications of our observations."
Automata on Infinite Objects and Church’s Problem (1972)

Basic definitions and results Closure properties of difusable sets The sequential calculus Automaton transformations and Church's problem> Regular trees The emptiness problem The solvability problem.
ChemInform Abstract: A Cubane‐Substituted Polyoxoanion: Structure and Magnetic Properties of Cs2 [H2PW9Ni4O34(OH)3 (H2O)6]×5H2O. (1999)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Development of Monoclonal Antibody-Based EIA for Tetranor-PGDM which Reflects PGD2 Production in the Body (2021)

Tetranor-PGDM is a metabolite of PGD<sub>2</sub>. Urinary tetranor-PGDM levels were reported to be increased in some diseases, including food allergy, Duchenne muscular dystrophy, and aspirin-intolerant asthma. In this study, we developed a monoclonal antibody (MAb) and a competitive enzyme immunoassay (EIA) for measuring tetranor-PGDM. Spleen cells isolated from mice immunized with tetranor-PGDM were utilized to generate Ab-producing hybridomas. We chose hybridomas and purified MAb against tetranor-PGDM to develop competitive EIA. The assay evaluated the optimal ionic strength, pH, precision, and reliability. Specificity was determined by cross-reactivity to tetranor-PGEM, tetranor-PGFM, and tetranor-PGAM. Recovery was determined by spiking experiments on artificial urine. Optimal ionic strength was 150 mM NaCl, and optimal pH was pH 7.5. Metabolites other than tetranor-PGDM did not show any significant cross-reactivity in the EIA. The assay exhibited a half-maximal inhibition concentration (IC<sub>50</sub>) of 1.79 ng/mL, limit of detection (LOD) of 0.0498 ng/mL, and range of quantitation (ROQ) value of 0.252 to 20.2 ng/mL. The intra- and inter-assay variation for tetranor-PGDM was 3.9-6.0% and 5.7-10.4%, respectively. The linearity-dilution effect showed excellent linearity under dilution when artificial urine samples were applied to solid-phase extraction (SPE). After SPE, recovery of tetranor-PGDM in artificial urine averaged from 82.3% to 113.5% and was within acceptable limits (80%-120%). We successfully generated one monoclonal antibody and developed a sensitive competitive EIA. The established EIA would be useful for routine detection and monitoring of tetranor-PGDM in research or diagnostic body fluids.
Acquired mechanisms of immune escape in cancer following immunotherapy (2018)

Immunotherapy has revolutionized the management of numerous cancers; however, a substantial proportion that initially respond subsequently acquire means of immune escape and relapse. Analysis of recent clinical trials permits us to preliminarily understand how immunotherapies exert evolutionary pressures: selecting cancer subclones deficient in antigenicity and/or immunogenicity, thereby facilitating immune escape.
Simultaneous Control Information and Power Transmission for Reconfigurable Intelligent Surfaces (2021)

Reconfigurable intelligent surfaces (RISs) are planar structures with attached electronic circuitry that enable a partially programmable communication environment. RIS operation can be regarded as nearly passive since it acts by simply reflecting the impinging traveling waves towards desired directions, thus requiring energy only for the reconfiguration of its reflective elements (REs). This paper tackles the problem of wirelessly powering RIS circuitry via control signaling. Simultaneous wireless information and power transfer (SWIPT) is considered by taking into account two basic principles: that signal quality of the control signals is sufficient for information detection, and that there is enough harvested energy for the reconfiguration. Some of the most common SWIPT receivers (time sharing, power splitting, dynamic power splitting, and antenna selection) are studied and the corresponding proposed optimization problems implementing the aforementioned principles are formulated and solved in closed form. Numerical results show the effectiveness of the proposed methods in the presence of received power fluctuations.
Relapse and mortality following cardioversion of new-onset vs. recurrent atrial fibrillation and atrial flutter in the elderly (2006)

DCCV is more successful in maintaining sinus rhythm in patients with new-onset atrial flutter than in patients with new-onset atrial fibrillation. Relapse of atrial arrhythmia after cardioversion is associated with increased mortality.