gebhart/patrepeval huggingface dataset:
Profiling antigen-specific T cell phenotypes with heavy metal labeled peptide-Major Histocompatibility Complex tetramers and single cell mass-spectroscopy (CyTOF) (65.40) (2011)

Abstract The direct detection of antigen-specific T cells using fluorescently tagged pMHC-tetramers is widely used in basic and clinical immunology, allowing the unperturbed assessment of T cell phenotypes by concurrent staining with surface and/or intracellular markers. However, the number of T cell specificities and phenotypic markers that can be assessed in a single sample is limited by fluorescence spectral overlap. We recently devised a way to label pMHC tetramers with heavy metals that allows for detection using single-cell mass spectroscopy (Cytometry via Time of Flight - CyTOF). The ability to use 30+ different isotopic labels in this system greatly extends the number of T cell specificities, phenotypic markers and intracellular cytokines that can be simultaneously evaluated. Using this approach, we find that CD8+ T cells from human blood display a much broader diversity of phenotypes and cytokine production capabilities than previously appreciated. Although the phenotypes for different pathogen specific T cells are diverse, cells specific for a given antigen display a distinct subset of phenotypes, which differs depending on the antigen specificity and the nature of the antigen. High-content single-cell phenotypic profiling of antigen-specific T cells should allow for more accurate predictions of T cell response outcomes. Application of CyTOF-based combinatorial tetramer staining, as we previously described for fluorescent labels, will extend the utility of this approach.
Perfusion signal processing for optimal detection performance (2014)

There is considerable interest in developing high-resolution power-Doppler imaging to assess dynamic scattering that lacks the coherence necessary for color-flow Doppler methods. These methods have applications in evaluating the vascularity of cancerous lesions as well as micro-vasculature associated some auto-immune disorders. The objective of this study is to demonstrate the degree to which incorporating additional statistical properties of the perfusion signal can improve power-Doppler imaging. The analytical contribution of the work is the derivation of an optimal perfusion detector tuned to the correlation structure of the power-Doppler signal. We use this to compare the statistically optimal detector to detection performance of the standard wall-filtered intensity as proof-of-principle for the incorporation of signal statistics into perfusion imaging.
Comparison of two commercial molecular tests for the detection of Clostridium difficile in the routine diagnostic laboratory (2011)

Two commercial real-time PCR assays for the detection of Clostridium difficile, BD GeneOhm Cdiff assay (BD Diagnostics) and Xpert C. difficile assay (Cepheid), were compared to each other and to toxigenic culture, which was used as a gold standard, on a set of 194 clinical stools submitted for routine diagnostic analysis. Of 28 (14.4 %) toxigenic culture positive samples 23 were positive with both assays, the BD and the Cepheid real-time PCR assays, 4 were positive only by Cepheid Xpert C. difficile assay and 1 sample was negative by both PCR assays, resulting in sensitivity, specificity, positive predictive value and negative predictive value of 82.1, 98.2, 88.5 and 97.0 %, respectively, for the BD GeneOhm Cdiff assay, and 96.4, 97.3, 87.1 and 99.3 %, respectively, for the Cepheid Xpert C. difficile assay. Altogether 26 out of 194 (13.4 %) samples were reported invalid by Cepheid. Toxigenic C. difficile positive samples contained 15 different PCR ribotypes distributed into toxinotype 0 and 2 different variant toxinotypes (III, IV). Clinical data were available for 24 out of 28 (85.7 %) toxigenic C. difficile positive patients and 18 (75.0 %) of them were diagnosed with diarrhoea, while others had other symptoms or risk factors related to possible C. difficile infection (antibiotics, bloody stool, peritonitis, Crohn's disease).
Application of In-Fusion™ Cloning for the Parallel Construction of E. coli Expression Vectors (2013)

In-Fusion™ cloning is a flexible DNA ligase-independent cloning technology that has wide-ranging uses in molecular biology. In this chapter we describe the protocols used in the OPPF-UK to design and construct expression vectors using In-Fusion™. Our method for small scale expression screening in Escherichia coli of constructs generated by In-Fusion™ is also outlined.
An anti-settling sample delivery instrument for serial femtosecond crystallography (2012)

Serial femtosecond crystallography (SFX) using X-ray free-electron laser (FEL) sources has the potential to determine the structures of macromolecules beyond the limitation of radiation damage and without the need for crystals of sufficient size for conventional crystallography. In SFX, a liquid microjet is used to inject randomly oriented crystals suspended in their storage solution into the FEL beam. Settling of crystals in the reservoir prior to the injection has been found to complicate the data collection. This article details the development of an anti-settling sample delivery instrument based on a rotating syringe pump, capable of producing flow rates and liquid pressures necessary for the operation of the injector. The device has been used successfully with crystals of different proteins, with crystal sizes smaller than 20 µm. Even after hours of continuous operation, no significant impairment of the experiments due to sample settling was observed. This article describes the working principle of the instrument and sets it in context with regard to the experimental conditions used for SFX. Hit rates for longer measuring periods are compared with and without the instrument operating. Two versions of the instrument have been developed, which both deliver sample at a constant flow rate but which differ in their minimum liquid flow rates and maximum pressures.
Studies on blast traumatic brain injury using in-vitro model with shock tube (2011)

One of the major limitations in studying the mechanisms of blast-induced traumatic brain injury (bTBI) or screening therapeutics for protection is the lack of suitable laboratory model systems that can closely mimic the complex blast exposure. Although animal models of bTBI that use shock tubes to mimic blast exposure are available, no high throughput shock tube-based in-vitro models have been reported. Here, we report an in-vitro bTBI model using a compressed air-driven shock tube and mouse neuroblastoma/rat glioblastoma hybrid cells (NG108-15) or SH-SY5Y human neuroblastoma cells in tissue culture plates. Our data showed significant neurobiological effects with decreased adenosine triphosphate levels, increased cellular injury, lactate dehydrogenase release, and reactive oxygen species formation after blast exposure.
Stable Binding of ATF6 to BiP in the Endoplasmic Reticulum Stress Response (2005)

Endoplasmic reticulum (ER) stress-induced activation of ATF6, an ER membrane-bound transcription factor, requires a dissociation step from its inhibitory regulator, BiP. It has been generally postulated that dissociation of the BiP-ATF6 complex is a result of the competitive binding of misfolded proteins generated during ER stress. Here we present evidence against this model and for an active regulatory mechanism for dissociation of the complex. Contradictory to the competition model that is based on dynamic binding of BiP to ATF6, our data reveal relatively stable binding. First, the complex was easily isolated, in contrast to many chaperone complexes that require chemical cross-linking. Second, ATF6 bound at similar levels to wild-type BiP and a BiP mutant form that binds substrates stably because of a defect in its ATPase activity. Third, ER stress specifically induced the dissociation of BiP from ER stress transducers while the competition model would predict dissociation from any specific substrate. Fourth, the ATF6-BiP complex was resistant to ATP-induced dissociation in vitro when isolated without detergents, suggesting that cofactors stabilize the complex. In favor of an active dissociation model, one specific region within the ATF6 lumenal domain was identified as a specific ER stress-responsive sequence required for ER stress-triggered BiP release. Together, our results do not support a model in which competitive binding of misfolded proteins causes dissociation of the BiP-ATF6 complex in stressed cells. We propose that stable BiP binding is essential for ATF6 regulation and that ER stress dissociates BiP from ATF6 by actively restarting the BiP ATPase cycle.
24 Combined analysis of antigen presentation and T cell recognition reveals restricted immune responses in melanoma (2018)

Introduction Studies in the past few years have suggested a key role for neo-antigens in cancer immunotherapy. Since neo-antigens are specifically expressed on the tumour, targeting them is not likely to induce tolerance or normal tissue toxicity, making them candidates for immunotherapy. Despite encouraging results in clinical trials using neo-antigens, peptide or RNA vaccines and adoptive cell transfer (ACT), only a handful of neo-antigens and their corresponding T-cells have been identified in patients. Material and methods In this study we are using a combination of a novel neo-antigen prediction pipeline and human leukocyte antigen (HLA) peptidomics to unbiasedly identify tumour associated antigens (TAAs) and neo-antigens in tumours derived from melanoma patients, characterise their interactions with their tumour infiltrating lymphocytes (TILs) and identifying their matched T-cell receptor (TCR) sequences. Results and discussions For the analysis we used few metastases derived from the same patients and observed high similarity in the metastases antigenic and T-cells repertoires. Using interferon gamma release measurements, tetramer staining and killing assays in vivo and in vitro we were able to show that neo-antigen-specific T-cell clones are more abundant, reactive and proliferative than T-cell clones against TAAs. These methods in combination with TCR sequencing of the neo-antigen clones and bulk TILs enabled us to identify the specificity and identity of 87.4% of the TIL population. Furthermore we were able to show that only few reactive neo-antigens are responsible for the complete killing of the autologous melanoma cells and the rejection of the tumour in vivo . Conclusion Suggesting that our combined pipeline can help to characterise patient antigen and T-cell repertoires and select antigens that would be beneficial for designing personalised immunotherapy.
Real-World Vehicle Exhaust Emissions Monitoring: Review and Critical Discussion (2009)

Traffic-related emissions represent a major component of airborne pollution. Historically, dynamometer testing has been most widely used to estimate vehicle emission rates, and these emission rates, in turn, have been used as inputs when modeling traffic-related air quality impacts. However, such conventional drive cycle testing is not considered strictly representative of vehicles under real driving conditions. Therefore, in recent years, significant scientific effort has been focused on the measurement and analysis of real-world vehicle emissions. Here, the use of vehicle emissions monitoring methods (e.g., in-situ methods such as tunnel, inverse dispersion, and remote sensing studies, and in-traffic measures such as probe vehicle and “car chaser” studies) to provide real-world emission estimates is reviewed and discussed in detail. Advantages and disadvantages are identified for the different vehicle emissions monitoring methods, both relative to dynamometer-based approaches and each other. Potential applications of different approaches are also discussed, with particular attention being placed on their complementary use.
Support Vector Machines on a Budget (2007)

The standard Support Vector Machine formulation does not provide its user with the ability to explicitly control the number of support vectors used to define the generated classifier. We present a modified version of SVM that allows the user to set a budget parameter B and focuses on minimizing the loss attained by the B worst-classified examples while ignoring the remaining examples. This idea can be used to derive sparse versions of both L1-SVM and L2-SVM. Technically, we obtain these new SVM variants by replacing the 1-norm in the standard SVM formulation with various interpolation-norms. We also adapt the SMO optimization algorithm to our setting and report on some preliminary experimental results.
Nanoscale Solid State Batteries Enabled by Thermal Atomic Layer Deposition of a Lithium Polyphosphazene Solid State Electrolyte (2017)

Several active areas of research in novel energy storage technologies, including three-dimensional solid state batteries and passivation coatings for reactive battery electrode components, require conformal solid state electrolytes. We describe an atypical atomic layer deposition (ALD) process for a member of the lithium phosphorus oxynitride (LiPON) family, which is employed as a thin film lithium-conducting solid electrolyte. The reaction between lithium tert-butoxide (LiOtBu) and diethyl phosphoramidate (DEPA) produces conformal, ionically conductive thin films with a stoichiometry close to Li2PO2N between 250 and 300 °C. Unusually, the P/N ratio of the films is always 1, indicative of a particular polymorph of LiPON that closely resembles a polyphosphazene. Films grown at 300 °C have an ionic conductivity of (6.51 ± 0.36) × 10–7 S/cm at 35 °C and are functionally electrochemically stable in the window from 0 to 5.3 V versus Li/Li+. We demonstrate the viability of the ALD-grown electrolyte by integrating it into full solid state batteries, including thin film devices using LiCoO2 as the cathode and Si as the anode operating at up to 1 mA/cm2. The high quality of the ALD growth process allows pinhole-free deposition even on rough crystalline surfaces, and we demonstrate the successful fabrication and operation of thin film batteries with ultrathin (<100 nm) solid state electrolytes. Finally, we show an additional application of the moderate-temperature ALD process by demonstrating a flexible solid state battery fabricated on a polymer substrate.
Reduced sphingosine kinase-1 and enhanced sphingosine 1-phosphate lyase expression demonstrate deregulated sphingosine 1-phosphate signaling in Alzheimer’s disease (2014)

Collectively, these results highlight the importance of S1P in AD suggesting the existence of a global deregulation of S1P signaling in this disease from its synthesis by SphK1 and degradation by SPL to its signaling by the S1P1 receptor.
Design, Synthesis, and Application of Chiral <i>C</i><sub>2</sub>‐Symmetric Spiroketal‐Containing Ligands in Transition‐Metal Catalysis (2018)

Abstract We present an expedient and economical route to a new spiroketal‐based C 2 ‐symmetric chiral scaffold, termed SPIROL. Based on this spirocyclic scaffold, several chiral ligands were generated. These ligands were successfully employed in an array of stereoselective transformations, including in iridium‐catalyzed hydroarylations (up to 95 % ee ), palladium‐catalyzed allylic alkylations (up to 97 % ee ), intermolecular palladium‐catalyzed Heck couplings (up to 94 % ee ), and rhodium‐catalyzed dehydroalanine hydrogenation (up to 93 % ee ).
Prolonged interferon‐alpha therapy of hepatitis B virus‐related decompensated cirrhosis (1997)

Interferon alpha therapy of hepatitis B virus-related decompensated cirrhosis with the dose and the duration generally used is frequently associated with severe side-effects and reactivations. Between 1989 and 1996, 15 patients with hepatitis B virus-related decompensated cirrhosis received prolonged (3-48 months) low-dose (3 million units) IFN-alpha therapy. Ten patients (66%) had a sustained loss of serum hepatitis B virus DNA and hepatitis Be antigen (if present initially) associated with a decrease of aminotransferase levels into the normal range. During follow-up of these 10 patients, seven had a marked clinical improvement and are alive and fully active. One has an hepatocellular carcinoma, and two died without reactivation. Among the five other patients, two had a transient loss of serum HBV DNA followed by reactivation and three did not respond to therapy. During follow-up, one of these five patients died and one underwent liver transplantation. Severe complications, possibly related to interferon were uncommon and included bacterial infection in one case and variceal bleeding in two cases. Eleven of the 15 patients treated are alive after 1.5-7 years of follow-up. Hence, in patients with hepatitis B-related cirrhosis, prolonged low-dose IFN-alpha therapy is relatively well tolerated and may induce a sustained inhibition of hepatitis B virus replication with marked clinical improvement.
Pork products associated with human infection caused by an emerging phylotype of hepatitis E virus in England and Wales (2017)

Since 2010, human hepatitis E infections have increased in England and Wales. Most cases are locally acquired and caused by hepatitis E virus genotype 3 (HEV G3). HEV G3 is linked to the consumption of pork products. The increase is associated with the emergence of a new phylotype, HEV G3-group 2 (G3-2, also known as G3abcdhij). Sixty individuals with confirmed hepatitis E infection and no history of travel outside the UK were recruited: 19 were infected with HEV G3-group 1 (G3-1 or G3efg) and 41 with G3-2. Epidemiological data relating to usual shopping habits and consumption of ham and sausages were analysed together with typing data to identify any associations with HEV phylotype. Study participants who purchased ham and/or sausage from a major supermarket were more likely to have HEV G3-2 infection (Relative risks 1·85, P = 0·06, CI 0·97-3·53). The HEV G3-2 phylotype has not been detected in indigenous UK pigs and it is suggested that human infections could be the result of consumption of products made from pork originating outside the UK. This does not infer blame on the supermarket but the epidemiology of HEV is dynamic and reflects complex animal husbandry practices which need to be explored further.
Direct composition profiling in III-V nanostructures by cross-sectional STM (2003)

Using cross-sectional STM we have studied the local compo-sition in III–V nanostructures such as GaAs/InGaAs quantum wells, InGaNAs/InP quantum wells and quantum dots, and InAs/GaAs self-assembled quantum dots. We are able to determine the local composition by either simply counting the constituent atoms, measuring the local lattice constant or measuring the relaxation of the cleaved surface due to the elastic field of the buried strained nanostructures.
A single-hop F/sub 2/ propagation model for frequencies above 30 MHz and path distances greater than 4000 km (1990)

Standard textbook explanations of ionosphere propagation suggest that 30 MHz and 4000 km are the limiting frequency and distance for single-hop communications. During the peak of sunspot cycle 22, however, there have been hundreds of reports of F/sub 2/ communications exceeding great-circle distance of 4200 km at 50 MHz. It is shown that parabolic F/sub 2/ ionospheric models explain this propagation irregularity, although textbooks and reference books fail to show that such long distances at VHF are possible.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Development, implementation and cost‐effectiveness of a protocol for review of combination diuretic prescribing (2003)

Of prescribed PSDs, 59% were found to be unnecessary. Using the developed protocol potentially improves drug safety and enables cost savings.
A modular kernel approach for integrative analysis of protein domain boundaries (2009)

The experimental results in this study are encouraging, however, more work is need to extend it to a broader range of applications. We are currently developing a novel interactive (human in the loop) profiling that can provide information from more distantly related homology. This approach will further enhance the current study.
Red-Emitting (&lt;inline-formula&gt; &lt;tex-math notation="TeX"&gt;\(\lambda = 610\) &lt;/tex-math&gt;&lt;/inline-formula&gt; nm) In&lt;sub&gt;0.51&lt;/sub&gt;Ga&lt;sub&gt;0.49&lt;/sub&gt;N/GaN Disk-in-Nanowire Light Emitting Diodes on Silicon (2014)

We have investigated the properties of In <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.51</sub> Ga <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.49</sub> N/GaN disk-in-nanowire light emitting diodes (LEDs) epitaxially grown on silicon substrates by plasma-assisted molecular beam epitaxy. The radiative efficiency of the nanowire ensemble, obtained from the temperature-dependent photoluminescence measurements, under optimized growth conditions is 43%, which increases to 55% after parylene passivation. From high resolution transmission electron microscopy, it is evident that there is significant coalescence between nanowires when the areal density approaches 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sup> cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-2</sup> . We have identified and characterized deep level electron and hole traps in the GaN nanowires and it is found that the trap densities increase with nanowire density, or with the degree of coalescence. It is therefore believed that the deep levels originate from dislocations and stacking faults arising from nanowire coalescence. The best output characteristics are measured in a LED having a nanowire density of 2 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">10</sup> cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-2</sup> , which exhibits a maximum internal quantum efficiency of ~55% at an injection level of 10 A/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . It is seen that the maximum efficiency would increase to 60% in the absence of deep level traps.
Measurement of Bottom-Quark Hadron Masses in Exclusive<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mi>J</mml:mi><mml:mo>/</mml:mo><mml:mi>ψ</mml:mi></mml:math>Decays with the CDF Detector (2006)

We measure the masses of b hadrons in exclusively reconstructed final states containing a J/psi --> mu-mu+ decay using 220 pb(-1) of data collected by the CDF II experiment. We find: m(B+) = 5279.10 +/- 0.41(stat.) +/- 0.36(sys.) MeV/c2, m(B0) = 5279.63 +/- 0.53(stat.) +/- 0.33(sys.) MeV/c2, m(B(s)0) = 5366.01 +/- 0.73(stat.) +/- 0.33(sys.) MeV/c2, m(lambda(b)0) = 5619.7 +/- 1.2(stat.) +/- 1.2(sys.) MeV/c2. m(B+) - m(B0) = -0.53 +/- 0.67(stat.) +/- 0.14(sys.) MeV/c2, m(B(s)0) - m(B0) = 86.38 +/- 0.90(stat.) +/- 0.06(sys.) MeV/c2, m(lambda(b)0) - m(B0) = 339.2 +/- 1.4(stat.) +/- 0.1(sys.) MeV/c2. The measurements of the B(s)0, lambda(b)0 mass, m(B(s)0) - m(B0) and m(lambda(b)0) - m(B0) mass difference are of better precision than the current world averages.
Repeated epinephrine doses during prolonged cardiopulmonary resuscitation have limited effects on myocardial blood flow: a randomized porcine study (2014)

In an experimental CA-CPR pig model repeated doses of intravenous EPI results in a significant increase in APV only after the first injection despite increments in CPP also during the following 2 injections indicating inappropriate changes in coronary vascular resistance during subsequent EPI administration.