gebhart/patrepeval huggingface dataset:
Directed evolution of human T cell receptor CDR2 residues by phage display dramatically enhances affinity for cognate peptide‐MHC without increasing apparent cross‐reactivity (2006)

The mammalian alpha/beta T cell receptor (TCR) repertoire plays a pivotal role in adaptive immunity by recognizing short, processed, peptide antigens bound in the context of a highly diverse family of cell-surface major histocompatibility complexes (pMHCs). Despite the extensive TCR-MHC interaction surface, peptide-independent cross-reactivity of native TCRs is generally avoided through cell-mediated selection of molecules with low inherent affinity for MHC. Here we show that, contrary to expectations, the germ line-encoded complementarity determining regions (CDRs) of human TCRs, namely the CDR2s, which appear to contact only the MHC surface and not the bound peptide, can be engineered to yield soluble low nanomolar affinity ligands that retain a surprisingly high degree of specificity for the cognate pMHC target. Structural investigation of one such CDR2 mutant implicates shape complementarity of the mutant CDR2 contact interfaces as being a key determinant of the increased affinity. Our results suggest that manipulation of germ line CDR2 loops may provide a useful route to the production of high-affinity TCRs with therapeutic and diagnostic potential.
Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor (2015)

Treatment of tenosynovial giant-cell tumors with PLX3397 resulted in a prolonged regression in tumor volume in most patients. (Funded by Plexxikon; ClinicalTrials.gov number, NCT01004861.).
Interstitial Lung Disease of Systemic Sclerosis (1995)

Fibrosis of the pulmonary parenchyma is a frequent and serious complication of scleroderma (systemic sclerosis, SSc), resulting in significant morbidity and mortality. During the past decade data have accumulated in support of an inflammatory process affecting the alveoli and distal airways that culminates in irreversible fibrosis in many SSc patients. Recent findings indicate the presence of lung fibroblasts with altered phenotype and biologic activity (myofibroblasts), perhaps arising from the influence of cytokines on resident lung fibroblasts. Acute-phase inflammatory cytokines such as IL-1 alpha, TNF-alpha, MIP-1 alpha, IL-8 and RANTES are increased in SSc bronchoalveolar lavage (BAL) fluid, as is thrombin, a potent mitogen for lung fibroblasts. Chronic-phase inflammatory and fibrogenic cytokines such as PDGF and TGF-beta are also present in increased amounts in SSc BAL fluid. The inciting event(s) and the process(es) leading to the perpetuation of fibrosis in SSc are unknown. Treatment of SSc lung disease has been empiric and generally disappointing, and it is likely that effective treatment awaits a better understanding of the biological events that regulate collagen and other extracellular matrix synthesis.
A Droplet‐Based, Composite PDMS/Glass Capillary Microfluidic System for Evaluating Protein Crystallization Conditions by Microbatch and Vapor‐Diffusion Methods with On‐Chip X‐Ray Diffraction (2004)

Aus einem Tröpfchen: Proteine können mit Mikrobatch- und Dampfdiffusionstechniken in PDMS/Glas-Kompositbauteilen aus Volumina von wenigen Nanolitern kristallisiert werden (PDMS=Polydimethylsiloxan). Die Qualität der Kristalle kann direkt mithilfe von On-Chip-Röntgenbeugung beurteilt werden (siehe Bild). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2004/z53974_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
A review and analysis of electrical percolation in carbon nanotube polymer composites (2008)

We review experimental and theoretical work on electrical percolation of carbon nanotubes (CNT) in polymer composites. We give a comprehensive survey of published data together with an attempt of systematization. Parameters like CNT type, synthesis method, treatment and dimensionality as well as polymer type and dispersion method are evaluated with respect to their impact on percolation threshold, scaling law exponent and maximum conductivity of the composite. Validity as well as limitations of commonly used statistical percolation theories are discussed, in particular with respect to the recently reported existence of a lower kinetic (allowing for re-aggregation) and a higher statistical percolation threshold.
Cancer Statistics, 2004 (2004)

Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival rates based on incidence data from the National Cancer Institute and mortality data from the National Center for Health Statistics. Incidence and mortality rates are age standardized to the 2000 US standard million population. A total of 1,368,030 new cancer cases and 563,700 deaths are expected in the United States in 2004. Incidence rates stabilized among men from 1995 through 2000 but continued to increase among females by 0.4% per year from 1987 through 2000. Mortality rates have decreased by 1.5% per year since 1992 among men, but have stabilized from 1998 through 2000 among women. Cancer death rates continued to decrease from the three major cancer sites in men (lung and bronchus, colon and rectum, and prostate) and from female breast and colorectal cancers in women. In analyses by race and ethnicity, African-American men and women have 40% and 20% higher death rates from all cancers combined compared with White men and women, respectively. Cancer incidence and mortality rates are lower in other racial and ethnic groups than in Whites and African Americans for all sites combined and for the four major cancer sites. However, these groups generally have higher rates for stomach, liver, and cervical cancers than do Whites. Furthermore, minority populations are more likely to be diagnosed with advanced stage disease than are Whites. Progress in reducing the burden from cancer can be accelerated by applying existing cancer control knowledge into practice among all segments of the population.
Focal waveform of a prolate‐spheroidal impulse‐radiating antenna (2007)

This paper develops some analytical approximations for the transient focal waveform produced at the second focus of a prolate‐spheroidal reflector due to a pulse TEM wave launched from the first focus. This is extended to consider the spot size of the peak field near the second focus.
Architectural Support for Software Transactional Memory (2006)

Transactional memory provides a concurrency control mechanism that avoids many of the pitfalls of lock-based synchronization. Researchers have proposed several different implementations of transactional memory, broadly classified into software transactional memory (STM) and hardware transactional memory (HTM). Both approaches have their pros and cons: STMs provide rich and flexible transactional semantics on stock processors but incur significant overheads. HTMs, on the other hand, provide high performance but implement restricted semantics or add significant hardware complexity. This paper is the first to propose architectural support for accelerating transactions executed entirely in software. We propose instruction set architecture (ISA) extensions and novel hardware mechanisms that improve STM performance. We adapt a high-performance STM algorithm supporting rich transactional semantics to our ISA extensions (called hardware accelerated software transactional memory or HASTM). HASTM accelerates fully virtualized nested transactions, supports language integration, and provides both object-based and cache-line based conflict detection. We have implemented HASTM in an accurate multi-core IA32 simulator. Our simulation results show that (1) HASTM single-thread performance is comparable to a conventional HTM implementation; (2) HASTM scaling is comparable to a STM implementation; and (3) HASTM is resilient to spurious aborts and can scale better than HTM in a multi-core setting. Thus, HASTM provides the flexibility and rich semantics of STM, while giving the performance of HTM
Is the Fibronectin‐Aggrecan Complex Present in Cervical Disk Disease? (2011)

Biochemical analysis of injured cervical intervertebral disks reveals the presence of inflammatory markers such as MCP, fragments of structural matrix proteins such as FAC, and a correlation with pH. Further evaluation of the FAC as a potential diagnostic biomarker or therapeutic target is warranted in the cervical spine.
The Cytoskeleton Regulatory Protein hMena (ENAH) Is Overexpressed in Human Benign Breast Lesions with High Risk of Transformation and Human Epidermal Growth Factor Receptor-2–Positive/Hormonal Receptor–Negative Tumors (2006)

Our data provide new insights into the relevance of actin-binding proteins in human breast carcinogenesis and indicate hMena overexpression as a surrogate indicator in breast disease management.
A Continuous, Implantable Lactate Sensor (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Continuous, Implantable Lactate SensorDale A. Baker and David A. GoughCite this: Anal. Chem. 1995, 67, 9, 1536–1540Publication Date (Print):May 1, 1995Publication History Published online1 May 2002Published inissue 1 May 1995https://pubs.acs.org/doi/10.1021/ac00105a010https://doi.org/10.1021/ac00105a010research-articleACS PublicationsRequest reuse permissionsArticle Views878Altmetric-Citations69LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The Tat pathway in bacteria and chloroplasts (Review) (2005)

Both in prokaryotic organisms and in chloroplasts, a specialized protein transport pathway exists which is capable of translocating proteins in a fully folded conformation. Transport is mediated in both instances by signal peptides harbouring a twin-arginine consensus motif (twin-arginine translocation (Tat) pathway). The Tat translocase comprises the three functionally different membrane proteins TatA, TatB, and TatC. While TatB and TatC are involved in the specific recognition of the substrate, TatA might be the major pore-forming component. Current evidence suggests that a functional Tat translocase is assembled from separate TatBC and TatA assemblies only on demand, i.e., in the presence of transport substrate and a transmembrane H+-motive force.
EDG1 Is a Functional Sphingosine-1-phosphate Receptor That Is Linked via a Gi/o to Multiple Signaling Pathways, Including Phospholipase C Activation, Ca2+Mobilization, Ras-Mitogen-activated Protein Kinase Activation, and Adenylate Cyclase Inhibition (1998)

In Chinese hamster ovary (CHO) cells transiently transfected with an expression vector for EDG1, but not an empty vector, sphingosine-1-phosphate (SP) at a concentration as low as 10(-10) M caused an increase in the intracellular free Ca2+ concentration ([Ca2+]i) as a result of mobilization of Ca2+ from both intracellular and extracellular pools. In a CHO clone stably expressing EDG1 receptor (CHO-EDG1 cells), SP induced increases in the production of inositol phosphates and the [Ca2+]i and inhibited forskolin-induced increase in the cellular cAMP content, all in a manner sensitive to pertussis toxin. SP also activated mitogen-activated protein kinase in CHO-EDG1 cells in pertussis toxin-sensitive and Ras-dependent manners. To evaluate the spectrum of agonists for EDG1, we used human erythroleukemia (HEL) cells, which at naive state do not respond to SP or structurally related lipids with an increase in the [Ca2+]i. In HEL cells stably expressing EDG1 receptor (HEL-EDG1 cells), SP dose-dependently increased the [Ca2+]i with half-maximal and maximal concentration values of 10(-9) and 3 x 10(-7) M, respectively; sphingosylphosphorylcholine at exclusively high concentrations, but not sphingosine at all, also increased the [Ca2+]i. HEL-EDG1 cells bound 32P-labeled SP, which was displaced dose dependently by unlabeled SP. These results indicate that EDG1, a member of the EDG family G protein-coupled receptors, is a specific, high-affinity SP receptor.
Ring Strain and Other Factors Governing the Basicity of Nitrogen Heterocycles – An Interpretation by Triadic Analysis (2012)

2X/6-311++G(2df,2pd)//M06-2X/6-31+G(d) computations were employed to investigate the intrinsic gas phase basicity of strained nitrogen heterocycles involving aziridine, azetidine, pyrrolidine and piperidine, together with their N-methyl and N-phenyl derivatives, NR(CH 2 ) n (n = 2-5; R = H, Me and Ph). Basicity constants were compared with the corresponding acyclic counterparts, NR(CH 3 ) 2 (R = H, Me and Ph), and were, based on triadic analysis, resolved into contributions mirroring features of both initial base and the final protonated form as well as their interplay, thus offering quantitative insight into the obtained results. In general, the N-methyl derivatives provided strongest bases investigated here, and, within each group of molecules, the basicity increased on going from three-to six-membered rings, consistent with a decrease in ring strain, with four-membered systems already surpassing or coming close to the basicity of the acyclic gauge molecule. Calculated basicities were found in a very good agreement with available experimental data, except for N-methylazetidine, where a remarkable discrepancy was revealed, suggesting that this system should be experimentally reassessed and its gas-phase basicity parameters revised. Triadic analysis showed different behaviour of individual contributions governing basicities, both among and within distinct families of molecules. It also convincingly demonstrated that, if a proper and a quantitatively accurate interpretation of observed basicity trends is desired, one should not rely only on concepts such as localized reactive hybrid orbitals (RHO) or thus derived nitrogen electron-donating ability (T. Ohwada et al., J. Org. Chem. 69 (2004) 7486), which take into account only properties of the initial base in question, but rather consider protonation reaction in its entirety. (
Biotin Uptake in Biotin Regulatory Mutant of Escherichia coli (1973)

A transport system for biotin in Escherichia coli is regulated by biotin and is not affected by the mutation (bioR) that causes the constitutive synthesis of the bio operon enzymes.
Real-time optoacoustic monitoring of temperature in tissues (2005)

To improve the safety and efficacy of thermal therapy, it is necessary to map tissue temperature in real time with submillimetre spatial resolution. Accurate temperature maps may provide the necessary control of the boundaries of the heated regions and minimize thermal damage to surrounding normal tissues. Current imaging modalities fail to monitor tissue temperature in real time with high resolution and accuracy. We investigated a non-invasive optoacoustic method for accurate, real-time monitoring of tissue temperature during thermotherapy. In this study, we induced temperature gradients in tissue and tissue-like samples and monitored the temperature distribution using the optoacoustic technique. The fundamental harmonic of a Q-switched Nd : YAG laser (λ = 1064 nm) was used for optoacoustic wave generation and probing of tissue temperature. The tissue temperature was also monitored with a multi-sensor temperature probe inserted in the samples. Good agreement between optoacoustically measured and actual tissue temperatures was obtained. The accuracy of temperature monitoring was better than 1°C, while the spatial resolution was about 1 mm. These data suggest that the optoacoustic technique has the potential to be used for non-invasive, real-time temperature monitoring during thermotherapy.
SPEECH PATTERNS IN A MUSCULAR HYDROSTAT: LIP, TONGUE AND GLOSSECTOMY MOVEMENT. (2007)

Abstract. This paper aims to use the muscular hydrostat model to explain patterns of strain and motion in soft tissue structures of the oral cavity. The lips and tongue are both muscular hydrostats in that they are composed entirely of soft tissue and moved by local deformation. Muscles are organized in orthogonal directions, which allow finely controlled and reciprocal motion. The structures also are volume preserving, so that every local compression is compensated for by an expansion. This paper presents lip data as an example muscular hydrostat structures and shows how high resolution MRI and tagged cine-MRI depict muscle anatomy and associated local strains. Normal tongue data are then presented, which extends the principals of mapping compression patterns to motion patterns and infering the relationship between muscle activity and large tongue motions using tagged cine-MRI. Finally, patient data show considerable asymmetry and unusual motion patterns reflecting the resected anatomy and compensatory strategies used to improve speech production. The goal of this conference is to learn and study tongue behavior in normal and glossectomy speech. It is worthwhile, therefore, to be aware of the differences between the tongue and most other structures in the human body. The tongue is one of a group of structures known as muscular hydrostats (Kier and Smith 1984, Smith and kier, 1989). Muscular hydrostats, such as tentacles,
Autoregulated Splicing of muscleblind-like 1 (MBNL1) Pre-mRNA (2011)

Muscleblind-like 1 (MBNL1) is a splicing factor whose improper cellular localization is a central component of myotonic dystrophy. In myotonic dystrophy, the lack of properly localized MBNL1 leads to missplicing of many pre-mRNAs. One of these events is the aberrant inclusion of exon 5 within the MBNL1 pre-mRNA. The region of the MBNL1 gene that includes exon 5 and flanking intronic sequence is highly conserved in vertebrate genomes. The 3'-end of intron 4 is non-canonical in that it contains a predicted branch point that is 141 nucleotides from the 3'-splice site and an AAG 3'-splice site. Using a minigene that includes exon 4, intron 4, exon 5, intron 5, and exon 6 of MBNL1, we showed that MBNL1 regulates inclusion of exon 5. Mapping of the intron 4 branch point confirmed that branching occurs primarily at the predicted distant branch point. Structure probing and footprinting revealed that the highly conserved region between the branch point and 3'-splice site is primarily unstructured and that MBNL1 binds within this region of the pre-mRNA. Deletion of the MBNL1 response element eliminated MBNL1 splicing regulation and led to complete inclusion of exon 5, which is consistent with the suppressive effect of MBNL1 on splicing.
Atherogenic levels of low-density lipoprotein increase endocytotic activity in cultured human endothelial cells. (1992)

Cultured human umbilical vein endothelial cells (EC) exposed to atherogenic low-density lipoprotein (LDL) levels for protracted periods demonstrated heightened endocytosis. Confluent EC were incubated with LDL 90 to 240 mg/dl cholesterol for 1 to 4 days and endocytosis was measured by 14C-sucrose uptake. Control EC and cells incubated with 90 mg/dl LDL cholesterol showed similar uptakes of 14C-sucrose during all measured time periods. In contrast, EC exposed to 240 mg/dl LDL cholesterol showed an increase in endocytosis beginning at 2 days, whereas 160 mg/dl LDL cholesterol promoted increased uptake by 4 days. The endocytotic activity of LDL-perturbed EC is reduced to levels seen in control cells by cytochalasin B, an actin polymerization inhibitor. This finding suggests a modulatory role for the cytoskeleton in endocytosis changes. Examination of LDL-perturbed EC cytoskeleton reveals structural remodeling resulting in a marked increase in stress fibers. Cytochalasin B exposure causes a loss of stress fibers with the formation of globular filamental aggregates. Such LDL-induced cellular functional changes may contribute mechanistically to endothelial dysfunction, which is widely held to be a major contributing factor in the pathogenesis of atherosclerosis.
Simple Device for Multiplexed Electrophoretic Separations Using Gradient Elution Moving Boundary Electrophoresis with Channel Current Detection (2008)

A new microfluidic electrophoresis device and technique is described that is designed specifically for multiplexed, high-throughput separations. The device consists of an array of short (3 mm) capillaries connecting individual sample reservoirs to a common buffer reservoir. Each capillary in the array functions as both a separation channel and as a conductivity-based detection cell. The new technique is based upon the recently described gradient elution moving boundary electrophoresis (GEMBE) technique, which uses a combination of an electric field and buffer counterflow to achieve electrophoretic separations in short capillaries or microfluidic channels. A high voltage drives electrophoresis of the sample analytes through each separation channel. At the start of a separation, the bulk counterflow of buffer through the channel is high, and none of the analytes of interest can enter the channel. The counterflow is then gradually reduced until each analyte, in turn, is able to enter the channel where it is detected as a moving boundary or step. With very short capillaries, only one step at a time is present in each capillary, and the electric current through the channels can then be used as the detector signal, without any extra detector hardware. The current vs time signal for each channel is then smoothed and differentiated to produce a set of simultaneous electropherograms. Because there is no light source or other added hardware required for detection, the system is simple and can be easily and inexpensively scaled up to perform large numbers of simultaneous analyses. As a first demonstration, a 16-channel array device is used for high-throughput, time-series measurements of enzyme activity and inhibition.
Enhanced photogeneration of carriers in a semiconductor via coupling across a nonisothermal nanoscale vacuum gap (2001)

Enhanced generation of carriers when a thermophotovoltaic cell is placed in submicron proximity to a heated surface is demonstrated using custom-designed InAs photodiodes and special silicon-based heater chips produced using microelectromechanical system techniques. The short-circuit current of the photocells is shown to increase sharply (up to fivefold) when the spacing between the heater and photodiode surfaces is reduced, while at the same time, the heater temperature decreases, consistent with increased radiative transfer between the two surfaces. By varying the spacing sinusoidally (at up to 1 kHz), it is demonstrated that the increase in the short-circuit current occurs in phase with the decrease in separation, thereby ruling out thermal effects. It is argued that the increase in short-circuit current is due to increased evanescent coupling of blackbody radiation from the hot surface to the cold photocell, consistent with recent theoretical predictions. The demonstration of this effect is the initial step in the development of a class of energy conversion devices.