gebhart/patrepeval huggingface dataset:
CD161 (NKR-P1A) Costimulation of CD1d-dependent Activation of Human T Cells Expressing Invariant Vα24JαQ T Cell Receptor α Chains (1998)

A population of human T cells expressing an invariant V alpha 24 J alpha Q T cell antigen receptor (TCR) alpha chain and high levels of CD161 (NKR-P1A) appears to play an immunoregulatory role through production of both T helper (Th) type 1 and Th2 cytokines. Unlike other CD161(+) T cells, the major histocompatibility complex-like nonpolymorphic CD1d molecule is the target for the TCR expressed by these T cells (V alpha 24(invt) T cells) and by the homologous murine NK1 (NKR-P1C)+ T cell population. In this report, CD161 was shown to act as a specific costimulatory molecule for TCR-mediated proliferation and cytokine secretion by V alpha 24(invt) T cells. However, in contrast to results in the mouse, ligation of CD161 in the absence of TCR stimulation did not result in V alpha 24(invt) T cell activation, and costimulation through CD161 did not cause polarization of the cytokine secretion pattern. CD161 monoclonal antibodies specifically inhibited V alpha 24(invt) T cell proliferation and cytokine secretion in response to CD1d+ target cells, demonstrating a physiological accessory molecule function for CD161. However, CD1d-restricted target cell lysis by activated V alpha 24(invt) T cells, which involved a granule-mediated exocytotic mechanism, was CD161-independent. In further contrast to the mouse, the signaling pathway involved in V alpha 24(invt) T cell costimulation through CD161 did not appear to involve stable association with tyrosine kinase p56(Lck). These results demonstrate a role for CD161 as a novel costimulatory molecule for TCR-mediated recognition of CD1d by human V alpha 24(invt) T cells.
Heart Failure Epidemiology: European Perspective (2013)

Heart failure poses an increasing problem for global healthcare systems. The epidemiological data which has been accrued over the last thirty years has predominantly been accumulated from experience within North America and Europe. Initial large cohort, prospective longitudinal studies produced the first publications; however latterly the focus has shifted onto epidemiological data governing hospitalisation and mortality. The emphasis behind this shift has been the resource implications with regards to repetitive, costly and prolonged hospitalisation. The European experience in heart failure, though similar to North America has recently demonstrated differences in hospitalisation which may underlie the differences between healthcare system configuration. Heart failure however remains an increasing global problem and the endpoint of a variety of cardiovascular diseases. Allied with the fact of increasingly elderly populations and prior data demonstrating a steep rise in prevalent cases within more elderly populations, it is likely that the increasing burden of disease will continue to pose challenges for modern healthcare. Despite the predicted increase in the number of patients affected by heart failure, over the last thirty years, a clear management algorithm has evolved for the use of pharmacotherapies (neuro-hormonal antagonists), device based therapies (Implantable Cardioverting Defibrillator (ICD) and Cardiac Resynchronisation Therapy (CRT)) and mechanical therapies including left ventricular assist devices and cardiac transplantation. Though the management of such patients has been clearly delineated in national and international guidelines, the underuse of all available and appropriate therapies remains a significant problem. When comparing various epidemiological studies from different settings and timepoints, it should be remembered that rates of prevalence and incidence may vary depending upon the definition used, methods of accumulating information (with the possibility of bias) and the chosen cut point of defining left ventricular systolic dysfunction (LVSD).
Conversion of Human Fibroblasts to Functional Endothelial Cells by Defined Factors (2013)

Pluripotent factor-induced transdifferentiation can be successfully applied for generating functional autologous ECs for therapeutic applications.
Transcranial diffuse optical monitoring of microvascular cerebral hemodynamics after thrombolysis in ischemic stroke (2014)

The ultimate goal of therapeutic strategies for ischemic stroke is to reestablish the blood flow to the ischemic region of the brain. However, currently, the local cerebral hemodynamics (microvascular) is almost entirely inaccessible for stroke clinicians at the patient bed-side, and the recanalization of the major cerebral arteries (macrovascular) is the only available measure to evaluate the therapy, which does not always reflect the local conditions. Here we report the case of an ischemic stroke patient whose microvascular cerebral blood flow and oxygenation were monitored by a compact hybrid diffuse optical monitor during thrombolytic therapy. This monitor combined diffuse correlation spectroscopy and near-infrared spectroscopy. The reperfusion assessed by hybrid diffuse optics temporally correlated with the recanalization of the middle cerebral artery (assessed by transcranial-Doppler) and was in agreement with the patient outcome. This study suggests that upon further investigation, diffuse optics might have a potential for bed-side acute stroke monitoring and therapy guidance by providing hemodynamics information at the microvascular level.
Massively parallel adhesion and reactivity measurements using simple and inexpensive magnetic tweezers (2002)

Single molecule techniques to measure biological molecules and reactions have provided an alternative way to probe and visualize bond characteristics and reaction dynamics. However, these techniques, such as atomic force microscopy, optical tweezers, and micropipettes often require expensive and complicated equipment and are very time intensive, because each measurement gives the results of one-single reaction or a property of one-single molecule. Here, we report on a technique that allows for massively parallel measurements on many individual single molecules in microfluidic systems. We demonstrate the effectiveness of a simple, robust, inexpensive apparatus, by using it to differentiate between deoxyribonucleic acid (DNA) assemblies that are merely annealed from others that are ligated, and by measuring the rate at which annealed DNA denatures as function of temperature.
Recognition of viral nucleic acids in innate immunity (2009)

Abstract Viral infections are detected by sensor molecules, which initiate innate antiviral responses, including the activation of type I interferons (IFNs) and proinflammatory cytokines. These cytokines are responsible for not only inhibiting viral replication in infected cells but also regulating the induction of adaptive immunity, leading to the swift eradication of viruses. Recent advances in the identification of pathogen receptors in the innate immune system have revealed that distinct types of sensors play a role in the detection of viral nucleic acids in different ways; Toll‐like receptors (TLRs), which detect viral DNA or RNA in endosomal compartments in immune cells, retinoic acid inducible gene‐I (RIG‐I)‐like receptors (RLRs), which recognise viral RNA in the cytoplasm, and DNA sensors, which detect cytoplasmic viral DNA. Since these sensors have to exclusively recognise viral infections, it is intriguing to understand how they distinguish self nucleic acids from foreign viral ones. Here, we review the current knowledge of the recognition of viral nucleic acids by these sensor molecules and the signal transduction machinery. Copyright © 2009 John Wiley &amp; Sons, Ltd.
Progression rate of ALSFRS-R at time of diagnosis predicts survival time in ALS (2006)

The authors calculated the progression rate (DeltaFS) using the total revised ALS Functional Rating Scale (ALSFRS-R) and symptom duration at diagnosis in 82 Japanese patients with ALS. Survival (death or tracheostomy) differed significantly with the DeltaFS and postdiagnostic period according to log-rank testing, but Cox proportional hazards modeling revealed no strong association between total ALSFRS-R and mortality, suggesting that the DeltaFS provides an additional predictive index beyond ALSFRS-R alone.
Metabolic Reconstruction for Metagenomic Data and Its Application to the Human Microbiome \n (2012)

Microbial communities carry out the majority of the biochemical activity on the planet, and they play integral roles in processes including metabolism and immune homeostasis in the human microbiome. Shotgun sequencing of such &#13;\ncommunities’ metagenomes provides information complementary to organismal abundances from taxonomic markers, but the resulting data typically comprise short reads from hundreds of different organisms and are at best challenging to assemble comparably to single-organism genomes. Here, we describe an alternative approach to infer the functional and &#13;\nmetabolic potential of a microbial community metagenome. We determined the gene families and pathways present or absent within a community, as well as their relative abundances, directly from short sequence reads. We validated this methodology using a collection of synthetic metagenomes, recovering the presence and abundance both of large pathways and of small functional modules with high accuracy. We subsequently applied this method, HUMAnN, to the microbial communities of 649 metagenomes drawn from seven primary body sites on 102 individuals as part of the Human Microbiome Project (HMP). This provided a means to compare functional diversity and organismal ecology in the human microbiome, and we determined a core of 24 ubiquitously present modules. Core pathways were often implemented by &#13;\ndifferent enzyme families within different body sites, and 168 functional modules and 196 metabolic pathways varied in metagenomic abundance specifically to one or more niches within the microbiome. These included glycosaminoglycan degradation in the gut, as well as phosphate and amino acid transport linked to host phenotype (vaginal pH) in the posterior fornix. An implementation of our methodology is available at http://huttenhower.sph.harvard.edu/humann. This provides a means to accurately and efficiently characterize microbial metabolic pathways and functional modules directly from high-throughput sequencing reads, enabling the determination of community roles in the HMP cohort and in future &#13;\nmetagenomic studies. &#13;\n
T-Coffee: a web server for the multiple sequence alignment of protein and RNA sequences using structural information and homology extension (2011)

This article introduces a new interface for T-Coffee, a consistency-based multiple sequence alignment program. This interface provides an easy and intuitive access to the most popular functionality of the package. These include the default T-Coffee mode for protein and nucleic acid sequences, the M-Coffee mode that allows combining the output of any other aligners, and template-based modes of T-Coffee that deliver high accuracy alignments while using structural or homology derived templates. These three available template modes are Expresso for the alignment of protein with a known 3D-Structure, R-Coffee to align RNA sequences with conserved secondary structures and PSI-Coffee to accurately align distantly related sequences using homology extension. The new server benefits from recent improvements of the T-Coffee algorithm and can align up to 150 sequences as long as 10,000 residues and is available from both http://www.tcoffee.org and its main mirror http://tcoffee.crg.cat.
Role of Tissue Culture in Prediction of Malignancy (1978)

It is now clear that tissue culture has a role to play in the prediction of the degree of malignancy of human brain tumors. The fact that virtually all human brain tumors grow at least for some interval in culture allows application of tissue culture to the study of all tumors. This almost universal culturability of tumors is truly a singular virtue of intracranial neoplasms. No other human solid tumor group has been so amenable to in vitro growth or study. Up to the present time, despite our experience with over 1100 human brain tumor cultures, we have been extremely conservative in altering patient management on the basis of in vitro data. As is now apparent, the basis for direct input into the clinical milieu exists and it is necessary to work on a patient by patient basis to see how well the existing criteria can be applied to help guide management. Indeed the emphasis given to tissue culture by Rubinstein already confirms the current interest in the applicability of tissue culture data to neuropathological study of tumors (48). Clearly for certain tumors which tend to be benign, tissue culture can serve to alert the clinician to the perhaps unexpected malignant potential of the lesion. For the malignant tumors, the degree of malignancy, the probable biological behavior, the role of host defense factors and therapeutic agents can all be more quantitatively defined for the individual patient by the detailed study of the patient's cultured cells. With improvement in the surgical treatment of benign tumors and with better chemotherapeutic and radiotherapeutic measures for malignant neoplasms this more detailed and precise characterization of tumor behavior has become increasingly relevant to the optimization of the clinical management of the brain tumor patient.
Augmented state Kalman filtering for AUV navigation (2003)

Addresses the problem of estimating the motion of an autonomous underwater vehicle (AUV), while it constructs a visual map ("mosaic" image) of the ocean floor. The vehicle is equipped with a down-looking camera which is used to compute its motion with respect to the seafloor. As the mosaic increases in size, a systematic bias is introduced in the alignment of the images which form the mosaic. Therefore, this accumulative error produces a drift in the estimation of the position of the vehicle. When the arbitrary trajectory of the AUV crosses over itself, it is possible to reduce this propagation of image alignment errors within the mosaic. A Kalman filter with augmented state is proposed to optimally estimate both the visual map and the vehicle position.
Mechanisms of lymphocyte-mediated cytotoxicity. II. biochemical and serologic identification of a precursor lymphotoxin form (pre-LT) produced by MLC-sensitized human T lymphocytes in vitro. (1981)

Abstract The biochemical and immunologic properties of a cell toxin(s) released into the fluid phase and expressed on the surface of lectin-activated alloimmune human cytotoxic lymphocytes has been investigated. The results indicate that the initial cytotoxin(s) released into the supernatant from alloimmune lymphocytes represents a precursor form of lymphotoxin (pre-LT), and in this precursor form, the α and β antigens exist as masked or cryptic determinants. The pre-LT form in unfractionated supernatants was defined immunologically by neutralization with a polyspecific anti-LT antisera (anti-WS), and its lack of reactivity with anti-α and anti-β LT antisera. However, gel filtration chromatographic profile of the pre-LT cytotoxic activity was heterogeneous and showed multiple m.w. classes that were characteristic of the chromatograms of traditionally defined LT. These fractionated components were now readily neutralized with anti-α LT antiserum. In addition, the pre-LT cytotoxic activity in unfractionated supernatants treated by various physical or chemical means rendered the cytotoxic activity neutralizable by an anti-α LT antiserum, indicating an immunologic relationship between the pre-LT form and components of the LT system. The antigens associated with pre-LT form were detectable, in part, on the LT-Cx and γ LT molecules by a fluid phase immunoadsorption assay. A functional immunoadsorption assay was used to detect the antigenic determinants of the pre-LT form on the cell surface of alloimmune lymphocytes before and after lectin activation, α LT-associated antigens were detectable on cytotoxic effectors only after lectin activation. These results imply LT may function as cell surface delivered cytotoxic molecules. LT activity was not detected in supernatants obtained from alloimmune cytotoxic reactions, however, the pre-LT and α-LT neutralizing activities of the anti-LT sera were significantly diminished after the incubation of these sera in the cytotoxic reaction and indicated that LT molecules were produced during the cytotoxic reaction, and LT remained closely associated with the lymphocyte:target cell conjugates. The relationship of the pre-LT form to the capacity of the various anti-LT antisera to affect the human alloimmune cytotoxic reaction is discussed. The results provide additional support to the concept that the LT system is involved in the lytic mechanism of cytotoxic T cells.
Pravastatin attenuates allergic airway inflammation by suppressing antigen sensitisation, interleukin 17 production and antigen presentation in the lung (2008)

Pravastatin suppresses the systemic sensitisation to allergen with downregulation of IL17 production. It also suppresses an ongoing immune response in the airway partly by suppressing antigen presentation in the lung. Therefore, statins could be a novel therapeutic option for treatment of asthma.
Inherited human sex reversal due to impaired nucleocytoplasmic trafficking of SRY defines a male transcriptional threshold (2013)

Human testis determination is initiated by SRY (sex determining region on Y chromosome). Mutations in SRY cause gonadal dysgenesis with female somatic phenotype. Two subtle variants (V60L and I90M in the high-mobility group box) define inherited alleles shared by an XY sterile daughter and fertile father. Whereas specific DNA binding and bending are unaffected in a rat embryonic pre-Sertoli cell line, the variants exhibited selective defects in nucleocytoplasmic shuttling due to impaired nuclear import (V60L; mediated by Exportin-4) or export (I90M; mediated by chromosome region maintenance 1). Decreased shuttling limits nuclear accumulation of phosphorylated (activated) SRY, in turn reducing occupancy of DNA sites regulating Sertoli-cell differentiation [the testis-specific SRY-box 9 (Sox9) enhancer]. Despite distinct patterns of biochemical and cell-biological perturbations, V60L and I90M each attenuated Sox9 expression in transient transfection assays by twofold. Such attenuation was also observed in studies of V60A, a clinical variant associated with ovotestes and hence ambiguity between divergent cell fates. This shared twofold threshold is reminiscent of autosomal syndromes of transcription-factor haploinsufficiency, including XY sex reversal associated with mutations in SOX9. Our results demonstrate that nucleocytoplasmic shuttling of SRY is necessary for robust initiation of testicular development. Although also characteristic of ungulate orthologs, such shuttling is not conserved among rodents wherein impaired nuclear export of the high-mobility group box and import-dependent phosphorylation are compensated by a microsatellite-associated transcriptional activation domain. Human sex reversal due to subtle defects in the nucleocytoplasmic shuttling of SRY suggests that its transcriptional activity lies near the edge of developmental ambiguity.
Nanomicellar Formulations for Sustained Drug Delivery: Strategies and Underlying Principles (2010)

Micellar delivery systems smaller than 100 nm can be readily prepared. While micelles allow a great depth of tissue penetration for targeted drug delivery, they usually disintegrate rapidly in the body. Thus, sustained drug delivery from micellar nanocarriers is a challenge. This article summarizes various key strategies and underlying principles for sustained drug delivery using micellar nanocarriers. Comparisons are made with other competing delivery systems such as polymeric microparticles and nanoparticles. Amphiphilic molecules self-assemble in appropriate liquid media to form nanoscale micelles. Strategies for sustained release nanomicellar carriers include use of prodrugs, drug polymer conjugates, novel polymers with low critical micellar concentration or of a reverse thermoresponsive nature, reverse micelles, multi-layer micelles with layer by layer assembly, polymeric films capable of forming micelles in vivo and micelle coats on a solid support. These new micellar systems are promising for sustained drug delivery.
Bacteria as vectors for gene therapy of cancer (2010)

Anti-cancer therapy faces major challenges, particularly in terms of specificity of treatment. The ideal therapy would eradicate tumor cells selectively with minimum side effects on normal tissue. Gene or cell therapies have emerged as realistic prospects for the treatment of cancer, and involve the delivery of genetic information to a tumor to facilitate the production of therapeutic proteins. However, there is still much to be done before an efficient and safe gene medicine is achieved, primarily developing the means of targeting genes to tumors safely and efficiently. An emerging family of vectors involves bacteria of various genera. It has been shown that bacteria are naturally capable of homing to tumors when systemically administered resulting in high levels of replication locally. Furthermore, invasive species can deliver heterologous genes intra-cellularly for tumor cell expression. Here, we review the use of bacteria as vehicles for gene therapy of cancer, detailing the mechanisms of action and successes at preclinical and clinical levels.
Human factor VIIIa subunit structure. Reconstruction of factor VIIIa from the isolated A1/A3-C1-C2 dimer and A2 subunit (1991)

Heterodimeric human factor VIII was proteolytically activated by catalytic levels of thrombin to yield the (labile) active cofactor factor VIIIa possessing an initial specific activity of approximately 80 units/microgram. Activation paralleled the generation of fragments A1 and A2 derived from the heavy chain and A3-C1-C2 derived from the light chain. Chromatography of factor VIIIa, on Mono-S buffered at pH 6.0 resulted in separation of the bulk of the A2 fragment from a fraction composed predominantly of A1/A3-C1-C2 dimer plus low levels of A2 fragment. Only the latter fraction contained clotting activity (approximately 20 units/microgram) which was stable and represented a less than 10% yield when compared with the peak activity of unfractionated factor VIIIa. Further depletion of A2 fragment from Mono-S-purified factor VIIIA, achieved using an immobilized monoclonal antibody to the A2 domain, yielded a relatively inactive A1/A3-C1-C2 dimer (less than 0.4 unit/microgram). Factor VIIIa (greater than 40 units/microgram) was reconstituted from the A1/A3-C1-C2 dimer plus the A2 fragment in a reaction that was Me(2+)-independent and inhibited by moderate ionic strength. Reassociation of A2 required the A1 subunit in that the A2 subunit associated weakly if at all to A3-C1-C2 in the absence of A1. These results indicated that human factor VIIIa is a trimer represented by the subunits A1/A2/A3-C1-C2 and that the A2 subunit is required for expression of factor VIIIa activity.
Iodine quantification with dual-energy CT: phantom study and preliminary experience with VX2 residual tumour in rabbits after radiofrequency ablation (2013)

Iodine quantification with DECT may help in differentiating benign periablational reactive tissue from residual tumour in VX2 carcinoma in rabbits after RFA.