gebhart/patrepeval huggingface dataset:
Qualitative difference between the cytotoxic T lymphocyte responses to melanocyte antigens in melanoma and vitiligo (2005)

Vitiligo is a skin disorder characterized by depigmented macules secondary to melanocyte loss. An unusual facet is its relation to melanoma: cytotoxic T lymphocytes directed to melanocyte antigens are found in both conditions and imply a breakdown of tolerance, yet the resulting immune reaction is the opposite. The mechanisms at the basis of these opposite effects are not known. Here, we performed a direct comparison of whole melanocyte-specific T cell populations in the two diseases. We demonstrate that neither precursor frequencies of Melan-A/MART-1-specific T lymphocytes nor their status of activation differ significantly. However, by using a tetramer-based T cell receptor down-regulation assay, we documented a higher affinity of vitiligo T cells. We calculated that the peptide concentration required for 50% of maximal receptor down-regulation differed by 6.5-fold between the two diseases. Moreover, only vitiligo T cells were capable of efficient receptor down-regulation and IFN-gamma production in response to HLA-matched melanoma cells, suggesting that this difference in receptor affinity is physiologically relevant. The differences in receptor affinity and tumor reactivity were confirmed by analyzing Melan-A/MART-1-specific clones established from the two diseases. Our results suggest that the quality, and not the quantity, of the melanocyte-specific cytotoxic responses differs between the two pathologies.
Assessment and Optimization of Cell Engraftment After Transplantation Into the Heart (2010)

Myocardial regeneration using stem and progenitor cell transplantation in the injured heart has recently become a major goal in the treatment of cardiac disease. Experimental studies and clinical applications have generally been encouraging, although the functional benefits that have been attained clinically are modest and inconsistent. Low cell retention and engraftment after myocardial delivery is a key factor limiting the successful application of cell therapy, irrespective of the type of cell or the delivery method. To improve engraftment, accurate methods for tracking cell fate and quantifying cell survival need to be applied. Several laboratory techniques (histological methods, real-time quantitative polymerase chain reaction, radiolabeling) have provided invaluable information about cell engraftment. In vivo imaging (nuclear medicine modalities, bioluminescence, and MRI) has the potential to provide quantitative information noninvasively, enabling longitudinal assessment of cell fate. In the present review, we present several available methods for assessing cell engraftment, and we critically discuss their strengths and limitations. In addition to providing insights about the mechanisms mediating cell loss after transplantation, these methods can evaluate techniques for augmenting engraftment, such as tissue engineering approaches, preconditioning, and genetic modification, allowing optimization of cell therapies.
Costimulatory Pathways in Rheumatoid Synovitis and T‐Cell Senescence (2005)

The pathogenesis of rheumatoid arthritis (RA) is determined by a complex interaction of genetic and environmental factors. Of all risk factors, age has the largest impact. RA occurs most often during the postmenopausal period of life, with incidence rates peaking in the eighth decade. While age is generally accepted as an etiologic factor for failure of immunocompetence, much less is understood about the role of T-cell senescence in autoimmunity. We have hypothesized that senescent T cells are particularly prone to be activated in specialized microenvironments, such as the synovial membrane. CD4 T cells in the senescence program were identified by the loss of CD28. Gene expression profiling documented that CD28- T cells have acquired a spectrum of regulatory receptors that are usually seen only on NK cells. Such regulatory receptors include stimulatory and inhibitory members of the killer immunoglobulin-like receptor (KIR) family, the stimulatory c-type lectin receptor NKG2D, and CX3CR1, the receptor for the chemokine fractalkine. Synovial fibroblasts express the relevant ligands, thus providing stimulatory signals to tissue-infiltrating T cells. The signaling pathways of these regulatory receptors are complex and dependent on the individual T cells, some of which express important adapter molecules such as DAP10 and DAP12. Inhibitory KIRs on T cells are often only partially functional. Our data suggest that, by virtue of altered receptor profiles, conventional tolerance mechanisms can be evaded in the aging host. By acquiring a new set of regulatory receptors, senescent CD4 T cells become responsive to novel environmental cues and find ideal stimulatory conditions in the synovial microenvironment.
Ultrasonic focusing through inhomogeneous media by application of the inverse scattering problem (1998)

A new approach is introduced for self-focusing phased arrays through inhomogeneous media for therapeutic and imaging applications. This algorithm utilizes solutions to the inverse scattering problem to estimate the impulse response (Green's function) of the desired focal point(s) at the elements of the array. This approach is a two-stage procedure, where in the first stage the Green's functions is estimated from measurements of the scattered field taken outside the region of interest. In the second stage, these estimates are used in the pseudoinverse method to compute excitation weights satisfying predefined set of constraints on the structure of the field at the focus points. These scalar, complex valued excitation weights are used to modulate the incident field for retransmission. The pseudoinverse pattern synthesis method requires knowing the Green's function between the focus points and the array, which is difficult to attain for an unknown inhomogeneous medium. However, the solution to the inverse scattering problem, the scattering function, can be used directly to compute the required inhomogeneous Green's function. This inverse scattering based self-focusing is noninvasive and does not require a strong point scatterer at or near the desired focus point. It simply requires measurements of the scattered field outside the region of interest. It can be used for high resolution imaging and enhanced therapeutic effects through inhomogeneous media without making any assumptions on the shape, size, or location of the inhomogeneity. This technique is outlined and numerical simulations are shown which validate this technique for single and multiple focusing using a circular array.
Characterization of Cyanobacterial Carotenoid Ketolase CrtW and Hydroxylase CrtR by Complementation Analysis in Escherichia coli (2008)

The pathway from beta-carotene to astaxanthin is a crucial step in the synthesis of astaxanthin, a red antioxidative ketocarotenoid that confers beneficial effects on human health. Two enzymes, a beta-carotene ketolase (carotenoid 4,4'-oxygenase) and a beta-carotene hydroxylase (carotenoid 3,3'-hydroxylase), are involved in this pathway. Cyanobacteria are known to utilize the carotenoid ketolase CrtW and/or CrtO, and the carotenoid hydroxylase CrtR. Here, we compared the catalytic functions of CrtW ketolases, which originated from Gloeobacter violaceus PCC 7421, Anabaena (also known as Nostoc) sp. PCC 7120 and Nostoc punctiforme PCC 73102, and CrtR from Synechocystis sp. PCC 6803, Anabaena sp. PCC 7120 and Anabaena variabilis ATCC 29413 by complementation analysis using recombinant Escherichia coli cells that synthesized various carotenoid substrates. The results demonstrated that the CrtW proteins derived from Anabaena sp. PCC 7120 as well as N. punctiforme PCC 73102 (CrtW148) can convert not only beta-carotene but also zeaxanthin into their 4,4'-ketolated products, canthaxanthin and astaxanthin, respectively. In contrast, the Anabaena CrtR enzymes were very poor in accepting either beta-carotene or canthaxanthin as substrates. By comparison, the Synechocystis sp. PCC 6803 CrtR converted beta-carotene into zeaxanthin efficiently. We could assign the catalytic functions of the gene products involved in ketocarotenoid biosynthetic pathways in Synechocystis sp. PCC 6803, Anabaena sp. PCC 7120 and N. punctiforme PCC 73102, based on the present and previous findings. This explains why these cyanobacteria cannot produce astaxanthin and why only Synechocystis sp. PCC 6803 can produce zeaxanthin.
Reliability and degradation of organic light emitting devices (1994)

We present a simple encapsulation technique for organic light emitting devices (OLEDs). By studying the degradation of a population of OLEDs, we show that the lifetime of encapsulated devices is increased by more than two orders of magnitude over that of unencapsulated devices. In both cases, degradation is primarily due to the formation of nonemissive regions, or dark spot defects. By studying the structure and evolution of the dark spots, we infer that the growth of electrode defects limits device lifetime. Hermetic packaging of OLEDs is essential if they are to be used in commercially viable flat panel displays.
The t(14;18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile (2002)

Recently we have identified subgroups of de novo primary diffuse large B-cell lymphoma (DLBCL) based on complementary DNA microarray-generated gene expression profiles. To correlate the gene expression profiles with cytogenetic abnormalities in these DLBCLs, we examined the occurrence of the t(14;18)(q32;q21) in the 2 distinctive subgroups of DLBCL: one with the germinal center B-cell gene expression signature and the other with the activated B cell-like gene expression signature. The t(14;18) was detected in 7 of 35 cases (20%). All 7 t(14;18)-positive cases had a germinal center B-cell gene expression profile, representing 35% of the cases in this subgroup, and 6 of these 7 cases had very similar gene expression profiles. The expression of bcl-2 and bcl-6 proteins was not significantly different between the t(14;18)-positive and -negative cases, whereas CD10 was detected only in the group with the germinal center B-cell expression profile, and CD10 was most frequently expressed in the t(14;18)-positive cases. This study supports the validity of subdividing DLBCL into 2 major subgroups by gene expression profiling, with the t(14;18) being an important event in the pathogenesis of a subset of DLBCL arising from germinal center B cells. CD10 protein expression is useful in identifying cases of DLBCL with a germinal center B-cell gene expression profile and is often expressed in cases with the t(14;18).
Mobilization of bone marrow-derived progenitor cells in acute coronary syndromes. (2005)

Two hypotheses explain the role of adult progenitor cells in myocardial regeneration. Stem cell plasticity which involves mobilization of stem cells from the bone marrow and other niches, homing to the area of tissue injury and transdifferentiation into functional cardiomyocytes. Alternative hypothesis is based on the observations that bone marrow harbors a heterogenous population of cells positive for CXCR4 - receptor for chemokine SDF-1. This population of non-hematopoietic cells expresses genes specific for early muscle, myocardial and endothelial progenitor cells (EPC). These tissue-committed stem cells circulate in the peripheral blood at low numbers and can be mobilized by hematopoietic cytokines in the setting of myocardial ischemia. Endothelial precursors capable of transforming into mature, functional endothelial cells are present in the pool of peripheral mononuclear cells in circulation. Their number significantly increases in acute myocardial infarction (AMI) with subsequent decrease after 1 month, as well as in patients with unstable angina in comparison to stable coronary heart disease (CHD). There are numerous physiological and pathological stimuli which influence the number of circulating EPC such as regular physical activity, medications (statins, PPAR-gamma agonists, estrogens), as well as numerous inflammatory and hematopoietic cytokines. Mobilization of stem cells in AMI involves not only the endothelial progenitors but also hematopoietic, non-hematopoietic stem cells and most probably the mesenchymal cells. In healthy subjects and patients with stable CHD, small number of circulating CD34+, CXCR4+, CD117+, c-met+ and CD34/CD117+ stem cells can be detected. In patients with AMI, a significant increase in CD34+/CXCR4+, CD117+, c-met+ and CD34/CD117+ stem cell number the in peripheral blood was demonstrated with parallel increase in mRNA expression for early cardiac, muscle and endothelial markers in peripheral blood mononuclear cells. The maximum number of stem cells was found early in ST-segment elevation myocardial infarction (<12 hours) with subsequent decrease through the 7-day follow-up and with concomitant changes in the levels of cytokines involved in the inflammatory response and stem cell recruitment. Moreover, peak expression of cardiac muscle and endothelial markers occurred at the same time as the most significant increase in CD34/CXCR4+ stem cell number. The SDF-1/CXCR-4 axis seems particularly important in stem/muscle progenitor cell homing, chemotaxis, engraftment and retention in ischaemic myocardium. The significance of autologous stem cells mobilization in terms of cardiac salvage and regeneration needs to be proved in humans but it seems to be a reparative mechanism triggered early in the course of acute coronary syndromes.
Prevalence of Hearing Loss and Differences by Demographic Characteristics Among US Adults<subtitle>Data From the National Health and Nutrition Examination Survey, 1999-2004</subtitle> (2008)

Hearing loss is more prevalent among US adults than previously reported. The prevalence of US hearing loss differs across racial/ethnic groups, and our data demonstrate associations with risk factors identified in prior smaller-cohort studies. Our findings also suggest that hearing loss prevention (through modifiable risk factor reduction) and screening should begin in young adulthood.
Biodegradable implants from poly-(alpha-hydroxy acid) polymers for isoniazid delivery. (1999)

An INH-containing polymer was developed that was structurally stable in an aqueous environment and that released INH over a period of at least 15 weeks. Studies with infected animals will be necessary to determine the dose required for prophylaxis and treatment of active disease.
Pore properties and pharmacological features of the P2X receptor channel in airway ciliated cells (2006)

Airway ciliated cells express an ATP-gated P2X receptor channel of unknown subunit composition (P2X(cilia)) which is modulated by Na+ and by long exposures to ATP. P2X(cilia) was investigated by recording currents from freshly dissociated rabbit airway ciliated cells with the patch-clamp technique in the whole-cell configuration. During the initial continuous exposure to extracellular ATP, P2X(cilia) currents gradually increase in magnitude (priming), yet the permeability to N-methyl-D-glucamine (NMDG) does not change, indicating that priming does not arise from a progressive change in pore diameter. Na+, which readily permeates P2X(cilia) receptor channels, was found to inhibit the channel extracellular to the electric field. The rank order of permeability to various monovalent cations is: Li+, Na+, K+, Rb+, Cs+, NMDG+ and TEA+, with a relative permeability of 1.35, 1.0, 0.99, 0.91, 0.79, 0.19 and 0.10, respectively. The rank order for the alkali cations follows an Eisenman series XI for a high-strength field site. Ca2+ has been estimated to be 7-fold more permeant than Na+. The rise in [Ca2+]i in ciliated cells, induced by the activation of P2X(cilia), is largely inhibited by either Brilliant Blue G or KN-62, indicating that P2X7 may be a part of P2X(cilia). P2X(cilia) is augmented by Zn2+ and by ivermectin, and P2X4 receptor protein is detected by immunolabelling at the basal half of the cilia, strongly suggesting that P2X4 is a component of P2X(cilia) receptor channels. Taken together, these results suggest that P2X(cilia) is either assembled from P2X4 and P2X7 subunits, or formed from modified P2X4 subunits.
L-Type Amino Acid Transporter-1 Expressed in Human Astrocytomas, U343MGa (2007)

LAT1 (L-type amino acid transporter 1), one of the L-type amino acid transporters, transports the branched and aromatic amino acids. LAT1 requires the heavy chain of 4F2 antigen (4F2hc) for the functional expression as an amino acid transporter. The expression of this transporter is up-regulated in tumor cells and rapidly-growing cells to support their proliferation. Here, we studied the expression of LAT1 and 4F2hc in human cultured cells by real-time PCR and Western blot, and found that human brain astrocytomas, U343MGa, highly expressed LAT1 and 4F2hc mRNAs and proteins. The uptake of [14C]leucine by U343MGa cells is Na+-independent and inhibited by BCH (2-amino-2-norbornane carboxylic acid), and branched and aromatic amino acids, indicating that the LAT1 is expressed at the cell surface. Pulse chase labeling and surface labeling experiments of this cell line indicate that the protein synthesis of LAT1 and 4F2hc is slow, however, the heterodimeric complex assembled in the cells is very stable, and that the disulfide bond between the LAT1 and 4F2hc is not directly involved in the stability of the heterodimer.
Soluble TNF binding proteins modulate the negative inotropic properties of TNF-alpha in vitro (1995)

Soluble tumor necrosis factor (TNF) binding proteins (TNF-BPs) were characterized with respect to their capacity to modulate the negative inotropic properties of TNF-alpha in isolated contracting cardiac myocytes. Three TNF-BPs were evaluated: two natural monomeric human TNF monomeric binding proteins, TNF-BP1 and TNF-BP2, and sTNFR:Fc, a dimer of two molecules of human TNF-BP2 linked by the Fc portion of the human immunoglobulin G1 molecule. When TNF-alpha (25 pM) was allowed to form TNF-BP-TNF-alpha complexes, the negative inotropic effects of TNF-alpha were completely prevented by "neutralizing concentrations" of TNF-BPs, whereas lesser concentrations of TNF-BPs only partially attenuated the negative inotropic effects of TNF-alpha. The dimeric binding protein sTNFR:Fc was more effective on a molar basis than either of the monomeric binding proteins (TNF-BP1 or TNF-BP2) with respect to blocking the negative inotropic effects of TNF-alpha. When cardiac myocytes that had been treated with TNF-alpha (25 pM) were exposed to neutralizing concentrations of TNF-BP1, TNF-BP2, and sTNFR:Fc, the negative inotropic effects were completely reversed within 30 min. Thus these studies show for the first time that TNF-BPs are sufficient to prevent, as well as reverse, the negative inotropic properties of TNF-alpha in vitro.
Photo-thermo-refractive glasses for high-efficiency Bragg gratings in UV, visible, and IR regions (2000)

Summary form only given. The wide spread use of holographic elements is constrained by the lack of available holographic materials. Hariharan's recent book notes that among the photosensitive materials available for high efficiency hologram recording, each have merits, as well as drawbacks. This paper describes properties and performance of inorganic glass as a medium for volume hologram recording, which meets most requirements cited. The use of inorganic photosensitive glasses for phase hologram recording was described several years ago. The two-step process of exposure to UV radiation and thermal development (photo-thermo-refractive process) has been used to record phase patterns in glass defined as photo-thermo-refractive (PTR). Relative diffraction efficiency of up to 90% was recorded at that time, however, strong scattering from the thermal development process resulted in a low absolute diffraction efficiency, not exceeding 45%.
A Classifier for the SNP-Based Inference of Ancestry (2003)

Ancestral inference from DNA could serve as an important adjunct for both standard and future human identity testing procedures. However, current STR methods for the inference of ancestral affiliation have inherent statistical and technical limitations. In an effort to identify bi-allelic markers that can be used to infer ancestral affiliation from DNA, we screened 211 SNPs in the human pigmentation and xenobiotic metabolism genes. Allele frequencies of 56 SNPs (most from pigmentation genes) were dramatically different between groups of unrelated individuals of Asian, African, and European descent, and both observed and simulated log likelihood ratios revealed that the markers were of exceptional value for ancestral inference. Log likelihood ratios of the multilocus estimates of biological ancestry (EAE/EBA) ranged from 7 to 10, which are on par with the best of the STR batteries yet described. A linear classification method was developed for incorporating these SNPs into a classifier model that was 99, 98, and 100% accurate for identifying individuals of European, African, and Asian descent, respectively. The methods and markers we describe are therefore an important first step for the development of a practical multiplex test for the inference of ancestry in a forensics setting.
Checkpoint repair for out-of-order execution machines (1987)

Out-of-order execution and branch prediction are two mechanisms that can be used profitably in the design of Supercomputers to increase performance. Unfortunately this means there must be some kind of repair mechanism, since situations do occur that require the computing engine to repair to a known previous state. One way to handle this is by checkpoint repair. In this paper we derive several properties of checkpoint repair mechanisms. In addition, we provide algorithms for performing checkpoint repair that incur very little overhead in time and modest cost in hardware. We also note that our algorithms require no additional complexity or time for use with write back cache memory systems than they do with write through cache memory systems, contrary to statements made by previous researchers.
Structural Colors in Nature: The Role of Regularity and Irregularity in the Structure (2005)

Coloring in nature mostly comes from the inherent colors of materials, but it sometimes has a purely physical origin, such as diffraction or interference of light. The latter, called structural color or iridescence, has long been a problem of scientific interest. Recently, structural colors have attracted great interest because their applications have been rapidly progressing in many fields related to vision, such as the paint, automobile, cosmetics, and textile industries. As the research progresses, however, it has become clear that these colors are due to the presence of surprisingly minute microstructures, which are hardly attainable even by ultramodern nanotechnology. Fundamentally, most of the structural colors originate from basic optical processes represented by thin-film interference, multilayer interference, a diffraction grating effect, photonic crystals, light scattering, and so on. However, to enhance the perception of the eyes, natural creatures have produced various designs, in the course of evolution, to fulfill simultaneously high reflectivity in a specific wavelength range and the generation of diffusive light in a wide angular range. At a glance, these two characteristics seem to contradict each other in the usual optical sense, but these seemingly conflicting requirements are realized by combining appropriate amounts of regularity and irregularity of the structure. In this Review, we first explain the fundamental optical properties underlying the structural colors, and then survey these mysteries of nature from the viewpoint of regularity and irregularity of the structure. Finally, we propose a general principle of structural colors based on structural hierarchy and show their up-to-date applications.