gebhart/patrepeval huggingface dataset:
Distribution of human CMV-specific memory T cells among the CD8pos. subsets defined by CD57, CD27, and CD45 isoforms (1999)

Chronic antigenic stimulation has been associated with peripheral blood expansions of CD8pos. T cells characterized by CD57 expression, loss of CD27 expression, and reversal of the CD45RO(bright) /RA(dim) phenotype usually associated with immunological memory towards a CD45RO(dim) /RA(bright) phenotype. However, the relationship and functional significance of these subset(s) has remained controversial. Here, this issue was addressed using a novel flow cytometric technique that allows simultaneous detection of human cytomegalovirus (HCMV)-specific CD8pos. memory T cells by rapid (< 6 h) HCMV peptide-specific induction of cytokine synthesis, and their phenotypic characterization, including CD57, CD27 and CD45RA/RO. The vast majority of resting CD8(pos.) T cells capable of rapid induction of IFN-gamma and TNF-alpha synthesis in response to HCMV peptides were found in a subset characterized by intermediate to high expression of CD57, down-regulation/loss of CD27, and varying degrees of reversal of the classical "memory" CD45RO(bright) /RA(dim) phenotype. This subpopulation likely includes the fully differentiated memory cells responsible for the long-term immune defense against HCMV reactivation.
Resettlement Policy Framework (2019)

The development objective of the Karachi Water and Sewerage Services Improvement Project for Pakistan is to improve access to safe water services in Karachi and to increase Karachi Water and Sanitation Board (KW and SB’s) financial and operational performance. Some of the negative impacts and mitigation measures include: (1) land for land compensation through provision of plots of equal value and productivity as that of lost; (2) cash compensation at full replacement cost (RC) including fair market value plus 15 percent compulsory acquisition surcharge all transaction costs, applicable fees and taxes and any other payment applicable; (3) rental fee payment for period of occupation of land, as mutually agreed by the parties; (4) for vulnerable households, provide legal and affordable access to adequate housing to improve their living standard to at least national minimum standard; (5) cash compensation (one year crop) at current market rate proportionate to size of lost plot, based on crop type and highest average yield over past 3 years or as assessed through the respective agricultural departments; (6) if project based relocation, Project Affected People (PAPs) will be provided with access to civic amenities including electricity, water supply, and sewage as well as school and health center; (7) rental assistance as a lump sum amount computed on the basis of prevailing rental rate for a period as agreed between the PAP and project team, to assist the PAPs in renting house or commercial structure; and (8) cash compensation equal to lost income during period of business interruption up to 3 months based on tax record or, in its absence, comparable rates from registered businesses of the same type with tax records, or computed based on officially designated minimum wage rate.
Quantumly Entangled: Cosmic Consciousness in the Classroom (2018)

The main problem with Western education is the dualistic perspective which separates the teacher/tutor and the student into two separate identities. However, modern physics, specifically the theory of quantum entanglement, is showing that the atoms which compose the false identity of a “self” are intertwined in a mutual state of causality. These quantum revelations are affirming the ancient wisdom teaching of “That art thou” which is found in religions and spiritualities across the globe which an individual arrives at in an ego death and rebirth experience. The system of cosmic consciousness in the classroom expunges the dualistic perspective of “you” and “me” and focuses on only “us,” fostering an environment of co-habitation and learning.
Exposure to Carbon Nanotube Material: Assessment of Nanotube Cytotoxicity using Human Keratinocyte Cells (2003)

Carbon nanotubes are new members of carbon allotropes similar to fullerenes and graphite. Because of their unique electrical, mechanical, and thermal properties, carbon nanotubes are important for novel applications in the electronics, aerospace, and computer industries. Exposure to graphite and carbon materials has been associated with increased incidence of skin diseases, such as carbon fiber dermatitis, hyperkeratosis, and naevi. We investigated adverse effects of single-wall carbon nanotubes (SWCNT) using a cell culture of immortalized human epidermal keratinocytes (HaCaT). After 18 h of exposure of HaCaT to SWCNT, oxidative stress and cellular toxicity were indicated by formation of free radicals, accumulation of peroxidative products, antioxidant depletion, and loss of cell viability. Exposure to SWCNT also resulted in ultrastructural and morphological changes in cultured skin cells. These data indicate that dermal exposure to unrefined SWCNT may lead to dermal toxicity due to accelerated oxidative stress in the skin of exposed workers.
Hypothalamic Y2 receptors regulate bone formation (2002)

Neuropeptide Y (NPY) is a downstream modulator of leptin action, possibly at the level of the arcuate nucleus where NPY neurons are known to express both leptin receptors and Y2 receptors. In addition to the well-described role of NPY and leptin in energy balance and obesity, intracerebroventricular administration of NPY or leptin also causes bone loss. Here we show that Y2 receptor-deficient mice have a twofold increase in trabecular bone volume as well as greater trabecular number and thickness compared with control mice. We also demonstrate that central Y2 receptors are crucial for this process, since selective deletion of hypothalamic Y2 receptors in mature conditional Y2 knockout mice results in an identical increase in trabecular bone volume within 5 weeks. This hypothalamus-specific Y2 receptor deletion stimulates osteoblast activity and increases the rate of bone mineralization and formation, with no effect on osteoblast or osteoclast surface measurements. The lack of any changes in plasma total calcium, leptinemia, or hypothalamo-pituitary-corticotropic, -thyrotropic, -somatotropic, or -gonadotropic output suggests that Y2 receptors do not modulate bone formation by humoral mechanisms, and that alteration of autonomic function through hypothalamic Y2 receptors may play a key role in a major central regulatory circuit of bone formation.
Multidrug-ResistantAcinetobacterExtremity Infections in Soldiers (2005)

War wound infection and osteomyelitis caused by multidrug-resistant (MDR) Acinetobacter species have been prevalent during the 2003-2005 military operations in Iraq. Twenty-three soldiers wounded in Iraq and subsequently admitted to our facility from March 2003 to May 2004 had wound cultures positive for Acinetobacter calcoaceticus-baumannii complex. Eighteen had osteomyelitis, 2 burn infection, and 3 deep wound infection. Primary therapy for these infections was directed antimicrobial agents for an average of 6 weeks. All soldiers initially improved, regardless of the specific type of therapy. Patients were followed up to 23 months after completing therapy, and none had recurrent infection with Acinetobacter species. Despite the drug resistance that infecting organisms demonstrated in this series, a regimen of carefully selected extended antimicrobial-drug therapy appears effective for osteomyelitis caused by MDR Acinetobacter spp.
Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction (1992)

We report on the development and application of a rapid assay for detecting and typing dengue viruses. Oligonucleotide consensus primers were designed to anneal to any of the four dengue virus types and amplify a 511-bp product in a reverse transcriptase-polymerase chain reaction (PCR). First, we produced a cDNA copy of a portion of the viral genome in a reverse transcriptase reaction in the presence of primer D2 and then carried out a standard PCR (35 cycles of heat denaturation, annealing, and primer extension) with the addition of primer D1. The resulting double-stranded DNA product of the RT-PCR was typed by two methods: dot blot hybridization of the 511-bp amplified product to dengue virus type-specific probes or a second round of PCR amplification (nested PCR) with type-specific primers, yielding DNA products the unique sizes of which were diagnostic for each dengue virus serotype. The accumulated data demonstrated that dengue viruses can be accurately detected and typed from viremic human serum samples.
Cationic Liposome Conjugation to Recombinant Adenoviral Vector Reduces Viral Antigenicity (2000)

Adenoviral (Ad) vectors are commonly used in gene therapy trials because of their efficiency in gene transfer. However, their use is limited by immune responses that reduce transgene expression and decrease the efficacy of repeated vector administration. In this study, we demonstrated that conjugation of Ad vector with our novel cationic liposomes could reduce viral antigenicity in vivo. Mice subcutaneously injected with liposome-conjugated Ad vector showed a 6.5-fold reduction of anti-Ad antibodies with neutralizing activity, compared to those with unconjugated Ad vector. Interestingly, we also found that the conjugated vector is less susceptible to inactivation by neutralizing antibodies in vitro and in vivo. Our results suggest that liposome conjugation reduces viral antigenicity, shields vectors from neutralizing antibody, and may allow repeated Ad vector administration.
Visualization of biomass solubilization and cellulose regeneration during ionic liquid pretreatment of switchgrass (2009)

Auto-fluorescent mapping of plant cell walls was used to visualize cellulose and lignin in pristine switchgrass (Panicum virgatum) stems to determine the mechanisms of biomass dissolution during ionic liquid pretreatment. The addition of ground switchgrass to the ionic liquid 1-n-ethyl-3-methylimidazolium acetate resulted in the disruption and solubilization of the plant cell wall at mild temperatures. Swelling of the plant cell wall, attributed to disruption of inter- and intramolecular hydrogen bonding between cellulose fibrils and lignin, followed by complete dissolution of biomass, was observed without using imaging techniques that require staining, embedding, and processing of biomass. Subsequent cellulose regeneration via the addition of an anti-solvent, such as water, was observed in situ and provided direct evidence of significant rejection of lignin from the recovered polysaccharides. This observation was confirmed by chemical analysis of the regenerated cellulose. In comparison to untreated biomass, ionic liquid pretreated biomass produces cellulose that is efficiently hydrolyzed with commercial cellulase cocktail with high sugar yields over a relatively short time interval.
MHC Class I-Presented T Cell Epitopes Identified by Immunoproteomics Analysis Are Targets for a Cross Reactive Influenza-Specific T Cell Response (2012)

Influenza virus infection and the resulting complications are a significant global public health problem. Improving humoral immunity to influenza is the target of current conventional influenza vaccines, however, these are generally not cross-protective. On the contrary, cell-mediated immunity generated by primary influenza infection provides substantial protection against serologically distinct viruses due to recognition of cross-reactive T cell epitopes, often from internal viral proteins conserved between viral subtypes. Efforts are underway to develop a universal flu vaccine that would stimulate both the humoral and cellular immune responses leading to long-lived memory. Such a universal vaccine should target conserved influenza virus antibody and T cell epitopes that do not vary from strain to strain. In the last decade, immunoproteomics, or the direct identification of HLA class I presented epitopes, has emerged as an alternative to the motif prediction method for the identification of T cell epitopes. In this study, we used this method to uncover several cross-specific MHC class I specific T cell epitopes naturally presented by influenza A-infected cells. These conserved T cell epitopes, when combined with a cross-reactive antibody epitope from the ectodomain of influenza M2, generate cross-strain specific cell mediated and humoral immunity. Overall, we have demonstrated that conserved epitope-specific CTLs could recognize multiple influenza strain infected target cells and, when combined with a universal antibody epitope, could generate virus specific humoral and T cell responses, a step toward a universal vaccine concept. These epitopes also have potential as new tools to characterize T cell immunity in influenza infection, and may serve as part of a universal vaccine candidate complementary to current vaccines.
An analysis of the timing of turn-taking in a corpus of goal-oriented dialogue (1998)

This paper presents a context-based analysis of the intervals between different speakers' utterances in a corpus of taskoriented dialogue (the Human Communication Research Centre's Map Task Corpus.See Anderson et al. 1991).In the analysis, we assessed the relationship between inter-speaker intervals and various contextual factors, such as the effects of eye contact, the presence of conversational game boundaries, the category of move in an utterance, and the degree of experience with the task in hand.The results of the analysis indicated that the main factors which gave rise to significant differences in inter-speaker intervals were those which related to decision-making and planning -the greater the amount of planning, the greater the inter-speaker interval.Differences between speakers were also found to be significant, although this effect did not necessarily interact with all other effects.These results provide unique and useful data for the improved effectiveness of dialogue systems.
Site-selected transposon mutagenesis at the hcf106 locus in maize. (1995)

The High chlorophyll fluorescence106 (Hcf106) gene in maize is required for chloroplast membrane biogenesis, and the hcf106-mum1 allele is caused by the insertion of a Robertson's Mutator Mu1 element into the promoter of the gene. Seedlings homozygous for hcf106-mum1 are pale green and die 3 weeks after germination, but only in the presence of Mutator activity conferred by active, autonomous Mu regulatory transposons elsewhere in the genome. When Mutator activity is lost, the mutant phenotype is suppressed, and homozygous plants have an almost wild-type phenotype. To isolate derivative alleles at the hcf106 locus that no longer require Mutator activity for phenotypic expression, we have developed a method for site-selected transposon mutagenesis in maize. This procedure, first described for Caenorhabditis elegans and Drosophila, involves using polymerase chain reaction (PCR) to screen pools of individuals for insertions and deletions in genes of known sequence. Pools of seedlings segregating for the progenitor allele hcf106-mum1 were screened by PCR for insertions and deletions associated with Robertson's Mutator. In a 360-bp target region, two new insertions and one deletion were identified in only 700 Mu-active gametes screened. One of the insertions was in the progenitor hcf106-mum1 allele and the other was in the wild-type allele, but all three new alleles were found to have break-points at the same nucleotide in the first intron. Unlike the hcf-106-mum1 progenitor allele, the deletion and one of the insertions conferred pale green seedling lethal phenotypes in the absence of mutator activity. However, the second insertion had a weak, viable phenotype under these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Paradoxical Vasoconstriction Induced by Acetylcholine in Atherosclerotic Coronary Arteries (1986)

Acetylcholine is believed to dilate normal blood vessels by promoting the release of a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). By contrast, if the endothelium is removed experimentally, acetylcholine constricts blood vessels. We tested the hypothesis that muscarinic cholinergic vasodilation is impaired in coronary atherosclerosis. Graded concentrations of acetylcholine and, for comparison, the nonendothelial-dependent vasodilator nitroglycerin were infused into the left anterior descending artery of eight patients with advanced coronary stenoses (greater than 50 percent narrowing), four subjects with angiographically normal coronary arteries, and six patients with mild coronary atherosclerosis (less than 20 percent narrowing). Vascular responses were evaluated by quantitative angiography. In several segments each of four normal coronary arteries, acetylcholine caused a dose-dependent dilation from a control diameter of 1.94 +/- 0.16 mm to 2.16 +/- 0.15 mm with the maximal acetylcholine dose (P less than 0.01). In contrast, all eight of the arteries with advanced stenoses showed dose-dependent constriction, from 1.05 +/- 0.05 to 0.32 +/- 0.16 mm at the highest concentration of acetylcholine (P less than 0.01), with temporary occlusion in five. Five of six vessels with minimal disease also constricted in response to acetylcholine. All vessels dilated in response to nitroglycerin, however. We conclude that paradoxical vasoconstriction induced by acetylcholine occurs early as well as late in the course of coronary atherosclerosis. Our preliminary findings suggest that the abnormal vascular response to acetylcholine may represent a defect in endothelial vasodilator function, and may be important in the pathogenesis of coronary vasospasm.
Direct evidence for native CD4 oligomers in lymphoid and monocytoid cells (1999)

CD4 is expressed by T lymphocytes and monocytes and is generally considered a monomer even though its structure was originally modelled on the REI Bence-Jones homodimer. However, native CD4 was demonstrated as both monomer and dimers of 55 and 110 kDa in lymphoid and monocytoid cells by immunoprecipitation and immunoblotting after solubilization with alkylating (iodoacetamide) or reducing (dithiothreitol, 2-mercaptoethanol) reagents. Full reduction yielded only the 55-kDa monomeric form. Purified CD4 oligomers from CEM-T4 cells were also resolved as homodimers by MALDI-Tof mass fingerprinting after tryptic digestion. Cell treatment with the membrane impermeable, free-thiol reactive, 5,5'-dithiobis-2-nitrobenzoic acid enhanced cell surface CD4 dimers and tetramers. The interaction sites producing dimerization were probably in the D4 domain as OKT4 inhibited self association of recombinant CD4 (rCD4). Oligomerization of rCD4 by glutathione and thioredoxin indicates that thiol exchange interactions were responsible. Enhanced CD4 dimer expression was also observed after PMA (20 ng/ml) activation of THP-1 cells. These findings demonstrate that different quaternary forms of CD4 such as monomers, homodimers and tetramers are expressed by T lymphocytes and monocytes/macrophages.
Localization of transglutaminase-reactive glutamine residues in bovine osteopontin (1994)

Here we report the identification of two transglutaminase-reactive glutamines (Gln-34 and Gln-36) in bovine osteopontin (OPN). Sequence alignment revealed that these glutamines are conserved in all known OPN sequences, indicating a functional importance of this region of the protein. Furthermore, immunological analysis of bovine bone demonstrated that OPN is present in high-molecular-mass complexes in vivo. These findings support the functional aspects of a transglutaminase-catalysed cross-linking of OPN in facilitating cellular attachment and tissue calcification.
Antigen-based immunotherapy for autoimmune disease: current status (2014)

Autoimmune diseases are common chronic disorders that not only have a major impact on the quality of life but are also potentially life-threatening. Treatment modalities that are currently favored have conferred significant clinical benefits, but they may have considerable side effects. An optimal treatment strategy for autoimmune disease would specifically target disease-associated antigens and limit systemic side effects. Similar to allergen-specific immunotherapy for allergic rhinitis, antigen-specific immunotherapy for autoimmune disease aims to induce immune deviation and promote tolerance to specific antigens. In this review, we present the current status of studies and clinical trials in both human and animal hosts that use antigen-based immunotherapy for autoimmune disease.
Gene Transfer into Humans — Immunotherapy of Patients with Advanced Melanoma, Using Tumor-Infiltrating Lymphocytes Modified by Retroviral Gene Transduction (1990)

These studies demonstrate the feasibility and safety of using retroviral gene transduction for human gene therapy and have implications for the design of TIL with improved antitumor potency, as well as for the possible use of lymphocytes for the gene therapy of other diseases.
Efficient Nash equilibrium approximation through Monte Carlo counterfactual regret minimization (2012)

Recently, there has been considerable progress towards algorithms for approximating Nash equilibrium strategies in extensive games. One such algorithm, Counterfactual Regret Minimization (CFR), has proven to be effective in two-player zero-sum poker domains. While the basic algorithm is iterative and performs a full game traversal on each iteration, sampling based approaches are possible. For instance, chance-sampled CFR considers just a single chance outcome per traversal, resulting in faster but less precise iterations. While more iterations are required, chance-sampled CFR requires less time overall to converge. In this work, we present new sampling techniques that consider sets of chance outcomes during each traversal to produce slower, more accurate iterations. By sampling only the public chance outcomes seen by all players, we take advantage of the imperfect information structure of the game to (i) avoid recomputation of strategy probabilities, and (ii) achieve an algorithmic speed improvement, performing O(n2) work at terminal nodes in O(n) time. We demonstrate that this new CFR update converges more quickly than chance-sampled CFR in the large domains of poker and Bluff.
Endgame: Glybera Finally Recommended for Approval as the First Gene Therapy Drug in the European Union (2012)

In an Editorial published earlier this year in Molecular Therapy,1 I described the regulatory uncertainty surrounding the evaluation of Glybera (alipogene tiparvovec) by the European Medicines Agency (EMA). Glybera is an adeno-associated viral vector engineered to express lipoprotein lipase in the muscle for the treatment of lipoprotein lipase deficiency. As with a typical TV serial, its regulatory saga has now had four acts, leading recently to a final recommendation by the EMA to approve Glybera in the European Union.
Transcriptional profiling reveals developmental relationship and distinct biological functions of CD16+ and CD16- monocyte subsets (2009)

These results suggest that CD16+ and CD16- Mo originate from a common myeloid precursor, with CD16+ Mo having a more MPhi - and DC-like transcription program suggesting a more advanced stage of differentiation. Distinct transcriptional programs, together with their recruitment into tissues via different mechanisms, also suggest that CD16+ and CD16- Mo give rise to functionally distinct DC and MPhi in vivo.