gebhart/patrepeval huggingface dataset:
Induction of antigen-specific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising Foxp3+CD25+CD4+ regulatory T cells (2004)

Naturally arising CD25(+)CD4(+) regulatory T (T(R)) cells can be exploited to establish immunologic tolerance to non-self antigens. In vivo exposure of CD25(+)CD4(+) T cells from normal naive mice to alloantigen in a T cell-deficient environment elicited spontaneous expansion of alloantigen-specific CD25(+)CD4(+) T(R) cells, which suppressed allograft rejection mediated by subsequently transferred naive T cells, leading to long-term graft tolerance. The expanded T(R) cells, which became CD25(low) in the absence of other T cells, stably sustained suppressive activity, maintained expression levels of other T(R) cell-associated molecules, including Foxp3, CTLA-4 and GITR, and could adoptively transfer tolerance to normal mice. Furthermore, specific removal of the T(R) cells derived from originally transferred CD25(+)CD4(+) T(R) cells evoked graft rejection in the long-term tolerant mice, indicating that any T(R) cells deriving from CD25(-)CD4(+) naive T cells minimally contribute to graft tolerance and that natural T(R) cells are unable to infectiously confer significant suppressive activity to other T cells. Similar antigen-specific expansion of T(R) cells can also be achieved in vitro by stimulating naturally present CD25(+)CD4(+) T cells with alloantigen in the presence of IL-2. The expanded CD25(+)CD4(+) T cells potently suppressed even secondary MLR in vitro and, by in vivo transfer, established antigen-specific long-term graft tolerance. Thus, in vivo or in vitro, direct or indirect ways of antigen-specific expansion of naturally arising Foxp3(+)CD25(+)CD4(+) T(R) cells can establish antigen-specific dominant tolerance to non-self antigens, and would also be instrumental in re-establishing self-tolerance in autoimmune disease and antigen-specific negative control of pathological immune responses.
Effect of a bcl-2 transgene on production and localization of precursor B cells in mouse bone marrow. (1998)

Many B cell precursors die while differentiating in mouse bone marrow. To ascertain the mechanisms involved in this process, populations of B lineage cells and their tissue localization were analyzed in bone marrow of transgenic mice overexpressing the apoptosis inhibitor, Bcl-2. Immunofluorescence labeling and mitotic arrest were used to quantitate the number and proliferative activity of mu- pro-B cells (terminal deoxynucleotidyl transferase [TdT]+B220-, TdT+B220+, and TdT-B220+); pre-B cells (cmu+); and B cells (smu+). Mature B cells (IgM+IgD+) were increased 16- to 20-fold. In addition, immature B lymphocytes (IgM+IgD-/low), representing newly formed cells, were increased three- to sixfold, whereas pre-B cells and late pro-B cells were increased 30 to 60% in production rate. Earlier pro-B cells expressing TdT were unaffected. In spleen, both mature and immature B cells were greatly increased, but cells of precursor phenotype were few and TdT+ cells were absent. The in vivo location of B cells was examined by autoradiography using light and electron microscopy after intravenous injection of 125I-labeled antibodies. B lineage cells (B220+) were increased throughout bone marrow, often within dilated venous sinusoids, particularly in subosteal regions. Many intravascular and perisinusoidal cells were IgDhigh mature B lymphocytes. In contrast, many other IgM+ and IgDlow immature B lymphocytes clustered extravascularly around the central venous sinus. Plasma cells with distended endoplasmic reticulum were numerous. These findings provide evidence that, in addition to expanding the recirculating pool of B cells entering bone marrow from the blood stream, high levels of Bcl-2 can inhibit some of the apoptosis occurring during B cell differentiation, thereby expanding populations of B lymphopoietic precursor cells within the bone marrow parenchyma.
Telaprevir for Previously Untreated Chronic Hepatitis C Virus Infection (2011)

BACKGROUND: In phase 2 trials, telaprevir, a hepatitis C virus (HCV) genotype 1 protease inhibitor, in combination with peginterferon-ribavirin, as compared with peginterferon-ribavirin alone, has shown improved efficacy, with potential for shortening the duration of treatment in a majority of patients.&#13;\nMETHODS: In this international, phase 3, randomized, double-blind, placebo-controlled trial, we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups: a group receiving telaprevir combined with peginterferon alfa-2a and ribavirin for 12 weeks (T12PR group), followed by peginterferon-ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point; a group receiving telaprevir with peginterferon-ribavirin for 8 weeks and placebo with peginterferon-ribavirin for 4 weeks (T8PR group), followed by 12 or 36 weeks of peginterferon-ribavirin on the basis of the same HCV RNA criteria; or a group receiving placebo with peginterferon-ribavirin for 12 weeks, followed by 36 weeks of peginterferon-ribavirin (PR group). The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment (sustained virologic response).&#13;\nRESULTS: Significantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response (75% and 69%, respectively, vs. 44%; P&lt;0.001 for the comparison of the T12PR or T8PR group with the PR group). A total of 58% of the patients treated with telaprevir were eligible to receive 24 weeks of total treatment. Anemia, gastrointestinal side effects, and skin rashes occurred at a higher incidence among patients receiving telaprevir than among those receiving peginterferon-ribavirin alone. The overall rate of discontinuation of the treatment regimen owing to adverse events was 10% in the T12PR and T8PR groups and 7% in the PR group.&#13;\nCONCLUSIONS: Telaprevir with peginterferon-ribavirin, as compared with peginterferon-ribavirin alone, was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment, with only 24 weeks of therapy administered in the majority of patients
A strategic plan for ubiquitous laptop computing (1998)

f educators are to communicate effectively with their students, they must also be able to speak the language of a computernurtured generation. We would argue the best way for a university to accomplish these goals is to place a computer in the hands of every student and faculty member. This article reports on the experience of one university that has realized a campus-wide computer initiative, and the two-prong strategy that is making this initiative a success: standardization of platforms, and decentralization of implementation.
A compressive sensing approach for expression-invariant face recognition (2009)

We propose a novel technique based on compressive sensing for expression-invariant face recognition. We view the different images of the same subject as an ensemble of intercorrelated signals and assume that changes due to variation in expressions are sparse with respect to the whole image. We exploit this sparsity using distributed compressive sensing theory, which enables us to grossly represent the training images of a given subject by only two feature images: one that captures the holistic (common) features of the face, and the other that captures the different expressions in all training samples. We show that a new test image of a subject can be fairly well approximated using only the two feature images from the same subject. Hence we can drastically reduce the storage space and operational dimensionality by keeping only these two feature images or their random measurements. Based on this, we design an efficient expression-invariant classifier. Furthermore, we show that substantially low dimensional versions of the training features, such as (i) ones extracted from critically-downsampled training images, or (ii) low-dimensional random projection of original feature images, still have sufficient information for good classification. Extensive experiments with publically-available databases show that, on average, our approach performs better than the state-of-the-art despite using only such super-compact feature representation.
Lysophosphatidic acid-induced Ca2+ mobilization in human A431 cells: structure-activity analysis (1995)

Lysophosphatidic acid (LPA; 1-acyl-sn-glycero-3-phosphate) is a platelet-derived lipid mediator that activates its own G-protein-coupled receptor to trigger phospholipase C-mediated Ca2+ mobilization and other effector pathways in numerous cell types. In this study we have examined the structural features of LPA that are important for activation of the Ca(2+)-mobilizing receptor in human A431 carcinoma cells, which show an EC50 for oleoyl-LPA as low as 0.2 nM. When the acyl chain at the sn-1 position is altered, the rank order of potency is oleoyl-LPA > arachidonoyl-LPA > linolenoyl-LPA > linoleoyl-LPA > stearoyl-LPA = palmitoyl-LPA > myristoyl-LPA. The shorter-chain species, lauroyl- and decanoyl-LPA, show little or no activity. Ether-linked LPA (1-O-hexadecyl-sn-glycero-3-phosphate) is somewhat less potent than the corresponding ester-linked LPA; its stereoisomer is about equally active. Deletion of the glycerol backbone causes a 1000-fold decrease in potency. Replacement of the phosphate group in palmitoyl-LPA by a hydrogen- or methyl-phosphonate moiety results in complete loss of activity. A phosphonate analogue with a methylene group replacing the oxygen at sn-3 has strongly decreased activity. All three phosphonate analogues induce cell lysis at doses > 15 microM. Similarly, the methyl and ethyl esters of palmitoyl-LPA are virtually inactive and become cytotoxic at micromolar doses. None of the LPA analogues tested has antagonist activity. Sphingosine 1-phosphate, a putative messenger with some structural similarities to LPA, elicits a transient rise in intracellular [Ca2+] only at micromolar doses; however, cross-desensitization experiments indicate that sphingosine 1-phosphate does not act through the LPA receptor. The results indicate that, although many features of the LPA structure are important for optimal activity, the phosphate group is most critical, suggesting that this moiety is directly involved in receptor activation.
Vaccines against tuberculosis: the impact of modern biotechnology. (1990)

Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis which worldwide afflicts approximately 50 million people with 3 million deaths and 10 million new cases per year. Immunity against M. tuberculosis is mediated by T lymphocytes and mononuclear phagocytes. Probably, interleukin secretion and target cell lysis contribute to protection. Although a vaccine is available, its efficacy, particularly in developing countries, remains a matter of controversy. Thus, strategies aimed at the development of a novel vaccine generation remain an important goal. These strategies comprise the identification of protective protein antigens and peptide epitopes, the construction of recombinant carrier systems, and the development of potent adjuvants.
A Portable Ultrasound Guidance and Training System Using High Fidelity Virtual Human Models (2006)

This paper presents a novel application of computer animated digital human technology applied to portable healthcare. It describes an advanced solution for patientspecific ultrasound guidance system which permits medics with minimal training to take highly accurate ultrasound scans in remote locations and transmit that information to doctors situated in another location. We implemented a demonstration system using a portable "back-pack" ultrasound device connected to our telemedicine program interface. It allows rapid diagnosis in the critical first hours after injury, without actually transporting the wounded person to a medical facility. Doctors are able to participate in diagnosis and treatment decisions through full access to the ultrasound scan from a remote hospital or field station via a digital network and use their own computer, PDA or even cell phone to view the images.
Tuneable surface acoustic waves for fluid and particle manipulations on disposable chips (2010)

We establish a powerful new acoustic technique to programme complex fluidic functions such as droplet movement, merging, mixing and concentration, on a disposable superstrate.
Identification of two novel transmembrane γ-carboxyglutamic acid proteins expressed broadly in fetal and adult tissues (2001)

The proline-rich gamma-carboxyglutamic acid (Gla) proteins (PRGPs) 1 and 2 are the founding members of a family of vitamin K-dependent single-pass integral membrane proteins characterized by an extracellular amino terminal domain of approximately 45 amino acids that is rich in Gla. The intracellular carboxyl terminal region of these two proteins contains one or two copies of the sequence PPXY, a motif present in a variety of proteins involved in such diverse cellular functions as signal transduction, cell cycle progression, and protein turnover. In this report, we describe the cloning of the cDNAs for two additional human transmembrane Gla proteins (TMG) of 20-24 kDa named TMG3 and TMG4. These two proteins possess extracellular Gla domains with 13 or 9 potential Gla residues, respectively, followed by membrane-spanning hydrophobic regions and cytoplasmic carboxyl terminal regions that contain PPXY motifs. This emerging family of integral membrane Gla proteins includes proline-rich Gla protein (PRGP) 1, PRGP2, TMG3, and TMG4, all of which are characterized by broad and variable distribution in both fetal and adult tissues. Members of this family can be grouped into two subclasses on the basis of their gene organization and amino acid sequence. These observations suggest novel physiological functions for vitamin K beyond its known role in the biosynthesis of proteins involved in blood coagulation and bone development. The identification and characterization of these proteins may allow a more complete understanding of the teratogenic consequences of exposure in utero to vitamin K antagonists, such as warfarin-based anticoagulants.
From Styrenes to Enantiopure α-Arylglycines in Two Steps (1998)

Direct enantioselective synthesis of (R)- and (S)-N-Cbz- or N-BOC-protected α-arylglycinols from styrenes via catalytic asymmetric aminohydroxylation, with enantioselectivities up to 99% and isolated yields up to 80%, is described. In a subsequent oxidation step, these glycinols yield the corresponding carbamate-protected α-arylglycines.
Co‐ordinate transcriptional regulation of dopamine synthesis genes by α‐synuclein in human neuroblastoma cell lines (2003)

Abnormal accumulation of alpha-synuclein in Lewy bodies is a neuropathological hallmark of both sporadic and familial Parkinson's disease (PD). Although mutations in alpha-synuclein have been identified in autosomal dominant PD, the mechanism by which dopaminergic cell death occurs remains unknown. We investigated transcriptional changes in neuroblastoma cell lines transfected with either normal or mutant (A30P or A53T) alpha-synuclein using microarrays, with confirmation of selected genes by quantitative RT-PCR. Gene products whose expression was found to be significantly altered included members of diverse functional groups such as stress response, transcription regulators, apoptosis-inducing molecules, transcription factors and membrane-bound proteins. We also found evidence of altered expression of dihydropteridine reductase, which indirectly regulates the synthesis of dopamine. Because of the importance of dopamine in PD, we investigated the expression of all the known genes in dopamine synthesis. We found co-ordinated downregulation of mRNA for GTP cyclohydrolase, sepiapterin reductase (SR), tyrosine hydroxylase (TH) and aromatic acid decarboxylase by wild-type but not mutant alpha-synuclein. These were confirmed at the protein level for SR and TH. Reduced expression of the orphan nuclear receptor Nurr1 was also noted, suggesting that the co-ordinate regulation of dopamine synthesis is regulated through this transcription factor.
Gauss-Seidel accelerated: implementing flow solvers on field programmable gate arrays (2006)

Non-linear steady-state power flow solvers have typically relied on the Newton-Raphson method to efficiently compute solutions on today's computer systems. Field programmable gate array (FPGA) devices, which have recently been integrated into high-performance computers by major computer system vendors, offer an opportunity to significantly increase the performance of power flow solvers. However, only some algorithms are suitable for an FPGA implementation. The Gauss-Seidel (GS) method of solving the AC power flow problem is an excellent example of such an opportunity. In this paper we discuss algorithmic design considerations, optimization, implementation, and performance results of the implementation of the Gauss-Seidel method running on a Silicon Graphics Inc. Altix-350 computer equipped with a Xilinx Virtex II 6000 FPGA
Layer-by-Layer-Assembled Multilayer Films for Transcutaneous Drug and Vaccine Delivery (2009)

We describe protein- and oligonucleotide-loaded layer-by-layer (LbL)-assembled multilayer films incorporating a hydrolytically degradable polymer for transcutaneous drug or vaccine delivery. Films were constructed based on electrostatic interactions between a cationic poly(beta-amino ester) (denoted Poly-1) with a model protein antigen, ovalbumin (ova), and/or immunostimulatory CpG (cytosine-phosphate diester-guanine-rich) DNA oligonucleotide adjuvant molecules. Linear growth of nanoscale Poly-1/ova bilayers was observed. Dried ova protein-loaded films rapidly deconstructed when rehydrated in saline solutions, releasing ova as nonaggregated/nondegraded protein, suggesting that the structure of biomolecules integrated into these multilayer films is preserved during release. Using confocal fluorescence microscopy and an in vivo murine ear skin model, we demonstrated delivery of ova from LbL films into barrier-disrupted skin, uptake of the protein by skin-resident antigen-presenting cells (Langerhans cells), and transport of the antigen to the skin-draining lymph nodes. Dual incorporation of ova and CpG oligonucleotides into the nanolayers of LbL films enabled dual release of the antigen and adjuvant with distinct kinetics for each component; ova was rapidly released, while CpG was released in a relatively sustained manner. Applied as skin patches, these films delivered ova and CpG to Langerhans cells in the skin. To our knowledge, this is the first demonstration of LbL films applied for the delivery of biomolecules into skin. This approach provides a new route for storage of vaccines and other immunotherapeutics in a solid-state thin film for subsequent delivery into the immunologically rich milieu of the skin.
Electrochemistry at carbon nanotubes: perspective and issues (2009)

Electrochemistry at carbon nanotubes (CNTs) is a large and growing field, but one in which there is still uncertainty about the fundamental activity of CNTs as electrode materials. On the one hand, there are many reports which focus on the favourable electrochemical properties of CNT electrodes, such as enhanced detection sensitivity, electrocatalytic effects and reduced fouling. On the other hand, other studies suggest that CNTs may be no more electroactive than graphitic powder. Furthermore, it has been proposed that the catalytic nanoparticles from which CNTs are formed may dominate the electrochemical characteristics in some instances. A considerable body of the literature presumes that the CNT sidewall is inert and that edge-plane-graphite-like open ends and defect sites are responsible for the electron transfer activity observed. In contrast, studies of well characterised single-walled nanotube (SWNT) electrodes, either as individual tubes or as two-dimensional networks, suggest sidewall activity. This review highlights how the various discrepancies in CNT electrochemistry may have arisen, by taking a historical view of the field and identifying crucial issues that still need to be solved. When assessing the behaviour of CNT electrodes, it is vitally important that careful consideration is given to the type of CNT used (SWNT or multi-walled), the quality of the material (presence of impurities), the effect of chemical processing steps in the fabrication of electrodes and the experimental arrangements adopted. Understanding these key features is an essential requirement to develop a fundamental understanding of CNT electrochemistry, to allow a wide range of electroanalytical applications, and to move the field forward rationally. As part of this process, high resolution electrochemical and electrical imaging techniques are expected to play a significant role in the future, as well as theoretical developments which examine the fundamentals of electron transfer at different types of CNTs and their characteristic surface sites.
Characterization and crystal structure of two polymorphic forms of racemic thalidomide (1994)

There are two polymorphic forms of racemic thalidomide. The α-polymorph was formed by crystallization from 2-ethoxyethanol, methanol or dichloromethane, while the β-polymorph was formed by crystallization from a supersaturated solution in refluxing 2-ethoxyethanol. The two polymorphs were characterized by IR spectra, differential scanning calorimetry (DSC), melting points, powder X-ray diffraction patterns, and X-ray crystallography. They were easily differentiated by IR (KBr) in which the α polymorph absorbed at 3196, 3098 and 859 cm–1 and the β at 3276 and 755 cm–1. DSC scans of the α and β forms showed endothermic peaks at 272.3 and 275.7 °C, respectively. During this measurement the α form was partially or fully converted into the β form if the rate of temperature change was slow or if the α form contained some β which provided seed crystals for the interconversion. Upon remelting both forms gave one peak corresponding to the β polymorph. The powder X-ray diffraction patterns for the two forms differ significantly. The crystal structures of the two polymorphs differ primarily in their mode of hydrogen bonding. In the α polymorph the molecules form dimers, while in the β the dimers form infinite linear strings linked by bifurcated hydrogen bonds along the b-axis.