gebhart/patrepeval huggingface dataset:
Aerosol Insulin Induces Regulatory CD8 γδ T Cells That Prevent Murine Insulin-dependent Diabetes (1996)

Cellular immune hyporesponsiveness can be induced by the presentation of soluble protein antigens to mucosal surfaces. Most studies of mucosa-mediated tolerance have used the oral route of antigen delivery and few have examined autoantigens in natural models of autoimmune disease. Insulin is an autoantigen in humans and nonobese diabetic (NOD) mice with insulin-dependent diabetes mellitus (IDDM). When we administered insulin aerosol to NOD mice after the onset of subclinical disease, pancreatic islet pathology and diabetes incidence were both significantly reduced. Insulin-treated mice had increased circulating antibodies to insulin, absent splenocyte proliferation to the major epitope, insulin B chain amino acids 9-23, which was associated with increased IL-4 and particularly IL-10 secretion, and reduced proliferation to glutamic acid decarboxylase, another islet autoantigen. The ability of splenocytes from insulin-treated mice to suppress the adoptive transfer of diabetes to nondiabetic mice by T cells of diabetic mice was shown to be caused by small numbers of CD8 gamma delta T cells. These findings reveal a novel mechanism for suppressing cell-mediated autoimmune disease. Induction of regulatory CD8 gamma delta T cells by aerosol insulin is a therapeutic strategy with implications for the prevention of human IDDM.
Bit-serial reed-solomon decoders in vlsi (coding theory) (1985)

Reed-Solomon codes are known to provide excellent error-correcting capabilities on many types of communication channels. Although efficient decoding algorithms have been known for over fifteen years, currently available decoder systems are large both in size and in power consumption. Such systems typically use a single, very fast, fully parallel finite-field multiplier in a sequential architecture. Thus, more processing time is required as the code redundancy increases. By using many arithmetic units on a single chip, it is possible to exploit the concurrency inherent in the decoding algorithms to attain performance levels previously possible only with large ECL systems.
An investigation into the structure of binary extension fields reveals that the common arithmetic operations used in decoding can be implemented quite efficiently in a bit-serial fashion, using any of several bases over GF(2). Berlekamp's dual-basis multiplier is generalized to the product of two arbitrary field elements, and a necessary and sufficient condition is then derived for the existence of a self-dual basis. Efficient methods for bit-serial multiplicative inversion are also discussed, greatly reducing the complexity traditionally associated with this operation.
Using these bit-serial techniques, several architectures for implementing each phase of the known Reed-Solomon decoding algorithms are presented and compared. Simple methods are presented to allow power-sum syndrome decoders to handle codes with a variety of block lengths and redundancies. Each approach comes within a factor of log n (where n is the block length of the code) of the recently derived asymptotic lower bounds for both time and area. Results from a student project to lay out a prototype decoder chip using the Berlekamp-Massey algorithm are also discussed. By utilizing the parallelism inherent in the key equation solution, these architectures can decode received words at a speed independent of the redundancy of the code.
Emerging Techniques for Evaluation of the Hemodynamics of Intracranial Vascular Pathology (2014)

Advances in imaging modalities have improved the assessment of intracranial hemodynamics using non-invasive techniques. This review examines new imaging modalities and clinical applications of currently available techniques, describes pathophysiology and future directions in hemodynamic analysis of intracranial stenoses, aneurysms and arteriovenous malformations and explores how hemodynamic analysis may have prognostic value in predicting clinical outcomes and assist in risk stratification. The advent of new technologies such as pseudo-continuous arterial spin labeling, accelerated magnetic resonance angiography (MRA) techniques, 4D digital subtraction angiography, and improvements in clinically available techniques such as phase-contrast MRA may change the landscape of vascular imaging and modify current clinical practice guidelines.
1998 Summary: National Hospital Discharge Survey (2000)

Objectives—This report presents national estimates of the use of non-Federal short-stay hospitals in the United States during 1998. Numbers and rates of discharges, diagnoses, and procedures are shown by age and sex. Discharges are also shown by geographic region of hospitals. Average lengths of stay are presented for all discharges and for selected diagnostic categories by age and by sex. Methods—The estimates are based on medical abstract data collected through the National Hospital Discharge Survey for 1998. The survey has been conducted annually by the National Center for Health Statistics since 1965. Diagnoses and procedures presented are coded according to the International Classification of Diseases, 9th Revision, Clinical Modification, or ICD–9–CM. Results—In 1998, there were an estimated 31.8 million discharges of inpatients, excluding newborn infants, from short-stay non-Federal hospitals in the United States. The discharge rate was 1,165.3 per 10,000 population and the average length of stay was 5.1 days. Six diagnostic categories each accounted for more than a million discharges. These were heart disease, delivery, malignant neoplasms, pneumonia, psychoses, and cerebrovascular disease. There were 41.5 million procedures performed on hospital inpatients during the same year. Almost threefourths of all procedures were in four ICD–9–CM chapters: miscellaneous diagnostic and therapeutic procedures, obstetrical procedures, operations on the cardiovascular system, and operations on the digestive system.
Structural and functional diversity of phosphoinositide 3-kinases (1996)

Phosphoinositide 3-kinases (PI3-kinases) have been shown to be recruited to cell surface receptor signal complexes whose formation is triggered by growth factors, cytokines and other ligands. PI3-kinases are also involved in protein sorting phenomena. A number of PI3-kinase isotypes have been characterised in several laboratories. Here the relations between the PI3-kinases, PI4-kinases and PI5-kinases and other potential phosphoinositide kinases are analysed. A study of the relation of structure to function for sequence motifs defined through the use of homology searches and protein modelling techniques is described and used to assign the family of phosphoinositide kinases to subgroups.
Direct Preparation of 3-Iodochromenes from 3-Aryl- and 3-Alkyl-2-propyn-1-ols with Diaryliodonium Salts and NIS (2016)

On the basis of a study of the O-phenylation of 3-phenyl-2-propyn-1-ol with diphenyliodonium triflate and t-BuONa, a variety of 4-aryl-3-iodo-2H-benzopyrans were prepared in good to moderate yields in one pot from the reaction of 3-aryl-2-propyn-1-ols with diaryliodonium triflates and t-BuONa, followed by the treatment with N-iodosuccinimide and BF3·OEt2, under transition-metal-free and mild conditions. The formed 4-phenyl-3-iodo-2H-benzopyran was converted into 4-phenyl-2H-benzopyran derivatives through C-C bond formations at the 3-position by Pd-catalyzed coupling reactions and into coumarin with oxidants.
Androgen Receptor Splice Variants Activate Androgen Receptor Target Genes and Support Aberrant Prostate Cancer Cell Growth Independent of Canonical Androgen Receptor Nuclear Localization Signal (2012)

Synthesis of truncated androgen receptor (AR) splice variants has emerged as an important mechanism of prostate cancer (PCa) resistance to AR-targeted therapy and progression to a lethal castration-resistant phenotype. However, the precise role of these factors at this stage of the disease is not clear due to loss of multiple COOH-terminal AR protein domains, including the canonical nuclear localization signal (NLS) in the AR hinge region. Despite loss of this NLS, we show that diverse truncated AR variant species have a basal level of nuclear localization sufficient for ligand-independent transcriptional activity. Whereas full-length AR requires Hsp90 and importin-β for active nuclear translocation, basal nuclear localization of truncated AR variants is independent of these classical signals. For a subset of truncated AR variants, this basal level of nuclear import can be augmented by unique COOH-terminal sequences that reconstitute classical AR NLS activity. However, this property is separable from ligand-independent transcriptional activity. Therefore, the AR splice variant core consisting of the AR NH(2)-terminal domain and DNA binding domain is sufficient for nuclear localization and androgen-independent transcriptional activation of endogenous AR target genes. Indeed, we show that truncated AR variants with nuclear as well as nuclear/cytoplasmic localization patterns can drive androgen-independent growth of PCa cells. Together, our data demonstrate that diverse truncated AR species with varying efficiencies of nuclear localization can contribute to castration-resistant PCa pathology by driving persistent ligand-independent AR transcriptional activity.
The History of Affirmative Action in the USA: A Teaching and Learning Guide (2014)

Abstract This Teaching and Learning Guide is designed to accompany my Sociology Compass article on affirmative action. The sample syllabus is organized historically beginning with FDR's New Deal and the first use of the term affirmative action and ending with the most recent Supreme Court's deliberations on this policy. In doing so, it attends not only to the varied meanings and forms of affirmative action across time but also the different interest groups arguing for and against this remedial policy. Along the way, it explores the changing history of race relations in the USA, considers the value of personal narratives as sources in exploring meaning and personhood, examines the ways the news media has framed the debate in contemporary America, and finally, speculates about the future of this controversial policy.
Characterization of N-linked oligosaccharides assembled on secretory recombinant glucose oxidase and cell wall mannoproteins from the methylotrophic yeast Hansenula polymorpha (2003)

Presently almost no information is available on the oligosaccharide structure of the glycoproteins secreted from the methylotrophic yeast Hansenula polymorpha, a promising host for the production of recombinant proteins. In this study, we analyze the size distribution and structure of N-linked oligosaccharides attached to the recombinant glycoprotein glucose oxidase (GOD) and the cell wall mannoproteins obtained from H. polymorpha. Oligosaccharide profiling showed that the major oligosaccharide species derived from the H. polymorpha-secreted recombinant GOD (rGOD) had core-type structures (Man(8-12)GlcNAc(2)). Analyses using anti-alpha 1,3-mannose antibody and exoglycosidases specific for alpha 1,2- or alpha 1,6-mannose linkages revealed that the mannose outer chains of N-glycans on the rGOD have very short alpha 1,6 extensions and are mainly elongated in alpha 1,2-linkages without a terminal alpha 1,3-linked mannose addition. The N-glycans released from the H. polymorpha mannoproteins were shown to contain mostly mannose in their outer chains, which displayed almost identical size distribution and structure to those of H. polymorpha-derived rGOD. These results strongly indicate that the outer chain processing of N-glycans by H. polymorpha significantly differs from that by Saccharomyces cerevisiae, thus generating much shorter mannose outer chains devoid of terminal alpha 1,3-linked mannoses.
Inhibition of tumor necrosis factor-alpha (TNF-alpha) production and arthritis in the rat by GW3333, a dual inhibitor of TNF-alpha-converting enzyme and matrix metalloproteinases. (2001)

Tumor necrosis factor-alpha (TNF)-converting enzyme (TACE) cleaves the precursor form of TNF, allowing the mature form to be secreted into the extracellular space. GW3333, a dual inhibitor of TACE and matrix metalloproteinases (MMPs), was compared with an anti-TNF antibody to evaluate the importance of soluble TNF and MMPs in rat models of arthritis. Oral administration of GW3333 completely blocked increases in plasma TNF after LPS for up to 12 h. In a model wherein intrapleural zymosan injection causes an increase in TNF in the pleural cavity, GW3333 completely inhibited the increase in TNF in the pleural cavity for 12 h. Under these dosing conditions, the plasma levels of unbound GW3333 were at least 50-fold above the IC(50) values for inhibition of individual MMPs in vitro. In a model wherein bacterial peptidoglycan polysaccharide polymers reactivate a local arthritis response in the ankle, a neutralizing anti-TNF antibody completely blocked the ankle swelling over the 3-day reactivation period. GW3333 administered b.i.d. over the same period also inhibited ankle swelling, with the highest dose of 80 mg/kg being slightly less active than the anti-TNF antibody. In a 21-day adjuvant arthritis model, the anti-TNF antibody did not inhibit the ankle swelling or the joint destruction, as assessed by histology or radiology. GW3333, however, showed inhibition of both ankle swelling and joint destruction. In conclusion, GW3333 is the first inhibitor with sufficient duration of action to chronically inhibit TACE and MMPs in the rat. The efficacy of GW3333 suggests that dual inhibitors of TACE and matrix metalloproteinases may prove therapeutic as antiarthritics.
The CD40–CD40L Dyad in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis (2017)

The CD40-CD40L dyad is an immune checkpoint regulator that promotes both innate and adaptive immune responses and has therefore an essential role in the development of inflammatory diseases, including multiple sclerosis (MS). In MS, CD40 and CD40L are expressed on immune cells present in blood and lymphoid organs, affected resident central nervous system (CNS) cells, and inflammatory cells that have infiltrated the CNS. CD40-CD40L interactions fuel the inflammatory response underlying MS, and both genetic deficiency and antibody-mediated inhibition of the CD40-CD40L dyad reduce disease severity in experimental autoimmune encephalomyelitis (EAE). Both proteins are therefore attractive therapeutic candidates to modulate aberrant inflammatory responses in MS. Here, we discuss the genetic, experimental and clinical studies on the role of CD40 and CD40L interactions in EAE and MS and we explore novel approaches to therapeutically target this dyad to combat neuroinflammatory diseases.
Ticagrelor — Is There Need for a New Player in the Antiplatelet-Therapy Field? (2009)

The thienopyridine clopidogrel, which irreversibly blocks the adenosine diphosphate (ADP) receptor P2Y12 on platelets, has become an essential component of therapy in patients with acute coronary syndromes, because it significantly improves the outcomes.1 However, clopidogrel has at least three drawbacks: delayed onset of action, large interindividual variability in platelet response, and irreversibility of its inhibitory effect on platelets (Figure 1). The two-step activation process, involving a series of cytochrome P-450 (CYP) isoenzymes, is susceptible to the interference of genetic polymorphisms2 and drug–drug interactions.3 Patients with a poor response to clopidogrel have an increased risk of coronary thrombosis.4 The increased risk . . .
Supramolecular Design for Multivalent Interaction:  Maltose Mobility along Polyrotaxane Enhanced Binding with Concanavalin A (2003)

High molecular mobility of maltose-conjugated alpha-cyclodextrins (alpha-CDs) along a poly(ethylene glycol) (PEG) chain due to the mechanically locked structure of polyrotaxanes enhanced multivalent interactions between maltose and concanavalin A (Con A). When maltose groups are conjugated with alpha-CDs that were threaded onto a PEG capped with benzyloxycarbonyl l-tyrosine (polyrotaxane), Con A-induced hemagglutination was greatly inhibited by polyrotaxanes with a certain threading % of alpha-CDs. Such an inhibitory effect was significantly superior to the other type of conjugates, in which poly(acrylic acid) was used as a backbone for maltose conjugation. The spin-spin relaxation time (T2) of the maltose C(1) proton in the polyrotaxane at a typical alpha-CD threading % was significantly larger than that of any other conjugate, which was well related to the inhibitory effect. Therefore, we concluded that the high mobility of maltose groups along the polyrotaxane structure contributes to enhanced Con A recognition.
Identification of a novel isoform of the cyclic-nucleotide phosphodiesterase PDE3A expressed in vascular smooth-muscle myocytes (2000)

We have identified a new cyclic-nucleotide phosphodiesterase isoform, PDE3A, and cloned its cDNA from cultured aortic myocytes. The nucleotide sequence of its coding region is similar to that of the previously cloned myocardial isoform except for the absence of the initial 300-400 nt that are present in the latter, as confirmed by reverse-transcriptase-mediated PCR, 5' rapid amplification of cDNA ends and a ribonuclease protection assay. Expression in Spodoptera frugiperda (Sf9) cells yields a protein with catalytic activity and inhibitor sensitivity typical of the PDE3 family. The recombinant protein's molecular mass of approx. 131 kDa is compatible with translation from an ATG sequence corresponding to nt 436-438 of the myocardial PDE3A coding region. Antibodies against residues 424-460 (nt 1270-1380) and 1125-1141 (nt 3373-3423) of the myocardial isoform react with an approx. 118 kDa band in Western blots of homogenates of human aortic myocytes, whereas antibodies against residues 29-42 (nt 85-126) do not react with any bands in these homogenates. Our results suggest that a vascular smooth-muscle isoform ('PDE3A2') is a product of the same gene as the longer myocardial ('PDE3A1') and the shorter placental ('PDE3A3') isoforms and is generated pre-translationally in a manner that results in the absence of the 145 N-terminal amino acids of PDE3A1.
Therapeutic Inflammatory Monocyte Modulation Using Immune-Modifying Microparticles (2014)

Inflammatory monocyte-derived effector cells play an important role in the pathogenesis of numerous inflammatory diseases. However, no treatment option exists that is capable of modulating these cells specifically. We show that infused negatively charged, immune-modifying microparticles (IMPs), derived from polystyrene, microdiamonds, or biodegradable poly(lactic-co-glycolic) acid, were taken up by inflammatory monocytes, in an opsonin-independent fashion, via the macrophage receptor with collagenous structure (MARCO). Subsequently, these monocytes no longer trafficked to sites of inflammation; rather, IMP infusion caused their sequestration in the spleen through apoptotic cell clearance mechanisms and, ultimately, caspase-3-mediated apoptosis. Administration of IMPs in mouse models of myocardial infarction, experimental autoimmune encephalomyelitis, dextran sodium sulfate-induced colitis, thioglycollate-induced peritonitis, and lethal flavivirus encephalitis markedly reduced monocyte accumulation at inflammatory foci, reduced disease symptoms, and promoted tissue repair. Together, these data highlight the intricate interplay between scavenger receptors, the spleen, and inflammatory monocyte function and support the translation of IMPs for therapeutic use in diseases caused or potentiated by inflammatory monocytes.
Molecular cloning of the mouse proteasome subunits MC14 and MECL‐1: reciprocally regulated tissue expression of interferon‐γ‐modulated proteasome subunits (1997)

The primary structures of the interferon-gamma-inducible mouse 20S proteasome subunit MECL-1 and its alternate homolog MC14 were determined. Northern analysis of mouse tissues revealed that MECL-1 mRNA predominantly occurred in thymus, lymph nodes, and spleen, whereas small amounts were detected in non-lymphoid tissues such as kidney, muscle, and testis. Unexpectedly, probing RNA blots with MC14 showed that tissues with high MECL-1 expression contained little MC14 and vice versa. A very similar reciprocal tissue expression was subsequently found for the homologous subunit pairs LMP2 and delta as well as LMP7 and MB1. The subunit protein composition of 20S proteasomes purified from liver, thymus, and lung reflected RNA expression. The impact of a regulated reciprocal tissue expression is discussed with respect to thymic selection and the induction of tolerance in potentially autoreactive T cells.
Fabrication and characterization of room temperature silicon single electron memory (1997)

A single electron memory was demonstrated in crystalline silicon that has a transistor channel width of ∼10 nm and a nanoscale floating gate of dimension ∼(7 nm × 7 nm × 2 nm), patterned by electron beam lithography, lift-off, and reactive ion etching. Quantized shift in the threshold voltage and self-limited charging process have been observed at room temperature. Analysis has shown that these quantized characteristics are the results of single electron charging effect in the nanoscale floating gate.
The immunogenicity and antigenicity of lipid A are influenced by its physicochemical state and environment (1987)

We investigated the immunogenicity and antigenicity of synthetic lipid A and partial structures thereof. Included in the study were compounds which varied in the position of phosphate (1-mono-, 4'-mono-, and 1,4'-bisphosphates) and in the acylation (type, number, and distribution of fatty acids) and, in the case of monosaccharide compounds, the nature of the backbone sugar (D-glucosamine, D-glucose, 3-amino-3-deoxy-D-glucose, and 2,3-diamino-2,3-dideoxy-D-glucose). With the aid of the passive-hemolysis and passive-hemolysis-inhibition assays and by absorption experiments, five distinct antibody specificities were detected in polyclonal rabbit antisera raised against sheep erythrocyte-coated lipid A and lipid A incorporated into the membrane of liposomes (liposome-incorporated immunogens). Three antibody specificities reacted with disaccharide antigens specific for a 1-mono-, 4'-mono-, and 1,4'-bisphosphorylated beta-1,6-linked D-glucosamine disaccharide. Two antibodies reacted with either 1- or 4-phosphates of acylated D-gluco-configured monosaccharides and exhibited no cross-reaction with each other. However, they cross-reacted with disaccharide antigens with phosphate groups in the appropriate positions. We found that the physicochemical state and the environment of lipid A modulated its immunoreactivity. The immunogenicity was best expressed by erythrocyte-coated and liposome-incorporated immunogens. The antigenicity of lipid A was also greatly influenced by its physical surroundings. The reaction pattern of the above antibodies was highly specific in the hemolysis assay and in absorption experiments (the antibody reacted with antigen embedded in a cell membrane), whereas some cross-reactivities were observed in inhibition studies (the antibody reacts with antigen in aqueous solution). By using liposome-incorporated antigens as inhibitors, nonspecific reactions were avoided and specific ones were enhanced. Thus the antibodies described above against lipid A recognize epitopes in the hydrophilic backbone, the exposure of which depends on the intrinsic physicochemical properties of lipid A on the one hand and the physical environment on the other.