gebhart/patrepeval huggingface dataset:
Humanized anti-CD154 antibody therapy for the treatment of allograft rejection in nonhuman primates (2002)

The anti-CD154 antibody hu5C8 prevents acute allograft rejection and prolongs allograft survival after withdrawal of therapy in nonhuman primates. This study describes the use of hu5C8 as a rescue agent for rejection developing after the withdrawal of hu5C8. Twelve rhesus monkeys that had received renal allografts under hu5C8 induction and subsequently rejected were studied. Rescue with hu5C8 was analyzed based on the histological character of the rejection (acute versus chronic) and whether conventional therapy was received at the time of rescue or induction. The diagnosis of rejection and response to therapy was based on allograft function and histology. Four monkeys that had acute rejection associated with conventional immunosuppression and hu5C8 were not reversed by hu5C8 rescue. Four animals with isolated chronic rejection following prolonged rejection-free survival after the withdrawal of hu5C8 did not respond to hu5C8 rescue therapy. Hu5C8 rescue therapy effectively reversed acute rejection occurring in two monkeys after hu5C8 withdrawal. One of two animals with combined acute on chronic rejection responded to hu5C8 rescue therapy. Hu5C8 effectively reverses acute but not chronic allograft rejection and appears to have no synergistic effect with conventional rescue agents.
The First Well‐Defined Silver(I)‐Complex‐Catalyzed Cycloaddition of Azides onto Terminal Alkynes at Room Temperature (2011)

Silver(I)-catalyzed click chemistry: Substituted 1,2,3-triazoles are versatile intermediates with an expanding array of applications. The discovery and application of a general AgI-catalyzed azide–alkyne cycloaddition reaction (AAC) leading to 1,2,3-triazoles is reported. The synthesis of a stable, well-defined AgI complex of type [AgI(L2)(OAc)] is described, along with the unprecedented ability of this complex to promote the general Ag-AAC at room temperature (see scheme). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Evaluation of metaiodobenzylguanidine heart and lung extraction fraction by first-pass analysis in pigs. (1992)

Metaiodobenzylguanidine (MIBG) is a norepinephrine analog that can be used to study cardiac sympathetic innervation. Most of the kinetic data on MIBG, however, have been obtained in vitro from adrenal chromaffin cells. To elucidate MIBG cardiac kinetics in vivo, we measured the first-pass extraction fraction (EF) of MIBG in pig heart and lungs and determined the relationship between the cardiac EF and myocardial blood flow (MBF) before and after dipyridamole, cocaine and imipramine. The first-pass lung EF was 24% +/- 0.80% (mean +/- s.e.). The baseline cardiac EF of MIBG was 79% +/- 1.6%. With dipyridamole, MBF increase significantly and the EF fell (82% +/- 2.5% to 71% +/- 3.5% baseline compared to 0.03 mg/kg/min dipyridamole, p less than 0.001), indicating that the cardiac EF of MIBG is dependent on MBF. Cocaine infusion had no effect on MBF or EF. Imipramine caused a significant increase in the EF (72% +/- 3.5% versus 77% +/- 2.5%, baseline versus imipramine p = 0.032) without a change in MBF. In adrenal chromaffin cells, cocaine and imipramine decrease MIBG uptake, suggesting that adrenal chromaffin cells may be an inappropriate model for studying MIBG kinetics in cardiac sympathetic neurons.
The Influence of Food on the Bioavailability of a Twice‐Daily Controlled Release Carbamazepine Formulation (2001)

Carbatrol, a new dosage form of carbamazepine (CBZ), was developed consisting of three different types of pellets (immediate release, controlled release, and enteric release). The objective of this study was to explore the influence of food on absorption of CBZ. This was a randomized, open-label, single-dose crossover study conducted in 12 healthy volunteers. Treatments were 2 x 200 mg Carbatrol with a high-fat meal, fasted, or sprinkled over applesauce (but otherwise fasted). Each subject received one dose of each treatment separated by a washout period of at least 2 weeks. CBZ bioequivalence was established based on the equivalence of AUC (extent of absorption) in all three conditions. Carbatrol may be taken with or without food or the capsule opened and sprinkled on food.
Changing the Paradigm: Omegaven for the Treatment of Liver Failure in Pediatric Short Bowel Syndrome (2009)

Omegaven is associated with restoration of liver function in patients with SBS and advanced liver disease. Parenteral omega-3 fatty acids, such as Omegaven, have the potential to fundamentally alter the paradigm of neonatal SBS from one of early death or transplantation from liver failure to a more chronic disease. More children with SBS should achieve full enteral tolerance and those who do not have the capacity for intestinal adaptation should be able to survive and receive an intestinal graft when older.
Differential Regulation of microRNAs by p53 Revealed by Massively Parallel Sequencing: miR-34a is a p53 Target That Induces Apoptosis and G1-arrest (2007)

In a genome-wide screen for microRNAs regulated by the transcription factor encoded by the p53 tumor suppressor gene we found that after p53-activation the abundance of thirty-four miRNAs was significantly increased, whereas sixteen miRNAs were suppressed. The induction of miR-34a was most pronounced among all differential regulations. Also expression of the primary miR-34a transcript was induced after p53 activation and by DNA damage in a p53-dependent manner. p53 occupied an evolutionarily conserved binding site proximal to the first non-coding exon of miR-34a. Ectopic miR-34a induced apoptosis and a cell cycle arrest in the G1-phase, thereby suppressing tumor cell proliferation. Other p53-induced miRNAs identified here may also have tumor suppressive potential as they are known to suppress the anti-apoptotic factor Bcl2 (miR-15a/16) and the oncogenes RAS and HMGA2 (let-7a). Our results for the first time directly integrate the regulation of miRNA expression into the transcriptional network regulated by p53. siRNAs corresponding to p53-induced miRNAs may have potential as cancer therapeutic agents as RNA interference based therapies are currently emerging.
A Complement Inhibitor Produced by Stachybotrys complementi, nov. sp. K‐76, a New Species of Fungi Imperfecti (1980)

A complement inhibitor, K-76, was isolated and purified from the culture supernatant of a fungus, Stachybotrys complementi, nov. sp. K-76, isolated from soil of Ishigaki Island, Okinawa. K-76 is a sesquiterpene compound and it can be oxidized to a monocarboxylic derivative (K-76 COOH), the sodium salt of which is very soluble and much less toxic than K-76. K-76 and K-76 COOH both inhibited complement activation by either the classical or alternative pathway. They inhibited generation of the factor chemotactic to human polymorphonuclear leukocytes from human serum by aggregated immunoglobulin. When sensitized erythrocytes were treated with complement in the presence of K-76 COOH, the resulting unlysed cells were found to be in the state of EACl, 4b, 2a, 3b. Thus K-76 COOH is considered to block mainly the C5 intermediate step. K-76 COOH did not inhibit any proteases or esterases tested, except when tested at high concentration.
Simultaneous quantitation of folic acid and 5-methyltetrahydrofolic acid in human plasma by HPLC–MS/MS and its application to a pharmacokinetic study (2015)

A sensitive method based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the simultaneous determination of folic acid (FA) and its active metabolite, 5-methyltetrahydrofolic acid (5-M-THF), in human plasma. The analytes were extracted from plasma with methanol solution containing 10 mg/mL of 2-mercaptoethanol and 0.025% (v/v) ammonium hydroxide. FA and 5-M-THF were more stable after the addition of 2-mercaptoethanol and ammonium hydroxide in the sample preparation procedures of this study than they were in the previously published methods. Chromatographic separation was performed on a Hedera ODS-2 column using a gradient elution system of acetonitrile and 1 mM ammonium acetate buffer solution containing 0.6% formic acid as mobile phase. LC-MS/MS was carried out with an ESI ion-source and operated in the multiple reaction monitoring (MRM) mode. The assay was linear over the concentration ranges of 0.249-19.9 ng/mL for FA, and 5.05-50.5 ng/mL for 5-M-THF. The developed LC-MS/MS method offers increased sensitivity for quantification of FA and 5-M-THF in human plasma and was applicable to a pharmacokinetic study of FA and 5-M-THF.
Noise figure limits for circular loop MR coils (2009)

Circular loops are the most common MR detectors. Loop arrays offer improved signal-to-noise ratios (SNRs) and spatial resolution, and enable parallel imaging. As loop size decreases, loop noise increases relative to sample noise, ultimately dominating the SNR. Here, relative noise contributions from the sample and the coil are quantified by a coil noise figure (NF), NF(coil), which adds to the conventional system NF. NF(coil) is determined from the ratio of unloaded-to-loaded coil quality factors Q. Losses from conductors, capacitors, solder joints, eddy currents in overlapped array coils, and the sample are measured and/or computed from 40 to 400 MHz using analytical and full-wave numerical electromagnetic analysis. The Qs are measured for round wire and tape loops tuned from 50 to 400 MHz. NF(coil) is determined as a function of the radius, frequency, and number of tuning capacitors. The computed and experimental Qs and NF(coil)s agree within approximately 10%. The NF(coil) values for 3 cm-diameter wire coils are 3 dB, 1.9 dB, 0.8 dB, 0.2 dB, and 0.1 dB, at 1T, 1.5T, 3T, 7T, and 9.4T, respectively. Wire and tape perform similarly, but tape coils in arrays have substantial eddy current losses. The ability to characterize and reliably predict component- and geometry-associated coil losses is key to designing SNR-optimized loop and phased-array detectors.
Interleukin-6 receptor-interleukin-6 fusion proteins with enhanced interleukin-6 type pleiotropic activities. (1997)

An sIL-6R/IL-6 chimera, directly fusing the natural forms of soluble IL-6 receptor and IL-6, as found in human body fluids, was produced in transfected human cells. The secreted p85 glycoprotein was active at a concentration of 120 pM to produce growth-arrest and spindleoid differentiation of murine melanoma F10.9 cells, which do not respond to IL-6 alone. This fusion protein was as active as the yeast-produced p56 fusion protein containing a shortened sIL-6R, linked through a flexible peptide chain to IL-6 (Hyper IL-6). The concentration of Hyper IL-6 needed to arrest the growth of F10.9 cells was much lower than that needed of a combination of IL-6 and sIL-6R, added separately. Hyper IL-6 was also more active than IL-6 in stimulating growth of murine plasmacytoma T1165 cells, the half maximal stimulation being obtained at 2 pM Hyper IL-6 versus 23 pM for IL-6. In order to evaluate the effect of the fused sIL-6R/IL-6 proteins on human hematopoietic primitive progenitor cells, they were added to suspension cultures of CD34+ cells from human cord blood in addition to both flt3/flk2 ligand (FL) and stem cell factor (SCF). Fused sIL-6R/IL-6 produced a marked stimulation of cell expansion and a marked increase in the number of colony forming units when subsequently plated in semi-solid medium with IL-3, GM-CSF, SCF and erythropoietin. Ex-vivo maintenance and expansion of early progenitor cells in bone marrow transplantation protocols may be a potential application for the sIL-6R/IL-6 chimeric glycoproteins.
A Novel Human Opsin in the Inner Retina (2000)

Here we report the identification of a novel human opsin, melanopsin, that is expressed in cells of the mammalian inner retina. The human melanopsin gene consists of 10 exons and is mapped to chromosome 10q22. This chromosomal localization and gene structure differs significantly from that of other human opsins that typically have four to seven exons. A survey of 26 anatomical sites indicates that, in humans, melanopsin is expressed only in the eye. In situ hybridization histochemistry shows that melanopsin expression is restricted to cells within the ganglion and amacrine cell layers of the primate and murine retinas. Notably, expression is not observed in retinal photoreceptor cells, the opsin-containing cells of the outer retina that initiate vision. The unique inner retinal localization of melanopsin suggests that it is not involved in image formation but rather may mediate nonvisual photoreceptive tasks, such as the regulation of circadian rhythms and the acute suppression of pineal melatonin. The anatomical distribution of melanopsin-positive retinal cells is similar to the pattern of cells known to project from the retina to the suprachiasmatic nuclei of the hypothalamus, a primary circadian pacemaker.
Regulation of the Initiation of Endospore Formation inBacillus subtilis (2014)

Under certain environmental conditions, cells of the bacterium Bacillus subtilis can initiate a developmental process leading to the formation of dormant endospores. Much of the work on sporulation in B. subtilis has focused on several key questions such as What are the environmental conditions that control sporulation? The authors describe some of the regulatory circuits that control the initiation of sporulation and the conditions that influence the activity of the regulatory factors. The responses of the gram-positive soil bacterium B. subtilis to changing nutrient conditions have been studied extensively. Regulatory mechanisms exist to help ensure that cells do not initiate sporulation unless it is likely that they will be able to complete the process successfully. spo0A and spo0H encode transcription factors that are required for the initiation of sporulation. Both spo0A and spo0H are required for asymmetric division and for transcription of the genes required for establishing cell-type-specific gene expression. The genes controlled by Spo0A that are involved in formation of the axial filament and the polar FtsZ rings are not known. Extracellular and intracellular signals are generated by nutrient deprivation, cell density, DNA replication, DNA damage, glucose metabolism, the tricarboxylic acid (TCA) cycle, and chromosome-partitioning proteins. Understanding both the signals that regulate these pathways and the organization of the pathways into networks regulating gene expression will contribute significantly to an integrated view of the interplay among cell physiology, gene expression, adaptation, and development.
CD4+CD25+ Regulatory T Cells in Patients with Acute Lymphocytic Leukemia. (2007)

Abstract Human CD4+CD25+ regulatory T (Treg) cells suppress antigen-specific T cell immune response and contribute to peripheral tolerance. However, little is known about the role of Treg cells in the pathogenesis of acute lymphocytic leukemia (ALL). In this study, the proportion of CD4+CD25+ Treg cells in the peripheral blood of three groups of people [the patients with ALL who had never received any chemotherapy before, the patients with ALL who had achieved partial remission (PR) or complete remission (CR) after chemotherapy and the healthy donors] was evaluated by flow cytometry. The expression level of Foxp3 mRNA of each group was examined by real-time RT-PCR. In vitro, the peripheral blood mononuclear cells (PBMC) from healthy donors were cultured in the serum of ALL patients without chemotherapy; each group was divided into sub-groups according to various serum doses. After co-cultured for 72 hours, the cells of all the groups were harvested separately and further tested the number of CD4+CD25+ Treg cells and the mRNA expression of Foxp3. The results showed that both the percentage of CD4+CD25+ T cells and the mRNA expression level of Foxp3 in patients with chemotherapy were significantly higher than those of the healthy donors and patients without chemotherapy (P&lt;0.01 and P&lt;0.01). Although the population of CD4+CD25+ T cells in ALL patients without chemotherapy was almost the same to that in the healthy donors (P&gt;0.05), the expression of Foxp3 mRNA in former was higher (P&lt;0.05) .The serum derived from ALL patients without chemotherapy remarkably increased the proportion of CD4+CD25+ T cells and the expression level of Foxp3 mRNA in co-cultured system, both of which were statistically higher than those in controls (P&lt;0.05 and P&lt;0.01) and did not vary with the serum dose. These results suggest that the chemotherapy may exert an influence on the production of CD4+CD25+ Treg cells and CD4+CD25+ Treg cells may play an important role in the pathogenesis of ALL.
Sir2: An NAD-dependent Histone Deacetylase That Connects Chromatin Silencing, Metabolism, and Aging (2000)

Aging is a biological process that shows deleterious,progressive, intrinsic, and universal changes in an organism over time (Strehler 1982). These destructive changeseventually produce an exponential increase of mortalityrate (Gompertz 1825), which can be widely observed in avariety of organisms including the budding yeast Saccharomyces cerevisiae (Sinclair et al. 1998). Different typesof damage, especially oxidative damage, and variousforms of genomic instability have been suggested to beinvolved in the aging process (Johnson et al. 1999). In thecase of budding yeast, longevity is measured by the number of daughter cells that a mother cell can produce (Mortimer and Johnston 1959). The stability of ribosomalDNA (rDNA) repeats is crucial to determine thelongevity of the yeast mother cell (Sinclair and Guarente1997). The rDNA region consists of 100–200 tandemcopies of an approximately 9.0-kb rDNA unit and therefore presents a large target for homologous recombination. Playing a major part in the regulation of the frequency of recombination at this locus is the yeastsilencing protein Sir2 (Gottlieb and Esposito 1989),which is also a limiting component for longevity (Kaeberlein et al. 1999). Deletion of SIR2 shortens life span toabout one half of wild type, and an extra copy of SIR2 significantly extends life span. Sir2 is one of the principalregulators of transcriptional silencing in yeast, along withSir3 and Sir4 at telomeres and silent mating-type (HM)loci (Rine and Herskowitz 1987; Gottschling et al. 1990)and Net1 and Cdc14 at the rDNA locus (Bryk et al. 1997;Smith and Boeke 1997; Straight et al. 1999). The extension of life span by Sir2 likely results from an increasedsilencing in the rDNA that reduces recombination. This,in turn, reduces the production of extrachromosomalrDNA circles (ERCs), a known cause of senescence inaging mother cells (Sinclair and Guarente 1997). Sir2proteins are highly conserved in evolution, from bacteriato humans (Brachmann et al. 1995), suggesting that theseproteins may also mediate silencing in higher eukaryotesand raising the possibility that they are involved in theregulation of aging in a similar fashion. A novel biochemical activity of Sir2, nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase, was discovered recently (Imai et al. 2000). This activity isessential for Sir2 functions in vivo, including silencing,suppression of rDNA recombination, and promotion ofyeast longevity, and is highly conserved between yeastand mouse. The extraordinary requirement of NAD in adeacetylation reaction opens an intriguing possibility thatSir2 can function as sensors of the energy status of cells,converting the energy level represented by availableNAD to chromatin silencing. In this paper, we summarizeour recent studies of this Sir2 enzymatic activity and discuss implications of the function of Sir2 for the epigeneticregulation of aging...
ADMAD: Application-Driven Metadata Aware De-duplication Archival Storage System (2008)

There is a huge amount of duplicated or redundant data in current storage systems. So data de-duplication, which uses lossless data compression schemes to minimize the duplicated data at the inter-file level, has been receiving broad attention in recent years. But there are still research challenges in current approaches and storage systems, such as: how to chunking the files more efficiently and better leverage potential similarity and identity among dedicated applications; how to store the chunks effectively and reliably into secondary storage devices. In this paper, we propose ADMAD: an application-driven metadata aware de-duplication archival storage system, which makes use of certain meta-data information of different levels in the I/O path to direct the file partitioning into more meaningful data chunks (MC) to maximally reduce the inter-file level duplications. However, the chunks may be with different lengths and variable sizes, storing them into storage devices may result in a lot of fragments and involve a high percentage of random disk accesses, which is very inefficient. Therefore, in ADMAD, chunks are further packaged into fixed sized objects as the storage units to speed up the I/O performance as well as to ease the data management. Preliminary experiments have demonstrated that the proposed system can further reduce the required storage space when compared with current methods (from 20% to near 50% according to several datasets), and largely improves the writing performance (about 50%-70% in average).
Anti-CD3-stimulated T cells induce the production of multiple Ig H chain isotypes by individual human peripheral B lymphocytes (1992)

Polyclonal activation of human B cells is achieved by coculture with T cells stimulated by mAb to the CD3 molecular complex. By formal limiting dilution analysis, approximately 60% of human peripheral blood B cells were found to produce Ig in this system. When individual B cells were cultured in microtiter wells with anti-CD3-activated T cells, more than one-third of cultures producing Ig contained multiple Ig H chain isotypes. Similar results were observed when individual IgM-expressing B cells, selected and dispersed by FACS were cultured with anti-CD3-activated T cells. The clonality of the B cells producing multiple Ig isotypes was supported by L chain analysis of the secreted Ig. Of the wells containing more than one H chain isotype, nearly 85% contained only a single L chain type. Clonality was further examined by polymerase chain reaction amplification of cDNA harvested from cultures originally seeded with individual B cells. In general, only a single VH gene family could be amplified from cultures producing more than one Ig isotype. Three separate VH regions were cloned and sequenced. One, a VHIV-mu was nearly identical to a previously described VH gene VH71.4; as second, a VHIV-gamma was very similar to a previously described VH gene segment V-79, whereas a third, a VHIII-gamma differed by 14% in nucleotide sequence from its closest germline counterpart VH3005. These results indicate that anti-CD3-activated T cells not only stimulate the majority of B cells to secrete Ig, but also induce individual B cells to produce multiple Ig H chain isotypes. Additionally, the procedure described provides a reliable method to sample a large proportion of the human peripheral B cell repertoire.
Nonintrusive Load Monitoring and Diagnostics in Power Systems (2008)

This paper describes a transient event classification scheme, system identification techniques, and implementation for use in nonintrusive load monitoring. Together, these techniques form a system that can determine the operating schedule and find parameters of physical models of loads that are connected to an AC or DC power distribution system. The monitoring system requires only off-the-shelf hardware and recognizes individual transients by disaggregating the signal from a minimal number of sensors that are installed at a central location in the distribution system. Implementation details and field tests for AC and DC systems are presented.