gebhart/patrepeval huggingface dataset:
INTERFERENCE WITH T CELL ACTIVATION SIGNAL ONE AND SIGNAL TWO WITH A COMBINATION OF ANTI-CD45RB AND ANTI-CD40L MONOCLONAL ANTIBODIES INDUCES LONG-TERM ISLET ALLOGRAFT SURVIVAL IN MICE (1998)

245 T cell activation requires signals through both the T cell antigen receptor (TCR) (Signal 1) and costimulatory molecules (Signal 2) which include the interaction between CD40 and its T cell-based ligand CD40L. Monoclonal antibodies (mAbs) against CD45RB and against CD40L are presumed to interfere with Signal 1 and Signal 2, respectively, and have each been shown to prolong the survival of MHC mismatched allografts in animal models. For example, we have recently reported that a short treatment course of anti-CD45RB (MB23G2) is able to induce tolerance in ∼50% of BALB/c islet allografts placed into chemically diabetic C57BL/6 recipients. Likewise, anti-CD40L alone has been shown to induce tolerance in ∼40% of islet allograft recipients using the same strain combination. In this study, we examine the efficacy of combined therapy with mAbs targeting both CD45RB and CD40L. Streptozotocin-induced diabetic C57BL/6 (H2-b) recipients received 400 islets from BALB/c (H-2d) donors under the left kidney capsule. Recipient mice were left untreated (Group 1), received combination therapy (Group 2) with anti-CD45RB (100 µg IV on days-1, 0 and 5) and anti-CD40L (250 µg IP on days 0, 2, and 4), or were treated with anti-CD40L alone (Group 3). TableTableWhereas animals in Group 1 rapidly rejected their allografts, 5/5 animals in Group 2 show continued islet graft function (ranging from 40-58 days). In one recipient*, only borderline BS was ever achieved (200-300). However, following L nephrectomy on day 40, this animal became frankly diabetic (BS>450) and died. Although all animals in Group 3 are normoglycemic at this early time-point, a 40% graft survival was previously shown (Parker, PNAS.92:9560). Histologic analysis on day 6 revealed that treatment with anti-CD45RB, anti-CD40L, or their combination, were each associated with a significant peri-islet infiltrate, virtually indistinguishable from that observed in untreated animals (day 6). Analysis of histology on day 40 in an animal receiving combination therapy, revealed very well-preserved islets with continued peri-islet lymphocytic infiltration. In conclusion: A short course treatment with anti-CD45RB and anti-CD40L causes significant prolongation of islet allotransplantation in mice in virtually 100% of cases. This study demonstrates the efficacy of a novel treatment strategy targeting both TCR-mediated and co-stimulatory signals
Deletion of the tobacco plastid psbA gene triggers an upregulation of the thylakoid‐associated NAD(P)H dehydrogenase complex and the plastid terminal oxidase (PTOX) (2003)

We have constructed a tobacco psbA gene deletion mutant that is devoid of photosystem II (PSII) complex. Analysis of thylakoid membranes revealed comparable amounts, on a chlorophyll basis, of photosystem I (PSI), the cytochrome b6f complex and the PSII light-harvesting complex (LHCII) antenna proteins in wild-type (WT) and DeltapsbA leaves. Lack of PSII in the mutant, however, resulted in over 10-fold higher relative amounts of the thylakoid-associated plastid terminal oxidase (PTOX) and the NAD(P)H dehydrogenase (NDH) complex. Increased amounts of Ndh polypeptides were accompanied with a more than fourfold enhancement of NDH activity in the mutant thylakoids, as revealed by in-gel NADH dehydrogenase measurements. NADH also had a specific stimulating effect on P700+ re-reduction in the DeltapsbA thylakoids. Altogether, our results suggest that enhancement of electron flow via the NDH complex and possibly other alternative electron transport routes partly compensates for the loss of PSII function in the DeltapsbA mutant. As mRNA levels were comparable in WT and DeltapsbA plants, upregulation of the alternative electron transport pathways (NDH complex and PTOX) occurs apparently by translational or post-translational mechanisms.
Joint BSAC-NVC Congress 2019: A colourful world. (2020)

In November 2019, the Belgian Society for the Advancement of Cytometry (BSAC) and the Dutch Society for Cytometry (NVC) jointly organised a two-day international congress on developments in (flow) cytometry. With over 150 participants, the congress was well attended and received. Here we briefly discuss the most important highlights from this congress.
Moisture-induced degradation and its mechanism of (Sr,Ca)AlSiN3:Eu2+, a red-color-converter for solid state lighting (2015)

The degradation of (Sr,Ca)AlSiN<sub>3</sub>:Eu<sup>2+</sup> induced by the water steam attack results in remarkable changes in luminescence, microstructure and phase purity.
Phylogenomic Analysis of a 55.1-kb 19-Gene Dataset Resolves a MonophyleticFusariumthat Includes theFusarium solaniSpecies Complex (2020)

Scientific communication is facilitated by a data-driven, scientifically sound taxonomy that considers the end-user's needs and established successful practice. In 2013, the <i>Fusarium</i> community voiced near unanimous support for a concept of <i>Fusarium</i> that represented a clade comprising all agriculturally and clinically important <i>Fusarium</i> species, including the <i>F. solani</i> species complex (FSSC). Subsequently, this concept was challenged in 2015 by one research group who proposed dividing the genus <i>Fusarium</i> into seven genera, including the FSSC described as members of the genus <i>Neocosmospora</i>, with subsequent justification in 2018 based on claims that the 2013 concept of <i>Fusarium</i> is polyphyletic. Here, we test this claim and provide a phylogeny based on exonic nucleotide sequences of 19 orthologous protein-coding genes that strongly support the monophyly of <i>Fusarium</i> including the FSSC. We reassert the practical and scientific argument in support of a genus <i>Fusarium</i> that includes the FSSC and several other basal lineages, consistent with the longstanding use of this name among plant pathologists, medical mycologists, quarantine officials, regulatory agencies, students, and researchers with a stake in its taxonomy. In recognition of this monophyly, 40 species described as genus <i>Neocosmospora</i> were recombined in genus <i>Fusarium</i>, and nine others were renamed <i>Fusarium.</i> Here the global <i>Fusarium</i> community voices strong support for the inclusion of the FSSC in <i>Fusarium</i>, as it remains the best scientific, nomenclatural, and practical taxonomic option available.
Time-Reversed Waves in Complex Media (2010)

Time-reversal invariance is a very powerful concept in classical and quantum mechanics. In the field of classical waves (acoustics and electromagnetism), where timereversal invariance also occurs, time-reversal mirrors (TRMs) may be made simply with arrays of transmit–receive antennae, allowing an incident broadband wave field to be sampled, recorded, time-reversed, and re-emitted.
A high performance, high voltage output buffer in a low voltage CMOS process (2006)

The proposed output buffer circuit uses 1.8V transistors in 90nm CMOS process to develop I/Os for 2.5V and 3.3V interfaces. A voltage clamp circuit, bias generators, and a feedback circuit are used to ensure reliability and noise decoupling. Use of these circuits enables achieving low power (130/spl mu/A) and high performance (up to 275MHz) in a comparative area of an equivalent I/O in 90nm 3.3V process.
A new method for fluxgate magnetometers using the coupling property of odd and even harmonics (1995)

A new method suitable for the single core fluxgate magnetometer has been proposed. The method makes use of the coupling property of odd and even harmonics generated by the self-product of the induced voltage during the magnetization of ferromagnetic material by an external field superposed on the AC driving magnetic field. The power difference between the two half-periods of magnetization was expressed by the coupling of odd and even harmonics, which is proportional to the external field under the condition that Hext<<HAC and HAC is constant, where Hext and HAC are the external magnetic field and AC driving field amplitude respectively.
Analysis of diagnostic product portfolios using the Portfolio-To-Impact modelling tool (2021)

<ns3:p> <ns3:bold>Background:</ns3:bold> The Portfolio-To-Impact version 2 (P2I v.2) financial forecasting tool estimates funding requirements for development of portfolios of candidate health products (drugs, biologics, vaccines or diagnostics). The assumptions and archetypes relating to diagnostics in P2I v.2 are based on limited data and may not accurately describe research and development costs, timelines and probability of success. This study aimed to revise the P2I v.2 tool by modifying the diagnostic assumptions to improve accuracy of predictions for diagnostic portfolios. </ns3:p> <ns3:p> <ns3:bold>Methods:</ns3:bold> Data from expert interviews and historical information on development of 26 existing diagnostics were used to determine approximate research and development costs, timelines and probability of success for development of diagnostics, and to revise diagnostic archetypes and development phases. To compare the revised tool with P2I v.2, data on 27 candidates from the Foundation for Innovative New Diagnostics (FIND) tuberculosis and pandemic preparedness portfolios were input into both versions. </ns3:p> <ns3:p> <ns3:bold>Results:</ns3:bold> The number of diagnostic archetypes increased from two in P2I v.2 to three in the revised tool. Total estimated costs to move the 27 candidates along the pipeline to launch were US$641.62 million with P2I v.2 and US$274.00 million with the revised model. The number of expected launches was 21.65 over five years with P2I v.2 and 11.48 over eight years with the revised model. Development timelines were extended and probability of success was lower with the revised model compared with P2I v.2. </ns3:p> <ns3:p> <ns3:bold>Conclusions:</ns3:bold> Outputs from the revised tool were in line with expert experience, suggesting that the proposed revisions improve the accuracy of the tool for estimating research and development costs, timelines and probability of success relating to diagnostic portfolios. Additional improvements to the tool could include further refinement of archetypes, incorporation of a measure of potential public health impact, and addition of a commercialization phase for diagnostics. </ns3:p>
High performance ZnO nanowire field effect transistor (2005)

A zinc oxide (ZnO) nanowire field effect transistor having the highest mobility and lowest subthreshold slope obtained to date (from ZnO) is reported. The device consists of a single nanowire with self-aligned gate electrodes having well defined nanoscale spacing, independent of lithographic definition. The fabricated device exhibits a transconductance of 3.06 /spl mu/S, a mobility of 450 cm/sup 2//Vs and a subthreshold swing of 129 mV/decade. The transistor also shows an on/off current ratio of 10/sup 6/.
Characteristics of point defects on the optical properties of ZnO: revealed by Al–H co-doping and post-annealing (2013)

Understanding the influences of lattice defect evolution on the optical properties of ZnO is of significance. To clarify this, we adopted typical treatments on ZnO using Al–H co-doping and post-annealing, combined with comprehensive characterization (absorption spectrum, Raman scattering, photoluminescence, electronic paramagnetic resonance and positron annihilation). The results reveal that the visible luminescence can arise from the VO, VZn and AlZn–Oi defects, while the defect centers responsible for the blue band optical absorption are assigned to ionized Zni and V+O. SEM images illustrated that H+ implantation diluted the ZnAl2O4 second phase, which reaccumulated after O2 annealing.
INCB24360 (Epacadostat), a Highly Potent and Selective Indoleamine-2,3-dioxygenase 1 (IDO1) Inhibitor for Immuno-oncology (2017)

A data-centric medicinal chemistry approach led to the invention of a potent and selective IDO1 inhibitor <b>4f</b>, INCB24360 (epacadostat). The molecular structure of INCB24360 contains several previously unknown or underutilized functional groups in drug substances, including a hydroxyamidine, furazan, bromide, and sulfamide. These moieties taken together in a single structure afford a compound that falls outside of "drug-like" space. Nevertheless, the <i>in vitro</i> ADME data is consistent with the good cell permeability and oral bioavailability observed in all species (rat, dog, monkey) tested. The extensive intramolecular hydrogen bonding observed in the small molecule crystal structure of <b>4f</b> is believed to significantly contribute to the observed permeability and PK. Epacadostat in combination with anti-PD1 mAb pembrolizumab is currently being studied in a phase 3 clinical trial in patients with unresectable or metastatic melanoma.
Multiplexed site-specific electrode functionalization by combining electrografting and click chemistry (2016)

status: Accepted
Proteoglycan 4 metabolism and boundary lubrication of articular cartilage (2006)

Articular cartilage is the lubricious, load bearing connective tissue at the end of long bones in synovial joints that normally facilitates low-friction and low-wear articulation via a number of lubrication mechanisms. Boundary lubrication is particularly important for the protection and maintenance of the articular surface, which unfortunately often becomes roughened and eroded in aging and arthritis, with the eventual development of pain and dysfunction. Synovial fluid (SF) contains molecules, such as proteoglycan 4 (PRG4) and hyaluronan (HA), that interact with and adsorb to the articular surface, and are therefore ideally positioned to contribute to boundary lubrication. This dissertation aims to contribute to the understanding of PRG4 metabolism by chondrocytes of the superficial zone of cartilage, and the mechanics of, and contributors to, boundary lubrication of articular cartilage. PRG4 metabolism by chondrocyte subpopulations in various culture systems was regulated differentially by various biochemical stimuli. The phenotype of PRG4 secretion by chondrocytes was generally maintained in that PRG4 was expressed to a much greater degree by chondrocytes from the superficial zone than by those from the middle and deep zones. PRG4 expression and secretion by chondrocytes near the articular surface was highly inhibited by IL-1a and stimulated by TGF-B1, in a dose- dependent manner, in explant cultures of cartilage. An in vitro articular cartilage-on-cartilage boundary lubrication test was implemented and extended to establish conditions where a boundary mode of lubrication was dominant. SF functioned as an effective friction-lowering boundary lubricant, even with a 3-fold decrease in constituent concentration. SF constituents, PRG4 and HA, contributed individually and in combination, both at physiological and pathophysiological concentrations, to the boundary lubrication of apposing articular cartilage surfaces. Collectively these results provide insight into the nature of PRG4 metabolism, the biomechanics of boundary lubrication of articular cartilage, and the role of PRG4, alone and in combination with other putative lubricants. The ability to modulate the dynamic regulation of PRG4, whether in homeostasis or degeneration, may ultimately be useful in prolonging the maintenance or slowing the deterioration of articular cartilage's critical mechanical functions at the end of long bones
Modelling-Based Diagnostic Method for Ex Situ Characterization of Pt Degradation (2013)

Abstract not Available.
Genome Alert!: a standardized procedure for genomic variant reinterpretation and automated genotype-phenotype reassessment in clinical routine (2021)

Abstract Numerous countries have set up population genomics plans, allowing an unprecedented growth in the ability of interpreting variants in human diseases. Retrospective interpretation of sequenced data in the light of the current literature is a major concern of the field. Moreover, such reinterpretation is manual and both the human resources and the variable operating procedures are main bottlenecks. This work describes the Genome Alert! standardized procedure. This open-source method automatically reports changes with potential clinical significance in variant classification between releases of the ClinVar database. Using ClinVar submissions across time, this method assigns gene-disease associations validity category. Genome Alert! was assessed on a retrospective 29 months multicentric series of 5,959 consecutive individuals screened by targeted or exome sequencing. Between July 2017 and December 2019, the retrospective analysis of ClinVar submissions revealed a monthly median of 1,247 changes in variant classification with potential clinical significance and 23 new gene-disease associations. Reexamination of 4,929 targeted sequencing files highlighted 45 changes, which 89% classifications were expert validated, leading to four additional diagnoses. Genome Alert! gene-disease association catalog provided 75 high-confidence associations not available in the OMIM morbid list, where 20% became OMIM morbid 8 months later. Over 356 negative exome sequencing data that were reannotated for variants in these 75 genes, this elective approach led to a new diagnosis. Genome Alert! ( https://genomealert.univ-grenoble-alpes.fr/ ) enables the systematic and reproducible reinterpretation of acquired sequencing data in a clinical routine with a limited human resource impact. Graphical abstract
T-cell-specific expression of interleukin 2: evidence for a negative regulatory site. (1988)

To understand the basis for T-cell-specific induction of interleukin 2 (IL-2), we have analyzed nuclear factors from the Jurkat T-lymphoid leukemia cell, which can be induced to secrete IL-2. We have used an electrophoretic mobility shift assay to examine binding of proteins to the upstream regulatory region, before and after activation with mitogens. We find two types of binding sites. One resembles an inducible enhancer element, but the protein that recognizes it is found in non-T cells and is unlikely to determine T-cell-specific expression of IL-2. A second site negatively regulates expression in resting T cells. A complex that binds to a DNA fragment containing this site is modified only when IL-2 is expressed, and it lies near a specific inducible DNase hypersensitive region. We suggest that negative regulation at this site, mediated by its associated protein(s), may contribute to the cell-specific expression of IL-2.
Vaccines for birch pollen allergy based on genetically engineered hypoallergenic derivatives of the major birch pollen allergen, Bet v 1 (2004)

Genetically modified hypoallergenic rBet v 1 derivatives induce blocking antibodies in vivo. Their safety and efficacy for the treatment of birch pollen and associated plant allergies can now be evaluated in clinical immunotherapy studies.
Prediction of Clinical Response After Renal Angioplasty: Respective Value of Renal Doppler Sonography and Scintigraphy (2003)

Measurements of kidney length and unilateral and bilateral resistive indexes before and after captopril administration were useful in predicting the outcome after renal angioplasty. Renal scintigraphy had no significant predictive value.
Abstract 2683: Identification of tumor antigens in neu transgenic mice as diagnostic targets for the early detection of human breast cancer (2011)

Abstract Tumor antigens, expressed early in disease, which can induce specific antibody response could serve as biomarkers for early detection of human breast cancer. However, the ability to obtain sera from women prior to the development of breast cancer is limited, which makes it difficult to identify early antigens directly from breast cancer patients. Transgenic mouse models have been proved to demonstrate similar antigen repertoire to breast cancer patients. Therefore, we propose to identify early tumor antigens in neu transgenic mice and use them as diagnostic targets for early detection of human breast cancer. We have collected serial sera from neu transgenic mice, sera collected before the animals develop palpable tumor “pre-diagnostic sera”. With serological analysis of recombinant cDNA expression libraries (SEREX) approach, we were able to identify nine tumor antigens from pre-diagnostic sera, Rpl5, TNFaip3/A20, Pdhx, Otud6b, Stk39, Zfp238, Dnajc10, Lgals8 and Vps35. These antigens demonstrated detectable IgG antibody response prior to tumor development in neu transgenic mice. IgM is the first antibody to be produced during a humoral immune response, so we questioned whether including antigen specific IgM with IgG responses could achieve a better diagnostic performance. Firstly, we analyzed receiver-operating-characteristic (ROC) curves of these antigens by IgG and IgM ELISA analysis in neu transgenic mice and 26 FVB control mice. By combining IgG and IgM ELISA, we were able to achieve a higher AUC: Otud6b and Stk39 show an AUC of 0.882, and adding Lgals8 IgG ELISA to this panel can achieve an AUC of 0.924 in discriminating cases from control mice. We documented that these autoantibodies are also detectable in the serum of women with breast cancer and then screened a panel of sera derived from the Women's Health Initiative cohort (samples obtained 6-18 months prior to the development of breast cancer) and case matched controls. We evaluated serum for the presence of IgG and IgM specific autoantibodies to Pdhx, Otud6b, and Stk39. With both IgG and IgM ELISA analysis, a panel combining the three antigens demonstrates an AUC of 0.633 in patients diagnosed within 5 month and an AUC of 0.688 in patients diagnosed within 5-18 month of the blood draw. In summary, we conclude that tumor antigens identified in neu transgenic mouse model can be used for early detection and diagnosis of breast cancer in women. The combination of antigen specific IgG and IgM antibodies may enhance the sensitivity of the assay for early detection. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2683. doi:10.1158/1538-7445.AM2011-2683
Object-oriented recovery for non-volatile memory (2018)

New non-volatile memory (NVM) technologies enable direct, durable storage of data in an application's heap. Durable, randomly accessible memory facilitates the construction of applications that do not lose data at system shutdown or power failure. Existing NVM programming frameworks provide mechanisms to consistently capture a running application's state. They do not, however, fully support object-oriented languages or ensure that the persistent heap is consistent with the environment when the application is restarted. In this paper, we propose a new NVM language extension and runtime system that supports object-oriented NVM programming and avoids the pitfalls of prior approaches. At the heart of our technique is object reconstruction, which transparently restores and reconstructs a persistent object's state during program restart. It is implemented in NVMReconstruction, a Clang/LLVM extension and runtime library that provides: (i) transient fields in persistent objects, (ii) support for virtual functions and function pointers, (iii) direct representation of persistent pointers as virtual addresses, and (iv) type-specific reconstruction of a persistent object during program restart. In addition, NVMReconstruction supports updating an application's code, even if this causes objects to expand, by providing object migration. NVMReconstruction also can compact the persistent heap to reduce fragmentation. In experiments, we demonstrate the versatility and usability of object reconstruction and its low runtime performance cost.