gebhart/patrepeval huggingface dataset:
Gene Expression Profiling of Peripheral Blood Leukocytes Shows Consistent Longitudinal Downregulation of TOMM40 and Upregulation of KIR2DL5A, PLOD1, and SLC2A8 Among Fast Progressors in Early Alzheimer's Disease (2013)

We previously reported TOMM40 was significantly down-regulated in whole blood of Alzheimer's disease (AD) subjects. In this study, we examined whole blood gene profiling differences over a one-year period comparing early AD subjects based on disease progression. 6-monthly assessments and blood sampling on 29 probable AD subjects compared with age- and gender-matched controls were performed. AD subjects with change in Clinical Dementia Rating-Sum of Boxes (CDR-SB) score of ≥2 points/year were classified as fast-progressors and those with CDR-SB change of <2 points/year were classified as slow-progressors. We found statistically significant upregulation in KIR2DL5A, SLC2A8, and PLOD1 for fast- (n = 8) compared with slow-progressors (n = 21) across the time-points. TOMM40 gene expression remained significantly lower in AD patients at all time-points compared to controls, supporting our previous findings. Our novel findings of specific gene expression differences between fast- and slow-progressors in combination with consistently lower TOMM40 expression, suggest their potential role as prognostic blood biomarkers to predict progression in early AD.
Chronic Lymphocytic Leukemia: Studies on the Effect of Drug Treatment on Different Lymphocytic Subpopulations (1976)

In the present work the effect of drug treatment on different lymphocyte populations in chronic lymphocytic leukemia was studied. During therapy there was evidence of an increased number of cells unidentifiable by conventional surface markers, provisionally termed lymphocyte surface-marker-negative cells. In addition, evidence of increased numbers of T lymphocytes in untreated patients and further evidence of IgG chronic lymphocytic leukemia cells were obtained.
Novel Genetic Rearrangements Termed “Structural Variation Polymorphisms“ Contribute to the Genetic Diversity of Orthohepadnaviruses (2019)

The genetic diversity of orthohepadnaviruses is not yet fully understood. This study was conducted to investigate the role of structural variations (SVs) in their diversity. Genetic sequences of orthohepadnaviruses were retrieved from databases. The positions of sequence gaps were investigated, since they were found to be related to SVs, and they were further used to search for SVs. Then, a combination of pair-wise and multiple alignment analyses was performed to analyze the genomic structure. Unique patterns of SVs were observed; genetic sequences at certain genomic positions could be separated into multiple patterns, such as no SV, SV pattern 1, SV pattern 2, and SV pattern 3, which were observed as polymorphic changes. We provisionally referred to these genetic changes as SV polymorphisms. Our data showed that higher frequency of sequence gaps and lower genetic identity were observed in the pre-S1-S2 region of various types of HBVs. Detailed examination of the genetic structure in the pre-S region by a combination of pair-wise and multiple alignment analyses showed that the genetic diversity of orthohepadnaviruses in the pre-S1 region could have been also induced by SV polymorphisms. Our data showed that novel genetic rearrangements provisionally termed SV polymorphisms were observed in various orthohepadnaviruses.
Plasma levels of soluble CD30 are increased in children with chronic renal failure and with primary growth deficiency and decrease during treatment with recombination human growth hormone (2001)

The finding that rhGH treatment decreased sCD30 plasma levels in children with CRF, and that children with primary GH deficiency had higher sCD30 plasma levels than controls, suggest that GH may regulate CD30 expression and possibly the balance of Th1/Th2. Whether the uraemia-induced increase in sCD30 is due to decreased renal excretion, to overproduction or both, remains to be determined.
Cell-Surface Thioredoxin-1: Possible Involvement in Thiol-Mediated Leukocyte-Endothelial Cell Interaction Through Lipid Rafts (2007)

Human thioredoxin-1 (hTrx) exhibits a disulfide reducing activity and was originally identified as a soluble cytokine-like factor secreted from cells of a human T-cell leukemia virus type I (HTLV-I)-transformed cell line. Recent studies have revealed that endogenous Trx plays an important role in cytoprotection against various oxidative stress-associated disorders. However, the function of exogenous Trx is still not fully understood. We report here that a cysteine-modified mutant of recombinant human Trx (rhTrx-C35S) binds to human umbilical vein endothelial cells (HUVECs) as well as stimulated T cells and rapidly enters these cells via lipid rafts. In addition, we found that endogenous Trx is expressed on the surface of HUVECs, including lipid rafts. These events suggest cell-surface Trx as a possible target of rhTrx-C35S. Furthermore, we found that anti-human Trx mouse monoclonal antibody inhibits adherence of LPS-stimulated human peripheral blood polymorphonuclear cells (PMNs) to HUVECs. This adherence was also suppressed by a recombinant human Trx (rhTrx), but not by a mutant rhTrx (rhTrx-C32S/C35S) with no reducing activity. Cell-surface Trx may be involved in the process of interaction between PMNs and HUVECs and a possible target of cysteine-modified exogenous Trx as well as wild-type exogenous Trx through redox regulation.
Cocrystallising Rotamers of a Pentacoordinate Silicon Complex with a Chiral Aminodiol Ligand (2013)

Abstract Crystal structure analysis reveals the cocrystallysation of two turnstyle rotamers of a pentacoordinate silicon complex with a chiral backbone derived from 2‐amino‐1,1,2‐triphenylethanol. The structures of the two epimers are well reproduced by DFT calculations. In addition, the coexistence of two rotamers, which readily interconvert in solution, is confirmed by their solid‐state NMR spectroscopic data. Possible mechanisms of their interconversion are discussed, and preference is given to a turnstile‐like rotation of three ligands at the silicon atom about 120°.
Novel Therapeutic Target for the Treatment of Lupus (2013)

Abstract : Many therapeutic strategies for SLE focus on the central role that autoantibody-producing B cells play in the pathology of this disorder. One general immunotherapeutic theme employs monoclonal antibodies (mAb) to interfere with, and/or deplete, B cells to ultimately reduce disease causing autoantibody levels. However, current strategies are inherently limited because they are not specific for the disease state. Thus, treatments that can specifically block autoantibody production without compromising B cell function are needed. In our application we presented preliminary evidence in an in vivo model of a related autoimmune disease (rheumatoid arthritis) that showed antibodies to RhoB, a small GTPase blocked autoantibody secretion without affecting the overall B cell repertoire. This data led us to propose the objective of this DOD-Discovery Award, to evaluate the ability of anti-RhoB antibodies to reduce levels of pathologic autoantibodies, ultimately attenuating the severity of symptoms in the MRL-lpr murine model of SLE. Our results demonstrate that dosing with an anti- RhoB mAb reduces serum anti-dsDNA titers in MRL-lpr mice. Interestingly, the two anti-RhoB Igs tested exhibited differing effects on renal disease pathology in the SLE model. One anti-RhoB antibody reduced renal inflammation while the other did not. We plan to seek new funding to extend these intriguing observations, and better understand the therapeutic potential of these novel anti-RhoB biologics.
Development of compact high pressure COIL (2005)

An advanced nozzle, also known as ejector nozzle, suitable for a 500 W class COIL employing an active medium flow of nearly 12 gm/s has been developed and used instead of conventional slit nozzle. The nozzle has been tested in both cold as well as hot run conditions of COIL achieving a typical cavity pressure of nearly 10 torr, pitot pressure of ~ 85 torr and a cavity Mach number of ~2.5. The present study details the gas dynamic aspects and detailed numerical studies of this ejector nozzle and highlights its potential as a COIL pressure recovery device. This nozzle in conjunction with a diffuser is capable of achieving pressure recovery of ~ 60 torr, equivalent to the much cumbersome first stage of the pressure recovery system used in case of conventional slit nozzle based system. . Thus use of this nozzle in place of conventional slit nozzle can achieve the atmospheric discharge using single stage ejector system thereby making the pressure recovery system quite compact.
Liposomal 1,25 (OH)2 vitamin D3 compounds block proliferation and induce differentiation in myelomonocytic leukaemia cells (1997)

The vitamin D3 derived hormone 1.25 (OH)2 vitamin D3 (1,25 D3) is able to induce growth arrest and differentiation in myelomonocytic leukaemia cells. In order to allow for specific delivery to leukaemic cells the lipophilic compound was incorporated into the lipid membranes of liposomes. Liposomal 1.25 D3 reduced proliferation as measured by 3H-thymidine incorporation in HL60 leukaemia cells by up to 60%. When liposomes were prepared at different concentrations of 1,25 D3 65% inhibition was achieved at 48 nM. The MC 1288 stereoisomer of 1,25 D3 was more potent and had the same activity at 4.8 nM. The effect of the liposomal compounds was specific to myeloid cells as they reduced proliferation in myelomonocytic HL60, monoblastic U937 and monocytic Mono Mac 6 cells but not in the T-cell lines Jurkat and Molt 4. The antiproliferative effect of liposomal 1,25 D3 was associated with an induction of differentiation since treated HL60 cells showed a monocytic morphology, increased expression of CD14 and decreased expression of CD33. When peripheral blood leukaemic cells from M4 and M5 acute myeloid leukaemia (AML) patients were admixed with liposomal compounds an antiproliferative effect was seen in all five cases, including the two cases where free compounds led to enhanced growth. Liposomal delivery of 1,25 (OH)2 vitamin D3 may offer a novel approach to treatment of myelomonocytic leukaemia.
Genetic polymorphisms in neonatal sepsis (2009)

There is presently a great deal of interest in linking genetic and phenotypic variation in the form of severity of, and susceptibility to, common multifactorial diseases such as sepsis. The genetic background has recently been recognized as an important element in the host response to infection, contributing to the variability in the clinical outcome of critically ill neonates. Host genetic variability in the regulatory and coding region of genes for components of innate immune system may have some bearing on the wide variability existing in the susceptibility to and outcome from sepsis even within similar neonatal intensive care unit populations. The completion of the Human Genome Project has provided insight into human genetic variation, most commonly represented by single-nucleotide polymorphisms, and has generated vast expectations. Polymorphisms in genes coding for proteins involved in the recognition of bacterial pathogens (Toll-like receptor 4, CD14) and the response to bacterial pathogens (tumor necrosis factor (TNF)-α, interleukin (IL)-1, interleukin-1 receptor antagonist (IL-1RA), IL-6, IL-10) can influence the amount or function of the protein produced in response to bacterial stimuli. Combining population genomics, bio-informatics, and clinical data may lead to the discovery of the variations that exist among the genes involved in determining susceptibility to sepsis in neonates. This review provides a background to recent advances in genetics, focusing on the application to neonatal sepsis and the practical difficulties of genetic association studies, as well as underlining the potential impact on clinical practice. Evidence is discussed suggesting that some genetic polymorphisms influence the susceptibility to and outcome from sepsis. Although still in its beginnings in neonatology, genomics will transform also this field but it will take years for the clinical implications to be revealed.
Bacteriophage-Induced Lipopolysaccharide Mutations in Escherichia coli Lead to Hypersensitivity to Food Grade Surfactant Sodium Dodecyl Sulfate (2020)

Bacteriophages (phages) are considered as one of the most promising antibiotic alternatives in combatting bacterial infectious diseases. However, one concern of employing phage application is the emergence of bacteriophage-insensitive mutants (BIMs). Here, we isolated six BIMs from <i>E. coli</i> B in the presence of phage T4 and characterized them using genomic and phenotypic methods. Of all six BIMs, a six-amino acid deletion in glucosyltransferase WaaG likely conferred phage resistance by deactivating the addition of T4 receptor glucose to the lipopolysaccharide (LPS). This finding was further supported by the impaired phage adsorption to BIMs and glycosyl composition analysis which quantitatively confirmed the absence of glucose in the LPS of BIMs. Since LPSs actively maintain outer membrane (OM) permeability, phage-induced truncations of LPSs destabilized the OM and sensitized BIMs to various substrates, especially to the food-grade surfactant sodium dodecyl sulfate (SDS). This hypersensitivity to SDS was exploited to design a T4-SDS combination which successfully prevented the generation of BIMs and eliminated the inoculated bacteria. Collectively, phage-driven modifications of LPSs immunized BIMs from T4 predation but increased their susceptibilities as a fitness cost. The findings of this study suggest a novel strategy to enhance the effectiveness of phage-based food safety interventions.
Shortlisting genes important in seed maturation by principal component analysis of gene expression data (2020)

Abstract Transcriptome data are widely used for functional analysis of genes. De-novo assembly of transcriptome gives a large number of unigenes. A large proportion of them remain unannotated. Efficient computational methods are required for identifying genes and modeling those for regulatory and functional roles. Principal component analysis (PCA) was used in a novel approach to shortlist genes, independently of annotation in genome expression data, taking seed development in Arabidopsis thaliana as a representative case. PCA was applied to published genome expression data from four lines of Arabidopsis, mutated in seed development. The PC separating all the developmental stages between a mutant and its respective wild type was selected for shortlisting genes as functionally more important. The shortlisted genes identified by PCA belong to a number of biological functions. The genes reported to give sensitivity to desiccation were identified in PCA analysis also in desiccation intolerant lines only. With respect to the network of 98 genes targeted by ABI3, a higher number of genes was identified as important in the mutants abi 3-5, fus 3-3 andlec 1-1 in comparison to abi 3-1. Ontological analysis and comparison with earlier studies suggest that PCA of genome expression data is useful for shortlisting functionally important genes.
Field tests of elongated Na LGS wavefront sensing for the E-ELT (2013)

International audience
The effect of three-layer weft knitted material structure and composition upon performance properties (2017)

The effect of three-layer weft knitted spacer material content and structure upon the characteristics of uniaxial tension, biaxial punching before and after fatigue punching, and at multi cycle low-stress (wearing level) punching were investigated. Three different spacer structures were knitted using four types of the same 20 tex linear density spun yarns. For three-layer weft knitted samples, innovative fibers, which are used in the production of functional clothing, were selected: Coolplus® 100% polyester (PES); Trevira CS® 100% PES; 60% PES; 40%PES, 60% PES with 0.02% carbon fiber and 67% cotton, 33% PES with 0.02% carbon fiber. It was defined that the samples, which have a plain jersey knitting pattern in the face and back layers, and a similar position of spacer yarns on the dial and cylinder needles, have the highest values of mass per unit area, but 1 × 1 tuck stitches in the face layer have a greater effect for material thickness. Besides, 1 × 1 tuck stitches in the face layer have a greater effect upon the uniaxial behavior and anisotropy of three-layer weft knitted spacer materials than on spacer yarn position in the connecting layer. The investigations of biaxial fatigue punching up to 50 N, which corresponds to wearing conditions, showed that the most stable and less deformable materials were the three-layer weft knitted spacer materials with a plain jersey knitting pattern in the face and back layers and a similar position of spacer yarns on the dial and cylinder needles. They also were characterized by the highest mass per unit area and medium thickness.
<title>Ultrasonic inspection of CFRP plates using surface-bonded optical fiber sensors</title> (1996)

This paper describes a non-destructive inspection technique based on the interaction of ultrasonic S<SUB>O</SUB> Lamb waves with holes, regions of impact damage, and delaminations, in carbon fiber composite plates. The Lamb waves were detected using a surface bonded, single mode optical fiber sensor operating at a wavelength of 633 nm forming one arm of an optical fiber Mach Zehnder interferometer. Lamb generation was accomplished by use of perspex coupled piezo-electric transducers.
Preservation of the 3D Phenotype Upon Dispersal of Cultured Cell Spheroids Into Monolayer Cultures (2016)

In functional cytometric studies, cultured cells are exposed to effectors (e.g., drugs), and the heterogeneity of cell responses are studied using cytometry techniques (e.g., image cytometry). Such studies are difficult to perform on 3D cell cultures. A solution is to disperse 3D clusters and transfer the cells to the 2D state before applying effectors and using cytometry. This approach requires that the lifetime of the 3D phenotype be longer than the duration of the experiment. Here we studied the dynamics of phenotype transformation from 3D to 2D and searched for means of slowing this transformation down in dispersed spheroids of MCF7 cells. We found three functional biomarkers of the 3D phenotype in MCF7 cell spheroids that are absent in the 2D cell culture: (i) the presence of a subpopulation with an elevated drug-expelling capacity; (ii) the presence of a subpopulation with an elevated cytoprotective capacity; and (iii) the accumulation of cells in the G1 phase of the cell cycle. Monitoring these biomarkers in cells transferred from the 3D state to the 2D state revealed their gradual extinction. We found that the combined application of an elevated cell density and thiol-containing medium supplements increased the lifetime of the 3D phenotype by several fold to as long as 96 h. Our results suggest that extending the lifetime of the 3D phenotype in the cells transferred from the 3D state to the 2D state can facilitate detailed functional cytometric studies, such as measurements of population heterogeneity of cytotoxicity, chemosensitivity, and radiosensitivity. J. Cell. Biochem. 118: 154-162, 2017. © 2016 Wiley Periodicals, Inc.
Mountain system monitoring at Senator Beck Basin, San Juan Mountains, Colorado: A new integrative data source to develop and evaluate models of snow and hydrologic processes (2014)

A hydrologic modeling data set is presented for water years 2006 through 2012 from the Senator Beck Basin (SBB) study area. SBB is a high altitude, 291 ha catchment in southwest Colorado exhibiting a continental, radiation-driven, alpine snow climate. Elevations range from 3362 m at the SBB pour point to 4118 m. Two study plots provide hourly forcing data including precipitation, wind speed, air temperature and humidity, global solar radiation, downwelling thermal radiation, and pressure. Validation data include snow depth, reflected solar radiation, snow surface infrared temperature, soil moisture, temperatures and heat flux, and stream discharge. Snow water equivalence and other snowpack properties are captured in snowpack profiles. An example of snow cover model testing using SBB data is discussed. Serially complete data sets are published including both measured data as well as alternative, corrected data and, in conjunction with validation data, expand the physiographic scope of published mountain system hydrologic data sets in support of advancements in snow hydrology modeling and understanding.
Wave propagation in elastic media with a periodic array of discrete inclusions (1974)

This study concerns the propagation of time harmonic waves in a continuous medium in which is embedded a three-dimensional periodic array of discrete inclusions. Both phases are taken to be elastic, and the symmetry characteristics of the combination are of the type of cubic crystals. A perturbation method of analysis is employed to obtain the steady-state periodic wave solution where full account is given to the multiple interacting reflections of shear and dilatational waves. When the solution is specialized to the case of constant moduli with only the density being variable, an attenuation factor for transient waves is extracted heuristically.
PEGylated human IL-10 (AM0010) monotherapy in refractory metastatic colorectal cancer. (2017)

3571 Background: Colorectal Cancer (CRC) has been refractory to immune therapies. The clinical benefit of immunotherapy is thought to depend on the expansion of activated, intratumoral, tumor specific cytotoxic CD8+ T cells which are low in most CRCs. AM0010 stimulates the survival, expansion and cytotoxicity of intratumoral CD8+ T cells. Patients with CRC who have progressed on SOC first and second line of therapy have a reported 7.1 months OS with TAS-102 (Meyer et al. NEJM372;20, 2015). In this Phase 1 study the efficacy of AM0010 was studied in refractory metastatic CRC patients. Methods: CRC pts progressing on a median of 4 prior therapies (range 2-7) were treated daily with AM0010 in doses of 1 ug/kg SQ daily to 40 ug/kg in a dose escalation design. Tumor responses were assessed using irRC. Serum cytokines, activation of blood derived T cells and peripheral T cell clonality were analyzed. Pretreatment archival tissue samples were evaluated by IHC for tumor infiltration by CD8+T cells. Results: AM0010 was tolerated with reversible TrAEs. 10 pts (of 27) had a G3/4 TrAE. There were no objective responses. 11 patients were treated in dose escalation cohorts (1-10 ug/kg) and 16 pts were treated at or above RP2D (20 ug/kg or 40 ug/kg). Seven of 25 pts with at least one radiographic response evaluation had stable disease at 8 weeks. One patient had SD for 19.4 months. The mPFS (ITT n = 27 pts) was 1.6 months, mOS was 11.7 (range 2.4 – 32+) months. The median follow-up is 25.2 months (range 13-35). AM0010 increased Th1 cytokines IL-18 and IFNg in the serum of patients, while decreasing mediators of chronic, tumor promoting inflammation (Th17 cytokines) and TGFb. Tumor infiltrating granzyme B+ CD8+ T cells increased during the treatment. AM0010 induced de-novo oligoclonal expansion of T cell clones in patients. Conclusions: AM0010 is well tolerated in patients with refractory CRC. Although objective tumor responses were not seen in this very advanced CRC population, the observed immune activation including clonal T cell expansion, prolonged stable disease, and the mOS of 11.7 months is encouraging in this advanced CRC population. Future study of AM0010 in combination with FOLFOX in a second – line of therapy colorectal cancer patients is being planned. Clinical trial information: NCT02009449.