gebhart/patrepeval huggingface dataset:
Effects of synergistic cytokine combinations, low oxygen, and irradiated stroma on the expansion of human cord blood progenitors (1992)

Expansion of hematopoietic progenitor cells in the mononuclear cell (MNC) fraction of human cord blood was evaluated under atmospheres containing reduced (5%) and normal (20%) oxygen tensions. Cells were cultured with synergistic cytokine combinations in suspension (without stroma) and on irradiated bone marrow stroma. Addition of interleukin (IL)-3 and IL-6 (IL-3/IL-6) provided a greater expansion of both total and progenitor cells than IL-1 and IL-3 (IL-1/IL-3). IL-3/IL-6 maintained a higher level of progenitors throughout the 8-week culture period, whereas progenitors disappeared earlier from cultures with IL- 1/IL-3. This indicates that an earlier cell type was affected by IL- 3/IL-6, and/or that IL-3/IL-6 favored self-renewal while IL-1/IL-3 induced differentiation. Reduced oxygen tension enhanced the productivity of these long-term hematopoietic cultures (LTHC) under all conditions tested. In suspension cultures, reduced oxygen increased cumulative total cell production by 125% and 167%, and cumulative progenitor production by 68% and 21%, with IL-1/IL-3 and IL-3/IL-6, respectively. The presence of irradiated stroma increased cumulative progenitor cell production almost threefold in cultures without cytokines. In cultures with cytokines, the beneficial effect of stroma was less significant, but was greater under 20% O2 than 5% O2. Cultures under 5% O2 provided more progenitors and often maintained progenitors for 1 to 2 weeks longer than those under 20% O2. To quantitate more precisely the shift in cell populations induced by IL-3/IL-6 and stroma in cultures under 5% O2, flow cytometry analysis was used. By week 3, the addition of IL-3/IL-6 stimulated a 15-fold and 25-fold expansion of promyelocytes (CD15+CD11b-) in suspension and stromal cultures, respectively. Addition of IL-3/IL-6 also increased mature granulocyte (CD15hiCD11b+) and monocyte (CD15loCD11b+) numbers, while no effect was seen on T-(CD3+) or B- (CD19+) lymphocytes. Endogenous production of IL- 6 was significantly higher under 5% O2 in both suspension and stromal cultures, and IL-6 production was increased threefold by the addition of IL-1/IL-3. Very little IL-1 beta was produced in these cultures, and endogenous IL-3 and tumor necrosis factor (TNF)-alpha were undetectable by enzyme-linked immunosorbent assay (ELISA) analysis.
Highly oriented thin films of a substituted oligo(para‐phenylenevinylene) on friction‐ transferred PTFE substrates (1997)

Highly oriented thin films of oligo( p ‐phenylenevinylene)s , oligoPPVs, provide information about the structure of polyPPV and structure‐property relationships. It is shown that deposition of a substituted oligoPPV onto highly preoriented PTFE substrates leads to highly oriented thin films and that annealing produces a remarkable morphological change (see Figure and also the cover), an indication of epitaxial growth. magnified image
Stress Urinary Incontinence (2006)

Stress urinary incontinence (SUI) was studied in 125 women who were subjected to simultaneous urodynamic and radiologic evaluation. This included cystometry, urethral pressure profiles, measurement of effective urethral length, estimation of urethral mobility, and alterations in the urethrovesical angles during stress. The most common abnormality was a hypermobility of the proximal urethra with loss of its intraabdominal position during stress, associated with changes in the urethrovesical angle. Fixation of the posterior urethra, loss of effective urethral length, low resting urethral pressure, and true neurovesical dysfunction were also found in some of the patients. Uninhibited bladder contractions were found in 22% of cases, but in most instances they were the result of SUI and ceased after surgical repair.
Straintronics-Based True Random Number Generator for High-Speed and Energy-Limited Applications (2015)

Random number generators are well known for their ubiquitous use in cryptography, statistical sampling, and computer simulations. In order to establish secure data transfers in cryptographic applications, these number generators need to reliably produce unpredictable numbers at a high rate. In this paper, by exploiting the metastability of the stressed straintronics (STR) device, we theoretically propose a proof-of-concept nanomagnetic-based scheme to generate random numbers at very high rates with low-energy overhead. The dynamic modeling of the device, including the Langevin thermal noise field, is discussed, and the effect of process variation on the energy barrier and reliability is analyzed. The device is interfaced with CMOS circuitry and simulated in the 65 nm technology. At 1 V supply level, the system can generate random numbers as fast as 510 MHz. The entire circuit, including the CMOS peripherals, consumes 12.5 uW at 100 MHz random number generation rate while dissipating merely 0.125 pJ/bit. By reducing the supply level to 0.5 V, the energy per bit can be reduced further to 19 fJ. Since the STR device can be placed on the top of the CMOS circuitry, the total area of the design is estimated to be 0.001 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> .
MicroRNAs in the pathogenesis of systemic lupus erythematosus (2013)

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease, characterized by the production of autoantibodies against multiple organs. MicroRNAs (miRNAs) are non-coding, single-stranded small RNAs that post-transcriptionally regulate gene expression. Evidence is accumulating that miRNAs play a pivotal role in the pathogenesis of SLE. This article reviews the pertinent publications (searched from the PubMed database) involving the mechanisms of actions of miRNA associated with the pathogenesis of SLE. The search of related literature was extended as far back as 1979. In this mini-review we first introduce the miRNAs briefly and later discuss their regulatory roles in the DNA methylation pathway, type I interferon pathway, estrogen and regulatory T-cells in the pathogenesis of SLE.
A Novel Membrane Reactor for Direct Hydrogen Production From Coal (2006)

Gas Technology Institute has developed a novel concept of a membrane reactor closely coupled with a coal gasifier for direct extraction of hydrogen from coal-derived syngas. The objective of this project is to determine the technical and economic feasibility of this concept by screening, testing and identifying potential candidate membranes under the coal gasification conditions. The best performing membranes were selected for preliminary reactor design and cost estimate. The overall economics of hydrogen production from this new process was assessed and compared with conventional hydrogen production technologies from coal. Several proton-conducting perovskite membranes based on the formulations of BCN (BaCe{sub 0.8}Nd{sub 0.2}O{sub 3-x}), BCY (BaCe{sub 0.8}Y{sub 0.2}O{sub 3-x}), SCE (Eu-doped SrCeO{sub 3}) and SCTm (SrCe{sub 0.95}Tm{sub 0.05}O{sub 3}) were successfully tested in a new permeation unit at temperatures between 800 and 1040 C and pressures from 1 to 12 bars. The experimental data confirm that the hydrogen flux increases with increasing hydrogen partial pressure at the feed side. The highest hydrogen flux measured was 1.0 cc/min/cm{sup 2} (STP) for the SCTm membrane at 3 bars and 1040 C. The chemical stability of the perovskite membranes with respect to CO{sub 2} and H{sub 2}S can be improved by doping with Zr, as demonstrated from the TGA (Thermal Gravimetric Analysis) tests in this project. A conceptual design, using the measured hydrogen flux data and a modeling approach, for a 1000 tons-per-day (TPD) coal gasifier shows that a membrane module can be configured within a fluidized bed gasifier without a substantial increase of the gasifier dimensions. Flowsheet simulations show that the coal to hydrogen process employing the proposed membrane reactor concept can increase the hydrogen production efficiency by more than 50% compared to the conventional process. Preliminary economic analysis also shows a 30% cost reduction for the proposed membrane reactor process, assuming membrane materials meeting DOE's flux and cost target. Although this study shows that a membrane module can be configured within a fluidized bed gasifier, placing the membrane module outside the gasifier in a closely coupled way in terms of temperature and pressure can still offer the same performance advantage. This could also avoid the complicated fluid dynamics and heat transfer issues when the membrane module is installed inside the gasifier. Future work should be focused on improving the permeability and stability for the proton-conducting membranes, testing the membranes with real syngas from a gasifier and scaling up the membrane size.
Endothelial Heparan Sulfate 6-O-Sulfation Levels Regulate Angiogenic Responses of Endothelial Cells to Fibroblast Growth Factor 2 and Vascular Endothelial Growth Factor (2012)

Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor 165 (VEGF(165)) are potent pro-angiogenic growth factors that play a pivotal role in tumor angiogenesis. The activity of these growth factors is regulated by heparan sulfate (HS), which is essential for the formation of FGF2/FGF receptor (FGFR) and VEGF(165)/VEGF receptor signaling complexes. However, the structural characteristics of HS that determine activation or inhibition of such complexes are only partially defined. Here we show that ovarian tumor endothelium displays high levels of HS sequences that harbor glucosamine 6-O-sulfates when compared with normal ovarian vasculature where these sequences are also detected in perivascular area. Reduced HS 6-O-sulfotransferase 1 (HS6ST-1) or 6-O-sulfotransferase 2 (HS6ST-2) expression in endothelial cells impacts upon the prevalence of HS 6-O-sulfate moieties in HS sequences, which consist of repeating short, highly sulfated S domains interspersed by transitional N-acetylated/N-sulfated domains. 1-40% reduction in 6-O-sulfates significantly compromises FGF2- and VEGF(165)-induced endothelial cell sprouting and tube formation in vitro and FGF2-dependent angiogenesis in vivo. Moreover, HS on wild-type neighboring endothelial or smooth muscle cells fails to restore endothelial cell sprouting and tube formation. The affinity of FGF2 for HS with reduced 6-O-sulfation is preserved, although FGFR1 activation is inhibited correlating with reduced receptor internalization. These data show that 6-O-sulfate moieties in endothelial HS are of major importance in regulating FGF2- and VEGF(165)-dependent endothelial cell functions in vitro and in vivo and highlight HS6ST-1 and HS6ST-2 as potential targets of novel antiangiogenic agents.
NARMAX-model-based time series modeling and prediction: feedforward and recurrent fuzzy neural network approaches (2003)

Brown adipocytes increase energy production in response to induction of PGC-1alpha, a dominant regulator of energy metabolism. We have found that the orphan nuclear receptor SHP (NR0B2) is a negative regulator of PGC-1alpha expression in brown adipocytes. Mice lacking SHP show increased basal expression of PGC-1alpha, increased energy expenditure, and resistance to diet-induced obesity. Increased PGC-1alpha expression in SHP null brown adipose tissue is not due to beta-adrenergic activation, since it is also observed in primary cultures of SHP(-/-) brown adipocytes that are not exposed to such stimuli. In addition, acute inhibition of SHP expression in cultured wild-type brown adipocytes increases basal PGC-1alpha expression, and SHP overexpression in SHP null brown adipocytes decreases it. The orphan nuclear receptor ERRgamma is expressed in BAT and its transactivation of the PGC-1alpha promoter is potently inhibited by SHP. We conclude that SHP functions as a negative regulator of energy production in BAT.
Novel IHC reagents targeted by gene expression data predict recurrence in a retrospective breast cancer cohort at the Comprehensive Cancer Institute of Huntsville (CCIH) (2004)

9612 Background: Recent gene expression studies have identified novel classes of breast cancer including a basal/myoepithelial class and a subclass of estrogen receptor-expressing patients which have poor outcomes. It remains unclear how many genes or proteins will need to be measured in order to develop diagnostic tools for patient stratification. Methods: Several hundred affinity-purified anti-peptide antisera were generated to targets chosen on the basis of gene expression data. A selected panel of 24 were tested on tissue arrays which contained 422 diagnostic paraffin blocks from breast cancer patients diagnosed at CCIH from 1989 to 2000 (mean follow-up of 65 months). Results: A panel of only four antibodies had a sensitivity of 57% and specificity of 73% (HR=3.0 p<0.01) for identifying patients who recurred. The prognostic values of these markers were independent of ER, lymph node status, stage, grade, and each other as assessed by a Cox multivariate proportional hazard model. Included in the panel were antisera directed at a predicted “Basal” target, BPAG1 (p<0.01), at a predicted “Luminal B” target, SLC7A5 (p<0.01), at a novel cadherin-related protein (p=0.01), and at an antisera directed at a putative methyltransferase expressed in a cell cycle dependent manner (p<0.01). Furthermore, the novel cadherin-related protein and the putative cell cycle regulated methyltransferase showed significant correlations with survival. Conclusions: Novel subclasses of breast cancer associated with poor outcome identified by gene expression studies can be distinguished by a panel of novel IHC antisera. These reagents should prove useful for patient stratification in early stage breast cancer patients. The expanded panel, which distinguishes broader biologic diversity in breast cancer, should prove useful for retrospective and prospective studies designed to identify responder populations in adjuvant clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Applied Genomics, Inc. Applied Genomics, Inc. Applied Genomics, Inc.
Copper Rich Cu1-xNix Alloys (0.05 < x < 0.15) Electrodeposited from Acid Sulfate-Based Electrolyte with Benzotriazole Additive for Microbump Metallization for 3D Stacked Integrated Circuits (2019)

sponsorship: The author is SB PhD fellow at FWO (project No 1S64517N) and wishes to acknowledge the Research Foundation Flanders for the financial support for this work. (Research Foundation Flanders|1S64517N)
Mechanism of interferon action. Translational control and the RNA-dependent protein kinase (PKR): antagonists of PKR enhance the translational activity of mRNAs that include a 161 nucleotide region from reovirus S1 mRNA. (1994)

The interferon-inducible, RNA-dependent protein kinase (PKR) is an important regulator of viral protein synthesis. Activated PKR inhibits protein synthesis by phosphorylating initiation factor eIF-2 alpha. The reovirus S4 gene, whose 1196 nucleotide mRNA transcript does not activate the PKR kinase, is efficiently expressed in vector-transfected monkey COS cells. By contrast, the 1463 nucleotide S1 gene of reovirus, which is a potent activator of PKR, is poorly expressed in COS cells. Virus genetic engineering was therefore used to examine the effect of the PKR activator sequence from the reovirus S1 gene on the expression of chimeric genes of reovirus in transfected COS cells. Chimeric S1/S4 and S4/S1/S4 reovirus constructions that included the PKR activator sequence from S1 in the sigma 3 ORF of S4 were expressed much less efficiently than wild-type S4. However, expression of sigma 3 from S4 (3'UTR/S1), which included the PKR activator sequence from S1 within the 3'-UTR of S4, was comparable to that from wild-type S4. Treatment of COS cells with 2-aminopurine, an inhibitor of PKR, increased the expression of the reovirus S1, S1/S4, and S4/S1/S4 chimeric genes but not the S4 gene or S4 (3'UTR/S1) chimera in transfected COS cells. Likewise, coexpression of the phosphotransfer-negative mutant PKR (K296R) increased the expression of reovirus S1, S1/S4 and S4/S1/S4 chimeric genes but not the S4 gene or S4 (3'UTR/S1) chimera in cotransfected COS cells. Truncated PKR(1-243) which includes the dsRNA binding domain but not the kinase catalytic subdomains was able to enhance the expression of reovirus S1, but did not affect S4 expression. The dsRNA binding protein E3L encoded by vaccinia virus also increased S1 expression similar to PKR (1-243) and PKR(K296R). These results suggest that the translational repression in vivo mediated by PKR is selective for mRNAs that possess the kinase activator region, and that the dominant negative effect of PKR on gene expression is likely mediated by the RNA binding activity of the PKR protein.
CD4 Glycoprotein Degradation Induced by Human Immunodeficiency Virus Type 1 Vpu Protein Requires the Function of Proteasomes and the Ubiquitin-Conjugating Pathway (1998)

The human immunodeficiency virus type 1 (HIV-1) vpu gene encodes a type I anchored integral membrane phosphoprotein with two independent functions. First, it regulates virus release from a post-endoplasmic reticulum (ER) compartment by an ion channel activity mediated by its transmembrane anchor. Second, it induces the selective down regulation of host cell receptor proteins (CD4 and major histocompatibility complex class I molecules) in a process involving its phosphorylated cytoplasmic tail. In the present work, we show that the Vpu-induced proteolysis of nascent CD4 can be completely blocked by peptide aldehydes that act as competitive inhibitors of proteasome function and also by lactacystin, which blocks proteasome activity by covalently binding to the catalytic beta subunits of proteasomes. The sensitivity of Vpu-induced CD4 degradation to proteasome inhibitors paralleled the inhibition of proteasome degradation of a model ubiquitinated substrate. Characterization of CD4-associated oligosaccharides indicated that CD4 rescued from Vpu-induced degradation by proteasome inhibitors is exported from the ER to the Golgi complex. This finding suggests that retranslocation of CD4 from the ER to the cytosol may be coupled to its proteasomal degradation. CD4 degradation mediated by Vpu does not require the ER chaperone calnexin and is dependent on an intact ubiquitin-conjugating system. This was demonstrated by inhibition of CD4 degradation (i) in cells expressing a thermally inactivated form of the ubiquitin-activating enzyme E1 or (ii) following expression of a mutant form of ubiquitin (Lys48 mutated to Arg48) known to compromise ubiquitin targeting by interfering with the formation of polyubiquitin complexes. CD4 degradation was also prevented by altering the four Lys residues in its cytosolic domain to Arg, suggesting a role for ubiquitination of one or more of these residues in the process of degradation. The results clearly demonstrate a role for the cytosolic ubiquitin-proteasome pathway in the process of Vpu-induced CD4 degradation. In contrast to other viral proteins (human cytomegalovirus US2 and US11), however, whose translocation of host ER molecules into the cytosol occurs in the presence of proteasome inhibitors, Vpu-targeted CD4 remains in the ER in a transport-competent form when proteasome activity is blocked.
Advances in the management of follicular lymphoma (2012)

A wealth of new substances has entered various stages of clinical trials and has yet to show superiority over rituximab-based immunochemotherapy. Intelligent therapeutic regimens containing these drugs have to be developed. Large randomized trials comparing promising treatment options are urgently needed.
A Research Agenda for Malaria Eradication: Vector Control (2011)

Different challenges are presented by the variety of malaria transmission environments present in the world today. In each setting, improved control for reduction of morbidity is a necessary first step towards the long-range goal of malaria eradication and a priority for regions where the disease burden is high. For many geographic areas where transmission rates are low to moderate, sustained and well-managed application of currently available tools may be sufficient to achieve local elimination. The research needs for these areas will be to sustain and perhaps improve the effectiveness of currently available tools. For other low-to-moderate transmission regions, notably areas where the vectors exhibit behaviours such as outdoor feeding and resting that are not well targeted by current strategies, new interventions that target predictable features of the biology/ecologies of the local vectors will be required. To achieve elimination in areas where high levels of transmission are sustained by very efficient vector species, radically new interventions that significantly reduce the vectorial capacity of wild populations will be needed. Ideally, such interventions should be implemented with a one-time application with a long-lasting impact, such as genetic modification of the vectorial capacity of the wild vector population.
Inactivation of Retinoblastoma (RB) Tumor Suppressor by Oncogenic Isoforms of the p53 Family Member p73 (2003)

The p53 family includes three members that share significant sequence homology, yet exhibit fundamentally different functions in tumorigenesis. Whereas p53 displays all characteristics of a classical tumor suppressor, its homologues p63 and p73 do not. We have previously shown, that NH(2)-terminally truncated isoforms of p73 (Delta TA-p73), which act as dominant-negative inhibitors of p53 are frequently overexpressed in cancer cells. Here we provide evidence that Delta TA-p73 isoforms also affect the retinoblastoma protein (RB) tumor suppressor pathway independent of p53. Delta TA-p73 isoforms inactivate RB by increased phosphorylation, resulting in enhanced E2F activity and proliferation of fibroblasts. By inactivating the two major tumor suppressor pathways in human cells they act functionally analogous to several viral oncoproteins. These findings provide an explanation for the fundamentally different functions of p53 and p73 in tumorigenesis.
Resonance enhancement in piezoresponse force microscopy: Mapping electromechanical activity, contact stiffness, and Q factor (2006)

Piezoresponse force microscopy (PFM) and spectroscopy of domain structure and switching dynamics at small excitation voltages require resonance enhancement of the surface displacements. The contact stiffness depends strongly on local elastic properties and topography resulting in significant variations of the resonant frequency. Moreover, the resonant response is determined both by the Q factor and the electromechanical activity. Here we develop a resonance-enhanced PFM that allows mapping of the local electromechanical activity, contact stiffness, and loss factor, thus avoiding limitations inherent to conventional frequency tracking. We anticipate that this method will be instrumental in imaging weakly piezoelectric materials and probing inelastic phenomena in ferroelectrics.
Combination Flucytosine and High‐Dose Fluconazole Compared with Fluconazole Monotherapy for the Treatment of Cryptococcal Meningitis: A Randomized Trial in Malawi (2009)

The results suggest that optimal oral treatment for cryptococcal meningitis is high-dose fluconazole with flucytosine. Efforts are needed to increase availability of flucytosine in Africa. Clinical trials registration. isrctn.org Identifier: ISRCTN02725351.