gebhart/patrepeval huggingface dataset:
New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463 (2017)

Senescent cells accumulate with aging and at sites of pathology in multiple chronic diseases. Senolytics are drugs that selectively promote apoptosis of senescent cells by temporarily disabling the pro-survival pathways that enable senescent cells to resist the pro-apoptotic, pro-inflammatory factors that they themselves secrete. Reducing senescent cell burden by genetic approaches or by administering senolytics delays or alleviates multiple age- and disease-related adverse phenotypes in preclinical models. Reported senolytics include dasatinib, quercetin, navitoclax (ABT263), and piperlongumine. Here we report that fisetin, a naturally-occurring flavone with low toxicity, and A1331852 and A1155463, selective BCL-X<sub>L</sub> inhibitors that may have less hematological toxicity than the less specific BCL-2 family inhibitor navitoclax, are senolytic. Fisetin selectively induces apoptosis in senescent but not proliferating human umbilical vein endothelial cells (HUVECs). It is not senolytic in senescent IMR90 cells, a human lung fibroblast strain, or primary human preadipocytes. A1331852 and A1155463 are senolytic in HUVECs and IMR90 cells, but not preadipocytes. These agents may be better candidates for eventual translation into clinical interventions than some existing senolytics, such as navitoclax, which is associated with hematological toxicity.
Cytokine secretion induced by superantigens in peripheral blood mononuclear cells, lamina propria lymphocytes, and intraepithelial lymphocytes (1995)

Superantigens are potent inducers of T-cell proliferation and induce a broad range of cytokines, including tumor necrosis factor (TNF), gamma interferon, and interleukin 2 (IL-2). In the present study, we compared the abilities of different staphylococcal superantigens (staphylococcal enterotoxin B [SEB], staphylococcal enterotoxin E [SEE], and toxic shock syndrome toxin 1 [TSST-1]) to stimulate distinct cytokine profiles in peripheral blood mononuclear cells (PBMC), lamina propria lymphocytes (LPL), and intraepithelial lymphocytes (IEL). One million PBMC, LPL, and IEL were stimulated with various concentrations of superantigen (10 to 0.001 ng/ml) for 24, 48, and 72 h. Maximum cytokine production by PBMC, LPL, and IEL was observed for all three superantigens at 48 h at a concentration of 1 ng/ml. In PBMC, SEE and TSST-1 stimulated more IL-2 and gamma interferon than SEB. SEE and TSST-1 also stimulated more TNF and IL-4 production than SEB. In contrast, SEB stimulated more IL-6 than either SEE or TSST-1. In LPL, there was no SEE-induced IL-2 or IL-4 production, but IL-6, TNF, and gamma interferon were induced. SEB similarly induced no IL-2 or gamma interferon from the LPL, but IL-4, IL-6, and TNF were detected. TSST-1 stimulation of LPL resulted in IL-2 and TNF production but no IL-4, IL-6, or gamma interferon. In IEL, SEE induced no IL-2, IL-4, or gamma interferon but produced IL-6 and TNF, while SEB stimulation resulted in no IL-2 or gamma interferon but did result in detectable IL-4, IL-6, and TNF. Taken together, these data indicate that there are significant differences in the cytokine profiles induced by superantigens in LPL and IEL compared with those in PBMC, and these differences may relate to differences in activation requirements.
Step‐wise specification of retinal stem cells during normal embryogenesis (2005)

The specification of embryonic cells to produce the retina begins at early embryonic stages as a multi-step process that gradually restricts fate potentials. First, a subset of embryonic cells becomes competent to form retina by their lack of expression of endo-mesoderm-specifying genes. From these cells, a more restricted subset is biased to form retina by virtue of their close proximity to sources of bone morphogenetic protein antagonists during neural induction. During gastrulation, the definitive RSCs (retinal stem cells) are specified as the eye field by interactions with underlying mesoderm and the expression of a network of retina-specifying genes. As the eye field is transformed into the optic vesicle and optic cup, a heterogeneous population of RPCs (retinal progenitor cells) forms to give rise to the different domains of the retina: the optic stalk, retinal pigmented epithelium and neural retina. Further diversity of RPCs appears to occur under the influences of cell-cell interactions, cytokines and combinations of regulatory genes, leading to the differentiation of a multitude of different retinal cell types. This review examines what is known about each sequential step in retinal specification during normal vertebrate development, and how that knowledge will be important to understand how RSCs might be manipulated for regenerative therapies to treat retinal diseases.
Fat Cell–Specific Ablation of Rictor in Mice Impairs Insulin-Regulated Fat Cell and Whole-Body Glucose and Lipid Metabolism (2010)

Rictor/mTORC2 in fat cells plays an important role in whole-body energy homeostasis by mediating signaling necessary for the regulation of glucose and lipid metabolism in fat cells.
Wnt Coreceptor Lrp5 is a Driver of Idiopathic Pulmonary Fibrosis (2014)

We show that the Wnt coreceptor, Lrp5, is a genetic driver of lung fibrosis in mice and a marker of disease progression and severity in humans with IPF. Evidence that TGF-β signaling can override a loss in Lrp5 has implications for patient selection and timing of Wnt pathway inhibitors in lung fibrosis.
Prescription profile of potentially aristolochic acid containing Chinese herbal products: an analysis of National Health Insurance data in Taiwan between 1997 and 2003 (2008)

About one-third of people in Taiwan have been prescribed with AA-CHPs between 1997 and 2003. Although the cumulated doses were not large, further actions should be carried out to ensure the safe use of AA-CHPs.
Mutant human immunodeficiency virus type 1 genomes with defects in RNA dimerization or encapsidation (1997)

Retrovirus particles each contain two copies of the viral genome in the form of a noncovalently linked RNA dimer. Earlier studies have mapped a cis-acting region near the 5' end of the human immunodeficiency virus type 1 (HIV-1) genome, termed the psi locus, which appears essential for initiation of genomic dimerization, as well as for interactions with the HIV-1 Gag protein that are thought to target the RNA into nascent virions. This HIV-1 psi locus is proposed to be organized in four independent RNA stem-loops; at least three (SL1, SL3, and SL4) contain binding sites for Gag, and one of these (SL1) is implicated in dimer initiation through a kissing-loop mechanism. In this study, we have created HIV-1 proviruses containing psi mutations that affect in vitro Gag binding, RNA dimerization, or both, and we have characterized the effects of these mutations on viral assembly and infectivity by using a single-step infectious assay. We find that various mutations which eliminate the Gag binding sites in SL1 or SL3 produce marked defects in genomic RNA packaging and viral infectivity. In each case, the reduced genomic content of the mutant virions is associated with an increased content of spliced viral transcripts, suggesting that both SL1 and SL3 contribute to the discrimination between spliced and unspliced RNAs. The structures, but not the specific sequences, of the SL1 and SL3 stems appear critical for RNA packaging. Disruption of the stem or deletion of SL1 also results in abnormal genomic dimerization, as assessed by nondenaturing gel electrophoresis of virion-derived RNA. Virions carrying less extensive mutations in the SL1 loop that are known to prevent in vitro dimerization have impaired infectivity despite normal virion RNA content. This suggests that RNA dimerization is not a prerequisite for genomic packaging but instead serves an independent function in the retroviral infectious cycle.
Detection of hepatitis B virus in serum using amplification of viral DNA by means of the polymerase chain reaction (1989)

A new assay was developed for the detection of hepatitis B virus (HBV) in human serum using amplification of a short viral DNA sequence by means of the polymerase chain reaction. As little as 0.4 fg viral DNA, corresponding to about 130 genome equivalents, per ml serum could be detected after the amplification procedure. This assay detected viral DNA in a number of patients with proven or suspected chronic HBV infection who were all negative for HBV DNA in the conventional hybridisation assay. We found HBV DNA in all of six HBeAg-positive and in three of eight HBeAg-negative HBsAg carriers, as well as in all of 11 patients with chronic liver disease with antibodies against the HBV core antigen (anti-HBc) as the sole marker for HBV infection, and in three of five apparently healthy individuals showing only anti HBc. Thus, this method is an important improvement for the diagnosis of persistent HBV infections, especially in patients where a definitive serological diagnosis is not possible.
A human monoclonal antibody blocking SARS-CoV-2 infection (2020)

The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking. Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV) in cell culture. This cross-neutralizing antibody targets a communal epitope on these viruses and may offer potential for prevention and treatment of COVID-19.
The Effects of Co-channel Interference on Spatial Diversity Techniques (2007)

This paper investigates the effects of co-channel interference on spatial diversity techniques. By analyzing distributions of post-processing signal to noise plus interference ratio (SINR) after matched filtering, we capture the performance characteristics of spatial diversity techniques in an interference limited environment. Using intuition from the theoretical analysis of a single carrier system, the performance of spatial diversity techniques in an OFDMA system with co-channel interference is also characterized. Our analytical and simulation results show that space time block code (STBC) schemes are more sensitive to co-channel interference than other spatial diversity techniques so their performance gain in a noise-limited environment can be lost in an interference-limited environment.
Lack of TXNIP Protects Against Mitochondria-Mediated Apoptosis but Not Against Fatty Acid–Induced ER Stress–Mediated β-Cell Death (2009)

Our results demonstrate that unlike glucose, fatty acids do not induce beta-cell expression of proapoptotic TXNIP. They further reveal that TXNIP deficiency specifically inhibits the mitochondrial death pathway underlying beta-cell glucotoxicity, whereas it has very few protective effects against ER stress-mediated lipoapoptosis.
Taxi Emergency and Location System for Metropolitan Toronto (1991)

&lt;div class="htmlview paragraph"&gt;Recent advances in computer and communications technologies have fostered significant developments in mobile information systems, not only to locate vehicles in distress situations but also to permit central monitoring of their positions for management purposes.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;This paper will focus on investigations carried out by the Ministry of Transportation of Ontario on Emergency Location Systems with the prime objective to identify a functional and cost-effective solution for Metropolitan Toronto's taxi operations and other municipal fleets and to investigate as well, opportunities to enhance vehicle dispatching and real-time traffic data collection, using the location system's communications infrastructure.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The approach taken was to investigate existing and upcoming commercial systems, evaluate them and recommend the appropriate course of action. The outcome of the study is a list of systems recommended for further investigations and small-scale demonstrations.&lt;/div&gt;
AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma (2019)

Lenalidomide improved efficacy of rituximab in patients with recurrent indolent lymphoma, with an acceptable safety profile.
Plasma-assisted cleaning by electrostatics (PACE) (2007)

The need for a non-contact contamination removal technique has been exhibited by various companies. While an EUV compatible pellicle is being researched, contamination will become an ongoing problem to overcome. Some techniques that are being considered for contamination removal include the use of shockwaves which are potentially damaging, as well as rolling contamination off of a surface. Depending on feature size, rolling or moving of contamination horizontally across a surface is limited as there is a strong possibility that the contamination will get trapped in between features. Plasma- Assisted Cleaning by Electrostatics (PACE) is a non-contact removal method that utilizes charge imbalances to remove particles perpendicular to the surface. A positive bias is applied to the top of the sample for conducting samples or to the substrate behind an insulating sample. This positive bias draws in net electrons from the plasma to the entire surface. The contamination charges negatively and the positive bias is removed and switched with a negative bias. The combination of substrate/particle charge imbalance as well as electric field effects from the plasma sheath provide for the removal mechanism. Surface damage has been avoided by staying below the sputtering threshold for the surface materials of the samples. Recent tests on 2.5 nm ruthenium on Si/Quartz using the PACE technique coupled with Atomic Force Microscopy data has shown no roughening of the surface and approximately 90% removal efficiency of contamination. In addition, Auger Electron Spectroscopy scans show no removal of the 2.5 nm ruthenium capping layer. Removal results for 30 nm to 220 nm PSL particles as well as select other contamination materials on samples comparable with EUV masks in addition to damage assessments will be presented.
Evidence for a functional subclass of the RTVL-H family of human endogenous retrovirus-like sequences (1993)

We report the discovery of a subgroup of RTVL-H human endogenous retroviral elements, designated RTVL-Hp, that is intact in the pol region which is deleted in the vast majority of RTVL-H elements. As a consequence, RTVL-Hp elements contain critical functional domains in their pol region that other RTVL-H elements lack. We estimate that the haploid genomes of humans, apes, and Old World monkeys contain 50 to 100 copies of RTVL-Hp elements and 800 to 1,000 deleted sequences. The major amplification of deleted elements appears to have occurred after the divergence of Old World and New World monkeys, since we have obtained evidence that a few intact RTVL-Hp elements, but no deleted forms, are present in marmoset DNA. Using the polymerase chain reaction coupled with a direct screen for open reading frames, we have isolated fragments from four RTVL-Hp elements amplified from human DNA that contain an open reading frame throughout a region of pol that is disrupted by diagnostic mutations in all other RTVL-H sequences that we had previously analyzed. Northern (RNA) hybridization analysis shows that unit-length RTVL-Hp transcripts are expressed in the human teratocarcinoma cell line Tera-1. Together, the results presented here suggest that a small functional subfamily of RTVL-H elements is present in the human genome.
Oligopeptide antigens of the angiotensin lineage compete for presentation by paraformaldehyde-treated accessory cells to T cells. (1986)

The heptapeptide antigen angiotensin III can be presented to guinea pig T cells by paraformaldehyde-treated antigen-presenting cells, which are incapable of processing antigens and presumably cannot even ingest them. We demonstrate here that the decapeptide angiotensin I can outcompete angiotensin III for presentation by paraformaldehyde-treated antigen-presenting cells. It seems likely that the competition is for a site on the surface of the presenting cell. This extends earlier findings of competition for presentation between antigens. We also demonstrate that the antigens of the angiotensin series are highly susceptible to proteolytic destruction in cultures containing prefixed accessory cells. The proteases responsible for the destruction of these peptides are apparently located in the plasma membrane of accessory cells. These enzymes represent a methodologic problem in studies of competition between antigens for presentation; but since they presumably are active also in untreated cells, they may play a physiologic role in the normal immune response.
Epithelial Na+ Channel (ENaC), Hormones, and Hypertension (2010)

This minireview examines both the basic science and clinical observations over the past 20 years to show how and why overstimulation of the amiloride-sensitive epithelial Na(+) channel (ENaC) expressed by epithelial principal cells of the renal collecting duct may be responsible for a large portion of hypertension in modern society. This idea is based on the finding that, in Liddle syndrome, a mutation of the beta- and/or gamma-subunits of ENaC produces an activated ion channel, in turn resulting in severe hypertension that is resistant to most forms of conventional antihypertensive therapy. ENaC can also be stimulated to conduct sodium by two hormones: aldosterone and insulin. These hormones are both often elevated in obese individuals with therapy-resistant hypertension. Thus, overstimulation of ENaC by metabolic abnormalities in obese individuals may be a likely cause of the hypertension that accompanies obesity. The molecular mechanisms underlying both Liddle syndrome and obesity-related hypertension are different (i.e. genetic and hormonal, respectively), but both have the same end result, namely increased ENaC activity.
PLD integrates dedicated high-speed data buffering, complex state machine, and fast decode array (2002)

Many designs contain both complex synchronous logic and fast asynchronous logic which must be integrated in Programmable Logic Devices (PLDs). For example, some systems have a need for a specialized memory controller, usually a big state machine, as well as a need to decode high speed combinatorial signals such as chip selects, RAS and CAS, bank switching signals, etc. If the PLD is to be synchronized with the rest of the system, additional flip-flops will also be needed to buffer input signals. Implementing such designs in standard PLDs can be difficult since a PLD must meet the conflicting demands of control logic complexity and high-speed data buffering/decoding. In situations like this, the designer may wish to try a unique solution like the MAPL244 PLD from National Semiconductor. This paper utilizes a multiport buffer memory controller application to illustrate how to take advantage of the MAPL244's integrated state machine/control logic array, fast decode array, and high speed input data buffers.
Mouse vaccination with dendritic cells loaded with prion protein peptides overcomes tolerance and delays scrapie (2009)

Prion diseases are presumed to be caused by the accumulation in the brain of a pathological protein called prion protein (PrP) scrapie which results from the transconformation of cellular PrP, a ubiquitous glycoprotein expressed in all mammals. Since all isoforms of PrP are perceived as self by the host immune system, a major problem in designing efficient immunoprophylaxis or immunotherapy is to overcome tolerance. The present study was aimed at investigating whether bone-marrow-derived dendritic cells (DCs) loaded with peptides previously shown to be immunogenic in PrP-deficient mice, can overcome tolerance in PrP-proficient wild-type mice and protect them against scrapie. Results show that, in such mice, peptide-loaded DCs elicit both lymphokine release by T cells and antibody secretion against native cellular PrP. Repeated recalls with peptide-loaded DCs reduces the attack rate of 139A scrapie inoculated intraperitoneally and retards disease duration by 40 days. Most interestingly, survival time in individual mice appears to be correlated with the level of circulating antibody against native cellular PrP.
Specim IQ: Evaluation of a New, Miniaturized Handheld Hyperspectral Camera and Its Application for Plant Phenotyping and Disease Detection (2018)

Hyperspectral imaging sensors are promising tools for monitoring crop plants or vegetation in different environments. Information on physiology, architecture or biochemistry of plants can be assessed non-invasively and on different scales. For instance, hyperspectral sensors are implemented for stress detection in plant phenotyping processes or in precision agriculture. Up to date, a variety of non-imaging and imaging hyperspectral sensors is available. The measuring process and the handling of most of these sensors is rather complex. Thus, during the last years the demand for sensors with easy user operability arose. The present study introduces the novel hyperspectral camera Specim IQ from Specim (Oulu, Finland). The Specim IQ is a handheld push broom system with integrated operating system and controls. Basic data handling and data analysis processes, such as pre-processing and classification routines are implemented within the camera software. This study provides an introduction into the measurement pipeline of the Specim IQ as well as a radiometric performance comparison with a well-established hyperspectral imager. Case studies for the detection of powdery mildew on barley at the canopy scale and the spectral characterization of Arabidopsis thaliana mutants grown under stressed and non-stressed conditions are presented.
Bottom-up Filling of Submicrometer Features in Catalyst-Enhanced Chemical Vapor Deposition of Copper (2002)

A formation process for copper bottom-up filling of submicrometer via holes and trenches using iodine as a catalytic surfactant and hexafluoroacetylacetonate-copper-vinyltrimethylsilane in catalyst-enhanced chemical vapor deposition of copper is presented. The film growth rate of copper at the bottom of the submicrometer features is continuously accelerated until the features are filled, and this results in the bottom-up filling of submicrometer features previously considered not viable in vacuum deposition techniques. The accelerated film growth appears to be due to the accumulation of the catalytic surfactant iodine on the surface of the copper films growing at the bottom of the submicrometer features believed to result from reduction of the sidewall area in the submicrometer features as the film grows. The newly developed technique for the copper bottom-up filling of submicrometer features will have a great impact on on-chip copper interconnects for the next generation of microelectronic devices. Moreover, this bottom-up growth mode in submicrometer features is expected to be universal to other systems of chemical vapor deposition in which a catalytic surfactant is used. (C) 2001 The Electrochemical Society. [DOI: 10.1149/1.1430230] All rights reserved.