gebhart/patrepeval huggingface dataset:
Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis (2006)

Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disorder characterized by activation of fibroblasts and overproduction of extracellular matrix (ECM). Caveolin-1 (cav-1), a principal component of caveolae, has been implicated in the regulation of numerous signaling pathways and biological processes. We observed marked reduction of cav-1 expression in lung tissues and in primary pulmonary fibroblasts from IPF patients compared with controls. We also demonstrated that cav-1 markedly ameliorated bleomycin (BLM)-induced pulmonary fibrosis, as indicated by histological analysis, hydroxyproline content, and immunoblot analysis. Additionally, transforming growth factor beta1 (TGF-beta1), the well-known profibrotic cytokine, decreased cav-1 expression in human pulmonary fibroblasts. cav-1 was able to suppress TGF-beta1-induced ECM production in cultured fibroblasts through the regulation of the c-Jun N-terminal kinase (JNK) pathway. Interestingly, highly activated JNK was detected in IPF- and BLM-instilled lung tissue samples, which was dramatically suppressed by ad-cav-1 infection. Moreover, JNK1-null fibroblasts showed reduced smad signaling cascades, mimicking the effects of cav-1. This study indicates a pivotal role for cav-1 in ECM regulation and suggests a novel therapeutic target for patients with pulmonary fibrosis.
Role of macrophage migration inhibitory factor (MIF) in murine antigen-induced arthritis: interaction with glucocorticoids (2001)

(MIF) is a broad-spectrum proinflammatory cytokine implicated in human rheumatoid arthritis. The synthesis of MIF by synovial cells is stimulated by glucocorticoids, and previous studies suggest that MIF antagonizes the anti-inflammatory effects of glucocorticoids. This has not been established in a model of arthritis. We wished to test the hypothesis that MIF can act to reverse the anti-inflammatory effects of glucocorticoids in murine antigen-induced arthritis (AIA). Cutaneous DTH reactions and AIA were induced by intradermal injection and intra-articular injection, respectively, of methylated bovine serum albumin in presensitized mice. Animals were treated with anti-MIF MoAbs, recombinant MIF, and/or dexamethasone (DEX). Skin thickness of DTH reactions was measured with callipers and arthritis severity was measured by blinded quantitative histological assessment of synovial cellularity. Cutaneous DTH to the disease-initiating antigen was significantly inhibited by anti-MIF MoAb treatment (P < 0.001). AIA was also significantly inhibited by anti-MIF MoAb (P < 0.02). DEX treatment induced a dose-dependent inhibition of AIA, which was significant at 0.2 mg/kg (P < 0.05). MIF treatment reversed the effect of therapeutic DEX on AIA (P < 0.001). DEX also significantly inhibited DTH reactions (P < 0.05) but rMIF had no effect on this effect of DEX. DTH and AIA are MIF-dependent models of inflammation and arthritis. The reversal of glucocorticoid suppression of AIA by MIF supports the concept that MIF is a counter-regulator of glucocorticoid control of synovial inflammation. Although DTH was observed to be MIF-dependent and glucocorticoid-sensitive, rMIF had no reversing effect on the suppression of DTH by glucocorticoids. This suggests that inflammatory processes in specific tissues may respond differently to MIF in the presence of glucocorticoids.
Human papillomavirus type distribution in invasive cervical cancer and high‐grade cervical lesions: A meta‐analysis update (2007)

Data on human papillomavirus (HPV) type distribution in invasive and pre-invasive cervical cancer is essential to predict the future impact of HPV16/18 vaccines and HPV-based screening tests. A meta-analyses of HPV type distribution in invasive cervical cancer (ICC) and high-grade squamous intraepithelial lesions (HSIL) identified a total of 14,595 and 7,094 cases, respectively. In ICC, HPV16 was the most common, and HPV18 the second most common, type in all continents. Combined HPV16/18 prevalence among ICC cases was slightly higher in Europe, North America and Australia (74-77%) than in Africa, Asia and South/Central America (65-70%). The next most common HPV types were the same in each continent, namely HPV31, 33, 35, 45, 52 and 58, although their relative importance differed somewhat by region. HPV18 was significantly more prevalent in adeno/adenosquamous carcinoma than in squamous cell carcinoma, with the reverse being true for HPV16, 31, 33, 52 and 58. Among HSIL cases, HPV16/18 prevalence was 52%. However, HPV 16, 18 and 45 were significantly under-represented, and other high-risk HPV types significantly over-represented in HSIL compared to ICC, suggesting differences in type-specific risks for progression. Data on HPV-typed ICC and HSIL cases were particularly scarce from large regions of Africa and Central Asia.
Cutting Edge: Heat Shock Protein gp96 Induces Maturation and Migration of CD11c+ Cells In Vivo (2000)

Immunization of mice with the heat shock protein (HSP) gp96 but not control proteins leads to 5- to 7-fold enlargement of draining lymph nodes (LNs) resulting from accumulation of large numbers of mature CD11c(+) cells, but not T or B lymphocytes in them. The increase in size and cellularity is time-dependent; the draining LNs reach their peak size between 12 and 24 h after injection and regress to their normal size between 48 and 72 h after injection. The increment is elicited specifically in the draining LN but not in other LNs. This observation uncovers a novel aspect of HSP-APC interaction and adds to the mechanistic explanation for the unusually high immunogenicity of HSP-peptide complexes.
Circumferential Radiofrequency Ablation of Pulmonary Vein Ostia (2000)

Radiofrequency PV isolation with electroanatomic guidance is safe and effective in either paroxysmal or permanent AF.
Inhaled remdesivir reduces viral burden in a nonhuman primate model of SARS-CoV-2 infection (2021)

Remdesivir (RDV) is a nucleotide analog prodrug with demonstrated clinical benefit in patients with coronavirus disease 2019 (COVID-19). In October 2020, the US FDA approved intravenous (IV) RDV as the first treatment for hospitalized COVID-19 patients. Furthermore, RDV has been approved or authorized for emergency use in more than 50 countries. To make RDV more convenient for non-hospitalized patients earlier in disease, alternative routes of administration are being evaluated. Here, we investigated the pharmacokinetics and efficacy of RDV administered by head dome inhalation in African green monkeys (AGM). Relative to an IV administration of RDV at 10 mg/kg, an approximately 20-fold lower dose administered by inhalation produced comparable concentrations of the pharmacologically active triphosphate in lower respiratory tract tissues. Distribution of the active triphosphate into the upper respiratory tract was also observed following inhaled RDV exposure. Inhalation RDV dosing resulted in lower systemic exposures to RDV and its metabolites as compared with IV RDV dosing. An efficacy study with repeated dosing of inhaled RDV in an AGM model of SARS-CoV-2 infection demonstrated reductions in viral replication in bronchoalveolar lavage fluid and respiratory tract tissues compared with placebo. Efficacy was observed with inhaled RDV administered once daily at a pulmonary deposited dose of 0.35 mg/kg beginning approximately 8 hours post-infection. Moreover, the efficacy of inhaled RDV was similar to that of IV RDV administered once at 10 mg/kg followed by 5 mg/kg daily in the same study. Together, these findings support further clinical development of inhalation RDV.
ChemInform Abstract: Synthesis of Pyrrolidinone PNA: A Novel Conformationally Restricted PNA Analogue. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Adherence column and buoyant density separation of bone marrow stem cells and more differentiated cells (1971)

Abstract Mouse bone marrow cells were separated by adherence column and albumin density gradient procedures, assaying for spleen colony forming units ( in vivo CFU's), agar colony forming cells ( in vitro CFC's) and cluster forming cells. Column filtrates were enriched for CFU's whereas in vitro CFC's and cluster‐forming cells were enriched in adherent fractions. Gradient separation of these column fractions gave density distribution profiles indicating the non‐identity and heterogeneity of CFU's and in vitro CFC's.
The LD4 motif of paxillin regulates cell spreading and motility through an interaction with paxillin kinase linker (PKL) (2001)

The small GTPases of the Rho family are intimately involved in integrin-mediated changes in the actin cytoskeleton that accompany cell spreading and motility. The exact means by which the Rho family members elicit these changes is unclear. Here, we demonstrate that the interaction of paxillin via its LD4 motif with the putative ARF-GAP paxillin kinase linker (PKL) (Turner et al., 1999), is critically involved in the regulation of Rac-dependent changes in the actin cytoskeleton that accompany cell spreading and motility. Overexpression of a paxillin LD4 deletion mutant (paxillinDeltaLD4) in CHO.K1 fibroblasts caused the generation of multiple broad lamellipodia. These morphological changes were accompanied by an increase in cell protrusiveness and random motility, which correlated with prolonged activation of Rac. In contrast, directional motility was inhibited. These alterations in morphology and motility were dependent on a paxillin-PKL interaction. In cells overexpressing paxillinDeltaLD4 mutants, PKL localization to focal contacts was disrupted, whereas that of focal adhesion kinase (FAK) and vinculin was not. In addition, FAK activity during spreading was not compromised by deletion of the paxillin LD4 motif. Furthermore, overexpression of PKL mutants lacking the paxillin-binding site (PKLDeltaPBS2) induced phenotypic changes reminiscent of paxillinDeltaLD4 mutant cells. These data suggest that the paxillin association with PKL is essential for normal integrin-mediated cell spreading, and locomotion and that this interaction is necessary for the regulation of Rac activity during these events.
Performance of an RCPC-coded OFDM-based digital audio broadcasting (DAB) system (2002)

A system proposal for DAB is investigated. The kernel is orthogonal frequency division multiplexing (OFDM) with 4-DPSK (differential phase shift keying) modulation, rectangular pulse-shaping, and a guard interval to reject multipath distortions. Emphasis is on the use of source-adapted channel coding with rate-compatible punctured convolutional (RCPC) codes. Based on analytical and simulated BER (bit error rate) curves for several propagation conditions and on preliminary source significance information (SSI), a static code design with unequal error protection (UEP) is presented that also takes auxiliary data services into account. The gain due to UEP is on the order of 8dB in signal power or 25% in bandwidth.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
C-terminal half of tetanus toxin fragment C is sufficient for neuronal binding and interaction with a putative protein receptor (2000)

Tetanus neurotoxin (TeNT) is a powerful bacterial protein toxin that cleaves VAMP/synaptobrevin, an essential protein of the synaptic vesicle fusion machinery, and consequently blocks neurotransmission. The extreme neurospecificity of TeNT is determined by the binding of its C-terminal domain (fragment C or HC) to neuronal receptors. Whereas polysialogangliosides are known acceptors for the toxin, the existence of additional protein receptors has also been suggested. We have reported previously on a 15 kDa cell-surface glycoprotein that interacts with TeNT in neuronal cell lines and motoneurons [Herreros, Lalli, Montecucco and Schiavo (2000) J. Neurochem., in the press]. Here, on the basis of the structural information provided by the crystallization of fragment C of TeNT, we have expressed its C-and N-terminal halves as recombinant proteins and analysed their binding abilities to rat phaeochromocytoma (PC12) cells differentiated with nerve growth factor. We found that the C-terminal subdomain of the fragment C of TeNT is necessary and sufficient for cell binding and for the interaction with the 15 kDa putative receptor. In contrast, the N-terminal half showed a very poor interaction with the cell surface. These results restrict the binding domain of TeNT to the C-terminal half of the fragment C and highlight the importance of this domain for the neurospecific interaction of the toxin with the synapse. Furthermore, these findings support the use of this portion of TeNT as a neurospecific targeting device, pointing to an involvement of the N-terminal subdomain in later steps of the intoxication pathway.
Sensitivity of Stormwater Conveyance System Cost to Design Recurrence Interval (1999)

(No paper) The cost of a piped and/or swaled stormwater system is determined principally by the storm recurrence interval (e.g., 5-year design storm) used to design it. That is, the present worth or the annualized cost of the storm drains for a new residential development increase as the severity of the design storm increases. The owner should know how sensitive cost is to recurrence interval. With this information, the optimum system is more likely to be selected and constructed. Presented in this paper is a methodology for determining drainage system costs as the function of design storm recurrence interval. The Manning equation and sewer and swale cost data were combined to yield a relationship giving the cost per unit length of sewer or swale as a function of design flow. A typical residential development was created and a stormwater modeling computer program (Rational Method and Manning equation) along with derived cost functions were repeatedly used to design and cost the drainage system for a range of recurrence intervals. The process was applied using rainfall intensity-duration-frequency data for three different locations in the United States. One finding is that the cost of conveyance systems is relatively insensitive to recurrence interval. That is, a large degree of additional flood protection can be obtained for little additional cost. For example, the cost of the 50-year recurrence interval storm sewer systems was only about 20 percent more than the cost of the 5-year recurrence interval systems. This paper presents a practical process that can be used by a drainage designer to determine cost as a function of recurrence interval. The authors hope this will improve the design of stormwater systems.
Abstract 4039: Exploration of a potent E-Selectin antagonist (GMI-1271) as a potential novel therapeutic for treating breast cancer metastasis to the bone and lung (2014)

Abstract The propensity of breast cancer to metastasize to the lung and bone with high frequency presents an attractive opportunity for specific therapeutic intervention. Targeting the initial steps of metastasis, such as survival in circulation, arrest, and extravasation, may constitute a more effective approach than treatment during the later steps. E-Selectin has been implicated as a pro-metastatic endothelial receptor which mediates the initial stages of tumor cell arrest and extravasation to the lung, liver and bone. We examined the ability of the potent E-selectin antagonist GMI-1271 (Kd = 0.54 μM) to inhibit E-selectin binding to lung and bone metastatic cells. Flow cytometry and ELISA analysis was used to evaluate the effects of GMI-1271 in vitro while treatment of bone and lung metastasis with GMI-1271 during the initial stages of metastatic seeding was used in xenograft models. Results demonstrated that metastatic breast cancer cells express carbohydrates ligands recognized by E-selectin as determined by interaction with E-selectin-Fc chimeric protein and the antibody HECA-452. GMI-1271 could significantly reduce metastatic breast cancer cell binding to E-selectin in vitro. Treatment of mice following intracardiac injection resulted in a significant reduction of mortality (HR = 0.29, p = 0.044) while treatment following tail vein injection demonstrated a directional increase in survival (p = 0.061 and p = 0.055). These results designate GMI-1271 as a potential therapeutic for treatment of late stage breast cancer. Citation Format: Mark Esposito, John L. Magnani, Yibin Kang. Exploration of a potent E-Selectin antagonist (GMI-1271) as a potential novel therapeutic for treating breast cancer metastasis to the bone and lung. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4039. doi:10.1158/1538-7445.AM2014-4039
In vivo gene transfer to the human biliary tract. (1996)

The human biliary tract offers an excellent model for gene transfer studies for a variety of diseases localized to the liver. The aim of this study was to determine if a viable liver might be employed to study viral transfection of the human biliary system in order to mimic in vivo human experiments. Using a normal human liver initially procured for transplantation, but subsequently found unsuitable, and with an intact biliary tree, the hepatic vascular supply was accessed for continuous perfusion. The common and left hepatic biliary system was isolated by balloon catheterization. A replication defective adenoviral vector containing the Escherichia coli beta-galactosidase (lac Z) reporter gene (AdCMVLacZ) was injected into the catheter-isolated left and common bile duct lumen. Viral exposure to the right duct system was prevented by ligation. The bile duct segments were excised and prepared for enzymatic (X-gal) staining. Intense staining was observed in the biliary epithelium exposed to the adenoviral vector. No evidence of beta-galactosidase staining was noted in the unexposed biliary mucosa. We report direct transfection of biliary epithelial cells from normal human liver with a recombinant adenovirus. Our data suggest potential therapeutic applications for gene therapy of hepatobiliary disorders.
Effect of Continuous Heat Exposure on Sleep Stages in Humans (1988)

Six young men were exposed to a thermoneutral environment of air temperature (Ta) 20 degrees C for 5 days and nights followed by an acclimation period of 5 days and nights at Ta 35 degrees C and 2 recovery days and nights at Ta 20 degrees C. Electrophysiological measures of sleep, esophageal temperature, and mean skin temperature were continuously monitored. The total nocturnal body weight loss was measured by a sensitive platform scale. Compared with the 5 nights of the baseline period at 20 degrees C, sleep patterns showed disturbances at 35 degrees C. Total sleep time was significantly reduced, while the amount of wakefulness increased. The subjects exhibited fragmented sleep patterns. The mean duration of REM episodes was shorter at 35 degrees C than at 20 degrees C of Ta, while the REM cycle length shortened. In the acclimation period, there was no change in sleep pattern from night to night, despite adaptative adjustments of the thermoregulatory response. The protective mechanisms of deep body temperature occurring with heat adaptation did not interact with sleep processes. Upon return to baseline condition, a recovery effect was observed on a number of sleep parameters which were not significantly affected by the preceding exposure to prolonged heat. This would suggest that during exposure to dry heat, the demand for sleep could overcome that of other regulatory functions that are temperature-dependent. Therefore, a complete analysis of the effect of heat on sleep parameters can be assessed only if heat exposure is compared with both baseline and recovery periods.
The Generation of Zinc Finger Proteins by Modular Assembly (2010)

The modular assembly (MA) method of generating engineered zinc finger proteins (ZFPs) was the first practical method for creating custom DNA-binding proteins. As such, MA has enabled a vast exploration of sequence-specific methods and reagents, ushering in the modern era of zinc finger-based applications that are described in this volume. The first zinc finger nuclease to cleave an endogenous site was created using MA, as was the first artificial transcription factor to enter phase II clinical trials. In recent years, other excellent methods have been developed that improved the affinity and specificity of the engineered ZFPs. However, MA is still used widely for many applications. This chapter will describe methods and give guidance for the creation of ZFPs using MA. Such ZFPs might be useful as starting materials to perform other methods described in this volume. Here, we also describe a single-strand annealing recombination assay for the initial testing of zinc finger nucleases.
When Worlds Collide: The Altered State of Private Equity-A Conference Summary (2009)

The Federal Reserve System?s Private Equity Merchant Banking Knowledge Center, formed at the Chicago Fed in 2000 after the passage of the Gramm-Leach-Bliley Act, sponsors an annual conference on new industry developments. This article summarizes the ninth annual conference, held on June 25-26, 2009.
Reliable spectrum sensing for resource allocation of cognitive radio based WiMAX femtocells (2012)

Femtocells are perceived as having a strong potential to provide high data-rate services with increased coverage at low cost. In this paper, we consider a WiMAX network with both macro base stations (BS) and low-power, low-cost Femto Access Points (APs). We assume that Femto-APs share the same bandwidth as macro BS and Femto-APs are connected to the macro BS by wired backhaul such as cable or DSL. One of the important technical challenges in this framework is to mitigate the interference from macro users by avoiding their spectrum. Robust and dynamic spectrum sensing for channel occupancy by macro users is therefore necessary to schedule resources for femto users. An efficient cyclostationary-based spectrum sensing method is presented to facilitate cognitive radio (CR) aided resource allocation in femtocell networks for maximizing system throughput while minimizing inter-tier interference. Contrary to the classical energy detection (ED) approach, a cyclostationary-based spectrum sensing is more effective in dealing with imperfect knowledge of in-band noise variance in practical radio signals. Also, this method is more efficient than ED in low signal-to-noise ratio which is a very important requirement in WiMAX based macrocell-femtocell overlay network.
Neural Question Generation from Text: A Preliminary Study (2017)

Automatic question generation aims to generate questions from a text passage where the generated questions can be answered by certain sub-spans of the given passage. Traditional methods mainly use rigid heuristic rules to transform a sentence into related questions. In this work, we propose to apply the neural encoder-decoder model to generate meaningful and diverse questions from natural language sentences. The encoder reads the input text and the answer position, to produce an answer-aware input representation, which is fed to the decoder to generate an answer focused question. We conduct a preliminary study on neural question generation from text with the SQuAD dataset, and the experiment results show that our method can produce fluent and diverse questions.