gebhart/patrepeval huggingface dataset:
Interleukin 4 inhibits hepatocyte growth factor‐induced invasion and migration of colon carcinomas (1996)

Hepatocyte growth factor (HGF) is known to have a number of biological properties including promoting tumor progression of human carcinomas. Metastasis involves a number of events that are attributed to induction by paracrine factors such as HGF. Identification of natural inhibitors of these events would allow better control of tumor progression. Recently we demonstrated that interleukin 4 (IL-4) can regulate proliferation of various human carcinoma cell lines. In the present study, we used established human colon carcinoma cell lines and primary colon carcinoma cell cultures to determine if IL-4 could regulate HGF-induced cell proliferation and other events of tumor progression such as MMP (matrix metalloproteinases)-1, -2, and -9 production, cell migration and cell-matrix invasive activity. All colon carcinoma cell lines expressed HGF and IL-4 receptors. IL-4 significantly inhibited HGF-induced proliferation of one cell line. Cell-matrix invasion was significantly enhanced by HGF (0.1–10 ng/ml); IL-4 (1–10 U/ml) significantly inhibited HGF-induced invasion in a dose-dependent manner. IL-4 also inhibited HGF-induced cell-matrix invasion of metastatic colon carcinoma cells and HGF-induced cell migration. HGF enhanced MMP-1, -2, and -9 production by cell lines. This effect could be inhibited by IL-4. These findings indicate that IL-4 is a potent inhibitor of HGF-induced invasion and metastasis-related functions of human colon carcinoma cells. © 1996 Wiley-Liss, Inc.
The pendrin anion exchanger gene is transcriptionally regulated by uroguanylin: a novel enterorenal link (2011)

The pendrin/SLC26A4 Cl(-)/HCO(3)(-) exchanger, encoded by the PDS gene, is expressed in cortical collecting duct (CCD) non-A intercalated cells. Pendrin is essential for CCD bicarbonate secretion and is also involved in NaCl balance and blood pressure regulation. The intestinal peptide uroguanylin (UGN) is produced in response to oral salt load and can function as an "intestinal natriuretic hormone." We aimed to investigate whether UGN modulates pendrin activity and to explore the molecular mechanisms responsible for this modulation. Injection of UGN into mice resulted in decreased pendrin mRNA and protein expression in the kidney. UGN decreased endogenous pendrin mRNA levels in HEK293 cells. A 4.2-kb human PDS (hPDS) promoter sequence and consecutive 5' deletion products were cloned into luciferase reporter vectors and transiently transfected into HEK293 cells. Exposure of transfected cells to UGN decreased hPDS promoter activity. This UGN-induced effect on the hPDS promoter occurred within a 52-bp region encompassing a single heat shock element (HSE). The effect of UGN on the promoter was abolished when the HSE located between nt -1119 and -1115 was absent or was mutated. Furthermore, treatment of HEK293 cells with heat shock factor 1 (HSF1) small interfering RNA (siRNA) reversed the UGN-induced decrease in endogenous PDS mRNA level. In conclusion, pendrin-mediated Cl(-)/HCO(3)(-) exchange in the renal tubule may be regulated transcriptionally by the peptide hormone UGN. UGN exerts its inhibitory activity on the hPDS promoter likely via HSF1 action at a defined HSE site. These data define a novel signaling pathway involved in the enterorenal axis controlling electrolyte and water homeostasis.
Calibration of an electronically scanned white-light interferometric transducer for measurements of high pressure (1995)

The paper deals with an electronically scanned white-light interferometric transducer for high-pressure measurements which consists of a sensor, a conditioning circuit, an analog-to-digital converter, and a digital signal processor of the output signal from the sensor. The calibration of such a transducer consists of identifying a function modeling the relationship between the raw result of measurement y, which is the output of the transducer, and the measured pressure p, taking into account an influence quantity-temperature T. An algorithm for calibration is proposed and studied.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Development of New Methods for The Construction of Heterocycles Based on Cycloaddition Reaction of 1,3‐Dipoles (2014)

The development of a practical and efficient method for the construction of heterocycles is an essential part of programs to explore new medical and agrochemical agents. Asymmetric 1,3-dipolar cycloadditions of nitrile oxides, nitrones, and azomethine imines are developed in this chapter by the design of a novel chiral system possessing two- or three-metal centers utilizing tartaric acid ester as a chiral auxiliary. The strategy is applied to asymmetric hetero Diels-Alder reaction of nitroso compounds and Diels-Alder reaction of o-quinodimethanes. Synthesis of heterocycles based on a new strategy of stepwise nucleophilic addition-cyclization and related transformations consisting of [1,3]-sigmatropic rearrangement is developed in the chapter. A novel [5+1] cycloaddition reaction of N′-acyl azomethine imines as 1,5-dipoles, 1,3-dipoles with π-extended conjugation, is explored.
Cellulolytic Streptomyces Strains Associated with Herbivorous Insects Share a Phylogenetically Linked Capacity To Degrade Lignocellulose (2014)

Actinobacteria in the genus Streptomyces are critical players in microbial communities that decompose complex carbohydrates in the soil, and these bacteria have recently been implicated in the deconstruction of plant polysaccharides for some herbivorous insects. Despite the importance of Streptomyces to carbon cycling, the extent of their plant biomass-degrading ability remains largely unknown. In this study, we compared four strains of Streptomyces isolated from insect herbivores that attack pine trees: DpondAA-B6 (SDPB6) from the mountain pine beetle, SPB74 from the southern pine beetle, and SirexAA-E (SACTE) and SirexAA-G from the woodwasp, Sirex noctilio. Biochemical analysis of secreted enzymes demonstrated that only two of these strains, SACTE and SDPB6, were efficient at degrading plant biomass. Genomic analyses indicated that SACTE and SDPB6 are closely related and that they share similar compositions of carbohydrate-active enzymes. Genome-wide proteomic and transcriptomic analyses revealed that the major exocellulases (GH6 and GH48), lytic polysaccharide monooxygenases (AA10), and mannanases (GH5) were conserved and secreted by both organisms, while the secreted endocellulases (GH5 and GH9 versus GH9 and GH12) were from diverged enzyme families. Together, these data identify two phylogenetically related insect-associated Streptomyces strains with high biomass-degrading activity and characterize key enzymatic similarities and differences used by these organisms to deconstruct plant biomass.
Under-utilization of Narrow-Spectrum Antibiotics in the Ambulatory Management of Pediatric UTI: A Single-Center Experience (2021)

<b>Objective:</b> There are urinary tract infection (UTI) guidelines for treatment of patients <2 years old, but there is a paucity of data for other pediatric age groups including the potential role for stewardship to reduce prescription of broad-spectrum antibiotics. We assessed practice patterns for the diagnosis and empiric treatment of UTI for outpatient and school health sites affiliated with a large urban pediatric medical center. We hypothesized that outpatient providers under-utilize narrow-spectrum antibiotics, such as first-generation cephalosporins, for uncomplicated UTI. <b>Study Design:</b> Retrospective study from December 1st, 2015 to May 31st, 2016. <b>Results:</b> The study population included 903 children (70.1% female) with a median age of 11 years, evaluated in an outpatient clinic (<i>n</i> = 780, 86.4%) or school health site (<i>n</i> = 123, 13.6%). <i>E. coli</i> was the most common urinary pathogen (50.9%) and 92.6% of <i>E. coli</i> isolates were susceptible to cephalexin. However, cephalexin was prescribed empirically for only 12.8% of patients. In contrast, sulfamethoxazole-trimethoprim was commonly prescribed, but only 79% of <i>E. coli</i> isolates were susceptible. Antibiotics were discontinued in only three of 48 children who had negative urine cultures. <b>Conclusions:</b> Cephalexin may be the most appropriate first-line choice for management of outpatient UTI for our patient population. Antibiotics were rarely discontinued for those with negative urine cultures. Antibiotic stewardship in the outpatient setting could reduce unnecessary antibiotic exposure in the management of pediatric UTI.
Experimental results of reconfigurable non-binary cyclic ADC (2017)

This paper presents a reconfigurable non-binary cyclic analog-to-digital converter (ADC) which can achieve different resolution at different sampling frequency with the same analog conversion stage. The conversion resolution (bit number) of ADC can be increased with more conversion steps in the conventional cyclic manner; and the conversion speed of the cyclic ADC can be enhanced by our proposed multi-rate clock operation mode. The prototype ADC has been designed and fabricated in TSMC 90nm CMOS technology. The measured results of the proposed experimental ADC demonstrate that ENOB=12.42bit is achieved in conventional cyclic ADC mode while Fs=470kHz, and ENOB=9.96bit is achieved in our proposed multi-rate clock mode while Fs=889kHz with the same analog conversion stage and the simple radix-value estimation technique.
Effect of Heat Treatment on Si Electrodes Using Polyvinylidene Fluoride Binder (2008)

The electrochemical performance of Si electrodes using polyvinylidene fluoride (PVDF) binder heated at different temperatures ranging from 150°C to 350°C was investigated. Compared to unheated electrodes that have no capacity after the first formation cycle, the heat treated electrodes show an increasingly improved cycling performance as the heating temperature increases from 150°C to 300°C. In particular, Si electrodes heated at 300°C retain a specific capacity of about 600 mAh/g for 50 cycles with a lower cutoff potential of 0.170 V vs Li/Li+. The reasons for such improvements are considered based on results from thermal analysis, optical microscopy and adhesion tests. It is suggested that heat treatment improves the binder distribution, the adhesion to the Si particles and to the substrate, thereby leading to a better cycling performance. 2Introduction The ever-increasing demand for energy density has driven lithium ion battery researchers to new generation electrode materials with high energy density. One of the approaches is to replace the conventional carbonaceous negative electrode material by a
Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells (2023)

Emerging evidence suggests that chemotherapeutic agents and targeted anticancer drugs have serious side effects on the healthy cells/tissues of the patient. To overcome this, the use of non-oncology drugs as potential cancer therapies has been gaining momentum. Herein, we investigated one non-oncology drug named meticrane (a thiazide diuretic used to treat essential hypertension), which has been reported to indescribably improve the therapeutic efficacy of anti-CTLA4 in mice with AB1 HA tumors. In our hypothesis-driven study, we tested anti-cancer potential meticrane in hematological malignance (leukemia and multiple myeloma) and liver cancer cell lines. Our analysis showed that: 1) Meticrane induced alteration in the cell viability and proliferation in leukemia cells (Jurkat and K562 cells) and liver cancer (SK-hep-1), however, no evidence of apoptosis was detectable. 2) Meticrane showed additive/synergistic effects with epigenetic inhibitors (DNMT1/5AC, HDACs/CUDC-101 and HDAC6/ACY1215). 3) A genome-wide transcriptional analysis showed that meticrane treatment induces changes in the expression of genes associated with non-cancer associated pathways. Of importance, differentially expressed genes showed favorable correlation with the survival-related genes in the cancer genome. 4) We also performed molecular docking analysis and found considerable binding affinity scores of meticrane against PD-L1, TIM-3, CD73, and HDACs. Additionally, we tested its suitability for immunotherapy against cancers, but meticrane showed no response to the cytotoxicity of cytokine-induced killer (CIK) cells. To our knowledge, our study is the first attempt to identify and experimentally confirm the anti-cancer potential of meticrane, being also the first to test the suitability of any non-oncology drug in CIK cell therapy. Beyond that, we have expressed some concerns confronted during testing meticrane that also apply to other non-oncology drugs when considered for future clinical or preclinical purposes. Taken together, meticrane is involved in some anticancer pathways that are passively targeting cancer cells and may be considered as compatible with epigenetic inhibitors.
Phase I/II trial of a long peptide vaccine (LPV7) plus toll-like receptor (TLR) agonists with or without incomplete Freund’s adjuvant (IFA) for resected high-risk melanoma (2021)

NCT02126579.
Immune Response of Human Infants to Polysaccharide Vaccines of Groups A and C Neisseria meningitidis (1977)

Immunization of infants three to 24 months of age with polysaccharide vaccines derived from groups A and C Neisseria meningitidis induced no significant local or systemic adverse reactions. The antibody responses varied with age of the infant, quantity of vaccine, number of doses, molecular size of the vaccine polysaccharide, and the degree of preexisting, naturally acquired immunity to N. meningitidis. No response to group A vaccine was detected in three-month-old infants, but most seven- and 12-month-old infants responded to primary immunization, achieving geometric mean concentrations of antibody protein (measured as antibody to group A polysaccharide) of 0.39 and 0.84 ,µg/ml, respectively. Significant anamnestic responses were seen at seven and 12 months of age but not at 24 months. Primary immunization with group C vaccine elicited a response in 90% of three-month-old and in 100% of seven- and 12-month-old infants. The 100-µg dose of vaccine induced geometric mean concentrations of antibody to group C polysaccharide of 0.49, 1.41, and 2.62 ,µg/ml, at three, seven, and 12 months of age, respectively. These values were larger than those achieved with smaller doses. No anamnestic responses were observed with the group C vaccine. Booster injections resulted in lower concentrations of antibody to group C polysaccharide at seven and 12 months of age than did primary immunization, except after two booster doses of 10 µg. This depressed response to booster immunization was not observed in two-year-old children.
A Human/Murine Chimeric Fab Antibody Neutralizes Anthrax Lethal Toxin<i>In Vitro</i> (2013)

Human anthrax infection caused by exposure to Bacillus anthracis cannot always be treated by antibiotics. This is mostly because of the effect of the remaining anthrax toxin in the body. Lethal factor (LF) is a component of lethal toxin (LeTx), which is the major virulence of anthrax toxin. A murine IgG monoclonal antibody (mAb) against LF with blocking activity (coded LF8) was produced in a previous study. In this report, a human/murine chimeric Fab mAb (coded LF8-Fab) was developed from LF8 by inserting murine variable regions into human constant regions using antibody engineering to reduce the incompatibility of the murine antibody for human use. The LF8-Fab expressed in Escherichia coli could specifically identify LF with an affinity of 3.46 × 10(7) L/mol and could neutralize LeTx with an EC50 of 85 μ g/mL. Even after LeTx challenge at various time points, the LF8-Fab demonstrated protection of J774A.1 cells in vitro. The results suggest that the LF8-Fab might be further characterized and potentially be used for clinical applications against anthrax infection.
IEEE SSCS Toronto Chapter Holds First In-Person Wireline Workshop [Chapters] (2023)

The event began with handshakes and catching up with friends and peers who had not seen one another face to face since the COVID-19 pandemic started. The IEEE Solid-State Circuits Society (SSCS) Toronto Chapter last held an in-person event in October 2019. Judging by the smiles and record number of attendees (over 70) at this event, there was high demand for nonvirtual activities to restart in the Toronto area. All that people needed to motivate them to leave their home office was some free refreshments and an incredible lineup of talented local speakers.
Hyperthermic sensitization by the radical initiator 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH). I.<i>In vitro</i>studies (1994)

AAPH (2,2′-azobis-(2-amidinopropane dihydrochloride)) is a water-soluble, heat-labile azo compound which undergoes thermal decomposition to produce carbon-centred free radicals. These carbon-centred radicals might be directly cytotoxic or may react with oxygen to produce potentially cytotoxic alkoxyl and peroxyl radicals. The rate of free radical production as a result of AAPH thermal decomposition increases with increasing temperature. We have evaluated the efficacy of AAPH as a heat sensitizer for Chinese hamster V79 cells by the clonogenic assay. AAPH (50 mM) was not cytotoxic to V79 cells at 37°C for exposures up to 3 h. In contrast, AAPH (50 mM) was found to markedly sensitize cells exposed to 42, 43 and 45°C. For a 75 min exposure to 42°C alone, cell survival was reduced to 9×10-1; however, a 75 min exposure at 42°C + AAPH resulted in survival of 5·5×10-4. For 43 and 45·5°C heating, cell survival was potentiated by AAPH at the 1% survival level by 4·1 and 1·4-fold, respectively. AAPH was also found to sensitize both hypoxic cells and thermotolerant cells. These findings would encourage in vivo evaluation of AAPH (or analogues) as a temperature-dependent heat sensitizer. AAPH represents a new class of heat sensitizers which may have use in unravelling the mechanism(s) of heat killing and may have utility in local hyperthermia treatment.
Paludisme: Recherche de nouvelles approches thérapeutiques ciblant l'apicoplaste, un organite cellulaire d'origine algale (2012)

National audience
Increasing frame rate in ultrasound imaging by temporal morphing using tissue Doppler (2006)

The diagnostic value of echocardiographic images seems to diminish when the frame rate is low. In this work, morphing based on velocity information was used to improve the perceived smoothness of B-mode cine-loops with low frame rate. Based on an estimate of the velocity field calculated from B-mode speckle tracking and tissue Doppler measurements, morphed cine-loops with arbitrarily high frame rate were created. Morphing was applied to cardiac ultrasound cine-loops with apical insonation. The quality of the morphed data was evaluated by removing frames from duplex B-mode and tissue Doppler recordings, then replacing the removed B-mode frames with morphed ones. The decimated and morphed sequences were compared to the original ones. Wall motion scoring, a subjective evaluation technique for regional viability of the myocardium, was applied to data from 20 patients with varying pathology. Sixty cine-loops were scored twice, first with original data and later with morphed data. The results were compared for each recording, and the scorings were identical in the two cases for 94% of the segments. We conclude that much of the diagnostic value is retained in recordings with 15 frames per second when temporal morphing is applied.
Abstract 3840: Plocabulin, a tubulin inhibitor, presents antitumor activity in patient-derived xenograft (PDX) models of gastrointestinal stromal tumor (GIST) (2018)

Abstract Introduction: Advanced GIST is commonly treated with tyrosine kinase inhibitors (TKI) [e.g. imatinib (IMA)]. With time the vast majority of patients develops TKI-resistance. GIST is generally believed to be resistant to chemotherapy with cytotoxic agents. The aim of our study was to test plocabulin (PLO; PM060184, PharmaMar), a potent cytotoxic tubulin-dynamics modifier, in two PDX models of GIST, characterized by different sensitivity to IMA. Experimental set-up: NMRI nu/nu mice (n=34) were transplanted bilaterally with human xenografts UZLX-GIST3sens (KIT: exon 11 p.W557_V559delinsF; IMA-sensitive) or -GIST9res (KIT: exon 11+17: p.P577del;W557LfsX5;D820G; IMA-resistant). Xenografted animals were randomly assigned to three treatment groups: control [vehicle, 5ml/kg/QW intravenously (i.v.)], IMA (50mg/kg/BID orally) and PLO (16mg/kg/QW, i.v.). Treatment lasted 22 days and the antitumor activity was assessed by tumor volume measurement, histopathology and KIT signaling pathway by Western blotting. Histological response (HR) was evaluated as previously described by Antonescu et al. 2005. Mann Whitney U test was used for statistical analysis with p &amp;lt;0.05 considered as significant. Results: PLO treatment resulted in a reduction of tumor volume to 59% in GIST3sens and to 70% of the baseline volume in the GIST9res model. Good HR (grade 3, 4) was observed in 70% (GIST3sens) and 50% (GIST9res) of tumors. HR obtained with PLO was mainly characterized by necrosis, while IMA produced mainly myxoid degeneration in the sensitive model. In addition, in GIST3sens PLO decreased the microvessel area and increased apoptosis as assessed by immunohistochemistry, which was not observed in GIST9res. In the latter model PLO showed better activity than IMA in terms of tumor volume reduction (59% vs. 146%, p&amp;lt;0.01) and HR (grade 3, 4 in 50% vs. 0%). KIT signaling was not affected by PLO. The experimental drug was well tolerated throughout the experiment at the dose administered. Conclusions: PLO is the first anti-tubulin agent showing antitumor activity in GIST PDX, both in models sensitive or resistant to IMA. The drug causes cytotoxicity in GIST, mainly through necrosis, without affecting KIT signaling. Due to the different modes of action of PLO and established TKI our work provides a scientific rationale to combine PLO and IMA to overcome resistance to small molecule TKI. Citation Format: Agnieszka Wozniak, Yannick Wang, Jasmien Wellens, Yemarshet K. Gebreyohannes, Maria Jose Guillén, Carlos M. Galmarini, Pablo M. Avilés, Maria Debiec-Rychter, Raf Sciot, Patrick Schöffski. Plocabulin, a tubulin inhibitor, presents antitumor activity in patient-derived xenograft (PDX) models of gastrointestinal stromal tumor (GIST) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3840.