gebhart/patrepeval huggingface dataset:
Sustained Mucosal Healing in Adalimumab-Treated patients with moderate to severe Ileocolonic Crohnʼs Disease: Results of the EXTEND Trial (2009)

Adalimumab is effective for inducing and maintaining remission in Crohn's disease (CD), is steroid sparing, and produces sustained fistula closure. We evaluated the efficacy and safety of adalimumab for mucosal healing in EXTEND (EXTend the Safety and Efficacy of Adalimumab Through ENDoscopic Healing). EXTEND was a placebo-controlled study of patients with moderate to severe ileocolonic CD (Crohn's Disease Activity Index [CDAI]=220-450) and baseline mucosal ulceration (score of 2 or 3 on the ulcerated surface subscore of the Simple Endoscopic Score for Crohn's Disease [SES-CD] for ≥1 colon segments). All patients received openlabel adalimumab 160-/80-mg induction therapy at Weeks 0/2. At Week 4, patients were randomized to maintenance therapy with adalimumab 40 mg every other week (eow) or placebo (induction-only) through Week 52. Randomization and results were stratified by CR-70 response (CDAI decrease≥70 from baseline). From Week 8, patients with flares or nonresponse could receive open-label adalimumab 40 mg eow and could subsequently receive open-label adalimumab 40mg weekly for continued flares/nonresponse. Patients underwent colonoscopies at baseline, Week 12 (or unscheduled visit for patients who switched to open-label adalimumab before Week 12), time of switch to open-label adalimumab (if after Week 12), and Week 52 (or early termination). Primary endpoint was complete mucosal healing per the review committee's visual assessment of the Week-12 endoscopies. Secondary endpoints included clinical remission (CDAI<150); Crohn's Disease Endoscopic Index of Severity (CDEIS) remission (≤4); and mean change in SES-CD, all at Weeks 12 and 52. Of the135 patients enrolled, 129 were randomized. At baseline, mean CDAI was 320, mean CDEIS was 19, mean CD duration was 10 years, and 61% of patients had prior anti-tumor necrosis factor exposure. Concomitant medications included steroids for 26% of patients and immunosuppressants for 41%. Endoscopic endpoint data are provided (table). Clinical remission rates at Week 12 were 27.7% and 46.9% for the induction-only placebo and continuous adalimumab groups, respectively (nonresponder imputation [NRI] and intention to treat [ITT], p<0.05). At Week 52, 9.2% and 32.8% of patients were in clinical remission, respectively (p<0.05). There were no differences in frequency of serious adverse events/100-patient-years between groups. Adalimumab maintenance therapy was effective in healing the intestinal mucosa for patients with moderate to severe ileocolonic CD. Residual effects of the induction regimen may explain the large Week-12 placebo response. Mucosal healing was sustained for 1 year, as confirmed by CDEIS and SES-CD. Endoscopic Endpoints in EXTEND Endoscopic Endpoints in EXTEND Endoscopic Endpoints in EXTEND (Cont.) Endoscopic Endpoints in EXTEND (Cont.)
Nucleic Acid Therapeutics Using Polyplexes: A Journey of 50 Years (and Beyond) (2015)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTNucleic Acid Therapeutics Using Polyplexes: A Journey of 50 Years (and Beyond)Ulrich Lächelt*†‡ and Ernst Wagner*†‡View Author Information† Pharmaceutical Biotechnology, Department of Pharmacy, Ludwig Maximilians Universität, 81377 Munich, Germany‡ Nanosystems Initiative Munich (NIM), 80799 Munich, Germany*E-mail: [email protected]*E-mail: [email protected]Cite this: Chem. Rev. 2015, 115, 19, 11043–11078Publication Date (Web):April 15, 2015Publication History Received30 November 2014Published online15 April 2015Published inissue 14 October 2015https://pubs.acs.org/doi/10.1021/cr5006793https://doi.org/10.1021/cr5006793review-articleACS PublicationsCopyright © 2015 American Chemical SocietyRequest reuse permissionsArticle Views9095Altmetric-Citations486LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Gene delivery,Genetics,Nucleic acids,Polyethylenimine,Polymers Get e-Alerts
TRP channel activation by reversible covalent modification (2006)

Allyl isothiocyanate, the pungent principle of wasabi and other mustard oils, produces pain by activating TRPA1, an excitatory ion channel on sensory nerve endings. Isothiocyanates are membrane-permeable electrophiles that form adducts with thiols and primary amines, suggesting that covalent modification, rather than classical lock-and-key binding, accounts for their agonist properties. Indeed, we show that thiol reactive compounds of diverse structure activate TRPA1 in a manner that relies on covalent modification of cysteine residues within the cytoplasmic N terminus of the channel. These findings suggest an unusual paradigm whereby natural products activate a receptor through direct, reversible, and covalent protein modification.
A general phase noise relationship for four-wave mixing (2013)

We propose and verify the use of the power spectral density of the FM noise spectrum to study the phase noise relationship between the four-wave mixing components.
Clinical and genetic studies of ETV6/ABL1‐positive chronic myeloid leukaemia in blast crisis treated with imatinib mesylate (2003)

Most chronic myeloid leukaemia (CML) patients are genetically characterized by the t(9;22)(q34;q11), generating the BCR/ABL1 fusion gene. However, a few CML patients with rearrangements of 9q34 and 12p13, leading to ETV6/ABL1 chimaeras, have also been reported. Here we describe the clinical and genetic response to imatinib mesylate treatment of an ETV6/ABL1-positive CML patient diagnosed in blast crisis (BC). A chronic phase was achieved after acute myeloid leukaemia induction therapy. Then, treatment with imatinib mesylate (600 mg/d) was initiated and the effect was assessed clinically as well as genetically, including by repeated interphase fluorescence in situ hybridization studies. Until d 71 of imatinib mesylate therapy, stable improvements in the clinical and laboratory features were noted, and the frequency of ABL1-rearranged peripheral blood cells decreased from 56% to 11%. At d 92, an additional t(12;13)(p12;q13), with the 12p breakpoint proximal to ETV6, was found. The patient relapsed into BC 126 d after the start of the imatinib mesylate treatment and succumbed to the disease shortly afterwards. No mutations in the tyrosine kinase domain of ABL1 of the ETV6/ABL1 fusion were identified in the second BC. However, whereas the ETV6/ABL1 expression was seemingly the same at diagnosis and at second BC, the expression of ETV6 was markedly lower at the second BC. This decreased expression of wild-type ETV6 may have been a contributory factor for the relapse.
Spin-echo 1H n.m.r. spectroscopy: a new method for studying penicillin metabolism (1984)

J. R. Everett, K. R. Jennings, G. Woodnutt and M. J. Buckingham, J. Chem. Soc., Chem. Commun., 1984, 894 DOI: 10.1039/C39840000894
Abstract 2995: Thymoquinone attenuates breast cancer cell resistance to paclitaxel via targeting tumor associated stem cell population (2019)

Breast cancer remains the most common type of cancer in females, and remains to be one of the most leading causes of death worldwide. This led to increasing the interest to use adjuvant anti-cancer therapy to improve the efficacy of in-clinical use chemotherapeutic agents. Thymoquinone (TQ) is a naturally occurring bioactive compound which showed cumulative evidences of anticancer properties. Herein, we assessed the potential chemomodulatory effect of TQ as an adjuvant therapy in combination with paclitaxel (PTX) against breast cancer cells. Cytotoxic profiles of TQ alone or in combination with PTX were evaluated in MCF7 and T47D breast cancer cell lines. TQ showed cytotoxic effect against MCF7 and T47D cells with IC50’s of 64.93±14 µM and 165±2 µM, respectively. In MCF7, TQ did not change PTX’s IC50, and the combination index was indicative of antagonism (CI-value = 1.3). Similarly in T47D, combination of TQ with PTX increased PTX’s IC50 from 90±8 nM to 140±20 nM with CI-value of 1.5 indicating antagonism. However, it was found that TQ completely depleted PTX resistant fractions in both cancer cell lines under investigation. Moreover, apoptotic and autophagic cell death due to combination of PTX with TQ were significantly increased in T47D compared to PTX treatment alone by 5.6 and 1.7 folds, respectively. In MCF7, combination of TQ with PTX significantly increased autophagic cell death compared to PTX treatment alone. Furthermore, tumor associated stem cell clone (CD44(+)/CD24(-)/(low) was assessed by flow cytometry in MCF7 and T47D cells. TQ alone significantly decreased CD44+/CD24- tumor associated stem cell clone by 12.4±0.8%. In addition, combination of PTX with TQ further depleted CD44+/CD24- cell clone by 32.3±0.08%. Finally, TQ alone significantly downregulated TWIST-1, and upregulated SNAIL2 gene expression as an evidence to decreased cell resistance to PTX. In conclusion, TQ enhances PTX anticancer profile against breast cancer cells via depleting tumor associated stem cells clone rather than potentiating its direct cell killing effect.Citation Format: Hanan A. Bashmail, Aliaa A. Alamoudi, Gehan A. Hegazy, Ghada M.A. Agabnoor, Abdulwahab Noorwali, Ahmed M. Al-Abd. Thymoquinone attenuates breast cancer cell resistance to paclitaxel via targeting tumor associated stem cell population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2995.
A historical review of the histology of patent autogenous vein grafts and vein patches. (1975)

The literature on the histological changes occurring in autogenous vein grafts and patches was reviewed. Over 307 grafts (235 animal and 72 human) and 30 patches (28 animal and 2 human) have been described. Grafts were investigated from patients who died on the operating table up to 22 years after operation. Intimal thickening and various changes in the media (including necrosis and replacement fibrosis) occurred. Dilatation of vein grafts has occurred, and anerysm formation has been reported. Atheroma has been described in the grafts from 5 patients.
Handbook of Contemporary Neuropharmacology Volumes 1−3. Edited by David R. Sibley, Israel Hanin, Michael Kuhar, and Phil Skolnick. John Wiley & Sons, Inc., Hoboken, NJ. 2007. xx + 2992 pp. 18.5 × 26 cm. ISBN 978-0-471-66053-8. $760.00. (2007)

ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTHandbook of Contemporary Neuropharmacology Volumes 1−3. Edited by David R. Sibley, Israel Hanin, Michael Kuhar, and Phil Skolnick. John Wiley & Sons, Inc., Hoboken, NJ. 2007. xx + 2992 pp. 18.5 × 26 cm. ISBN 978-0-471-66053-8. $760.00.Richard A. GlennonView Author Information Department of Medicinal Chemistry School of Pharmacy Medical College of Virginia Virginia Commonwealth University Richmond, Virginia 23298-0540Cite this: J. Med. Chem. 2007, 50, 19, 4786–4787Publication Date (Web):August 23, 2007Publication History Published online23 August 2007Published inissue 1 September 2007https://pubs.acs.org/doi/10.1021/jm078017ghttps://doi.org/10.1021/jm078017gbook-reviewACS PublicationsCopyright © 2007 American Chemical SocietyRequest reuse permissionsArticle Views92Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Color,Diseases and disorders,Drug discovery,Pharmaceuticals,Receptors Get e-Alerts
Estudio de la de térmica del POLI(cloruro de Vinilo) modificado mediante reacciones de hidrogenación y cloración (2019)

&#x0D; En este trabajo se estudió la degradación térmica del poli(cloruro de vinilo) (PVC) después de ser sometido a: i) hidrogenación parcial usando como agentes reductores el tetrahidruro de litio y aluminio (HLi), el Hidruro de trietil-boro y litio (SH) y el hidruro de tri-n-butil estaño (HSn) y ii) reacción de cloración. Las muestras fueron degradadas a 180 °C en estado sólido hasta un 0,3% y la velocidad de la degradación fue obtenida mediante el método conductimétrico; mientras que la distribución de polienos fue investigada por espectroscopia ultravioleta/visible (UV/VIS). En el caso de las muestras de PVC hidrogenadas, los datos cinéticos indicaron que se produjo una fuerte estabilización del polímero de partida como consecuencia de la hidrogenación, obteniéndose el máximo grado de estabilización a conversiones en torno al 9 %. La correlación entre la tacticidad-conversión-velocidad de degradación térmica demostró el carácter lábil de las estructuras mmr terminales de secuencias isotácticas que desaparecieron de la cadena como consecuencia de la hidrogenación. Por otra parte en el caso de las muestras cloradas, los resultados obtenidos evidenciaron que la estabilización del polímero aumenta como consecuencia de la formación de estructuras 1,2-dicloradas. Mientras que, la aparición de estructuras 1,1,2-tricloradas (-CHCl-CCl2-) representan la presencia de estructuras lábiles nuevas.&#x0D; &#x0D; Palabras clave: Cloración; degradación térmica; hidrogenación; poli (cloruro de vinilo) (PVC); tacticidad.&#x0D; &#x0D; Abstract:&#x0D; &#x0D; In this work, the thermal degradation of polyvinyl chloride (PVC) was studied after being subjected to: i) partial hydrogenation, using lithium aluminum hydride (HLi), lithium triethylborohydride (SH) and tri-n-butyltin hydride (HSn), as reducing agents; and ii) chlorination reaction. The samples were degraded at 180 °C in the solid state up to 0.3% and the degradation rate was obtained by the conductimetric method; while the distribution of polyenes was investigated by ultraviolet/visible spectroscopy (UV/VIS). In the case of the hydrogenated PVC samples, the kinetic data indicated that there occurred a strong stabilization of the starting polymer as a consequence of the hydrogenation, obtaining the maximum degree of stabilization at conversions of around 9%. The correlation between the tacticity-conversion-degradation rate demonstrated the labile character of the mmr structures terminal of isotactic sequences that disappeared from the chain as a consequence of hydrogenation. On the other hand, in the case of the chlorinated samples, the results obtained showed that the stabilization of the polymer increases while the formation of 1,2-dichlorinated structures predominated. On the contrary, the appearance of 1,1,2-trichlorinated structures (-CHCl-CCl2-) represented the presence of new labile structures.&#x0D; &#x0D; Keywords: Chlorination; hydrogenation; poly (vinyl chloride) (PVC); tacticity; thermal degradation.
Voltage Instability Analysis via Hybrid System Reachability (2008)

Analysis of voltage instability of power systems is of basic importance for prevention of cascading outages and large blackouts. We propose to use reachability analysis of hybrid automaton for voltage instability analysis of power systems. Hybrid automaton is a well-known mathematical model of hybrid systems. Reachability analysis is performed by computing forward or backward reach sets for unsafe sets of a hybrid automaton. The automaton can represent the interaction between continuous voltage oscillation and discrete control of power equipments. The unsafe sets are also subsets of state space in which system voltages show unacceptable levels such as low or high values. For single machine-load bus (SMLB) system with controlled route switching, we show that computation of backward reach sets of hybrid automaton makes it possible to determine voltage instability in the SMLB system. The obtained result implies that voltage instability leading to cascading outages can be detected before its occurrence.
Sulfaphenazole and &#945;-Naphthoflavone Attenuate the Metabolism of the Synthetic Cannabinoids JWH-018 and AM2201 Found in K2/Spice (2013)

"K2" or "Spice" is an emerging drug of abuse that is laced with psychoactive synthetic cannabinoids JWH-018 and AM2201. Previous studies have identified hydroxylated (OH) and carboxylated (COOH) species as primary human metabolites, and kinetic studies have implicated CYP2C9 and -1A2 as major hepatic P450s involved in JWH-018 and AM2201 oxidation. The present study extends these findings by testing the hypothesis that CYP2C9- and 1A2-selective chemical inhibitors, sulfaphenazole (SFZ) and α-naphthoflavone (ANF), block oxidation of JWH-018 and AM2201 in human liver microsomes (HLM). A concentration-dependent inhibition of JWH-018 and AM2201 oxidation was observed in the presence of increasing concentration of SFZ (0.5 - 50 μM) and ANF (0.1 - 5.0 μM). No metabolic inhibition was observed with omeprazole, quinidine, and ketoconazole. The results presented herein further demonstrate the importance of CYP2C9- and 1A2-mediated oxidation of JWH-018 and AM2201 and the likelihood of adverse toxicity in populations with polymorphic alleles of these enzymes.
Analysis and network modeling of an aperture-coupled microstrip patch antenna (2001)

This paper describes a method for analyzing an aperture-coupled microstrip patch antenna in order to develop an improved transmission-line model that reflects the effects of structure parameters, including inclination angles and offset distances of the aperture with respect to the feed line or the patch. The equivalent circuit consists of three ideal transformers, extended slotlines terminated by a short circuit, and microstrip transmission lines with open stubs. Two transformers are introduced to take account of the interaction between the aperture field and two orthogonal patch modes, while the third transformer reflects the coupling between the aperture and the feed line. The turn ratios of the transformers are calculated efficiently. The microstrip open stubs in the patch are then replaced by well-known capacitance and radiation conductance equivalents. The proposed transmission-line model is then applied to several variations and shown to produce accurate antenna impedances.
Single photon detection using Geiger mode CMOS avalanche photodiodes (2005)

Geiger mode Avalanche Photodiodes fabricated using complementary metal-oxide-semiconductor (CMOS) fabrication technology combine high sensitivity detectors with pixel-level auxiliary circuitry. Radiation Monitoring Devices has successfully implemented CMOS manufacturing techniques to develop prototype detectors with active diameters ranging from 5 to 60 microns and measured detection efficiencies of up to 60%. CMOS active quenching circuits are included in the pixel layout. The actively quenched pixels have a quenching time less than 30 ns and a maximum count rate greater than 10 MHz. The actively quenched Geiger mode avalanche photodiode (GPD) has linear response at room temperature over six orders of magnitude. When operating in Geiger mode, these GPDs act as single photon-counting detectors that produce a digital output pulse for each photon with no associated read noise. Thermoelectrically cooled detectors have less than 1 Hz dark counts. The detection efficiency, dark count rate, and after-pulsing of two different pixel designs are measured and demonstrate the differences in the device operation. Additional applications for these devices include nuclear imaging and replacement of photomultiplier tubes in dosimeters.
Revealing the micromechanics driving cellular division: optical manipulation of force-bearing substructure in mitotic cells (2017)

During the anaphase stage of mitosis, a motility force transports genetic material in the form of chromosomes to the poles of the cell. Chromosome deformations during anaphase transport have largely been attributed to viscous drag force, however LaFountain et. al. found that a physical tether connects separating chromosome ends in crane-fly spermatocytes such that a backwards tethering force elongates the separating chromosomes. In the presented study laser microsurgery was used to deduce the mechanistic basis of chromosome elongation in rat-kangaroo cells. In half of tested chromosome pairs, laser microsurgery between separating chromosome ends reduced elongation by 7&plusmn;3% suggesting a source of chromosome strain independent of viscous drag. When microsurgery was used to sever chromosomes during transport, kinetochore attached fragments continued poleward travel while half of end fragments traveled towards the opposite pole and the remaining fragments either did not move or segregated to the proper pole. Microsurgery directed between chromosome ends always ceased cross-polar fragment travel suggesting the laser severed a physical tether transferring force to the fragment. Optical trapping of fragments moving towards the opposite pole estimates an upper boundary on the tethering force of 1.5 pN.
Heterogeneous generation of new cells in the adult echinoderm nervous system (2015)

Abstract Adult neurogenesis, generation of new functional cells in the mature central nervous system (CNS), has been documented in a number of diverse organisms, ranging from humans to invertebrates. However, the origin and evolution of this phenomenon is still poorly understood for many of the key phylogenetic groups. Echinoderms are one such phylum, positioned as a sister group to chordates within the monophyletic clade Deuterostomia. They are well known for the ability of their adult organs, including the CNS, to completely regenerate after injury. Nothing is known, however, about production of new cells in the nervous tissue under normal physiological conditions in these animals. In this study, we show that new cells are continuously generated in the mature radial nerve cord (RNC) of the sea cucumber Holothuria glaberrima . Importantly, this neurogenic activity is not evenly distributed, but is significantly more extensive in the lateral regions of the RNC than along the midline. Some of the new cells generated in the apical region of the ectoneural neuroepithelium leave their place of origin and migrate basally to populate the neural parenchyma. Gene expression analysis showed that generation of new cells in the adult sea cucumber CNS is associated with transcriptional activity of genes known to be involved in regulation of various aspects of neurogenesis in other animals. Further analysis of one of those genes, the transcription factor Myc showed that it is expressed, in some, but not all radial glial cells, suggesting heterogeneity of this CNS progenitor cell population in echinoderms.