gebhart/patrepeval huggingface dataset:
Phase II study of oral panobinostat (LBH589), a potent pan-deacetylase inhibitor, in patients with refractory Cutaneous T-cell Lymphoma (CTCL) (2008)

8555 Background: Panobinostat (LBH589) is a potent pan-deacetylase inhibitor (DACi) which has demonstrated activity in patients (pts) with CTCL in a phase I study (Prince et al, ASCO 2007). This phase II study aims to confirm that activity. Methods: This open-label study enrolled pts with CTCL (stage IB-IVA), including Mycosis fungoides (MF) and Sezary syndrome (SS), who have failed ≥2 prior systemic therapies, have adequate organ function and ECOG PS ≤2. Pts with significant cardiovascular abnormalities or QTcF >450 msec on screening ECG were excluded. Pts were accrued to Group 1 (Grp 1, previously treated with oral bexarotene) or Group 2 (Grp 2, bexarotene naïve); both following a Simon 2-stage design. Panobinostat (20 mg) was administered orally on days 1, 3, and 5 weekly until disease progression or intolerance. Primary endpoint is the response rate measured using a composite score derived from assessment of skin disease using modified Severity-Weighted Assessment Tool [mSWAT], evaluation of visceral and lymph nodes, and circulating Sezary Cell count. Intensive ECG monitoring for QTcF prolongation was performed. Results: 40 pts (Grp 1=25; Grp 2=15) have been treated to date (median age 57 yrs [range 30-83]; 24 male, 16 female; 28 MF, 12 SS). Median numbers of prior treatment regimens are 5 (Grp 1) and 3 (Grp 2). For Grp 1, best overall response is PR for 3 pts, SD for 4 pts, PD for 3 pts. Other pts in Grp 1 and most pts in Grp 2 have had ≤2 months of follow-up. Of evaluable pts, 5 achieved a confirmed skin response including 1 complete skin response. Also, 1 pt with PD improved to PR after initial flaring of disease. Most common (>15%) AEs (all grades) include diarrhea, thrombocytopenia, fatigue, asthenia, hypertriglyceridaemia, dysgeusia, nausea and pruritus. Among 1578 ECGs analyzed, there has been no QTcF >500ms, one QTcF >480ms, and one QTcF >60ms increased from baseline. Conclusions: Based on activity as documented by improvement in composite score and skin responses, enrollment to Stage 2 for Grp 1 and Stage 1 for Grp 2 is ongoing. Preliminary safety data suggest panobinostat is generally well tolerated with no major safety concerns. Available efficacy and safety data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Merck, Novartis Oncology Novartis Pharmaceuticals
Table S2 from Gamma Secretase Inhibition by BMS-906024 Enhances Efficacy of Paclitaxel in Lung Adenocarcinoma (2023)

&lt;p&gt;Supplementary Table S2. Immunoblotting antibodies&lt;/p&gt;
Alternative splicing of interleukin-33 and type 2 inflammation in asthma (2016)

Type 2 inflammation occurs in a large subgroup of asthmatics, and novel cytokine-directed therapies are being developed to treat this population. In mouse models, interleukin-33 (IL-33) activates lung resident innate lymphoid type 2 cells (ILC2s) to initiate airway type 2 inflammation. In human asthma, which is chronic and difficult to model, the role of IL-33 and the target cells responsible for persistent type 2 inflammation remain undefined. Full-length IL-33 is a nuclear protein and may function as an "alarmin" during cell death, a process that is uncommon in chronic stable asthma. We demonstrate a previously unidentified mechanism of IL-33 activity that involves alternative transcript splicing, which may operate in stable asthma. In human airway epithelial cells, alternative splicing of the IL-33 transcript is consistently present, and the deletion of exons 3 and 4 (Δ exon 3,4) confers cytoplasmic localization and facilitates extracellular secretion, while retaining signaling capacity. In nonexacerbating asthmatics, the expression of Δ exon 3,4 is strongly associated with airway type 2 inflammation, whereas full-length IL-33 is not. To further define the extracellular role of IL-33 in stable asthma, we sought to determine the cellular targets of its activity. Comprehensive flow cytometry and RNA sequencing of sputum cells suggest basophils and mast cells, not ILC2s, are the cellular sources of type 2 cytokines in chronic asthma. We conclude that IL-33 isoforms activate basophils and mast cells to drive type 2 inflammation in chronic stable asthma, and novel IL-33 inhibitors will need to block all biologically active isoforms.
Identification of MIMO systems by input-output TS fuzzy models (2002)

A number of techniques have been introduced to construct fuzzy models from measured data. Most attention has been focused on multiple-input, single-output (MISO) systems. This article concentrates on the identification of multiple-input multiple-output (MIMO) systems by means of product-space fuzzy clustering with adaptive distance measure (the Gustafson-Kessel algorithm). The MIMO model is represented as a set of coupled input-output MISO models of the Takagi-Sugeno type. Knowledge of the physical structure can easily be incorporated in the structure of the model. Software implementation in the form of a MATLAB toolbox is briefly described. A simulation example of four cascaded tanks is given.
A dual beam total internal reflection fluorescence spectrometer for dynamic depth resolved measurements of biochemical liquid-solid interface binding reactions in opaque solvents (1991)

The initiation of many physiologically important biochemical reactions is dependent on the binding of a molecule or molecules from solution to an appropriate solid surface such as a cell membrane. The quantitative study of dynamic interactions of molecules in solution with immobilized surfaces under physiologically relevant conditions presents a significant physical problem. Traditionally these measurements have been performed by discontinuous, nonequilibrium assays that cannot accurately model in vivo reaction mechanisms. Total internal reflection fluorescence spectroscopy (TIRFS) is an analytical technique that is based on the excitation of fluorescence by means of an exponentially decaying surface energy wave called the evanescent wave. The limited ‘‘penetration depth’’ of the evanescent wave leads to excitation of fluorescent molecules at or near the surface. This phenomena makes TIRFS uniquely qualified for the dynamic fluorescence study of liquid-solid interface binding reactions. The instrument described here permits the powerful technique of TIRFS to be used by biomedical researchers in their investigation of biochemical interface reactions. The fully automated, menu driven instrument allows the real time dynamic measurement of binding of fluorescent-labeled molecules in solution at physiologically relevant concentrations to appropriate immobilized surfaces. The novel design of the total internal reflection element enables the study of binding from essentially opaque and highly scattering solutions such as whole blood. Measurements may be performed under static, stirred, or flow conditions. The presently described TIRFS instrument is capable of tracking a binding reaction with evanescent fields established by two identical reflecting light beams with different reflection angles. This instrumental feature allows the dynamic measurement not only of the primary binding event but also of fluctuations in the distance between the optical interface and the point of signal generation. Data from experiments involving fluorescently labeled molecules binding to cell monolayers as well as binding experiments performed in whole blood are shown to verify the instrument performance. Due to its extraordinary capabilities and its user friendly design, the developed TIRFS instrument opens up a large number of relevant but previously unmeasurable experimental systems for investigation.
Influence of Rock Wettability Alteration on Dielectric Dispersion Data (2017)

Abstract Rock surface wettability controls the fluid distribution in the pore space of the formation and thus, has an influence on its electrical properties. The variation of dielectric dispersion data with the variation of formation wettability is not well understood at present time. In this study, we investigated the influence of wettability alteration on dielectric dispersion data by laboratory experiments using different dielectric data interpretation models. We used a reflection open-ended coaxial probe to measure dielectric dispersion of a 1.5-in. core plug in a frequency range of 10 MHz to 1 GHz. The studied rock wettability was varied in a coreflooding apparatus during a drainage experiment. We used low-polarity oil for the initial drainage to preserve the rock in the water-wet state and added different concentrations of surface-active stearic acid to the oilflood during later drainage stages to change the sample wettability. The used dielectric data interpretation models, in addition to standard interpretation answers, solve for geometrical parameters of the fluids and pore space, which allow us to evaluate wettability variation. Our results showed a decrease in dielectric dispersion at the low-megahertz frequency range as we inject higher acid concentrations into the rock. This decrease in the dispersion also corresponds to an increase of the inverted MN-parameter, which characterizes water phase tortuosity. The results of the inversion, using the textural model, showed a consistent decrease of the depolarization factor of water inclusions as we increase the acid concentration in the injected oil. At the highest acid concentration used (1 wt%), this depolarization factor drops down to 0.36, which is very close to the depolarization factor of spherical inclusions. It follows from our findings that water films, which are characteristic for water-wet rocks, are transformed to more spherical droplets due to the change of wettability to oil-wet state. NMR T2 measurements on the same plug and contact angle measurements on reference samples of same lithology support our conclusions on wettability variation. This study illustrates how to interpret the rock wettability state from dielectric dispersion data based on geometrical models and how to use the inverted geometrical parameters as a wettability indicator.
ChemInform Abstract: Cyanation of Arenes via Iridium‐Catalyzed Borylation. (2010)

Abstract The first copper‐mediated oxidative cyanation of arylboronate esters [freshly prepared by borylation of the arenes (I)] or of arylboronic acids such as (IV) or (VI) is reported to proceed with great functional group tolerance.
Impact of Body Composition Indices on Ten-year Mortality After Revascularization of Complex Coronary Artery Disease (From the Syntax Extended Survival Trial) (2021)

Numerous studies have demonstrated a paradoxical association between higher baseline body mass index (BMI) and lower long-term mortality risk after coronary revascularization, known as the "obesity paradox", possibly relying on the single use of BMI. The current study is a post-hoc analysis of the SYNTAX Extended Survival (SYNTAXES) trial, which is the extended follow-up of the SYNTAX trial comparing percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) in patients with left-main coronary artery disease (LMCAD) or three-vessel disease (3VD). Patients were stratified according to baseline BMI and/or waist circumference (WC). Out of 1,800 patients, 1,799 (99.9%) and 1,587 (88.2%) had available baseline BMI and WC data, respectively. Of those, 1,327 (73.8%) patients had High BMI (≥25 kg/m<sup>2</sup>), whereas 705 (44.4%) patients had High WC (>102 cm for men or >88 cm for women). When stratified by both BMI and WC, 10-year mortality risk was significantly higher in patients with Low BMI/Low WC (adjusted hazard ratio [HR]: 1.65; 95% confidence interval [CI]: 1.09 to 2.51), Low BMI/ High WC (adjusted HR: 2.74; 95% CI: 1.12 to 6.69), or High BMI/High WC (adjusted HR: 1.59; 95% CI: 1.11 to 2.27) compared to those with High BMI/Low WC. In conclusion, the "obesity paradox" following coronary revascularization would be driven by low long-term mortality risk of the High BMI/Low WC group. Body composition should be assessed by the combination of BMI and WC in the appropriate evaluation of the long-term risk of obesity in patients with LMCAD or 3VD.
Designing Tyrosine-Derived Polycarbonate Polymers for Biodegradable Regenerative Type Neural Interface Capable of Neural Recording (2010)

Next-generation neuroprosthetic limbs will require a reliable long-term neural interface to residual nerves in the peripheral nervous system (PNS). To this end, we have developed novel biocompatible materials and a fabrication technique to create high site-count microelectrodes for stimulating and recording from regenerated peripheral nerves. Our electrodes are based on a biodegradable tyrosine-derived polycarbonate polymer system with suitable degradation and erosion properties and a fabrication technique for deployment of the polymer in a porous, degradable, regenerative, multiluminal, multielectrode conduit. The in vitro properties of the polymer and the electrode were tuned to retain mechanical strength for over 24 days and to completely degrade and erode within 220 days. The fabrication technique resulted in a multiluminal conduit with at least 10 functioning electrodes maintaining recording site impedance in the single-digit kOhm range. Additionally, in vivo results showed that neural signals could be recorded from these devices starting at four weeks postimplantation and that signal strength increased over time. We conclude that our biodegradable regenerative-type neural interface is a good candidate for chronic high fidelity recording electrodes for integration with regenerated peripheral nerves.
Catalytic Processing of High-Sulfur Fuels for Distributed Hydrogen Production (2010)

In this work, the development of a new on-demand hydrogen production technology is reported.In this process, a liquid hydrocarbon fuel (e.g., high-S diesel) is first catalytically pre-reformed to shorter chain gaseous hydrocarbons (predominantly, C 1 -C 3 ) before being directed to the steam reformer, where it is converted to syngas and then to high-purity hydrogen.In the pre-reformer, most sulfurous species present in the fuel are catalytically converted to H 2 S. In the desulfurization unit, H 2 S is scrubbed and converted to H 2 and elemental sulfur.Desulfurization of the pre-reformate gas is carried out in a special regenerative redox system, which includes Fe(II)/Fe(III)-containing aqueous phase scrubber coupled with an electrolyzer.The integrated pre-reformer/scrubber/electrolyzer unit operated successfully on high-S diesel fuel for more than 100 hours meeting the required desulfurization target of >95% sulfur removal.
Polymer Synthesis Using Hydrofluorocarbon Solvents. 1. Synthesis of Cross-Linked Polymers by Dispersion Polymerization in 1,1,1,2-Tetrafluoroethane (2002)

ADVERTISEMENT RETURN TO ISSUECommunication to the...Communication to the EditorNEXTPolymer Synthesis Using Hydrofluorocarbon Solvents. 1. Synthesis of Cross-Linked Polymers by Dispersion Polymerization in 1,1,1,2-TetrafluoroethaneColin D. Wood, Kazunobu Senoo, Cristina Martin, Jorge Cuellar, and Andrew I. CooperView Author Information Donnan and Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Crown Street, Liverpool L69 3BX, United Kingdom, and Departamento de Ingenieria Quimica, Universidad de Salamanca, Plaza de los Caídos 1-5, 37008 Salamanca, Spain Cite this: Macromolecules 2002, 35, 18, 6743–6746Publication Date (Web):July 24, 2002Publication History Received11 February 2002Revised22 May 2002Published online24 July 2002Published inissue 1 August 2002https://doi.org/10.1021/ma025506bCopyright © 2002 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views455Altmetric-Citations23LEARN 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 InReddit Read OnlinePDF (146 KB) Get e-AlertsSUBJECTS:Colloids,Organic compounds,Polymerization,Polymers,Solvents Get e-Alerts
PROLACTIN‐INHIBITING ACTIVITY OF GnRH ASSOCIATED PEPTIDE IN CULTURED HUMAN PITUITARY CELLS (1989)

The 56-amino-acid extension of GnRH in the human GnRH precursor (pHGnRH 14-69 or GAP) has previously been shown to inhibit PRL secretion from cultured rat pituitary cells. We have studied the effect of GAP and shorter sequences on prolactin secretion from human and rat pituitary cells. Bacterially synthesized GAP inhibited PRL secretion from human pituitary cells. At 10(-6) M GAP inhibition of prolactin release was 67.7% which was similar to that observed in rat pituitary cells (65.5%). A series of shorter peptide sequences (pHGnRH 14-26, pHGnRH 14-36, pHGnRH 14-37.NH2, pHGnRH 28-36, pHGnRH 38-49 and pHGnRH 51-66) which are potentially processed from GAP at basic amino acid residues had no effect on prolactin secretion from human or rat pituitary cells at doses up to 10(-5) M.
InGaN/GaN multi-quantum-well structures and GaN micromechanical structures on silicon-on-insulator substrates (2008)

We report growth of InGaN/GaN multi-quantum-wells (MQWs) structures and GaN layers on silicon-on-insulator (SOI) substrates by metalorganic chemical vapor deposition (MOCVD). The growth conditions were tuned to realize blue-green emission peaks centered around 420-495 nm from such MQWs on SOI. X-ray diffraction, atomic force microscopy, scanning electron microscopy, and photoluminescence techniques were used to characterize the MQWs. Using a combination of selective dry etching techniques, GaN micromechanical structures are demonstrated on silicon-on-insulator (SOI) substrates. The dry releasing technique employs a controlled gas phase pulse etching with non-plasma xenon difluoride (XeF2), which selectively etches the Si overlayer of SOI, thus undercutting the GaN material on top. The mechanical properties of these released microstructures are characterized by micro-Raman spectroscopy. Such approach to realize multi-color light-emitting InGaN/GaN MQW structures and GaN micromechanical structures on SOI substrates is suitable for the integration of InGaN/GaN-based optoelectronic structures on SOI-based micro-opto-electromechanical systems (MOEMS) and sensors.
The physical meaning of the Sobolev norm in error estimation (2004)

Error estimates for the moment method have been obtained in terms of Sobolev norms of the current solution. Motivated by the historical relationship of Sobolev norms to measures of energy, we conjecture that the Sobolev norm is equivalent to a norm induced by the forward scattering amplitude, and prove this for the case of TM-polarized fields incident on a PEC circular cylinder.
TCR Affinity Controls the Dynamics but Not the Functional Specification of the Antimycobacterial CD4+ T Cell Response (2021)

The quality of T cell responses depends on the lymphocytes' ability to undergo clonal expansion, acquire effector functions, and traffic to the site of infection. Although TCR signal strength is thought to dominantly shape the T cell response, by using TCR transgenic CD4<sup>+</sup> T cells with different peptide:MHC binding affinity, we reveal that TCR affinity does not control Th1 effector function acquisition or the functional output of individual effectors following mycobacterial infection in mice. Rather, TCR affinity calibrates the rate of cell division to synchronize the distinct processes of T cell proliferation, differentiation, and trafficking. By timing cell division-dependent IL-12R expression, TCR affinity controls when T cells become receptive to Th1-imprinting IL-12 signals, determining the emergence and magnitude of the Th1 effector pool. These findings reveal a distinct yet cooperative role for IL-12 and TCR binding affinity in Th1 differentiation and suggest that the temporal activation of clones with different TCR affinity is a major strategy to coordinate immune surveillance against persistent pathogens.
Addition of Benzylic and Allylic Organozinc and Grignard Reagents to Resin-Bound Imines To Provide α-Branched Secondary Amines Bearing a Wide Variety of Functional Groups. Utility in the Synthesis of β-3 Adrenergic Receptor Agonists (2004)

Benzylic and allylic organozinc and Grignard reagents have been added to resin-bound imines to provide alpha-branched secondary amines. Many functional groups, including electrophilic groups, were compatible with this methodology. Three modules--a resin-bound primary amine, an aromatic aldehyde, and the organometallic--were independently varied to produce a combinatorial library of alpha-branched secondary amines designed as beta-3 adrenergic receptor agonists.
Proteolysis induces increased binding affinity of the monocyte type II FcR for human IgG. (1989)

Abstract Human monocytes express two types of IgG FcR, Fc gamma RI and Fc gamma RII. These can be assayed by using indicator E sensitized by human IgG (EA-human IgG) or mouse IgG1, (EA-mouse IgG1), respectively. On mouse macrophages, Fc gamma RI is sensitive to trypsin, whereas Fc gamma RII is trypsin resistant. We studied the effects of the proteolytic enzymes pronase and trypsin on human monocyte Fc gamma R. Neither enzyme caused a decrease in rosetting mediated by monocyte Fc gamma RI. Human Fc gamma RII is polymorphic, and monocytes interact either strongly or weakly with mouse IgG1. The interaction of low responder monocytes with mouse IgG1 was dramatically increased (to the level exhibited by high responder monocytes) by protease treatment. The effects of proteases on Fc gamma RII were investigated in more detail by using monocytes from which Fc gamma RI was selectively modulated by using immobilized immune complexes. Proteolysis of such modulated monocytes induced an increased interaction with EA-human IgG. Fc gamma RII appears to mediate this interaction. This conclusion is supported by the observation that after proteolysis, the Fc gamma RII-mediated binding of EA-mouse IgG1 becomes susceptible to inhibition by (monomeric) human IgG. To quantify the effect of proteolytic enzymes on Fc gamma RII, we performed binding studies with cell line K562, that expresses only Fc gamma RII. A significant increase in Ka of Fc gamma RII for dimeric human IgG complexes was observed when K562 cells were treated with protease. To elucidate the mechanism of this enhancement of Ka by proteolysis, we performed immunoprecipitation studies. Neither m.w., nor IEF pattern of Fc gamma RII were influenced by proteolysis. Moreover, the expression of Fc gamma RII was not affected by proteolysis as evidenced by immunofluorescence studies and Scatchard analysis, and neither were Fc gamma RI or Fc gamma RIII induced. We conclude that proteolysis increases the affinity of Fc gamma RII for human IgG, and speculate that such a proteolysis-induced change may also occur in vivo, e.g., at inflammatory sites.