gebhart/patrepeval huggingface dataset:
Surface-Induced First-Order Transition in Athermal Polymer-Nanoparticle Blends (2007)

We investigate the phase behavior of athermal polymer-nanoparticle blends near a substrate. We apply a recent fluids density functional theory of Tripathi and Chapman to a simple model of the blend as a mixture of hard spheres and freely jointed hard chains, near a hard wall. We find that there is a first-order phase transition in which the nanoparticles expel the polymer from the surface to form a monolayer. The nanoparticle transition density depends on the length of the polymer and the overall bulk density of the system. The effect is due both to packing entropy effects related to size asymmetry between the components and to the polymer configurational entropy. The simplicity of the system allows us to understand the so-called "entropic-push" observed in experiments.
World's First Thermoelectric Generator Made of Tailored Carbon Allotropes (2020)

Carbon and carbon‐based compounds are today's mostly used sources of energy. By burning them, their chemically stored energy can be transformed to mechanical energy and further on to electrical energy. These transformation steps entail huge thermal losses. Thermoelectric generators (TEGs) are devices that allow the direct conversion of thermal gradients into electrical energy through a smart combination of n‐ and p‐conducting materials and are therefore an appealing approach to tackle thermal losses. However, the materials in today's TEGs, e.g., Bi 2 Te 3 , show limited thermal stability and often are toxic or not abundantly available which only allow for niche applications like military and aerospace equipment. Herein, the fabrication of the first, fully functional all‐carbon TEG is shown. The used carbon materials, made by chemical vapor deposition (CVD) processes, are both, nontoxic and abundant, and potentially paves the way for the large‐scale use of TEGs. Not only the thermal losses of conventional combustion processes but also thermal gradients established by solar thermal systems are potential fields of application. The assay is anticipated to spark further interest in carbon‐based thermoelectric materials. Such materials can be produced on a large scale and combined to a fully functional thermoelectric device.
Effective Stimulation of Multilateral Completions in the James Lime Formation Achieved by Controlled Individual Placement of Numerous Hydraulic Fractures (2003)

Abstract Fracture stimulation of long openhole horizontal wells is known to be extremely difficult when conventional stimulation methods are used. The level of difficulty increases significantly when multiple fractures are to be placed in openhole multilateral wells. A relatively new hydrajetfracturing process may be one of only a few methods that can be used to fracture-stimulate multilateral wells effectively without the use of sealing devices. This process is unique because many fractures can be placed at precise locations as desired. After reviewing the recent effectiveness of the process in single-wellbore openhole completions, an operating company elected to evaluate this stimulation method for multilateral wells. This paper describes implementation of this new technology in three multilateral wells drilled through the James Lime formation in the east Texas/west Louisiana area. Past experiences of fracture acidizing James Lime wells with hydrochloric acid (HCl) indicate that this process can be successful as a stimulation process. However, the effectiveness of fracturing these types of wells with sand or proppants was not proven. The three wells were treated using three fracture-stimulation approaches: (1) multistage combining two stages each of HCl acid and proppantfracturing stimulation, (2) multistage with only a single acid stage, and (3) proppant-fracturing stimulation alone. Well production responses resulting from these three approaches are evaluated in this paper.
ChemInform Abstract: BIOMIMETIC SYNTHESES OF THE BISINDOLE ALKALOIDS VILLALSTONINE AND ALSTONISIDINE (1973)

Abstract Villalstonin (III) bzw. Alstonisidin (V) werden aus Macrolin (I) und Pleiocarpamin (II) bzw. Quebrachidin (IV) dargestellt.
Phase II study of nivolumab and salvage nivolumab + ipilimumab in treatment-naïve patients (pts) with advanced renal cell carcinoma (RCC) (HCRN GU16-260). (2020)

5006 Background: Nivolumab (nivo) is FDA approved for pts with VEGFR TKI-resistant RCC and the nivo + ipilimumab (nivo/ipi) combination is FDA approved for treatment naïve pts with IMDC intermediate and poor risk RCC. Little information is available on the efficacy and toxicity of nivo monotherapy in treatment naïve RCC or the efficacy of nivo/ipi salvage therapy in pts with tumors resistant to initial nivo monotherapy. Methods: Eligible pts with treatment naïve RCC received nivo 240mg IV q2 wk x 6 doses followed by 360mg IV q3 wk x 4 doses followed by 480 mg q4 wk until progressive disease (PD), toxicity, or completion of 96 wks of treatment (Part A). Pts with PD prior to or stable disease (SD) at 48 wks (pSD) were potentially eligible to receive salvage nivo (3mg/kg) /ipi (1 mg/kg) q3 wk x 4 doses followed by q4 wk nivo maintenance for up to 48 wks (Part B). All pts were required to submit tissue from a metastatic lesion obtained within 12 months (mo) prior to study entry and prior to Part B. Pathology specimens will be analyzed by immunohistochemistry, quantitative immunofluorescence, WES and RNAseq with results linked to clinical outcome. Results: 123 pts with clear cell(cc) RCC were enrolled between 5/2017 and 12/2019 at 12 participating HCRN sites. Median age 65 (range 32-86 years); 72% male. IMDC favorable 30 (25%), intermediate 79 (65%) and poor risk 12 (10%). 22 (18%) had a component of sarcomatoid histology (SARC). 117 pts are currently evaluable for response. RECIST defined ORR was: 34 (29.3%)[CR 5 (4.3%), PR 29 (24.8%)], SD 47 (40.2%), PD 36 (30.7%). ORR by irRECIST was 35%. ORR by IMDC was: favorable 12/29 (41.4%), intermediate/poor 22/87 (25.3%) and for SARC 6/22 (27.3%). Median DOR is 13.8 (10.9, NA) mo. Median PFS is 7.4 (5.5, 10.9) mo. 110 pts remain alive. 60 pts (54 PD, 6 pSD) to date were potentially eligible for salvage nivo/ipi (Part B), but 28 did not enroll due to symptomatic PD (17), grade 3-4 toxicity on nivo (8), other (3). 27 of 32 Part B pts are currently evaluable for efficacy and 30 for toxicity. Best response to nivo/ipi was PR (11%), SD (30%), PD (59%). ORR by irRECIST was 19%. Grade 3-5 Treatment-related AEs (TrAE) were seen in 35/123 (28)% on nivo with 1 death due to respiratory failure. Grade 3-4 TrAE were seen in 10/30 (33%) on nivo/ipi with 0 deaths. Correlative studies are pending. Conclusions: Nivo monotherapy is active in treatment naïve ccRCC across all IMDC groups. Toxicity is consistent with prior nivo studies. Salvage treatment with nivo/ipi after nivo monotherapy was feasible in 53% of pts with PD/pSD, with 11% responding. Clinical trial information: NCT03117309 .
A Kinetic and Conformational Study on the Interaction of Tetrahydropteridines with Tyrosine Hydroxylase (2000)

Tetrahydropterins are obligatory cofactors for tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis. A series of synthetic analogues of 6(R)-L-erythro-5,6,7, 8-tetrahydrobiopterin (BH(4)) with different substituents in positions C2, N3, C4, N5, C6, C7, and N8 on the ring were used as active site probes for recombinant human TH. The enzyme tolerates rather bulky substituents at C6, as seen by the catalytic efficiency (V(max)/K(m)) and the coupling efficiency (mol of L-DOPA produced/mol of tetrahydropterin oxidized) of the cofactors. Substitutions at C2, C4, N5, and N8 abolish the cofactor activity of the pterin analogues. Molecular docking of BH(4) into the crystal structure of the catalytic domain of ligand-free rat TH results in complexes in which the pteridine ring pi-stacks with Phe300 and the N3 and the amino group at C2 hydrogen bonds with Glu332. The pteridine ring also establishes interactions with Leu294 and Gln310. The distance between C4a in the pteridines and the active site iron was 4.2 +/- 0.5 A for the ensemble of docked conformers. Docking of BH(4) analogues into TH also shows that the most bulky substituents at C6 can be well-accommodated within the large hydrophobic pocket surrounded by Ala297, Ser368, Tyr371, and Trp372, without altering the positioning of the ring. The pterin ring of 7-BH(4) shows proper stacking with Phe300, but the distance between the C4a and the active site iron is 0.6 A longer than for bound BH(4), a finding that may be related to the high degree of uncoupling observed for 7-BH(4).
Alanine 101 and alanine 110 of the alpha subunit of Pseudomonas stutzeri OX1 toluene‐o‐xylene monooxygenase influence the regiospecific oxidation of aromatics (2005)

Abstract Saturation mutagenesis was used to generate 10 mutants of toluene‐ o ‐xylene monooxygenase (ToMO) at alpha subunit (TouA) positions A101 and A110: A101G, A101I, A101M, A101VE, A101V, A110G, A110C, A110S, A110P, and A110T; by testing the substrates toluene, o‐ cresol, m‐ cresol, p‐ cresol, phenol, naphthalene, o‐ methoxyphenol, m‐ methoxyphenol, p‐ methoxyphenol, o‐ xylene, and nitrobenzene, these positions were found to influence the regiospecific oxidation of aromatics. For example, compared to wild‐type ToMO, TouA variant A101V produced threefold more 3‐methoxycatechol from m ‐methoxyphenol as well as produced methylhydroquinone from o‐ cresol whereas wild‐type ToMO did not. Similarly, variant A110C synthesized 1.8‐fold more o ‐cresol from toluene and 1.8‐fold more 3‐methoxycatechol from m‐ methoxyphenol, and variant A110G synthesized more m‐ nitrophenol and twofold less p ‐nitrophenol from nitrobenzene. The A101V and A110C mutations did not affect the rate of reaction with the natural substrate toluene, so the variants had high activity. This is the first report that these or analogous residues influence the catalysis with this class of enzymes. Wild‐type ToMO was found to oxidize o ‐methoxyphenol to methoxyhydroquinone (60%) and 4‐methoxyresorcinol (40%), m ‐methoxyphenol to 4‐methoxycatechol (96%) and 3‐methoxycatechol (4%), and p ‐methoxyphenol to 4‐methoxycatechol (100%). © 2005 Wiley Periodicals, Inc.
ChemInform Abstract: AN ENANTIODIRECTED CYCLOPENTENONE ANNULATION. SYNTHESIS OF A USEFUL BUILDING BLOCK FOR CONDENSED CYCLOPENTANOID NATURAL PRODUCTS (1980)

Abstract Der durch eine Pd(O)‐katalysierte C‐Alkylierung des Methylcyclopentadions (I) mit 3‐Acetoxy‐2‐ethoxy‐propen‐( 1) in hoher Ausb. dargestellte Enolether (III) wird in das Phosphoniumbromid (V) übergeführt; das aus diesem Bromid in wäßrigem K 2 CO 3 entstehende Ylid läßt sich unter sehr milden Bedingungen zum bicyclischen Endion (VI) cyclisieren.
In vivo and in vitro Modulation of Immune Stimulatory Capacity of Primary Dendritic Cells by Adenovirus-Mediated Gene Transduction (1998)

Dendritic cells (DCs) are potent antigen-presenting cells which are key leukocytes in the initiation of cell-mediated organ graft rejection, antiviral immunity, and antitumor responses. In this study we demonstrate that genetic modification of primary human and mouse DCs by adenoviral gene transfer is an effective means of induction and modulation of antigen presentation by DCs. An adenovirus vector (AdLacZ) was used to express an intracellular model antigen beta-galactosidase (beta-gal) in DCs. Our results show that 30-40% of precursor dendritic cells (PDCs) derived from human umbilical cord blood and circulating mature blood DCs express high levels beta-galactosidase (beta-gal) after infection with AdLacZ with no cytopathic effect observed. In vitro, AdLacZ transduced PDCs and DCs demonstrated a 10- to 20-fold higher mixed lymphocyte reaction (MLR) stimulatory capacity as compared to that of monocytes. In vivo, immunization with AdLacZ transduced mouse DCs resulted in more potent cytotoxic T lymphocyte (CTL) responses against the predicted H-2 restricted beta-gal epitope as compared to CTL responses obtained by beta-gal peptide pulsed DCs. Modulations of the MLR stimulatory capacity of DCs were examined by expression of mouse B7 and CTLA-4Ig. The results show that expression of mouse B7 by a recombinant adenoviral vector (Ad7) significantly enhances the MLR stimulatory capacity of human DCs. In contrast, expression of CTLA-4Ig (AdCTLA-4Ig) reduces the MLR stimulatory capacity of the transduced cells. We conclude that recombinant adenovirus can readily be used for genetic modulation DC-induced immune responses in vivo and in vitro. DCs targeted for induction of specific antigen responses or for modulation of the immune stimulatory capacity may have a potential use in the control of transplantation rejection or viral infections.
Correlative Anatomy for the Invasive Electrophysiologist: Outflow Tract and Supravalvar Arrhythmia (2009)

Radiofrequency ablation in the outflow tract and great arteries is increasingly performed to treat a variety of symptomatic cardiac arrhythmias. The regional anatomy of these structures is among the most complex of those encountered by cardiac electrophysiologists. An exact appreciation of the relationships between these overlapping structures and their proximity to the coronary arterial and conduction system is essential for rational, safe, and effective ablation for these arrhythmias. A supravalvar portion of the aorta is a unique site for arrhythmia origin where the arrhythmogenic substrate for atrial arrhythmias, ventricular arrhythmias, and accessory pathways may all be located. Discussed in this review are the main principles of outflow tract and supravalvar arrhythmia, and these are correlated with fluoroscopy, electrograms, and electrocardiography that help guide the invasive electrophysiologist.
Cancer and Leukemia Group B 90203 (Alliance): Radical Prostatectomy With or Without Neoadjuvant Chemohormonal Therapy in Localized, High-Risk Prostate Cancer (2020)

The primary study end point, 3-year BPFS, was not met. Although some improvement was seen in secondary end points, any potential benefit must be weighed against toxicity. Our data do not support the routine use of neoadjuvant CHT and RP in patients with clinically localized, high-risk PC at this time.
Antisense therapy in a rat model of Alexander disease reverses GFAP pathology, white matter deficits, and motor impairment (2021)

Alexander disease (AxD) is a devastating leukodystrophy caused by gain-of-function mutations in <i>GFAP</i>, and the only available treatments are supportive. Recent advances in antisense oligonucleotide (ASO) therapy have demonstrated that transcript targeting can be a successful strategy for human neurodegenerative diseases amenable to this approach. We have previously used mouse models of AxD to show that <i>Gfap</i>-targeted ASO suppresses protein accumulation and reverses pathology; however, the mice have a mild phenotype with no apparent leukodystrophy or overt clinical features and are therefore limited for assessing functional outcomes. In this report, we introduce a rat model of AxD that exhibits hallmark pathology with GFAP aggregation in the form of Rosenthal fibers, widespread astrogliosis, and white matter deficits. These animals develop normally during the first postnatal weeks but fail to thrive after weaning and develop severe motor deficits as they mature, with about 14% dying of unknown cause between 6 and 12 weeks of age. In this model, a single treatment with <i>Gfap</i>-targeted ASO provides long-lasting suppression, reverses GFAP pathology, and, depending on age of treatment, prevents or mitigates white matter deficits and motor impairment. In this report, we characterize an improved animal model of AxD with myelin pathology and motor impairment, recapitulating prominent features of the human disease, and use this model to show that ASO therapy has the potential to not only prevent but also reverse many aspects of disease.
Synthesis of 4-Chloro-5-cyano-2-dimethylamino-6H-1,3-oxazin-6-one from the Salts of Alkyl Dicyanoacetates and Some of Its Reactions (1990)

The salts of alkyl dicyanoacetates and methyl 3-amino-3-chloro-2-cyanoacrylate react in chloroform with N-(dichloromethylene)dimethylammonium chloride to give 4-chloro-5-cyano-2-dimethyl- amino-6H,3-oxazin-6-one. The chloro atom of this compound can be easily substituted by alcohols or amines in good yield.
Etude par dynamique moléculaire de la réactivité des espèces neutres principales d’un plasma Ar/CH4 (2021)

National audience
Reply: The Use of Absorbable Mesh in Implant-Based Breast Reconstruction: A 7-Year Review (2021)

We would like to thank Drs. Li and Mu for their letter and interest in this study.1 Mean follow-up time was 37.4 months. Greater than 30 percent of patients in the database were followed for 60 months or longer. This supports the conclusion regarding long-term result stability. We appreciate the suggestion to utilize more mesh in unilateral cases, rather than discard the excess mesh. However, we believe that minimizing the amount of implanted foreign material is beneficial. We did not have any cases of delayed mastectomy flap ischemia in this review, indicating that the hydrolysis of the mesh does not affect vascular flow to the mastectomy flap. We apologize for the minor mathematical error and appreciate it being recognized. DISCLOSURE Dr. Faulkner has no financial interests to disclose. Dr. Austen is the founder or Cytrellis Biosystems and AuraGen Aesthetics, but has no financial interest relevant to the content of this communication. Heather R. Faulkner, M.D., M.P.H.William G. Austen, Jr., M.D.Division of Plastic and Reconstructive SurgeryMassachusetts General HospitalBoston, Mass.
P0946OXIDATIVE STRESS AND HEME METABOLISM IN RED BLOOD CELLS FROM HEMODIALYSIS PATIENTS (2020)

Abstract Background and Aims We have previously described that indoxyl sulfate promotes red blood cells (RBC) ROS generation through organic anion transporter 2 as well as NADPH oxidase activity-dependent and GSH-independent mechanisms (Dias et al., 2018). However, there is little information regarding pathways of antioxidant balance to protect RBC from extensive oxidative stress that occurs during hemodialysis (HD). Intracellular free heme is degraded by Heme Oxygenase 1 (HO-1), which is regarded as the major cytoprotective enzyme (Maines, 1988; Gozzelino et al., 2010). In the current study, we assessed HO-1 activity and ROS production in RBC from healthy subjects and hemodialysis (HD) patients before and after HD. Method Blood was drawn from 6 healthy individuals (CON-RBC) and 6 HD patients (HD-RBC) before (pre/HD-RBC) and after high flux HD (post/HD-RBC). Isolated RBC were stained with DCFH-DA (Abcam) for ROS measurements. To quantify HO-1, RBC were incubated with anti-HO-1 antibody (Abcam) and m-IgGκ BP-CFL 488 (Santa Cruz Biotechnology) as a secondary antibody. Samples were analyzed by flow cytometry. Results Our results show a 4-fold increase in ROS levels in pre/HD-RBC compared to CON-RBC. ROS levels were even further increased by 1.65-fold after HD treatment in post/HD-RBC (Figure 1). Both pre/HD-RBC and post/HD-RBC showed a similarly significant increase of 3.3-fold in HO-1 compared to CON-RBC. (Figure 1). Conclusion High levels of HO-1 may represent a defense against oxidative stress that occurs in ESKD and particularly during the HD session. Further research is needed to evaluate whether HO-1 overexpression could accelerate heme degradation and contribute to renal anemia.
The Integrated Hypersonic Aeromechanics Tool (IHAT), Build 4 (2004)

The IHAT System is a tool suite for configuration optimization of high speed airbreathing flight vehicles currently under development. The focus of the System is on high speed tactical weapons (Mach 4-8 regime) with relatively long range. The hypersonic flight regime of the weapons results in unique requirements for the analysis, design, and optimization tool suite. For highly integrated hypersonic configurations, the interaction between disciplines becomes more important as, for example, the structure becomes more tightly integrated with the propulsion system. Due to the highly integrated nature of the configurations, traditional stovepipe design methods have not been successful in defining a viable configuration for this type of mission. It is expected that an integrated system-level approach to the analysis and optimization of the entire vehicle will allow interactions between the disciplines to be understood and exploited. This will allow for the development of viable long range hypersonic vehicles. The IHAT System is an effort to provide such an integrated analysis/optimization toolset. IHAT is being developed by a government/ industry team using multiple, incremental builds. This paper discusses the IHAT development process and describes the capabilities of Build 4 of the IHAT System, which includes Modules for addressing the disciplines of Aerodynamics, Propulsion, Trajectory, Thermal, Structural, Stability & Control, Sensors, Lethality, and Cost Index.
A new switched-capacitor dc-dc converter with improved line and load regulations (2003)

A new switched-capacitor (SC) step-down dc-dc converter is presented. It exhibits smaller size, lighter weight and stronger regulation capabilities than previous SC converters of the same power ratings. Its operation principles and analysis are described in detail and an accurate as well as an approximate expression governing input, output and circuit parameters is presented. A discussion on the achievable conversion efficiency is also given. A 12 V/5 V prototype based on the proposed topology has been implemented and tested. Theoretical prediction of its regulation and efficiency is verified experimentally.
Dopamine receptors in the proximal tubule of the rabbit (1984)

Our laboratory has characterized dopamine receptors in glomeruli and tubular homogenates. Since the heterogeneity of kidney homogenates limits the interpretation of these studies, the [3H]haloperidol binding site and adenylate cyclase sensitivity to dopamine were studied in the isolated proximal convoluted tubule and pars recta of the rabbit kidney. [3H]Haloperidol binding sites were saturable, stereoselective, and of high affinity. The apparent dissociation constant was 31.5 X 10(-9) M (+/- 8.5) and the maximum receptor density was 0.31 X 10(-15) M (+/- 0.08) per millimeter. In pars recta specific binding was 53% of total [3H]-haloperidol binding. Dopamine stimulated adenylate cyclase activity in a dose-related manner, which was inhibited by cis-flupenthixol but not by trans-flupenthixol or (-)-propranolol. Moreover, the stimulatory effect of the dopamine 1 (D1) agonist SKF 82526 on adenylate cyclase activity was blocked by the D1 antagonist SCH 23390. Dopamine receptors in the proximal convoluted tubule appear to be of the D1 subtype since they are linked to stimulation of adenylate cyclase. This is further substantiated by the stereoselectivity for (+)-sulpiride (a D1 antagonist), which had a greater affinity for the [3H]haloperidol binding site than (-)-sulpiride (a D2 antagonist).
From the good old times of nostalgia to modern hype, (2009)

International audience
INCREASED INTESTINAL PERMEABILITY IS RELATED TO GUT BACTERIAL DYSBIOSIS AND BEHAVIORAL MARKERS OF ADDICTION SEVERITY IN ALCOHOL-DEPENDENT SUBJECTS (2015)

Leclercq, Sophie1; Matamoros, S.2; Cani, P. D.2; Francois, J.3; Starkel, P.4; Windey, K.5; Tremaroli, V.6; Backhed, F.6; Verbeke, K.5; de Timary, P.1; Delzenne, N. M.2 Author Information
Uniqueness of the SVM Solution (1999)

We give necessary and sufficient conditions for uniqueness of the support vector solution for the problems of pattern recognition and regression estimation, for a general class of cost functions. We show that if the solution is not unique, all support vectors are necessarily at bound, and we give some simple examples of non-unique solutions. We note that uniqueness of the primal (dual) solution does not necessarily imply uniqueness of the dual (primal) solution. We show how to compute the threshold b when the solution is unique, but when all support vectors are at bound, in which case the usual method for determining b does not work.