gebhart/patrepeval huggingface dataset:
Micro‐Flow Reaction Systems for Combinatorial Syntheses (2003)

Abstract Summary: Micro‐flow chemical processes, which are attracting great attention lately, offer more than the advantage of size. In microspaces, mass and heat transfer lengths are short, the specific interfacial area is large, and heat capacity is remarkably small compared with the situation in conventional scale reaction vessels. These characteristics make precise control of reaction conditions possible, and higher selectivity and conversion can be obtained. In some cases, reactions that are too dangerous to be carried out on a conventional scale can be safely done using micro‐flow reaction systems. Recently, some researchers have developed basic model systems for solution‐phase combinatorial synthesis by utilizing micro‐flow chemical processes. There are two types of combinatorial synthesis systems using micro‐flow chemical processes: parallel reaction systems and sequential reaction systems. In parallel reaction systems, components in starting libraries are simultaneously mixed in all possible combinations by using many micro reaction channels. In addition to needing as many pumps as the starting materials and as many reaction channels as members of the product library, complicated three‐dimensional piping is necessary to connect the pumps and the micro reaction channels. In sequential reaction systems, segments of starting materials are sequentially injected and reacted in a single micro reaction channel in all possible combinations. The latter systems are usually smaller than the former, however, relatively large fluid control devices are necessary in both of them, and improvement of micro‐fluid‐control devices is a critical issue for putting micro‐combinatorial‐synthesis systems to practical use. Parallel micro‐flow reaction system made up of multiple micro chemical chips for combinatorial 2 × 2 synthesis. magnified image Parallel micro‐flow reaction system made up of multiple micro chemical chips for combinatorial 2 × 2 synthesis.
Some reactions of polymers (1988)

Abstract Three topics are discussed. First, structural irregularities are considered in connection with polyformaldehyde,. poly(vinyl chloride) and poly(vinyl acetate) and with the stabilities of polymers in general. The second topic concerns the distribution of sites of reaction when polymers are modified chemically. The final section deals briefly with polymeric reagents, including some designed for photochemical systems.
A Rationally Designed A34R Mutant Oncolytic Poxvirus: Improved Efficacy in Peritoneal Carcinomatosis (2013)

Oncolytic poxviruses have demonstrated initial promising results in patients with cancer in clinical trials, yet further improvements are needed. It has been shown that a single point mutation in the A34R gene resulted in the production of more total progeny virus and more extracellular enveloped virus (EEV), a form that can be immune-evasive and with enhanced spread. We have genetically engineered a new oncolytic poxvirus (designated vA34R) by incorporating this mutated A34R gene into a viral backbone (vvDD) which was designed for tumor-selective replication. This rationally designed virus can evade neutralization from antipoxvirus antibodies and is highly cytotoxic to cancer cells. It demonstrates improved spread and increased replication within the peritoneal cavity resulting in improved antitumor effects in a peritoneal carcinomatosis (PC) model of MC38 colon cancer. Impressively, after carrier cell-mediated delivery in the preimmunized host, vA34R displayed high replication in tumor nodules yet low accumulation in normal tissues thus enhancing the therapeutic index leading to 70% long-term cures. These results demonstrate that vA34R gains an enhanced therapeutic index for PC via immune evasion, increased spread, and production of more progeny virus. Thus, vA34R may be a potent oncolytic virus (OV) for patients with PC, even after prior exposure to vaccinia virus (VV).
Familial Alzheimer Disease Presenilin-1 Mutations Alter the Active Site Conformation of γ-secretase (2012)

Presenilin-1 (PS1) is the catalytic subunit of γ-secretase, and mutations in this protein cause familial Alzheimer Disease (FAD). However, little is known about how these mutations affect the active site of γ-secretase. Here, we show that PS1 mutations alter the S2 subsite within the active site of γ-secretase using a multiple photoaffinity probe approach called "photophore walking." Moreover, we developed a unique in vitro assay with a biotinylated recombinant Notch1 substrate and demonstrated that PS1 FAD mutations directly and significantly reduced γ-secretase activity for Notch1 cleavage. Substitution of the Notch Cys-1752 residue, which interacts with the S2 subsite, with Val, Met, or Ile has little effect on wild-type PS1 but leads to more efficient substrates for mutant PS1s. This study indicates that alteration of this S2 subsite plays an important role in determining the activity and specificity of γ-secretase for APP and Notch1 processing, which provides structural basis and insights on how certain PS1 FAD mutations lead to AD pathogenesis.
AutoCAD Three Dimensional Drawing Technique and The Drawing of Engineering Drawing (2006)

Objective: To investigate a method of realizing solid modeling and Engineering drawing quickly in AutoCAD.Methods: Shape analysis of a complex model was made according to the feature of each part.A characteristic drawing was portrayed,and correspond solid was made,resulting in a 3D sculpt by combining and editing.Refine 2D、3D figure was distilled and 2D Engineering drawing and Axonometric Projection drawing was made.Conclusion: The method expressed the design intent accurately and completely,settling Engineering drawing.
Development and Validation of a New Technique for Ultrasound-Guided Stellate Ganglion Block (2009)

This study revealed that, at the C6 level, the cervical sympathetic trunk lies entirely subfascially. Subfascial injection via the lateral approach ensures reliable spread of a solution to the stellate ganglion.
Endothelial dysfunction and atherosclerosis | Dysfonctionnement endothelial et atherosclerose (1997)

Mammalian endothelium acts as a mediator in arterial and venous relaxation and contraction. Endothelium-dependant relaxation is due to endothelial release of powerful, non-prostanoid vasodilatory substances. The best known of these is the endothelial factor EDRF identified as nitrous oxide (NO). It is the end result of the metabolism of L-arginine by the NO synthetase of endothelial cells. In arterial smooth muscle, the relaxation induced by EDRF is explained by NO stimulation of soluble guanylate cyclase, leading to accumulation of GMPc (cyclic guanosine monophosphate). In some animal vessels and in human coronary arteries, endothelial cells release a substance which induces hyperpolarisation of the cell membrane (endothelial derived hyperpolarising factor, EDHF). Release of EDRF by the cell membrane may be mediated by G proteins sensitive to pertussis toxin (activation of the α2 adrenoreceptor, serotonin, platelet aggregation leukotrienes) or non- sensitive G proteins (adenosine-diphosphate (ADP), bradykinin). In animal blood vessels where the endothelium is regenerated and reperfused, and/or atherosclerotic, a selective loss of the mechanism of EDRF release is observed, sensitive to pertussis toxin, which favorises vasospasm, thrombosis and cellular proliferation. The available data on isolated or in situ human blood vessels concord with studies on isolated animal tissues. In addition to the relaxation factors, endothelial cells can also secreate contracting factors (endothelium derived contracting factors: EDCF): these include superoxide anions, endoparoxides, thromboxane A2 and endothelin. Animal studies indicate that the tendency to release EDCF is maintained or even increased in damaged vessels. The change from normally dominant EDRF release to EDCF release could play an important role in atherosclerosis.
Hypoxia, oxidative stress and rheumatoid arthritis (1995)

The synovial cavity has a negative pressure in health. When the joint is exercised, vascular patency is maintained, allowing for nutrition of the avascular cartilage. In rheumatoid synovitis, the situation is altered. The cavity pressure is raised and upon movement this pressure exceeds the capillary perfusion pressure, causing collapse of the blood vessels. This leads to the production of multiple episodes of 'hypoxic-reperfusion injury' generating reactive oxygen species (ROS). Such ROS oxidise: (a) IgG, inducing rheumatoid factor production (b) Hyaluronan, leading to hyaluronan fragmentation products which may alter immune function (c) Lipids, generating aldehydes which are toxic and may alter T cell/macrophage interactions (d) lipoproteins, leading to the production of monocyte chemotactic peptides Progressive hypoxia alters immune function, predominantly by calcium mediated pathways.
Jet Engine Control Using Ethernet with a BRAIN (Postprint) (2008)

Distributed control architectures are becoming increasingly prevalent as smart actuation and sensing technology becomes more cost-effective and realizable. However, achieving a distributed architecture that supports the increasing computational demands of engine control and prognostics strategies whilst surviving in the harsh on-engine environment remains to be a significant challenge. In this paper we present a Hybrid Ethernet based architecture that combines gigabit per second capacity for computational agreement and replication, with low complexity fault-tolerant Ethernet based braided ring segments for robust on-engine message distribution. To establish a rationale for the architecture the communications requirements for distributed control are briefly summarized and a discussion of current and emerging communications technologies is also presented. The BRAIN (Braided Ring Availability Integrity Network) dependability augmentation strategies are then presented to illustrate how the dependability issues of current communications may be mitigated.
Molecular Structure of 3,4-Difluorofuran-2,5-dione (Difluoromaleic Anhydride) As Determined by Electron Diffraction and Microwave Spectroscopy in the Gas Phase and by Theoretical Computations (1999)

The structure of 3,4-difluorofuran-2,5-dione has been determined experimentally in the gas phase by microwave spectroscopy using rotation constants derived from five isotopomers and by a combined analysis of electron-diffraction and microwave data. The geometry is planar with C2v symmetry. Structural parameters [distances (rα°)/pm, angles ∠α/deg, (1σ errors)] for the combined analysis are: r(CO) = 119.0(1); r(C−F) = 130.9(2); r(CC) = 133.2(3); r(O−C) = 139.3(1); r(C−C) = 148.5(2); ∠C−CC = 108.3(1); ∠CC−F = 129.9(1); ∠C−CO = 129.3(1); ∠C−O−C = 108.9(1); ∠O−C−C = 107.2(1). These values are in excellent agreement with those obtained in an ab initio study of the molecular geometry at the MP2/6-311+G*(2df) level of theory. The dipole moment of difluoromaleic anhydride has been determined experimentally by Stark-effect measurements to be 1.867(3) D.
Redirected T cell lysis in patients with metastatic uveal melanoma with gp100-directed TCR IMCgp100: Overall survival findings. (2018)

9521 Background: IMCgp100 is a bispecific biologic comprised of a soluble T cell receptor recognizing the gp100 antigen fused to a scFV anti-CD3 and redirects T cell lysis of melanoma cells expressing gp100. Safety and preliminary efficacy of IMCgp100 were assessed in a Ph 1/2 study in metastatic UM (mUM). Methods: HLA-A*0201+ pts with mUM were treated with QW dosing of IMCgp100 iv at Cycle 1, Day 1 (C1D1, 20 mcg) and C1D8 (30 mcg), followed by the escalated dose administered at C1D15 and beyond. Results: Pts with mUM (n = 19), elevated LDH (87%), liver metastases (100%), and median of 4 prior therapies (0 – 8) were treated across 4 doses (54 to 73 mcg) in Ph 1; 23 pts were treated in the Ph 2 RP2D (68 mcg) expansion cohort. Related AE included pruritus (90%), pyrexia and fatigue (84%), and hypotension (74%). Gr 3/4 related AE include AST elevation, erythema and hypotension (all, 16%). Ten of the 19 pts in Ph 1 were treated at or above the RP2D. Objective PR by RECIST in Ph 1 were observed in 2 pts and minor responses in 4 pts (6/19 responses); median duration of response was 30.6 wk. One year PFS rate by irRC was 66% (95% CI [39, 83]). One year OS rate in Ph 1 was 74% (95% CI [48, 88]). Median OS in this cohort has not been reached (median follow up of 15.9 mo). The PKPD relationship of exposure was modeled with extent and duration of lymphocyte trafficking. The EC50 for lymphocyte extravasation to the periphery was estimated at 1.4 ng/mL. At high doses, maximal trafficking of 50% was observed compared to baseline. The extent of lymphocyte trafficking is saturable, however the duration was dose dependent. The EC90 represents the dose of 70 mcg, supporting the RP2D. In the full cohort (n = 42), rash of Gr ≥2 within the first 3 weeks of dosing is associated with prolonged OS when compared to pts with mild (G1) or no occurrence of rash (HR 0.122, 95% CI [0.03, 0.45], p = 0.0015). Conclusions: IMCgp100 is tolerable with the intra-patient escalation dosing regimen and leads to prolonged OS. A potential association of prolonged OS with rash severity was observed. PKPD modeling demonstrates a relationship between lymphocyte trafficking and exposure to IMCgp100. Pivotal trials in the setting of metastatic UM continue to enroll (NCT03070392, NCT02570308). Clinical trial information: NCT02570308.
The Changing Pattern of Acute Kidney Injury: From One to Multiple Organ Failure (2010)

Acute kidney injury (AKI) is frequently encountered in the intensive care unit, and from its inception, morbidity and mortality increase in these patients compared to those without AKI. Despite numerous clinical trials and newer pharmacological agents, very little progress has been made to reduce the deaths that occur in this population. An important emerging concept is that AKI does not occur in isolation and it frequently involves other organs. Clinical conditions such as shock, trauma, and sepsis lead to an increase in fluid volume, cytokines/chemokines, uremic toxins and other soluble mediators that are known to affect distant organs. This critical loss of balance of these mediators appears to be due both to a reduction in clearance and increase in production as demonstrated by experimental studies of bilateral nephrectomy and ischemia-reperfusion, respectively. The evidence and mechanisms for distant organ injury following AKI will be discussed.
Closed-loop class E transcutaneous power and data link for MicroImplants (1992)

Magnetic transcutaneous coupling is frequently used for power and data transfer to implanted electronic devices. The proposed development of MicroImplants, small enough to be injected through a hypodermic needle suggest the need for a high-efficiency magnetic transcutaneous link. This paper describes the use of a multifrequency transmitter coil driver based upon the Class E topology. The development of a "high-Q approximation" which simplifies the design procedure is presented. A closed-loop controller to compensate for transmitter and receiver variations, and a method of data modulation, using synchronous frequency shifting are described. The closed-loop Class E circuit shows great promise, especially for circuits with unusually low coefficients of coupling. Currents of several amperes, at radio frequencies, can easily and efficiently be obtained.
Integration of Optimized Modulation Filter Sets Into Deep Neural Networks for Automatic Speech Recognition (2016)

Inspired by physiological studies on the human auditory system and by results from psychoacoustics, an amplitude modulation filter bank (AMFB) has been developed and successfully applied to feature extraction for automatic speech recognition (ASR) in earlier work. Here, we address the question as to which amplitude modulation (AM) frequency decomposition leads to optimal ASR performance by proposing a parameterized functional relationship between modulation center frequency and modulation bandwidth. Word error rates (WERs) of ASR experiments with 1551 different AMFBs are systematically evaluated and compared, resulting in the identification of a comparatively narrow range of optimal modulation frequency to modulation bandwidth characteristics. To integrate modulation processing with deep neural network (DNN) acoustic modeling, we propose merging of modulation filter coefficients with DNN weights prior to a final training step and an improved mean-variance normalization scheme for AMFBs. These modifications are shown to result in further reduction of WERs and are indicative of the proposed system's improved generalization ability, when compared across corpora of 100-960 h of data with mismatched training and test conditions. Analysis of DNN-learned temporal AM filtering properties is carried out and implications for the relevance of different modulation regions as well as the relation to psychoacoustic findings are discussed. ASR experiments with the proposed system demonstrate a high degree of robustness against extrinsic acoustic distortions, resulting in, e.g., an average WER of 9.79% on the Aurora-4 task.
Strong Organic Acids as Efficient Catalysts for the Chloromethylation of <i>m</i>-Xylene. The Synthesis of 1,3-bis(Chloromethyl)-4,6-dimethylbenzene (2009)

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionORIGINAL ARTICLEThis notice is a correctionStrong Organic Acids as Efficient Catalysts for the Chloromethylation of m-Xylene. The Synthesis of 1,3-bis(Chloromethyl)-4,6-dimethylbenzeneTohru Kishida, Noboru Ieda, Takayoshi Yamauchi, Kenichi Komura, and Yoshihiro Sugi*Cite this: Ind. Eng. Chem. Res. 2009, 48, 11, 5566Publication Date (Web):May 11, 2009Publication History Received2 May 2009Published online11 May 2009Published inissue 3 June 2009https://pubs.acs.org/doi/10.1021/ie900348nhttps://doi.org/10.1021/ie900348ncorrectionACS PublicationsCopyright © 2009 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views459Altmetric-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 PDF (497 KB) Get e-AlertscloseSUBJECTS:Catalysts,Organic acids,Organic reactions,Organic synthesis Get e-Alerts
Complement activation and the toxicity of stroma-free hemoglobin solutions in primates. (1988)

The toxicity of hemoglobin solutions was studied in the context of their ability to activate serum complement (C). Three bovine polymerized hemoglobin solutions (BPHSs) with different degrees of purity were used for experiments in vitro and in vivo. BPHS-1 contained bacterial endotoxins (E) (5 EU/ml) and stromal phospholipids (PLs) (1.2 mg/dl), BPHS-2 contained only PLs (2.0 mg/dl), while BPHS-3 was completely free of both contaminants. C-activation was studied by the direct measurement of C3a, C4a, and C5a des Arg fragments, using commercially available RIA kits. During 1 hour of incubation with fresh monkey plasma, BPHS-1 and -2 activated both pathways of C, while BPHS-3 caused no activation of any factor. In vivo, Hb solutions were used to replace one-third of blood volume in three groups of six Coebus monkeys each, while fresh homologous plasma was used in a control group of four animals. Impure solutions activated the alternative pathway of C and caused significant reactions of the circulating blood (thrombocytopenia, leukopenia, and disseminated intravascular coagulation) associated with multiorgan dysfunction (cardiac arrhythmias, hypoxemia, reduction of renal clearance of endogenous creatinine, and elevation of liver enzyme SGPT). The pure solution neither activated C nor caused any reaction in the circulating blood. However, it caused a moderate degree of direct tissue injury, evidenced by transient reduction of creatinine clearance and elevation of SGPT. These observations suggest that impure and pure Hb solutions carry separate mechanisms of toxicity. Complement, activated by toxic impurities, plays an active role in the toxicity of impure solutions. C-activation in vitro could be used as a screening test of biocompatibility.
A very-small-sized reversed-phase hybrid ring (2002)

This paper presents a design method of a reversed-phase hybrid ring based on the equivalent admittance approach, and successfully designs a very miniature hybrid ring with a 0.28-wavelength or less circumference by adding shunt capacitors at each port as a matching element. The present hybrid has a broad bandwidth comparable to the regular reversed-phase hybrid ring. The validity and usefulness of the design are demonstrated by electromagnetic simulation for a uniplanar hybrid.
Parametric tip model and force–distance relation for Hamaker constant determination from atomic force microscopy (1996)

Hamaker constants and dispersion forces interactions of materials are of increasing interest and the advent of atomic force microscopy (AFM) force measurements represents a new opportunity for quantitative studies of these interactions. A critical problem is the determination of a force–distance relation for realistic AFM probes. Due to the inadequacies of existing power-law sphere–plane models to describe the probe–sample system, we present a new parametric tip force–distance relation (PT/FDR). A surface integration method is developed to compute the interactions between arbitrarily shaped bodies. The method is based on the Hamaker pairwise integration in a continuous fashion, reducing the six-dimensional integration to a four-dimensional scheme. With this method, the PT/FDR is obtained and a nonlinear fitting routine is used to extract the model parameters and the Hamaker constant from AFM force–distance data. From the sensitivity analysis of the fitting of synthesized AFM force–distance data, one finds that, for large tip radius (compared to separation), the force is proportional to the product of the Hamaker constant and tip radius. Unique determination of the Hamaker constant can be achieved if a small radius tip is used in the AFM scan. By fitting to literature data, the effectiveness of the PT/FDR is shown.