gebhart/patrepeval huggingface dataset:
Grain Boundary Segregation Behavior and Thermodynamic Analysis Based on CALPHAD Method for B Added High Carbon Steel (2023)

The segregation behaviors on the prior austenite grain boundaries for the B added-high C case hardening steel (Fe-0.82C-0.22Si-0.86Mn-0.02P-1.1Cr-0.21Mo-0.005B (mass％)) were evaluated by three-dimensional atom probe (3DAP). The results revealed the intense segregation of C, Mo, Cr, and B on the grain boundaries. In contrast, it was confirmed that the segregation of P known as a strong segregation element for steel was suppressed. The thermodynamic analysis based on the parallel tangent law by McLean-Hillert was carried out in order to validate the segregation of each element. To evaluate the chemical potentials taking the interaction with multiple elements into account, the CALPHAD (CALculation of PHAse Diagram) method was employed, where liquid phase was adopted to estimate the Gibbs free energy of grain boundaries. The calculation results represented the segregation tendencies obtained from 3DAP. Detailed investigations of the interaction effects of C, B, and Mo on the other elements were also conducted. The results showed the suppression of the P segregation by increasing B content. Therefore, the efficiency of the segregation prediction method that implemented the CALPHAD method for the B added high C steel was demonstrated.
On the relocation of the amino functionality to the ethyl side chain in aminoglutethimide: Synthesis and aromatase‐inhibitory activity of 3‐(2′‐N,N‐diethyl‐amino)ethyl‐3‐phenylpiperidine‐2,6‐dione (1997)

Abstract Aminoglutethimide [3‐(4‐aminophenyl)‐3‐ethylpiperidine‐2,6‐dione] has been used clinically in the treatment of metastatic breast carcinoma. Inhibition of tumor growth is due to interference with estrogen biosynthesis. However, its action is not specific and its metabolism gives rise to toxic and non‐inhibitory metabolites. We sought to explore the impact of relocating the amino group in aminoglutethimide to the ethyl side chain. To that end, we now report the synthesis and aromatase‐inhibitory activity of 3‐(2′‐ N,N ‐diethylamino)ethyl‐3‐phenylpiperidine‐2,6‐dione 5. The introduction of the amino functionality on the ethyl group is accomplished via reductive animation of aldehyde 8, prepared in three steps from benzyl cyanide. The synthetic route presented can be used for the preparation of related derivatives of aminoglutethimide.
TOI-1634 b: An Ultra-short-period Keystone Planet Sitting inside the M-dwarf Radius Valley (2021)

Abstract Studies of close-in planets orbiting M dwarfs have suggested that the M-dwarf radius valley may be well explained by distinct formation timescales between enveloped terrestrials and rocky planets that form at late times in a gas-depleted environment. This scenario is at odds with the picture that close-in rocky planets form with a primordial gaseous envelope that is subsequently stripped away by some thermally driven mass-loss process. These two physical scenarios make unique predictions of the rocky/enveloped transition’s dependence on orbital separation such that studying the compositions of planets within the M-dwarf radius valley may be able to establish the dominant physics. Here, we present the discovery of one such keystone planet: the ultra-short-period planet TOI-1634 b ( P = 0.989 days, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mi>F</mml:mi> <mml:mo>=</mml:mo> <mml:mn>121</mml:mn> <mml:msub> <mml:mrow> <mml:mi>F</mml:mi> </mml:mrow> <mml:mrow> <mml:mo>⊕</mml:mo> </mml:mrow> </mml:msub> </mml:math> , <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msub> <mml:mrow> <mml:mi>r</mml:mi> </mml:mrow> <mml:mrow> <mml:mi>p</mml:mi> </mml:mrow> </mml:msub> <mml:mo>=</mml:mo> <mml:msubsup> <mml:mrow> <mml:mn>1.790</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>−</mml:mo> <mml:mn>0.081</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>+</mml:mo> <mml:mn>0.080</mml:mn> </mml:mrow> </mml:msubsup> </mml:math> R ⊕ ) orbiting a nearby M2 dwarf ( K s = 8.7, R s = 0.450 R ⊙ , M s = 0.502 M ⊙ ) and whose size and orbital period sit within the M-dwarf radius valley. We confirm the TESS-discovered planet candidate using extensive ground-based follow-up campaigns, including a set of 32 precise radial velocity measurements from HARPS-N. We measure a planetary mass of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msubsup> <mml:mrow> <mml:mn>4.91</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>−</mml:mo> <mml:mn>0.70</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>+</mml:mo> <mml:mn>0.68</mml:mn> </mml:mrow> </mml:msubsup> </mml:math> M ⊕ , which makes TOI-1634 b inconsistent with an Earth-like composition at <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mn>5.9</mml:mn> <mml:mi>σ</mml:mi> </mml:math> and thus requires either an extended gaseous envelope, a large volatile-rich layer, or a rocky composition that is not dominated by iron and silicates to explain its mass and radius. The discovery that the bulk composition of TOI-1634 b is inconsistent with that of Earth supports the gas-depleted formation mechanism to explain the emergence of the radius valley around M dwarfs with <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msub> <mml:mrow> <mml:mi>M</mml:mi> </mml:mrow> <mml:mrow> <mml:mi>s</mml:mi> </mml:mrow> </mml:msub> <mml:mo>≲</mml:mo> <mml:mn>0.5</mml:mn> </mml:math> M ⊙ .
Spheronization (2016)

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Metro Ring Node Module Based on Polymeric (2003)

is? cm and its length 2.5 cm. Propagation losses of the s-bend channel waveguides. tvmicallv 5 to 6 cm lane. were meas~ied~usind iib'ber dad-coupling technique [SI. Typically, light at 1.55 pm is coupled via a single mode fiber into the channel waveguide and output is recorded via either a single mode fiber or an objective lens. Using this technique, knowing the transmission of the objective lens and the fibers. both propagation and coupling losses are simultaneously measured. The lowest measured propagation losses are 0.4 dB/cm and coupling losses are typically around 1.5 dB. The coupling losses are primarily due to the mode mismatch between the Gaussian mode of fiber and the single mode solgel waveguide. The FWHM of the current sol-gel waveguide is estimated to be 6 pm to 7 Vm, while that of single mode fiber is 9 pm to I1 pm. Typical power uniformities are <OS dB and <I dB and the insertion losses are 15 dB to 20 dB for 1x8 and 1x16 splitters, respectively.
Post-receptor responses to hormonal stimuli (1976)

It is now recognised that hormones bind to specific receptors on the outer membranes of their target cells, and can exert their effects without entering the cells whose metabolic activities they regulate. However, the molecular events which follow the hormone-receptor interaction are very incompletely understood. This short review will mainly centre on a critical assessment of the current state of our knowledge regarding the regulation of glycogen metabolism by adrenalin, glucagon and insulin. This is not only the system for which the nature of the post-receptor responses are known in the greatest molecular detail, but is also that in which cyclic AMP was identified, a discovery which opened up the area of secondary hormone messengers as the intracellular mediators of hormone action. The implication of cyclic AMP in the action of a growing number of hormonal effects (Robison, Butcher and Sutherland, 1971) therefore makes an analysis of this system a model of unique general interest.
Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency (2017)

Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease cases. A mutation in 1 of over 40 monogenic genes can be detected in approximately 30% of individuals with SRNS whose symptoms manifest before 25 years of age. However, in many patients, the genetic etiology remains unknown. Here, we have performed whole exome sequencing to identify recessive causes of SRNS. In 7 families with SRNS and facultative ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects, we identified 9 different recessive mutations in SGPL1, which encodes sphingosine-1-phosphate (S1P) lyase. All mutations resulted in reduced or absent SGPL1 protein and/or enzyme activity. Overexpression of cDNA representing SGPL1 mutations resulted in subcellular mislocalization of SGPL1. Furthermore, expression of WT human SGPL1 rescued growth of SGPL1-deficient dpl1Δ yeast strains, whereas expression of disease-associated variants did not. Immunofluorescence revealed SGPL1 expression in mouse podocytes and mesangial cells. Knockdown of Sgpl1 in rat mesangial cells inhibited cell migration, which was partially rescued by VPC23109, an S1P receptor antagonist. In Drosophila, Sply mutants, which lack SGPL1, displayed a phenotype reminiscent of nephrotic syndrome in nephrocytes. WT Sply, but not the disease-associated variants, rescued this phenotype. Together, these results indicate that SGPL1 mutations cause a syndromic form of SRNS.
Pro-Survival Lipid Sphingosine-1-Phosphate Metabolically Programs T Cells to Limit Anti-tumor Activity (2019)

Sphingosine 1-phosphate (S1P), a bioactive lysophospholipid generated by sphingosine kinase 1 (SphK1), regulates lymphocyte egress into circulation via S1P receptor 1 (S1PR1) signaling, and it controls the differentiation of regulatory T cells (Tregs) and T helper-17 cells. However, the mechanisms by which receptor-independent SphK1-mediated intracellular S1P levels modulate T cell functionality remains unknown. We show here that SphK1-deficient T cells maintain central memory phenotype and exhibit higher mitochondrial respiration and reduced differentiation to Tregs. Mechanistically, we discovered a direct correlation between SphK1-generated S1P and lipid transcription factor PPARγ (peroxisome proliferator-activated receptor gamma) activity, which in turn regulates lipolysis in T cells. Genetic and pharmacologic inhibition of SphK1 improved metabolic fitness and anti-tumor activity of T cells against murine melanoma. Further, inhibition of SphK1 and PD1 together led to improved control of melanoma. Overall, these data highlight the clinical potential of limiting SphK1/S1P signaling for enhancing anti-tumor-adoptive T cell therapy.
Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes (2016)

Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P<5 × 10(-8)), rs1116357 near CCDC85A, rs147538848 in FAM60A, rs1575972 near DMRTA1, rs9309245 near ASB3, rs67156297 near ATP8B2, rs7107784 near MIR4686 and rs67839313 near INAFM2. Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P<0.007). These results indicate that expansion of single ethnic GWAS is still useful to identify novel susceptibility loci to complex traits not only for ethnicity-specific loci but also for common loci across different ethnicities.
Population pharmacokinetic‐pharmacodynamic modeling of omecamtiv mecarbil, a cardiac myosin activator, in healthy volunteers and patients with stable heart failure (2015)

Abstract Data from 3 clinical trials of omecamtiv mecarbil in healthy volunteers and patients with stable heart failure (HF) were analyzed using a nonlinear mixed‐effects model to investigate omecamtiv mecarbil's pharmacokinetics and relationship between plasma concentration and systolic ejection time (SET) and Doppler‐derived left ventricular outflow tract stroke volume (LVOTSV). Omecamtiv mecarbil pharmacokinetics were described by a linear 2‐compartment model with a zero‐order input rate for intravenous administration and first‐order absorption for oral administration. Oral absorption half‐life was 0.62 hours, and absolute bioavailability was estimated as 90%; elimination half‐life was approximately 18.5 hours. Variability in pharmacokinetic parameters was not explained by patient baseline characteristics. Omecamtiv mecarbil plasma concentration was directly correlated with increases in SET and LVOTSV between healthy volunteers and patients with HF. The maximum increase from baseline in SET (delta SET) estimated by an E max model was 137 milliseconds. LVOTSV increased linearly from baseline by 1.6 mL per 100 ng/mL of omecamtiv mecarbil. Model‐based simulations for several immediate‐release oral dose regimens (37.5, 50, and 62.5 mg dosed every 8, 12, and 24 hours) showed that a pharmacodynamic effect (delta SET ≥20 milliseconds) could be maintained in the absence of excessive omecamtiv mecarbil plasma concentrations.
The intestinal microbiota determines the clinical efficacy of immune checkpoint blockers targeting PD-1/PD-L1 (2018)

Cancer immunotherapists have been searching for biomarkers predicting patient responses to PD-1/PD-L1 blockade in neoplastic cells as well as in the immune system. Now, accumulating evidence indicates that the composition of the intestinal microflora has a major impact on patient prognosis. Here, we enumerate the bacterial species that are associated with favorable outcome of immunotherapy.
Acute bacterial diarrhoea in the emergency room: therapeutic implications of stool culture results. (1994)

Empiric treatment with ciprofloxacin and norfloxacin has been recommended recently for patients with acute diarrhoeal disease. In a retrospective 6-month study period the results of stool cultures from 209 patients with acute diarrhoea admitted to the emergency room were analysed. Seventy-eight cultures (37%) were positive for one or more bacteria. Shigella was the most commonly isolated pathogen (68%). Shigella sonnei comprised 72% and Shigella flexneri 19% of all the bacterial isolates. While no antimicrobial resistance to ciprofloxacin was found for both Shigella species, only 36 and 26% of the Shigella isolates were sensitive to ampicillin and trimethoprim-sulfamethoxazole (TMP-SMZ), respectively. These findings point out to the emergence of drug resistance to commonly used antimicrobial drugs. Shigella's high sensitivity to the newer quinolones should make this the treatment of choice for the very sick patient, although physicians should be cautioned to the fact that indiscriminate use of this drug could result in the emergence of resistance similar to that noted with ampicillin and TMP-SMZ.
645: Vascular Endothelial Growth Factor Receptor 3 (VEGFR-3) is Highly Expressed in the Tumor Endothelium of Clear Cell but not Papillary Renal Cell Carcinoma (RCC): Implications for Therapy (2005)

You have accessJournal of UrologyDiscussed Poster, Monday, May 23, 2005, 8:00 am - 12:00 pm1 Apr 2005645: Vascular Endothelial Growth Factor Receptor 3 (VEGFR-3) is Highly Expressed in the Tumor Endothelium of Clear Cell but not Papillary Renal Cell Carcinoma (RCC): Implications for Therapy John T. Leppert, John S. Lam, Hong Yu, David B. Seligson, Jun Dong, Steven Horvath, Allan J. Pantuck, Robert A. Figlin, and Arie S. Belldegrun John T. LeppertJohn T. Leppert , John S. LamJohn S. Lam , Hong YuHong Yu , David B. SeligsonDavid B. Seligson , Jun DongJun Dong , Steven HorvathSteven Horvath , Allan J. PantuckAllan J. Pantuck , Robert A. FiglinRobert A. Figlin , and Arie S. BelldegrunArie S. Belldegrun View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)34885-7AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "645: Vascular Endothelial Growth Factor Receptor 3 (VEGFR-3) is Highly Expressed in the Tumor Endothelium of Clear Cell but not Papillary Renal Cell Carcinoma (RCC): Implications for Therapy." The Journal of Urology, 173(4S), p. 176 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 173Issue 4SApril 2005Page: 176 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information John T. Leppert More articles by this author John S. Lam More articles by this author Hong Yu More articles by this author David B. Seligson More articles by this author Jun Dong More articles by this author Steven Horvath More articles by this author Allan J. Pantuck More articles by this author Robert A. Figlin More articles by this author Arie S. Belldegrun More articles by this author Expand All Advertisement PDF downloadLoading ...
On-line extraction of SCSI disk drive parameters (1995)

Sophisticated disk scheduling algorithms require accurate, detailed disk drive specifications, including data about mechanical delays, on-board caching and prefetching algorithms, command and protocol overheads, and logical-to-physical block mappings. Comprehensive disk models used in storage subsystem design require similar levels of detail. We describe a suite of general-purpose algorithms and techniques for acquiring the necessary information from a SCSI disk drive. Using only the ANSI-standard interface, we demonstrate how the important parameter values of a modern SCSI drive can be determined accurately and efficiently.
2 EFFECTS OF AN IBD-ASSOCIATED MICROBIAL COMMUNITY STATE ON INTESTINAL INFLAMMATION IN HUMANIZED GNOTOBIOTIC MICE (2020)

Abstract Background and Aims We previously reported that 20% of unaffected first-degree relatives of pediatric IBD patients share the same microbial community structure (OTU-type) as IBD patients. This suggests that a preexisting dysbiosis can predispose to the development of IBD. The aims of this study were to establish that microbial community types identified in the family cohort could be reconstituted in gnotobiotic mice for further translational studies and to assess for any direct effects of this microbiota on intestinal inflammation. Methods Over 100 germ-free wild-type C57/BL6 mice were colonized for 4 weeks in the UCLA gnotobiotic facility with fecal microbiota from 30 human donors belonging to each of four groups from the pediatric family cohort: unaffected first-degree relatives with OTU-type 1, unaffected first-degree relatives with the IBD-associated OTU-type 2, Crohn’s disease (CD) with OTU-type 1, CD with OTU-type 2. Each group was represented by 8 human donors (n=3–4 mice/donor) with the exception of CD OTU-type 1 (only 5 donors available in the cohort). In addition, 35 eight week old germ-free IL-10-/- C57/BL6 mice were colonized for 12 weeks with fecal microbiota from 4 CD OTU-type 2 donors and 4 unaffected OTU-type 1 donors (n=4–5/donor). Luminal and mucosal microbial composition in the colon and small intestine was evaluated by 16S rRNA sequencing. Intestinal inflammation was assessed in the small intestine and colon by semiquantitative scoring of H&amp;E stained sections. Results Donor-specific microbial composition was observed in the humanized gnotobiotic mice with clear separation between recipients of donor OTU-type 1 vs. OTU-type 2 stool. Parallel differences in differentially abundant microbes and microbial diversity were seen in these gnotobiotic mice as in the original human donors. No histologic evidence was found for colitis, enteritis, or fibrosis in wild-type colonized mice. However, fecal lipocalin was increased two-fold increase in recipients of OTU-type 2 microbiota from CD patients relative to the other three groups. CD humanized IL-10-/- mice exhibited lower microbial diversity and distinct microbial composition compared to non-IBD humanized IL-10-/- mice, mirroring differences in the human donors. Mice colonized with CD microbiota had increased histological disease severity in the colon and cecum (p=0.05) compared to mice colonized with non-IBD microbiota. Conclusion Our results demonstrate that human microbial community states identified in the pediatric IBD cohort could be reconstituted in gnotobiotic mice for translational studies. Moreover, CD-associated dysbiosis exacerbated colitis severity. These data support the concept that dysbiosis plays a direct role in promoting intestinal inflammation and provide an experimental framework for further mechanistic studies of IBD-associated microbial communities.
Data from Oncolytic Efficacy of Recombinant Vesicular Stomatitis Virus and Myxoma Virus in Experimental Models of Rhabdoid Tumors (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Rhabdoid tumors are highly aggressive pediatric tumors that are usually refractory to available treatments. The purpose of this study was to evaluate the therapeutic potential of two oncolytic viruses, myxoma virus (MV) and an attenuated vesicular stomatitis virus (VSV&lt;sup&gt;ΔM51&lt;/sup&gt;), in experimental models of human rhabdoid tumor.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Four human rhabdoid tumor cell lines were cultured &lt;i&gt;in vitro&lt;/i&gt; and treated with live or inactivated control virus. Cytopathic effect, viral gene expression, infectious viral titers, and cell viability were examined at various time points after infection. To study viral oncolysis &lt;i&gt;in vivo&lt;/i&gt;, human rhabdoid tumor cells were implanted s.c. in the hind flank or intracranially in CD-1 nude mice and treated with intratumoral (i.t.) or i.v. injections of live or UV-inactivated virus. Viral distribution and effects on tumor size and survival were assessed.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; All rhabdoid tumor cell lines tested &lt;i&gt;in vitro&lt;/i&gt; were susceptible to productive lethal infections by MV and VSV&lt;sup&gt;ΔM51&lt;/sup&gt;. I.t. injection of live MV or VSV&lt;sup&gt;ΔM51&lt;/sup&gt; dramatically reduced the size of s.c. rhabdoid tumor xenografts compared with control animals. I.v. administration of VSV&lt;sup&gt;ΔM51&lt;/sup&gt; or i.t. injection of MV prolonged the median survival of mice with brain xenografts compared with controls (VSV&lt;sup&gt;ΔM51&lt;/sup&gt;: 25 days versus 21 days, log-rank test, &lt;i&gt;P&lt;/i&gt; = 0.0036; MV: median survival not reached versus 21 days, log-rank test, &lt;i&gt;P&lt;/i&gt; = 0.0007). Most of the MV-treated animals (4 of 6; 66.7%) were alive and apparently “cured” when the experiment was arbitrarily ended (&gt;180 days).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; These results suggest that VSV&lt;sup&gt;ΔM51&lt;/sup&gt; and MV could be novel effective therapies against human rhabdoid tumor.&lt;/p&gt;&lt;/div&gt;
A specific QRS detector for electrocardiography during MRI: Using wavelets and local regularity characterization (2009)

Automatic electrocardiogram (ECG) analysis, especially QRS detection, is still a challenging task. This is even more the case when ECG is acquired during magnetic resonance (MR) examination. The MR environment highly distorts ECG, with Hall effect, due to the important static magnetic field, and artifacts, caused by fast switching magnetic field gradients. Detection of QRS complexes is then affected. In this paper, a new specific MR QRS detector is presented. This method is based on the modulus maximum lines and on the Lipschitz exponent estimation they offer. The use of this regularity characterization enables to distinguish between QRS complexes and MR artifacts. This detector outperforms existing algorithms with almost 99% sensitivity and positive prediction value.