gebhart/patrepeval huggingface dataset:
In Vivo Quantitative Monitoring of Subunit Stoichiometry for Metabolic Complexes (2018)

Metabolic pathways often employ assemblies of individual enzymes to facilitate substrate channeling to improve thermodynamic efficiency and confer pathway directionality. It is often assumed that subunits to multienzyme complexes are coregulated and accumulate at fixed levels in vivo, reflecting complex stoichiometry. Such assumptions can be experimentally tested using modern tandem mass spectrometry, and herein we describe such an approach applied toward an important metabolic complex. The committed step of de novo fatty acid synthesis in the plastids of most plants is catalyzed by the multienzyme, heteromeric acetyl-CoA carboxylase (hetACCase). This complex is composed of four catalytic subunits and a recently discovered regulatory subunit resembling the biotin carboxyl carrier protein but lacking the biotinylation motif necessary for activity. To better understand this novel form of regulation, a targeted tandem mass-spectrometry-based assay was developed to absolutely quantify all subunits to the Arabidopsis thaliana hetACCase. After validation against pure, recombinant protein, this multiplexed assay was used to quantify hetACCase subunits in siliques in various stages of development. Quantitation provided a developmental profile of hetACCase and BADC protein expression that supports a recently proposed regulatory mechanism for hetACCase and demonstrates a promising application of targeted mass spectrometry for in vivo analysis of protein complexes.
Volatile Organic Compounds in the Exhaled Breath as Biomarkers of Nonalcoholic Steatohepatitis in Obese Children (2014)

Introduction: Nonalcoholic steatohepatitis (NASH) is the most aggressive form of nonalcoholic fatty liver disease (NAFLD). Non-invasive methods to identify children with NASH are urgently needed. The aim of this study was to evaluate the use of exhaled volatile organic compounds (VOCs) as noninvasive biomarkers for NASH in obese children. Methods: Consecutive children evaluated at our childhood obesity program were included and breath samples were collected at the time of their clinic visit. All children underwent a liver ultrasonography (US) and ALT measurements to determine the presence of NAFLD. The diagnosis of NASH was based on the presence of fatty infiltration on US and ALT>45 U/L. The “no NASH” group included obese children with ALT<22 U/L for girls and <25 U/L for boys with and without fatty infiltration on US (steatosis and obese control groups, respectively). Exhaled breath was collected and analyzed per protocol using selective ion flow tube (SIFT-MS) to identify new markers of NAFLD. Results: A total of 96 subjects were included in the study. The mean age was 13.8 ± 2.8 years, and 53% were male. NASH was diagnosed in 22 patients with a median ALT of 61.5 (56-92 U/L). A comparison of the SIFT-MS results of patients with NASH to those with no NASH revealed differences in concentration of more 3 VOCs, namely ethanol (86.4 vs. 60.6 ppb; p=0.021), 3-methylhexane (15 vs. 11.4, p=0.022), and pentane (9.9 vs. 8.2, p=0.023). A combination of ethanol and 3-methylhexane showed good accuracy for diagnosing NASH with an area under the ROC curve of 0.73 (95% confidence interval [CI]; 0.62-0.84). We developed a predictive model for NASH using these 2 VOCs, which provided a 90% negative predictive value (good screening tool to rule out NASH). Conclusion: Exhaled ethanol and 3-methylhexane are promising noninvasive biomarkers for NASH in obese children. Future studies are needed to validate our findings in children with biopsy-proven NASH.
Laser forming of aerospace alloys (1997)

Laser forming has emerged as a candidate process for rapid prototyping of sheet metal. The dimensional accuracy of rapid prototypes is a topical issue. As the dimensions of a laser formed part depend on the temperature field induced in the workpiece, it is imperative that the correct selection of laser processing parameters be made. In this work a parametric investigation into the factors influencing the laser forming process on plates of an α-β titanium and a high strength AlCuMg aluminium alloy is reported. The influence of the energy parameters on the bend angle is examined empirically and compared with an analytical model. The effects of varying the energy supplied to the plate surface and hence the temperature gradient through the plate thickness are examined by altering the traverse velocity of the plate for a range of laser powers and beam diameters. Results from the experimental work show that the plastic strain, the bend angle and hence the dimensions of the part are critically dependent on the energy supplied to the workpiece surface. An optimum traverse velocity is identified for some power densities in terms of maximising the bend angle achieved per scan. The digressive course of the bend angle with increasing the number of scans over the same track is evident. This is attributed to a partial burn-off of the graphite coating used to increase the absorptivity of the samples, and an increase in the section modulus of the samples due to the thickening of the material along the bending edge. Edge effects are apparent in the samples. They are pronounced when the plate is heated slowly and the beam diameter is large compared to the thickness of the sample. It is shown that these effects can be minimised by varying the line energy supplied to the plate surface with in plate location. Conclusions drawn from this work indicate that the dimensions of the final part and the rate of bending can be controlled primarily from the temperature field. In addition, other factors, such as the increase in the section modulus and the edge effects, influence the accuracy of the process.
First in human phase I study of chlorogenic acid injection in recurrent high grade glioma. (2018)

e14081 Background: Chlorogenic acid (CHA) is a natural product with good antitumor activity in preclinical study. A phase I clinical trial of CHA injection was conducted to determine tolerance, safety, pharmacokinetics in patients with recurrent high grade glioma. Methods: Patients received CHA injection intramuscularly once daily for 30 days of each cycle following continuous treatment extension based on clinical evaluation. A standard 3+3 design was used for dose-escalation. The primary endpoints were to evaluate the tolerance and safety of CHA, determine the maximum-tolerate dose (MTD) and dose-limiting toxicity (DLT). The secondary endpoints included:pharmacokinetics, preliminary antitumor efficacy and potential biomarkers. Results: Twenty-six patients were enrolled at five doses: 2mg/kg (3), 3mg/kg (9), 4mg/kg (9), 5.5mg/kg (3) and 7mg/kg (2). Two patients were discontinued during treatment due to muscle-related injection induration and one patient was discontinued due to compliance. Among 26 patients for DLT evaluation, two DLTs were observed muscle-related injection induration. The MTD was determined as 5.5mg/kg. Common adverse events included thrombocytopenia (3.84%), pain in flank, shoulder and arms (each 3.84%), and muscle-related injection induration (92.3%). The maximum plasma concentration of CHA was increased after administration at all doses . The elimination half-life ranged from 1.12 to 1.27 h on day 1 and from 1.19 to 1.39 h on day 30. The disease control rate of 1 month and 3 months were 52.17% (SD, 12) and 33.33% (SD, 6), respectively. By the end of Feb. 6th, 2018 , the median OS in dose 2mg/kg is 9.6 months, 9.4 months in dose 4mg/kg, 12.2 months in dose 5.5mg/kg. In 3mg/kg dose 7/9 patients are still alive, two of them survival over 18 months since adminstration. In 5.5mg/kg dose 2/3 patients are survival. Among over 13 serum cytokines, IL12p70, IL-28A and IL-27 were identified to predict for both T cell immune response to CHA and clinical outcome. The serum level of sLAG3 is positively correlated with patient prognosis. Conclusions: This study demonstrated that CHA injection in patients with recurrent high grade glioma, at the MTD of 5.5mg/kg, was safety and well tolerated with potential antitumor activity. Clinical trial information: NCT02245204.
Migration, Memory and Longing in Haitian Songs (2022)

With over three million Haitians living abroad and the nation’s reliance on remittances and other forms of exchange for its survival, Haiti is shaped by an imagined transnational community found within and outside its geographic borders. In this article, we explore music as a prominent cultural form bound up in identity, examine the structural inequalities that have made migration the principal strategy for surviving social, political, and economic turmoil, and consider migration’s impact on transnational families. Through Haiti’s folk, konpa, and rap music genres, we explore how songs of migration evoke and suspend memory, express longing, and convey hope for (re)connection between migrants and those in Haiti. These songs exemplify cultural identity, authenticity, and innovation as they recount the perseverance, pain, and suffering of Haitians on both sides of the Caribbean Sea. This musical dialogue suggests solidarity but also signals antagonism between those living abroad and those who remain in the homeland. In examining this cultural form, we conclude that what is revealed in this music is what’s truly at stake in Haitian migration: more than the survival of families, it is also the hope for revival of a faltering nation.
Disruption of the Dopamine D2 Receptor Impairs Insulin Secretion and Causes Glucose Intolerance (2010)

The relationship between antidopaminergic drugs and glucose has not been extensively studied, even though chronic neuroleptic treatment causes hyperinsulinemia in normal subjects or is associated with diabetes in psychiatric patients. We sought to evaluate dopamine D2 receptor (D2R) participation in pancreatic function. Glucose homeostasis was studied in D2R knockout mice (Drd2(-/-)) mice and in isolated islets from wild-type and Drd2(-/-) mice, using different pharmacological tools. Pancreas immunohistochemistry was performed. Drd2(-/-) male mice exhibited an impairment of insulin response to glucose and high fasting glucose levels and were glucose intolerant. Glucose intolerance resulted from a blunted insulin secretory response, rather than insulin resistance, as shown by glucose-stimulated insulin secretion tests (GSIS) in vivo and in vitro and by a conserved insulin tolerance test in vivo. On the other hand, short-term treatment with cabergoline, a dopamine agonist, resulted in glucose intolerance and decreased insulin response to glucose in wild-type but not in Drd2(-/-) mice; this effect was partially prevented by haloperidol, a D2R antagonist. In vitro results indicated that GSIS was impaired in islets from Drd2(-/-) mice and that only in wild-type islets did dopamine inhibit GSIS, an effect that was blocked by a D2R but not a D1R antagonist. Finally, immunohistochemistry showed a diminished pancreatic beta-cell mass in Drd2(-/-) mice and decreased beta-cell replication in 2-month-old Drd2(-/-) mice. Pancreatic D2Rs inhibit glucose-stimulated insulin release. Lack of dopaminergic inhibition throughout development may exert a gradual deteriorating effect on insulin homeostasis, so that eventually glucose intolerance develops.
Diabetes management in Wolcott-Rallison syndrome: analysis from the German/Austrian DPV database (2020)

Insulin requirements of individuals with WRS registered in DPV appear to be comparable to those of preschool children with well-controlled type 1 diabetes, while glycaemic control tends to be worse and episodes of SH tend to be more common. The majority of individuals with WRS in the DPV registry does not reach glycaemic target for HbA1c as defined for preschool children (< 7.5%). International multicentre studies are required to further improve our knowledge on the care of children with WRS.
Regio‐ and Stereoselective Ring Opening of Vinyl Epoxides with MgBr2. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Long-term data on corticosteroids and mycophenolate mofetil treatment in lupus nephritis (2012)

Objective. We investigated the long-term outcome of patients with proliferative LN treated with CSs and MMF. Methods. This was a single-centre retrospective study on patients with biopsy-proven class III/IV ± V LN treated with prednisolone and MMF continuously as both early and maintenance immunosuppression. Results. Sixty-five patients were included, and followed for 91.9 (47.7) months. All received prednisolone and MMF as induction immunosuppression. In 31 patients, maintenance immunosuppression comprised prednisolone and MMF only (MMF–MMF group). MMF was replaced with AZA in 23 patients (MMF–AZA), and with calcineurin inhibitors (CNIs) in 11 patients (MMF–CNI) at sometime during follow-up. Ten-year patient and renal survival rates were 91% and 86%, respectively, and were similar in the three groups. MMF–MMF group showed better relapse-free survival than MMF–AZA and MMF–CNI patients (76% vs 56% vs 43%, respectively at 5 years; 69% vs 32% vs 0%, respectively at 10 years; MMF–MMF vs MMF–AZA or MMF–CNI, P = 0.049 or 0.019, respectively; MMF-AZA vs MMF-CNI, P = 0.490). Patients treated with MMF for >24 months had better relapse-free survival than those treated for shorter durations (88% vs 48% at 5 years; 81% vs 28% at 10 years; P < 0.001). Renal function at 10 years was better in the MMF–MMF group. Anaemia was associated with MMF treatment. Other adverse events were comparable and relatively minor with MMF, AZA or CNI as maintenance. Conclusion. Long-term treatment with CSs and MMF from induction to maintenance phase is associated with relatively favourable long-term outcome in Chinese LN patients. Discontinuation of MMF before 24 months may increase the risk of flares.
O ral C apecitabine C ompared W ith I ntravenous Fluorouracil P lus L eucovorin i n P atients W ith M etastatic Colorectal C ancer: R esults o f a L arge P hase I II S tudy (2001)

Purpose: To compare the efficacy and safety of orally administered capecitabine (Xeloda; Roche Laboratories, Inc, Nutley, NJ), a novel fluoropyrimidine carbamate designed to mimic continuous fluorouracil (5-FU) infusion but with preferential activation at the tumor site, with that of intravenous (IV) 5-FU plus leucovorin (5-FU/LV) as first-line treatment for metastatic colorectal cancer. Patients and Methods: We prospectively randomized 602 patients to treatment with capecitabine 1,250 mg/m 2 administered twice daily days 1 to 14 every 3 weeks, or to the 4-weekly Mayo Clinic regimen (5-FU/ LV) until disease progression or unacceptable toxicity. Results: The primary objective, to demonstrate at least equivalent response rates in the two treatment groups, was met. The overall response rate was 18.9% for capecitabine and 15.0% for 5-FU/LV. In the capecitabine and 5-FU/LV groups, respectively, median time to disease progression was 5.2 and 4.7 months (log-rank P .65); median time to treatment failure was 4.2 and 4.0 months (log-rank P .89); and median overall survival was 13.2 and 12.1 months (log-rank P .33). The toxicity profiles of both treatments were typical of fluoropyrimidines. However, capecitabine led to significantly lower incidences (P < .00001) of stomatitis and alopecia, but a higher incidence of cutaneous hand-foot syndrome (P < .00001). Capecitabine also resulted in lower incidences (P < .00001) of grade 3/4 stomatitis and neutropenia, leading to a lower incidence of grade 3/4 neutropenic fever and sepsis. Only grade 3 handfoot syndrome (P < .00001) and uncomplicated grade 3/4 hyperbilirubinemia (P < .0001) were reported more frequently with capecitabine. Conclusion: Oral capecitabine achieved an at least equivalent efficacy compared with IV 5-FU/LV. Capecitabine demonstrated clinically meaningful safety advantages and the convenience of an oral agent. J Clin Oncol 19:4097-4106. © 2001 by American Society of Clinical Oncology.
Brainstem Encephalitis With Low-Titer Acetylcholine Receptor Antibodies Mimicking Myasthenia Gravis (2019)

<b>Objective:</b> To report a rare case of brainstem encephalitis with low-titer acetylcholine receptor antibodies mimicking myasthenia gravis. <b>Methods:</b> The patient was investigated with repeated brain MRI, CSF examination, repetitive nerve stimulation, thoracic CT, and serologic screening. Our patient passed away and finally autopsy revealed a definitive diagnosis. Written informed consent was obtained from the relatives of the patient for access to clinical files for research purposes and publication. <b>Results:</b> We present a young woman with a subacute bulbar syndrome, who was initially diagnosed with myasthenia gravis based on clinical finding and elevated acetylcholine receptor antibodies. Episodes of numbness in the pharynx and tongue and moderate saccadic horizontal and vertical pursuits were atypical. Despite initial stabilization with intravenous immunoglobulins she developed acute asphyxia after regurgitation of food and had to be resuscitated with ultimately lethal outcome. Autopsy revealed an autoimmune T-cell mediated brainstem encephalitis. Serological screening revealed positive GAD and Ma2 autoantibodies, indicating its probable paraneoplastic nature. <b>Conclusions:</b> Brainstem encephalitis is an important differential diagnosis even in seropositive bulbar myasthenia gravis, as several autoimmune processes often co-occur. Sudden unexpected death must be taken into account in brainstem encephalitis, requiring prolonged monitoring of the patients.
Incision Activity of Human Apurinic Endonuclease (Ape) at Abasic Site Analogs in DNA (1995)

The major apurinic/apyrimidinic (AP) endonuclease of human cells, the Ape protein, incises DNA adjacent to abasic sites to initiate DNA repair and counteract the cytotoxic and mutagenic effects of AP sites. Here we address the determinants of Ape AP endonuclease activity using duplex DNA substrates that contain synthetic analogs of AP sites: tetrahydrofuranyl (F), propanediol (P), ethanediol (E), or 2-(aminobutyl)-1,3-propanediol (Q). The last of these, a branched abasic structure, was a poor substrate for which Ape had kcat > 1000-fold lower than for F. In contrast, the specificity constant (kcat/Km) for E or P of Ape purified from HeLa cells was only 5-8-fold lower than for F. Positioning a phosphorothioate ester immediately 5' to F inhibited Ape incision activity 20-fold (Rp isomer) or > 10,000-fold (Sp isomer). Although Ape did not have detectable endonuclease activity toward single-stranded substrates or unmodified double-stranded DNA, the enzyme displayed a low level of 3'-exonuclease activity for duplex DNA (< 0.03% of its AP endonuclease activity), which was influenced by the reaction conditions. The base positioned opposite F did not dramatically affect the cleavage efficiency of Ape, but an F:F arrangement was cleaved at approximately one-third of the efficiency of F:C. A 3'-mismatch diminished P and E cleavage only slightly and F not at all. A 5'-mismatch reduced the Ape cleavage rate 4-10-fold for F and approximately 100-fold for P and E. A series of substrates with F at different positions along the oligonucleotide showed that Ape requires > or = 4 base pairs 5' to the abasic site and > or = 3 base pairs on the 3'-side. The implications of these results for substrate recognition by Ape are discussed.
Deep Shape Analysis on Abdominal Organs for Diabetes Prediction (2018)

Morphological analysis of organs based on images is a key task in medical imaging computing. Several approaches have been proposed for the quantitative assessment of morphological changes, and they have been widely used for the analysis of the effects of aging, disease and other factors in organ morphology. In this work, we propose a deep neural network for predicting diabetes on abdominal shapes. The network directly operates on raw point clouds without requiring mesh processing or shape alignment. Instead of relying on hand-crafted shape descriptors, an optimal representation is learned in the end-to-end training stage of the network. For comparison, we extend the state-of-the-art shape descriptor BrainPrint to the AbdomenPrint. Our results demonstrate that the network learns shape representations that better separates healthy and diabetic individuals than traditional representations.
Monolithically integrated graded-index waveguide input couplers for silicon-photonics (2006)

A monolithically integrated asymmetric graded index (GRIN) waveguide structure for coupling light into high index contrast waveguides is described. When analyzed in terms of its waveguide modes, the GRIN coupler is shown to be a multimode interference (MMI) device. The design parameters and tolerances are calculated for quadratic index profile and uniform index amorphous silicon (a-Si) GRIN couplers optimized for coupling light into silicon-on-insulator waveguides. Calculations of coupling efficiencies into 0.5 &#956;m SOI waveguides show that asymmetric GRIN couplers operate over a very wide wavelength range with low polarization dependence, and fabrication requires lithographic resolution of only ±1 &#956;m. Experimental results are presented for a 3 &#956;m thick single layer a-Si coupler integrated with a 0.8 &#956;m SOI waveguide. The measured variation of coupling efficiency with coupler length is in agreement with theory, with an optimal coupling length of 15 &#956;m.
Surface Instabilities Due to Interfacial Chemical Reaction (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSurface Instabilities Due to Interfacial Chemical ReactionFriedrich K. von Gottberg, T. Alan Hatton, and Kenneth A. SmithCite this: Ind. Eng. Chem. Res. 1995, 34, 10, 3368–3379Publication Date (Print):October 1, 1995Publication History Published online1 May 2002Published inissue 1 October 1995https://pubs.acs.org/doi/10.1021/ie00037a024https://doi.org/10.1021/ie00037a024research-articleACS PublicationsRequest reuse permissionsArticle Views88Altmetric-Citations10LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts