gebhart/patrepeval huggingface dataset:
Dual-bottom-electrode CMUT based on standard CMOS process (2011)

A novel capacitive micromachined ultrasonic transducer (CMUT) with dual-bottom-electrode based on standard CMOS and post-CMOS processes is presented. Compared to the traditional CMUT with single-bottom-electrode, the presented one has larger equivalent gap in emission and smaller air gap in reception for the membrane is biased much closer to the bottom electrode. A structure model is proposed for the presented CMUT and finite element analysis (FEA) is carried out by commercial software ANSYS. Based on the simulation results, it is shown a 5.655dB improvement in maximum output pressure at 914 kHz without collapse, and a 9.3% improvement in maximum receive sensitivity for the presented CMUT compared with the traditional structure.
Comparative Study on Reversal Efficacy of SDZ PSC 833, Cyclosporin a and Verapamil on Multidrug Resistance in vitro and in vivo (1995)

A non-immunosuppressive cyclosporin, SDZ PSC 833 (PSC833), shows a reversal effect on multidrug resistance (MDR) by functional modulation of MDR1 gene product, P-glycoprotein. The objective of the present study was to compare the reversal efficacy of three multidrug resistance modulators, PSC833, cyclosporin A (CsA) and verapamil (Vp). PSC833 has approximately 3-10-fold greater potency than CsA and Vp with respect to the restoring effect on reduced accumulation of doxorubicin (ADM) and vincristine (VCR) in ADM-resistant K562 myelogenous leukemia cells (K562/ADM) in vitro and also on the sensitivity of K562/ADM to ADM and VCR in in vitro growth inhibition. The in vivo efficacy of a combination of modifiers (PSC833 and CsA: 50 mg/kg, Vp 100 mg/kg administered p.o. 4 h before the administration of anticancer drugs) with anticancer drugs (ADM 2.5 mg/kg i.p., Q4D days 1, 5 and 9, VCR 0.05 mg/kg i.p., QD days 1-5) was tested in ADM-resistant P388-bearing mice. PSC833 significantly enhanced the increase in life span by more than 80%, whereas CsA and Vp enhanced by less than 50%. This reversal potency, which exceeded that of CsA and Vp, was confirmed by therapeutic experiments using colon adenocarcinoma 26-bearing mice. These results demonstrated that PSC833 has significant potency to reverse MDR in vitro and in vivo, suggesting that PSC833 is a good candidate for reversing multidrug resistance in clinical situations.
Predictors of recurrence during years 5-14 in 46,138 women with ER+ breast cancer allocated 5 years only of endocrine therapy (ET). (2016)

505 Background: For operable ER+ breast cancer, 5 years of ET with tamoxifen and/or aromatase inhibitors reduces breast cancer mortality in years 0-4 and years 5-14 by about a third. Extending ET past year 5 further reduces risks in years 5-14, but has further side-effects. Knowledge of the effects of prognostic factors on absolute risks of distant recurrence and death in years 5-14 if ET stops at year 5 could help decide whether to extend ET after year 5 for lower-risk patients. Methods: Data on 46,138 individual patients with ER+ disease (diameter T1 or T2 only, pathological nodal status N0, N1-3 or N4-9 only) in trial groups allocated 5 years only of ET yielded the effects on outcomes in years 5-14 of tumor diameter, nodal status and, if available, grade, Ki-67, PR and HER-2 status. Cox regression analyses of each factor were adjusted for age, trial group, and the other factors. Results: In ER+ disease, recurrence rates continued steadily throughout the first 20 years. Distant recurrence rates in years 5-14 still depended on initial N-stage (N1-3 vs N0: RR = 2.08, 95%CI 1.87 – 2.32), T-stage (T2N0 vs T1N0: RR = 1.73, 1.53 – 1.95), grade (T1N0, high vs low: RR = 2.02, 1.44 – 2.83) and Ki67 ( ≥ 20% vs 0-13%: RR = 1.63, 1.23 – 2.16). Similar associations were seen for breast cancer mortality, but contralateral cancer rates (0.3%/year) were little related to these risk factors. For T1N0 disease of low, moderate, and high grade, the risks in years 5-14 were, respectively, 5%, 8%, and 10% for distant recurrence (Table) and 12%, 15% and 17% for any recurrence. Conclusions: Even after 5 years of ET, ER+ recurrence risk continued steadily over years 5-14. Although this risk was less for patients with favorable TN status and grade, even those with low-grade T1N0 disease had an appreciable risk of distant recurrence. Distant recurrence in years 5-14 in ER+ disease allocated 5 years only of endocrine therapy. No. of women Annual, Years 5-9 Rate (%), Years 10-14 Cumulative risk (%), years 5-14 Trend P Nodes: N0 23,870 1.0 1.1 9.8 1-3 16,630 2.0 1.5 15.6 4-9 5,638 4.1 2.6 27.7 < 0.0001 Diameter, N0 only: T1 16,286 0.7 0.9 7.9 T2 7,584 1.6 1.3 13.6 < 0.0001 Grade, T1N0 only: Low 2,996 0.4 0.7 5.4 Moderate 6,120 0.8 0.9 8.1 High 2,135 1.0 1.2 10.0 < 0.0001
Neuropathology of human T lymphotropic virus type I‐associated myelopathy (1997)

In order to clarify pathogenesis of human T lymphotropic virus type I (HTLV‐I)‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) a detailed neuropathological analysis of eight autopsy patients with HAM/TSP was performed. Inflammatory infiltrates of mononuclear cells and degeneration of myelin and axons were noted in the middle to lower thoracic spinal cords and were extended continuously to the entire spinal cord. Horizontal distribution of inflammatory lesions was symmetric at any spinal levels. Immunohistochemical analysis demonstrated T cell dominance. The numbers of CD4+ T cells and CD8+ T cells were present in equal numbers in patients with shorter clinical course. Apoptosis of helper/inducer T cells were observed in the presence of TIA1+ cytotoxic T cells in these active inflammatory lesions. Inflammatory infiltrates were markedly decreased and CD8+/TIA1‐ T cells were predominated over CD4+ cells in patients with prolonged clinical course. HTLV‐I proviral deoxyribonucleic acid (DNA) amounts in the freshly frozen spinal cord measured by quantitative polymerase chain reaction (PCR) were well correlated with the numbers of infiltrated CD4+ cells. In situ PCR of HTLV‐I provial DNA using multi‐primar pairs demonstrated the presence of HTLV‐I infected cells exclusively in the mononuclear infiltrates of perivascular areas. From these findings, it is suggested that the target of the inflammatory process seen in HAM/TSP lesions may be HTLV‐I infected CD4+ T cells infiltrating the spinal cord.
Atopic Dermatitis/Atopic Eczema (2014)

Atopic dermatitis was described in 1933 but exists since antiquity. We review descriptions of a childhood skin disease compatible with our modern diagnosis of atopic dermatitis, in ancient medicine and in nineteenth century dermatology texts. We identify Hebra's prurigo and Besnier's diathetic prurigo as forerunners of atopic dermatitis, the latter being a synthesis of infantile eczema and prurigo. The pathogenic theories which link atopic dermatitis to humoralistic medicine, to digestive diseases, to allergy may have had consequences on today's reluctance to consider atopic dermatitis as a skin disorder, the treatment of which relies mainly on topicals.
Aliphatic nitrile hydratase from Arthrobacter sp. J-1 purification and characterization. (1982)

A new enzyme, aliphatic nitrile hydratase, which hydrates acetonitrile to form acetamide was purified from the cell-free extract of acetonitrile-grown Arthrobacter sp. J-l. The overall purification was about 290-fold with a yield of 10%. The purified enzyme was homogeneous as judged by ultracentrifugation and disc gel electrophoresis. The enzyme catalyzed the stoichiometric hydration of acetonitrile to form acetamide according to the following scheme: CH3CN+H2O →CH3CONH2. The enzyme was inducibly formed and then amidase which hydrolyzed acetamide was formed. The molecular weight of the enzyme was determined to be about 420, 000 by gel filtration. The enzyme was composed of two kinds of subunits, of which the molecular weights were 24, 000 and 27, 000. The isoelectric point was 3.6. The enzyme was active toward low molecular weight aliphatic nitriles of 2 to 5 carbon atoms. The Km value for acetonitrile was determined to be 5.78mM. The enzyme was inactivated by sulfhydryl reagents. The enzyme was competitively inhibited by potassium cyanide: the Ki value was 1.5 μm.
Extended Stability of Oxytocin in Ringer's Lactate Solution at 4° and 25°C (2006)

Purpose Since IV admixtures of oxytocin in the final working concentrations are not commercially available, oxytocin admixtures must be prepared immediately before use or compounded in a sterile laminar flow hood and stored until needed. Although published reports indicate short-term stability of oxytocin in Ringer's lactate solution and Ringer's lactate-dextrose 5%, longer-term stability data at various temperatures are lacking. Methods A stability assay was developed, validated, and executed with oxytocin at two different concentrations in Ringer's lactate solution. Stability was assessed at 4 and 25°C over 31 days. Results This study shows that commonly used dilutions of oxytocin in Ringer's lactate solution retain greater than 90% of initial concentrations, when stored at room temperature or refrigerated for 31 days. These data show that oxytocin admixed with Ringer's lactate solution has extended chemical stability after preparation. Conclusions Demonstration of extended stability of oxytocin in Ringer's lactate solution will allow hospitals to give longer dating to oxytocin IV admixtures, provided they are prepared in a sterile environment and monitored in compliance with USP &lt;797&gt; guidelines. This should help minimize the potentially dangerous practice of admixing this IV solution at the bedside.
Simulated Basic Safety Message: Concept & Application. (2019)

In this paper, we introduce a concept called Simulated - BSM that leverages the combination of rich vehicular sensor feed (speed, object proximity, SLAM maps etc.), and emerging guaranteed low-latency communication protocols (DSRC, 5G) to enhance efficiency & safety of transport facilities. The main idea is that an ego-vehicle with local sensor feed capability creates a basic safety message for any identified rogue vehicles in its field of view, and broadcasts it to infrastructure for implementing efficient and safe control actions. System architecture details are discussed. The efficacy of S-BSM framework was successfully demonstrated in the context of enhancing safe & efficient operations at rural high-speed signalized intersection.
Evidence for a C4b binding site on the C2b domain of C2. (1988)

We raised murine mAb against human C protein C2. The representative mAb 3A3.3 (IgG1 kappa) recognized an epitope on the C2b domain of C2, as determined by binding and inhibition of binding radioassays. The hemolytic activity of purified human C2 and of C2 in normal human serum was inhibited by the mAb. The rate of decay of the C3-convertase at 30 degrees C was not affected by the mAb. C2 binding to EAC4b was inhibited by intact IgG and the Fab fragment of the mAb; 50% inhibition required 1 microgram/ml of either. The data suggest the presence of a C4b-binding site on the C2b domain of C2 and that the mAb recognizes an epitope at, or adjacent to, this site. The C2b portion of the C2 molecule may be important in assembly of the classical pathway C3-convertase.
Histone deacetylase inhibitors prevent exocytosis of interleukin-1β-containing secretory lysosomes: role of microtubules (2006)

A number of agents reducing interleukin-1beta (IL-1beta) activity are being developed as novel immunomodulatory and anti-inflammatory therapies. However, the elucidation of their molecular mechanism of action is required in the context of medical management of inflammatory diseases. Inhibitors of histone deacetylases (HDACs) are promising anticancer agents with pleiotropic activities. Of these, suberoylanilide hydroxamic acid has been reported to inhibit the production of several proinflammatory cytokines. In the present study, we investigated the effects of 2 HDAC inhibitors on IL-1beta secretion: suberoylanilide hydroxamic acid and a newly developed hydroxamic acid-derived compound ITF2357. These HDAC inhibitors do not affect the synthesis or intracellular localization of IL-1beta but both strongly reduce the levels of extracellular IL-1beta by preventing the exocytosis of IL-1beta-containing secretory lysosomes. At nanomolar concentrations, ITF2357 reduces the secretion of IL-1beta following ATP activation of the P2X7 receptor. Whereas the inhibition of HDACs results in hyperacetylation of tubulin, acetylation of HSP90 was unaffected. The reduction in IL-1beta secretion appears to be due to disruption of microtubules impairing lysosome exocytosis. Together, these observations indicate that a functional microtubule network is required for IL-1beta secretion and suggest that disruption of tubulin is the mechanism by which inhibitors of HDACs reduce the secretion of IL-1beta.
Structure and Dimensions of Core–Shell Nanoparticles Comparable to the Confocal Volume Studied by Means of Fluorescence Correlation Spectroscopy (2016)

In some applications the dye distribution within fluorescently labeled nanoparticles and its stability over long periods of time are important issues. In this article we study numerically and experimentally the applicability of fluorescence correlation spectroscopy (FCS) to resolve such questions. When the size of fluorescently labeled particles is comparable to or larger than the confocal volume, the effective confocal volume seen in FCS experiments is increasing. Such an effect has already been studied for uniformly labeled spherical particles. In this work we analyze the form of the FCS correlation functions (CFs) for core-labeled and shell-labeled core-shell particles. For shell-labeled particles an additional fast decay was found both in simulations and in experiments on custom-made surface-labeled particles. Universal scaling of FCS correlation times based on the squared ratio of the labeled part radius of gyration to the Gaussian radius of the beam profile was found. Recipes based on the analysis of simulated CFs, proposed for interpretation of experimental results, were successfully applied to the FCS results on suspensions of large core-labeled and surface-labeled particles.
Polishing Methods for Monoclonal IgG Purification (2006)

Protein A affinity chromatography has become well established as the preferred capture step for purification of human monoclonal IgG for in vivo applications, so much so that it has become largely regarded as generic. This has created the desire for an equally generic block of polishing methods to complete the purification. This chapter will discuss the suitability of anion exchange, cation exchange, hydrophobic interaction, and ceramic hydroxyapatite (CHT™ Bio-Rad) chromatography as candidates for this application. The strengths and limitations of each method will be discussed individually, and the merit of combining defined subsets with protein A toward the possibility of a generic overall IgG purification scheme will be considered.
Oxide dual-layer memory element for scalable non-volatile cross-point memory technology (2008)

We report a dual oxide layer as the active memory element of a scalable nonvolatile cross-point memory technology. The resistance change memory element is formed by a conductive metal oxide adjacent to an oxide tunnel barrier. Varying the as-deposited tunnel barrier thickness allows for control of the nominal current density and is targeted to meet the cell requirements for an ultra high density cross-point architecture. Excellent scaling of program and erase currents with electrode area and a continuous transition between program and erase state indicate that a uniform rather than a filamentary switching mechanism controls the device current both in the high and the low resistive state. A prior forming step is not required. The observed resistance change is caused by the exchange of oxygen ions between the conductive metal oxide and the tunnel oxide. Ion motion at room temperature is enabled by an exponential increase of the ion mobility under high electric fields during program and erase operations. The resistive switching effect of the device is explained by a change in the tunneling current due to an increase or decrease in effective tunnel barrier height. The barrier height varies due to changes in charge within the barrier as a result of oxygen ions moving in to or out of the tunnel barrier.
Genetics of familial adult myoclonus epilepsy: From linkage studies to noncoding repeat expansions (2023)

Familial adult myoclonus epilepsy (FAME) is a genetic epilepsy syndrome that for many years has resisted understanding of its underlying molecular cause. This review covers the history of FAME genetic studies worldwide, starting with linkage and culminating in the discovery of noncoding TTTTA and inserted TTTCA pentanucleotide repeat expansions within six different genes to date (SAMD12, STARD7, MARCHF6, YEATS2, TNRC6A, and RAPGEF2). FAME occurs worldwide; however, repeat expansions in particular genes have regional geographical distributions. FAME repeat expansions are dynamic in nature, changing in length and structure within germline and somatic tissues. This variation poses challenges for molecular diagnosis such that molecular methods used to identify FAME repeat expansions typically require a trade-off between cost and efficiency. A rigorous evaluation of the sensitivity and specificity of each molecular approach remains to be performed. The origin of FAME repeat expansions and the genetic and environmental factors that modulate repeat variability are not well defined. Longer repeats and particular arrangements of the TTTTA and TTTCA motifs within an expansion are correlated with earlier onset and increased severity of disease. Other factors such as maternal or paternal inheritance, parental age, and repeat length alone have been suggested to influence repeat variation; however, further research is required to confirm this. The history of FAME genetics to the present is a chronicle of perseverance and predominantly collaborative efforts that yielded a successful outcome. The discovery of FAME repeats will spark progress toward a deeper understanding of the molecular pathogenesis of FAME, discovery of new loci, and development of cell and animal models.
Acute regional improvement of myocardial function after interventional transfemoral aortic valve replacement in aortic stenosis: A speckle tracking echocardiography study (2012)

There is an acute improvement of myocardial longitudinal systolic function of the basal and medial segments measured by 2D Strain analysis immediately after TAVI. The radial, circumferential strain and LVEF does not change significantly in all patients acutely after TAVI. These data suggest that sensitive new echo methods can reliably detect early regional changes of myocardial function after TAVI before benefits in LVEF are detectable.
A mutant cotton fatty acid desaturase 2-1d allele causes protein mistargeting and altered seed oil composition (2023)

These results provide the biochemical underpinning that links a genetic lesion present in a limited group of South American pima cotton accessions and their rare seed oil oleic acid traits. Markers developed to the mutant desaturase allele are currently being used in breeding programs designed to introduce this trait into agronomic upland cotton varieties.
Production, Characterization, and Wear Behaviour of Plasma Jet CVD Diamond Films on Hard Metal Cutting Tools (1996)

The dc plasma jet chemical vapour deposition (CVD) process is one of the most promising processes for the synthesis of polycrystalline diamond films. The obtainable linear growth rates in the range of 100 μm/h are much higher than the growth rates for other CVD processes like microwave or hot filament CVD (1 to 10 μm/h). Wear resistant diamond coatings on cutting tools are very interesting for industrial applications. The poor adhesion of the diamond films is the main problem with these systems. Therefore a mechanical or chemical pretreatment of the substrate surface is used to improve the adhesion of the coating. The influence of mechanical pretreatment by grinding and polishing with diamond powder as well as chemical etching with different solutions or combinations of these pretreatments were examined on WC-Co hard metals. The diamond films were synthesized on these pretreated cutting tools by dc plasma jet CVD. Scanning electron microscopy, EDS analysis, X-ray diffraction, and Raman spectroscopy have been used to characterize the coatings. Adhesion and wear resistance of the diamond films have been investigated using turning tests on metal matrix composites without lubricant. The improvement in adhesion of the diamond coatings is found to be highest after a combined mechanical and chemical pretreatment.
First-line lenvatinib plus pembrolizumab plus chemotherapy versus chemotherapy in advanced/metastatic gastroesophageal adenocarcinoma (LEAP-015): Safety run-in results. (2023)

411 Background: LEAP-015 (NCT04662710) is a randomized, open-label, 2-part, phase 3 study of the safety and efficacy of lenvatinib + pembrolizumab + chemotherapy as a first-line treatment for advanced/metastatic gastroesophageal adenocarcinoma. We report findings from part 1, the safety run-in, of LEAP-015. Methods: Eligible patients had untreated, HER2-negative, locally advanced unresectable or metastatic gastroesophageal adenocarcinoma, measurable disease per RECIST v1.1, and ECOG performance status 0 or 1. In part 1, patients received induction with IV pembrolizumab 400 mg Q6W (×2) + oral lenvatinib 8 mg QD + investigator choice of chemotherapy (capecitabine + oxaliplatin [CAPOX] Q3W ×4 or 5-fluorouracil + leucovorin + oxaliplatin [mFOLFOX6] Q2W ×6) and consolidation with pembrolizumab 400 mg Q6W for ≤16 doses + lenvatinib 20 mg QD; dose-limiting toxicities (DLTs), defined as selected prespecified grade ≥3 adverse events (AEs) or any-grade thromboembolic events, were evaluated for 21 days after the first dose of study intervention. If ≥3 DLTs occurred in either oxaliplatin-containing regimen, then enrollment in part 2 may be delayed to allow for the examination of safety data and to consider design changes. In part 1, the primary end point was safety and tolerability in all patients. Preliminary efficacy was also assessed in part 1. Objective response and disease control rate were assessed per RECIST version 1.1 by blinded independent central review. Results: In part 1, 15 pts received ≥1 dose of lenvatinib + pembrolizumab + chemotherapy. 1 DLT of grade 3 asthenia occurred in the CAPOX cohort and 1 DLT of grade 4 neutropenia occurred in the FOLFOX cohort. Median time from first dose to data cutoff (Oct 13, 2021) was 7 mo (range, 7-9). Treatment-related AEs occurred in 14 patients (93%), with grade 3/4 events in 8 patients (53%). 4 patients (27%) discontinued any drug because of a treatment-related AE, and no patient discontinued all drugs because of a treatment-related AE. No patients died because of a treatment-related AE. No grade ≥3 immune-mediated AEs or infusion reactions occurred. Objective response was reported in 11 of 15 patients (73%; 95% CI, 45-92) who received ≥1 dose of treatment. Disease control rate was reported in 14 of 15 patients (93%; 95% CI, 68-100) who received ≥1 dose of treatment. Conclusions: In the safety run-in of LEAP-015, lenvatinib + pembrolizumab + chemotherapy was associated with a manageable safety profile in the first-line treatment of advanced/metastatic gastroesophageal adenocarcinoma. Preliminary antitumor activity was observed for lenvatinib + pembrolizumab + chemotherapy. Part 2 will evaluate the efficacy and safety of lenvatinib + pembrolizumab + chemotherapy versus chemotherapy in this same patient population and patient accrual is ongoing. Clinical trial information: NCT04662710 .