gebhart/patrepeval huggingface dataset:
The elusive hair cell gating spring, a potential role for the lipid membrane (2013)

Deflection of auditory hair cell hair bundle results in a nonlinear (i.e., non Hookean) force-displacement relationships whose molecular mechanism remains elusive. A gating spring model posits that mechanosensitive channels are in series with a spring such that channel opening puts the activation gate in series with the spring, thus reducing spring extension until further stimulation is provided. Here we present a theoretical analysis of whether the lipid membrane might be the source of nonlinearity. A hair bundle kinematic model is coupled with a lipid membrane model that includes a diffusible compartment into which the tip-link embeds and a minimally diffusive reservoir pool. Using physiological parameters, this model was capable of reproducing nonlinear force-displacement plots, including a negative stiffness component but required a standing tip-link tension. In addition, this model suggests the mechanotransducer channel is most sensitive to curvature forces that are located within 2 nm of the tip-link. [Work supported in part by Grant Nos. R01-DC07910 and R01-DC03896 from the NIDCD of NIH and by The Timoshenko fund from Mechanical Engineering Department at Stanford University].
Development of Novel Bifunctional Compounds That Induce Apoptosis in Prostate Cancer Cells (2004)

Abstract : The objective of our research is to develop more effective therapeutics for the treatment of prostate cancers. One novel bifunctional compound (11beta) that we have prepared rapidly induces apoptosis in several prostate cancer cell lines in vitro. The 11beta compound contains a chemically reactive nitrogen mustard linked to a steroid moiety that binds with high affinity to the androgen and progesterone receptor proteins. This compound was designed to create DNA adducts that form tight complexes with these steroid receptors that make the adducts difficult to repair in prostate cancer cells. Preliminary studies of 11beta in cell culture indicated that its effects on prostate cancer cells were different from those of other alkylating agents used in chemotherapy. The apoptotic responses of prostate cancer cells suggested that the 11beta compound might be a useful agent for chemotherapy. The Specific Aims of our research are to understand the fate of 11beta-DNA adducts in treated cells and investigate the mechanisms that lead to apoptosis. We also proposed experiments to assess the antitumor potential of 11beta in animal models of human prostate cancer.
Effects of the front surface field in n-type interdigitated back contact silicon heterojunctions solar cells (2010)

Previous simulations of interdigitated back contact silicon heterojunction (IBC-SiHJ) solar cells have indicated that front surface passivation is a critical factor in the performance of such cells. This is why we here focus on the effect of a front surface field (FSF) layer by 2D numerical modelling. A FSF layer made of a highly doped thin crystalline silicon top layer makes the cell performance insensitive to the surface recombination velocity up to quite high values (5000 cm/s). It also reduces the lateral resistance losses due to the increased lateral current through the doped layer particularly in IBC-SiHJ solar cells with large pitches. A FSF layer can also be produced by doped hydrogenated amorphous silicon due to the induced accumulation layer at the crystalline silicon surface. The positive effect of such layer strongly depends on the a-Si:H/c-Si interface quality.
Scale-up strategies for the blending of miscible liquids with large viscosity differences (2019)

International audience
Poynting Vector Analysis of Synchronous Generators Using Field Simulations (2007)

The Poynting vector has been used to gain an understanding of energy flow in rotating electrical machines. Previous studies of energy flow in rotating electrical machines have used the Poynting vector in crude formulas to obtain a qualitative picture. In this paper, we present a study based on numerically calculated fields and quantities entering the Poynting vector. We obtained a detailed understanding of how energy flows in the air gap and into the winding of a synchronous generator. In particular, we found that, at no-load, energy is flowing both to and from the stator as a result of cogging, while for normal load cases the energy flow is unidirectional.
Piecewise planar stereo for image-based rendering (2009)

We present a novel multi-view stereo method designed for image-based rendering that generates piecewise planar depth maps from an unordered collection of photographs.
Abstract 3600: Preclinical pharmacokinetic and biomarker analysis of AMG 900, an orally available small molecule inhibitor of aurora kinases, in human xenograft tumor and surrogate tissues (2010)

Abstract Background: The aurora family of serine-threonine kinases (Aurora-A, -B, -C) regulate cell-cycle progression in mammalian cells. Aurora kinases A and B are essential for proper chromosome congression, segregation, and cytokinesis during mitosis, whereas aurora kinase C function appears restricted to male meiosis. Aurora kinase B is responsible for the direct phosphorylation of histone H3 on serine-10 (p-histone H3). Aurora kinase A and B expression is elevated in a variety of human cancers and is associated with advanced clinical staging and poor prognosis. With the emergence of aurora kinases as key mitotic regulators and their potential role in tumorigenesis, we developed AMG 900, a novel ATP competitive small molecule inhibitor, that is highly potent and selective for aurora kinases A, B, and C. In vivo, AMG 900 inhibits the growth of multiple human tumor xenografts, including multidrug-resistant models. Objective: The aim of this study was to establish a pharmacokinetic-pharmacodynamic (PK-PD) relationship for AMG 900 in human tumor xenografts and surrogate tissues. Results: In nude mice, oral administration of AMG 900 inhibited p-histone H3 in tumors and bone marrow in a concentration- and dose-dependent manner. To further refine the AMG 900 PK-PD relationship, p-histone H3 IC50 values for bone marrow and dissociated COLO 205 tumors from mice were associated with plasma concentrations of 294 and 273 ng/mL, respectively. The duration of target coverage required for anti-tumor efficacy was determined to be &amp;gt; 6 hours per day above the in vivo p-histone H3 IC50 using different dosing schedules. To explore whether skin could be a suitable surrogate tissue for measuring p-histone H3 inhibition, tumor-bearing mice were administered AMG 900 at 3.75, 7.5, and 15 mg/kg for 3 hours. Significant suppression of p-histone H3 in skin was only observed at 15 mg/kg (p &amp;lt; 0.0001), whereas in tumor, a dose-dependent inhibition was achieved at all doses (p &amp;lt; 0.0015). To determine the feasibility of measuring p-histone H3 using fine-needle aspirate (FNA) tumor biopsies, tumor-bearing mice were administered AMG 900 at 15 mg/kg for 3 hours. Treatment with AMG 900 significantly inhibited p-histone H3 (&amp;gt; 99%, p &amp;lt; 0.0001) in COLO 205 tumors, suggesting that FNA biopsies may be a viable approach for assessing AMG 900 PD effects in the clinic. Conclusion: These studies demonstrate that AMG 900 inhibits p-histone H3 in tumors and surrogate tissues, although tissues such as skin may be less sensitive to assess PD effects. The use of p-histone H3 as a biomarker to determine plasma levels of AMG 900 required to inhibit aurora B activity may be useful in clinical studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3600.
Neurophysiology of lower urinary tract function and dysfunction. (2003)

With the continued aging of the population, the incidence of conditions associated with bladder control will continue to grow. In this article, we review the neurophysiology and pathophysiology of the bladder and urethra and discuss logical concepts for the development of novel drug therapy that can better help the expanding population of patients with bladder control problems.
CD28 dependence of T cell differentiation to IL-4 production varies with the particular type 2 immune response (1997)

T cell differentiation to effector cell function is required for the development of a type 2 immune response. The T cell surface molecule, CD28, is widely considered to be the principal costimulatory molecule involved in T cell differentiation to effector function, including IL-4 production, although this has been difficult to directly examine in vivo. We have studied in vivo differentiation to T cell effector function during two type 2 immune responses in CD28 knockout mice: the systemic immune response to goat anti-mouse IgD Ab and the mucosal immune response following oral inoculation with the nematode parasite, Heligmosomoides polygyrus. Our results show that in C57BL/6 CD28 knockout mice elevations in IL-4 gene expression and protein secretion are blocked during the immune response to goat anti-mouse IgD, and associated increases in serum IgG1 and IgE are also inhibited to untreated control levels. In marked contrast, T cell differentiation to IL-4 production is comparable in C57BL/6 CD28 -/- and CD28 +/+ H. polygyrus-inoculated mice, and elevations in both serum IgG1 and IgE levels occur. These results indicate that the specific kind of type 2 immune response determines whether T cell differentiation to IL-4 production is CD28 dependent.
Proctitis 1 Week after Stereotactic Body Radiation Therapy for Prostate Cancer: Implications for Clinical Trial Design (2016)

The rate and severity of acute proctitis following prostate SBRT peaked at 1 week after treatment and returned to baseline by 3 months. Toxicity assessment at 1 week can therefore minimize recall bias and should aid in the design of future clinical trials focused on accurately capturing and minimizing acute morbidity following SBRT.
Profili penali delle criptovalute (2019)

La blockchain: la tecnologia alla base delle criptovalute. Profili giuridici. L'innovazione tecnologica e le trasformazioni socio-economiche. Le criptovalute e profili di rilevanza penale. L'abusivismo bancario e finanziario. I profili processuali: digital forensics e prove elettroniche. I cybercrimes e le problematiche processuali.
MUC1* Ligand, NM23-H1, Is a Novel Growth Factor That Maintains Human Stem Cells in a More Naïve State (2013)

We report that a single growth factor, NM23-H1, enables serial passaging of both human ES and iPS cells in the absence of feeder cells, their conditioned media or bFGF in a fully defined xeno-free media on a novel defined, xeno-free surface. Stem cells cultured in this system show a gene expression pattern indicative of a more "naïve" state than stem cells grown in bFGF-based media. NM23-H1 and MUC1* growth factor receptor cooperate to control stem cell self-replication. By manipulating the multimerization state of NM23-H1, we override the stem cell's inherent programming that turns off pluripotency and trick the cells into continuously replicating as pluripotent stem cells. Dimeric NM23-H1 binds to and dimerizes the extra cellular domain of the MUC1* transmembrane receptor which stimulates growth and promotes pluripotency. Inhibition of the NM23-H1/MUC1* interaction accelerates differentiation and causes a spike in miR-145 expression which signals a cell's exit from pluripotency.
Analysis and synthesis of signal set with constrained magnitude spectrum (2002)

In this paper, a new method is introduced for designing signals with quadratic phase spectrum and constant magnitude spectrum at passband. This method is based on a recently found upper bound on the cross-correlation magnitude function. It is shown that in order to get lower values of the cross-correlation magnitude between any two signals in the set, the coefficients of phase function of signals should be equally spaced along one axis of an ellipse determined by the bandwidth and time duration of signals. Furthermore, a new tighter upper bound on maximum of cross-correlation magnitude is also given in the paper.
Screen‐printed silver‐ink antennas for frequency‐reconfigurable architectures in LTE phones (2014)

Screen printing is a proven manufacturing technology enabling high‐volume production at low cost. The achievable efficiency of a screen‐printed silver antenna structure for fourth generation (4G) mobile phone implementation is investigated, with a market‐ready solution. The contribution of each element of the solution to the total efficiency is detailed.
Studies on the mechanisms of food-stimulated gastric acid secretion in normal human subjects. (1976)

Liquid test meals were infused into the stomach and acid secretion was measured by intragastric titration at pH 5.0 Acid secretion after 500 or 750-ml sodium chloride meals was two to three times higher than basal secretion rates and was equivalent to 25-30% of the peak acid output in response to histamine. Since these meals did not cause a rise in serum gastrin concentration, it is assumed that they stimulate acid secretion by causing distention of the body and fundus of the stomach. Compared with this distention stimulus, glucose meals had no effect on acid secretion and fat-inhibited acid secretion; however, both glucose and fat caused an increase in serum gastrin concentration. Amino acids caused a much greater increase in serum gastrin concentration and enhanced acid secretion above that noted with distention alone. In contrast, albumin did not enhance the serum gastrin concentration or stimulate acid secretion to a statistically significant extent. There was a close correlation between the rise in serum gastrin concentration and rate of acid secretion after different test meals when average results for each test meal were plotted. However, there was a poor correlation between acid secretion and serum gastrin concentration when the responses of the individual subjects with a given test meal were compared. Our interpretations are: (a) Distention is an important stimulant of the acid-secretory response to a meal, and this is not mediated by gastrin release. (b) Gastrin is one but probably not the only mediator of the chemical phase of acid secretion, i.e., acid secretion noted with amino acids that cannot be explained by distention. (c) Glucose and fat also release gastrin; however, with glucose the rise in serum gastrin is too small and too transient to enhance acid secretion, and fat probably releases unmeasured inhibitors that overwhelm the effect of gastrin on acid secretion. (d) Albumin is not a stimulant of acid secretion.
Isoprenoid biosynthesis in bacteria: Two different pathways? (1993)

The biosynthesis of isopentenylpyrophosphate, a central intermediate of isoprenoid formation, was investigated in six different bacterial organisms. Cell-free extracts of Myxococcus fulvus, Staphylococcus carnosus, Lactobacillus plantarum and Halobacterium cutirubrum converted [14C]acetyl-CoA or [14C]hydroxymethylglutaryl-CoA to [14C]mevalonic acid. Furthermore, [14C]mevalonic acid, [14C]mevalonate-5-phosphate and [14C]mevalonate-5-pyrophosphate were metabolized to [14C]isopentenylpyrophosphate. These data demonstrated the in vitro operation of acetoacetate pathway for the formation of isopentenylpyrophosphate in bacteria. In contrast, no intermediates of this reaction sequence could be detected using cell-free extracts of Zymomonas mobilis and Escherichia coli. These results indicate that at least two different pathways for the biosynthesis of isopentenylpyrophosphate are present in bacteria.
High Q SiC on Silicon Microresonators (2013)

We demonstrate a 20um radius suspended microring resonator with Q=19,000 fabricated on SiC-on-silicon substrates. We estimate the fundamental material losses to be less than 3.3 dB/cm indicating that quality factors greater than 105 are possible.
The COI mitochondrial gene encodes a minor histocompatibility antigen presented by H2-M3 (1996)

We found that (LP x C57BL/6)F1 mice could raise a CTL response against parental C57BL/6 cells. These CTLs recognized a maternally transmitted, H2-M3wt-restricted, minor histocompatibility Ag (MiHA) that is widely distributed among many strains of mice and encoded by the COI mitochondrial gene. The wild-type MiHA is the COI N-terminal hexapeptide. Sequencing the 5' end of the COI gene in LP and C57BL/6 mice showed that the LP allele arose by a T-->C transition in the third codon, which caused substitution of threonine for isoleucine. Molecular characterization of this MiHA and the demonstration that it is presented exclusively by H2-M3: 1) support the concept that differential expression of MiHA in MHC-identical animals is caused by polymorphism of the MiHA gene proper; 2) expand our knowledge of the repertoire of self-peptides naturally presented by H2-M3 and show that this MHC class I molecule can present short endogenous peptide ligands; and 3) suggest that mitochondrial DNA mutations that modify the repertoire of H2-M3-associated mitochondrial peptides are representative of mitochondrial DNA mutations in general.
Investigation of heating risks during MR-guided microwave ablation using applicators without active shaft cooling (2023)

Execution of MR sequences (RF-heating) and/or microwave energy during MRgMWA may lead to harmful heating at tissue surface with non-cooled MR-conditional applicators. MR imaging was performed using a high SAR sequence and several geometric orientations of phantom/applicators to assess RF-heating impact. Applicator insertion depth (with/without ultrasound gel) and spacing of two applicators on shaft heating were evaluated. Negligible temperature changes due to RF-heating were observed. Significant temperature increases were measured during MWA due to action of MWA system/applicator, which can be mitigated by increasing the applicator insertion depth. Further reduction in temperature change can be achieved by using ultrasound gel.
The PARP Inhibitor AZD2461 Provides Insights into the Role of PARP3 Inhibition for Both Synthetic Lethality and Tolerability with Chemotherapy in Preclinical Models (2016)

The PARP inhibitor AZD2461 was developed as a next-generation agent following olaparib, the first PARP inhibitor approved for cancer therapy. In BRCA1-deficient mouse models, olaparib resistance predominantly involves overexpression of P-glycoprotein, so AZD2461 was developed as a poor substrate for drug transporters. Here we demonstrate the efficacy of this compound against olaparib-resistant tumors that overexpress P-glycoprotein. In addition, AZD2461 was better tolerated in combination with chemotherapy than olaparib in mice, which suggests that AZD2461 could have significant advantages over olaparib in the clinic. However, this superior toxicity profile did not extend to rats. Investigations of this difference revealed a differential PARP3 inhibitory activity for each compound and a higher level of PARP3 expression in bone marrow cells from mice as compared with rats and humans. Our findings have implications for the use of mouse models to assess bone marrow toxicity for DNA-damaging agents and inhibitors of the DNA damage response. Finally, structural modeling of the PARP3-active site with different PARP inhibitors also highlights the potential to develop compounds with different PARP family member specificity profiles for optimal antitumor activity and tolerability. Cancer Res; 76(20); 6084-94. ©2016 AACR.
Investigation of Buried-Well Potential Perturbation Effects on SEU in SOI DICE-Based Flip-Flop Under Proton Irradiation (2020)

The effects of buried-well potential perturbation under the buried-oxide (BOX) layer are studied in both a heavy-ion single event upset (SEU) test and a high-energy proton-SEU test of a silicon-on-insulator (SOI) dual interlocked storage cell (DICE)-based flip-flop. Their dependence on incident angle and back bias is discussed. We fabricated both DICE-based flip-flop and conventional flip-flop, which are designed as 80 000-stage shift-register chains. In a heavy-ion test, a considerable number of SEUs were observed at back bias exceeding 2.4 V, and a ten-times larger SEU-cross section was finally recorded at back bias of 3.0 V compared with the total active area of a DICE-based flip-flop cell. This marks the first case where DICE topology was found to be broken by buried-well potential perturbation on an SOI DICE-based flip-flop. In a proton test, one error was observed at back bias of 2.0 V. The SEU rate in the Van Allen belt at an altitude of 2300 km and an inclination of 90° was estimated as being once every 5 years.
The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium (2022)

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49–0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48–0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.
On Vinnicombe metrics and the stability robustness of linear time-varying systems (2004)

We present two novel approaches for obtaining stability robustness information about linear time-invariant systems with norm-bounded time-varying output multiplicative perturbations using Vinnicombe metrics. First, a time-varying Vinnicombe metric approximation between a nominal linear time-invariant system and the perturbed linear time-varying system is developed, and we show that a calculable tight upper bound may be placed on the approximation for a subclass of small, periodic output multiplicative errors. Second, we show that a worst-case time-invariant Vinnicombe metric may be used to obtain stability robustness information about the perturbed time-varying system.