gebhart/patrepeval huggingface dataset:
Phase I study of preoperative capecitabine and lenvatinib with external radiation therapy in locally advanced rectal adenocarcinoma. (2020)

125 Background: Neoadjuvant chemo-radiation is a standard of care for locally advanced rectal cancer. Patients with pathologic complete response (pCR) have improved outcomes with less local and systemic failure. Dual targeting with platelet derived growth factor (PDGF) and vascular endothelial growth factor receptor (VEGFR) in combination with radiation can escalate tumor response with radiation. Lenvatinib is an oral multi-kinase inhibitor and had shown potent anti-tumor activity in xenograft models cultured with human colorectal cancer (CRC) lines. Methods: Patients with stage II or III rectal cancer, confirmed by endoscopic ultrasound or MRI, were recruited in 3 cohorts of 3 patients per dose level, with an expansion cohort at the MTD. Lenvatinib oral daily dose started at 14 mg (cohort 1) and was escalated to 20 mg (cohort 2) followed by 24 mg (cohort 3). In this 3+3 design, patients received dose escalation of lenvatinib with standard doses of capecitabine (850 mg/m 2 PO BID) concurrent with external beam radiation on days 1-5 weekly for 28 treatments. Following completion patients underwent surgery in 6-10 weeks. Results: Twenty patients with median age of 55 were enrolled in 3 cohorts (1 patient was ineligible). There were no dose limiting toxicity at the maximum tested dose of lenvatinib (24 mg). Two patients are still awaiting surgery. 12 patients have undergone low anterior resection and 5 patients have had abdominoperineal resection. Therefore, out of 17 patients, 29.4% (5/17) showed pCR, and downstaging was observed in 71% of the patients (12/17). The mean neoadjuvant rectal cancer score (NAR) was 11.4 and median NAR was 8.43. Six patients had grade 3 adverse events (AEs) (1 rectal pain,1 transaminitis, 2 lymphopenia, 1 HTN, 1 with both leukocytosis and hyponatremia). No grade 4 AEs were noted. Most common AEs were hypertension, rectal pain, nausea, diarrhea, fatigue and dermatitis. No peri operative complications were observed. Conclusions: The study shows that the combination of lenvatinib and capecitabine with radiation is well tolerated in locally advanced rectal cancer with promising mean NAR score. The encouraging results will need to be validated in a randomized study. Clinical trial information: NCT02935309.
Force Control System for Autonomous Micro Manipulation (2002)

A dexterous micro manipulation system was developed for applications such as assembling micro machines, manipulating cells, and micro surgery. We have proposed a concept of a two-fingered micro hand, designed and built a prototype. We succeeded in performing basic micro manipulations with a teleoperation, including the grasp, release, and rotation of a microscopic object. The micro hand is controlled with a position control only. An operator has to guess a micro grasping force on the object from a microscope image. The accurate micro manipulation depends on a skill of the operator yet. For an easy manipulation and an automatic manipulation, it is necessary to measure the micro forces between the finger and the object. A micro force sensor has developed for a force control in micro manipulation on a corroboration research of AIST and Olympus Optical Co., Ltd. Its resolution is 0.5 nN in theoretically. In this paper, we will mention the micro force sensor and to perform an automatic micro manipulation with installing the sensor and a force control system. Basic experiment shows excellent micro capability.
Improving the quality of neural TTS using long-form content and multi-speaker multi-style modeling (2022)

Neural text-to-speech (TTS) can provide quality close to natural speech if an adequate amount of high-quality speech material is available for training. However, acquiring speech data for TTS training is costly and time-consuming, especially if the goal is to generate different speaking styles. In this work, we show that we can transfer speaking style across speakers and improve the quality of synthetic speech by training a multi-speaker multi-style (MSMS) model with long-form recordings, in addition to regular TTS recordings. In particular, we show that 1) multi-speaker modeling improves the overall TTS quality, 2) the proposed MSMS approach outperforms pre-training and fine-tuning approach when utilizing additional multi-speaker data, and 3) long-form speaking style is highly rated regardless of the target text domain.
Immunohistochemical study of the hnRNP A2 and B1 in the rat forebrain (2000)

Immunohistochemical techniques were employed to examine the distribution of RNA-binding proteins A2 and B1 in the rat forebrain. Intense A2 and B1 immunolabeling were observed in the nucleoplasm of the neurons in the cerebral cortices, hippocampal formation, olfactory regions, caudate-putamen as well as the supraoptic nucleus of hypothalamus. In contrast, within the bed nucleus of the stria terminalis, as well as the medial and lateral habenular nucleus of thalamus, immunoreactivity for both proteins was weak. Within the globus pallidus and thalamic nucleus immunoreactivity for A2 was hardly detectable despite of intense B1 immunolabeling, while within the endopiriform nucleus and lateral and basolateral nucleus of amygdala intensity of B1 immunolabeling was relatively weak compared to A2. Our study suggests that the distribution of A2 and B1 are not constant throughout the forebrain and this diversity may reflect the post-transcriptional regulation of cell-specific gene expression of neuronal cells.
A Mutation in Myo15 Leads to Usher-Like Symptoms in LEW/Ztm-ci2 Rats (2011)

The LEW/Ztm-ci2 rat is an animal model for syndromal deafness that arose from a spontaneous mutation. Homozygous animals show locomotor abnormalities like lateralized circling behavior. Additionally, an impaired vision can be observed in some animals through behavioral studies. Syndromal deafness as well as retinal degeneration are features of the Usher syndrome in humans. In the present study, the mutation was identified as a base substitution (T->C) in exon 56 of Myo15, leading to an amino acid exchange from leucine (Leu) to proline (Pro) within the carboxy-terminal MyTH4 domain in the proteins' tail region. Myo15 mRNA was expressed in the retina as demonstrated for the first time with the help of in-situ hybridization and PCR. To characterize the visual phenotype, rats were examined by scotopic and photopic electroretinography and, additionally, histological analyses of the retinas were conducted. The complete loss of sight was detected along with a severe degeneration of photoreceptor cells. Interestingly, the manifestation of the disease does not solely depend on the mutation, but also on environmental factors. Since the LEW/Ztm-ci2 rat features the entire range of symptoms of the human Usher syndrome we think that this strain is an appropriate model for this disease. Our findings display that mutations in binding domains of myosin XV do not only cause non-syndromic hearing loss but can also lead to syndromic disorders including retinal dysfunction.
Chronic Inflammatory Status Observed in Patients with Type 2 Diabetes Induces Modulation of Cytochrome P450 Expression and Activity (2021)

Diabetes mellitus is a metabolic disease that causes a hyperglycemic status which leads, over time, to serious damage to the heart, blood vessels, eyes, kidneys and nerves. The most frequent form of diabetes is type 2 diabetes mellitus (T2DM) which is often part of a metabolic syndrome (hyperglycaemia, hypertension, hypercholesterolemia, abdominal obesity) that usually requires the use of several medications from different drug classes to bring each of these conditions under control. T2DM is associated with an increase in inflammatory markers such as interleukin-6 (IL-6) and the tumor necrosis factor alpha (TNF-α). Higher levels of IL-6 and TNF-α are associated with a downregulation of several drug metabolizing enzymes, especially the cytochrome P450 (P450) isoforms CYP3As and CYP2C19. A decrease in these P450 isoenzymes may lead to unexpected rise in plasma levels of substrates of these enzymes. It could also give rise to a mismatch between the genotypes determined for these enzymes, the predicted phenotypes based on these genotypes and the phenotypes observed clinically. This phenomenon is described as phenoconversion. Phenoconversion typically results from either a disease (such as T2DM) or concomitant administration of medications inducing or inhibiting (including competitive or non-competitive inhibition) a P450 isoenzyme used by other substrates for their elimination. Phenoconversion could have a significant impact on drug effects and genotypic-focused clinical outcomes. As the aging population is exposed to polypharmacy along with inflammatory comorbidities, consideration of phenoconversion related to drug metabolizing enzymes is of importance when applying pharmacogenomic results and establishing personalized and more precise drug regimens.
Virtual Differential Passivity based Control for Tracking of\n Flexible-joints Robots (2017)

Based on recent advances in contraction methods in systems and control, in\nthis paper we present the virtual differential passivity based control (v-dPBC)\ntechnique. This is a constructive design method that combines the concept of\nvirtual systems and of differential passivity. We apply the method to the\ntracking control problem of flexible joints robots (FJRs) which are formulated\nin the port-Hamiltonian (pH) framework. Simulations on a single flexible joint\nlink are presented for showing the performance of a controller obtained with\nthis approach.\n
Frequent mutation of the 5' noncoding region of the BCL-6 gene in acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas. (1997)

Acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphomas (AIDS-NHL), a major source of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals, are derived from B cells and are classified into two major categories, Burkitt's lymphoma (BL) and diffuse large cell lymphoma (DLCL). Anaplastic large cell lymphoma (ALCL) and body-cavity-based lymphoma (BCBL) represent less frequent AIDS-NHL types. The molecular pathogenesis of AIDS-NHL is characterized by distinct genetic pathways, including chromosomal rearrangements of c-MYC and BCL-6 in AIDS-BL and AIDS-DLCL, respectively. In addition to gross rearrangements, recent evidence has suggested that BCL-6 may also be affected by mutations of the gene 5' noncoding regions. Here we have investigated the distribution of BCL-6 mutations in a panel representative of all the AIDS-NHL subtypes. Forty-three AIDS-NHL were analyzed for mutations in the first exon-first intron boundary region of BCL-6. Mutations were detected in all categories of AIDS-NHL (25 of 43 cases; 58%), including 12 of 20 AIDS-BL, 10 of 15 AIDS-DLCL, two of three AIDS-ALCL, and one of five of AIDS-BCBL. BCL-6 mutations occurred independent of BCL-6 rearrangements and presence of other genetic lesions frequently associated with AIDS-NHL. These results indicate that mutations of BCL-65' noncoding regions represent the most common genetic alteration presently detectable in AIDS-NHL. The frequency of these mutations, as well as their location in the proximity of BCL-6 regulatory sequences, suggest that they may play a role in AIDS-related lymphomagenesis.
Circadian patterns of gene expression in the human brain and disruption in major depressive disorder (2013)

A cardinal symptom of major depressive disorder (MDD) is the disruption of circadian patterns. However, to date, there is no direct evidence of circadian clock dysregulation in the brains of patients who have MDD. Circadian rhythmicity of gene expression has been observed in animals and peripheral human tissues, but its presence and variability in the human brain were difficult to characterize. Here, we applied time-of-death analysis to gene expression data from high-quality postmortem brains, examining 24-h cyclic patterns in six cortical and limbic regions of 55 subjects with no history of psychiatric or neurological illnesses ("controls") and 34 patients with MDD. Our dataset covered ~12,000 transcripts in the dorsolateral prefrontal cortex, anterior cingulate cortex, hippocampus, amygdala, nucleus accumbens, and cerebellum. Several hundred transcripts in each region showed 24-h cyclic patterns in controls, and >100 transcripts exhibited consistent rhythmicity and phase synchrony across regions. Among the top-ranked rhythmic genes were the canonical clock genes BMAL1(ARNTL), PER1-2-3, NR1D1(REV-ERBa), DBP, BHLHE40 (DEC1), and BHLHE41(DEC2). The phasing of known circadian genes was consistent with data derived from other diurnal mammals. Cyclic patterns were much weaker in the brains of patients with MDD due to shifted peak timing and potentially disrupted phase relationships between individual circadian genes. This transcriptome-wide analysis of the human brain demonstrates a rhythmic rise and fall of gene expression in regions outside of the suprachiasmatic nucleus in control subjects. The description of its breakdown in MDD suggests potentially important molecular targets for treatment of mood disorders.
Expression of the Rho-GEF Pbl/ECT2 is regulated by the UBE3A E3 ubiquitin ligase (2006)

We applied genetic tools available in Drosophila to identify candidate substrates of the UBE3A ubiquitin ligase, the gene responsible for Angelman syndrome (AS). Human UBE3A was expressed in Drosophila heads to identify proteins differentially regulated in UBE3A-expressing versus wild-type extracts. Using two-dimensional gel and MALDI-TOF analysis, we detected 20 proteins that were differentially regulated by over-expression of human UBE3A in Drosophila heads. One protein responsive to UBE3A was the Rho-GEF pebble (pbl). Here, we present three lines of evidence suggesting that UBE3A regulates Pbl. First, we show genetic evidence that UBE3A and the Drosophila de-ubiquitinase fat facets (faf) exert opposing effects on Pbl function. Secondly, we find that both Pbl and ECT2, the mammalian orthologue of Pbl called epithelial cell transforming sequence 2 oncogene, physically interact with their respective ubiquitin E3 ligases. Finally, we show that Ect2 expression is regulated by Ube3a in mouse neurons as the pattern of Ect2 expression is dramatically altered in the hippocampus and cerebellum of Ube3a null mice. These results suggest that an orthologous UBE3A post-translational regulatory pathway regulates neuronal outgrowth in the mammalian brain and that dysregulation of this pathway may result in neurological phenotypes including AS and possibly other autism spectrum disorders.
Improving Bed Movement Physics in Biomass Computational Fluid Dynamics Combustion Simulations (2019)

Abstract A detailed description of the first functional new approach to simulate the bed physics in biomass boilers in a Eulerian mathematical framework is presented. In particular, the analysis of the context of the collapse due to gravitational forces, the design of an automated algorithm that is responsible for its simulation under ANSYS‐Fluent, the concrete implementation of this algorithm, and its test with experimental contrasted data are described. The proposed solution can replicate the angle of repose of different fuels in biomass combustion boilers by implementing a series of geometric mechanisms applied to the mesh. The selected approach mainly responds to a computational efficiency requirement; both memory management and execution speed are relevant.
Hydrogen assisted growth of Fe/V superlattices (2006)

The functionality of magnetic heterostructures is strongly affected by the interface structure and morphology as well as by the crystalline quality. Using Fe/V superlattices, serving as model systems for exchange coupling and for superconducting spin valves, we show that the excellent interfacial properties can be further improved by hydrogen assisted growth. The role of the hydrogen thereby is twofold. It reduces thickness fluctuations and improves the crystalline quality. Sputter deposited Fe/V superlattices grown at a partial pressure of 2 × 10−6 mbar are atomically flat and possess a residual resistivity ratio which is significantly improved as compared to those of conventionally grown samples.
Discontinuous Conduction in Mouse Bundle Branches Is Caused by Bundle-Branch Architecture (2005)

Comparison of connexin expression/distribution, geometry of the BBs, and CV characteristics suggests that increased path length for activation resulting from BB geometry is responsible for the apparently reduced CV in the midseptal BB of the mouse heart.
Delayed release of drain in total knee replacement reduces blood loss. A prospective randomised study. (2006)

Total knee arthroplasty is sometimes associated with major post-operative bleeding, often requiring transfusion. A prospective, randomised study was undertaken to assess the effect on post-operative bleeding of delaying release of the clamp on the suction drains. One hundred patients were allocated into two groups: Group A- immediate release of drain following release of tourniquet, and Group B- delayed release of the drain clamp by one hour. There was a statistically significant reduction (p = < 0.001) in postoperative bleeding between group A (1050 ml; 95%CI 728 - 1172 ml) compared to group B (732 ml; 95% CI 620- 845 ml). Average drop in corrected haemoglobin and postoperative transfusion requirement were also less in the delayed group. The results show that delaying release of the drains by one hour reduces postoperative blood loss and transfusion requirement following total knee arthroplasty.
Adsorption properties of chalcogen atoms on a golden buckyball Au<sub>16</sub><sup>−</sup>from first principles (2011)

Using first-principles density functional theory, we investigate the adsorption properties of chalcogen elements (oxygen and sulfur) on an anionic golden nanocage Au(16)(-) and its effects on the structural and electronic properties of the golden cage. In particular, we find that when a sulfur atom is encapsulated inside Au(16)(-), its bonding character with Au atoms appears ionic due to electron transfer from sulfur to the gold nanocage. In contrast, the exohedrally adsorbed S atom tends to have strong orbital hybridization with the golden nanocage. For an oxygen adsorption case, electrons from the golden cage tend to be shared with the adsorbed O atom exhibiting strong orbital hybridization, regardless of its adsorption sites. To investigate the transition behaviors between the most stable exohedral and endohedral adsorption configurations, we calculate the activation and reaction energies in the transition. The oxygen atom experiences a lower energy barrier than the sulfur atom due to its smaller atomic radius. Finally, we explore the vibrational properties of S- or O-adsorbed Au(16)(-) buckyballs by calculating their infrared spectra.
Extended Mobile IPv6 Route Optimization for Mobile Networks in Local and Global Mobility Domain (2012)

Network mobility (NEMO) route optimization support is strongly demanded in next generation networks; without route optimization the mobile network (e.g., a vehicle) tunnels all traffic to its Home Agent (HA). The mobility may cause the HA to be geographically distant from the mobile network, and the tunneling causes increased delay and overhead in the network. It becomes peculiar in the event of nesting of mobile networks due to pinball routing, for example, a Personal Area Network (PAN) inside a vehicle. The authors propose an Extended Mobile IPv6 route optimization (EMIP) scheme to enhance the performance of nested mobile networks in local and global mobility domain. The EMIP scheme is based on MIPv6 route optimization and the root Mobile Router (MR) performs all the route optimization tasks on behalf of all active Mobile Network Nodes (MNNs). Thus, the network movement remains transparent to sub MRs and MNNs and modifies only MRs and MNNs leaving other entities untouched and is more efficient than the Network Mobility Basic Support protocol (NEMO BS). The authors carried out an extensive simulation study to evaluate the performance of EMIP.
Single-Cell and Bulk RNASeq Profiling of COVID-19 Patients Reveal Immune and Inflammatory Mechanisms of Infection-Induced Organ Damage (2021)

The SARS-CoV-2 virus's ability to induce hypercytokinemia and cause multiple organ failure makes it imperative to find effective treatments. To understand the mechanism of viral infection and its effects on organ tissues, we analyzed multiple single-cell and bulk RNAseq data from COVID-19 patients' organ samples. Various levels of severity of infection were accounted for, with comparative analyses between mild, moderate, and severely infected patients. Our analysis uncovered an upregulation of the innate immune response via several inflammatory genes, IL-2, IL-6, IL-8, IL-17A, and NF-κB. Consequently, we found that the upregulation of these downstream effects can lead to organ injury. The downregulated pathways such as eukaryotic initiation factor 2 (eIF2) and eIF4-mediated host translation, were found to lead to an increased viral translation. We also found that the loss of inhibitory peptides can suppress an overactive innate immune response via NF-κB and interleukin-mediated pathways. Investigation of viral-host protein mapping showed that the interaction of viral proteins with host proteins correlated with the down- and upregulation of host pathways such as decreased eIF2-mediated host translation and increased hypertrophy and fibrosis. Inflammation was increased via the stimulation of pro-inflammatory cytokines and suppression of host translation pathways that led to reduced inflammatory inhibitors. Cardiac hypertrophy and organ fibrosis were the results of increased inflammation in organs of severe and critical patients. Finally, we identified potential therapeutic targets for the treatment of COVID-19 and its deleterious effects on organs. Further experimental investigation would conclusively determine the effects of COVID-19 infection on organs other than the lungs and the effectiveness of the proposed therapeutic targets.
Cost-Effectiveness of Different Forms of Intra-Articular Injections for the Treatment of Osteoarthritis of the Knee (2016)

Ferring Pharmaceutics Inc.
Using Expressive Language Generation to Increase Authorial Leverage. (2013)

It is widely agreed that the interaction possibilities in interactive narrative are limited by the current approach to dialog creation, which typically relies on teams of scriptwriters.This paper reports on experiments testing whether authorial leverage can be increased by methods for natural language generation of dialog in a story world called Heart of Shadows.Our experiments show that (1) expert writers spend less time authoring dialogue variations by editing automatically generated content than creating it from scratch and (2) expert writers are more critical of automatically generated dialogue than amateur writers.
Chemical and Biological Reaction Engineering (PDF) (2007)

This course applies the concepts of reaction rate, stoichiometry and equilibrium to the analysis of chemical and biological reacting systems, derivation of rate expressions from reaction mechanisms and equilibrium or steady state assumptions, design of chemical and biochemical reactors via synthesis of chemical kinetics, transport phenomena, and mass and energy balances. Topics covered include: chemical/biochemical pathways; enzymatic, pathway, and cell growth kinetics; batch, plug flow and well-stirred reactors for chemical reactions and cultivations of microorganisms and mammalian cells; heterogeneous and enzymatic catalysis; heat and mass transport in reactors, including diffusion to and within catalyst particles and cells or immobilized enzymes.