gebhart/patrepeval huggingface dataset:
Ribavirin exposure after the first dose is predictive of sustained virological response in chronic hepatitis C (2008)

The impact of ribavirin exposure on sustained virological response (SVR) in patients with chronic hepatitis C is unknown. Preliminary studies showed marked inter-individual variability of ribavirin concentrations despite dose adjustment for body weight (BW) and suggested there was a correlation between single time point concentrations and SVR. None of them evaluated the global exposure to ribavirin. This study was conducted to determine whether early ribavirin global exposure is related with SVR. An exploratory pharmacokinetic-pharmacodynamic (PK-PD) study was conducted in genotype 1 hepatitis C patients treated with peginterferon alfa-2a and ribavirin (dose-adjusted for BW) for 12 weeks, to which amantadine was added for the following 36 weeks. Full and abbreviated ribavirin area under the concentration time curves (AUC0–12h, AUC0–4h) were derived from plasma concentration profiles at day 0 (D0), week 12 (W12), W12 + 1 day, and W24. Virological follow-up was performed at D0 (0, 12, and 24 hours), W2, W4, W6, and monthly until W72 (TaqMan polymerase chain reaction, cut-off 15 international units/mL). Twenty-eight patients were enrolled in the study and 24 completed it. Patients with a SVR had a significantly higher D0 AUC0–12h (3695 [1571–6916] versus 2937 [1266–4913] μg/hour/L, P = 0.03) and D0 AUC0–4h (2010 [615–3175] versus 1340 [622–2246] μg/hour/L, P = 0.03). Patients with D0 AUCs above the cut-off values defined by receiver operating characteristic curves (3014 μg/hour/L and 1755 μg/hour/L for AUC0–12h and AUC0–4h, respectively) had a significantly better chance of achieving an SVR than patients with AUCs under the thresholds (odds ratio = 16.0, 95% confidence interval 1.54–166.6, P = 0.02 and odds ratio = 8.9, 95% confidence interval, 1.4–56.6; P = 0.02). Conclusion : Ribavirin exposure at D0 is significantly related to SVR. To our knowledge, this is the first study to give an early pharmacokinetic predictor of SVR. We propose a minimum AUC0–4h threshold of 1755 μg/hour/L at D0 as a target for ribavirin dose adjustment.
Parallel transmission of a one-dimensional light distribution by a single optical fiber (1978)

A technique, based on the preservation of the axial angle, for transmitting one-dimensional light distribution through a single multimode step-index optical fiber is described. Extension to transmission of two-dimensional pictures is demonstrated.
Microbial Detection Systems (2006)

Abstract Infectious diseases accounted for 25–33% of the estimated 54 million deaths worldwide in 1988, of which more than half are attributed to tuberculosis, malaria, chronic hepatitis B, diarrheal diseases, and human immunodeficiency virus/Acquired Immune Deficiency Syndrome (HIV/AIDS). Additionally, the first known cases of human influenza caused by the avian influenza virus, N5N1, were identified in Hong Kong in 1997. To address rising national and worldwide public health needs, it is desirable that a sensitive, specific, fast, and simple‐to‐operate device be employed to detect infectious agents. Microbial detection systems that attempt to meet this need have been commercially available from the late 1970s and have progressed significantly with the molecular biotechnology revolution. Contemporary microbial detection systems or biosensors typically consist of a selective biorecognition molecule connected to a transducer that converts a biochemical interaction into a measurable signal. In the near future, biomedical science can realize the integration of all laboratory equipment used in molecular biology on a chip‐based platform arrayed to detect large numbers of pathogens in a high throughput, portable device.
Electroplated waveguides to enhance DNP and EPR spectra of silicon and diamond particles (2022)

Abstract. Electroplating the waveguide of a 7 T polarizer in a simple innovative way increased microwave power delivered to the sample by 3.1 dB. Silicon particles, while interesting for hyperpolarized MRI applications, are challenging to polarize due to inefficient microwave multipliers at the electron Lamour frequency at high magnetic fields and fast electronic relaxation times. Improving microwave transmission directly translates to significantly higher EPR signal at high-field, low-temperature conditions and promises faster and higher 29Si polarization build-up through DNP.
Batteries, camera, action! Learning a semantic control space for\n expressive robot cinematography (2020)

Aerial vehicles are revolutionizing the way film-makers can capture shots of\nactors by composing novel aerial and dynamic viewpoints. However, despite great\nadvancements in autonomous flight technology, generating expressive camera\nbehaviors is still a challenge and requires non-technical users to edit a large\nnumber of unintuitive control parameters. In this work, we develop a\ndata-driven framework that enables editing of these complex camera positioning\nparameters in a semantic space (e.g. calm, enjoyable, establishing). First, we\ngenerate a database of video clips with a diverse range of shots in a\nphoto-realistic simulator, and use hundreds of participants in a crowd-sourcing\nframework to obtain scores for a set of semantic descriptors for each clip.\nNext, we analyze correlations between descriptors and build a semantic control\nspace based on cinematography guidelines and human perception studies. Finally,\nwe learn a generative model that can map a set of desired semantic video\ndescriptors into low-level camera trajectory parameters. We evaluate our system\nby demonstrating that our model successfully generates shots that are rated by\nparticipants as having the expected degrees of expression for each descriptor.\nWe also show that our models generalize to different scenes in both simulation\nand real-world experiments. Data and video found at:\nhttps://sites.google.com/view/robotcam.\n
Aging-Related and Gender Specific Albumin Misfolding in Alzheimer’s Disease (2020)

Aging-related protein misfolding and aggregation may play critical roles in the pathogenesis of numerous diseases. In the brain, extracellular aggregated amyloid-β (Aβ) is closely related to the death of neurons in individuals with Alzheimer's disease (AD). Albumin-Aβ binding is important in preventing Aβ fibril aggregation. However, because albumin is the most abundant and important antioxidant in the circulation, aging-related oxidative stress could have a significant effect on the molecular conformation and binding capacities of albumin. To investigate the link between misfolded albumin and AD, we developed fluorescent assays to determine the effects of misfolded albumin on membrane integrity in the presence of a lipolytic, inflammatory response-like enzyme, secretory phospholipase A2 (sPLA2). We found that misfolded albumin increased degradation of phospholipids in highly fluid bilayer membranes in the presence of sPLA2 due to hydrophobic effects of misfolded albumin. High amounts of misfolded albumin were present in sera of elderly (average 74 years) versus young (average 24 years) subjects (<i>p</i> < 0.0001). Albumin in cerebrospinal fluid (CSF) of elderly subjects, though present in small concentrations, had a 2- to 3-fold increased capacity to promote sPLA2-catalyzed membrane phospholipid degradation as compared with the same amount of albumin in serum (<i>p</i> < 0.0001). In addition, the fatty acid binding capacity of albumin in CSF from female subjects was considerably lower than values obtained for men, especially for individuals diagnosed with AD (<i>p</i> = 0.0006). This study suggests that inflammation, misfolded albumin and/or other dysfunctional proteins, and changes in membrane fluidity could alter cell membrane integrity and homeostasis and contribute to the pathogenesis of aging-related dementia and AD.
Analysis of Gonadotropin-Releasing Hormone Gene Structure in Families with Familial Central Precocious Puberty and Idiopathic Hypogonadotropic Hypogonadism (1990)

We examined the GnRH gene structure in a family with familial central precocious puberty (eight members, four affected) and a family with idiopathic hypogonadotropic hypogonadism (eight members, three affected) using Southern blot analysis and sequencing of cloned polymerase chain reaction products. Genomic DNA samples were digested with restriction enzymes and hybridized to the human placental GnRH cDNA probe. BamHI digests revealed 6.5- and 2.7-kilobase (kb) bands; BglII, 6.0- and 4.0-kb bands; Ncol, 8.0- and 3.5-kb bands; Pstl, 4.2-kb, 2.8-kb, 1.3-kb and 950-basepair bands; XbaI, 6.5- and 5.0-kb bands. These sizes were the same as those found by this analysis in normal individuals. All family members with familial central precocious puberty or idiopathic hypogonadotropic hypogonadism showed the same size bands, except for one unaffected member of the family with idiopathic hypogonadotropic hypogonadism who had an additional band at 5.5 kb after digestion with NcoI, which is thought to be a rare polymorphism. Sequencing of exon 2 of the GnRH gene from these families, including the exon-intron borders, revealed a polymorphism in the signal sequence of GnRH that predicts an amino acid change from tryptophan (nucleotide sequence: TGG) to serine (TCG) at the -8 position of the GnRH preprohormone. Although this polymorphism did not cosegregate with the clinical disorder in either family, this novel polymorphism may prove useful in the evaluation of linkage to the GnRH gene in other families with pubertal disorders. No other nucleotide sequence abnormality was found in 1.2 kb of the 5' flanking region or the four exons and their splice sites.
M2 Macrophages Enhance Pathological Neovascularization in the Mouse Model of Oxygen-Induced Retinopathy (2015)

These results indicated that M2 macrophages, rather than M1, play an important role in promoting retinal pathological neovascularization probably by producing secreted factors. Thus, targeting M2 macrophages could be a potential therapeutic option for inhibiting retinal pathological neovascularization.
Structural and immunological comparison of arabinogalactan-proteins from Viscum album L. berries and herb (2007)

Mistletoe (Viscum album L.) is used as a medicine since ancient times. Today mistletoe extracts play an important role in adjuvant cancer treatment [1] because of their immunostimulating properties. Besides lectins, different polysaccharides from mistletoe berries are discussed to contribute to the in vivo activity [2]. For arabinogalactan-proteins (AGPs), especially from Echinacea, different immunomodulating activities have been proven in vitro, e.g. enhanced production of cytokines [3]. Therefore AGPs from mistletoe herb and berries were purified, characterized and immunologically tested.
Effect of Enzymatic Treatment for Sedimentation and Concentrate of Solid Particles in Waste Water Derived from Rice Washing Process (2006)

無洗米加工装置より排出される洗米排水の処理ならびに, 排水中に含まれている固形成分の再利用の観点から, 酵素添加による洗米排水成分への沈降性の付加ならびに, 濃縮について検討を行った。その結果, 酸性プロテアーゼ, ペプチダーゼを含有する酵素剤の添加により, 沈降定数43%, 汚泥容量指数7.2ml・g-1という, 高い沈降性を示した。また, 排水上静中の全炭素量を測定したところ, 洗米排水原液の15%前後と低く, 酵素処理をしていない遠心後の上静成分の値と殆ど変わらないこと明らかとなった。さらに, 酵素処理後の洗米排水中の粒子成分表: 層の表面電位と沈降性との関連について検討を行ったところ, 表面電位と汚泥容量とは高い相関関係を示した。以上の結果より, 洗米排水中へのプロテアーゼ添加による固形成分の沈降・濃縮は, 酵素添加により排水中の固形成分表層の負電荷が増大し, 至っては吸着等の静電的相互作用により, 沈降性が高められたものと考えられた。
Lifeguard und Mammakarzinom (2014)

Das 1999 beschriebene Protein Lifeguard (LFG) kann die durch externe Bindung von Liganden der TNF Superfamilie ausgelöste Signalkaskade, die zum programmierten Zelltod
DeepLesion: Automated Deep Mining, Categorization and Detection of Significant Radiology Image Findings using Large-Scale Clinical Lesion Annotations (2017)

Extracting, harvesting and building large-scale annotated radiological image datasets is a greatly important yet challenging problem. It is also the bottleneck to designing more effective data-hungry computing paradigms (e.g., deep learning) for medical image analysis. Yet, vast amounts of clinical annotations (usually associated with disease image findings and marked using arrows, lines, lesion diameters, segmentation, etc.) have been collected over several decades and stored in hospitals' Picture Archiving and Communication Systems. In this paper, we mine and harvest one major type of clinical annotation data - lesion diameters annotated on bookmarked images - to learn an effective multi-class lesion detector via unsupervised and supervised deep Convolutional Neural Networks (CNN). Our dataset is composed of 33,688 bookmarked radiology images from 10,825 studies of 4,477 unique patients. For every bookmarked image, a bounding box is created to cover the target lesion based on its measured diameters. We categorize the collection of lesions using an unsupervised deep mining scheme to generate clustered pseudo lesion labels. Next, we adopt a regional-CNN method to detect lesions of multiple categories, regardless of missing annotations (normally only one lesion is annotated, despite the presence of multiple co-existing findings). Our integrated mining, categorization and detection framework is validated with promising empirical results, as a scalable, universal or multi-purpose CAD paradigm built upon abundant retrospective medical data. Furthermore, we demonstrate that detection accuracy can be significantly improved by incorporating pseudo lesion labels (e.g., Liver lesion/tumor, Lung nodule/tumor, Abdomen lesions, Chest lymph node and others). This dataset will be made publicly available (under the open science initiative).
Phase I and pharmacokinetic trial of oral administration of CYC682, a novel 2’ deoxycytidine type anti-metabolite pro-drug, in patients with advanced solid tumors or lymphoma (2005)

2026 Background: CYC682 is converted by intestinal and plasma amidases to the active agent CNDAC [1-(2-C-cyano-2-deoxy-β -D-arabino-pentafuranosyl)-cytosine] and intracellularly activated by deoxycytidine kinase to CNDAC triphosphate. The mechanism of action includes inhibition of DNA polymerase, cessation of DNA strand elongation and DNA strand breakage. A previous phase I study of a 5 days/week, for 4 weeks every 6 weeks schedule determined a maximum tolerated dose (MTD) of 40 mg/m2/day (d), with neutropenia as the principal toxicity. To maximize plasma exposure we have evaluated twice daily oral administration on days 1–14 of a 21-day cycle (cyc), with the determination of the MTD and the recommended phase II dose (RD) as objectives. Methods: MTD was defined as ≥2/3 or 3/6 patients (pts) with dose limiting toxicity (DLT) in cyc 1 and RD as next lowest dose level (DL). DL of 20, 40, 66, 100 mg/m2/d were explored. Blood samples for pharmacokinetic (PK) analysis of CYC682 and CNDAC were drawn on d 1 and 14 of the 1st cyc and d 14 of the 3rd cyc. Results: 15 pts have received 22 cyc. M/F: 8/7; median age 59 (range 43–72); PS 0/1: 1/14; principal tumor types: breast (2 pts), NSCLC (3), ovarian (2), colon (2). All but one had been pre-treated with numerous chemotherapy regimes (median 4, range 1–6). DLT of febrile neutropenia (FN) and thrombocytopenia (T) occurred in 2/6 pts at DL3, with the MTD due to FN in 3/3 pts reached at DL4. Expanded accrual is ongoing at 66 mg/m2/d as the potential RD. Non-hematologic toxicities including diarrhea have been observed but are manageable. PK data are available for 12 pts, and demonstrate a moderate correlation between CNDAC exposure and CYC682 dose. The inter-patient variability of CYC682 Cmax and AUC0–8hr observed at DL3 is approximately 4-fold. Terminal half-life in DL3 is 2.3 ±0.9 hr. Conclusion: The MTD for this schedule is 100 mg/m2/d with febrile neutropenia as DLT. DL (mg/m2/d) No. pts (cyc) No. pts DLT NCI-CTC toxicity by pt (grade) Cmax (ng/mL) AUC0–8hr (hr*ng/mL) FN N T Diarrhea N/V 20 3 (4) - - - 1 (2) 1 (2) 2 (1) 1.8±2.3 4.7±7.6 40 3 (7) - - 1 (2) - 1 (2) 1 (2) 6.1±2.3 13.7±21.6 66 6 (4) 2 2 (DLT) 1 (3) 1 (4,DLT) 1 (1) - 5.2±2.8 12.0±6.4 100 3 (3) 3 3 (DLT) - - - - - - Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CAC SA, Kremlin-Bicetre, France, Cyclacel Ltd., Dundee, UK CAC SA, Kremlin-Bicetre, France
Essential Materials and Processes for Nano‐Imprinted Optics (2021)

Abstract Optical 3D sensors and augmented reality (AR) glasses are prime application examples of the rapidly growing interest in photonics‐based devices. Mobile devices are being equipped with 3D sensors for fingerprint and face recognition as well as with lidar, which is also utilized to help the navigation of autonomous vehicles. In addition, immersive AR glasses have been developed for augmented reality applications. These applications benefit from diffractive optics, whereas nanoimprint lithography (NIL) provides an affordable and reliable means to mass produce the same. The NIL‐compatible optical materials with a high refractive index presented here are proven to be pivotal in enabling the commercial breakthrough of these applications.
Foreword to the Special Section on “Stress-Induced Phenomena in Microelectronics” (2016)

This special section contains papers from the international workshop on “Stress-Induced Phenomena in Microelectronics” held at the University of Texas at Austin on October 12–14, 2014.
Selectivity and sensitivity in supercritical fluid and liquid chromatography, using capillary columns and microelectrochemical detection (1997)

The obtainable selectivity of capillary column supercritical fluid chromatography wasstudied by the direct and indirect enantiomeric separation of some medium polarcompounds, i.e., benzodiazepines. The possibility to complement this chromatographictechnique with sensitive detection was pursued by the development of a micro-electrochemical detector, which was based on the impinging-jet principle and a 25 μmplatinum electrode. The detector was evaluated in both capillary column supercritical fluidand liquid chromatography (SFC and LC).In capillary column SFC, the amperometric detector was shown to be compatible withboth oxidative and reductive detection, as well as, pressure programmed conditions usingcarbon dioxide, modified with small amounts (i.e., less than 8%) of water, acetonitrile ormethanol, as the mobile phase. The compatibility with various modifiers is important asthe use of modified mobile phases in SFC generally results in altered selectivity, shorteranalysis time and the possibility to analyse more polar compounds. Using the presentdetector, a total number of about 20 different compounds, including, e.g., ferrocenes,phenols and nitroaromatic compounds, have been detected in carbon dioxide basedmobile phases with medium to low picogram detection limits. The detector response wasfound to be linear for injections of between ~0.1 and 4 ng of the analytes for bothoxidative and reductive amperometric detection. The microelectrode assembly could beemployed for at least six days of continuous operation in the SFC system. The relativestandard deviation in the peak height for ng injections of analyte was found to be ca. 5%under both pressure programmed and isobaric conditions. The stability, detection limitand reproducibility of the response of the present detector are notably better than thosepreviously reported.The study of the detector in LC was focused on the detection problems associated witha miniaturisation of the separation system. It was found that the detector could be placedup to one column inner diameter (i.e., 200 μm) from the column outlet with preservedsensitivity and efficiency. No significant dependence of the peak current on the positionof the electrode in the y- and z-directions versus the column outlet was observed.Moreover, the detector current was found to be insensitive to variations of the mobilephase linear velocity and concentration of supporting electrolyte. These features shouldfacilitate a rapid and reproducible positioning of the electrode versus the column outletand, additionally, render detection in normal-phase LC possible.
Integrated analysis of multimodal single-cell data (2021)

The simultaneous measurement of multiple modalities represents an exciting frontier for single-cell genomics and necessitates computational methods that can define cellular states based on multimodal data. Here, we introduce "weighted-nearest neighbor" analysis, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities. We apply our procedure to a CITE-seq dataset of 211,000 human peripheral blood mononuclear cells (PBMCs) with panels extending to 228 antibodies to construct a multimodal reference atlas of the circulating immune system. Multimodal analysis substantially improves our ability to resolve cell states, allowing us to identify and validate previously unreported lymphoid subpopulations. Moreover, we demonstrate how to leverage this reference to rapidly map new datasets and to interpret immune responses to vaccination and coronavirus disease 2019 (COVID-19). Our approach represents a broadly applicable strategy to analyze single-cell multimodal datasets and to look beyond the transcriptome toward a unified and multimodal definition of cellular identity.
A vision for embedded software (2001)

In this paper we describe a vision for the future evolution of Embedded SW (ESW) design methodologies as part of overall Embedded Systems (ES) development. Fundamentally, we believe that the way in which embedded SW is developed today must change radically. The key steps are: first, to link embedded software upwards in the abstraction layers to system functionality; and second, to link embedded software to the programmable platforms that support it. This will provide the much-needed means to verify whether the constraints posed on Embedded Systems are met. We envisage an optimised, automated, transparent and mathematically correct flow from product specification through to implementation for SW-dominated products implemented with highly programmable platforms.
Inhibitors of the Menin-Mixed Lineage Leukemia (MLL) Interaction (2013)

Mitochondrial dysfunction in adipose tissue may contribute to obesity-related metabolic derangements such as type 2 diabetes mellitus (T2DM). Because mitochondria are a target for melatonin action, the goal of this study was to investigate the effects of melatonin on mitochondrial function in white (WAT) and beige inguinal adipose tissue of Zücker diabetic fatty (ZDF) rats, a model of obesity-related T2DM. In this experimental model, melatonin reduces obesity and improves the metabolic profile. At 6 wk of age, ZDF rats and lean littermates (ZL) were subdivided into two groups, each composed of four rats: control (C-ZDF and C-ZL) and treated with oral melatonin in the drinking water (10 mg/kg/day) for 6 wk (M-ZDF and M-ZL). After the treatment period, animals were sacrificed, tissues dissected, and mitochondrial function assessed in isolated organelles. Melatonin increased the respiratory control ratio (RCR) in mitochondria from white fat of both lean (by 26.5%, P < 0.01) and obese (by 34.5%, P < 0.01) rats mainly through a reduction of proton leaking component of respiration (state 4) (28% decrease in ZL, P < 0.01 and 35% in ZDF, P < 0.01). However, melatonin treatment lowered the RCR in beige mitochondria of both lean (by 7%, P < 0.05) and obese (by 13%, P < 0.05) rats by maintaining high rates of uncoupled respiration. Melatonin also lowered mitochondrial oxidative status by reducing nitrite levels and by increasing superoxide dismutase activity. Moreover, melatonin treatment also caused a profound inhibition of Ca-induced opening of mPTP in isolated mitochondria from both types of fat, white and beige, in both lean and obese rats. These results demonstrate that chronic oral melatonin improves mitochondrial respiration and reduces the oxidative status and susceptibility to apoptosis in white and beige adipocytes. These melatonin effects help to prevent mitochondrial dysfunction and thereby to improve obesity-related metabolic disorders such as diabetes and dyslipidemia of ZDF rats.