gebhart/patrepeval huggingface dataset:
P477 Clinical remission by legacy vs. FDA definitions: definition justification and results from UNIFI Study (2019)

Ustekinumab (UST), an interleukin-12/23 blocker, was evaluated as induction and maintenance for moderate–severe ulcerative colitis (UC). Clinical remission was analysed using a US-specific definition (FDA) excluding the PGA (Physician’s Global Assessment) and the legacy definition which includes the PGA to accommodate regional regulatory preference. Patients (pts) were randomised to receive a UST intravenous (IV) induction dose (either 130 mg [n = 320] or approximating 6 mg/kg [n = 322]), or PBO (n = 319). Responders to UST IV induction were randomised to SC maintenance of 90 mg UST (either every 12 weeks [n = 172] or every 8 weeks [n = 176]), or PBO (n = 175). The primary endpoint for induction (Week 8) and maintenance (Week 44) was clinical remission. In a prior UC induction study with golimumab, 87.5% had >3 stools per day at baseline and stool number ≤3 aligned with what approximately 98% of patients reported as normal. FDA clinical remission definition was developed after FDA requested PGA removal (ie, absolute stool number ≤3 [aligned with upper limit of normal stool number in the general population], Mayo rectal bleeding subscore 0, and Mayo endoscopy subscore 0/1). This differed from the legacy definition (total Mayo score ≤2 points, with no individual subscore >1). Using golimumab and infliximab UC study data, FDA definition was assessed for agreement with legacy definition, treatment effect, and clinical meaningfulness using the Inflammatory Bowel Disease Questionnaire and the 36-item short form health survey as anchor variables. UNIFI remission was analysed using both definitions. The FDA definition demonstrated high concordance, specificity and sensitivity with the legacy definition with a similar treatment effect, and defined patients who had clinically meaningful benefit. In the UNIFI study, Week 8 clinical remission rates among patients receiving IV UST at either 130 mg or ~6 mg/kg were significantly higher than PBO patients by both legacy (15.6%, 15.5%, and 5.3%, respectively p < 0.001 for both doses) and FDA definitions (16.6%, 18.9%, and 6.3%, respectively; p < 0.001 for both doses). Week 44 clinical remission rates among patients randomised to q12wk or q8wk UST were significantly higher than PBO patients by both legacy (38.4%, 43.8%, and 24.0%, respectively; p = 0.002 q12wk and p < 0.001 q8wk) and FDA definitions (39.5%, 42.6%, and 24.6% respectively; p = 0.002 q12wk and p < 0.001 q8wk). Using either legacy or FDA remission definition, IV UST induced remission and SC UST maintained remission in UST induction responders with moderately-to-severely active UC. Importantly, the FDA definition with absolute stool number ≤3 is clinically meaningful, easily understood by physicians and patients, and is not based on patients’ distant recall of normal stool pattern.
Novel non-contact retina camera for the rat and its application to dynamic retinal vessel analysis (2011)

We present a novel non-invasive and non-contact system for reflex-free retinal imaging and dynamic retinal vessel analysis in the rat. Theoretical analysis was performed prior to development of the new optical design, taking into account the optical properties of the rat eye and its specific illumination and imaging requirements. A novel optical model of the rat eye was developed for use with standard optical design software, facilitating both sequential and non-sequential modes. A retinal camera for the rat was constructed using standard optical and mechanical components. The addition of a customized illumination unit and existing standard software enabled dynamic vessel analysis. Seven-minute in-vivo vessel diameter recordings performed on 9 Brown-Norway rats showed stable readings. On average, the coefficient of variation was (1.1 ± 0.19) % for the arteries and (0.6 ± 0.08) % for the veins. The slope of the linear regression analysis was (0.56 ± 0.26) % for the arteries and (0.15 ± 0.27) % for the veins. In conclusion, the device can be used in basic studies of retinal vessel behavior.
Stroke survivors over-estimate their medication self-administration (MSA) ability, predicting memory loss (2014)

Assessing medication self-administration and MSA self-awareness may be useful in rehabilitation and successful community-return after stroke.
Repression of Hypoxia-Inducible Factor-1 Contributes to Increased Mitochondrial Reactive Oxygen Species Production in Diabetes (2021)

Abstract Background Excessive production of mitochondrial reactive oxygen species (ROS) is a central mechanism for the development of diabetes complications. Recently, hypoxia has been identified to play an additional pathogenic role in diabetes. In this study, we hypothesized that ROS overproduction was secondary to the impaired responses to hypoxia due to the inhibition of hypoxia-inducible factor-1 (HIF-1) by hyperglycemia. Methods The dynamic of ROS levels was analysed in the blood of healthy subjects and individuals with type 1 diabetes after exposure to hypoxia ( ClinicalTrials.gov registration no. NCT02629406 ). The relation between HIF-1, glucose levels, ROS production and its functional consequences were analyzed in renal mIMCD-3 cells and in kidneys of mouse models of diabetes. Results Exposure to hypoxia increased circulating ROS in subjects with diabetes, but not in subjects without diabetes. High glucose concentrations repressed HIF-1 both in hypoxic cells and in kidneys of animals with diabetes, through a HIF prolyl-hydroxylase (PHD) - dependent mechanism. The impaired HIF-1 signaling contributed to excess production of mitochondrial ROS through increased mitochondrial respiration that was mediated by Pyruvate dehydrogenase kinase 1 (PDK1) and was followed by functional consequences. The restoration of HIF-1 function attenuated ROS overproduction despite persistent hyperglycemia, and conferred protection against apoptosis and renal injury in diabetes. Conclusions We conclude that the repression of HIF-1 plays a central role in mitochondrial ROS overproduction in diabetes and is a potential therapeutic target for diabetic complications. These findings are highly significant and timely since the first PHD inhibitor that can activate HIF-1 has been newly approved for clinical use.
Nanowires: Synthesis, Applications and Challenges (2020)

Nanowires are structures of dimensions of the order of one
nanometer (10-9m). Alternatively, they can be defined as structures...
Reflectin needs its intensity amplifier: Realizing the potential of tunable structural biophotonics (2020)

Underwater camouflage and communication in a family of recently evolved squids are controlled, in part, by the reflectin proteins, which regulate dynamic changes in the color and intensity of light reflected from intracellular Bragg reflectors and Mie scatterers. The reflectins act as a signal transducer, precisely tuning the dimensions and refractive index of the membrane-bounded structural reflectors containing them to an extent exactly proportional to neuronal signaling. This calibration between the activating signal and the output color and intensity of reflectance is governed by the physics of the liquid state of reflectin assemblies, which osmotically fine-tune the dimensions and refractive index of the membrane-bounded structural reflectors containing them. While thin-film or genetically engineered assemblies of reflectin deliver changes in the colors of reflection approximating those of the biological system (as do other proteins and polymers), none has delivered the signal-activated increase in the intensity of reflectance characteristic of the native system. The membrane envelopes (Bragg reflector lamellae and Mie-scattering vesicles) containing the reflectins apparently serve as amplifiers, functionally “impedance matched” to the range of tunable sizes of the reflectin assemblies; reflectin films or assemblies lacking such an amplifier fail to deliver signal-activated increases in reflectance intensity.
Introduction to Nanoionic Elements for Information Technology (2016)

This chapter provides the basic definitions of nanoionic redox-based resistive switching elements, their main switching modes, and their most important performance parameters. Furthermore, it sketches the scope of this book, which spans from nanoscale physics and chemistry of the switching phenomenon to devices, technology, and application areas. Three types of redox-based resistive switching elements are introduced, and a brief history of the phenomenon and the designated device application is given. This is followed by a discussion of the performance requirements and the specific themes of the application in memories and of the application in logic circuits, concluding with prospects and challenges.
synaptotagminMutants Reveal Essential Functions for the C2B Domain in Ca2+-Triggered Fusion and Recycling of Synaptic VesiclesIn Vivo (2001)

Synaptotagmin has been proposed to function as a Ca<sup>2+</sup> sensor that regulates synaptic vesicle exocytosis, whereas the soluble<i>N</i>-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is thought to form the core of a conserved membrane fusion machine. Little is known concerning the functional relationships between synaptotagmin and SNAREs. Here we report that synaptotagmin can facilitate SNARE complex formation<i>in vitro</i> and that <i>synaptotagmin</i> mutations disrupt SNARE complex formation <i>in vivo</i>. Synaptotagmin oligomers efficiently bind SNARE complexes, whereas Ca<sup>2+</sup> acting via synaptotagmin triggers cross-linking of SNARE complexes into dimers. Mutations in <i>Drosophila</i>that delete the C2B domain of synaptotagmin disrupt clathrin AP-2 binding and endocytosis. In contrast, a mutation that blocks Ca<sup>2+</sup>-triggered conformational changes in C2B and diminishes Ca<sup>2+</sup>-triggered synaptotagmin oligomerization results in a postdocking defect in neurotransmitter release and a decrease in SNARE assembly <i>in vivo</i>. These data suggest that Ca<sup>2+</sup>-driven oligomerization via the C2B domain of synaptotagmin may trigger synaptic vesicle fusion via the assembly and clustering of SNARE complexes.
Stem cells, angiogenesis and muscle healing: a potential role in massage therapies? (2012)

Skeletal muscle injuries are among the most common and frequently disabling injuries sustained by athletes. Repair of injured skeletal muscle is an area that continues to present a challenge for sports medicine clinicians and researchers due, in part, to complete muscle recovery being compromised by development of fibrosis leading to loss of function and susceptibility to re-injury. Injured skeletal muscle goes through a series of coordinated and interrelated phases of healing including degeneration, inflammation, regeneration and fibrosis. Muscle regeneration initiated shortly after injury can be limited by fibrosis which affects the degree of recovery and predisposes the muscle to reinjury. It has been demonstrated in animal studies that antifibrotic agents that inactivate transforming growth factor (TGF)-β1 have been effective at decreasing scar tissue formation. Several studies have also shown that vascular endothelial growth factor (VEGF) can increase the efficiency of skeletal muscle repair by increasing angiogenesis and, at the same time, reducing the accumulation of fibrosis. We have isolated and thoroughly characterised a population of skeletal muscle-derived stem cells (MDSCs) that enhance repair of damaged skeletal muscle fibres by directly differentiating into myofibres and secreting paracrine factors that promote tissue repair. Indeed, we have found that MDSCs transplanted into skeletal and cardiac muscles have been successful at repair probably because of their ability to secrete VEGF that works in a paracrine fashion. The application of these techniques to the study of sport-related muscle injuries awaits investigation. Other useful strategies to enhance skeletal muscle repair through increased vascularisation may include gene therapy, exercise, neuromuscular electrical stimulation and, potentially, massage therapy. Based on recent studies showing an accelerated recovery of muscle function from intense eccentric exercise through massage-based therapies, we believe that this treatment modality offers a practical and non-invasive form of therapy for skeletal muscle injuries. However, the biological mechanism(s) behind the beneficial effect of massage are still unclear and require further investigation using animal models and potentially randomised, human clinical studies.
Discriminative Transfer Learning with Tree-based Priors (2013)

High capacity classifiers, such as deep neural networks, often struggle on classes that have very few training examples. We propose a method for improving clas-sification performance for such classes by discovering similar classes and trans-ferring knowledge among them. Our method learns to organize the classes into a tree hierarchy. This tree structure imposes a prior over the classifier’s param-eters. We show that the performance of deep neural networks can be improved by applying these priors to the weights in the last layer. Our method combines the strength of discriminatively trained deep neural networks, which typically re-quire large amounts of training data, with tree-based priors, making deep neural networks work well on infrequent classes as well. We also propose an algorithm for learning the underlying tree structure. Starting from an initial pre-specified tree, this algorithm modifies the tree to make it more pertinent to the task being solved, for example, removing semantic relationships in favour of visual ones for an image classification task. Our method achieves state-of-the-art classification results on the CIFAR-100 image data set and the MIR Flickr image-text data set. 1
ChemInform Abstract: Stereoselective Synthesis of Antifungal Sulfoximines, Novel Triazoles. Part 2. (1999)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Experiments with data flow on a general-purpose parallel computer. Memorandum report (1991)

The characteristics of rotavirus infection in 23 children with a variety of primary immunodeficiency diseases were studied. Stools and sera were tested for rotavirus by means of the enzyme-linked immunosorbent assay and the enzyme-linked fluorescent assay, respectively. Four immunodeficient patients had diarrhea during the study period and all had rotavirus infection; rotavirus was not detected in the stools of the 19 asymptomatic immunodeficient patients. Forty-six control children with diarrhea were tested and 22 had rotavirus infection; rotavirus was not detected in 39 asymptomatic control children. One immunodeficient patient with X-linked agammaglobulinemia and one with severe combined immunodeficiency had chronic, symptomatic rotavirus infection with rotavirus excretion lasting more than six weeks. The other two immunodeficient patients and eight control children eliminated the rotavirus from their stools in periods ranging from two to 12 days. Rotavirus antigen was detected in the sera of three of the four immunodeficient patients; none of the 14 control infants tested had rotavirus antigen detected in their sera. This study indicates that rotavirus may produce a chronic infection in immunodeficient children.
Silicon photonics (Conference Presentation) (2019)

In the past few years we went from the ability to miniaturize a handful of optical components to being able to print massive optical circuits on a microelectronic chip composed of thousands of optical components. These optical circuits enable one to control the flow of light in unprecedented ways and are opening the door to applications that only a decade ago were unimaginable. The idea for guiding light on silicon chip originated in the 1980s but only in the early 2000s the viability of the platform was demonstrated. I will describe the challenges that silicon photonic faced in its infancy, and the work that helped overcome these challenges. I will also discuss the current state of art of silicon photonics, where larger and more complex systems are now putting higher demands and setting up new challenges for the technology.
On the stability of (gas) plasma oxidized polymer surfaces (1996)

The stability of carbon dioxide (CO<sub>2</sub>) plasma treated polyethylene (PE) surfaces was studied. Reorganization processes on the oxidized surfaces were investigated using XPS and dynamic contact angle measurements. It was found that the restructuring phenomena at the surface is due to rotational and small segmental motions that minimize the free energy of these thermodynamically unstable surfaces. These motions also cause a decrease in wettability of the surface. The surface also stabilizes by sending its segments with functional groups into the bulk of the polymer, thus increasing the entropy of the system.
Nuclear factor-kappa B p65 evaluation on the Canadian Prostate Cancer Biomarker Network (CPCBN) TMA-series for biomarker validation. (2018)

80 Background: The CPCBN has assembled a TMA-based resource comprising the specimens of 1512 prostate cancer patients treated by radical prostatectomy. This richly annotated and multi-institutional resource is available to researchers who wish to access a large cohort to validate prognostic biomarkers (http://www.tfri.ca/en/research/translational-research/cpcbn.aspx). Over the last decade, our laboratory demonstrated with an independent cohort (Gannon PO, et al. Eur J Cancer. 2013 Jul;49(10):2441-8, Labouba I, et al. PLoS One. 2015 Jul 17;10(7):e0131024), the reproducible association of nuclear factor-kappa B (NF-kB) p65 with patient’s risk of biochemical recurrence. Here, we evaluated the CPCBN TMA-series for p65 expression. Methods: Two independent observers scored the frequency of p65 nuclear localisation on digital images obtained after automated immunohistochemistry analysis of p65. Over the available minimum 3 cores of tumour tissue per patient, an average percentage of positive nucleus frequency was used. Statistical analyses were performed using SPSS software. Results: High nuclear frequency of NF-kB p65 (cut-off at 3%) was associated with an increased risk for patients to experience a biochemical relapse (p &lt; 0.001; Exp(B) = 1.599; 95%CI = 1.321-1.937), develop bone metastasis (p = 0.007; Exp(B) = 2.126; 95%CI = 1.234-3.663)and die from their disease (p = 0.001; Exp(B) = 3.117; 95%CI = 1.55-6.266). In multivariate analyses, p65 also remained independent from clinical parameters (PSA, Gleason score and pTNM): biochemical relapse (p = 0.005; Exp(B) = 1.331; 95%CI = 1.092-1.623), bone metastasis (p = 0.033; Exp(B) = 1.82; 95%CI = 1.04- 3.158), mortality (p = 0.007; Exp(B) = 2.626; 95%CI = 1.298-5.312) Conclusions: Using a large cohort of Canadian men, our study reiterates the previous study linking NF-kB p65 with prostate cancer progression and highlights the suitability of CPCBN TMAs for biomarker validation. Our results also reveal the role of p65 as a predictor of bone metastasis development and prostate cancer-specific mortality.
Algorithms for $\ell_p$ Low Rank Approximation (2017)

We consider the problem of approximating a given matrix by a low-rank matrix so as to minimize the entrywise $\ell_p$-approximation error, for any $p \geq 1$; the case $p = 2$ is the classical SVD problem. We obtain the first provably good approximation algorithms for this version of low-rank approximation that work for every value of $p \geq 1$, including $p = \infty$. Our algorithms are simple, easy to implement, work well in practice, and illustrate interesting tradeoffs between the approximation quality, the running time, and the rank of the approximating matrix.
Tolyl Ion (2016)

This document contains recommendations for terminology in mass spectrometry. Development of standard terms dates back to 1974 when the IUPAC Commission on Analytical Nomenclature issued recommendations on mass spectrometry terms and definitions. In 1978, the IUPAC Commission on Molecular Structure and Spectroscopy updated and extended the recommendations and made further recommendations regarding symbols, acronyms, and abbreviations. The IUPAC Physical Chemistry Division Commission on Molecular Structure and Spectroscopy’s Subcommittee on Mass Spectroscopy revised the recommended terms in 1991 and appended terms relating to vacuum technology. Some additional terms related to tandem mass spectrometry were added in 1993 and accelerator mass spectrometry in 1994. Owing to the rapid expansion of the field in the intervening years, particularly in mass spectrometry of biomolecules, a further revision of the recommendations has become necessary. This document contains a comprehensive revision of mass spectrometry terminology that represents the current consensus of the mass spectrometry community.
Myosin II can be localized to the cleavage furrow and to the posterior region ofDictyostelium amoebae without control by phosphorylation of myosin heavy and light chains (1997)

To elucidate the role of phosphorylation in regulation of intracellular distribution of myosin II, we have characterized mutant Dictyostelium cells expressing myosin II that could not be regulated by the phosphorylation on the mapped heavy chain sites, the light chain site, or both sites. Immunofluorescence microscopy demonstrated that all three mutant myosin IIs were localized in the furrow region of dividing cells and in the tail region of migrating cells, similar to wild-type cells. Thus, regulation by phosphorylation is not required to direct myosin II toward the furrow region and the tail region in Dictyostelium. However, myosins that were deficient in heavy chain phosphorylation were distributed only in the cortical region of interphase cells, whereas some myosin IIs were present throughout the endoplasm in wild-type cells. Video microscopy showed that the rate of cell migration was significantly lower in cells that were deficient in heavy chain phosphorylation- than in light chain phosphorylation-deficient cells, myosin null cells and wild-type cells. Chemotactic behavior of cells that were deficient in heavy chain phosphorylation was also retarded. These results suggest that loss of regulation by heavy chain phosphorylation results in excessive myosin in the cortex, which leads to retarded motility.
Magnetic Sensor Based on Surface Acoustic Wave Resonators (2011)

In this paper, we describe a new type of magnetic surface acoustic wave (SAW) sensor that consists of interdigital transducers made of a magnetostrictive material, Ni, on a quartz substrate. This sensor can be used as an element of a resonator-type wireless SAW sensor system because it has a high Q. Moreover, it has the merits of being fabricated easily using the existing process for SAW devices because its structure is the same as that of general SAW resonators. When an external magnetic field of about 100 mT was applied perpendicularly to the direction of SAW propagation, the frequency change obtained was 200 ppm. In addition, the developed sensor was applied in a passive and wireless open/close sensing system and the reading distance obtained was 3 m.