gebhart/patrepeval huggingface dataset:
Community‐based high‐intensity cycling improves disease symptoms in individuals with Parkinson's disease: A six‐month pragmatic observational study (2022)

Participation in supervised, laboratory-based aerobic exercise protocols holds promise in slowing the progression of Parkinson's disease (PD). Gaps remain regarding exercise adherence and effectiveness of laboratory protocols translated to community-based programs. The aim of the project was to monitor exercise behaviour and evaluate its effect on disease progression over a 6 month period in people with PD participating in a community-based Pedalling for Parkinson's (PFP) cycling program. A pragmatic, observational study design was utilised to monitor exercise behaviour at five community sites. The Movement Disorders Society-Unified Parkinson's disease Rating Scale Motor III (MDS-UPDRS-III) and other motor and non-motor outcomes were gathered at enrollment and following 6 months of exercise. Attendance, heart rate, and cadence data were collected for each exercise session. On average, people with PD (N = 41) attended nearly 65% of the offered PFP classes. Average percent of age-estimated maximum heart rate was 69.3 ± 11.9%; average cadence was 74.9 ± 9.0 rpms. The MDS-UPDRS III significantly decreased over the 6-month exercise period (37.2 ± 11.7 to 33.8 ± 11.7, p = 0.001) and immediate recall significantly improved (42.3 ± 12.4 to 47.1 ± 12.7, p = 0.02). Other motor and non-motor metrics did not exhibit significant improvement. Participants who attended ~74% or more of available PFP classes experienced the greatest improvement in MDS-UPDRS III scores; of those who attended less than 74% of classes, cycling greater than or equal to 76 rpms lead to improvement. Attendance and exercise intensity data indicated that a laboratory-based exercise protocol can be successfully translated to a community setting. Consistent attendance and pedalling at a relatively high cadence may be key variables to PD symptom mitigation. Improvement in clinical ratings coupled with lack of motor and non-motor symptom progression over 6 months provides rationale for further investigation of the real-world, disease-modifying potential of aerobic exercise for people with PD.
An Aligned Rank Transform Procedure for Multifactor Contrast Tests (2021)

Data from multifactor HCI experiments often violates the assumptions of parametric tests (i.e., nonconforming data). The Aligned Rank Transform (ART) has become a popular nonparametric analysis in HCI that can find main and interaction effects in nonconforming data, but leads to incorrect results when used to conduct post hoc contrast tests. We created a new algorithm called ART-C for conducting contrast tests within the ART paradigm and validated it on 72,000 synthetic data sets. Our results indicate that ART-C does not inflate Type I error rates, unlike contrasts based on ART, and that ART-C has more statistical power than a t-test, Mann-Whitney U test, Wilcoxon signed-rank test, and ART. We also extended an open-source tool called ARTool with our ART-C algorithm for both Windows and R. Our validation had some limitations (e.g., only six distribution types, no mixed factorial designs, no random slopes), and data drawn from Cauchy distributions should not be analyzed with ART-C.
Analytical Modeling of Silicon Microring Photodetectors (2022)

We derive closed-form expressions for the small-signal response of microring photodiodes. The resonator shift resulting from thermo-optic nonlinearity is simulated and included in the model. Predicted responses are in excellent agreement with experiments.
Abstract LB029: Comprehensive structure-function evaluation of the SHOC2 holophosphatase reveals disease mechanisms and therapeutic opportunities (2022)

Abstract Receptor tyrosine kinase (RTK)-RAS signaling through the downstream mitogen activated protein kinase (MAPK) cascade regulate cell proliferation and survival. The SHOC2 holophosphatase functions as a key regulator of RTK-RAS signaling by removing an inhibitory phosphorylation on RAF family proteins to potentiate MAPK signaling. SHOC2 forms a ternary complex with MRAS and PP1C, and human germline gain-of-function mutations of this complex result in congenital RASopathy syndromes. However, the structure and the assembly of this complex are poorly understood. Here, we use cryogenic electron microscopy (cryo-EM) to resolve the structure of the SHOC2-PP1C-MRAS holophosphatase to 2.9Å resolution. Furthermore, we define the biophysical principles of SHOC2 holoenzyme interactions, elucidate the assembly order of the complex, and systematically interrogate the functional consequences of nearly all possible missense variants of SHOC2 through deep mutational scanning. We demonstrate that SHOC2 binds PP1C and MRAS through a concave surface created by the leucine-rich repeat region and further engages PP1C through the N-terminal disordered region containing a degenerate RVxF motif. Initial complex formation is mediated by SHOC2-PP1C interactions and is stabilized by binding of GTP-loaded MRAS. These observations define how clinical mutants in Noonan-like syndrome and cancer stabilize interactions of complex members to enhance holophosphatase activity. Together, this integrative structure-function model comprehensively defines key binding interactions within the SHOC2 holophosphatase, informing therapeutic development. Citation Format: Jason Kwon, Behnoush Hajian, Yuemin Bian, Alvaro Amor, James Fuller, Cara Fraley, Laura Baker, Jonathan So, David Mayhew, Abbey Sykes, Nicole Persky, Xiaoping Yang, David Root, Charles Perry, Christopher Lemke, William Hahn, Andrew Aguirre. Comprehensive structure-function evaluation of the SHOC2 holophosphatase reveals disease mechanisms and therapeutic opportunities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB029.
An offset multilayered optic sensor for shear and pressure measurement (2008)

Simultaneous recording of shear and pressure is an important requirement for study the causes of foot ulceration. In order to obtain a more robust and meaningful picture of what is occurring on the plantar surface of the foot, we have developed a multi-layered optical bend loss sensor that can be accommodated for shear and pressure measurement of an extended area. The sensor is made of two layers of crisscross fiberoptic sensor array separated by an elastomeric layer. Each sensing layer has multiple fibers molded into a thin polydimethylsiloxane (PDMS) substrate to form a mesh array. The top layer uses 6 fibers to create a 3 by 3 mesh with 9 intersection points and the bottom layer uses 8 fibers to create a 4 by 4 mesh with 16 intersection points. The space between the adjacent fibers is 0.5cm. Measuring changes of light intensity transmitted through the fiber provides information about the force induced changes of the fiber's radius of curvature. Pressure is measured based on the force induced light loss from the two affected crossing fibers divided by each sensing area. Shear was measured based on the relative position changes on these pressure points between the two fiber mesh layers. The design is an offset layout because the intersection points of the top and bottom layer are offset by 0.25 cm which can increase the shear sensing sensitivity. For testing the sensor with various loading condition, a neural network algorithm is induced to identify the loading pattern and the shear direction. Three loading patterns with 5 different loading directions were tested and a >90% accuracy was obtained using an algorithm using 2 neural networks.
Quantifying the Frequency of Alloreactive T Cells In Vivo: New Answers to an Old Question (2001)

Alloreactive T cell precursor frequency was measured in vivo using fluorescent dye labeling in combination with novel models based on lymphocyte activation and recovery. CFSE-labeled C57BL/6 (H-2(b)) spleen and lymph node cells were adoptively transferred to C57BL/6xDBA F(1) (H-2(b/d)) recipients, a parent-->F(1) MHC mismatch in which only donor cells respond. Recipients were sacrificed at serial time points to assess engraftment efficiency, and the extent of donor cell activation and proliferation. These data were used to calculate alloreactive T cell frequencies that varied 30-fold (0.71 +/- 0.31% to 21.05 +/- 3.62%), depending upon whether it was assumed that all donor cells injected became established and were capable of responding, or that only those present at later time points (24-72 h) were available to respond. By measuring the number of cells established in the recipient 24 h after transfer, before proliferation, we calculated an in vivo alloreactive frequency of approximately 7%. Using CD69 expression at 48 h to quantify activation, we found that 40-50% of the alloactivated CD4(+) donor T cells do not divide. Studies of cotransferred congenic and allogeneic cells demonstrated that bystander proliferation does not occur. We conclude that accurate calculations of alloreactive precursor frequency must account for both proliferation and cell engraftment. When this is done, a high percentage of alloreactive T cells exists across an MHC mismatch, but not all alloreactive cells proliferate in vivo. Bystander proliferation is negligible, revealing exquisite specificity to the alloresponse. These data provide a novel approach to quantify alloreactive T cell responses during specific immunomodulatory strategies in vivo.
Narrative Review of Noninvasive Brain Stimulation in Stroke Rehabilitation (2022)

Stroke is a disease with a high incidence and disability rate, resulting in changes in neural network and corticoid-subcortical excitability and various functional disabilities. The aim of the present study was to discuss the current status of research and limitations and potential direction in the application of noninvasive brain stimulation (NIBS) on post-stroke patients. This literature review focused on clinical studies and reviews. Literature retrieval was conducted in PubMed, Cochrane, Scopus, and CNKI, using the following keywords: Repeated transcranial magnetic stimulation, Transcranial direct current stimulation, Transcranial alternating current stimulation, Transcranial alternating current stimulation, Transcranial focused ultrasound, Noninvasive vagus nerve stimulation, Stroke, and Rehabilitation. We selected 200 relevant publications from 1985 to 2022. An overview of recent research on the use of NIBS on post-stroke patients, including its mechanism, therapeutic parameters, effects, and safety, is presented. It was found that NIBS has positive therapeutic effects on dysfunctions of motor, sensory, cognitive, speech, swallowing, and depression after stroke, but standardized stimulus programs are still lacking. The literature suggests that rTMS and tDCS are more beneficial to post-stroke patients, while tFUS and tVNS are currently less studied for post-stroke rehabilitation, but are also potential interventions.
Antimalarial Activity of Actinomycin D and Cyclophosphamide (1969)

SummaryCyclophosphamide and actinomycin D were highly active against Plasmodium vinckei parasitemia in NMRI mice, even more so than chloroquine. In fact, actinomycin D proved effective at the very low dose of 10 μg/kg. The efficacy of anticancer agents as antimalarials, and vice versa, seems worthy of further study.
Agriculture nordique sous serre. Des projets horticoles communautaires et participatifs peuvent-ils contribuer au développement d’un nouveau système alimentaire durable au Nunavik ? Etudes/Inuit/Studies, accepté. sous presse. (2016)

International audience
Identification of a novel 45 kDa protein (JP-45) from rabbit sarcoplasmic-reticulum junctional-face membrane (2000)

Using a biochemical/immunological approach to analyse the protein constituents of skeletal-muscle junctional-face membrane (JFM), we identified a 45 kDa protein. Its N-terminal amino acid was blocked, but the amino acid sequence obtained from several peptides after proteolytic treatment did not significantly match that of any protein present in the SwissProt and NCBI (National Center for Biotechnology Information) databases. We synthesized a peptide whose sequence matched that of one of the peptides obtained after CNBr cleavage of the 45 kDa protein; the peptide was conjugated to a carrier and used to raise antibodies. The antiserum was used to study in more detail the biochemical characteristics of the novel 45 kDa protein. Analysis of the proteins present in different subcellular membrane fractions show that the novel 45 kDa polypeptide: (i) is an integral membrane constituent present both in neonatal and adult skeletal-muscle sarcoplasmic reticulum; (ii) is selectively localized in the JFM; (iii) is not present in microsomes obtained from rabbit heart, liver or kidney. Immunoprecitation with anti-(45 kDa protein) antibody indicates that the 45 kDa protein is part of a complex which can be phosphorylated in vitro by the catalytic subunit of protein kinase A.
Detection of Impaired OFDM Waveforms Using Deep Learning Receiver (2022)

With wireless networks evolving towards mmWave and sub-THz frequency bands, hardware impairments such as IQ imbalance, phase noise (PN) and power amplifier (PA) nonlinear distortion are increasingly critical implementation challenges. In this paper, we describe deep learning based physical-layer receiver solution, with neural network layers in both time- and frequency-domain, to efficiently demodulate OFDM signals under coexisting IQ, PN and PA impairments. 5G NR standard-compliant numerical results are provided at 28 GHz band to assess the receiver performance, demonstrating excellent robustness against varying impairment levels when properly trained.
Adversarial Linear Contextual Bandits with Graph-Structured Side Observations (2020)

This paper studies the adversarial graphical contextual bandits, a variant of adversarial multi-armed bandits that leverage two categories of the most common side information: \emph{contexts} and \emph{side observations}. In this setting, a learning agent repeatedly chooses from a set of $K$ actions after being presented with a $d$-dimensional context vector. The agent not only incurs and observes the loss of the chosen action, but also observes the losses of its neighboring actions in the observation structures, which are encoded as a series of feedback graphs. This setting models a variety of applications in social networks, where both contexts and graph-structured side observations are available. Two efficient algorithms are developed based on \texttt{EXP3}. Under mild conditions, our analysis shows that for undirected feedback graphs the first algorithm, \texttt{EXP3-LGC-U}, achieves the regret of order $\mathcal{O}(\sqrt{(K+α(G)d)T\log{K}})$ over the time horizon $T$, where $α(G)$ is the average \emph{independence number} of the feedback graphs. A slightly weaker result is presented for the directed graph setting as well. The second algorithm, \texttt{EXP3-LGC-IX}, is developed for a special class of problems, for which the regret is reduced to $\mathcal{O}(\sqrt{α(G)dT\log{K}\log(KT)})$ for both directed as well as undirected feedback graphs. Numerical tests corroborate the efficiency of proposed algorithms.
Diastereoselective Control of Intramolecular Aza-Michael Reactions Using Achiral Catalysts (2011)

An intramolecular aza-Michael reaction with a Cbz carbamate and an enone is reported to result in 3,5-disubstituted nitrogen-containing heterocycles. Either cis or trans isomers were obtained selectively using chiral substrates and an achiral Pd(II) complex or strong Brønsted acid catalysis. A range of substrates undergoes these selective transformations. Functionalization of the resulting products yielding bicyclic heterocycles is also demonstrated.
Noninvasive photoacoustic computed tomography of mouse brain metabolismin vivo (2013)

To control the overall action of the body, brain consumes a large amount of energy in proportion to its volume. In humans and many other species, the brain gets most of its energy from oxygen-dependent metabolism of glucose. An abnormal metabolic rate of glucose and/or oxygen usually reflects a diseased status of brain, such as cancer or Alzheimer’s disease. We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood-brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for photoacoustic imaging of hemodynamic response. Glucose and hemodynamic responses were quantitatively unmixed by using two-wavelength measurements. We found that glucose uptake and blood perfusion around the somatosensory region of the contralateral hemisphere were both increased by stimulations, indicating elevated neuron activity. The glucose response amplitude was about half that of the hemodynamic response. While the glucose response area was more homogenous and confined within the somatosensory region, the hemodynamic response area showed a clear vascular pattern and spread about twice as wide as that of the glucose response. The PACT of mouse brain metabolism was validated by high-resolution open-scalp OR-PAM and fluorescence imaging. Our results demonstrate that 2-NBDG-enhanced PACT is a promising tool for noninvasive studies of brain metabolism.
Engineering Polymer Core–Silica Shell Size in the Composite Abrasives for CMP Applications (2008)

The dependence of chemical mechanical planarization (CMP) performance on both composite polymer core and colloidal silica shell particle sizes is examined. The highest removal rate is observed for the largest diameter cores combined with the smallest silica particles. The model used to explain the results takes into account both the total number of active silica particles still bonded to the polymer core but at the same time pressed against the wafer surface and the indentation depth of each single particle. A contact-area-based mechanism is dominant at the large core (600 nm)–small shell (15 nm) particle sizes, and an indentation mechanism takes over as the shell particle size increases (90 nm). Larger cores elastically deform and gently transfer the applied downforce to a higher number of silica particles with respect to smaller cores.
In situ characterization of the oxidative degradation of a polymeric light emitting device (1997)

Light-emitting devices with polymeric emissive layers have great promise for the production of large-area, lightweight, flexible color displays, but short lifetimes currently limit applications. We address mechanisms of bulk polymer degradation in these devices and show through in situ Fourier transform infrared characterization of working light-emitting devices with active layers of poly[2-methoxy,5-(2′-ethyl-hexoxy)-1,4-phenylene vinylene] that oxygen is responsible for the degradation of the polymer film. A mechanism is given based on the formation of singlet oxygen from oxygen impurities in the film via energy transfer from a nonradiative exciton. Fourier transform infrared and x-ray photoelectron spectroscopy results are consistent with the mechanism, involving singlet oxygen attack followed by free radical processes. We further show that oxygen readily diffuses into the active polymer layer, changing the electrical characteristics of the film even at low concentrations. Thus, polyphenylene-vinylene-based light-emitting devices will self-destruct during operation if fabricated without special attention to eliminating oxygen contamination during fabrication and device operation.
X-ray standing wave analysis for bromine chemisorbed on silicon (1982)

X-ray standing wave measurements on single crystals of silicon are used to determine the coverage and position of chemisorbed bromine. Detailed analysis of the position information leads to the conclusion that silicon surface atoms bonded to adsorbed bromine atoms are in extrapolated bulk-line positions. Direct measurement of the desorption of correlated bromine in air demonstrates the high stability of the Br/Si surface interface.
A GFP Expressing Influenza A Virus to Report In Vivo Tropism and Protection by a Matrix Protein 2 Ectodomain-Specific Monoclonal Antibody (2015)

The severity of influenza-related illness is mediated by many factors, including in vivo cell tropism, timing and magnitude of the immune response, and presence of pre-existing immunity. A direct way to study cell tropism and virus spread in vivo is with an influenza virus expressing a reporter gene. However, reporter gene-expressing influenza viruses are often attenuated in vivo and may be genetically unstable. Here, we describe the generation of an influenza A virus expressing GFP from a tri-cistronic NS segment. To reduce the size of this engineered gene segment, we used a truncated NS1 protein of 73 amino acids combined with a heterologous dimerization domain to increase protein stability. GFP and nuclear export protein coding information were fused in frame with the truncated NS1 open reading frame and separated from each other by 2A self-processing sites. The resulting PR8-NS1(1-73)GFP virus was successfully rescued and replicated as efficiently as the parental PR8 virus in vitro and was slightly attenuated in vivo. Flow cytometry-based monitoring of cells isolated from PR8-NS1(1-73)GFP virus infected BALB/c mice revealed that GFP expression peaked on day two in all cell types tested. In particular respiratory epithelial cells and myeloid cells known to be involved in antigen presentation, including dendritic cells (CD11c+) and inflammatory monocytes (CD11b+ GR1+), became GFP positive following infection. Prophylactic treatment with anti-M2e monoclonal antibody or oseltamivir reduced GFP expression in all cell types studied, demonstrating the usefulness of this reporter virus to analyze the efficacy of antiviral treatments in vivo. Finally, deep sequencing analysis, serial in vitro passages and ex vivo analysis of PR8-NS1(1-73)GFP virus, indicate that this virus is genetically and phenotypically stable.
A new location updating method for digital cellular systems (2002)

A novel location updating technique, the multilayer location updating method (MULTI). is proposed. The location updating signal traffic is distributed over all cells using this method, while, in the conventional method, it is concentrated on the cells located on the location area boundary. Short-term switching instability can be avoided. This method effectively reduces the required control channel number in the ultimate microcell system. The method was proposed as a Japanese digital cellular standard.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>