gebhart/patrepeval huggingface dataset:
Peripheral nerve stimulation measures in a composite gradient system (2014)

ABSTRACT Purpose: This work compared peripheral nerve stimulation (PNS) thresholds for the MRI scanner body gradients (BODY), a head/neck insert gradient (INSERT), and the combination of both gradient sets used simultaneously (COMPOSITE). Methods : For BODY, INSERT and COMPOSITE gradients, PNS thresholds were determined by exposing subject volunteers to stepped increases in gradient strength. For COMPOSITE mode, the INSERT was applied at equal (experiment 1) or double (experiment 2) the BODY gradient strength. Results: The locations and thresholds of peripheral nerve stimulation depended on the gradient system configuration, gradient axis, and gradient strength. Stimulation in the body occurred when using the BODY Y ‐gradient axis either singly (110 T/m/s) or in COMPOSITE mode (315 T/m/s experiment 2) and adding the insert gradient had negligible effect on stimulation. Stimulation in the head/sinus area generally occurred when using the INSERT X ‐gradient either singly (213 T/m/s) or in COMPOSITE mode (320 T/m/s) and adding the body gradient had negligible effect on stimulation. In the COMPOSITE mode, both the location of stimulation and the limiting gradient strength matched location and strength of the limiting component gradient. Conclusion: Stimulation, to a first‐order approximation, is independent for the two gradient systems. In COMPOSITE mode, PNS can be dominated by either of the individual gradient components, indicating that the contribution of each component can be increased until the threshold limit of each component gradient is reached. COMPOSITE gradients provide increased gradient performance with PNS thresholds higher than either component gradient system operating alone. © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 44B: 66–74, 2015
Modélisation de la condensation capillaire pour le micro-assemblage (2005)

info:eu-repo/semantics/published
The engineered CD80 variant fusion therapeutic davoceticept combines checkpoint antagonism with conditional CD28 costimulation for anti-tumor immunity (2022)

Despite the recent clinical success of T cell checkpoint inhibition targeting the CTLA-4 and PD-1 pathways, many patients either fail to achieve objective responses or they develop resistance to therapy. In some cases, poor responses to checkpoint blockade have been linked to suboptimal CD28 costimulation and the inability to generate and maintain a productive adaptive anti-tumor immune response. To address this, here we utilize directed evolution to engineer a CD80 IgV domain with increased PD-L1 affinity and fuse this to an immunoglobulin Fc domain, creating a therapeutic (ALPN-202, davoceticept) capable of providing CD28 costimulation in a PD-L1-dependent fashion while also antagonizing PD-1 - PD-L1 and CTLA-4-CD80/CD86 interactions. We demonstrate that by combining CD28 costimulation and dual checkpoint inhibition, ALPN-202 enhances T cell activation and anti-tumor efficacy in cell-based assays and mouse tumor models more potently than checkpoint blockade alone and thus has the potential to generate potent, clinically meaningful anti-tumor immunity in humans.
Oral immunotherapy with type V collagen in idiopathic pulmonary fibrosis (2015)

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. IPF appears to be heterogeneous in pathobiology with ∼40% of IPF patients found to have elevated levels of circulating antibodies to the autoantigen type V collagen (col(V)). Following a targeted, precision medicine approach, we conducted a phase 1 study to test the safety and explore potential efficacy of IW001, a col(V) oral immunotherapeutic developed to treat antibody-positive IPF patients. We divided 30 antibody-positive IPF patients into three cohorts for daily dosing over a 24-week period. All patients completed treatment without serious adverse events, acute exacerbations or IPF-related hospitalisations. A decline in lung function occurred in the lowest-dose cohort that was comparable to that reported in placebo arms of published IPF trials. In contrast, the highest-dose cohort showed a trend toward stabilisation of forced vital capacity and matrix metalloproteinase 7, and a reduction in binding of C1q to anti-col(V) antibodies. IW001 may modulate the immune response to col(V) and may represent a new therapeutic for col(V)- reactive IPF patients.
Analysis and Design of Concrete Traffic Railings (2011)

The current design methodology for concrete highway railings uses a yield line analysis procedure developed for Texas Department of Transportation (TxDOT) in the late 70’s by T. J. Hirsch of the Texas Transportation Institute. Review of various concrete bridge railings subjected to full-scale crash tests and field impacts shows concrete failures to be punching shear rather than moment or yield line failure. This paper reviews the supporting documentation and shows a proposed design procedure based on an anticipated two way punching shear failure at ultimate loading conditions.
Development of 3D Fused Quartz Hemi-Toroidal Shells for High-Q Resonators and Gyroscopes (2019)

In this paper, recent developments in the design and fabrication of micromachined fused quartz hemi-toroidal shells are presented. The fabrication is based on micro glassblowing process, demonstrated to enable the realization of high-Q MEMS resonators and gyroscopes. The design optimization of the shell geometry is performed using parametric finite element analysis. The effect of geometric parameters on the scaling of the resonant frequencies and energy dissipation are discussed. Three variations of the micro-glassblowing process are studied in the paper, concluding that shell resonators with a broad operational frequency range without losing the symmetry and Q-factor are feasible. Finite element models are presented to simulate the presented glassblowing processes, which are used to predict the final geometry of shell resonators accurately. Operational frequency as low as 5 kHz and Q-factor as high as 1.7 million is demonstrated on the fabricated shell resonators. The proposed process modifications demonstrate a low-cost and scalable fabrication of 3D shells for resonators and gyroscopes, which can be used in inertial navigation and timing applications.
High nuclearity Ni/Co polyoxometalates and colloidal TiO2assemblies as efficient multielectron photocatalysts under visible or sunlight irradiation (2010)

Visible or sunlight irradiation of high nuclearity cobalt- or nickel-centers containing polyoxometalates (POMs), alone or in association with colloidal TiO2, results in their neat, apparently direct, multielectron reduction. These materials prove very effective in the first example of visible or sunlight driven POM-based degradation of Acid Orange 7.
Identification of true-static predistorter using a sine wave and accurate quantification of memory effects in broadband wireless transmitters (2011)

This study proposes a new technique for the extraction of static non-linearities in wideband transmitters by launching a simple sinusoidal wave within the bandwidth of the system. The transmitter is first characterised under a two-carrier wideband code division multiple access (WCDMA) drive signal and modelled using a memory polynomial model. Two types of memoryless digital predistorters are then synthesised and applied to the amplifier model. The first predistorter is derived from the averaging of the measured data under the two-carrier WCDMA signal, while the second is derived using a sinusoidal wave signal excitation. Discrepancies between the two predistortion functions are illustrated, demonstrating that the predistorter using the averaging technique is biased by the presence of linear memory effects. The results show that the residual distortions at the output of the linearised power amplifier are different and more present when using the sine wave excitation technique compared with the averaging technique. This finding indicates that the sine wave-based technique is more rigorous for de-embedding the static non-linearity from the overall non-linear behaviour, which corroborates the validity of the proposed approach in extracting the true static behaviour of the system and its pertinence for the accurate extraction and quantification of memory effects.
Al(OTf)3 as a Highly Efficient Catalyst for the Rapid Acetylation of Alcohols, Phenols and Thiophenols under Solvent‐Free Conditions. (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Identification of 2-Imidazopyridine and 2-Aminopyridone Purinones as Potent Pan-Janus Kinase (JAK) Inhibitors for the Inhaled Treatment of Respiratory Diseases (2019)

Janus kinases (JAKs) have a key role in regulating the expression and function of relevant inflammatory cytokines involved in asthma and chronic obstructive pulmonary disease. Herein are described the design, synthesis, and pharmacological evaluation of a series of novel purinone JAK inhibitors with profiles suitable for inhaled administration. Replacement of the imidazopyridine hinge binding motif present in the initial compounds of this series with a pyridone ring resulted in the mitigation of cell cytotoxicity. Further systematic structure-activity relationship (SAR) efforts driven by structural biology studies led to the discovery of pyridone <b>34</b>, a potent pan-JAK inhibitor with good selectivity, long lung retention time, low oral bioavailability, and proven efficacy in the lipopolysaccharide-induced rat model of airway inflammation by the inhaled route.
Augmented Reality Chemistry: Transforming 2-D Molecular Representations into Interactive 3-D Structures (2018)

Spatial reasoning is defined as the ability to generate, retain, and manipulate abstract visual images. In chemistry, spatial reasoning skills are typically taught using 2-D paper-based models, 3-D handheld models, and computerized models. These models are designed to aid student learning by integrating information from the macroscopic, microscopic, and symbolic domains of chemistry. Research has shown that increased spatial reasoning abilities translate directly to improved content knowledge. The recent explosion in the popularity of smartphones and the development of augmented reality apps for them provide, a yet to be explored, way of teaching spatial reasoning skills to chemistry students. Augmented reality apps can use the camera on a smartphone to turn 2-D paper-based molecular models into 3-D models the user can manipulate. This paper will discuss the development, implementation, and assessment of an augmented reality app that transforms 2-D molecular representations into interactive 3-D structures.
Introduction (2011)

This chapter contains sections titled: Who Should Read This Book How This Book is Organized How to Read This Book and Learn from It Note for Instructors Book Web Site
Long-term Wear Data From a Prospective Multicenter Study of Second-Generation Highly Cross-linked Polyethylene Inserts in Total Hip Arthroplasty (2018)

In a prospective multicenter trial on highly cross-linked polyethylene inserts in patients undergoing total hip arthroplasty, 118 patients consented to 10-year follow-up. Medium-term follow-up results showed low wear at 5 and 7 years after surgery. The current study focuses on long-term data at 10 years. Patients were followed up by either phone or office visit to collect long-term clinical data including Harris hip score and adverse events. There were 2 deaths and 2 revisions, 1 at 6.5 years for pelvic cyst and severe pain and another at 8.0 years for recurrent dislocation. For wear analysis, suitable radiographic images for 48 patients (52 hips) at minimum 10-year follow-up were available. Mean age of the cohort was 62.5 years (62% female). Femoral head penetration was measured using Martell's method from the radiographic images between the 6-week and the subsequent follow-ups. Polyethylene wear rate was calculated from the penetration data. Descriptive statistics were performed. There was no evidence of significant oxidation or locking mechanism failure. Mean Harris hip score of the group was 94.3. No osteolysis was noted by an independent radiographic reviewer. The slope of the bestfit regression line to the femoral head penetration data, which represents the overall linear wear rate of the polyethylene, was 0.014 mm/y. The wear rate was significantly below the 0.100 mm/y critical threshold for development of osteolysis. Volumetric wear rate was calculated to be 11.6 mm<sup>3</sup>/y. The second-generation highly cross-linked polyethylene acetabular inserts had low wear in the long term (10.3 years) with no incidence of osteolysis. [Orthopedics. 2018; 41(4):e529-e533.].
Advancements on galvanometer scanners for high-end applications (2014)

Galvanometer-based scanners (GSs) are the most utilized devices for lateral scanning. Their applications range from commercial and industrial to biomedical imaging. They are used mostly for 2-D scanning (with typically two GSs), but also for 1-D or 3-D scanning (the latter by example with GSs in combination with Risley prisms). This paper presents an overview of our contributions in the field of GSs with regard to the requirements of their most challenging applications. Specifically, we studied the optimal scanning functions - to produce the maximum possible duty cycle&eta;, and we found that, contrary to what has been stated in the literature, the scanning function that provides the highest &eta; is not linear plus sinusoidal, but linear plus parabolic. The most common GS input signals (i.e., sawtooth, triangular, and sinusoidal) were investigated experimentally to determine the scanning regimes that produce the minimum image artifacts, for example in Optical Coherence Tomography (OCT). The triangular signal was thus shown to be the best from this point of view, and several rules-of-thumb were extracted to make the best of GSs in OCT. We also discuss aspects of the command functions of GSs that are necessary to achieve a trade-off between a performance criteria related to the duty cycle and voltage regimes of the device. We finally review aspects of the control solutions of GSs we investigated, to obtain the highest possible precision or the fastest possible response of the scanner.
Human Muscle Progenitor Cells Overexpressing Neurotrophic Factors Improve Neuronal Regeneration in a Sciatic Nerve Injury Mouse Model (2019)

The peripheral nervous system has an intrinsic ability to regenerate after injury. However, this process is slow, incomplete, and often accompanied by disturbing motor and sensory consequences. Sciatic nerve injury (SNI), which is the most common model for studying peripheral nerve injury, is characterized by damage to both motor and sensory fibers. The main goal of this study is to examine the feasibility of administration of human muscle progenitor cells (hMPCs) overexpressing neurotrophic factor (NTF) genes, known to protect peripheral neurons and enhance axon regeneration and functional recovery, to ameliorate motoric and sensory deficits in SNI mouse model. To this end, hMPCs were isolated from a human muscle biopsy, and manipulated to ectopically express brain-derived neurotrophic factor (BDNF), glial-cell-line-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF-1). These hMPC-NTF were transplanted into the gastrocnemius muscle of mice after SNI, and motor and sensory functions of the mice were assessed using the CatWalk XT system and the hot plate test. ELISA analysis showed that genetically manipulated hMPC-NTF express significant amounts of BDNF, GDNF, VEGF, or IGF-1. Transplantation of 3 × 10<sup>6</sup> hMPC-NTF was shown to improve motor function and gait pattern in mice following SNI surgery, as indicated by the CatWalk XT system 7 days post-surgery. Moreover, using the hot-plate test, performed 6 days after surgery, the treated mice showed less sensory deficits, indicating a palliative effect of the treatment. ELISA analysis following transplantation demonstrated increased NTF expression levels in the gastrocnemius muscle of the treated mice, reinforcing the hypothesis that the observed positive effect was due to the transplantation of the genetically manipulated hMPC-NTF. These results show that genetically modified hMPC can alleviate both motoric and sensory deficits of SNI. The use of hMPC-NTF demonstrates the feasibility of a treatment paradigm, which may lead to rapid, high-quality healing of damaged peripheral nerves due to administration of hMPC. Our approach suggests a possible clinical application for the treatment of peripheral nerve injury.
Enhanced Convolutional Neural Tangent Kernels (2019)

Recent research shows that for training with $\ell_2$ loss, convolutional neural networks (CNNs) whose width (number of channels in convolutional layers) goes to infinity correspond to regression with respect to the CNN Gaussian Process kernel (CNN-GP) if only the last layer is trained, and correspond to regression with respect to the Convolutional Neural Tangent Kernel (CNTK) if all layers are trained. An exact algorithm to compute CNTK (Arora et al., 2019) yielded the finding that classification accuracy of CNTK on CIFAR-10 is within 6-7% of that of that of the corresponding CNN architecture (best figure being around 78%) which is interesting performance for a fixed kernel. Here we show how to significantly enhance the performance of these kernels using two ideas. (1) Modifying the kernel using a new operation called Local Average Pooling (LAP) which preserves efficient computability of the kernel and inherits the spirit of standard data augmentation using pixel shifts. Earlier papers were unable to incorporate naive data augmentation because of the quadratic training cost of kernel regression. This idea is inspired by Global Average Pooling (GAP), which we show for CNN-GP and CNTK is equivalent to full translation data augmentation. (2) Representing the input image using a pre-processing technique proposed by Coates et al. (2011), which uses a single convolutional layer composed of random image patches. On CIFAR-10, the resulting kernel, CNN-GP with LAP and horizontal flip data augmentation, achieves 89% accuracy, matching the performance of AlexNet (Krizhevsky et al., 2012). Note that this is the best such result we know of for a classifier that is not a trained neural network. Similar improvements are obtained for Fashion-MNIST.
Dicationic Bis(9-methylphenazine-1-carboxamides):  Relationships between Biological Activity and Linker Chain Structure for a Series of Potent Topoisomerase Targeted Anticancer Drugs (2001)

Bis(9-methylphenazine-1-carboxamides) joined by a variety of dicationic (CH(2))(n)()NR(CH(2))(m)NR(CH(2))(n) linkers of varying length (carboxamide N-N distances from 11.0 to 18.4 A) and rigidity were prepared by reaction of 9-methylphenazine-1-carboxylic acid imidazolide with the appropriate polyamines. The compounds were evaluated for growth inhibitory properties in P388 leukemia, Lewis lung carcinoma, and wild-type (JL(C)) and mutant (JL(A) and JL(D)) forms of human Jurkat leukemia with low levels of topoisomerase II (topo II). The compounds all had IC(50) ratios of <1 in the resistant Jurkat lines, consistent with topo II inhibition not being the primary mechanism of action. Analogues joined by an (CH(2))(2)NR(CH(2))(2)NR(CH(2))(2) linker were extremely potent cytotoxins, with selectivity toward the human cell lines, but absolute potencies declined sharply from R = H through R = Me to R = Pr and Bu. In contrast, (CH(2))(2)NR(CH(2))(3)NR(CH(2))(2) compounds showed reverse effects, with the R = Me analogue being more potent than the R = H one as well as being the most potent in the series [IC(50) in JL(C) cells 0.08 nM; superior to that for the clinical bis(naphthalimide) LU 79553]. Overall, the IC(50)s of analogues with linker chains (CH(2))(n)NH(CH(2))(m)NH(CH(2))(n) were inversely proportional to linker length. Constraining the rigidity of the linker chain by incorporating a piperazine ring did not decrease potency significantly. A representative compound bound tightly to DNA with high selectivity for GC sites, compatible with recent work suggesting that compounds of this type place their side chains in the major groove, making specific contacts with guanine bases. Representative compounds were susceptible to transport mediated resistance, being much less effective in cells that overexpressed P-glycoprotein. Overall the results suggest these compounds have a similar mode of action, mediated primarily by poisoning of topo I (possibly with some involvement of topo II). The bis(9-methylphenazine-1-carboxamides) show very high in vitro growth inhibitory potencies compared to their monomeric analogues. Two compounds showed in vivo activity in murine colon 38 syngeneic and HT29 human colon tumor xenograft models using intraperitoneal dosing.
Diode-pumped narrow linewidth multi-kilowatt metalized Yb fiber amplifier (2016)

We investigate high brightness pumping of a multi-kilowatt Yb fiber amplifier in a bi-directional pumping configuration. Each pump outputs 2 kW in a 200 μm, 0.2 NA multimode fiber. Gold-coated specialty gain fibers, with a 17 μm mode field diameter and a 5 dB/m pump absorption, have been developed. The maximum fiber amplifier output power is 3.1 kW, limited by multimode instability, with 90% O-O efficiency and M<sup>2</sup><1.15. The fiber amplifier linewidth is 12 GHz.
Data from MDM2 Inhibition Enhances Immune Checkpoint Inhibitor Efficacy by Increasing IL15 and MHC Class II Production (2023)

&lt;div&gt;Abstract&lt;p&gt;The treatment of patients with metastatic melanoma with immune checkpoint inhibitors (ICI) leads to impressive response rates but primary and secondary resistance to ICI reduces progression-free survival. Novel strategies that interfere with resistance mechanisms are key to further improve patient outcome during ICI therapy. P53 is often inactivated by mouse-double-minute-2 (MDM2), which may decrease immunogenicity of melanoma cells. We analyzed primary patient-derived melanoma cell lines, performed bulk sequencing analysis of patient-derived melanoma samples, and used melanoma mouse models to investigate the role of MDM2-inhibition for enhanced ICI therapy. We found increased expression of IL15 and MHC-II in murine melanoma cells upon p53 induction by MDM2-inhibition. MDM2-inhibitor induced MHC-II and IL15-production, which was p53 dependent as &lt;i&gt;Tp53&lt;/i&gt; knockdown blocked the effect. Lack of IL15-receptor in hematopoietic cells or IL15 neutralization reduced the MDM2-inhibition/p53-induction–mediated antitumor immunity. P53 induction by MDM2-inhibition caused anti-melanoma immune memory as T cells isolated from MDM2-inhibitor–treated melanoma-bearing mice exhibited anti-melanoma activity in secondary melanoma-bearing mice. In patient-derived melanoma cells p53 induction by MDM2-inhibition increased IL15 and MHC-II. &lt;i&gt;IL15&lt;/i&gt; and &lt;i&gt;CIITA&lt;/i&gt; expressions were associated with a more favorable prognosis in patients bearing WT but not &lt;i&gt;TP53&lt;/i&gt;-mutated melanoma.&lt;/p&gt;Implications:&lt;p&gt;MDM2-inhibition represents a novel strategy to enhance IL15 and MHC-II–production, which disrupts the immunosuppressive tumor microenvironment. On the basis of our findings, a clinical trial combining MDM2-inhibition with anti–PD-1 immunotherapy for metastatic melanoma is planned.&lt;/p&gt;&lt;/div&gt;