gebhart/patrepeval huggingface dataset:
IMMU-05. DISRUPTION OF THE CCR2 CHEMOKINE RECEPTOR PATHWAY OVERCOMES THERAPEUTIC RESISTANCE TO PD-1 BLOCKADE IN MALIGNANT GLIOMA (2019)

Abstract INTRODUCTION Large scale clinical trials have failed to determine efficacy of adjuvant PD-1 blockade in recurrent glioblastoma (GBM). However, recent phase 2 clinical trial results demonstrating the potential of neo-adjuvant anti-PD-1 treatment have renewed enthusiasm for the use of immune checkpoint inhibitors (ICIs) in GBM. Additional benefit of ICIs in GBM will likely derive from development of novel therapies directed against immunosuppressive resistance mechanisms. Chemokine receptor 2 (CCR2) expressing tumor infiltrative immune suppressive myeloid cells represent a targetable axis within ICI resistant gliomas. We have established that CCR2 disruption unmasks an effect of anti-PD-1 therapy in ICI resistant murine glioma models. However, the mechanism(s) by which combined inhibition of PD-1 and CCR2 achieves efficacy is unknown. OBJECTIVE Determine the impact of combination anti-PD-1 and CCR2 antagonism on immune cells within anti-PD-1 resistant gliomas. METHODS Immune cell characteristics were determined in CCR2 antagonist (CCX872)/anti-PD-1 treated KR158 or 005 GSC glioma-bearing wild type or CCR2+/rfp/CX3CR1+/gfp reporter mice. RESULTS CCX872 increased median survival (32 vs. 50 days, P=.002) in KR158 tumor-bearing animals and in combination with anti-PD-1 significantly increased durable survival (P=.0005). In 005 GSC glioma-bearing mice, combination therapy also enhanced median survival (30 vs. 49 days, P=.005). CCX872 decreased CD45+/CD11bhi/Ly6Chi MDSCs (40%, P=.038) within gliomas, and increased these cells within bone marrow in both models (74%, P=.020). Three distinct intra-tumoral populations of CCR2+ and CX3CR1+ cells were identified in both glioma models including CCR2+/CX3CR1-/CD45hi/CD11blo, CCR2+/CX3CR1+/CD45hi/CD11bhi/Ly6Chi, and CX3CR1+/CD45lo/CD11bhi/F4/80+/MHCII+, with both CCR2+ populations being reduced by CCX872 treatment. Examination of tumor infiltrating lymphocytes revealed both increased presence and decreased exhaustion (PD-1+/Tim3+) of CD4+ (P=.029) and CD8+ (P=.011) T-cells following CCX872/anti-PD-1 treatment. CONCLUSION CCX872/anti-PD-1 combination therapy is effective in clinically relevant murine glioma models, providing a basis to progress this novel combinatorial treatment to human clinical trials.
Estrous Cycle Patterns in Cattle Monitored by Electrical Resistance and Milk Progesterone (1979)

An electronic probe with parallel stainless steel electrodes was designed to measure changes in electrical resistance in the anterior vagina associated with increased cervical mucus secretion at estrus. Three groups of Holsteins were probed, and a sample of residual milk after milking was taken for progesterone assay every 2nd day for 28 to 40 days. Group I consisted of 29 cycling virgin heifers, Group II consisted of 24 lactating cows in the Cornell herd, and Group III consisted of 62 lactating cows in three commercial herds. Lactating cows were 26 or more days postpartum when sampling began. In Group I, 77% of the measurements at the ventral surface of the anterior vagina were lowest on the day of estrus and correlated well with days KaMaR Heatmount Detectors were triggered or chalk was erased. In Groups II and III, average electrical resistance also was minimal at estrus and was correlated .92 to .99 with average milk progesterone during the 4 days preceding and including estrus. The electronic probe appears to enable one to detect which cows are cycling normally and to aid in determining when to expect estrus.
Ghrelin: Structural and Functional Properties (2007)

Abstract Ghrelin is a gastro‐intestinal peptide hormone acting on important brain including the hypothalamus where it modulates appetite, metabolism and the autonomous nervous system. In the pariphery ghrelin has been described as a modulator of the cardiovascular system and various endocrine tissues involved in metabolism. Importantly, ghrelin is the only peptide hormone modified by a fatty acid chain, being essential for its activity. The receptor for ghrelin is a member of the 7TM/G‐protein coupled receptor super family and signal mainly through Gq coupling. Interestingly, the ghrelin receptor is constitutively active providing increased signaling by increased receptor expression independent of thc endogenous ligand.
Language-level persistency (2017)

The commercial release of byte-addressable persistent memories, such as Intel/Micron 3D XPoint memory, is imminent. Ongoing research has sought mechanisms to allow programmers to implement recoverable data structures in these new main memories. Ensuring recoverability requires programmer control of the order of persistent stores; recent work proposes persistency models as an extension to memory consistency to specify such ordering. Prior work has considered persistency models at the abstraction of the instruction set architecture. Instead, we argue for extending the language-level memory model to provide guarantees on the order of persistent writes. We explore a taxonomy of guarantees a language-level persistency model might provide, considering both atomicity and ordering constraints on groups of persistent stores. Then, we propose and evaluate Acquire-Release Persistency (ARP), a language-level persistency model for C++11. We describe how to compile code written for ARP to a state-of-the-art ISA-level persistency model. We then consider enhancements to the ISA-level persistency model that can distinguish memory consistency constraints required for proper synchronization but unnecessary for correct recovery. With these optimizations, we show that ARP increases performance by up to 33.2% (19.8% avg.) over coding directly to the baseline ISA-level persistency model for a suite of persistent-write-intensive workloads.
Design and Testing of Low Pole Dual-Stator Flux-Switching Permanent Magnet Machine for Electric Vehicle Applications (2019)

This paper investigates the design and testing of a high-speed dual-stator 6/4 flux-switching permanent magnet (FSPM) machine. A dual-stator design is used to solve the issue of second harmonic presented in the flux linkage of conventional 6/4 FSPM machine. Different dual-stator designs are investigated and compared against each other in terms of the performance and manufacturability. Comparison between the proposed dual-stator 6/4 FPSM machine and a commonly seen 12/10 FSPM machine is done at 10 kW, 15000 rpm condition. Due to the 60% reduction of the fundamental frequency, a significant reduction in iron loss and magnet eddy current loss is observed, which leads to higher efficiency. A prototype dual-stator 6/4 FSPM motor is built and tested on a dynamometer set up to verify the analytical calculation and finite element analysis results. A comparison is made between measured data and simulation results, and good agreements are achieved.
Novel 2,3-Dihydrobenzofuran-2-carboxylic Acids:  Highly Potent and Subtype-Selective PPARα Agonists with Potent Hypolipidemic Activity (2005)

The design and synthesis of a novel class of 2,3-dihydrobenzofuran-2-carboxylic acids as highly potent and subtype-selective PPARalpha agonists are reported. Systematic study of structure-activity relationships has identified several key structural elements within this class for maintaining the potency and subtype selectivity. Select compounds were evaluated in animal models of dyslipidemia using Syrian hamsters and male Beagle dogs, and all these compounds displayed excellent cholesterol- and triglyceride-lowering activity at dose levels that were much lower than the marketed weak PPARalpha agonist fenofibrate.
Division-of-amplitude Photopolarimeter (DOAP) for the Simultaneous Measurement of All Four Stokes Parameters of Light (1982)

Abstract To measure all four Stokes parameters of a light beam simultaneously, the beam is divided into four separate beams using a beamsplitter and two Wollaston prisms. Linear detection of the light fluxes of the four component beams gives four signals that determine the four Stokes parameters. This division-of-amplitude photopolarimeter (DOAP) is completely characterized by a wavelength-dependent 4 2 4 matrix that can be determined directly by calibration. The instrument has a fast response (that is limited only by the photodetectors) as it has no moving parts or modulation. Notes See, for example, [1], p. 491.
Cellometer Vision as an alternative to flow cytometry for cell cycle analysis, mitochondrial potential, and immunophenotyping (2011)

Cell phenotyping and cell cycle analysis are two commonly used assays in both clinical diagnosis and biomedical research. Cell phenotyping by identifying different biomarkers is essential for the diagnosis of hematologic malignancy, sub-classifying diseases, monitoring response to treatment, predicting prognosis, detecting rare cell populations and residual malignant cells. Cell cycle analysis distinguishes cells in different phases of cell cycle and is often used to determine the cellular response to drugs and biological stimulations. These assays have been traditionally carried out by sensitive fluorescence detection methods such as flow cytometry and laser scanning cytometry for fluorescence-based cell population analysis. However, these instruments remain relatively expensive, large in size, and require a considerable amount of maintenance, which may not be feasible for smaller research groups that do not have access to these equipments or field clinics that require quick diagnostic results on site. Recently, a small portable imaging cytometry system (Cellometer Vision) has been developed by Nexcelom Bioscience LLC (Lawrence, MA) for automated cell concentration and viability measurement using bright-field and fluorescent imaging methods. Here we report new applications of the Cellometer imaging cytometry for fluorescence-based cell population analysis and compared them with conventional flow cytometry. Cell population analysis assays such as immunophenotyping, cell cycle, and mitochondrial membrane potential detection methods have not yet been reported for the Cellometer Vision system. Using this imaging cytometry method for fluorescence-based assays that are typically done by flow cytometry offers a quick, simple, and inexpensive alternative method for biomedical research, which may be beneficial for smaller research laboratories and clinics.
Phase function design of a diffraction grating lens for an optical imaging system from a Fraunhofer diffraction perspective (2013)

The potential exists to apply diffraction gratings to optical imaging systems to improve camera resolution and shorten optical length. However, we have noted the generation of striped flare lights, which differ from unnecessary-order diffraction lights, under intense lighting. We have elucidated the generation principle of these new striped lights and have discovered that they are caused by narrow diffraction grating rings. In this paper, using an analysis based on Fraunhofer diffraction, we suggest a way of minimizing them by designing an appropriate phase function structure, and test the efficacy of this design using our own manufactured prototype.
Ultrafast Laser Driven Micro-Lens to Focus and Energy Select MeV Protons (2008)

International audience
Versatile BIST: an integrated approach to on-line/off-line BIST (2002)

In this paper we report a versatile BIST approach (VBIST) that targets both off-line and on-line self test. VBIST uses off-line BIST circuitry for on-line testing as well. Unlike traditional on-line self test approaches, VBIST does not use functional data as test inputs. Rather, VBIST generates test patterns and compacts test responses during the normal mode of operation. Furthermore, VBIST coordinates this generation and application of test patterns and compaction of test responses with the usage profile of the modules in the design. VBIST entails little additional impact on performance and area of the design (vis-a-vis the performance and area of a design with off-line BIST). We validated the VBIST approach using the Synopsys Behavioral Compiler as the synthesis framework and by writing synthesis scripts for incorporating VBIST constraints.
Lithium Batteries and Supercapacitors Capable of Operating at Low Temperatures for Planetary Exploration (2012)

Demonstrated improved performance with wide operating temperature electrolytes containing ester co - solvents (i.e., methyl propionate and ethyl butyrate) in a number of prototype cells: center dot Successfully scaled up low temperature technology to 12 Ah size prismatic Li - ion cells (Quallion, LCC), and demonstrated good performance down to - 60 o C. center dot Demonstrated wide operating temperature range performance ( - 60 o to +60 o C) in A123 Systems LiFePO 4 - based lithium - ion cells containing methyl butyrate - based low temperature electrolytes. These systems were also demonstrated to have excellent cycle life performance at ambient temperatures, as well as the ability to be cycled up to high temperatures.
Glutamate-Weighted Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Detects Glutaminase Inhibition in a Mouse Model of Triple-Negative Breast Cancer (2018)

Glutamate is an important metabolite of glutaminolysis, a metabolic pathway used by many aggressive cancers, including triple-negative breast cancer (TNBC). With the exception of the brain, <i>in vivo</i> detection of glutamate in tissues using <sup>1</sup>H magnetic resonance spectroscopy (MRS) is challenging. Compared with MRS, glutamate-weighted chemical exchange saturation transfer MR imaging (GluCEST MRI) offers a more sensitive detection mechanism that is free of glutamine interference. Here, we developed a robust, highly repeatable GluCEST MRI protocol in mice bearing human TNBC xenografts and treated with a potent glutaminase inhibitor, CB-839. In paired studies, treatment with CB-839 for 2 days reduced the GluCEST asymmetry value compared with baseline (<i>P</i> < 0.05, <i>n</i> = 10). The absolute change of the GluCEST asymmetry value was -2.5 percent points after CB-839 treatment versus +0.3 after vehicle (<i>P</i> < 0.01). Correspondingly, treatment with CB-839 reduced tumor glutamate concentrations by 1.5 mmol/L, consistent with prior calibration between changes of the GluCEST value versus tissue glutamate concentration; CB-839, however, did not change tumor intracellular pH. These results demonstrate in a mouse model of breast cancer the utility of GluCEST MRI to detect the early response to glutaminase inhibition.<b>Significance:</b> A sensitive method enables noninvasive detection of tumor response to inhibitors of glutamine metabolism. <i>Cancer Res; 78(19); 5521-6. ©2018 AACR</i>.
Expression Analysis and Physical Mapping of a cDNA Library of Fusarium Head Blight Infected Wheat Spikes (2006)

Resistance to Fusarium head blight (FHB) (caused mainly by Fusarium graminearum Schw.) is difficult to obtain because of the quantitative nature and the numerous types of resistance involved. cDNA expression arrays have become a rapidly growing area for the identification and characterization of genes involved in complex pathways. A cDNA library was made from wheat ( Triticum aestivum L.) spikes of the variety ‘Sumai 3’, 24 h after inoculation with F. graminearum . Clones were sequenced and putative function assigned to each clone based on BLASTX alignments. Nylon membrane arrays were made from the 580 unigenes present in the library, of which 75 expressed clones were induced in the first 24 h after inoculation. Of these unigenes, 14 are involved in defense response, 9 in gene expression and regulation, 29 in other cell functions, and 24 are without a known function. The induced genes catalyze key steps in the formation of lignin, energy production, and production of phytoalexins suggesting that resistance in wheat to Fusarium is provided by a different pathway than that of the hypersensitive response. Two of the induced genes, BE585589 and BE585627, were physically mapped to regions of chromosomes 3AS and 6BL, respectively, known to contain major QTL for FHB resistance.
609. Systemic Delivery of Dysferlin Overlap Vectors Mediates Functional Recovery of Dysferlin Deficiency (2015)

Dysferlinopathies comprise a family of disorders caused by mutations in the dysferlin (DYSF) gene leading to absent or mutant protein. Dysferlin protein has been implicated in multiple functional roles specifically in membrane stabilization/repair, t-tubule formation and vesicle trafficking. The loss of dysferlin causes a progressive dystrophy characterized by chronic muscle fiber loss, fat replacements and fibrosis resulting in deteriorating muscle weakness. Efforts made in the gene therapy arena with dysferlin or surrogate gene replacement have shown some efficacy in restoring membrane repair, however, only delivery of full-length DYSF has been able to correct the underlying histopathology. Therefore, there is a strong rationale to develop therapies that deliver the entire DYSF cDNA. A potential issue with this is the size of the DYSF gene (6.5 kb) which is too large for canonical AAV packaging. To circumvent this, we have developed and previously shown efficacy with a unique dual vector system using AAV to deliver and express DYSF specifically in muscle cells. This two vector system (AAV.DYSF.DV) packaged in the rh. 74 serotype is defined by a 1 kb region of homology between the two vectors. Following delivery to muscle, this overlap serves as a substrate for recombination/repair to generate the full-length gene. Our previous work studied the efficacy of this treatment strategy through intramuscular and regional vascular delivery routes. However, as generalized muscle weakness is common in dysferlinopathies, therapies targeting all muscle groups are warranted to maximize clinical efficacy. In this update, we have treated dysferlin-deficient mice systemically by intravenous injection to target all muscles through the vasculature for efficacy and safety studies. Mice were evaluated at 3 and 6 months post-treatment for dysferlin expression, restoration of membrane repair capability, diaphragm specific force measurements and muscle histology. Additional animals are awaiting MRI analysis following 1 year of treatment. A single systemic dose of 6×1012 vector genomes (3×1012 vg of each vector) resulted in widespread gene expression exceeding 30% of muscle fibers. Treated muscles showed a significant decrease in central nucleation and collagen deposition. Membrane repair ability was improved toward wild-type and force deficits in the diaphragm were restored to wildtype levels. The mice showed no evidence of local or systemic toxicity, further confirming previous safety data. This study, in conjunction with our previous work, lays the foundation for clinical trial.
Microbiota-Regulated IL-25 Increases Eosinophil Number to Provide Protection during Clostridium difficile Infection (2016)

Clostridium difficile infection (CDI) is the most common cause of hospital-acquired infection in the United States. Host susceptibility and the severity of infection are influenced by disruption of the microbiota and the immune response. However, how the microbiota regulate immune responses to mediate CDI outcome remains unclear. Here, we have investigated the role of the microbiota-linked cytokine IL-25 during infection. Intestinal IL-25 was suppressed during CDI in humans and mice. Restoration of IL-25 reduced CDI-associated mortality and tissue pathology even though equivalent levels of C. difficile bacteria and toxin remained in the gut. IL-25 protection was mediated by gut eosinophils, as demonstrated by an increase in intestinal eosinophils and a loss of IL-25 protection upon eosinophil depletion. These findings support a mechanism whereby the induction of IL-25-mediated eosinophilia can reduce host mortality during active CDI. This work may provide targets for future development of microbial or immune-based therapies.
Spatiotemporal Complexity of Fibroblast Networks Screens for Alzheimer's Disease (2012)

Drugs to treat Alzheimer's disease (AD) have been unsuccessful in preventing its devastating cognitive deficits and progressive neurodegeneration. The lack of a definitive diagnostic for AD has been a major obstacle to AD drug discovery. Here, we describe a novel, highly accurate peripheral diagnostic for AD patients based on quantitatively measured complexity of skin-sampled fibroblast networks. A significant number of samples were studied under double-blind conditions and had autopsy and/or genetic validation. An additional sample confirmed the diagnostic discrimination on freshly obtained skin samples. A sub-sample of these diagnostic differences were induced by oligomerized amyloid-β1-42. Based on the accuracy of these measures that utilize physical principles such as fractal dimension and lacunarity as well as the significant correlation with disease duration, this biomarker profile appears to identify accurately AD patients for therapeutic intervention.
Moving beam helical CT scanning (1996)

Images generated with helical scanning are degraded by partial volume artifacts caused by an increased slice thickness when compared to conventional computed tomography (CT) scanning. The slice thickness for a helical scan is proportional to the sum of the thickness of the fan of radiation and the distance the patient moves during data acquisition. The authors present a method called moving beam helical scanning (MBHS) which significantly reduces the partial volume artifacts caused by helical scanning. The key element of MBHS is a rotatable collimator that is placed between the X-ray source and the patient. As the patient is translated, the collimator is used to aim the fan on a fixed position in the patient. Once sufficient data are obtained to reconstruct a slice, the collimator is quickly reset to scan a target in the next slice. The authors examined the performance of MBHS by scanning wires and phantoms on a modified scanner. The full-width-at-tenth-maximum of the slice profile at iso-center for MBHS is identical to conventional CT versus a 59% increase for conventional helical scanning. It is concluded that MBHS can be used to obtain the scan rate advantages of helical scanning with image quality comparable to conventional scanning.