gebhart/patrepeval huggingface dataset:
Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis (2016)

Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD-abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions.
JAK Family Inhibitors for Autoimmune Diseases (2021)

Abstract The JAK family of non‐receptor tyrosine kinases mediates the signaling of proinflammatory cytokines that contribute to the pathogenesis of numerous autoimmune diseases. While cytokine‐directed therapies are available to treat immune‐driven diseases, oral small‐molecule inhibitors of the JAK family (Jakinibs) have been approved as viable alternatives for the treatment of RA, PsA, and IBD. These first‐generation pan‐JAK inhibitors target the highly conserved catalytically active kinase domains in a reversible, ATP‐competitive manner, albeit in a nonselective fashion. Novel approaches to target alternative binding modes through, for example irreversible or allosteric kinase inhibition, have led to the identification of the next generation of agents, which demonstrate improved JAK family selectivity. This improved selectivity offers the potential for greater and perhaps broader efficacy by allowing for higher dosing, while avoiding undesired side effects. This article provides an overview of the JAK‐STAT signaling pathway and outlines the challenges associated with the discovery of selective JAK inhibitors while highlighting a unique allosteric TYK2 inhibitor. For each of the agents discussed, a synopsis of the medicinal chemistry efforts leading to a particular molecule is provided along with a brief summary of available preclinical and clinical efficacy and safety data.
A Biomechanical Comparison of Short Segment Long Bone Fracture Fixation Techniques (2012)

This study suggests that in situations where anatomy or other limitations limit the length of bone segments available for fixation, it may be preferable to use 2 small plates with more screws rather than 1 large plate with few screws.
Micro fluidic system for single molecule imaging (2023)

Laminar flow of a carrier liquid and polymeric molecules through micro-channels is used to straighten the polymeric molecules and attach the straightened molecules to a wall of the micro-channel for subsequent treatment and analysis. Micro-channels can be manufactured using an elastic molding material. One micro-channel embodiment provides fluid flow using a standard laboratory centrifuge.
Effects of Surface Waviness on Fan Blade Boundary Layer Transition and Profile Loss — Part I: Methodology and Computational Results (2021)

Abstract This two-part paper describes a new approach to determine the effect of surface waviness, arising from manufacture of composite fan blades, on transition onset location movement and hence fan profile losses. The approach includes analysis and computations of unsteady disturbances in boundary layers over a wavy surface, assessed and supported by wind tunnel measurements of these disturbances and the transition location. An integrated framework is developed for analysis of surface waviness effects on natural transition. The framework, referred to as the extended eN method, traces the evolution of disturbance energy transfer in flow over a wavy surface, from external acoustic noise through exponential growth of Tollmien-Schlichting (TS) waves, to the start and end of the transition process. The computational results show that surface waviness affects the transition onset location due to the interaction between the surface waviness and the TS boundary layer instability, and that the interaction is strongest when the geometric and TS wavelengths match. The condition at which this occurs, and the initial amplitude of the boundary layer disturbances that grow to create the transition onset is maximized, is called receptivity amplification. The results provide first-of-a-kind descriptions of the mechanism for the changes in transition onset location as well as quantitative calculations for the effects of surface waviness on fan performance due to changes in surface wavelength, surface wave amplitude, and the location at which the waviness is initiated on the fan blade.
Deepening the understanding of CNVs on chromosome 15q11–13 by using hiPSCs: An overview (2023)

The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is widely expressed in the central and peripheral nervous systems. This receptor is implicated in both brain development and adult neurogenesis thanks to its ability to mediate acetylcholine stimulus (Ach). Copy number variations (CNVs) of CHRNA7 gene have been identified in humans and are genetically linked to cognitive impairments associated with multiple disorders, including schizophrenia, bipolar disorder, epilepsy, Alzheimer's disease, and others. Currently, α7 receptor analysis has been commonly performed in animal models due to the impossibility of direct investigation of the living human brain. But the use of model systems has shown that there are very large differences between humans and mice when researchers must study the CNVs and, in particular, the CNV of chromosome 15q13.3 where the CHRNA7 gene is present. In fact, human beings present genomic alterations as well as the presence of genes of recent origin that are not present in other model systems as well as they show a very heterogeneous symptomatology that is associated with both their genetic background and the environment where they live. To date, the induced pluripotent stem cells, obtained from patients carrying CNV in CHRNA7 gene, are a good <i>in vitro</i> model for studying the association of the α7 receptor to human diseases. In this review, we will outline the current state of hiPSCs technology applications in neurological diseases caused by CNVs in CHRNA7 gene. Furthermore, we will discuss some weaknesses that emerge from the overall analysis of the published articles.
Mammalian Luciferase Detection Vectors and Applications (2008)

The light‐emitting reaction of the marine bioluminescent bacterium Vibrio harveyi is catalyzed by the bacterial luciferase enzyme which exists as an alpha‐beta heterodimer encoded by the luxA and luxB genes with subunit molecular weights of 42K and 37K respectively. The enzyme catalyzes a reaction with FMNH2, oxygen and a long‐chain aldehyde as substrates to yield visible light at 490 nm. A new luciferase marker gene detection system has been developed based upon this bacterial luciferase isolated from Vibrio harveyi . Sequences encoding the two luciferase subunits, luxA and luxB have been cloned into two separate vectors. These vectors also include a CMV promoter for expression in mammalian cells as well as an ampicillin resistance gene (amp) for selection and amplification, the SV40 polyadenylation sequence and the SD/SA‐RNA splice donor and acceptor sequence for maximum expression. The vectors were tested for light emission parameters in a live mammalian cell format and with cell lysate samples from NIH3T3 murine fibroblasts in conjunction with transfection using vector GC:11726 Mus musculus biliverdin reductase B (flavin reductase (NADPH)) sequence for production of the reduced flavin mononucleotide (FMNH2) cofactor intracellularly. These systems are being developed to monitor regulation of expression for two independent vector constructs, upon the dual expression.
Size characterization of stress cracks in corn kernels (1984)

SCANNING electron microscopic pictures were taken of corn kernels from four different varieties, all dried at a high temperature. Stress cracks were observed to originate at the inner core of the floury endosperm and propagate radially outward along the boundary of starch granules. Many cracks did not advance far enough to open up at the surface underneath the pericarp. An average stress crack was measured to be 58 ± 14 /^m in width at its widest part.
10W single-mode Nd3+ fiber laser at 1428nm (2018)

We present 10W single-mode fiber laser based on Nd<sup>&plus;3</sup> fiber operating at 1428nm. All-solid fused silica microstructured waveguide fiber design is employed to suppress amplification at 1&mu;m. The Nd<sup>&plus;3</sup> fiber is pumped by commercial multi-mode 880nm diode.
Single-Cell Measurements of Enzyme Levels as a Predictive Tool for Cellular Fates during Organic Acid Production (2013)

Organic acids derived from engineered microbes can replace fossil-derived chemicals in many applications. Fungal hosts are preferred for organic acid production because they tolerate lignocellulosic hydrolysates and low pH, allowing economic production and recovery of the free acid. However, cell death caused by cytosolic acidification constrains productivity. Cytosolic acidification affects cells asynchronously, suggesting that there is an underlying cell-to-cell heterogeneity in acid productivity and/or in resistance to toxicity. We used fluorescence microscopy to investigate the relationship between enzyme concentration, cytosolic pH, and viability at the single-cell level in Saccharomyces cerevisiae engineered to synthesize xylonic acid. We found that cultures producing xylonic acid accumulate cells with cytosolic pH below 5 (referred to here as "acidified"). Using live-cell time courses, we found that the probability of acidification was related to the initial levels of xylose dehydrogenase and sharply increased from 0.2 to 0.8 with just a 60% increase in enzyme abundance (Hill coefficient, >6). This "switch-like" relationship likely results from an enzyme level threshold above which the produced acid overwhelms the cell's pH buffering capacity. Consistent with this hypothesis, we showed that expression of xylose dehydrogenase from a chromosomal locus yields ∼20 times fewer acidified cells and ∼2-fold more xylonic acid relative to expression of the enzyme from a plasmid with variable copy number. These results suggest that strategies that further reduce cell-to-cell heterogeneity in enzyme levels could result in additional gains in xylonic acid productivity. Our results demonstrate a generalizable approach that takes advantage of the cell-to-cell variation of a clonal population to uncover causal relationships in the toxicity of engineered pathways.
A Bulk PZT Microsensor for In-Situ Tissue Contrast Detection During Fine Needle Aspiration Biopsy of Thyroid Nodules (2006)

This paper describes a piezoelectric sensor integrated into a cavity at the tip of a biopsy needle intended for fine needle aspiration (FNA) of thyroid nodules. Located on a steel diaphragm of 300 µ m radius and 23 µ m average thickness, it is intended to aid in tissue differentiation, providing information that is complementary to any imaging method that may be used concurrently. The sensor is fabricated from bulk lead zirconate titanate (PZT) using a customized process. Micro electro-discharge machining is used to form a steel tool that is subsequently used for batch-mode ultrasonic machining of bulk PZT ceramic. The resulting sensor is 50 µ m thick and 200 µ m in diameter. Devices were tested in materials that mimic the texture of human tissue in the training of physicians, and were separately tested with porcine fat and muscle tissue. The magnitude and frequency of a resonant peak shows tissue-specific characteristics as the needle is inserted into tissue. For example, in the porcine tissue sample, the magnitude and peak frequency respectively change from ≈2118 Ω and ≈163 MHz to ≈562 Ω and ≈150 MHz as the needle moves from fat to muscle tissue.
High-Inductance Bi-SQUID (2016)

We performed an in-depth numerical analysis of high-inductance bi-SQUIDs with normalized inductance of its one junction loop l ≫ 1. This is desired for better coupling with the external signals and for the high-temperature superconductor implementations. Typically the high linearity (up to 90 dB) can be achieved in bi-SQUIDs at l ≫ 1 at which its flux-to-voltage characteristic has a distinct triangular shape. We showed that the high linearity can be also achieved at l > 1, when the bi-SQUID has a hysteretic response. The critical current of the third Josephson junction is to be of the same order as the one of the other two Josephson junctions, and the inductance lDC of the second (two junction) loop is allowed to be as high as about one-fourth in the presence of the high linearity.
Gold‐Catalyzed Phosgene‐Free Synthesis of Polyurethane Precursors (2010)

Golden catalyst: In a two-step one-pot catalytic process gold nanoparticles supported on CeO2 are able to convert nitroaromatics into aromatic carbamates, thereby providing an alternative phosgene-free route towards aromatic polyurethanes (see figure). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Analytical results on the Beauchemin model of lymphocyte migration (2013)

The Beauchemin model is a simple particle-based description of stochastic lymphocyte migration in tissue, which has been successfully applied to studying immunological questions. In addition to being easy to implement, the model is also to a large extent mathematically tractable. This article provides a comprehensive overview of both existing and new analytical results on the Beauchemin model within a common mathematical framework. Specifically, we derive the motility coefficient, the mean square displacement, and the confinement ratio, and discuss four different methods for simulating biased migration of pre-defined speed. The results provide new insight into published studies and a reference point for future research based on this simple and popular lymphocyte migration model.
Identification of the Benign Mesenchymal Tumor Gene HMGA2 in Lymphangiomyomatosis (2007)

The normal expression pattern of HMGA2, an architectural transcription factor, is primarily restricted to cells of the developing mesenchyme before their overt differentiation during organogenesis. A detailed in situ hybridization analysis showed that the undifferentiated mesoderm of the embryonic lung expressed Hmga2 but it was not expressed in the newborn or adult lung. Previously, HMGA2 was shown to be misexpressed in a number of benign, differentiated mesenchymal tumors including lipomas, uterine leiomyomas, and pulmonary chondroid hamartomas. Here, we show that HMGA2 is misexpressed in pulmonary lymphangiomyomatosis (LAM), a severe disorder of unknown etiology consisting of lymphatic smooth muscle cell proliferation that results in the obstruction of airways, lymphatics, and vessels. Immunohistochemistry was done with antibodies to HMGA2 and revealed expression in lung tissue samples obtained from 21 patients with LAM. In contrast, HMGA2 was not expressed in sections of normal adult lung or other proliferative interstitial lung diseases, indicating that the expression of HMGA2 in LAM represents aberrant gene activation and is not due solely to an increase in cellular proliferation. In vivo studies in transgenic mice show that misexpression of HMGA2 in smooth muscle cells resulted in increased proliferation of these cells in the lung surrounding the epithelial cells. Therefore, similar to the other mesenchymal neoplasms, HMGA2 misexpression in the smooth muscle cell leads to abnormal proliferation and LAM tumorigenesis. These results suggest that HMGA2 plays a central role in the pathogenesis of LAM and is a potential candidate as a therapeutic target.
Role of the buffer layer thickness on the formation of basal plane stacking faults in a-plane GaN epitaxy on r-sapphire (2008)

The thickness of low temperature AlGaN buffer layers grown on r-sapphire substrates has been found to directly affect the crystalline structure of the buffer layer as well as the structural and optical properties of subsequently grown a-plane GaN films. A buffer layer with a thickness of 30nm results in randomly distributed fine domains without extended defects. Increasing the thickness to 90nm leads to a uniform and largely coalesced crystalline structure, with well-defined stacking faults. GaN films grown on the thinner buffer layer contain a lower density of larger stacking faults, and exhibit brighter stacking-fault luminescence as compared to films grown on thicker buffer layers. Our studies indicate that the optimum buffer layer thickness for growth of a-plane GaN is about 30nm.
Concept learning as motor program induction: A large-scale empirical study (2012)

Human concept learning is particularly impressive in two re-spects: the internal structure of concepts can be representation-ally rich, and yet the very same concepts can also be learned from just a few examples. Several decades of research have dramatically advanced our understanding of these two aspects of concepts. While the richness and speed of concept learn-ing are most often studied in isolation, the power of human concepts may be best explained through their synthesis. This paper presents a large-scale empirical study of one-shot con-cept learning, suggesting that rich generative knowledge in the form of a motor program can be induced from just a single example of a novel concept. Participants were asked to draw novel handwritten characters given a reference form, and we recorded the motor data used for production. Multiple drawers of the same character not only produced visually similar draw-ings, but they also showed a striking correspondence in their strokes, as measured by their number, shape, order, and direc-tion. This suggests that participants can infer a rich motor-based concept from a single example. We also show that the motor programs induced by individual subjects provide a pow-erful basis for one-shot classification, yielding far higher accu-racy than state-of-the-art pattern recognition methods based on just the visual form.
High Performance Computing: CUDA as a Supporting Technology for Next Generation Augmented Reality Applications (2010)

The main purpose of this survey is presenting the potential ofGPGPU technology for real time markerless augmented reality related processing. CUDA is a GPGPU technology developed by NVIDIA that allows programmers to use the C programming language to code algorithms for execution on the GPU. Applications that require mathematically intensive computation of large amounts of data are ideal targets for GPU computing. In this survey, CUDA architecture will be depicted, together with an optimized programming model for obtaining better results using the parallel approach. A case study, mainly related to tracking algorithms, will also be shown in order to demonstrate the performance improvement in comparison to sequential approaches.
Ein stark fluoreszierender zweikerniger Aluminiumkomplex mit nahezu 100 %iger Quantenausbeute** (2022)

Abstract Aufgrund der hohen natürlichen Häufigkeit von Aluminium sind die entsprechenden Fluorophore für verschiedene optische Anwendungen attraktiv, jedoch wurden bislang keine Photolumineszenz‐Quantenausbeuten über 0.7 für Lösungen von Aluminiumkomplexen beschrieben. In diesem Beitrag beschreiben wir einen zweikernigen Aluminium(III)‐Komplex, der verbesserte Photolumineszenzeigenschaften aufweist und dessen einfache Synthese von einem gut verfügbaren Protio‐Liganden und Trimethylaluminium ausgeht. In Lösung zeigt der Komplex eine bislang nicht beschriebene Photolumineszenz‐Quantenausbeute nahe 100 % (Φ absolut 1.0±0.1), und der angeregte Zustand weist eine Lebensdauer von 2.3 ns auf. Im festen Zustand kommt es zu J‐Aggregation und aggregations‐bedingter Löschung, aber es können noch immer Quantenausbeuten von 0.6 beobachtet werden. Die Einbettung des Komplexes in elektrogesponnene Fasern führt zu einem stark fluoreszierenden Vlies mit einer Quantenausbeute von 0.9±0.04.
N-Acetylcysteine Prevents Retrograde Motor Neuron Death after Neonatal Peripheral Nerve Injury (2017)

Proximal neonatal nerve injuries, such as obstetric brachial plexus injury, produce significant retrograde neuronal death after injury. High-dose N-acetylcysteine significantly increases motor neuron survival, which may improve functional outcomes after obstetrical brachial plexus injury.
Extremely highly isospecific polymerization of olefins using solvay‐type TiCl3 and Cp2TiMe2 as catalyst (1988)

Abstract Polymerizations of various olefins (ethylene, propene, 1‐butene, 4‐methyl‐1‐pentene,1‐hexene, and 1‐octene) were carried out using the Solvay‐type TiCl 3 catalyst combined with Cp 2 TiMe 2 . The polymers produced were characterized by DSC, solvent fractionation, GPC, and 13 C NMR. It was found that the present catalyst gives linear polyethylene without ethyl branches and extremely highly isotactic poly(α‐olefins) containing very few steric defects. The catalyst seems to be most isospecific among the Ziegler‐Natta catalysts reported so far.
Pathways in the Diagnosis and Management of Diabetic Polyneuropathy (2015)

Distal symmetric polyneuropathy (DSPN), the most common form of diabetic neuropathy, has a complex pathophysiology and can be a major source of physical and psychologic disability. The management of DSPN can be frustrating for both patient and physician. This article provides a general overview of typical patient pathways in DSPN, and highlights variations in diagnosis, management, and referral patterns among different providers. DSPN is managed in several settings by primary care physicians (PCPs), specialists, and nurse practitioners. The initial clinical management of the patient is often dependent on the presenting complaint, the referral pattern of the provider, level of comfort of the PCP in managing diabetic complications, and geographic access to specialists. The primary treatment of DSPN focuses mainly on glycemic control and adjustment of modifiable risk factors, but other causes of neuropathy should also be investigated. Several pharmacologic agents are recommended by treatment guidelines, and as DSPN typically exists with comorbid conditions, a multimodal therapeutic approach should be considered. Barriers to effective management include failure to recognize DSPN, and misdiagnosis. Patient education also remains important. Referral patterns vary widely according to geographic location, access to services, provider preferences, and comfort in managing complex aspects of the disease. The variability in patient pathways affects patient education, satisfaction, and outcomes. Standardized screening tools, a multidisciplinary team approach, and treatment algorithms for diabetic neuropathy should improve future care. To improve patient outcomes, DSPN needs to be diagnosed sooner and interventions made before significant nerve damage occurs.