gebhart/patrepeval huggingface dataset:
A Restricted Role for TYK2 Catalytic Activity in Human Cytokine Responses Revealed by Novel TYK2-Selective Inhibitors (2013)

TYK2 is a JAK family protein tyrosine kinase activated in response to multiple cytokines, including type I IFNs, IL-6, IL-10, IL-12, and IL-23. Extensive studies of mice that lack TYK2 expression indicate that the IFN-α, IL-12, and IL-23 pathways, but not the IL-6 or IL-10 pathways, are compromised. In contrast, there have been few studies of the role of TYK2 in primary human cells. A genetic mutation at the tyk2 locus that results in a lack of TYK2 protein in a single human patient has been linked to defects in the IFN-α, IL-6, IL-10, IL-12, and IL-23 pathways, suggesting a broad role for TYK2 protein in human cytokine responses. In this article, we have used a panel of novel potent TYK2 small-molecule inhibitors with varying degrees of selectivity against other JAK kinases to address the requirement for TYK2 catalytic activity in cytokine pathways in primary human cells. Our results indicate that the biological processes that require TYK2 catalytic function in humans are restricted to the IL-12 and IL-23 pathways, and suggest that inhibition of TYK2 catalytic activity may be an efficacious approach for the treatment of select autoimmune diseases without broad immunosuppression.
Automatic thesaurus generation for an electronic community system (1995)

This research reports an algorithmic approach to the automatic generation of thesauri for electronic community systems. The techniques used included term filtering, automatic indexing, and cluster analysis. The testbed for our research was the Worm Community System, which contains a comprehensive library of specialized community data and literature, currently in use by molecular biologists who study the nematode worm C. elegans. The resulting worm thesaurus included 2709 researchers' names, 798 gene names, 20 experimental methods, and 4302 subject descriptors. On average, each term had about 90 weighted neighboring terms indicating relevant concepts. The thesaurus was developed as an online search aide. We tested the worm thesaurus in an experiment with six worm researchers of varying degrees of expertise and background. The experiment showed that the thesaurus was an excellent “memory-jogging” device and that it supported learning and serendipitous browsing. Despite some occurrences of obvious noise, the system was useful in suggesting relevant concepts for the researchers' queries and it helped improve concept recall. With a simple browsing interface, an automatic thesaurus can become a useful tool for online search and can assist researchers in exploring and traversing a dynamic and complex electronic community system. © 1995 John Wiley & Sons, Inc.
In vivo light dosimetry for motexafin lutetium‐mediated PDT of recurrent breast cancer (2002)

A conversion factor was determined to convert the irradiance to fluence rate on the tissue surface. However, the fluence (or the ratio) on patient surface varied by 70% due to the heterogeneity of optical properties. This supports the use of real-time in vivo dosimetry during photodynamic therapy.
Exploring membrane protein dynamics by multicolor single quantum dot imaging using wide field, TIRF, and hyperspectral microscopy (2007)

The development of colloidal quantum dots (QDs) for biological imaging has brought a new level of sensitivity to live cell imaging. Single particle tracking (SPT) techniques in particular benefit from the superior photostability, high extinction coefficient and distinct emission spectra of QDs. Here we describe the use of QDs for SPT to study the dynamics of membrane proteins in living cells. We work with the RBL-2H3 mast cell model that signals through the high affinity IgE receptor, Fc&Vegr;RI. Using wide field or Total Internal Reflection Fluorescence (TIRF) microscopy we have achieved simultaneous imaging of two spectrally distinct QDs with frame rates of up to 750 frames/s and localization accuracy of ~10 nm. We also describe the imaging and analysis of QDs using a novel hyperspectral microscope and multivariate curve resolution analysis for multi-color QD tracking. The same QD-tag used for SPT is used to localize proteins at <10 nm resolution by electron microscopy (EM) on fixed membrane sheets.
CC270 Fuel Storage (2014)

Campaign Circular 270: This circular is about fuel storage, fuel caps, filler caps, tank colors, tank locations, fuel quality, fuel loss examples, and recommendations. At the head of the title it has Farm Energy Tips...Use Energy Wisely
A Convolutional Neural Network Feature Detection Approach to Autonomous Quadrotor Indoor Navigation (2019)

Object detection, extended to recognize and localize indoor structural features, is used to enable a quadrotor drone to autonomously navigate through indoor environments. The video stream from a monocular front-facing camera on-board a quadrotor drone is fed to an off-board system that runs a Convolutional Neural Network (CNN) object detection algorithm to identify specific features such as dead-ends, doors, and intersections in hallways. Using pixel-scale dimensions of the bounding boxes around the recognized objects, the distance to intersections, dead-ends and doorways can be estimated accurately using a Support Vector Regression (SVR) model to generate flight control commands for consistent real-time autonomous navigation at flight speeds approaching 2 m/s.
A Universal In Situ Cross‐Linking Strategy Enables Orthogonal Processing of Full‐Color Organic Microlaser Arrays (2021)

Abstract Large‐scale red, green, and blue (RGB) microlaser arrays capable of exhibiting full‐color laser emissions are urgently desired for high‐performance flat‐panel laser displays. With excellent solution processability and optoelectronic properties, organic materials are promising candidates for full‐color microlasers; however, the heterogeneous integration of full‐color microlasers remains a challenge due to their poor solution stability to withstand multistage solution processing. Here, a robust in situ cross‐linking strategy is proposed to enable orthogonal processing of organic microlasers to heterogeneously integrate large‐scale full‐color organic microlaser arrays. The organic microlasers with controlled physical dimensions and spatial locations are fabricated with an electron beam (e‐beam) induced in situ polymerization reaction. Profiting from enhanced orthogonality of microlasers, large‐scale pixelated RGB microlaser arrays are monolithically integrated through successive e‐beam patterning processes. Laser emissions in the RGB microlaser pixels cover a color gamut 41% larger than the standard RGB space, with which flexible full‐color organic laser display patterns with a resolution of 254 dpi on a centimeter scale is obtained. The scalable heterogeneous integration platform reported in this work will pave a new avenue for the efficient construction of large‐scale high‐performance organic integrated optoelectronic devices.
Burglars’ IoT Paradise: Understanding and Mitigating Security Risks of General Messaging Protocols on IoT Clouds (2020)

With the increasing popularity of the Internet of Things (IoT), many IoT cloud platforms have emerged to help the IoT manufacturers connect their devices to their users. Serving the device-user communication is general messaging protocol deployed on the platforms. Less clear, however, is whether such protocols, which are not designed to work in the adversarial environment of IoT, introduce new risks. In this paper, we report the first systematic study on the protection of major IoT clouds (e.g., AWS, Microsoft, IBM) put in place for the arguably most popular messaging protocol - MQTT. We found that these platforms' security additions to the protocol are all vulnerable, allowing the adversary to gain control of the device, launch a large-scale denial-of-service attack, steal the victim's secrets data and fake the victim's device status for deception. We successfully performed end-to-end attacks on these popular IoT clouds and further conducted a measurement study, which demonstrates that the security impacts of our attacks are real, severe and broad. We reported our findings to related parties, which all acknowledged the importance. We further propose new design principles and an enhanced access model MOUCON. We implemented our protection on a popular open-source MQTT server. Our evaluation shows its high effectiveness and negligible performance overhead.
PGC-1α promotes recovery after acute kidney injury during systemic inflammation in mice (2011)

Sepsis-associated acute kidney injury (AKI) is a common and morbid condition that is distinguishable from typical ischemic renal injury by its paucity of tubular cell death. The mechanisms underlying renal dysfunction in individuals with sepsis-associated AKI are therefore less clear. Here we have shown that endotoxemia reduces oxygen delivery to the kidney, without changing tissue oxygen levels, suggesting reduced oxygen consumption by the kidney cells. Tubular mitochondria were swollen, and their function was impaired. Expression profiling showed that oxidative phosphorylation genes were selectively suppressed during sepsis-associated AKI and reactivated when global function was normalized. PPARγ coactivator-1α (PGC-1α), a major regulator of mitochondrial biogenesis and metabolism, not only followed this pattern but was proportionally suppressed with the degree of renal impairment. Furthermore, tubular cells had reduced PGC-1α expression and oxygen consumption in response to TNF-α; however, excess PGC-1α reversed the latter effect. Both global and tubule-specific PGC-1α-knockout mice had normal basal renal function but suffered persistent injury following endotoxemia. Our results demonstrate what we believe to be a novel mechanism for sepsis-associated AKI and suggest that PGC-1α induction may be necessary for recovery from this disorder, identifying a potential new target for future therapeutic studies.
Reconstruction of Metabolic Networks from High‐Throughput Metabolite Profiling Data (2007)

We investigate the ability of algorithms developed for reverse engineering of transcriptional regulatory networks to reconstruct metabolic networks from high-throughput metabolite profiling data. For benchmarking purposes, we generate synthetic metabolic profiles based on a well-established model for red blood cell metabolism. A variety of data sets are generated, accounting for different properties of real metabolic networks, such as experimental noise, metabolite correlations, and temporal dynamics. These data sets are made available online. We use ARACNE, a mainstream algorithm for reverse engineering of transcriptional regulatory networks from gene expression data, to predict metabolic interactions from these data sets. We find that the performance of ARACNE on metabolic data is comparable to that on gene expression data.
Conjugate gradient coupled with multigrid for an indefinite problem (1984)

An iterative algorithm for the Helmholtz equation is presented. This scheme was based on the preconditioned conjugate gradient method for the normal equations. The preconditioning is one cycle of a multigrid method for the discrete Laplacian. The smoothing algorithm is red-black Gauss-Seidel and is constructed so it is a symmetric operator. The total number of iterations needed by the algorithm is independent of h. By varying the number of grids, the number of iterations depends only weakly on k when k(3)h(2) is constant. Comparisons with a SSOR preconditioner are presented.
A Novel Birefrigent Photonic Crystal Fiber Surface Plasmon Resonance Biosensor (2014)

A numerical analysis of a novel birefringent photonic crystal fiber (PCF) biosensor constructed on the surface plasmon resonance (SPR) model is presented in this paper. This biosensor configuration utilizes circular air holes to introduce birefringence into the structure. This PCF biosensor model shows promise in the area of multiple detection using HE <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sup> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sub> and HE <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">y</sup> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sub> modes to sense more than one analyte. A numerical study of the biosensor is performed in two interrogation modes: amplitude and wavelength. Sensor resolution values with spectral interrogation yielded 5 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-5</sup> RIU (refractive index units) for HE <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sup> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sub> modes and 6 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-5</sup> RIU for HE <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">y</sup> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sub> modes, whereas 3 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-5</sup> RIU for HE <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sup> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sub> modes and 4 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-5</sup> RIU for HE <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">y</sup> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sub> modes are demonstrated for the amplitude interrogation.
Papillary Serous Carcinoma of the Uterine Cervix (1998)

The clinical and pathologic features of 17 cases of papillary serous adenocarcinoma of the cervix (PSCC) were studied in women who ranged in age from 26 to 70 years. There was a bimodal age distribution, with one peak occurring before the age of 40 years and the second peak after the age of 65. The presenting symptoms were abnormal vaginal bleeding (11 patients), abnormal exfoliative cervical cytology (four patients), or watery vaginal discharge (two patients). On pelvic examination, eight patients had a polypoid or exophytic cervical mass and two patients had an ulcerated or indurated cervix; no abnormality was detected in seven patients. Two tumors were stage Ia, 12 were stage Ib, two were stage II, and one was stage III. Nine patients were treated by radical hysterectomy and one by simple hysterectomy; six of these patients received postoperative radiotherapy. The other patients received primary radiotherapy. On microscopic examination, all of the tumors had a complex papillary architecture with epithelial stratification and tufting. Six tumors were grade 2/3 and 11 were grade 3/3. All of the tumors had >10 mitotic figures per 10 high-power fields. An intense acute and chronic inflammatory infiltrate was typically present within the cores of the papillae and in areas of stromal invasion. Occasional psammoma bodies were present in three cases. Five of 12 tumors stained positively for p53, with six and nine of 12 tumors, respectively, immunoreactive for carcinoembryonic antigen and CA-125. Seven tumors were mixed with another histologic subtype of cervical adenocarcinoma, most commonly low-grade villoglandular adenocarcinoma. Fifteen patients were followed from 6 months to 11 years (mean 56 months). Six patients died of extensive metastases within 5 years of diagnosis; an additional patient experienced tumor recurrence with malignant ascites 2 years after diagnosis. The most common metastatic sites were pelvic and periaortic lymph nodes; other sites included cervical lymph nodes, lung, peritoneum, liver, and skin. Eight patients were alive without evidence of tumor at last follow-up. Age <65 years, stage >I, tumor size >2 cm, tumor invasion >10 mm, the presence of lymph node metastases, and elevation of serum CA-125 were associated with a poor prognosis. Tumor grade or composition (pure or mixed) did not correlate with patient outcome. Papillary serous adenocarcinoma of the cervix resembles microscopically its counterparts elsewhere in the female genital tract and peritoneum. The tumors can behave aggressively with supradiaphragmatic metastases and a rapidly fatal course when diagnosed at an advanced stage, but the outcome for patients with stage I tumors is similar to that of patients with cervical adenocarcinomas of the usual type.
Drug Discovery Strategies for Inherited Retinal Degenerations (2022)

Inherited retinal degeneration is a group of blinding disorders afflicting more than 1 in 4000 worldwide. These disorders frequently cause the death of photoreceptor cells or retinal ganglion cells. In a subset of these disorders, photoreceptor cell death is a secondary consequence of retinal pigment epithelial cell dysfunction or degeneration. This manuscript reviews current efforts in identifying targets and developing small molecule-based therapies for these devastating neuronal degenerations, for which no cures exist. Photoreceptors and retinal ganglion cells are metabolically demanding owing to their unique structures and functional properties. Modulations of metabolic pathways, which are disrupted in most inherited retinal degenerations, serve as promising therapeutic strategies. In monogenic disorders, great insights were previously obtained regarding targets associated with the defective pathways, including phototransduction, visual cycle, and mitophagy. In addition to these target-based drug discoveries, we will discuss how phenotypic screening can be harnessed to discover beneficial molecules without prior knowledge of their mechanisms of action. Because of major anatomical and biological differences, it has frequently been challenging to model human inherited retinal degeneration conditions using small animals such as rodents. Recent advances in stem cell-based techniques are opening new avenues to obtain pure populations of human retinal ganglion cells and retinal organoids with photoreceptor cells. We will discuss concurrent ideas of utilizing stem-cell-based disease models for drug discovery and preclinical development.
A Simplified Method to Minimize Systematic Bias of Single-Optimized Intraocular Lens Power Calculation Formulas (2023)

The proposed method allows surgeons without special expertise to optimize an IOL constant to nullify the ME on a documented dataset without coding the different formulas. The influence of individual eyes is proportional to the squared power of the implanted IOL.
Resource-efficient machining through physics-informed machine learning (2023)

Resource-efficient machining has been at the forefront of sustainable manufacturing for many years. However, the total life of the cutting tool is often not fully exploited to avoid the severe consequences of excessive wear. This conservative strategy increases production time, cost per part, and the carbon footprint of the machining process. The present contribution focuses on resource-efficient machining through physics-informed machine learning, exploiting the benefits of both physics-based and data-driven modelling to accurately predict cutting tool life. The results demonstrate the utility and superiority of this hybrid approach relative to traditional methods and the recent trends towards purely data-driven techniques.
ChemInform Abstract: REGIO‐ AND STEREOCHEMISTRY OF ACID‐CATALYZED OPENING OF (1,2‐EPOXYALKYNE)DICOBALT HEXACARBONYLS (1984)

Abstract Das l‐Octan‐B‐in (I) liefert das Epoxid (II), das in den Cobaltcarbonyl‐Komplex (III) übergeführt wird.
Interleukin‐8 is a chemo‐attractant for eosinophils purified from subjects with a blood eosinophilia but not from normal healthy subjects (1993)

Interleukin-8 (IL-8), a pro-inflammatory cytokine with potent neutrophil chemotactic activity, was studied for its effect on eosinophil migration responses, in vitro. Normal density eosinophils were isolated from healthy, non-atopic subjects (<0.35 x 10(9) eosinophils/l) and individuals with various diseases associated with a blood eosinophilia (range 0.56 x 10(9)-12.2 x 10(9) eosinophils/l). IL-8 produced a dose-dependent migrational response for eosinophils from subjects with an eosinophilia, optimal at 10(-8) M (P < 0.01) and the major component of the migrational response was chemokinesis. On a molar basis, IL-8 (EC50 approximately 10(10) M) was 100-fold more potent than platelet activating factor (PAF), although a comparison of the migrational responses showed that at optimal concentrations IL-8 (10(-8) M) produced only 30% maximal responses stimulated by PAF (10(-6) M). In contrast, IL-8 tested over a wide concentration range had a negligible effect on eosinophils from normal subjects. A direct correlation between the total blood eosinophil counts for all subjects and the absolute magnitude of the migrational response to IL-8 (r = 0.727, P < 0.01 at 10(-8) M), PAF (r = 0.551, P < 0.03 at 10(-6) M) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) (r = 0.689, P < 0.02 at 10(-8) M), suggested that heightened eosinophil migrational responses to inflammatory mediators may arise as a consequence of in vivo priming mechanism(s) associated with the development of an eosinophilia. In this regard, eosinophils derived from human cord blood mononuclear cells cultured in the presence of eosinophilopoietic cytokines IL-3 and IL-5, produced migrational responses to IL-8 and PAF, that were comparable with that of eosinophils from eosinophilic subjects. Furthermore, incubation of eosinophils from normal donors with IL-5 (optimal concentration 10(-9) M), significantly enhanced the subsequent migrational responses to both IL-8 (10(-8) M, P < 0.01) and PAF (10(-8) M, P < 0.05). Therefore, the increased responsiveness of eosinophils from eosinophilic subjects may reflect in vivo priming by IL-5 and this phenomenon may contribute partly to the mechanism(s) by which eosinophils preferentially accumulate at sites of allergic inflammation.
An Automated Cost-effective System for Real-time Slope Mapping in Commercial Wild Blueberry Fields (2010)

The development of site-specific agriculture has increased the need for knowledge regarding within-field variability in factors such as soil/plant characteristics and topography that influence wild blueberry ( Vaccinium angustifolium ) production. Surface soil properties are the first type of information most frequently used by blueberry producers in developing management plans. Topographic features are not yet routinely used to guide within-field management. The majority of blueberry fields in eastern Canada have gentle to severe topography. An automated slope measurement and mapping system (SMMS) consisting of low-cost accelerometers used as tilt sensors, differential global positioning system (DGPS), and laptop and custom software was developed. The SMMS was mounted on an all-terrain vehicle for real-time slope measurement and mapping. Six commercial wild blueberry fields were surveyed in central Nova Scotia to evaluate the performance of SMMS. The automatically sensed slopes (SS) were also compared with manually measured slopes (MS) at 20 randomly selected points in each field to examine the accuracy of SMMS. The SMMS measured slope reliably in the selected fields with root mean square error ranging from 0.12 to 0.56 degrees and correlations of SS with MS of R 2 = 0.95 to 0.99. The selected fields had substantial variation in slope (ranging from 0.8 to 31.0 degrees). Therefore, the use of low-cost and reliable accelerometers with a DGPS is a better option than expensive real-time kinematic DGPS for developing cost-effective SMMS to quantify and map slopes (real-time) for planning site-specific management practices in commercial fields. The SS maps or real-time SMMS could also be used to adjust vehicle speed at particularly steep slopes.