gebhart/patrepeval huggingface dataset:
[Non-opioid analgesics in cancer pain]. (2001)

Non-opioid analgesics such as NSAIDs play a central role for patients with cancer pain as well as for those with acute pain. Pain management using non-opioid analgesics need to avoid potential side effects, and the analgesic action of NSAIDs, cyclooxygenase inhibitors, would synergistically potentiate opioids' effects via the activation of the periaquaductal grey of the midbrain. The analgesic action of opioids would also be potentiated by the activation of alpha 2-adrenoceptors of the spinal cord. Thus the use of non-opioid analgesics for cancer patients taking opioid needs meticulous care. Undertreatment of pain is a persistent clinical problem for patients with cancer. Although changing medical practice is difficult and improving pain management with the rational use of combination of drugs may especially difficult, supplementation of non-opioid analgesics for opioid treatment would provide a better quality of life of cancer patients.
Expression of Constitutively Activated Giα2 in Vivo Ameliorates Streptozotocin-induced Diabetes (1998)

Streptozotocin treatment in vivo generates a model of insulin-dependent diabetes mellitus via destruction of the pancreatic beta-cells responsible for insulin secretion. Tissue-specific expression of the Q205L constitutively activated mutant form of the G-protein Gialpha2 in vivo ameliorates streptozotocin-induced insulin-dependent diabetes mellitus in transgenic mice. Conditional expression of Q205L Gialpha2 in vivo in liver, skeletal muscle, and adipose tissue markedly rectifies glucose tolerance, fasting glucose levels, and glycogen synthase activation in the mice with insulin-dependent diabetes mellitus, providing a novel therapeutic target for diabetes.
Thornton Guide for Radial Keratotomy Incisions and Optical Zone Size (1985)

ABSTRACT: The Thornton Guide is designed to provide a predictable correction of myopia and astigmatism without overcorrection by following a specific set of guidelines based on 98% depth at the optical zone margin with eight or more incisions. The object of the guide is to provide maximum correction with the largest possible optical zone. The rationale for the number of incisions and how to apply various modifiers such as age, sex, corneal curvature, and intraocular pressure are explained.
Machine Learning-Assisted Directed Evolution Navigates a Combinatorial Epistatic Fitness Landscape with Minimal Screening Burden (2020)

Abstract Due to screening limitations, in directed evolution (DE) of proteins it is rarely feasible to fully evaluate combinatorial mutant libraries made by mutagenesis at multiple sites. Instead, DE often involves a single-step greedy optimization in which the mutation in the highest-fitness variant identified in each round of single-site mutagenesis is fixed. However, because the effects of a mutation can depend on the presence or absence of other mutations, the efficiency and effectiveness of a single-step greedy walk is influenced by both the starting variant and the order in which beneficial mutations are identified—the process is path-dependent. We recently demonstrated a path-independent machine learning-assisted approach to directed evolution (MLDE) that allows in silico screening of full combinatorial libraries made by simultaneous saturation mutagenesis, thus explicitly capturing the effects of cooperative mutations and bypassing the path-dependence that can limit greedy optimization. Here, we thoroughly investigate and optimize an MLDE workflow by testing a number of design considerations of the MLDE pipeline. Specifically, we (1) test the effects of different encoding strategies on MLDE efficiency, (2) integrate new models and a training procedure more amenable to protein engineering tasks, and (3) incorporate training set design strategies to avoid information-poor low-fitness protein variants (“holes”) in the training data. When applied to an epistatic, hole-filled, four-site combinatorial fitness landscape of protein G domain B1 (GB1), the resulting focused training MLDE (ftMLDE) protocol achieved the global fitness maximum up to 92% of the time at a total screening burden of 470 variants. In contrast, minimal-screening-burden single-step greedy optimization over the GB1 fitness landscape reached the global maximum just 1.2% of the time; ftMLDE matching this minimal screening burden (80 total variants) achieved the global optimum up to 9.6% of the time with a 49% higher expected maximum fitness achieved. To facilitate further development of MLDE, we present the MLDE software package ( https://github.com/fhalab/MLDE ), which is designed for use by protein engineers without computational or machine learning expertise.
Location-specific tweet detection and topic summarization in Twitter (2013)

Automatic detection of tweets that provide Location-specific information will be extremely useful in conveying geo-location based knowledge to the users. However, there is a significant challenge in retrieving such tweets due to the sparsity of geo-tag information, the short textual nature of tweets, and the lack of pre-defined set of topics. In this paper, we develop a novel framework to identify and summarize tweets that are specific to a location. First, we propose a weighting scheme called Location Centric Word Co-occurrence (LCWC) that uses the content of the tweets and the network information of the twitterers to identify tweets that are location-specific. We evaluate the proposed model using a set of annotated tweets and compare the performance with other weighting schemes studied in the literature. This paper reports three key findings: (a) top trending tweets from a location are poor descriptors of location-specific tweets, (b) ranking tweets purely based on users' geo-location cannot ascertain the location specificity of tweets, and (c) users' network information plays an important role in determining the location-specific characteristics of the tweets. Finally, we train a topic model based on Latent Dirichlet Allocation (LDA) using a large collection of local news database and tweet-based Urls to predict the topics from the location-specific tweets and present them using an interactive web-based interface.
Out-of-Shape DNA Minor Groove Binders:  Induced Fit Interactions of Heterocyclic Dications with the DNA Minor Groove (2005)

DB921 and DB911 are benzimidazole-biphenyl isomers with terminal charged amidines. DB911 has a central meta-substituted phenyl that gives it a shape similar to those of known minor groove binding compounds. DB921 has a central para-substituted phenyl with a linear conformation that lacks the appropriate radius of curvature to match the groove shape. It is thus expected that DB911, but not DB921, should be an effective minor groove binder, but we find that DB921 not only binds in the groove but also has an unusually high binding constant in SPR experiments (2.9 x 10(8) M(-)(1), vs 2.1 x 10(7) M(-)(1) for DB911). ITC thermodynamic analysis with an AATT sequence shows that the stronger binding of DB921 is due to a more favorable binding enthalpy relative to that of DB911. CD results support minor groove binding for both compounds but do not provide an explanation for the binding of DB921. X-ray crystallographic analysis of DB921 bound to AATT shows that an induced fit structural change in DB921 reduces the twist of the biphenyl to complement the groove, and places the functional groups in position to interact with bases at the floor of the groove. The phenylamidine of DB921 forms indirect contacts with the bases through a bound water. The DB921-water pair forms a curved binding module that matches the shape of the minor groove and provides a number of strong interactions that are not possible with DB911. This result suggests that traditional views of compound curvature required for minor groove complex formation should be reevaluated.
Prediabetes Induced by Fructose-Enriched Diet Influences Cardiac Lipidome and Proteome and Leads to Deterioration of Cardiac Function prior to the Development of Excessive Oxidative Stress and Cell Damage (2019)

Prediabetes is a condition affecting more than 35% of the population. In some forms, excessive carbohydrate intake (primarily refined sugar) plays a prominent role. Prediabetes is a symptomless, mostly unrecognized disease which increases cardiovascular risk. In our work, we examined the effect of a fructose-enriched diet on cardiac function and lipidome as well as proteome of cardiac muscle. Male Wistar rats were divided into two groups. The control group received a normal diet while the fructose-fed group received 60% fructose-supplemented chow for 24 weeks. Fasting blood glucose measurement and oral glucose tolerance test (OGTT) showed slightly but significantly elevated values due to fructose feeding indicating development of a prediabetic condition. Both echocardiography and isolated working heart perfusion performed at the end of the feeding protocol demonstrated diastolic cardiac dysfunction in the fructose-fed group. Mass spectrometry-based, high-performance lipidomic and proteomic analyses were executed from cardiac tissue. The lipidomic analysis revealed complex rearrangement of the whole lipidome with special emphasis on defects in cardiolipin remodeling. The proteomic analysis showed significant changes in 75 cardiac proteins due to fructose feeding including mitochondria-, apoptosis-, and oxidative stress-related proteins. Nevertheless, just very weak or no signs of apoptosis induction and oxidative stress were detected in the hearts of fructose-fed rats. Our results suggest that fructose feeding induces marked alterations in the cardiac lipidome, especially in cardiolipin remodeling, which leads to mitochondrial dysfunction and impaired cardiac function. However, at the same time, several adaptive responses are induced at the proteome level in order to maintain a homeostatic balance. These findings demonstrate that even very early stages of prediabetes can impair cardiac function and can result in significant changes in the lipidome and proteome of the heart prior to the development of excessive oxidative stress and cell damage.
Prednisolone (Meti-Derm) as an Aerosol for Dermatoses (1959)

Topical applications of hydrocortisone<sup>1</sup>and, more recently, prednisone or prednisolone<sup>2-4</sup>are widely used in the treatment of many types of dermatologic disease. A new vehicle for prednisolone (Meti-Derm) aerosol with 50 mg. of the steroid, isopropyl myristate, and Freon as a propellant, in a 150 gm. spray applicator, was made available to us for clinical study. A three-second spray delivers approximately 0.5 mg. of prednisolone. Method This series consisted of 79 patients with dermatologic disease, most commonly eczema of various types, including eczematous dermatitis. Patients were instructed to apply the aerosol to lesions in very short bursts of spray from a distance of 1 to 2 in. Examinations were made weekly and progress noted. No other therapy was used. Results were graded as "excellent" if lesions involuted promptly and completely, "good" if response was somewhat slower or not complete, "fair" if some
Standardization of innovations in Russia (2013)

In terms of actual tendency of innovations being the driven part of the world economy development it is necessary to describe the situation with innovations and standardization in Russia. The article is describing Russian innovations eco-system, regulations in innovations and standardization of innovations. Main standardization bodies and challenges in standardization are briefly described. Possible ideas for the development of innovations system in Russia are proposed.
Three‐dimensional kinematics of the equine spine during canter (2001)

Most research on equine kinematics has previously been performed in the walking and/or trotting animal. This is also true for the few studies on the kinematics of the equine back. These studies have, for the major part, focused on the flexion-extension movement in the sagittal plane. However, vertebrae can rotate in 3 dimensions. This study was designed to determine all 3 rotations in various segments of the vertebral column of a cantering horse. Five Dutch Warmblood horses were measured during treadmill canter (7.3 m/s). Steinmann pins were inserted into the dorsal spinous processes of 8 thoracic (T), lumbar (L) and sacral (S) vertebrae and into both tubera coxae. A set of 4 markers was rigidly attached to each pin. The marker data were used to calculate a rotation matrix that was subsequently decomposed into 3 orthogonal rotations (flexion/extension [FE]; lateral bending [LB] and axial rotation [AR]). For the 3 rotations the variability between the horses was low for FE, slightly larger for AR and largest for LB. The maximal range of motion (mean +/- s.d.) for FE, LB and AR was 15.8 +/- 1.3 degrees, 5.2 +/- 0.7 degrees and 7.8 +/- 1.2 degrees, respectively. With respect to relative angles, the largest FE motion was found between L5 and S3 with values for the range of motion up to 8.6 degrees. Simultaneous rotation of successive vertebrae was observed particularly during the single support and suspension phases in the stride cycle, which increases spinal stability. For all rotations, a close correlation was observed between the timing of the vertebral rotations and the pro- and retraction of the limbs.
DOA and Doppler frequency estimation with sensor gain and phase uncertainties (2003)

In the presence of sensor gain and phase uncertainties for sensor array, this paper addressed the problem of High-resolution estimation of DOA-Doppler frequency for multiple signals. By utilizing rotational invariance technique and collecting data of signals at two different carrier frequencies, the proposed method can precisely estimate DOA-Doppler frequency of multiple signals and sensor gain and phase factors. Simulation results illustrate that this method has superior performance.
An unexpected fragmentation reaction of tetracyanoethylene with isobenzimidazoles (1972)

J. Herbert, D. W. S. Latham, O. Meth-Cohn and H. Suschitzky, J. Chem. Soc., Chem. Commun., 1972, 1302 DOI: 10.1039/C39720001302
Treatment of CHO cells with Taxol and reversine improves micronucleation and microcell-mediated chromosome transfer efficiency (2023)

Microcell-mediated chromosome transfer is an attractive technique for transferring chromosomes from donor cells to recipient cells and has enabled the generation of cell lines and humanized animal models that contain megabase-sized gene(s). However, improvements in chromosomal transfer efficiency are still needed to accelerate the production of these cells and animals. The chromosomal transfer protocol consists of micronucleation, microcell formation, and fusion of donor cells with recipient cells. We found that the combination of Taxol (paclitaxel) and reversine rather than the conventional reagent colcemid resulted in highly efficient micronucleation and substantially improved chromosomal transfer efficiency from Chinese hamster ovary donor cells to HT1080 and NIH3T3 recipient cells by up to 18.3- and 4.9-fold, respectively. Furthermore, chromosome transfer efficiency to human induced pluripotent stem cells, which rarely occurred with colcemid, was also clearly improved after Taxol and reversine treatment. These results might be related to Taxol increasing the number of spindle poles, leading to multinucleation and delaying mitosis, and reversine inducing mitotic slippage and decreasing the duration of mitosis. Here, we demonstrated that an alternative optimized protocol improved chromosome transfer efficiency into various cell lines. These data advance chromosomal engineering technology and the use of human artificial chromosomes in genetic and regenerative medical research.
Synthese des ersten α-Methylen-β-peroxylactons – regiospezifische En-Reaktion von1O2 mit α,β-ungesättigten Carbonsäuren (1985)

Unerwartet hohe thermische Stabilität zeichnet 5-Methyl-4-methylen-1,2-dioxolan-3on 2 aus. Das erste α-Methylen-β-peroxylacton konnte durch regiospezifische Photooxygenierung der α,β-ungesättigten carbonsäure 1 zum Hydroperoxid und dessen säurekatalysierte Dehydratisierung erhalten werden.
An experimental 80-ns 1-Mbit DRAM with fast page operation (1985)

An experimental general purpose 5-V 1-Mb dynamic RAM has been designed for increased performance, high density, and enhanced reliability. The array consists of a one-device overlapped I/O cell with a metal bitline architecture. The cell measures 4.1 /spl mu/m by 8.8 /spl mu/m, which yields a chip size of 5.5 mm by 10.5 mm with an array to chip area ratio of 65.5%. The chip was designed in a double-poly single-metal NMOS technology with selected 1-/spl mu/m levels and an average feature size of 1.5 /spl mu/m. Key design features include a fast page mode cycle with minimum column precharge delay and improved protection for short error rate using a boosted word-line after sense amplifier set scheme. The CAS access time is 40 ns and the cycle is 65 ns at 4.5 V and 85/spl deg/C. The RAS access time is 80 ns and the cycle is 160 ns at 4.5 V and 85/spl deg/C with a typical active power of 625 mW. The chip is usable as a X1, X2, or X4 with the use of block select inputs and the selected package option. The package options include a 500-mil/SUP 2/ pin grid array module with 23 pins, and a 22 pin or 26 pin 300-mil surface solder plastic package.
Phosphoinositide 3-Kinase in Nitric Oxide Synthesis in Macrophage (2006)

Phosphoinositide 3-kinase (PI3K) has important functions in various biological systems, including immune response. Although the role of PI3K in signaling by antigen-specific receptors of the adaptive immune system has been extensively studied, less is known about the function of PI3K in innate immunity. In the present study, we demonstrate that macrophages deficient for PI3K (p85alpha regulatory subunit) are impaired in nitric oxide (NO) production upon lipopolysaccharide and interferon-gamma stimulation and thus vulnerable for intracellular bacterial infection such as Chlamydophila pneumoniae. Although expression of inducible nitric-oxide synthase (iNOS) is induced normally in PI3K-deficient macrophages, dimer formation of iNOS protein is significantly impaired. The amount of intracellular tetrahydrobiopterin, a critical stabilizing cofactor for iNOS dimerization, is decreased in the absence of PI3K. In addition, induction of GTP cyclohydrolase 1, a rate-limiting enzyme for biosynthesis of tetrahydrobiopterin, is greatly reduced. Our current results demonstrate a critical role of class IA type PI3K in the bactericidal activity of macrophages by regulating their NO production through GTP cyclohydrolase 1 induction.
Hierarchical skeleton extraction based on a deformable particle system (1998)

The use of a particle system as a skeleton extractor is introduced here. This system behaves as an active contour model embedding variable topology properties. As the particles propagate inside tree-shaped objects, we build their skeleton which is useful to determine the neighborhoods used for the computation of the regularization and interaction forces. This connected skeleton is directly returned and avoids a two-step approach based on a morphological operation followed by a tree analysis. In addition, the method gives information on the hierarchy of structures. Using this method, it is possible to generate a cartography of structures such as veins or channels.
Akt/Ezrin Tyr353/NF-κB pathway regulates EGF-induced EMT and metastasis in tongue squamous cell carcinoma (2013)

Our data suggest that Akt/Ezrin Tyr353/NF-κB pathway regulates EGF-induced EMT and metastasis inTSCC, and Ezrin may serve as a therapeutic target to reverse EMT in tongue cancers and prevent TSCC progression.
Kronos: a scalable group re-keying approach for secure multicast (2002)

The authors describe a novel approach to scalable group re-keying for secure multicast. Our approach, which we call Kronos, is based upon the idea of periodic group re-keying. We first motivate our approach by showing that if a group is re-keyed on each membership change, as the size of the group increases and/or the rate at which members leave and join the group increases, the frequency of rekeying becomes the primary bottle neck for scalable group re-keying. In contrast, Kronos can scale to handle large and dynamic groups because the frequency of re-keying is independent of the size and membership dynamics of the group. Next, we describe how Kronos can be used in conjunction with distributed key management frameworks such as IGKMP (T. Hardjono et al., 1998) that use a single group-wide session key for encrypting communications between members of the group. Using a detailed simulation, we compare the performance tradeoffs between Kronos and other key management protocols.
Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhGM-CSF) after Chemotherapy in Patients with Non-Hodgkin's Lymphoma; a Placebo-Controlled Double Blind Phase III Trial (1993)

To assess the clinical and hematopoietic effects of rhGM-CSF, a placebo-controlled double blind multicenter phase III study was undertaken in patients with non-Hodgkin's lymphoma receiving cytotoxic chemotherapy. Sixty-two patients who had granulocytopenia (< 1 x 10(3)/microliters) after the first cycle of chemotherapy with cyclophosphamide, adriamycin, vincristine, and prednisolone were enrolled. After the second cycle of chemotherapy with the same regimen, patients randomly received either rhGM-CSF (125 micrograms/m2/day) or placebo for 14 days (rhGM-CSF; 31 patients and placebo; 31 patients). Administration of rhGM-CSF induced a significant increase in granulocytes mainly with neutrophils, eosinophils and monocytes, but elevation of lymphocytes, platelets, and reticulocytes was not induced. Median days of granulocytes less than 1 x 10(3)/microliters in patients receiving rhGM-CSF were significantly shorter than in patients receiving placebo (p = 0.001). Adverse reactions encountered with rhGM-CSF, and observed in 58% of the patients were never life-threatening and always rapidly reversible. They included fever, nausea and vomiting, diarrhea, skin eruption, and malaise. These results suggest that rhGM-CSF can be safely administered to prevent neutropenia after chemotherapy in patients with non-Hodgkin's lymphoma.
Optical imaging of bacterial infections (2016)

The rise in multidrug resistant (MDR) bacteria has become a global crisis. Rapid and accurate diagnosis of infection will facilitate antibiotic stewardship and preserve our ability to treat and cure patients from bacterial infection. Direct in situ imaging of bacteria offers the prospect of accurately diagnosing disease and monitoring patient outcomes and response to treatment in real-time. There have been many recent advances in the field of optical imaging of infection; namely in specific probe and fluorophore design. This combined with the advances in imaging device technology render direct optical imaging of infection a feasible approach for accurate diagnosis in the clinic. Despite this, there are currently no licensed molecular probes for clinical optical imaging of infection. Here we report some of the most promising and interesting probes and approaches under development for this purpose, which have been evaluated in in vivo models within the laboratory setting.