gebhart/patrepeval huggingface dataset:
RANTES and Chemotactic Activity in Synovial Fluids From Patients With Rheumatoid Arthritis andOsteoarthritis (2005)

A massive accumulation of inflammatory cells in synovial tissues is a major pathological feature of rheumatoid arthritis (RA). Neutrophiles dominate synovial fluid while rheumatoid synovium is infiltrated with mononuclear cells. Mechanisms regulating influx of particular subpopulations of leukocytes into articular cavity and synovium compartment are not completely defined. An increasing amount of data supports a crucial role of a C-C chemokine RANTES in the RA pathogenesis. Our objective is to evaluate chemotactic activity for neutrophils (NCA), lymphocytes (LCA), and monocytes (MoCA) in SFs obtained from patients with RA and osteoarthritis (OA). We also aimed to characterise the relation between chemotactic activity, RANTES, and percentage distribution of leukocytes in SF. SFs from 11 patients with RA and 6 with OA were included in the study. Modified microchamber Boyden method was employed to assess chemotactic activity. Cytological and biochemical analysis of SF was performed. RANTES was measured with ELISA. Rheumatoid SFs were rich in cells with predominance of neutrophiles while osteoarthritic fluids were lymphocytic. RA SFs were also characterised by increased lactoferrin level. Both NCA and LCA were higher in SF from patients with RA (62 +/- 12 and 24 +/- 6 cells/HPF, resp) as compared to patients with OA (23 +/- 6; P < .05 and 6 +/- 2 cells/HPF; P < 0.05). The chemoattractive effect of RA SF was more pronounced on neutrophiles than on lymphocytes. RA SF expressed high RANTES levels (145+/- 36 pg/mL), while OA SF was characterised by only trace amount of this chemokine (2 +/- 1 pg/mL). We found positive correlation of RANTES with chemotactic activity for mononuclear cells (LCA + MoCA; R = 0.61; P < .05). Surprisingly, RANTES correlated also positively with neutrophiles number (R = 0.77; P < 0.001). Rheumatoid SF possesses strong chemotactic potency for leukocytes. RANTES is overexpressed in RA SF and is a potential mediator influencing intensity and composition of cellular infiltration in joints affected with inflammatory arthritis.
Disulfide Bonds and Membrane Topology of the Vaccinia Virus A17L Envelope Protein (2000)

The envelope protein encoded by the vaccinia virus A17L open reading frame is essential for virion assembly. Our mutagenesis studies indicated that cysteines 101 and 121 form an intramolecular disulfide bond and that cysteine 178 forms an intermolecular disulfide linking two A17L molecules. This arrangement of disulfide bonds has important implications for the topology of the A17L protein and supports a two-transmembrane model in which cysteines 101 and 121 are intraluminal and cysteine 178 is cytoplasmic. The structure of the A17L protein, however, was not dependent on these disulfide bonds, as a recombinant vaccinia virus with all three cysteine codons mutated to serines retained infectivity.
Accelerating chimeric antigen receptor therapy in chronic lymphocytic leukemia: The development and challenges of chimeric antigen receptor T‐cell therapy for chronic lymphocytic leukemia (2019)

Studies of chimeric antigen receptor (CAR) T-cell therapy in chronic lymphocytic leukemia (CLL) have demonstrated the potential to produce deep remissions-and possibly cures-in some patients with heavily pretreated, high-risk, relapsed, and refractory disease. Unfortunately, most clinical trials of CAR T cells in CLL report complete responses only in the minority of patients, although recent studies have begun to elucidate the factors most predictive of response. These studies have suggested strategies for optimizing CAR T-cell fitness as well as the pre-existing host immune response, approaches that will likely lead to improvements in the efficacy of CAR T cells in CLL. Treating patients earlier in the course of their disease or using combination therapies with CAR T cells may further enhance efficacy. In this review, we summarize the existing literature on CAR T cell therapy in CLL, discuss mechanisms of response and resistance, and describe challenges facing the field.
Synthesis of 6-Substituted 3-(Alkoxycarbonyl)-5-aryl-α-pyrones (2013)

An efficient synthesis of 6-substituted 3-(alkoxycarbonyl)-5-aryl-α-pyrones is reported. This methodology consists of the successive manipulation of an addition–elimination reaction between benzyl ketone derivatives and dimethyl methoxymethylenemalonate, and an acid-catalyzed condensation reaction. The synthesis is applicable to various 5-<i>p</i>-substituted-aryl 6-substituted α-pyrones and good to excellent yields were obtained over two steps from benzyl ketone derivatives that were easily prepared from phenylacetic acid by the Negishi coupling or the Claisen decarboxylation reaction.
Identifying the proteins to which small-molecule probes and drugs bind in cells (2009)

Most small-molecule probes and drugs alter cell circuitry by interacting with 1 or more proteins. A complete understanding of the interacting proteins and their associated protein complexes, whether the compounds are discovered by cell-based phenotypic or target-based screens, is extremely rare. Such a capability is expected to be highly illuminating--providing strong clues to the mechanisms used by small-molecules to achieve their recognized actions and suggesting potential unrecognized actions. We describe a powerful method combining quantitative proteomics (SILAC) with affinity enrichment to provide unbiased, robust and comprehensive identification of the proteins that bind to small-molecule probes and drugs. The method is scalable and general, requiring little optimization across different compound classes, and has already had a transformative effect on our studies of small-molecule probes. Here, we describe in full detail the application of the method to identify targets of kinase inhibitors and immunophilin binders.
Therapeutic Metabolic Inhibition: Hydrogen Sulfide Significantly Mitigates Skeletal Muscle Ischemia Reperfusion Injury In Vitro and In Vivo (2010)

These findings confirm that the preischemic delivery of hydrogen sulfide limits ischemia-reperfusion injury-induced cellular damage in myotubes and skeletal muscle and suggests that, when given in the appropriate dose, this molecule may have significant therapeutic applications in multiple clinical scenarios.
Increased Myocardial Release of Prostacyclin in Dogs with Heart Failure (1983)

We studied myocardial release of the endogenous vasodilator, prostacyclin, in dogs with cardiac hypertrophy and heart failure because of previous reports of reduced coronary blood flow reserve in various models of cardiac hypertrophy. Myocardial release of prostacyclin was estimated by measuring the concentration of its stable metabolite, 6-keto prostaglandin F1α (6-K F1α), found in a physiological buffer instilled into the pericardial space. In anesthetized dogs with chronic heart failure resulting from aortocaval fistula, the basal release of 6-KF1α was over twofold higher than normal. Dogs with heart failure released 1301 ± 226 pg 6-KF1α per square centimeter of ventricular surface area during the 4.5 min that the buffer was in the pericardial space compared to 553 ± 82 pg/cm2 for control dogs (p < 0.01). Simultaneously released thromboxane B2 (TxB2), the stable metabolite of the vasoconstrictor thromboxane A2, was measured and found not to be different in the two groups of dogs. In control dogs, isoproterenol administration was associated with a dose-dependent increase in myocardial release of 6-KF1α, while the release of TxB2 was constant. In contrast, 6-KF1α levels remained high and unaffected by isoproterenol administration in dogs with heart failure. These alterations in myocardial release of 6-KF1α were parallelled by changes in coronary vascular resistance. Resting coronary vascular resistance was significantly lower than normal in dogs with heart failure (0.8 ± 0.23 mm Hg·min/ml 1112 vs. 2.1 ± 0.1 mm Hg·min/ml control, p < 0.01). Coronary vascular resistance decreased in a dose-dependent manner in response to isoproterenol in control dogs but did not change in dogs with heart failure. These results are compatible with the idea that enhanced myocardial release of prostacyclin may play a role in the altered coronary vascular responses seen in heart failure.
Crystalline Halide Substituted Li-Argyrodites as Solid Electrolytes for Lithium Secondary Batteries (2010)

Apparent lithium ionic conductivity of crystalline Li-Argyrodite materials (Li6PS5X, X = Cl, Br) was measured to be about 10 exp(-4) S/cm, which is higher than that of common solid electrolytes like LiPON. The materials are electrochemically stable at least up to 5 V vs. Li/Li+ and thus applicable as electrolyte with standard cathode active materials in lithium secondary batteries. An all-solid-state battery using Li-Argyrodite as electrolyte with lithium titanate as cathode and lithium aluminum alloy anode was fabricated, showing a specific capacity of 150 mAh/g at a current rate of C/50 at 75 degC. However, the cell shows poor rate capability and a large polarization at room temperature.
Multi-band color image deblurring using contourlets for fluid lens camera systems (2009)

Fluidic lens camera systems present a new field of exploration for both the optics and image processing communities. Developed for surgical applications, these cameras do not have moving parts while zooming and they have better miniaturization possibilities. However, the lens causes non-uniform color blur between color planes which creates an image processing problem. We propose the use of a contourlet filter bank system to deblur color images without estimating a point spread function. This multi-band deblurring method uses sharper color planes to improve blurred ones. Compared to the conventional Lucy-Richardson and Wiener filtering, our previous wavelet-based method significantly improves sharpness and ghosting artifacts. The proposed contourlet-based system better adjusts to the natural image contours. This effect produces an image with a similar level of sharpness, but fewer ghosting artifacts. Furthermore, we analyze conditions for when this algorithm will reduce the mean squared error. We also use an ant colony optimization algorithm to detect sharp edges. This algorithm naturally extends to many systems for multi-band deblurring that have high edge correlation.
Microemulsions for improved peptide absorption from the gastrointestinal tract. (1991)

Results on gastrointestinal absorption of three peptides, insulin, cyclosporin from microemulsions, obtained from studies in our laboratories during the past years have been summarized. The routes of administration were period, intralumenal or rectal. The experiments were carried out in dogs, rabbits and rats. An absorption model for peptides using microemulsions as delivery systems is presented.
A canine model for determination of the therapeutic index of cytokine inhibitors. (1995)

Using tumor necrosis factor (TNF) inhibition in dog blood as a measure of efficacy, and canine emesis as a measure of toxicity, we were able to assign a therapeutic index to rolipram, a prototypic anti-inflammatory compound. Because both assays were performed in the same species, the ambiguities associated with comparing the physiologic effects of drugs on various species was avoided. Rolipram, a standard phosphodiesterase type IV inhibitor, was a prototypic test compound characterized by a number of cardiovascular and central nervous system side effects, as well as its in vitro and in vivo inhibition of TNF. Initial experiments with canine whole blood incubated with lipopolysaccharide resulted in nanogram-per-milliliter concentrations of TNF that could be significantly reduced by in vitro addition of a 0.03 microM concentration of rolipram. Because rolipram inhibited canine TNF production in vitro, a protocol was devised in which TNF inhibitory activity was measured in a series of blood samples from dogs infused with increasingly high doses of rolipram. This yielded the efficacy half of the therapeutic index, whereas the emetogenic dose represented the side effect portion of the index. Rolipram was infused stepwise into conscious dogs at gradually increasing doses. The infusion was stopped when vomiting occurred, and the cumulative dose was reported as the emetic dose. Rolipram caused emesis in dogs at a cumulative dose of 0.1 mg/kg. At each dose of rolipram, blood was collected. The whole blood was incubated in vitro with lipopolysaccharide to induce TNF production, which in turn was quantified by the L929 bio-assay. Theoretically, if the rolipram infusion raised blood values high enough, the rolipram in whole blood would inhibit TNF production and be reflected by a lack of TNF activity in the L929 assay. In this assay system, rolipram's 50% effective dose in the TNF assay was always at least 33-fold lower than its emetic dose of 0.1 mg/kg. This gave rolipram a therapeutic index of at least 33:1 (0.003 versus 0.1 mg/kg) on the basis of its activity in a canine efficacy model (TNF inhibition) and a toxicity model (emesis induction). Experimental compounds were tested for their emetic dose as well as TNF 50% effective dose, with the goal of obtaining a therapeutic index better than that of rolipram. Thus the coupling of cytokine activity with overt toxicity was used to arrive at the therapeutic index of a compound. The therapeutic index was used to rank compounds as to their efficacy/toxicity profile. This ranking was used to eliminate several anti-inflammatory compounds that had a therapeutic index less than that of rolipram.
Automatic Dent-landmark detection in 3-D CBCT dental volumes (2011)

Orthodontic craniometric landmarks provide critical information in oral and maxillofacial imaging diagnosis and treatment planning. The Dent-landmark, defined as the odontoid process of the epistropheus, is one of the key landmarks to construct the midsagittal reference plane. In this paper, we propose a learning-based approach to automatically detect the Dent-landmark in the 3D cone-beam computed tomography (CBCT) dental data. Specifically, a detector is learned using the random forest with sampled context features. Furthermore, we use spacial prior to build a constrained search space other than use the full three dimensional space. The proposed method has been evaluated on a dataset containing 73 CBCT dental volumes and yields promising results.
Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States (2022)

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.
Homodyne en face optical coherence tomography (2006)

We demonstrate, for what we believe to be the first time, the use of a 3 x 3 fiber-optic coupler to realize a homodyne optical coherence tomography (OCT) system for en face imaging of highly scattering tissues and turbid media. The homodyne OCT setup exploits the inherent phase shifts between different output ports of a 3 x 3 fiber-optic coupler to extract amplitude information of a sample. Our homodyne en face OCT system features a measured resolution of 14 microm axially and 9.4 microm laterally with a 90 dB signal-to-noise ratio at 10 micros integration time. En face OCT imaging of a stage 52 Xenopus laevis was successfully demonstrated at a depth of 600 microm within the sample.
Unifying Mechanisms of Action of the Anticancer Activities of Triterpenoids and Synthetic Analogs (2012)

Triterpenoids such as betulinic acid (BA) and synthetic analogs of oleanolic acid [2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO)] and glycyrrhetinic acid [2-cyano-3,11-dioxo-18β-oleana-1,12-dien-30-oc acid (CDODA)] are potent anticancer agents that exhibit antiproliferative, antiangiogenic, anti-inflammatory and pro-apoptotic activities. Although their effects on multiple pathways have been reported, unifying mechanisms of action have not been reported. Studies in this laboratory have now demonstrated that several triterpenoids including BA and some derivatives, celastrol, methyl ursolate, β-boswellic acid derivatives, and the synthetic analogs CDDO, CDODA and their esters decreased expression of specificity protein (Sp) transcription factors and several pro-oncogenic Sp-regulated genes in multiple cancer cell lines. The mechanisms of this response are both compound- and cell context-dependent and include activation of both proteasome-dependent and -independent pathways. Triterpenoid-mediated induction of reactive oxygen species (ROS) has now been characterized as an important proteasome-independent pathway for downregulation of Sp transcription factors. ROS decreases expression of microRNA-27a (miR-27a) and miR-20a/miR-17-5p and this results in the induction of the transcriptional "Sp-repressors" ZBTB10 and ZBTB4, respectively, which in turn downregulate Sp and Sp-regulated genes. Triterpenoids also activate or deactive nuclear receptors and G-protein coupled receptors, and these pathways contribute to their antitumorigenic activity and may also play a role in targeting Sp1, Sp3 and Sp4 which are highly overexpressed in multiple cancers and appear to be important for maintaining the cancer phenotype.
Parallel Task Routing for Crowdsourcing (2014)

An ideal crowdsourcing or citizen-science system would route tasks to the most appropriate workers, but the best assignment is unclear because workers have varying skill, tasks have varying difficulty, and assigning several workers to a single task may significantly improve output quality. This paper defines a space of task routing problems, proves that even the simplest is NP-hard, and develops several approximation algorithms for parallel routing problems. We show that an intuitive class of requesters' utility functions is submodular, which lets us provide iterative methods for dynamically allocating batches of tasks that make near-optimal use of available workers in each round. Experiments with live oDesk workers show that our task routing algorithm uses only 48% of the human labor compared to the commonly used round-robin strategy. Further, we provide versions of our task routing algorithm which enable it to scale to large numbers of workers and questions and to handle workers with variable response times while still providing significant benefit over common baselines.
Electronic remote identification-a case study (2002)

The specification, design, and development of an electronic identification system are discussed. The system has the advantages of long-read-range, orientation-independent, low-cost, passive tags, which are easy to manufacture, require simple installation procedures, and are suitable for use in many countries, over a wide and diverse set of application areas.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
MRI of Articular Cartilage: Revisiting Current Status and Future Directions (2005)

Articular cartilage plays an essential role in the function of the diarthrodial joints of the body but is frequently the target of degeneration or traumatic injury. The recent development of several surgical procedures that hold the promise of forming repair tissue that is hyaline or hyalinelike cartilage has increased the need for accurate, noninvasive assessment of both native articular cartilage and postoperative repair tissue. MRI is the optimal noninvasive method for assessment of articular cartilage.
In-pipe bristled micromachine (2003)

This paper deals with in-pipe micromachine, which moves in pipes with inner diameter under 25 mm. The micromachine locomotion principle is based directional friction force between bristle tip and pipe wall. At first we have theoretically analysed the locomotion principle. The next part consist of analysis of bristle tip connection with inner pipe wall. Finally, the analysis is supported with experiments.
Bioengineering of noncoding <scp>RNAs</scp> for research agents and therapeutics (2016)

The discovery of functional small noncoding RNAs (ncRNAs), such as microRNAs and small interfering RNAs, in the control of human cellular processes has opened new avenues to develop RNA-based therapies for various diseases including viral infections and cancers. However, studying ncRNA functions and developing RNA-based therapeutics relies on access to large quantities of affordable ncRNA agents. Currently, synthetic RNAs account for the major source of agents for RNA research and development, yet carry artificial modifications on the ribose ring and phosphate backbone in sharp contrast to posttranscriptional modifications present on the nucleobases or unmodified natural RNA molecules produced within cells. Therefore, large efforts have been made in recent years to develop recombinant RNA techniques to cost-effectively produce biological RNA agents that may better capture the structure, function, and safety properties of natural RNAs. In this article, we summarize and compare current in vitro and in vivo methods for the production of RNA agents including chemical synthesis, in vitro transcription, and bioengineering approaches. We highlight the latest recombinant RNA approaches using transfer RNA (tRNA), ribosomal RNA (rRNA), and optimal ncRNA scaffold (OnRS), and discuss the applications of bioengineered ncRNA agents (BERAs) that should facilitate RNA research and development.
Arachidonic Acid Production by Fungi (1991)

After preliminary screening, Mortierella alpina and Mortierella elongata were compared with respect to arachidonic acid content. M. alpina ATCC 16266 produced 2.1 g of arachidonic acid per liter in media containing 10% glucose while the highest percentage of arachidonic acid in lipid (43.3%) was observed at a glucose concentration of 2%. Arachidonic acid content in lipids increased to 66% during storage.