cssi/SciSciGPT-SciSciNet huggingface dataset:
Novel therapy for Hodgkin lymphoma

The treatment of Hodgkin lymphoma (HL) relies on multimodality treatment with standard chemotherapy, radiation therapy, and autologous or allogeneic stem cell transplantation in cases of relapsed disease. Genomic advances in HL provided insights into deregulation of key nodal signaling pathways, including the PI3K, NF-κB, and JAK/STAT pathways, which are amenable to small-molecule targeting. Understanding how HL cells interact and depend on their microenvironment for survival signals and immune protection may uncover other such pathways. Small-molecule targeting has the potential to dramatically improve treatment outcomes, especially in patients with highly refractory disease and those with poor tolerance to existing chemotherapies. As novel therapies continue to be developed for HL, the challenge will be to address the needs of high-risk groups, reduce long-term therapy-related morbidity, position current established treatments with novel therapies, and concurrently develop biomarkers to aid in patient selection. Brentuximab vedotin, which was approved in 2011, is already shifting the treatment paradigm of HL. Undoubtedly, other novel therapeutics in the pipeline will affect positively the landscape of treatment in HL.
Anatomic distribution of [18F] fluorodeoxyglucose-avid lymph nodes in patients with cervical cancer

Abstract Purpose Current information about the anatomic distribution of lymph node (LN) metastases from cervical cancer is not precise enough for optimal treatment planning for highly conformal radiation therapy. To accurately define the anatomic distribution of these LN metastases, we mapped [ 18 F] fluorodeoxyglucose positron emission tomography (FDG PET)-positive LNs from 50 women with cervical cancer. Methods and Materials Records of patients with cervical cancer treated from 2006 to 2010 who had pretreatment PET/computed tomography (CT) scans available were retrospectively reviewed. Forty-one consecutive patients (group 1) with FDG-avid LNs were identified; because there were few positive paraortic LNs in group 1, 9 additional patients (group 2) with positive paraortic LNs were added. Involved LNs were contoured on individual PET/CT images, mapped to a template CT scan by deformable image registration, and edited as necessary by a diagnostic radiologist and radiation oncologists to most accurately represent the location on the original PET/CT scan. Results We identified 190 FDG-avid LNs, 122 in group 1 and 68 in group 2. The highest concentrations of FDG-avid nodes were in the external iliac, common iliac, and paraortic regions. The anatomic distribution of the 122 positive LNs in group 1 was as follows: external iliac, 78 (63.9%); common iliac, 21 (17.2%); paraortic, 9 (7.4%); internal iliac, 8 (6.6%); presacral, 2 (1.6%); perirectal, 2 (1.6%); and medial inguinal, 2 (1.6%). Twelve pelvic LNs were not fully covered when the clinical target volume was defined according to Radiation Therapy Oncology Group guidelines for intensity modulated radiation therapy for cervical cancer. Conclusions Our findings clarify nodal volumes at risk and can be used to improve target definition in conformal radiation therapy for cervical cancer. Our findings suggest several areas that may not be adequately covered by contours described in available atlases.
Morphology of ventricular premature beats as an aid in the electrocardiographic diagnosis of myocardial infarction

To determine whether morphologic analysis of ventricular premature beats (VPBs) can aid in the electrocardiographic diagnosis of myocardial infarction (MI), 12-lead electrocardiograms were evaluated in 760 consecutive patients who underwent cardiac catheterization, and 2-minute multiple-lead rhythm strips were evaluated in 515 of these patients. VPBs occurred in 58 patients; 21 had prior MI diagnosed by regional akinesia or dyskinesia on left ventricular cineangiography. Standard criteria were used to diagnose prior MI from the sinus beats of the electrocardiogram. Infarction was diagnosed from the morphology of a VPB when it had a QR or QRS pattern with Q wave greater than or equal to 0.04 second. Morphologic analysis of VPBs had a low sensitivity (29%) but high specificity (97%) and high predictive value (86%) for the diagnosis of MI. Sinus beats diagnosed MI with higher sensitivity (52%, and 69% if patients with left bundle branch block and left ventricular hypertrophy were excluded from analysis) than VPB morphologic analysis (p less than 0.05), but with similar specificity (97%) and predictive value (92%). Two patients with angiographic MI had no MI according to standard electrocardiographic criteria, but did have an MI manifest by VPB morphologic analysis. Despite low sensitivity, analysis of the morphology of VPBs may be useful for the diagnosis of MI when the morphology of sinus beats is not diagnostic. Therefore, VPB analysis is complementary to the standard electrocardiographic diagnosis of MI.
Utility of carotid duplex ultrasonography in a general inner-city hospital

Background Carotid Duplex Ultrasonography (CDUS) is one of the non-invasive imaging modalities used to evaluate for carotid artery stenosis. However, it is often used in patients with coronary artery disease (CAD), peripheral artery disease (PAD), before heart surgery, syncope and non-specific neurological symptoms although its value is unclear. Our study aimed to further investigate the yield of CDUS in these conditions.
Low RCS Target Tracking in Estimated Rapidly Varying Sea Clutter Using a Kronecker Product Approximation Algorithm

We propose a method for estimating the space-time covariance matrix of rapidly-varying sea clutter following a dynamic state space matrix model. The covariance matrix dimension can become computationally infeasible as it increases with the number of range bins and dwell pulses required for coherent processing. In order to reduce the computational complexity, we apply the Kronecker product (KP) approximation and particle filtering to estimate the space-time covariance matrix, and we demonstrate the proposed method's validity using real clutter data. We also demonstrate that the method ensures that the covariance matrix estimate is always positive definite. The covariance matrix estimation is integrated with a track-before-detect filter for tracking a low radar cross-section (RCS) target in strong sea clutter.
Compressive Imaging and Spectroscopy – Beyond the Single Pixel Camera

The development of visible and infrared imaging systems continues to be an extremely active area of physics and engineering research despite the already considerable history of its development and accomplishments. This is due to the significant breakthroughs in the mathematics of image processing and the substantial advances in device performance over the last decade. Recently, many efforts in imaging that combine the relatively inexpensive and readily available computational power of microprocessors with new optical schemes have been undertaken to increase image resolution while decreasing acquisition time. One such approach that we have been investigating in our lab is based on compressive sensing mathematics coupled with micro-optoelectronic modulators. In essence, imaging via compressive sensing is a new strategy for imaging with a single detector in place of an imaging array. Additionally, the single detector can be replaced with a spectrometer to perform compressive hyperspectral imaging.
Evaluating Outcome Research for Hypersexual Behavior

Despite the decision to omit hypersexual behavior or hypersexuality from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), research regarding the nature of hypersexual behavior has flourished in recent years. One area in which there is still a distinct and present need for more work has been outcome research related to the efficacious treatment of hypersexual behavior. Although prior reviews have systematically delineated the necessary changes and improvements in outcome research related to the treatment of hypersexuality, the present review seeks to evaluate the current state of outcome research in light of recent advances in the understanding of hypersexual behavior. Prior reviews are synthesized, recent outcome studies are examined, recent advances in the treatment of related disorders are reviewed, recent advances in hypersexual behavior research are evaluated in terms of treatment implications, and recommendations for future research are offered.
Anthracycline-Enhanced Cardiac Oxygen Radical Metabolism

The anthracycline quinones play an important role in the chemotherapeutic management of a wide variety of human malignancies including acute myelogenous and lymphocytic leukemias, the non-Hodgkin’s lymphomas, and carcinomas of the breast, lung, and thyroid (1). The clinical usefulness of these drugs may be limited, however, by the development of a dose-related, congestive cardiomyopathy that is sometimes fatal (2). There is currently a substantial body of experimental data supporting the hypothesis that the myocardial injury produced by anthracycline antibiotics is related to drug-induced reactive oxygen production in the heart (3–6). These investigations include studies which show that the morphologic expression of doxorubicin cardiac toxicity may be enhanced by inhibition of cardiac antioxidant defense systems; that damage to the heart may be reduced or abolished by pretreatment of experimental animals with various free radical scavengers; and that cyclical reduction and oxidation of the doxorubicin quinone leads to the depletion of critical cardiac energy stores, as well as to the inability of intact myocytes to maintain calcium homeostasis (7–10).
Modeling the survival kinetics of Salmonella in tree nuts for use in risk assessment

Salmonella has been shown to survive in tree nuts over long periods of time. This survival capacity and its variability are key elements for risk assessment of Salmonella in tree nuts. The aim of this study was to develop a mathematical model to predict survival of Salmonella in tree nuts at ambient storage temperatures that considers variability and uncertainty separately and can easily be incorporated into a risk assessment model. Data on Salmonella survival on raw almonds, pecans, pistachios and walnuts were collected from the peer reviewed literature. The Weibull model was chosen as the baseline model and various fixed effect and mixed effect models were fit to the data. The best model identified through statistical analysis testing was then used to develop a hierarchical Bayesian model. Salmonella in tree nuts showed slow declines at temperatures ranging from 21°C to 24°C. A high degree of variability in survival was observed across tree nut studies reported in the literature. Statistical analysis results indicated that the best applicable model was a mixed effect model that included a fixed and random variation of δ per tree nut (which is the time it takes for the first log10 reduction) and a fixed variation of ρ per tree nut (parameter which defines the shape of the curve). Higher estimated survival rates (δ) were obtained for Salmonella on pistachios, followed in decreasing order by pecans, almonds and walnuts. The posterior distributions obtained from Bayesian inference were used to estimate the variability in the log10 decrease levels in survival for each tree nut, and the uncertainty of these estimates. These modeled uncertainty and variability distributions of the estimates can be used to obtain a complete exposure assessment of Salmonella in tree nuts when including time-temperature parameters for storage and consumption data. The statistical approach presented in this study may be applied to any studies that aim to develop predictive models to be implemented in a probabilistic exposure assessment or a quantitative microbial risk assessment.
Recent Studies on the Application of Enzymes in the Synthesis of Polyesters

Enzyme-catalyzed preparation of polymers offers several potentially valuable advantages over the usual polymerization procedures. This paper summarizes our successful use of lipase-catalyzed polycondensations to prepare both a series of achiral [AA-BB]x polyesters from bis(2,2,2- trichloroethyl) alkanedioates and diols and of an optically active, epoxy-substituted polyester having a stereochemical purity estimated to be greater than 96%, from racemic bis(2,2,2-trichloroethyl) trans-3,4-epoxyhexanedioate and 1,4-butanediol. All of the reactions were carried out at ambient temperature in anhydrous, low to intermediate polarity, organic solvents such as ether, THF, 2-ethoxyethyl ether, dibenzyl ether, o-dichlorobenzene, or methylene choride, using porcine pancreatic lipase (PPL) as the catalyst. The molecular weight achieved by the polycondensation is limited by accumulation of the trihaloethanol that forms as the reaction progresses, probably because it frees enzyme-bound water permitting hydrolysis of the polymer to occur. This problem has been alleviated by using a high boiling solvent and removing the alcohol by placing the re’action mixture under vacuum.
Fracture of an uncemented tantalum patellar component

A 62-year-old man presented with the acute, atraumatic onset of pain 3 years after uncemented right total knee arthroplasty. He complained of new mechanical locking with the knee held in extension on examination and unable to flex the knee. On the plain radiographs, the patellar component peg was fractured and the plate was dislocated. The knee was immobilized, and revision to a cemented 3-peg component was performed. Fracture of a single-peg, tantalum-backed uncemented patellar component has not been described. Clinical suspicion for this should be given in the setting of acute locking. We recommend revision with a cemented polyethylene component.
Improving GaAs Chip yield And Enhancing Reliability of GaAs Devices

The purpose of this research is to improve GaAs yield and enhance the reliability of GaAs MMICs (Monolithic Microwave Integrated Circuits) by first understanding the physical mechanisms of GaAs, Ni,Au-Ge eutectic and Au alloying process. Ohmic ooze has been driving force for this research. Variety of innovative experiments has been designed, so that contact resistance may be guaranteed to be within the permissible range. This resulted into the development of analytical techniques to measure contact resistance to GaAs as a result of alloying process employing Ni,Au-Ge and Au.
Sulfur Corrosion Research and Protection of Transformer Oil in Anhui Grid

To solve the problem of sulfur corrosion in large transformer of 220kV and above in Anhui power grid,the causes are analyzed,as well as influencing factor and its damage to equipment operation.Based on that,countermeasures are studied,and the sulfur corrosion optimum detection is determined,and the solution of adding the passivator to the transformer oil to avoid sulfur corrosion is proposed.Application of passivator technique to 220kV and above transformers of Anhui power grid is presented.
Studying on Application of Online Monitoring Device for Generator Hydrogen Leakage

The monitoring device of generator hydrogen leakage has the important function for the earlier warning of fault. The basic requirements for this device are to be able to stabilize work for a long period, not mistake and fail to report for the earlier warning of fault. This paper analyzes the working principles and application effects of two major hydrogen leakage devices, hydrogen sensing transducer with palladium grid and thermal conductivity, which possess the greater home market now. It is convenient for power plant to operate, maintenance and choose the equipments as reference.
Rapid detection of human seasonal influenza virus by RT-LAMP assay

Objective To establish and apply RT-LAMP,for the rapid clinical detection of human seasonal influenza virus.Methods The specific primers of the conserved regions of influenza virus gene for subtype A1,A3 and type B were selected and composed which used to detect 400 samples of influenza virus from throat swabs of influenza-like cases of illness during November 2007 and February 2009 in Nanjing.Those samples were also detected by traditional isolation with MDCK cell lines and the subtype was identifi ed by monoclonal antibodies.Results Fifty-seven specimens were determined as positive by RT-LAMP and 49 as subtype A1,6 as subtype A3 and 2 as type B.While 55 specimens were determined as positive by cellular isolation and 47 as subtype A1,6 as subtype A3 and 2 as type B.There was no statistic difference(P0.05) between these two methods.RT–LAMP assay was performed in water oven and the results could be directly determined by eyes under visible light or UV lamp.Conclusion The RT–LAMP assay was specific for human seasonal influenza virus and had no cross reaction with avian influenza virus H5 or H9.This assay was also be used in identifying of subtype of influenza virus.
Irreversible enzyme inhibitors. LXXXII. Candidate active-site-directed irreversible inhibitors of dihydrofolic reductase. VII. Derivatives of 2,4-diaminopyrimidine. I.

Fusion of α-benzoyl-α-phenylazoacetonitrile (V) with guanidine carbonate gave 2, 4-diamino-6-phenyl-5-phenylazopyrimidine (VII) in 52 per cent yield; catalytic reduction of VII to 6-phenyl-2, 4, 5-triaminopyrimidine (VI) proceeded smoothly. Condensation of the triaminopyrimidine (VI) with p-nitrocinnamaldehyde to an anil followed by a two-stage reduction afforded 5-(p-aminophenylpropylamino)-2, 4-diamino-6-phenylpyrimidine (XI); selective bromoacetylation on the p-amino group gave the candidate irreversible inhibitor, 5-(p-bromoacetamidophenylpropylamino)-2, 4-diamino-6-phenylpyrimidine (XII). When XII was incubated with dihydrofolic reductase in the presence or absence of TPNH, no inactivation occurred; the possible conformational differences in binding to dihydrofolic reductase between XII and other successful active-site-directed irreversible inhibitors are discussed.
The abortifacient effectiveness and plasma prostaglandin concentrations with 15(S)-15-methyl prostaglandin F2alpha methyl ester-containing vaginal silastic devices.

The abortifacient effectiveness of three intravaginal Silastic devices impregnated with 15(S)-15-methyl prostaglandin F2α (15(S)-Me-PGF2α) methyl ester in concentrations of 0.25%, 0.5%, and 1.0% was investigated. Each concentration was tested in 10 patients with gestations ranging from 8 to 19 weeks. Abortion was successfully induced by prostaglandin alone in 6 patients with the 0.25% device, in 9 patients with the 0.5% device, and all 10 patients treated with the 1.0% device. Additionally, three patients treated with the 0.25% device and one patient treated with the 0.5% device aborted with concomitant, continuous, intravenous oxytocin therapy. The mean abortion time with the 0.25% device was 16.43 hours; with the 0.5% device, 16.49 hours; and with the 1.0% device, 10.18 hours. The peripheral plasma levels of 15(S)-Me-PGF2α methyl ester were the most variable with the 0.5% device. The plasma levels of 15(S)-Me-PGF2α methyl ester of patients receiving the 0.25% device were similar to the levels of patients receiving the 1.0% device. The intravaginal Silastic device impregnated with 15(S)-Me-PGF2α methyl ester appears to be an effective abortifacient, but further study is indicated to determine the most efficient device with the fewest side effects.
Soil abiotic and biotic controls on plant performance during primary succession in a glacial landscape

Summary Plant–soil interactions are temporally dynamic in ways that are important for the development of plant communities. Yet, during primary succession, the degree to which changing soil characteristics (e.g. increasing nutrient availabilities) and developing communities of soil biota influence plant growth and species turnover is not well understood. We conducted a two-phase glasshouse experiment with two native plant species and soils collected from three ages (early, mid- and late succession) of an actively developing glacial chronosequence ranging from approximately 5 to <100 years in age. The first phase assessed how soil abiotic characteristics and soil biota immediately influenced plant performance. In the second phase, we used conditioned soils to grow the same plant species and assessed how the direction and strength of plant–soil feedback (PSF) varied through succession. We used high and low nutrient and soil sterilization treatments to isolate effects of abiotic and biotic factors on plant performance and to assess how patterns of PSF related to soil nutrients. For both species, our experiments revealed that the initial effect of soil biota on plant performance depended on successional stage. In soils collected from early-, mid- and late-succession stages, we observed neutral to negative, negative and positive effects of soil biota on plant performance, respectively. Plant–soil feedback varied with successional stage and depended on whether microcosms were supplied with nutrients. Under low nutrient conditions, soil conditioning by plants, unrelated to initial soil biota, was an important mechanism for positive PSF. Under high nutrient conditions, PSFs differed by plant species in early- and mid-succession soils, but were consistently neutral in late succession. Synthesis. Soil biota can affect the performance of pioneer plants over short gradients of ecosystem development, but the strength and direction of interactions depend on nutrient availability. Conceptual frameworks describing mechanisms of primary succession should acknowledge soil conditioning by previous plants as a potential mechanism of positive feedback.
Prolactin molecular heterogeneity: Response to thyrotropin-releasing hormone stimulation of concanavalin A-bound and -unbound immunoassayable prolactin during human pregnancy

Abstract Since the milieu of pregnancy stimulates physiologic hyperprolactinemia, we questioned whether prolactin secreted during normal pregnancy contains a large-molecular weight component that binds to concanavalin A and whether this large-molecular weight prolactin contributes to the thyrotropin-releasing hormone (TRH)-releasable pool. Serum was collected from pregnant patients (n = 28) undergoing TRH stimulation tests. This serum was passed through a concanavalin A column and eluted with 0.2M α-methylmannoside. Concanavalin A-bound prolactin, as determined by radioimmunoassay, ranged from 10% to 30% of the total immunoassayable prolactin. An increase in the basal serum concentration of both concanavalin A-bound and -unbound prolactin occurred as pregnancy progressed. However, throughout gestation, only the concanavalin A-unbound prolactin increased after TRH stimulation. The concanavalin A-bound prolactin was found to have a molecular weight of 60,000 by means of Sephadex G-100 permeation chromatography.
Hepatitis C treatment in patients on the liver transplant waiting list.

PURPOSE OF REVIEW Hepatitis C virus (HCV) infection remains the leading indication for liver transplant, and viral eradication prior to liver transplant to prevent disease recurrence has traditionally been challenging because of the poor tolerability and efficacy of available therapies. However, with the recent introduction of potent interferon (IFN)-free direct acting antiviral regimens, viral eradication prior to liver transplant is now possible. RECENT FINDINGS Although data are limited, several proof of concept studies have now shown high rates of safety and efficacy in patients with compensated as well as mild-to-moderately decompensated cirrhosis. Although, treatment on the liver transplant waiting list can safely prevent postliver transplant recurrence in selected patients, the ideal regimen and treatment duration have yet to be determined. SUMMARY Although IFN-free therapies represent a tremendous advance in our ability to cure this previously difficult to treat population, additional data on the safety of these regimens, particularly in patients with severely decompensated cirrhosis, the consequences of virologic failure and the impact of viral eradication on short- and long-term liver function are urgently needed.
Non—Cooperative Differential Games

Here we shall consider non-cooperative play in the sense of Nash. Again, we shall restate the definitions and results of Chapter 1 as they apply to the situation discussed in Chapter 2.
Chest wall dose assessment in stereotactic ablative radiotherapy delivered with volumetric modulated arc therapy for peripheral lung tumors

Abstract Background No consensus on how to best predict for chest wall injury following SABR exists. We report our experience in chest wall dose assessment when treating peri-pleural lung lesions with stereotactic ablative radiotherapy (SABR) delivered with volumetric modulated arc therapy (VMAT). Methods 40 patients with peri-pleural peripheral lung tumors underwent SABR between July, 2012 and February, 2015. Chest wall toxicity, dose distribution, and the influence of chest wall delineation method were investigated. Results After a median follow up of 16 months, no rib fracture or skin toxicity was observed. 4 patients (10%) reported persistent chest wall pain (grade 1–2). High dose rate's association with chest wall pain trended toward statistical significance ( p =0.06). PTV exclusion and reducing chest wall expansion to 1 cm led to significant dose reduction in the chest wall dose volume parameters ( p Conclusions The risk of chest wall pain following SABR delivered with VMAT is low. High dose rate, which is 1400 MU/min with flattening filter free (FFF) beams vs. 500–600 MU/min with non-flattening filter free (non-FFF) beams, may contribute to it. Chest wall dose volume parameters may vary with PTV exclusion; while chest wall expansion of 1 cm may fail to account for some high dose regions in the chest wall.
Alkali Cation Chelation in Cold β-O-4 Tetralignol Complexes

We employ cold ion spectroscopy (UV action and IR–UV double resonance) in the gas phase to unravel the qualitative structural elements of G-type alkali metal cationized (X = Li+, Na+, K+) tetralignol complexes connected by β-O-4 linkages. The conformation-specific spectroscopy reveals a variety of conformers, each containing distinct infrared spectra in the OH stretching region, building on recent studies of the neutral and alkali metal cationized β-O-4 dimers. The alkali metal ion is discovered to bind in penta-coordinate pockets to ether and OH groups involving at least two of the three β-O-4 linkages. Different binding sites are distinguished from one another by the number of M+···OH···O interactions present in the binding pocket, leading to characteristic IR transitions appearing below 3550 cm–1. This interaction is mitigated in the major conformer of the K+ adduct, demonstrating a clear impact of the size of the charge center on the three-dimensional structure of the tetramer.
Molecular Mechanisms of Melanoma Metastasis

The recent development of powerful and efficient systemic gene delivery techniques has allowed the identification of a number of genes and pathways critical to the progression of melanoma in murine models. Using this approach, the nuclear factor-κB (NF-κB)-signaling pathway has been identified as playing an important role in the metastatic progression of melanoma. Moreover, recent prognostic analyses using a large cohort of patients from the University of California at San Francisco Melanoma Center database have identified interactions between tumor cells and the tumor vasculature that play a dominant role in the survival associated with melanoma. Translational studies using tissue microarrays have identified expression of the p65 subunit of NF-κB to be tightly correlated with the development of tumor vascularity and vascular invasion. Finally, recent studies on tumor lymphangiogenesis have clarified the nature of the relevant vasculature in the progression of cutaneous melanoma. This chapter will discuss the recent understanding of the molecular mechanisms and pathways underlying the development of traditional and novel histological prognostic markers in melanoma.
Updating HF Noise models using modern open source datasets

A modern data-driven update to the ITU-R Recommendation 372 on Radio Noise is discussed. Publicly available datasets are considered, particularly human population density.
DYNAMIC CONTROL OF MULTI-STRUCTURE ROBOT SYSTEMS AT THE MANIPULATION OBJECT LEVEL

ABSTRACT The paper discusses basic methodologies developed within the operational space framework for the analysis and control of robot systems involving combinations of serial and in-parallel mechanical structures. First, we present the fundamentals of the operational space framework and describe the unified approach for motion and active force control of manipulators. For serial structures such as a macro/-manipulator, the effective inertial characteristics of the combined system are shown to be dominated by the inertial properties of the micro-manipulator. This result is the basis for the development of a new approach for dextrous dynamic coordination. In this approach, the combined system is treated as a single redundant manipulator. The dexterity is achieved by minimizing the deviation from the neutral (mid-range) joint positions of the micro-manipulator. In the case where several arms, i.e. in-parallel structures, are involved in the manipulation of object, the multi-effector/object system is treated as an augmented object representing the total masses and inertias perceived at some operational point actuated by the total effector forces acting at that point. This model is used for the dynamic decoupling, motion, and active force control of the system using a criterion based on the minimization of the total actuator joint force activities.
The Exon Junction Complex and Srp54 Contribute to Hedgehog Signaling via ci RNA Splicing in Drosophila melanogaster

Hedgehog (Hh) regulates the Cubitus interruptus (Ci) transcription factor in Drosophila melanogaster by activating full-length Ci-155 and blocking processing to the Ci-75 repressor. However, the interplay between the regulation of Ci-155 levels and activity, as well as processing-independent mechanisms that affect Ci-155 levels, have not been explored extensively. Here, we identified Mago Nashi (Mago) and Y14 core Exon Junction Complex (EJC) proteins, as well as the Srp54 splicing factor, as modifiers of Hh pathway activity under sensitized conditions. Mago inhibition reduced Hh pathway activity by altering the splicing pattern of ci to reduce Ci-155 levels. Srp54 inhibition also affected pathway activity by reducing ci RNA levels but additionally altered Ci-155 levels and activity independently of ci splicing. Further tests using ci transgenes and ci mutations confirmed evidence from studying the effects of Mago and Srp54 that relatively small changes in the level of Ci-155 primary translation product alter Hh pathway activity under a variety of sensitized conditions. We additionally used ci transgenes lacking intron sequences or the presumed translation initiation codon for an alternatively spliced ci RNA to provide further evidence that Mago acts principally by modulating the levels of the major ci RNA encoding Ci-155, and to show that ci introns are necessary to support the production of sufficient Ci-155 for robust Hh signaling and may also be important mediators of regulatory inputs.
Automatically diagnosing and repairing error handling bugs in C

Correct error handling is essential for building reliable and secure systems. Unfortunately, low-level languages like C often do not support any error handling primitives and leave it up to the developers to create their own mechanisms for error propagation and handling. However, in practice, the developers often make mistakes while writing the repetitive and tedious error handling code and inadvertently introduce bugs. Such error handling bugs often have severe consequences undermining the security and reliability of the affected systems. Fixing these bugs is also tiring-they are repetitive and cumbersome to implement. Therefore, it is crucial to develop tool supports for automatically detecting and fixing error handling bugs. To understand the nature of error handling bugs that occur in widely used C programs, we conduct a comprehensive study of real world error handling bugs and their fixes. Leveraging the knowledge, we then design, implement, and evaluate ErrDoc, a tool that not only detects and characterizes different types of error handling bugs but also automatically fixes them. Our evaluation on five open-source projects shows that ErrDoc can detect error handling bugs with 100% to 84% precision and around 95% recall, and categorize them with 83% to 96% precision and above 90% recall. Thus, ErrDoc improves precision up to 5 percentage points, and recall up to 44 percentage points w.r.t. the state-of-the-art. We also demonstrate that ErrDoc can fix the bugs with high accuracy.
LEAS: A Load-Aware Energy-Efficient Adaptive Scheduling for Heterogeneous Wireless Sensor Networks

The growing interest in applications that demand certain end-to-end performance guarantees and the introduction of imaging and video sensors have posed additional challenges. Transmission of data in such cases requires both energy and QoS aware network management in order to ensure efficient usage of the sensor resources and effective access to the gathered measurements. In this paper we present LEAS, a Lightweight Energy-efficient Scheduling Scheme, a novel power management and routing scheme for heterogeneous wireless sensor networks.
Allopurinol augmentation in acute mania: A meta-analysis of placebo-controlled trials.

Abstract Background Allopurinol is a xanthine oxidase inhibitor commonly used in the treatment of gout. Recent studies have also shown its promise as an adjunctive treatment for manic episodes in bipolar 1 disorder, possibly through mechanisms involving the purinergic pathway. However, its efficacy across studies has been inconsistent, so we conducted a meta-analysis of the published controlled studies with the goal of determining the efficacy profile of allopurinol as an adjunctive treatment for mania in bipolar disorder. Methods An online search was conducted using PubMed for placebo-controlled, randomized, double-blind, clinical trials (RCTs) using the terms “allopurinol,” “bipolar,” “mania,” “manic,” and “YMRS” and a meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. Results Five studies met the criteria for inclusion. Three of the five studies were inpatient treatments, one study was outpatient treatment, and one study had a mixture of both. All studies used allopurinol as an adjunct in treating acute mania in bipolar disorder subjects. Four of the studies showed efficacy in the primary outcome measure between allopurinol vs. placebo groups with significantly reduced YMRS scores while one showed no significant effect size between the allopurinol and placebo groups. The overall effect size for the four studies is d = 0.294. No significant difference in side effects were found between groups for any of the studies. Conclusion The data suggest that allopurinol may have some efficacy as an adjunct in reducing mania symptoms during acute manic episodes in patients with bipolar disorder. Adjunctive allopurinol efficacy may be related to the mood stabilizer used. Additional controlled trials with greater sample sizes, homogenous dosing, and consistent treatment modalities are needed to determine optimal clinical application.
A Hybrid Approach to Data Assimilation for Reconstructing the Evolution of Mantle Dynamics

Quantifying past mantle dynamic processes represents a major challenge in understanding the temporal evolution of the solid earth. Mantle convection modeling with data assimilation is one of the most powerful tools to investigate the dynamics of plate subduction and mantle convection. Although various data assimilation methods, both forward and inverse, have been created, these methods all have limitations in their capabilities to represent the real earth. Pure forward models tend to miss important mantle structures due to the incorrect initial condition and thus may lead to incorrect mantle evolution. In contrast, pure tomography-based models cannot effectively resolve the fine slab structure and would fail to predict important subduction-zone dynamic processes. Here we propose a hybrid data assimilation approach that combines the unique power of the sequential and adjoint algorithms, which can properly capture the detailed evolution of the downgoing slab and the tomographically constrained mantle structures, respectively. We apply this new method to reconstructing mantle dynamics below the western U.S. while considering large lateral viscosity variations. By comparing this result with those from several existing data assimilation methods, we demonstrate that the hybrid modeling approach recovers the realistic 4-D mantle dynamics the best.
Beyond Precision Weed Control: A Model for True Integration

Precision means being exact and accurate and is an important management component for cropping systems. However, precision does not mean integration, which encompasses spatial and temporal dimensions and is a necessary practice rivaling precision. True IWM merges precision and integration by incorporating advanced technology that allows for greater flexibility of inputs and enhanced responsiveness to field conditions. Examples of this approach are non-existent due to a lack of suitable technological tools and a need for a paradigm shift. Herein a potential model startup company is offered as a guide to advance beyond precision weed control to true integration. The critical components of such a company include grower connections, investor support, proven and reliable technology, and adaptability and innovation in the agricultural technology market. The company with the vision and incentive to make true IWM a reality will be the first to more fully integrate available tools using technology, thus helping many growers overcome ongoing challenges associated with resistance, soil erosion, drift, and weed seedbanks.
Temporal Metamaterials with Non-Foster Networks

We theoretically explore instantaneous time mirrors (ITM) for real-time amplification of electrometric wave using non-Foster networks to engineer the required dispersion. Our analytical and numerical results demonstrate various salient features of this phenomenon.
Transforming Smart Cities with Spatial Computing

Spatial methods have a rich history of reforming city infrastructure. For example, John Snow’s 1854 London Cholera map spurred cities to protect drinking water via sewer systems and to increase green spaces for public health. Today, geospatial data and mapping are among the technologies that cities use the most due to strategic (e.g., long-term planning, land-use), tactical (e.g., property tax, site selection, asset tracking) and operational (e.g., E-911, situation awareness, gunshot location) use cases. Moreover, they (e.g., Google Maps) help citizens navigate, drones stay clear of restricted spaces (e.g., airports, NFL games), and sharing-economy (e.g., Uber) match consumers with nearby providers. Future spatial computing opportunities for smart cities are even more compelling. GIS promises to help re-imagine, redesign, see, and compare alternative infrastructure futures to address risks (e.g., climate change, rising inequality, population growth) and opportunities (e.g., autonomous vehicles, distributed energy production). This paper surveys recent spatial computing accomplishments and identifies research needs for smart-city use-cases.
The Dignity Assaults Initiative Implementation within the Michigan Corrections Organization: Staff Acceptance and Application of a Contemporary Policy Approach

This study examined the implementation of one facet of the Dignity Assaults Initiative (DAI) in the state of Michigan. The DAI focused upon the corrections environment and the consistent management...
Serum uric acid as a risk factor of all-cause mortality and cardiovascular events among type 2 diabetes population: Meta-analysis of correlational evidence

Abstract Aims To explore the association between serum uric acid (SUA) level and the risk of cardiovascular complications and all-cause mortality rates among individuals with type 2 diabetes. Methods Web of Science and PubMed database were searched for studies reported associations between SUA level and cardiovascular complications and all-cause mortality among individuals with type 2 diabetes. Hazard ratios (HRs) were independently extracted by two investigators and synthesized through meta-analysis across selected studies. Results 6 (n = 11,750 patients), 4 (n = 3044 patients) and 2 studies (n = 7792 patients) were identified reporting associations between SUA level and all-cause mortality, coronary heart disease (CHD) and stroke respectively. HR for all-cause mortality, CHD, and stroke per 59 μmol/l increase was 1.06 (95% CI: 1.03, 1.09), 1.09 (95% CI: 0.94, 1.26) and 1.19 (95% CI: 1.08, 1.31), respectively. Conclusions Overall, the SUA level was associated with a higher risk of all-cause mortality and stroke. We found no significant association between SUA level and CHD among type 2 diabetes population.
LRP5-deficiency in OsxCreERT2 mice models intervertebral disc degeneration by aging and compression

Osterix is a critical transcription factor of mesenchymal stem cell fate, where its loss or loss of WNT signaling diverts differentiation to a chondrocytic lineage. Intervertebral disc (IVD) degeneration activates differentiation of prehypertrophic chondrocyte-like cells and inactivates WNT signaling, but their interacting role with osterix is unclear. First, compared to young-adults (5mo), mechanical compression of old (18mo) IVD induced greater IVD degeneration. Aging (5 vs 12mo) and/or compression reduced the transcription of osterix and notochordal marker T by 40-75%. Compression elevated transcription of hypertrophic chondrocyte marker MMP13 and pre-osterix transcription factor RUNX2, but less so in 12mo IVD. Next, using an Ai9/td reporter and immunohistochemistry, annulus fibrosus and nucleus pulposus cells of 5mo IVD expressed osterix, but aging and compression reduced its expression. Lastly, in vivo LRP5-deficiency in osterix-expressing cells degenerated the IVD, inactivated WNT signaling, reduced the biomechanical properties by 45-70%, and reduced transcription of osterix, notochordal markers and chondrocytic markers by 60-80%. Overall, these data indicate that age-related inactivation of WNT signaling in osterix-expressing cells may limit regeneration by depleting progenitors and attenuating the expansion of chondrocyte-like cells.
Distribution of Tritium in the Near Surface of Type 316 Stainless Steel

AbstractThe distribution of tritium in the near surface of Type 316 stainless steel has been measured using a combination of a zinc chloride (ZnCl2) wash and acid etching with diluted aqua regia. T...
Directed energy phased array for deep space exploration: phase noise tests using polarization diversity technology

We evaluate the feasibility of implementing a polarization diverse scheme to facilitate beacon based phase locking of a long baseline laser phased array.
Structure-based engineering of pH-dependent antibody binding for selective targeting of solid-tumor microenvironment

Recent development of monoclonal antibodies as mainstream anticancer agents demands further optimization of their safety for use in humans. Potent targeting and/or effector activities on normal tissues is an obvious toxicity concern. Optimization of specific tumor targeting could be achieved by taking advantage of the extracellular acidity of solid tumors relative to normal tissues. Here, we applied a structure-based computational approach to engineer anti-human epidermal growth factor receptor 2 (Her2) antibodies with selective binding in the acidic tumor microenvironment. We used an affinity maturation platform in which dual-pH histidine-scanning mutagenesis was implemented for pH selectivity optimization. Testing of a small set of designs for binding to the recombinant Her2 ectodomain led to the identification of antigen-binding fragment (Fab) variants with the desired pH-dependent binding behavior. Binding selectivity toward acidic pH was improved by as much as 25-fold relative to the parental bH1-Fab. In vitro experiments on cells expressing intact Her2 confirmed that designed variants formatted as IgG1/k full-size antibodies have high affinity and inhibit the growth of tumor spheroids at a level comparable to that of the benchmark anti-Her2 antibody trastuzumab (Herceptin®) at acidic pH, whereas these effects were significantly reduced at physiological pH. In contrast, both Herceptin and the parental bH1 antibody exhibited strong cell binding and growth inhibition irrespective of pH. This work demonstrates the feasibility of computational optimization of antibodies for selective targeting of the acidic environment such as that found in many solid tumors.
BK polyomavirus—pathogen, paradigm and puzzle

BK virus is a polyomavirus with seroprevalence rates of 80% in adults. Infection is usually acquired during childhood, and the virus is benign or pathologic depending on immune status. The virus reactivates in immunodeficiency states, mostly among transplant (either kidney or bone marrow) recipients. There are approximately 15 000 renal transplants every year in the USA, of which 5-10% develop BK polyomavirus nephropathy; 50-80% of patients who develop nephropathy go on to develop graft failure. BK virus is associated with BK polyomavirus nephropathy, ureteral stenosis, late-onset hemorrhagic cystitis, bladder cancer and other nonlytic large T-expressing carcinomas. The renal spectrum begins with viruria and can end with graft failure. The clinical spectrum and outcomes vary among transplant patients. New noninvasive diagnostic methods, such as urinary polyomavirus Haufen detected by electron microscopy, are currently under study. Treatment is primarily directed at decreasing immunosuppression but may be associated with graft rejection. Repeat transplantation is encouraged as long as viral clearance in plasma prior to transplant is accomplished. There remain no definitive data regarding the utility of transplant nephrectomy.
Evaluation of flow characteristics in an onshore horizontal separator using computational fluid dynamics

Abstract In the petrochemical industry, separation of oil from water is a very important process. Wells produce mixtures of gas, oil, and water which undergo a primary stage of separation inside horizontal gravity separators. The performance of these vessels is evaluated by measuring mean residence time (MRT) and residence time distribution (RTD). Although many researchers studied flow characteristics in horizontal separators, limited number of articles exist that discuss separator MRT and RTD with varying water-cuts. In this article, the authors study an experiment using a horizontal gravity separator by previous researchers and perform computational fluid dynamics (CFD) simulations on the same geometry under similar conditions. The simulation results show qualitative agreement with the experiments by previous researchers. As shown by experiments before, CFD results showed that MRT of the organic phase increased with increase in water-cut. In addition, the RTD characteristics show very similar trends between CFD and experimental results.