cssi/SciSciGPT-SciSciNet huggingface dataset:
Adherence, Persistence of Use, and Costs Associated With Second-Generation Antipsychotics for Bipolar Disorder

Objective:A retrospective study using Medicaid claims identified patients with bipolar disorder for whom oral second-generation antipsychotics were prescribed and compared rates of adherence, persistence of use, and costs across five groups of patients taking aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone. Methods:Medicaid claims data for 2,446 bipolar patients were analyzed from eight states. The 18-month observation period included the six months before and the 12 months after the index prescription date. Adherence was defined as a medication possession ratio >80%. Persistence of use was measured by the number of days of medication therapy before a 30-day gap. Mental health-related prescription costs, total prescription costs, total mental health-related costs, and total costs were assessed. Ziprasidone was the comparator. Results:Clinically recommended doses of second-generation antipsychotic medications were prescribed for 45% of the patients (N=1,102). Of these, 58% (N=642 of 1,102...
Leukocyte depletion filters: a comparison of efficiency.

Four commercially available leukocyte depletion filters were evaluated using a flow cytometric technique to determine the efficiency of each type of filter. The Sepacell R-500A® and the PALL RC50® were the most efficient in leukocyte depletion having a mean depletion percentage of 99.3% and 99.5%, respectively. The PALL RC100® which is used for two units also had a 99.3% depletion with the first unit but with the second unit the depletion dropped to 94.2%. The Imugard IG-500® had a 97.3% depletion. Red cell recovery ranged from 87.4% for the PALL RC50® to 92.2% for the Sepacell R-500A®.
A novel method for cultivating soil bacteria

Ribosomal RNA analyses of soil microbial communities consistently indicate that the majority of microorganisms in soil have never been cultivated or described in the laboratory. It has been suggested that microorganisms fail to grow in traditional culture media because the media fails to simulate the organisms' natural environment. We designed a unique culture technique that can cultivate an average of 40% and as high as 90% of the bacteria present in a soil sample. The 16S rDNA of 50 of these isolates were PCR amplified, sequenced, and analyzed. Nineteen, 26, 2 and 3 of the isolates were affiliated with the phyla Actinobacteria, Proteobacteria, Firmicutes, and Bacteroidetes, respectively. Ten isolates possessed less than 98% sequence similarity to any previously characterized organism.
Policing Development: Urban Renewal as Neo-liberal Security Strategy

This paper examines the evolution of policing in the townships of Cape Town in the context of a neo-liberalising city. Policing is situated in relation to the shifting meaning of security, the city’s emphasis on economic growth and attempts to develop the townships through a law-enforcement-driven urban renewal process. Research conducted in the city suggests that current approaches to urban renewal risk exacerbating social instability by reproducing aggressive forms of policing associated with the apartheid era. Further, as crime is framed as a security threat because of the danger it is thought to pose to market-led growth, urban governance in the townships increasingly takes on the character of a containment strategy. Current security ideology and policing practice create an expanding law enforcement web in which millions of poor residents are caught annually and which appears to undermine the very developmental goals used to justify its expansion.
Predicted driver response to a cordon toll around Fort Myers Beach, Florida

Fort Myers Beach experiences severe traffic congestion from January to April when many travelers visit the island. Throughout this four-month period, drivers routinely wait 30 to 45 minutes in congestion stretching as far as 1.2 miles in order to cross Matanzas Pass Bridge at the north end of Estero Island. Cordon tolls have been suggested as a possible method of traffic congestion mitigation. This paper examines the results from a voluntary survey conducted in March of 2003 in order to predict driver response to this potential toll. The findings indicate that a cordon toll would remove 6.6 percent to 31.3 percent of current bridge traffic at toll levels ranging from $1 to $4. This does not take into account any latent demand that is likely to occur due to this predicted traffic reduction. These traffic diversion estimates are reasonable when compared to other cordon tolls outside of the United States.
Development and validation of the cough severity index: a severity index for chronic cough related to the upper airway.

Objectives/hypothesis To develop and validate a cough severity index (CSI) which quantifies patients' symptoms associated with upper airway chronic cough and to provide a tool for treatment outcome measures. Methods Two hundred patients who had a complaint of chronic cough and/or dyspnea were given a 49- item questionnaire developed through a clinical consensus of the most common symptoms of chronic cough of upper airway origin. The instrument was reduced to 10 questions using statistical methodology. Fifty subsequent patients were given the CSI to measure test-retest reliability at two different moments in time. Twenty healthy controls (HC) were given the instrument to obtain validity. An additional 95 participants provided pre- and posttreatment outcomes using the CSI. Results Principle Component Analysis (PCA) revealed a single factor with the original 49 questions. A combination of PCA, rank-ordering item-total correlation and communality, as well as clinical consensus further reduced the questionnaire to 10 items. Internal consistency of the CSI was 0.97. Test-retest reliability was r = 0.83. An r = 0.60 for divergent validity between the CSI and the Cough-Specific Quality-of-Life Questionnaire (CQLQ) demonstrated two fairly separate instruments, although both measured cough. Mann-Whitney test was significant between symptomatic patients and healthy controls (P Conclusion The CSI is a short, simple instrument that can be used in the clinical setting to quantify a patient's symptoms of chronic cough of upper airway origin. It represents a statistically reliable, valid, and clinically relevant instrument that can be used to measure treatment outcomes for chronic cough.
Growth of single crystal cuprous oxide

Abstract Single crystals of Cu 2 O in sizes up to 1 cm dia and several cm long have been grown by a floating zone technique in a controlled oxygen pressure of 0.4 Toor. Total cation impurities in the crystals were determined to be
Initial puffing behaviors and subjective responses differ between an electronic nicotine delivery system and traditional cigarettes

Background Electronic nicotine delivery systems (ENDS) present an emerging issue for tobacco control and data on product use behaviors are limited.
A general adaptive control structure

A general adaptive control structure is given which provides flexibility in defining the plant and controller parameterizations and the goal of the adaptation. A special case is conventional model-reference adaptive control with independent uncertainty in all of the plant transfer function coefficients, although a much broader class of systems can be represented. A single derivation of the error equations for parameter estimation purposes is provided and is valid for the entire class of systems. The form of the resulting error equations is appropriate for application of common parameter estimation techniques. >
A descriptive overview of treatment modalities in federally funded drug abuse treatment programs.

This study presents descriptive information on treatment modality units of drug treatment clinics participating in the Client Oriented Data Acquisition Process (CODAP) and the National Drug Abuse Treatment Utilization Survey (NDATUS) data systems. The units described were (1) drug-free outpatient-nonopiate orientation (DFO-N), (2) drug-free outpatient-opiate orientation (DFO-O), (3) methadone maintenance (MM), (4) drug-free residential (DFR), (5) detoxification-outpatient (DTOP), (6) detoxification-inpatient (DTIP), and (7) day care (DC). The major focus was on the first five units since there were relatively few DTIP and DC units which met the criteria for inclusion in the study. The study was based on 1,077 units. These units represented 73,856 admissions in the first half of 1977. The different types of modality units were compared on client flow information, client aggregate background characteristics, client aggregate drug use at admission, client aggregate outcomes at discharge (drug use, employment...
Effects of low dose metformin in adolescents with type I diabetes mellitus: a randomized, double-blinded placebo-controlled study.

Background Insulin resistance increases during adolescence in those with type 1 diabetes (T1DM), complicating glycemic control and potentially increasing cardiovascular disease (CVD) risk. Metformin, typically used in type 2 diabetes (T2DM), is a possible adjunct therapy in T1DM to help improve glycemic control and insulin sensitivity.
Kaposi's Sarcoma-Associated Herpesvirus-Encoded LANA Contributes to Viral Latent Replication by Activating Phosphorylation of Survivin

UNLABELLED Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus casually linked to Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). Previously, we showed that LANA encoded by KSHV upregulates expression of survivin, a member of the inhibitor of apoptosis (IAP) family. This leads to an increase in the rate of cell proliferation of KSHV-infected B cells. LANA is required for tethering of the KSHV episome to the host chromosomes and efficiently segregates the viral genomes into dividing tumor cells. Here we show that LANA interacts with Aurora kinase B (AK-B) and induces phosphorylation of survivin at residue T34. Phosphorylation of survivin specifically on residue T34 enhances the activity of p300 and inhibits the activity of histone deacetylase 1 (HDAC-1), which then leads to an increase in acetylation of histone H3 on the viral genome. Phosphorylation of survivin specifically on residue T34 upregulates the activities of histone acetyltransferases and deacetylases, which then leads to an increase in viral copy number in KSHV-infected B cells. This results in a boost of KSHV replication in latently infected B-lymphoma cells. The studies showed that LANA can also function to regulate viral replication prior to mitosis of the latently infected cells, suggesting that LANA possesses a novel role in regulating KSHV replication in infected B cells. IMPORTANCE This work represents a report of KSHV latent protein LANA and its interactions with AK-B leading to induction of phosphorylation of the oncoprotein survivin at residue T34. Phosphorylation of survivin specifically on residue T34 upregulates the activities of histone acetyltransferases and deacetylases. This leads to an increase in viral copy number in KSHV-infected B cells. These studies support a role for LANA in regulating KSHV replication through posttranslation modification in KSHV-infected B cells.
Multiplicative BRST renormalization of the SU(2) Higgs model.

We reformulate the proof of the renormalization of a spontaneously broken gauge theory by multiplicatively renormalizing the vacuum expectation value of the Higgs field in the SU(2) Higgs model.
Power system for new MBARI ROV

MBARI is developing a remotely operated vehicle (ROV) capable of 4000 m depth and designed exclusively for support of oceanographic research. Performance and operational requirements led to an all electric design for the basic core vehicle. The vehicle's electric power system, described in this paper, delivers 15 kW to the various onboard loads, and allocates power using preset priorities when demand exceeds supply. Features of the power system include ground fault and overcurrent detection, switch isolation of all loads, motor regeneration control, and limited dual redundancy. A novel transformer cooling scheme minimizes acoustic emissions from the main power transformer. >
Alaskan Earthquake of 1964 and Chilean Earthquake of 1960: Implications for Arc Tectonics

The 1964 Alaskan earthquake (Ms ≈ 8.4) involved a segment of the eastern Aleutian arc 800 gm long; the 1960 Chilean earthquake sequence (Ms ≈ 8.5) affected roughly 100 km of the southern Peru-Chile arc. These two major events are strikingly similar in that (1) seismicity was shallow (<70 km), the earthquake focal regions and most of the associated tectonic deformation being between the oceanic trenches and volcanic chains of the two arcs; (2) regional vertical displacements were characterized by broad asymmetric downwarps elongate parallel to the arcs with flanking zones of marked uplift on the seaward sides and minor, possibly local, uplift on the landward sides; and (3) horizontal displacements, where determined by retriangulation, involved systematic shifts in a generally seaward direction and transverse tensile strains across the zones of subsidence. Surface displacements and seismicity for both events are compatible with dislocation models involving predominantly dip-slip movement of 20 meters or more on major complex thrust faults (megathrusts) inclined at average angles of about 9° beneath the eastern Aleutian arc and perhaps 20° beneath the Peru-Chile arc. The thrust-fault mechanism deduced for both the Alaskan and Chilean earthquakes is broadly consistent with the concept that the sectors of the Pacific rim in which they occurred are major zones of convergence along which the oceanic plates progressively underthrust the less mobile America plate. Directions of convergence between lithospheric plates at these arcs as deduced primarily from paleomagnetic data are in reasonably good agreement with the observed earthquake-related deformation; the deduced rates of convergence, however, appear to be too high in the eastern Aleutian arc and too low in the southern Peru-Chile arc. Despite gross similarities in tectonic setting and the present style of earthquake-related deformation, the geologies of the continental margins in the eastern Aleutian arc and southern Peru-Chile arc differ significantly. This difference suggests that Mesozoic and Cenozoic sediments and volcanic rocks conveyed into the eastern Aleutian trench have progressively accreted to the Alaskan continental margin, whereas most or all of the material carried into the southern Peru-Chile trench has disappeared beneath the Chilean continental margin.
CONSTANTS AND CORRELATIONS IN THE COLEMAN CALCULUS

The argument used by Coleman to claim the vanishing of the cosmological constant requires a prescription for comparing different zeroes. The predicted low energy physics will differ depending upon the particular regulator used to make this comparison. We also elucidate the interpretation of the measure by calculating some correlation functions.
Information, Resources and Transaction Cost Economics: The Effects of Informal Network Centrality on Teams and Team Performance

This study presents a theoretical framework for studying the effects of extra-group social networks on teams. Building on a transaction cost economics framework, an individual’s extra-group friendship network centrality is proposed to relate to communication network centrality. This is because the individual will utilize the network to establish an informational hierarchy thereby reducing the transaction costs associated with finding information and resources. Through this network the individual will be perceived as a higher team contributor. The team effects of extra-group network centrality are proposed as higher team performance and innovativeness. Future research opportunities and implications for practical use are presented.
An intra-annular 'hemispherical' annuloplasty frame for aortic valve repair.

Background and aim of the study: A ‘Hemispherical’ model of aortic valve geometry was developed in which normal human cadaveric aortic valve leaflets could be represented as three hemispheres nested within a cylindrical aorta. By mathematically describing the junction between the leaflets and aorta, the normal three-dimensional annular geometry of the aortic valve could be defined. In this study, a prototype annuloplasty frame based on this model was tested as a repair device in isolated porcine aortic root preparations. Methods: Eight isolated porcine aortic roots were perfused with water at a constant pressure of 75 mmHg, and valve leakage was measured before and after the vertical incision of one to three sub-commissural areas to create valve incompetence. Annuloplasty frames then were sutured directly to the valve annuli, and the degree of leakage re-determined. The model predicted that the leaflet free-edge length could be used to define the valve diameter necessary to create competence, and this interaction was tested by varying frame size within the protocol. Postrepair leaflet function also was evaluated using highspeed video. Differences were assessed using a twotailed paired t-test. Results: All eight normal porcine aortic valves had negligible baseline leak. With sub-commissural incision, the mean (±SD) regurgitant volume was increased to 522 ± 378 ml/min. After annuloplasty frame insertion, the measured leak decreased to 52 ± 40 ml/min (p = 0.004). The best results were obtained with a frame diameter 5-6 mm smaller than the leaflet free-edge length. Data recorded using highspeed video suggested a normal dynamic valve function after frame insertion. Conclusion: A three-dimensional ‘Hemispherical’ intra-annular annuloplasty frame was developed for aortic valve repair. Insertion of the frame into the disrupted porcine valve annuli routinely and effectively restored valve competence. These positive initial results support the continued testing and application of this aortic annuloplasty device.
Temporal Structure and Trends of Parasites and Pathologies in U.S. Oysters and Mussels: 16 Years of Mussel Watch

ABSTRACT Parasites and pathologies of oysters and mussels were sampled yearly from 1995 to 2010 from the Gulf of Maine to Alaska and the Great Lakes as part of the National Oceanic and Atmospheric Administration Status and Trends Mussel Watch Program. Sentinel bivalves included mytilid mussels, dreissenid mussels, and oysters. This comprehensive dataset provides a unique opportunity to examine long-term temporal dynamics of parasites, pathologies, and physiological indices of these sentinel bivalves. Temporal dynamics fell into a few clear categories. Significant differences between years occurred commonly for parasites, pathologies, and physiological indices; the absence of significant change over time was more noteworthy. In a few cases, these trends were characterized by multiyear increases or decreases in value within the time series. Such behavior might be produced by a multiyear cycle and, in fact, such behavior was much more common along the southern East Coast, the Gulf Coast, and Southern Califor...
Clinical Supervision in the Addictions Field: A Case Example of Effective Gatekeeping

ABSTRACTClinical supervision is essential to the development of competent, ethical, and professional practice among substance abuse counselors. A vital role of supervisors is to act as gatekeepers responsible for protecting clients and the profession. Many supervisors in the addictions field lack formal education and training in supervision and, hence, could benefit from information and guidance in performing challenging supervisory tasks such as gatekeeping. This article focuses on the key elements of effective supervision, particularly with regard to supervisee assessment, remediation, and dismissal, all while considering the common pitfalls experience and encountered by those receiving supervision. These processes are presented and illustrated through a case example as a means of providing practical guidance to those who supervise current and aspiring substance abuse counselors.
Wide Variation in the Diffusion of a New Technology: Practice-Based Trends in Intensity-Modulated Radiation Therapy (IMRT) Use in the State of Michigan, With Implications for IMRT Use Nationally

IMRT use grew significantly across the state of Michigan over time, with four-fold variability among centers, which was related to facility characteristics.
Effectiveness of health education on drinking-water fluorosis in Zhejiang province in 2011

Objective To evaluate the effectiveness of health education on endemic fluorosis prevention and control.Methods A uniform questionnaire was applied to target population on health education of endemic fluorosis.Results The awareness rate of school students improved from 67.24% to 98.45%,got an increase of 31.15% averagely(χ2=640.94,P0.01);The awareness rate of housewives improved from 67.89% to 97.60%,got an increase of 31.30% averagely(χ2=296.86,P0.01).Conclusion The awareness rates of endemic fluorosis prevention and control among students and housewives were remarkably increased after implementing the health education projects.The sense of self protection from public was strengthened.
Aftershock sequence simulations using synthetic earthquakes and rate-state seismicity formulation

We use an efficient earthquake simulator that incorporates rate-state constitutive properties and uses boundary element method to discretize the fault surfaces, to generate the synthetic earthquakes in the fault system. Rate-and-state seismicity equation is subsequently employed to calculate the seismicity rate in a region of interest using the Coulomb stress transfer from the main shocks in the fault system. The Coulomb stress transfer is obtained by resolving the induced stresses due to the fault patch slips onto the optimal-oriented fault planes. The example results show that immediately after a main shock the aftershocks are concentrated in the vicinity of the rupture area due to positive stress transfers and then disperse away into the surrounding region toward the background rate distribution. The number of aftershocks near the rupture region is found to decay with time as Omori aftershock decay law predicts. The example results demonstrate that the rate-and-state fault system earthquake simulator and the seismicity equations based on the rate-state friction nucleation of earthquake are well posited to characterize the aftershock distribution in regional assessments of earthquake probabilities.
Investigating Virtual World Dynamics Using AST: A Research Agenda

The purpose of this paper is to develop a research agenda that will assist in deepening our understanding of the social dynamics of virtual worlds. Virtual worlds are computer-based simulated worlds that are populated by human-controlled avatars, or graphical representations of individuals. These worlds are real-time, interactive societies based on three-dimensional Internet technology. Interaction in virtual worlds has developed a set of behaviors, which are unique to each world.
Exercise as an adjunctive treatment for cannabis use disorder.

ABSTRACTBackground: Despite cannabis being the most widely used illicit substance in the United States, individuals diagnosed with cannabis use disorder (CUD) have few well-researched, affordable treatment options available to them. Although found to be effective for improving treatment outcomes in other drug populations, exercise is an affordable and highly accessible treatment approach that has not been routinely investigated in cannabis users. Objectives: The aim of this paper is to inform the topic regarding exercise’s potential as an adjunctive treatment for individuals with CUD. Methods: We reviewed the evidence surrounding cannabis use and its current treatment in the United States, explored the rationale for including exercise in the treatment of substance use disorders (SUDs), and in particular, proposed a biological mechanism (i.e., endocannabinoids (eCBs)) that should be examined when utilizing exercise for the treatment of CUD. Results: Cannabis use is widespread and increasing in the United S...
Comprehensiveness of Outcome Reporting in Studies of Articular Cartilage Defects of the Knee.

Purpose To assess the comprehensiveness of outcome reporting after treatment of focal articular cartilage defects in the knee. Methods A systematic review of literature published over the past 5 years (October 2010 to October 2015) in 5 high-impact orthopaedic journals was completed to identify all recent clinical studies tracking outcomes after surgery for focal articular cartilage defects in the knee. A metric reporting score was calculated for each study, according to reporting of 6 cardinal domains: pain, satisfaction, osteoarthritis progression, subjective knee function, objective knee function, and patient-reported outcomes. Results Of the 122 studies included for review, 117 (96%) tracked patient-reported outcomes during follow-up. Nearly two-thirds of studies (63%) monitored progression of osteoarthritis at follow-up. Fewer than half of studies (39%) specifically monitored pain outcomes in patients. One-third of studies (30%) tracked patient satisfaction. Only 21% of studies monitored subjective knee function using proxies such as return to play, and only 17% of studies reported on objective knee function during return visits to the clinic. The average metric reporting score of all studies was 2.6, and nearly half of studies (48%) reported on only 1 or 2 domains of interest. Conclusions There is substantial variability in outcome reporting after cartilage surgery in high-impact orthopaedic journals. Furthermore, most studies do not comprehensively track outcomes across domains. Both factors hinder comparison of results across studies. Future outcome metrics should focus on patient-centered factors to improve both accuracy of results reporting and standardization across studies. Level of Evidence Level IV, systematic review of Level I-IV studies.
Emergency Department Management of Suspected Calf-Vein Deep Venous Thrombosis: A Diagnostic Algorithm.

Introduction: Unilateral leg swelling with suspicion of deep venous thrombosis (DVT) is a common emergency department (ED) presentation. Proximal DVT (thrombus in the popliteal or femoral veins) can usually be diagnosed and treated at the initial ED encounter. When proximal DVT has been ruled out, isolated calf-vein deep venous thrombosis (IC-DVT) often remains a consideration. The current standard for the diagnosis of IC-DVT is whole-leg vascular duplex ultrasonography (WLUS), a test that is unavailable in many hospitals outside normal business hours. When WLUS is not available from the ED, recommendations for managing suspected IC-DVT vary. The objective is to use current evidence and recommendations to (1) propose a diagnostic algorithm for ICDVTwhen definitive testing (WLUS) is unavailable; and (2) summarize the controversy surrounding IC-DVTtreatment. Discussion: The Figure combines D-dimer testing with serial CUS or a single deferred FLUS for the diagnosis of IC-DVT. Such an algorithm has the potential to safely direct the management of suspected IC-DVT when definitive testing is unavailable. Whether or not to treat diagnosed IC-DVT remains widely debated and awaiting further evidence. Conclusion: When IC-DVT is not ruled out in the ED, the suggested algorithm, although not prospectively validated by a controlled study, offers an approach to diagnosis that is consistent with current data and recommendations. When IC-DVT is diagnosed, current references suggest that a decision betwee nanticoagulation and continued follow-up outpatient testing can be based on shared decision-making. The risks of proximal progression and life-threatening embolization should be balanced against the generally more benign natural history of such thrombi, and an individual patient’s risk factors for both thrombus propagation and complications of anticoagulation.
Binding of Telomestatin to a Telomeric G-Quadruplex DNA Probed by All-Atom Molecular Dynamics Simulations with Explicit Solvent

Telomestatin, a natural product isolated from Streptomyces anulatus, stabilizes telomeric DNA G-quadruplexes. Treatment with this ligand induces apoptosis of various cancer cells with a relatively low effect on somatic cells because of its high selectivity toward G-quadruplex over duplex DNA. A high-resolution structure of a G-quadruplex in complex with telomestatin does not yet exist because of its low solubility, and the binding nature of this ligand remains elusive. In this study, we utilized molecular binding simulations and MMGBSA binding energy analysis to decipher the nature of the binding of telomestatin to a telomeric G-quadruplex. We identified three major binding poses: bottom intercalation, top stacking, and groove binding. The top stacking mode resembles the pose observed in an NMR complex of the same G-quadruplex with the telomestatin analogue L2H. The bottom intercalation and groove binding poses were not observed in the previous studies of L2H. The bottom intercalation mode exhibited the m...
Energy efficiency limits of logic and memory

We address practical limits of energy efficiency scaling for logic and memory. Scaling of logic will end with unreliable operation, making computers probabilistic as a side effect. The errors can be corrected or tolerated, but overhead will increase with further scaling. We address the tradeoff between scaling and error correction that yields minimum energy per operation, finding new error correction methods with energy consumption limits about 2× below current approaches. The maximum energy efficiency for memory depends on several other factors. Adiabatic and reversible methods applied to logic have promise, but overheads have precluded practical use. However, the regular array structure of memory arrays tends to reduce overhead and makes adiabatic memory a viable option. This paper reports an adiabatic memory that has been tested at about 85× improvement over standard designs for energy efficiency. Combining these approaches could set energy efficiency expectations for processor-in-memory computing systems.
Complex Dynamic Systems Approaches to Educational Research

THIS SPECIAL ISSUE seeks to engender new understanding of educational phenomena by bringing together empirical examples of research grounded conceptually, methodologically, and analytically in Comp...
Abstract 1795: Potent anti-tumor activity of talazoparib (BMN673) in combination with radiation for squamous cell carcinoma of the head and neck

Background: Squamous cell carcinoma of the head and neck (SCCHN) is a radiation-sensitive disease. Standard frontline treatment of locally advanced SCCHN entails concurrent chemotherapy with radiation. Treatment of relapsed or metastatic SCCHN often utilizes re-irradiation to the primary tumor for local control. However, there is no standard systemic treatment for relapsed or metastatic SCCHN in combination with radiation. Many SCCHN tumors display alterations in expression of DNA repair genes. To this end, we evaluated the effect of talazoparib (BMN-673), a potent poly-ADP ribose polymerase (PARP) inhibitor, alone or in combination with radiation, in vitro and in vivo. Methods: The 50% inhibitory concentration (IC50) of talazoparib was determined in 30 SCCHN cell lines in vitro. Using clonogenic assays, the effects of 0, 10 or 100nM talazoparib, alone or in combination with a single fraction of 4Gray radiation were determined in four cell lines (two sensitive and two resistant to talazoparib). Effects on DNA damage of talazoparib, alone or in combination with radiation were also determined by flow cytometric analysis of Gamma-H2A.X. Finally, the FaDu head and neck cells were implanted onto female J/nude. After tumors were established, mice were treated with talazoparib for 5 days and a total of 20 Gray radiation, alone or in combination, and effects on body weight and tumor size were determined. Results: Among 30 SCCHN cell lines treated with talazoparib alone, 18 displayed sensitivity with 50% inhibitory concentration (IC50) of 1μM or less. In clonogenic assays, addition of radiation to BMN673 in two sensitive (UMSCC-6 and UMSCC-38) and two resistant (UMSCC-5 and UMSCC-12) cell lines resulted in synergistic cytotoxicity at doses ranging from 0-100nM BMN673. Increased gamma-H2A.X was seen when cell lines were treated with talazoparib, radiation, or the combination, compared to controls. Combining radiation with talazoparib resulted in a transient decrease in body weight in J/nude mice, but resulted in statistically significant and prolonged decrease in tumor volume. These anti-tumor effects were sustained out to 60 days post inoculation. Conclusions: The PARP inhibitor talazoparib with radiation synergistically inhibited tumor growth in vitro and in vivo in SCCHN cell lines. Further evaluation of this combination is underway. Citation Format: Deborah JL Wong, David D. Shin, Josephine Ratikan, Meenal Chalukya, Kanthinh Manivong, Leonard Post, Dorthe Schaue, Richard S. Finn, Yuqiao (Jerry) Shen, William McBride, Dennis J. Slamon. Potent anti-tumor activity of talazoparib (BMN673) in combination with radiation for squamous cell carcinoma of the head and neck. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1795. doi:10.1158/1538-7445.AM2015-1795
Paclitaxel-induced increase in mitochondrial volume mediates dysregulation of intracellular Ca2+ in putative nociceptive glabrous skin neurons from the rat.

We have recently demonstrated that in a rat model of chemotherapy-induced peripheral neuropathy (CIPN), there is a significant decrease in the duration of the depolarization-evoked Ca2+ transient in small diameter, IB4+, and capsaicin-responsive neurons innervating the glabrous skin of the hindpaw. This change was specific to the transient duration and significantly smaller if not undetectable in neurons innervating the dorsal skin of the hindpaw or the skin of the inner thigh. Given the importance of mitochondria in intracellular Ca2+ regulation and the findings of chemotherapy-associated increase in mitotoxicity along the sensory neuron axons, we hypothesized that CIPN is due to both increases and decreases in mitochondria function, with changes manifest in distinct subpopulations of afferents. To begin to test this hypothesis, we used confocal microscopy and Ca2+ imaging in combination with pharmacological manipulations to study paclitaxel-induced changes in retrograde tracer-labeled neurons from naive, vehicle-treated, and paclitaxel-treated rats. Paclitaxel treatment was not associated with decreased mitochondrial membrane potential or increased superoxide levels in the somata of putative nociceptive glabrous skin neurons. However, it was associated with significant increases in the relative contribution of mitochondria to the control of the evoked Ca2+ transient duration in putative nociceptive glabrous skin neurons, as well as increases in mitotracker and Tom20 staining which reflected an increase in mitochondrial volume. Furthermore, the relative contribution of the sarco-endoplasmic reticulum Ca2+ ATPase to the regulation of the duration of the depolarization evoked Ca2+ transient was also increased in this subpopulation of neurons from paclitaxel treated rats. Our results indicate that the paclitaxel-induced decrease in the duration of the evoked Ca2+ transient is due to both direct and indirect influences of mitochondria. It remains to be determined if and how these changes contribute to the manifestation of CIPN.
Prostate-specific mRNA detection in whole blood as an analytically validated prognostic biomarker for patients with castration-resistant prostate cancer (CRPC).

45 Background: To estimate the association between molecular biomarkers and outcomes, robust assays are needed before qualification in prospective trials. Although tumor specific transcripts detected in blood by PCR have been associated with outcome, an analytically validated PCR platform enabling detection of CTC-associated transcripts in clinical settings remains to be identified. Here we explore detecting a panel of prostate specific transcripts in conjunction with conventional markers in CRPC. Methods: Blood was collected from 97 patients with progressive CRPC in PAXgene tubes (2.5 ml) for total RNA extraction. Five genes expressed in prostate but not in nucleated blood cells were analyzed by primer-specific RT-PCR. Fluidigm Dynamic Array platform was analytically validated for KLK3, KLK2, HOXB13, GHRL2 and FOXA1 assays. Each PCR-reaction was run in 6 replicates, detection thresholds for each gene were chosen by ROC analysis of an independent set of 56 CRPC patients versus 51 healthy volunteers, and r...
The Plant Orthology Browser: An Orthology and Gene-Order Visualizer for Plant Comparative Genomics

Worldwide genome sequencing efforts for plants with medium and large genomes require identification and visualization of orthologous genes, while their syntenic conservation becomes the pinnacle of any comparative and functional genomics study. Using gene models for 20 fully sequenced plant genomes, including model organisms and staple crops such as Coss., (L.) Heynh., (L.) Beauv., turnip ( L.), barley ( L.), rice ( L.), sorghum [ (L.) Moench], wheat ( L.), red wild einkorn ( Tumanian ex Gandilyan), and maize ( L.), we computationally predicted 1,021,611 orthologs using stringent sequence similarity criteria. For each pair of plant species, we determined sets of conserved synteny blocks using strand orientation and physical mapping. Gene ontology (GO) annotations are added for each gene. Plant Orthology Browser (POB) includes three interconnected modules: (i) a gene-order visualization module implementing an interactive environment for exploration of gene order between any pair of chromosomes in two plant species, (ii) a synteny visualization module providing unique interactive dot plot representations of orthologous genes between a pair of chromosomes in two distinct plant species, and (iii) a search module that interconnects all modules via free-text search capability with online as-you-type suggestions and highlighting that allows exploration of the underlining information without constraint of interface-dependent search fields. The POB is a web-based orthology and annotation visualization tool, which currently supports 20 completely sequenced plant species with considerably large genomes and offers intuitive and highly interactive pairwise comparison and visualization of genomic traits via gene orthology.
On Automatic Question Answering Using Efficient Primal-Dual Models

Automatic question answering has been a major problem in natural language processing since the early days of research in the field. Given a large dataset of question-answer pairs, the problem can be tackled using text matching in two steps: find a set of similar questions to a given query from the dataset and then provide an answer to the query by evaluating the answers stored in the dataset for those questions. In this paper, we treat the text matching problem as an instance of the inexact graph matching problem and propose an efficient approximate matching scheme. We utilize the well known quadratic optimization problem metric labeling as the framework of graph matching. In order to solve the text matching, we first embed the sentences given in natural language into a weighted directed graph. Next, we present a primal-dual approximation algorithm for the linear programming relaxation of the metric labeling problem to match text graphs. We demonstrate the utility of our approach on a question answering task over a large dataset which involves matching of questions as well as plain text.
SCAT Mobile Data Collection - California's Ongoing Experience

The California Department of Fish and Wildlife, Office of Spill Prevention and Response (OSPR) since its inception in 1991 has been collecting SCAT (Shoreline Cleanup Assessment Technique) data. OS...
Lifetime and universal distribution of seed runaway electrons

The lifetime of pre-existing runaway electrons determines how likely the runaways will undergo avalanche multiplication. We estimate the lifetime of runaway electrons via kinetic analysis. We show that the rate of runaway decay depends on the combination of parameters α≡(Z+1)/τ¯rad (where τ¯rad is the synchrotron timescale normalized to the collisional timescale and Z is the ion charge) compared to the electric field. We identify two cases where the decay rate is slow enough to enable a quasi-steady shape of the runaway distribution function. This distribution and its lifetime represent the eigenfunction and the lowest eigenvalue of the kinetic equation. In one case, α≪1: the field required to sustain the pre-existing runaways is barely larger than the Connor-Hastie critical value. In the same manner as by Aleynikov and Breizman [Phys. Rev. Lett. 114, 155001 (2015)], we solve the kinetic equation perturbatively but extend the work to demonstrate that the lifetime grows exponentially with the field at a ra...
Development of Activity-Based Chemical Probes for Human Sirtuins.

Sirtuins consume stoichiometric amounts of nicotinamide adenine dinucleotide (NAD+) to remove an acetyl group from lysine residues. These enzymes have been implicated in regulating various cellular events and have also been suggested to mediate the beneficial effects of calorie restriction (CR). However, controversies on sirtuin biology also peaked during the past few years because of conflicting results from different research groups. This is partly because these enzymes have been discovered recently and the intricate interaction loops between sirtuins and other proteins make the characterization of them extremely difficult. Current molecular biology and proteomics techniques report protein abundance rather than active sirtuin content. Innovative chemical tools that can directly probe the functional state of sirtuins are desperately needed. We have obtained a set of powerful activity-based chemical probes that are capable of assessing the active content of sirtuins in model systems. These probes consist ...
Exploring the influence of community volunteerism on adult L2 learners’ willingness to communicate

Abstract One of the biggest challenges for second language (L2) learners is finding the confidence to communicate with native speakers, and the construct of willingness to communicate (WTC) is often at the center of this challenge. The goal of this longitudinal case study was to examine the impact of a supportive communicative environment on adult L2 learners' WTC. Participants included four Chinese university students studying in the US, two of whom volunteered in a kindergarten classroom for five weeks (30 h) while all four continued university ESL instruction. All students were pre- and posttested using a WTC scale, and their language use tracked through weekly logs. Quantitative analyses of the WTC scales, logs, and adapted COLT observations as well as analysis of the target participants' coded exit journal excerpts revealed an improvement in the students’ WTC extending to their L2 use outside kindergarten (3.3–20.0% increase in overall WTC), and substantial growth in social language use, with the kindergarten environment cited as the primary catalyst for change. Results support the importance of nonthreatening volunteer opportunities as vehicles for increasing WTC as a supplement to traditional instruction.
Accounting for the various contributions to pyroelectricity in lead zirconate titanate thin films

An understanding of the pyroelectric coefficient and particularly its relationship with the applied electric field is critical to predicting the device performance for infrared imaging, energy harvesting, and solid-state cooling devices. In this work, we compare direct measurements of the pyroelectric effect under pulsed heating to the indirect extraction of the pyroelectric coefficient from adiabatic hysteresis loops and predictions from Landau-Devonshire theory for PbZr0.52Ti0.48O3 (PZT 52/48) on platinized silicon substrates. The differences between these measurements are explained through a series of careful measurements that quantify the magnitude and direction of the secondary and field-induced pyroelectric effects. The indirect measurement is shown to be up to 25% of the direct measurement at high fields, while the direct measurements and theoretical predictions converge at high fields as the film approaches a mono-domain state. These measurements highlight the importance of directly measuring the ...
Design and analysis of a dual-input single-resonant tank LLC converter for PV applications

This paper proposes a dual-input LLC resonant converter that interfaces with two PV panels. The topology is a dual half-bridge LLC circuit with four active switches. This topology allows the two sources to share the same resonant tank for transferring energy to the load without the need for additional circuit components. A phase-shift pulse width modulation (PWM) control is employed to implement independent maximum power point tracking (MPPT) for each PV panel. Independent MPPT is achieved by varying the PWM phase shift of each source. Zero-voltage-switching (ZVS) is realized in all switches over the entire range of source voltage and load conditions. In addition, voltage stress across switches does not exceed the input PV voltage. A 500-W prototype was built to demonstrate the performance of the proposed topology. The input voltage range was selected between 25 V to 50 V with an output voltage regulated at 440 V DC. Experimental results show that the proposed converter can achieve the peak efficiency of 95.8% while maintaining a wide input voltage range and implementing MPPT for each PV panel.
Depressive Subtypes Defined by Response to Pharmacotherapy

Unipolar, bipolar, atypical, and psychotic depressions are discussed in terms of patients’ responses to tricyclic antidepressants, lithium, monoamine oxidase inhibitors, and antipsychotic agents, respectively. Acute and prophylactive effects of the medications are discussed where data are available.
Consistency and Change in Temperament

In this chapter, we address two central issues in the study of development: change and consistency. The longitudinal research methodology is best suited to address the nature of temperament with advancement in age during childhood, as it allows examination of both the consistency of the individual’s rank position compared to others (i.e., stability) as well as change/consistency in the dimensions of temperament across individuals as a function of age (i.e., continuity). As noted in chapter 1, a particularly unique aspect of the Fullerton Longitudinal Study (FLS) is the frequency and continuity of temperament assessments; 10 assessment waves were conducted at designated and regular intervals from infancy (1.5 years) through adolescence (16 years). The temperament measures used during each developmental era and dimensions assessed on each measure are summarized in Table 3.01.
Biophotonics: Harnessing Light for Biology and Medicine

Biophotonics is a new multidisciplinary frontier which utilizes light–matter interactions for bioimaging, sensing diagnostics and light activated as well as optically tracked therapies. This article is focused on use of nonlinear optical processes for bio imaging as well as for light induced therapy. Examples illustrating recent achievements in these research fields are provided from our work at the Institute for Lasers, Photonics and Biophotonics. We present our progress in multimodal bioimaging using a combination of nonlinear optical phenomena such as two-photon induced fluorescence, coherent anti-Stokes Raman scattering (CARS), second harmonic generation and sum frequency generation. Synergy of the techniques employing these phenomena in a multimodal imaging approach enables chemically selective imaging and probing of the local macro molecular content in biological specimens. We also provide examples of two-photon induced fluorescence microscopy and two-photon induced therapy using specially designed molecules and nanoparticles.