cssi/SciSciGPT-SciSciNet huggingface dataset:
Utility of cranial boost in addition to total body irradiation in the treatment of high risk acute lymphoblastic leukemia

Purpose: Total body irradiation (TBI) as part of a conditioning regimen before hematopoietic stem cell transplant (HSCT) is an important component in the management of acute lymphoblastic leukemia (ALL) that has relapsed or has other certain high-risk features. Controversy exists, however, as to whether a cranial boost in addition to TBI is necessary to prevent central nervous system (CNS) recurrences in these high-risk cases. Previous national trials have included a cranial boost in the absence of data to justify its use. Therefore, the aim of this study was to assess risk of CNS recurrence in ALL patients treated with TBI, to identify subsets of these high-risk patients at an increased or decreased risk of CNS recurrence after TBI, and to investigate whether regimens with higher doses of cranial irradiation further reduce the risk of CNS recurrence. Methods and Materials: Charts of 67 consecutively treated patients with ALL who received TBI before HSCT were reviewed. Data including patient demographics, clinical features at presentation, conditioning regimen, donor source, use of a cranial boost, remission stage at transplant, histologic subtype, cytogenetics, and extramedullary site of presentation were retrospectively collected and correlated with the risk of subsequent CNS recurrence. Results: At the time of analysis, 30 (45%) patients were alive with no evidence of disease, 8 (12%) were alive with recurrence of leukemia, 7 (10.5%) had recurrent ALL but with successful salvage, 7 (11%) died subsequent to recurrence, 14 (21%) died from complications related to HCST, and 1 patient was lost to follow-up (1.5%). Of the patients who recurred after HSCT, the relapses were hematologic in 13 (57%), CNS with or without simultaneous marrow involvement in 3 (13%), and other sites in 7 (30%). Forty-one (61%) patients did not receive an extracranial boost of irradiation with TBI. Two of these patients (4.9%) suffered CNS failures compared with 1 of 26 (3.8%) who received a cranial boost ( p = 0.84). None of the 40 patients who presented only with hematologic disease developed a CNS recurrence despite the fact that only 13 of 40 of these patients received a cranial boost after TBI. Cranial boost was therefore not associated with a reduction in CNS recurrence, especially in patients with only hematologic disease at presentation for which there were no failures regardless of the use of additional cranial radiotherapy. Conclusions: Patients who present with hematologic disease only at the time of HSCT have a low risk of CNS recurrence after TBI regardless of the use of a cranial boost, suggesting that a cranial boost may not be necessary in these patients.
Neural Network Interpretation of High Frequency Electromagnetic Ellipticity Data Part I: Understanding the Half-Space and Layered Earth Response

This first part of the two part paper on neural network interpretations of high-frequency electromagnetic ellipticity data examines the sensitivity of ellipticity to changes in resistivity and relative dielectric constant for half-space and two-layer earth models in the frequency range of 31 kHz to 4 MHz. For an 8 m receiver offset we find that the relative dielectric constant cannot be resolved for frequencies below 500 kHz in a half-space. In the range of 500 kHz to 4 MHz, the relative dielectric constant for a half-space cannot be resolved for resistivities below approximately 200 Om. As frequency increases above 4 MHz the dielectric constant can be resolved for increasingly conductive material. A radial basis function neural network is used to analyze large numbers of half-space models to determine the best set of frequencies and receiver offsets to produce the most accurate estimates of resistivity and dielectric constant. For an 8 m receiver offset the ellipticity value over a half-space is never less than -0.447 for a frequency range between 31 kHz and 2 MHz. For two-layer earth models we find that the relative dielectric constant of the second layer cannot be resolved for our frequency range using a modular neuralmore » network. Ellipticities from 2 frequencies are sufficient to determine a resistivity, but increasing the number of ellipticities using different frequencies and more than one separation improves the accuracy of resistivity and relative dielectric constant values. We anticipate a second part of this work which will examine the ellipticity response over three-dimensional targets.« less
Leptin stimulates esophageal adenocarcinoma growth by nonapoptotic mechanisms.

Abstract Background Leptin is a hormone primarily produced by adipocytes and serum leptin is elevated in obese persons. One risk factor associated with adenocarcinoma of the esophagus is obesity. We hypothesized that leptin would have stimulatory effects on esophageal adenocarcinoma and alter apoptosis in vitro. Methods Barrett's esophageal adenocarcinoma cells (BIC-1 and SEG-1) were cultured with human recombinant leptin (80 ng/mL) for 24 hours. Cell growth was determined by MTT assay. Apoptosis and necrosis was measured after 16 hours of treatment with leptin using a Cell Death Kit. Results Exogenous leptin stimulated cell proliferation in both cell lines. No changes in apoptosis or necrosis resulted between control and leptin-treated groups. Conclusions We have shown that leptin increases the proliferation of human esophageal adenocarcinoma, but does not alter cell apoptosis or necrosis. The data suggest that leptin stimulates esophageal adenocarcinoma growth by nonapoptotic mechanisms. Leptin antagonism may have potential efficacy in esophageal cancer therapy.
Regulation of stability of cyclin-dependent kinase CDK11p110 and a caspase-processed form, CDK11p46, by Hsp90

CDK11p110 (cyclin-dependent kinase 11p110, formerly known as PITSLRE) is a member of the CDK superfamily. It associates with cyclin L and is involved in the regulation of transcription and in premRNA splicing. During staurosporine-, Fas- and tumour necrosis factor a-induced apoptosis, CDK11p110, is cleaved by caspases to generate smaller 46-50 kDa proteins containing the catalytic kinase domain. Ectopic expression of the caspase-processed form CDK11p46 induces apoptosis. The mechanisms that regulate activation and stability of CDK11 isoforms are still unclear. In the present study, we demonstrate that in human melanoma cells CDK11p110 and CDK11p46 interact with Hsp90 (heat-shock protein 90) and its co-chaperone cdc37. Furthermore, we show that the treatment of cells with the Hsp90-specific inhibitor geldanamycin leads to ubiquitination and enhanced degradation of both CDK11p110 and CDK11p46 through a proteasome-dependent pathway. We also determined that geldanamycin-triggered degradation of CDK11p46 slows down the progression of apoptosis. These results indicate that Hsp90 and cdc37 stabilize CDK11 kinase, and suggest that this stabilization is crucial for its pro-apoptotic function.
Sulfonylurea Receptors, Ion Channels, and Fruit Flies

Recent studies have identified a high-affinity receptor on the plasma membrane of the β-cell that is specific for all of the sulfonylureas. The most potent secondgeneration drugs, glyburide and glipizide, bind to the receptor and trigger insulin release at nanomolar concentrations. The affinity to the receptor-ligand interaction of all sulfonylureas correlates with their potency as insulin secretagogues, further implicating receptor occupancy with signal transduction. These drugs also inhibit the electrical activity of ATPsensitive K+ channels and K+ efflux through these channels. The channels are also closed by the metabolism of the major insulin secretagogues, glucose and the amino acids, which signal insulin release by increasing the ATP level or the [ATP]-to-[ADP] ratio on the cytoplasmic side of the channel. Based on the channel number and the amount of K+ current they pass, it is possible to calculate that these channels control the resting membrane potential of the β-cell. Inactivation of the ATP-inhibitable K+ channel results in a fall in the resting membrane potential, cell depolarization, and influx of extracellular Ca2+ through the voltage-dependent Ca2+ channel. The rise in intracellular free Ca2+ level triggers exocytosis. Thus, it is now possible to link either a stimulus from the metabolism of insulin secretagogues or the sulfonylureas to ionic and electrical events that elicit insulin release. These data also suggest that the sulfonylurea receptor or a closely associated protein is an ATP-sensitive K+ channel.
A Student’s Guide to and Review of Moment Tensors

A review of a moment tensor for describing a general seismic point source is presented to show a second order moment tensor can be related to simpler seismic source descriptions such as centers of expansion and double couples. A review of literature is followed by detailed algebraic expansions of the moment tensor into isotropic and deviatoric components. Specific numerical examples are provided in the appendices for use in testing algorithms for moment tensor decomposition.
Adding subqueries to MySQL, what does it take to have a decision-support engine?

MySQL is an OLTP system without the ability to handle SQL subqueries. As part of our project in query optimization, we add subquery processing to MySQL through rewriting. First, we incorporate the ability to handle subqueries in the FROM clause; then rewrite queries with subqueries in the WHERE clause by moving the subquery to the FROM clause and introducing suitable conditions to link the subquery and the main query tables. The result is a complete and correct unnesting procedure for SQL queries. The idiosyncrasies of SQL semantics make some rewritings tricky. While optimization issues are not directly addressed, the rewriting opens up the possibility of more efficient query processing in several cases.
Molecular determinants of origin discrimination by Orc1 initiators in archaea

Unlike bacteria, many eukaryotes initiate DNA replication from genomic sites that lack apparent sequence conservation. These loci are identified and bound by the origin recognition complex (ORC), and subsequently activated by a cascade of events that includes recruitment of an additional factor, Cdc6. Archaeal organisms generally possess one or more Orc1/Cdc6 homologs, belonging to the Initiator clade of ATPases associated with various cellular activities (AAA+) superfamily; however, these proteins recognize specific sequences within replication origins. Atomic resolution studies have shown that archaeal Orc1 proteins contact double-stranded DNA through an N-terminal AAA+ domain and a C-terminal winged-helix domain (WHD), but use remarkably few base-specific contacts. To investigate the biochemical effects of these associations, we mutated the DNA-interacting elements of the Orc1-1 and Orc1-3 paralogs from the archaeon Sulfolobus solfataricus, and tested their effect on origin binding and deformation. We find that the AAA+ domain has an unpredicted role in controlling the sequence selectivity of DNA binding, despite an absence of base-specific contacts to this region. Our results show that both the WHD and ATPase region influence origin recognition by Orc1/Cdc6, and suggest that not only DNA sequence, but also local DNA structure help define archaeal initiator binding sites.
Volumetric quantitative computed tomography of the proximal femur: Precision and relation to bone strength

We have developed a three-dimensional computed tomography (CT) scanning and image analysis method for measurement of trabecular and integral bone mineral density (BMD) and geometry in automatically determined femoral-neck and trochanteric subregions of the proximal femur. We measured the correlation of the density and geometry variables to femoral strength assessed in vitro under loading simulating a single-limb condition and a fall to the side. While BMD alone accounted for 48%-77% of the variability in strength for the stance loading configuration, femoral neck cross-sectional area (minCSA) and femoral neck axis length (FNAL) also contributed independently to femoral strength, and a combination of BMD and geometry variables explained 87%-93% of the variance in the data. For the fall loading configuration, trochanteric trabecular BMD alone explained 87% of the variability of strength. The reproducibility in vivo of the technique was assessed in a group of seven postmenopausal women, who underwent repeat scans with repositioning. For trabecular BMD, the precision was 1.1% and 0.6% for the femoral neck and trochanteric subregions, respectively, compared to 3.3% and 1.6% for the corresponding integral envelopes. Thus, trabecular BMD measurements were reproducible and highly correlated to biomechanical strength measurements. These results support further exploration of quantitative CT for assessment of osteoporosis at the proximal femur.
Positive Impact of a Follow-up Phone Call to Community Pharmacies in a Medicaid Drug Utilization Program

OBJECTIVE:To evaluate the impact of including community pharmacists in strategies to alter excessive prescribing of antiulcer medications (AUMs) in a statewide drug utilization review (DUR) program. Mailing educational materials to physicians is a common intervention strategy of retrospective DUR programs. However, pharmacists are typically left out of this process, ignoring a possibly influential healthcare provider.METHODOLOGY:Patients without gastroesophageal reflux disease who received ≥1.0 normalized therapeutic equivalents (e.g., 1.0 NTE = ranitidine 300 mg/d or omeprazole 20 mg/d) for five of six prior months were included. The pharmacists and physicians of these patients were divided into one of three geographically distinct groups: group 1 physicians received mailed materials only (pharmacists were not contacted); group 2 physicians and pharmacists received mailed materials only; and group 3 physicians and pharmacists received mailed materials, and the pharmacists were contaced by phone. Mean NTE...
Growth inhibition of human embryonic and fetal rat bones in organ culture by rubella virus.

Paired organ cultures of metacarpal, metatarsal, and long bones of previable human embryos, of 7 to 12 weeks' gestation, and tibias of 17-day rat fetuses were inoculated with live or ultraviolet-inactivated rubella virus or control fluids and the growth of the bones was measured by increase in wet weight. In several cultures the ability of the human bones to incorporate 35S, a measure of rate of mucopolysaccharide synthesis, was tested. Growth of human and rat bones was retarded in cultures inoculated with live virus but not in cultures inoculated with inactivated virus or control fluids. Mean 35S uptake was increased by approximately 25% in virus-inoculated cultures of bones of 9- to 12-week human embryos. No histological abnormalities were seen. These findings suggest that (1) defective bone growth in congenital rubella is a direct effect of viral infection of bone, (2) a disorder of mucopolysaccharide syntheses may contribute to the osseous lesions that occur in this disease, and (3) organ cultures of human embryonic and fetal rat bones may serve as convenient models for studying the pathogenesis of this virus-induced congenital osteopathy.
A decentralized control mechanism for stream processing networks

Data streaming applications are becoming more and more common due to the rapid development in emerging areas such as sensor networks, multimedia streaming, and on-line data mining, etc. These applications are often running in a decentralized, distributed environment. The requirements for processing large volumes of streaming data at real time have posed many great design challenges. One of the critical issues is to optimize the ongoing resource consumption of multiple, distributed, cooperating processing units. In this paper, we consider a generic model for the general stream data processing systems. We address the resource allocation problem for a collection of processing units so as to maximize the weighted sum of the throughput of different streams. Each processing unit may require multiple input data streams simultaneously and produce one or many valuable output streams. We develop decentralized control mechanisms that maximize the overall system throughput in such data stream processing networks. Performance analysis on the optimality and complexity of these mechanisms are also provided.
Pharmacokinetic/pharmacodynamic studies in drug product development.

In the quest of ways for rationalizing and accelerating drug product development, integrated pharmacokinetic/pharmacodynamic (PK/PD) concepts provide a highly promising tool. PK/PD modeling concepts can be applied in all stages of preclinical and clinical drug development, and their benefits are multifold. At the preclinical stage, potential applications might comprise the evaluation of in vivo potency and intrinsic activity, the identification of bio-/surrogate markers, as well as dosage form and regimen selection and optimization. At the clinical stage, analytical PK/PD applications include characterization of the dose-concentration-effect/toxicity relationship, evaluation of food, age and gender effects, drug/drug and drug/disease interactions, tolerance development, and inter- and intraindividual variability in response. Predictive PK/PD applications can also involve extrapolation from preclinical data, simulation of drug responses, as well as clinical trial forecasting. Rigorous implementation of the PK/PD concepts in drug product development provides a rationale, scientifically based framework for efficient decision making regarding the selection of potential drug candidates, for maximum information gain from the performed experiments and studies, and for conducting fewer, more focused clinical trials with improved efficiency and cost effectiveness. Thus, PK/PD concepts are believed to play a pivotal role in streamlining the drug development process of the future.
Hierarchies of stabilizability preserving linear systems

Hierarchical decompositions of control systems are important for reducing the analysis and design of large scale systems. Such decompositions depend on the notion of abstraction: given a large scale system and a desired property, one tries to extract an abstracted model with equivalent properties, while ignoring details that are irrelevant. Checking the property on the abstraction should be equivalent to checking the property on the original system. In this paper, we focus on large scale linear systems and the property of stabilizability. This results in a hierarchy of linear abstractions that are equivalent from a stabilizability point of view. This is important as high level controller designs are guaranteed to have lower level implementations.
Primary Lesions of the Root of the Tongue

In the assessment of the head and neck, differential diagnoses can be formulated by subdividing the anatomy into spaces along identifiable and logical boundaries. In the oral cavity, the root of the tongue is notably unlike adjacent regions due to structural and tissue-specific differences. The majority of lesions found in the root of the tongue are congenital and benign, representing ectopic tissues of thyroidal, epidermal, dermal, foregut, venous, and lymphatic origin. A greater number of acquired neoplasms and infections are seen in the adjacent sublingual, submandibular, and oropharyngeal regions of the base of the tongue, presumably due to their greater exposure to mucosal surfaces and lymphatic tissues. Many lesions of the root of the tongue have clinical and imaging characteristics that can help narrow the differential diagnosis, and surgical management may be required. Familiarity with these lesions and how they differ from other lesions of the oral cavity and oropharynx can significantly aid in their diagnosis and treatment.
Limitations of perceptual evaluation of speech quality on VoIP systems

This paper presents the shortcomings of perceptual evaluation of speech quality, an objective method of end-to-end voice quality measurement for narrow band telephone networks and speech codec. The main focus of the paper is to discuss practical problems associated with perceptual evaluation of speech quality method in evaluating jitter buffer performance and quality assurance testing of VoIP terminals. The majority of the limitations of PESQ were observed during voice quality tuning experiments for VoIP feature. In our implementation, VoIP link is provided in the Wi-Fi mode of Unlicensed Mobile Access system. AMR NB is the speech codec used in VoIP terminal to compress and decompress speech as preferred by 3GPP standards. The experiments were carried out in controlled lab environment which is well suited for speech quality assessment.
c-axis Josephson Tunneling between YBa 2 Cu 3 O 7-δ and Pb: Direct Evidence for Mixed Order Parameter Symmetry in a High- T c Superconductor

We report a new class of $c$-axis Josephson tunneling experiments in which a conventional superconductor (Pb) is deposited across a single twin boundary of a $\mathrm{YBa}{}_{2}{\mathrm{Cu}}_{3}{\mathrm{O}}_{7\ensuremath{-}\ensuremath{\delta}}$ (YBCO) crystal. We measure the critical current as a function of the magnitude and angle of a magnetic field applied in the plane of the junction. In all samples, we observe a clear experimental signature of an order parameter phase shift across the twin boundary. These results provide strong evidence for mixed $d$- and $s$-wave pairing in YBCO, with a reversal in the sign of the $s$-wave component across the twin boundary.
Reactions of 51V and 27Al with 7–120 MeV α-particles (equilibrium and non-equilibrium statistical analyses)

Abstract Excitation functions for formation of 54 Mn, 52 Mn, 51 Cr, 48 V, 47 Sc, 46 Sc and 44m Sc from 4 He ion bombardment of 51 V and of 22 Na and 24 Na from 4 He ion bombardment of 27 Al are reported. Incident 4 He ion energies varied between 7 and 120 MeV. Mean recoil ranges are reported for all products except 48 Sc. The experimental excitation functions are compared with standard statistical-model calculations, calculations using shell-dependent level densities due to Newton and to Rosenweig, calculations in which compound nucleus and particle angular momenta are coupled using a spin-dependent level density, calculations in which the s-wave approximation is performed and with Griffin's new non-equilibrium statistical model which includes intermediate resonances. No strong evidence is found for shell-structure effects on level densities in the 51 V region. The calculations with spin-dependent level density give satisfactory predictions of the positions and shapes of excitation functions over the energy span for which ranges indicate a compound nucleus mechanism, using a level density parameter of a = 1 8 A. The s-wave approximation is shown to get progressively worse with increasing excitation relative to the experimental results. The extreme high-energy tails shown by many of the excitation functions are reproduced reasonably well with varying admixtures of Griffin's pre-compound particle energy distribution.
Synthesis and Properties of Polyamides, Polyimides, and a Polyamide-Imide Based on Trimethylene Glycol-Di-p-Aminobenzoate

Abstract New polyamides, polyimides, and a polyamide-imide containing ester linkages were prepared by the reaction of trimethylene glycol di-p-aminobenzoate with terephthaloyl chloride, isophthaloyl chloride, adipoyl chloride, pyromellitic dianhydride, benzophenone tetracarboxylic dianhydride, and trimellitoyl chloride. the low temperature solution and interfacial polymerization techniques were utilized to prepare the above-mentioned polymers. the polymers thus prepared were found to be soluble in solvents like DMAC and DMSO and had inherent viscosities in the 0.15-0.60 range. the polyimides prepared formed transparent and flexible films.
Internal Audit, Sarbanes-Oxley And Athletic Departments: An Examination And Recommendations For Reform

During the past fifteen to twenty years the integrity of intercollegiate athletics has been seriously questioned as a result of an increased awareness of problems associated with institutional controls over athletic departments. Limited empirical evidence has been used in the debate regarding institutional controls pertaining to the athletic department. This paper provides empirical evidence regarding the use of the internal audit function as an institutional control. Our findings indicate that while the internal audits of athletic departments are adequate, the communication of these audit results is inadequate. We also discuss the applicability of recent legislation, Sarbanes-Oxley Act of 2002, to colleges and universities. Recommendations to enhance institutional controls regarding intercollegiate athletics are provided.
Wet webs work better: Humidity, supercontraction and the performance of spider orb webs

Like many biomaterials, spider silk responds to water through softening and swelling. Major ampullate silk, the main structural element of most prey capture webs, also shrinks dramatically if unrestrained or develops high tension if restrained, a phenomenon called 'supercontraction'. While supercontraction has been investigated for over 30 years, its consequences for web performance remain controversial. Here, we measured prey capture performance of dry and wet (supercontracted) orb webs of Argiope and Nephila using small wood blocks as prey. Prey capture performance significantly increased at high humidity for Argiope while the improvement was less dramatic for Nephila. This difference is likely due to Argiope silk supercontracting more than Nephila silk. Web deflection, measured as the extension of the web upon prey impact, also increased at high humidity in Argiope, suggesting that silk softening upon supercontraction explains the improved performance of wet webs. These results strongly argue that supercontraction is not detrimental to web performance.
Adaptive Strategy for Air Pollution

The author and his colleagues have pursued a complex path along which they have glimpsed some vistas where investigations might lead to a sharper definition of an adaptive strategy. They have learned that this strategy will involve full participation by government, industry, science, and the public. It was seen that, as the Daddario Subcommittee noted, ''Pollution abatement is affected by so many factors that no one existing institution can have control over all of them.'' The author agrees with the view of this Subcommittee (Daddario, l966) that ''A consortium of public and private interests will be necessary to accomplish what - in very real terms - may be a marked change in the American way of life.''
An accurate low cost method for determining electric motors' efficiency for the purpose of plant energy management

As the cost of energy increases it is increasingly more important to remove inefficient motors from operation. The first step towards achieving this goal is to estimate accurately the existing motors' efficiencies to determine how much saving will be achieved by using more efficient motors. The problem with estimating. the efficiency of motors in the field is the practicality,and cost associated with measuring the output power. This paper describes the results of a very low cost and accurate method for determining the motor efficiency without the need for removing the motors and without the need for measuring the output power or torque. Test results indicate that the novel method has an accuracy of over 99%. As a result of the high accuracy it is possible to estimate the potential savings with great confidence.
An Improved Number-Theoretic Method for Constructing Approximately Universal Codes

Cyclic division algebras have been extensively utilized to design approximately universal codes. Their error probabilities can be intrinsically improved by a small integer non-norm element. This paper proves the insufficiency of existing encoding methods for obtaining the non-norm element 1+i over QAM and the numbers of transmit antennas: {n:8|n}. An improved method is then presented to overcome this difficulty by number theory. As a by-product, we show that 1+i is one of the smallest integer non-norm elements over QAM and n>=5.
Cognitive responses to minority‐ or majority‐based communications: Factors that underlie minority influence

This study is concerned with reactions aroused when a person encounters a pro- or counter-attitudinal message presented by a source of majority, in-group/minority or out-group/minority status. It is proposed that these reactions may help explain the pattern of delayed, indirect, attitude change observed in instances of minority influence, and the direct and immediate changes often found in majority influence. Employing a standard attitude change design, the research demonstrates that participants exposed to a communication attributed to a minority in-group are more prone than those exposed to either a majority or out-group minority to approbate the source's message, elaborate and recall the message's contents, and approbate the communication source. The manner in which this pattern of responses explicates common findings in the minority influence literature is discussed.
Polynomials, Computers, and Kinematics for the 21st Century

A review of the history of kinematics and machine theory shows a direct connection between the ability to solve polynomial systems using algebraic and numerical techniques and the advancement of the analysis and synthesis of machine systems including robots. Research challenges in kinematic synthesis, compliant mechanisms and cable and tensegrity systems show an ever increasing need for the solutions of complex polynomial systems.
Genistein and tyrphostin 47 stimulate CFTR-mediated Cl- secretion in T84 cell monolayers

The involvement of tyrosine phosphorylation in the regulation of epithelial cell Cl- secretion is unknown. Therefore, the purpose of these studies was to determine if tyrosine kinase activation was involved in the regulation of Cl- secretion, using the tyrosine kinase inhibitors, genistein and tyrphostin 47, and human intestinal epithelial cells (T84 cells) as an intestinal Cl- secretory model. Genistein rapidly but reversibly stimulated sustained apical Cl- secretion in monolayers of T84 cells without increasing intracellular cyclic nucleotides or Ca2+ levels. Tyrphostin 47 also stimulated Cl- secretion in T84 monolayers, although it was short-lived. Transfection experiments in 3T3 fibroblasts and IEC-6 intestinal cells utilizing wild-type cystic fibrosis transmembrane conductance regulator (CFTR) showed that genistein and tyrphostin 47 stimulated 125I efflux only in CFTR-transfected cells and not in CFTR-negative cells. Thus genistein- and tyrphostin 47-stimulated Cl- secretion involved CFTR. Genistein also acted synergistically with the Ca(2+)- and protein kinase C-dependent acetylcholine analogue, carbachol, to stimulate Cl- secretion in T84 monolayers. However, the Cl- secretory response to saturating concentrations of the adenosine 3',5'-cyclic monophosphate (cAMP) agonist, forskolin, or the guanosine 3',5'-cyclic monophosphate (cGMP) agonist, Escherichia coli heat-stable enterotoxin, was not further enhanced by genistein. Although the mechanism of activation of Cl- secretion is unclear, these data suggest that tyrosine kinase activity limits basal Cl- secretion in T84 cells and that inhibition of T84 cell tyrosine kinase(s) stimulates apical membrane Cl- secretion, most likely through activation of the CFTR-Cl- channel. Moreover, genistein does not itself act through cAMP or cGMP elevation but appears to share a common Cl- secretory pathway with cyclic nucleotide-dependent agonists, whereas it augments the secretory responses to a Ca(2+)- and protein kinase C-dependent agonist.
Making Medicine Precise and Personalized: What Can We Learn from the Past?

Like the famous dog in the night in Conan-Doyle’s Sherlock Holmes mystery, Silver Blaze, the study by Khazanie et al1 in this issue of Circulation: Heart Failure is most remarkable for what it does not do, rather than what it does do! It represents a well-intentioned attempt to fill a large knowledge gap on the impact of treatment with combined nitrates and hydralazine (ISDN/HYD) on outcomes in patients with heart failure and reduced ejection fractions (HFrEF). This detailed analysis of a heterogeneous observational cohort seems to examine the broader application of the findings from the sole contemporary randomized controlled clinical trial of ISDN/HYD, the African American Heart Failure Trial (A-HeFT).2 Completed 11 years ago, the A-HeFT trial found a 47% reduction in mortality associated with treatment of ISDN/HYD added to neurohormonal blockade.2 Despite this hefty mortality benefit, and a recommendation by the American Heart Association/American College of Cardiology Guidelines for the Management of Heart Failure3 for usage in self-identified blacks with class III–IV HFrEF (class I indication, level of evidence, A), usage of the combination has remained remarkably low and still more remarkably no further clinical trials that would generate data that could be classified as level of evidence A have followed. There are 2 questions prompted by this study: first, does the current analysis help us to better understand the treatment of HF with this drug combination, and second, what do we really need to better understand the use of ISDN/HYD in HFrEF? See Article by Khazanie et al Khazanie et al1 used an observational study design and registry data of patients with HFrEF generated from the American Heart Association’s Get With the Guidelines-HF project linked to Medicare data, to relate all-cause mortality, all-cause readmission to hospital, and cardiovascular readmission to hospital to treatment …
Auditor Sharing in the Mutual Fund Industry: Empirical Evidence on Determinants and Audit Fees

This study examines auditor sharing by mutual fund trusts (collections of mutual funds) and parents (administrators of fund operations). We examine the determinants of auditor sharing and whether an association exists between trust audit fees and auditor sharing. Employing a sample of 2,369 trust-year observations during 2005-2010, we find that auditor sharing is positively associated with proxies for parent accounting capabilities, trustee fund ownership, and the presence of trustees who are retired or former employees of the parent. Conversely, auditor sharing is less likely for trusts with larger boards, longer-tenured trustees, and longer auditor tenure. We find that trusts with shared auditors pay higher audit fees, suggesting either a premium for shared auditors’ specialized knowledge or additional audit effort to compensate for shareholders’ concerns about trustees’ monitoring. Our findings offer insights into the audits of mutual funds and have implications for trustees as they consider auditor appointments.
Does choice of mutation tool matter

Though mutation analysis is the primary means of evaluating the quality of test suites, it suffers from inadequate standardization. Mutation analysis tools vary based on language, when mutants are generated (phase of compilation), and target audience. Mutation tools rarely implement the complete set of operators proposed in the literature and mostly implement at least a few domain-specific mutation operators. Thus different tools may not always agree on the mutant kills of a test suite. Few criteria exist to guide a practitioner in choosing the right tool for either evaluating effectiveness of a test suite or for comparing different testing techniques. We investigate an ensemble of measures for evaluating efficacy of mutants produced by different tools. These include the traditional difficulty of detection, strength of minimal sets, and the diversity of mutants, as well as the information carried by the mutants produced. We find that mutation tools rarely agree. The disagreement between scores can be large, and the variation due to characteristics of the project--even after accounting for difference due to test suites--is a significant factor. However, the mean difference between tools is very small, indicating that no single tool consistently skews mutation scores high or low for all projects. These results suggest that experiments yielding small differences in mutation score, especially using a single tool, or a small number of projects may not be reliable. There is a clear need for greater standardization of mutation analysis. We propose one approach for such a standardization.
Prediabetes Diagnosis and Treatment in Primary Care

Background: The increasing prevalence of diabetes is a major health problem. The detection and treatment of prediabetes can delay the onset of diabetes and presents an important diabetes prevention strategy. Methods: Using data from the 2012 National Ambulatory Medical Care Survey, we studied visits by adults aged ≥45 years without diagnosed diabetes who had an HbA1c test within 90 days of the visit (n = 518 unweighted visits; n = 11,167,004 weighted visits). HbA1c results were categorized into normal, prediabetes, and diabetes, and we examined patient characteristics (age, sex, race, payer type, body mass index) and treatment of prediabetes. Results: Among visiting adults, 54.6% had a normal HbA1c value, 33.6% had prediabetes, and 11.9% had diabetes. Of those patient visits with HbA1c consistent with prediabetes, the number of patients diagnosed with prediabetes was too low for a reliable population estimate. Indication of treatment in the medical record (lifestyle modification counseling and/or metformin) was present in 23.0% of those with diagnosed or undiagnosed prediabetes. The most common treatment was lifestyle modification counseling. Conclusions: Our findings show that there are missed opportunities for diabetes prevention in primary care. Providers need to change their approach to prediabetes and play a more effective role in preventing diabetes.
Shell-Model Spectroscopy of f − p -Shell Nuclei with A ≤ 44

The properties of all $f\ensuremath{-}p$-shell nuclei with $42\ensuremath{\le}A\ensuremath{\le}44$ have been calculated from one consistent shell model. The model space includes all Pauli-allowed states for all configurations of two, three, or four particles distributed among the four $f\ensuremath{-}p$ shell orbits. The model Hamiltonian is a one-body plus two-body operator very similar to the "realistic" effective Hamiltonian of Kuo and Brown. Calculated results are given for excitation energies, single-particle transfer spectroscopic factors, electric-quadrupole and magnetic dipole moments, and $B(M1)$'s and $B(E2)$'s for transitions between low-lying states. The calculated results are in fair agreement with experimental information on these various observables. The results suggest that core-excitation effects are more important in the lower half of the ${f}_{\frac{7}{2}}$ shell than in the $s\ensuremath{-}d$ shell.
Aerodynamic damping derivatives of low aspect ratio wings at low Reynolds numbers

This paper focuses on experimentally measuring the aerodynamic damping stability derivatives of a harmonically oscillating low aspect ratio (LAR) wing at a Reynolds number of 7.5× 10. Recent publications by the authors have demonstrated that the developing tip vortex asymmetry for an LAR wing in sideslip leads to a significant roll moment despite the lack of dihedral, sweep, fuselage interference or vertical tail surfaces, indicating that aerodynamic lateral damping may exist for pure flat plate wings. To date, the dearth of experimental data for LAR damping derivatives has prevented the formation of a dynamic model to be used in solving the equations of motion; to address this, a forced oscillation technique is implemented, described and validated for a wing with an aspect ratio of unity. Damping in yaw and pitch are reported for a variety of incidence angles (α and β) and frequencies of motion (f = [0.5, 1, 1.5, 2, 1.5 and 3]Hz); damping of normal force in pitch (CNF,q) is found to be the most significant derivative by at least an order of magnitude. The damping derivatives converge to near-constant values at mid to high range frequencies for all incidence angles, suggesting that constant values of the derivatives may potentially be implemented in linearized forms of the equations of motion during flight dynamics simulations.
FRI0489 Improvement of Lower Esophageal Sphincter Function in Systemic Sclerosis After Long Term Administration of Buspirone, An Orally Available 5-HT1A Receptor Agonist: A 4-Week Pilot Study

Background Esophagus is commonly affected in Systemic Sclerosis (SSc) and esophageal function is compromised in about 75% of patients. Previous studies have shown that buspirone, an orally available 5-HT 1 A receptor agonist, enhances esophageal motility in healthy volunteers (1). Recently, we observed that a single dose of buspirone (10mg) improves acutely lower esophageal sphincter (LES) function in patients with SSc and esophageal involvement (2). Objectives To test the hypothesis that buspirone has a sustained beneficial effect on esophageal dysfunction and related symptoms in SSc patients in an open pilot study. Methods Consecutive, consenting symptomatic SSc patients (n=22, aged 51.3±11.8 years and disease duration 8.7±6.7 of years, 19 women, 8 with diffuse SSc, all receiving proton pump inhibitors) completed a 4-week treatment with buspirone (10mg, twice daily). Concomitant therapies remained unchanged. Supra- and infra-aortic coronal diameters of esophagus were measured in computing tomography (CT) performed within the previous 3 months. Possible changes in LES resting pressure, integrated relaxation pressure, amplitude, duration, and velocity of distal esophageal body contractions were examined by high resolution manometry (HRM) at baseline and at 4 weeks. Changes in the severity of esophageal symptoms using a 0-100 VAS scale score were recorded, in parallel. Results CT evaluations revealed that 12 patients had supra-, and 21 had infra-aortic esophagus dilatation (mean diameters 12.4±5.3 and 22.5±11.0 mm, respectively, normal Conclusions Administration of buspirone may exert a beneficial effect on impaired LES function and improve esophageal symptoms in patients with SSc, suggesting a role of 5-HT1A receptor-mediated interactions. Placebo-controlled studies to confirm that buspirone is of therapeutic value are warranted. References Di Stefano et al. Effect of Buspirone, a 5-HT1A receptor agonist on esophageal motility in healthy volunteers. Dis esophagus, 2012;5:470-6 S. Panopoulos et al. Beneficial effect of acute administration of buspirone on lower esophageal sphincter function in patients with systemic sclerosis. United European Gastroenterol J, 2015 in press Disclosure of Interest None declared
On Railroad Tank Car Puncture Performance: Part II — Estimating Metrics

This paper is the second in a two-part series on the puncture performance of railroad tank cars carrying hazardous materials in the event of an accident. Various metrics are often mentioned in the open literature to characterize the structural performance of tank cars under accident loading conditions. One of the consequences in terms of structural damage to the tank during accidents is puncture. This two-part series of papers focuses on four metrics to quantify the performance of tank cars against the threat of puncture: (1) speed, (2) force, (3) energy, and (4) conditional probability of release.In Part I, generalized tank car impact scenarios were illustrated. Particular focus is given to the generalized shell impact scenario because performance-based requirements for shell puncture resistance are being considered by the regulatory agencies in United States and Canada. Definitions for the four performance metrics were given. Physical and mathematical relationships among these metrics were outlined. Strengths and limitations of these performance metrics were discussed.In this paper (Part II), the multi-disciplinary approach to develop engineering tools to estimate the performance metrics is described. The complementary connection between testing and modeling is emphasized. Puncture performance metrics, which were estimated from other sources, are compared for different tank car designs. These comparisons are presented to interpret the metrics from a probabilistic point of view. In addition, sensitivity of the metrics to the operational and design factors is examined qualitatively.
Revised Thomas-Fermi approximation for singular potentials

Approximations for the many-fermion free-energy density functional that include the Thomas-Fermi (TF) form for the noninteracting part lead to singular densities for singular external potentials (e.g., attractive Coulomb). This limitation of the TF approximation is addressed here by a formal map of the exact Euler equation for the density onto an equivalent TF form characterized by a modified Kohn-Sham potential. It is shown to be a ``regularized'' version of the Kohn-Sham potential, tempered by convolution with a finite-temperature response function. The resulting density is nonsingular, with the equilibrium properties obtained from the total free-energy functional evaluated at this density. This new representation is formally exact. Approximate expressions for the regularized potential are given to leading order in a nonlocality parameter, and the limiting behavior at high and low temperatures is described. The noninteracting part of the free energy in this approximation is the usual Thomas-Fermi functional. These results generalize and extend to finite temperatures the ground-state regularization by R. G. Parr and S. Ghosh [Proc. Natl. Acad. Sci. U.S.A. 83, 3577 (1986)] and by L. R. Pratt, G. G. Hoffman, and R. A. Harris [J. Chem. Phys. 88, 1818 (1988)] and formally systematize the finite-temperature regularization given by the latter authors.
Early diagnosis and prognosis in congenital hypothyroidism.

Congenital hypothyroidism is a preventable cause of mental retardation and in most instances can be diagnosed in the first six months of life.The pessimism often expressed concerning the prognosis in these cases has led to an erroneous belief that early diagnosis and treatment are relatively unimportant. To obtain the best possible results with therapy, diagnosis must be early and treatment must be adequate.Insufficient emphasis has been placed on several early symptoms and signs which, though not specific for congenital hypothyroidism, should arouse suspicion of the condition. Laboratory determinations to confirm the diagnosis of congenital hypothyroidism are generally available.
France: More reforms on the way

As French researchers take to the streets to demonstrate against the government's plans for reforms to the national research council (CNRS), the minister for research and education, Claude AllA¨gre, has met his critics head on with proposals for yet more reforms. He wants to force all CNRS researchers to spend periods teaching in universities and working in industry. Researchers have objected, however, saying that the quality of their research is likely to suffer.
The link between soda intake and asthma: science points to the high-fructose corn syrup, not the preservatives: a commentary.

Recent research conducted by investigators at the National Center for Chronic Disease Prevention and Health Promotion—a division of the US Centers for Disease Control and Prevention (CDC)—found that 'Regular-Soda Intake, Independent of Weight Status, is Associated with Asthma among US High School Students.' On the basis of their review of prior studies, researchers hypothesized that the association may be due to high intake of sodium benzoate, a commonly used preservative in US soft drinks. But a closer look at these prior research studies suggests that there is no strong scientific evidence that the preservatives in US soft drinks are associated with asthma. Importantly, other recent research suggests that the association may be with the unpaired (excess free) fructose in high fructose corn syrup.