cssi/SciSciGPT-SciSciNet huggingface dataset:
SU‐E‐T‐87: Commissioning of a 50‐100 KV X‐Ray Unit for Skin Cancer Treatment

Purpose: To provide dosimetric data for a 50–100 kV X‐ray unit for skin cancer treatments. Discrepancy of measurements using two different types of chambers was investigated. Methods: Two superficial treatment units SRT‐100 from Sensus were studied. The unit has three energies: 50, 70 and 100 kV x‐ray and five cones from 1.5 to 5 cm diameters. Data collected during commission were: (a) HVL, (b) dose rate, cGy/minute at 15 cm target‐to‐skin distance in air under a 5 cm cone, and (c) cone size factors. A Farmer‐type thimble chamber, PTW 23333, and a thin‐window parallel plate (PP) ion‐chamber, PTW23342 were used. Measured data were compared with vendor provided values. Results: Average HVL values for 50, 70 and 100 kV of the two units were 0.52, 1.15 and 2.2 mm Al, respectively. HVL values were 5–9 % lower if the thimble chamber was used for 70 and 100 kV. Dose rate were found 3–4% lower with the thimble chamber compared with the value from the PP chamber. As expected, the two type chambers measured the same cone size factors, from 0.97 to 1.0 for 1.5 to 5 cm cone. When the same PP chamber was used for another SRT‐100 unit with a similar HVL value, the dose rates were found with a 2–9% difference for 50–100 kV between the two units. Dosimetric data from vendor should be used as a reference only. Conclusions: Data obtained from a thimble chamber underestimated the dose by 3–4% compared with measured by a PP chamber. Dose rate from two identical treatment units can differ by 9%. Commissioning of a soft X‐ray machine should be done with proper dosimetric methods.
Should Dihydropyridines Be Used as First-Line Drugs in the Treatment of Hypertension?: The Con Side

THE GOALin the treatment of hypertension is to reduce the increased risk of cardiovascular complications—stroke, acute myocardial infarction (MI), congestive heart failure, and renal dysfunction—not just to lower an elevated blood pressure (BP). Reliance on a surrogate outcome in the evaluation of a new intervention may lead to inferences that are incorrect in terms of the overall benefit to patients. For example, potent drugs typically have multiple effects, some beneficial and others perhaps harmful. The sum of these effects determines the overall clinical or health benefit to the patient. Recently, several examples of the disparity between surrogate efficacy and health efficacy for cardiovascular interventions have emerged. Antiarrhythmic treatment with encainide and flecainide effectively suppressed ventricular premature contractions after MI, but they also increased the risk of sudden arrhythmic death through a proarrhythmic action. 1 Although newer inotropic agents improved hemodynamics and symptoms in patients with congestive heart
Oxidative Dimerization of Methane Over Sodium-Promoted Calcium Oxides

Sodium-promoted calcium oxides are active and selective catalysts for the partial oxidation of methane to ethane and ethylene using molecular oxygen as an oxidant. In a conventional fixed-bed flow reactor, operating at atmospheric pressure, a 45% C2 (sum of ethane and ethylene) selectivity was achieved to a 33% methane conversion over 2.0 g of the catalyst at 725°C with a gas mixture of CH4/O2 = 2. The other products were CO and CO2. EPR results indicate that [Na+O-] centers in Na/CaO are responsible for the catalytic production of CH3 from methane through hydrogen-atom abstraction. These CH3 radicals dimerize, primarily in the gas-phase, to form C2H6 which further oxidizes to C2H4. Increasing temperatures reverse the gas-phase equilibrium CH3+O2 ⇌ CH3O2 to produce more CH3 and increase the C2 selectivity. The CH3O2 eventually is converted to carbon oxides under the reaction conditions employed, therefore increasing O2 pressures decrease the C2 selectivity. There is evidence that CH3O2 in the presence of C2H6 initiates a chain reaction which enhances the methane conversion. The addition of Na to CaO also reduces the surface area of the catalysts, thus minimizing a nonselective oxidation pathway via surface methoxide intermediates.
Evapotranspiration by Eichhornia crassipes (Mart.) Solms and Typha latifolia L.

Abstract Evapotranspiration ( E ) by Eichhornia crassipes (Mart.) Solms and Typha latifolia L. growing in 5.77-m 2 tanks and evaporation ( E 0 ) from control tanks were measured over a 6-month period at Auburn, Alabama (32.5° N latitude). The E / E 0 ratios for E. crassipes and T. latifolia were 1.31–2.52 (mean = 1.75) and 1.05–2.50 (mean = 1.62), respectively. Evidence is presented which demonstrates that E / E 0 values were similar to those which occur in natural populations of the two species. Both plant characteristics and meteorological variables influenced evapotranspiration. Equations for estimating evapotranspiration were E Ec = (4.19 + (7.32 × 10 −8 ) S 2 + (0.00035 × 10 −3 ) H 2 ) D R 2 = 0.92 E Tl = (1.43 + (2.79 × 10 −15 ) S 4 + 1.44 L ) D R 2 = 0.93 where E Ec and E Tl are monthly water loss in mm/month for E. crassipes and T. latifolia , respectively; S is the average daily solar radiation in W m −2 integrated over 24 h for the month; H is plant height in m; L is leaf area index (dimensionless); and D is the number of days in the month.
Kinetic behaviour and allosteric regulation of human deoxycytidylate deaminase derived from leukemic cells.

Deoxycytidylate deaminase has been highly purified (1232-fold) from human leukemia CCRF-CEM cells. The native molecular weight of the enzyme is 108 000 and subunit molecular weight 50 500, suggesting that the native enzyme exists as a dimer. The enzyme exhibits a sigmoidal initial velocity vs substrate concentration curve and is regulated by allosteric effectors, dCTP and TTP. The curve relating substrate concentration to initial velocity was changed from a sigmoidal shape to a hyperbolic one by the activator dCTP, while the inhibitor TTP increased the sigmoidicity of the curve. The molecular weight of deoxycytidylate deaminase was unchanged in the presence of allosteric effectors, indicating that aggregation-disaggregation is not the basis of regulation. Deoxycytidylate deaminase exhibited the greatest affinity for the substrate dCMP, with lesser affinity for ara-CMP, and least affinity for CMP. Ara-CMP was an effective substrate in the presence of dCTP concentrations exceeding 4 μM. These data indicate that human neoplastic cell deoxycytidylate deaminase is a highly regulated allosteric enzyme, which is likely to have a significant influence on cellular dUMP, dCTP and TTP pools. These findings further suggest, that the enzyme through its influence on dUMP levels is likely to modulate the biochemical effects of pyrimidine antimetabolites active against the thymidylate synthetase reaction and in the presence of elevated dCTP pools will promote deamination of ara-CMP to the inactive ara-UMP.
Theoretical analysis of eletrochemical reactions involving two successive one-electron transfers with dimerization of intermediate-applicaiton to NAD+/NADH redox couple

Abstract The mechanism of an electrode reaction consisting of two successive one-electron (1 e ) transfer steps, coupled with dimerization of the intermediate product under conditions of steady-state convective diffusion, has been theoretically analyzed for the situation where the second electron-transfer step is accompanied or preceded by protonation of the intermediate product. The resulting relationship have been used to examine the electrochemical behavior of the biologically important NAD + /NADH redox couple. The model, which seems best to fit the experimental data involves: (a) 1 e reduction NAD + to NAD, which can dimerize, followed at more negative potential by concerted protonation and 1 e reduction of NAD to NADH, where the proton donor is an HB species such as H 3 O + or NH 4 + ; (b) an apparently single-step 2 e oxidation of NADH to NAD + . Possible causes for the differences in electrochemical NAD + reduction and NADH oxidation are considered in terms of the implications of theory.
Electrocardiographic "Peri-Infarction Block" A Clinical and Pathologic Correlation

Detailed analysis for the presence and type of heart disease was made in 96 deceased patients who had electrocardiographic "peri-infarction block." Evidence for disease of the left ventricle was found in 80 per cent of these patients. Left ventricular hypertrophy and diffuse scarring of the left ventricle were the most common abnormalities on pathologic examination. Definite myocardial infarction was found in only 12 of the 55 patients (22 per cent) subjected to postmortem examination. Electrocardiographic "peri-infarction block" was therefore not specific for myocardial infarction although it was often associated with it. Use of the term should be restricted to left intraventricular conduction defect of the "peri-infarction block type." In spite of the nonspecificity of this type of intraventricular conduction defect, it can be a useful clinical sign. If chronic obstructive airway disease and emphysema can be excluded, the presence of some type of left ventricular disease is almost assured.
Inhibition of Aflatoxin B1 Production by Aspergillus parasiticus Using Nonaflatoxigenic Strains: Role of Vegetative Compatibility

Abstract The effect of vegetative compatibility on the inhibition of aflatoxin B1 production by Aspergillus parasiticus was examined using nonaflatoxigenic strains. Nonaflatoxigenic white-conidial mutants were paired in different proportions on an agar medium with aflatoxigenic yellow-conidial mutants belonging to the same isolate, to the same vegetative compatibility group but with the original wild types differing in phenotype, and to different vegetative compatibility groups. Heterokaryosis as a result of hyphal anastomosis was detected by the presence of conidiogenous structures with a mixture of green and parental (white and/or yellow) chains of conidia. Sclerotium production (number and dry weight) was significantly greater in pairings of compatible strains that formed heterokaryons than in pairings of strains from different vegetative compatibility groups. In contrast, there were no consistent differences in aflatoxin B1 inhibition by nonaflatoxigenic strains in pairings from the same vegetative compatibility group and pairings from different groups. Therefore, the composition of vegetative compatibility groups within a population may be of minor importance in predicting the efficacy of a particular nonaflatoxigenic strain for the biological control of aflatoxin contamination of crops.
The Interpersonal Competence Instrument for Nurses

A new tool, the Interpersonal Competence Instrument for Nurses, was evaluated for content validity and readability. Evaluators consisted of a panel of 10 nursing experts. The instrument measures four categories of the patient-nurse interaction: translating, getting to know you, establishing trust, and going the extra mile. The content validity indexes (CVI) for 14 of 15 behaviors within the four categories rangedfrom .8 to 1.0 and are considered to have content validity. The CVIfor the 15th behavior, clicking, was calculated as. 7, and, thus, was modified. The CVIfor the entire instrument of 111 items was determined to be .84. Readability analyzed with the SMOGformula established a grade level of 8.09. Additional psychometric testing of the tool is in progress. Internal consistency reliability is being evaluated through the use of coefficient alpha and item analysis. Construct validity is being estimated through the experimental approach. The internal structure of the instrument is being assessed throughf...
Institutional Review Boards

Institutional Review Boards play an extremely important role in protecting human research subjects in the United States. As we will see, they are a recent result of increased interest in human rights. The designation, “Institutional Review Board” (IRB), was not in general use until the mid-1970s, although such groups have been required since 1966 for research funded by the Public Health Service. Earlier groups of professionals performing the functions of IRBs were simply referred to as committees under various names (e.g., review committee, ethics committee).
Metabolic tumor burden predicts for disease progression and death in lung cancer.

Purpose In lung cancer, stage is an important prognostic factor for disease progression and survival. However, stage may be simply a surrogate for underlying tumor burden. Our purpose was to assess the prognostic value of tumor burden measured by 18 F-fluorodeoxyglucose–positron emission tomography (FDG-PET) imaging. Patients and Methods We identified 19 patients with lung cancer who had staging PET-CT scans before any therapy, and adequate follow-up (complete to time of progression for 18, and death for 15 of 19). Metabolically active tumor regions were segmented on pretreatment PET scans semi-automatically using custom software. We determined the relationship between times to progression (TTP) and death (OS) and two PET parameters: total metabolic tumor volume (MTV), and standardized uptake value (SUV). Results The estimated median TTP and OS for the cohort were 9.3 months and 14.8 months. On multivariate Cox proportional hazards regression analysis, an increase in MTV of 25 ml (difference between the 75th and 25th percentiles) was associated with increased hazard of progression and of death (5.4-fold and 7.6-fold), statistically significant ( p = 0.0014 and p = 0.001) after controlling for stage, treatment intent (definitive or palliative), age, Karnofsky performance status, and weight loss. We did not find a significant relationship between SUV and TTP or OS. Conclusions In this study, high tumor burden assessed by PET MTV is an independent poor prognostic feature in lung cancer, promising for stratifying patients in randomized trials and ultimately for selecting risk-adapted therapies. These results will need to be validated in larger cohorts with longer follow-up, and evaluated prospectively.
Two-phase mini-separator to separate alpha-fetoProtein from fibrinogen and Immunoglobulin

This paper reports a two-phase mini-column separator that depletes Immunoglobulin G (IgG) and separates α-fetoProtein (AFP) and fibrinogen. A mixture of IgG, fibrinogen, and AFP goes through the two-phase separator, where IgG is depleted by an affinity mini-column using Protein A/G agarose beads in the first phase. In the second phase, AFP is separated from fibrinogen by Size Exclusion Chromatography (SEC). The IgG depletion and SEC separation results are confirmed by evaluating fluorescent intensity of the eluents. Red (IgG), green (AFP), and blue (fibrinogen) intensities show that over 99.5% of IgG is depleted and, in 10 min, the second phase SEC mini-column separates AFP (1 µg/mL) from fibrinogen-rich solution (10 µg/mL) with 2.78 resolution and 0.0056 mm plate height.
A Fortunate Life in Physical Chemistry

This article contains a very personal account of my evolution as a physical chemist/chemical physicist, with commentary on some of the influences on that evolution and summary accounts of research accomplishments in four of the subject areas that have engaged my attention, ranging from isolated molecules to condensed matter.
High-resolution atmospheric observations by the Mars Odyssey Thermal Emission Imaging System

High-resolution observations of atmospheric phenomena by the Mars Odyssey Thermal Emission Imaging System (THEMIS) during its first mapping year are presented. An atmospheric campaign was implemented on the basis of previous spacecraft imaging. This campaign, however, proved of limited success. This appears to be due to the late local time of the Odyssey orbit (the locations of activity at 4–6 p.m. appear to be different from those at 2 p.m.). Ironically, images targeting the surface were more useful for study of the atmosphere than those images specifically targeting atmospheric features. While many previously recognized features were found, novel THEMIS observations included persistent clouds in the southern polar layered deposits, dust or condensate plumes on the northern polar layered deposits, dust plumes as constituent parts of local dust storms, and mesospheric clouds. The former two features tend to be aligned parallel and normal to polar troughs, respectively, suggesting a wind system directed normal to troughs and radially outward from the center of the polar deposits. This is consistent with katabatic drainage of air off the polar deposits, analogous to flow off Antarctica. The observation of dust lifting plumes at unprecedented resolution associated with local dust storms not only demonstrates the importance of mean wind stresses (as opposed to dust devils) in initiation of dust storms, but is also seen to be morphologically identical to dust lifting in terrestrial dust storms. As Odyssey moves to earlier local times, we suggest that the atmospheric campaign from the first mapping year be repeated.
Marginality, Modernity, and Anxiety in Indochinese Refugees:

Indochinese refugees to the United States face major psychological adjustments to a modern, industrialized society. This exploratory study measures marginality, modernity, and anxiety in a group of Vietnamese and Laotian refugees. As predicted, the refugees score higher in marginality and anxiety and lower in modernity than a random sample of Americans. A negative relationship is found for marginality and anxiety for the Laotians, and no significant relationship between these two variables is found for the Vietnamese. On the other hand, a positive relationship between anxiety and marginality was found for the American sample. These findings question the relevance of the concept of marginality when studying the psychological states of refugees.
Putative Transposases Conserved in Exiguobacterium Isolates from Ancient Siberian Permafrost and from Contemporary Surface Habitats

Gram-positive bacteria of the genus Exiguobacterium have been repeatedly isolated from Siberian permafrost ranging in age from 20,000 to 2 to 3 million years and have been sporadically recovered from markedly diverse habitats, including microbial mats in Lake Fryxell (Antarctic), surface water, and food-processing environments. However, there is currently no information on genomic diversity of this microorganism or on the physiological strategies that have allowed its survival under prolonged freezing in the permafrost. Analysis of the genome sequence of the most ancient available Exiguobacterium isolate (Exiguobacterium sp. strain 255-15, from 2 to 3 million-year-old Siberian permafrost) revealed numerous putative transposase sequences, primarily of the IS200/IS605, IS30, and IS3 families, with four transposase families identified. Several of the transposase genes appeared to be part of insertion sequences. Southern blots with different transposase probes yielded high-resolution genomic fingerprints which differentiated the different permafrost isolates from each other and from the Exiguobacterium spp. type strains which have been derived from diverse surface habitats. Each of the Exiguobacterium sp. strain 255-15 transposases that were used as probes had highly conserved homologs in the genome of other Exiguobacterium strains, both from permafrost and from modern sites. These findings suggest that, prior to their entrapment in permafrost, Exiguobacterium isolates had acquired transposases and that conserved transposases are present in Exiguobacterium spp., which now can be isolated from various modern surface habitats.
Investigation of Polymer Stabilized Liquid Crystal Formation Using Fluorinated and Aliphatic Monoacrylates

This study focuses on the photo-polymerization of a fluorinated monoacrylate monomer and aliphatic analog within a room temperature smectic liquid crystal (LC) in an effort to understand how factors such as LC order, monomer segregation, and monomer chemical structure affects the polymerization mechanism in polymer stabilized liquid crystalline systems (PSLC). Specifically, a fluorinated monoacrylate exhibits significantly enhanced polymerization rates when compared to an aliphatic monoacrylate. Moreover, this rate enhancement is particularly pronounced in the smectic phase of the LC, where the fluorinated monoacrylate displays a polymerization rate in the smectic phase that is over three times faster than the aliphatic monoacrylate in the smectic phase. Also the fluorinated monoacrylate exhibits enhanced segregation between the smectic layers of the LC both before and after polymerization, whereas the aliphatic monoacrylate phase separates during polymerization. The results of this study demonstrate how changes in the monomer chemical structure (i.e. fluorination) can significantly impact the polymerization mechanism and segregation in polymer stabilized systems. This study also offers the potential to further the understanding of tailoring these unique systems for display applications.
Electrodeposition and characterization of very thin film II–VI compounds for novel superlattice solar cells

Thin films of lead telluride (PbTe) and zinc telluride (ZnTe) have been electrodeposited on indium tin oxide (ITO)-coated glass substrates. The electrochemical deposition procedures for fabricating these films are described. The as-deposited films have been characterized by scanning electron microscopy, electron dispersive spectroscopy, and optical absorption spectrometry. The results of this structural and optical characterization are presented in this paper.
Factors affecting sperm recovery rates and survival after centrifugation of equine semen.

Conventional centrifugation protocols result in important sperm losses during removal of the supernatant. In this study, the effect of centrifugation force (400 or 900 × g), duration (5 or 10 min), and column height (20 or 40 mL; Experiment 1); sperm concentration (25, 50, and 100 × 106/mL; Experiment 2), and centrifugation medium (EZ-Mixin CST [Animal Reproduction Systems, Chino, CA, USA], INRA96 [IMV Technologies, Maple Grove, MN, USA], or VMDZ [Partnar Animal Health, Port Huron, MI, USA]; Experiment 3) on sperm recovery and survival after centrifugation and cooling and storage were evaluated. Overall, sperm survival was not affected by the combination of centrifugation protocol and cooling. Total sperm yield was highest after centrifugation for 10 min at 400 × g in 20-mL columns (95.6 ± 5%, mean ± SD) or 900 × g in 20-mL (99.2 ± 0.8%) or 40-mL (91.4 ± 4.5%) columns, and at 900 × g for 5 min in 20-mL columns (93.8 ± 8.9%; P < 0.0001). Total (TMY) and progressively motile sperm yield followed a similar pattern (P < 0.0001). Sperm yields were not significantly different among samples centrifuged at various sperm concentrations. However, centrifugation at 100 × 106/mL resulted in significantly lower total sperm yield (83.8 ± 10.7%) and TMY (81.7 ± 6.8%) compared with noncentrifuged semen. Centrifugation in VMDZ resulted in significantly lower TMY (69.3 ± 22.6%), progressively motile sperm yield (63.5 ± 18.2%), viable yield (60.9 ± 36.5%), and survival of progressively motile sperm after cooling (21 ± 10.8%) compared with noncentrifuged semen. In conclusion, centrifuging volumes of ≤ 20 mL minimized sperm losses with conventional protocols. With 40-mL columns, it may be recommended to increase the centrifugal force to 900 × g for 10 min and dilute the semen to a sperm concentration of 25 to 50 × 106/mL in a milk- or fractionated milk-based medium. The semen extender VMDZ did not seem well suited for centrifugation of equine semen.
Immortal Activated Human Hepatic Stellate Cells Generated by Ectopic Telomerase Expression

Telomere shortening controls the entry of cells into senescence. Functional expression of the telomerase catalytic subunit (human telomerase reverse transcriptase or hTERT) stabilizes telomere length and extends the life span of various normal human cells. Our aim was to assess the role of telomerase activity and telomere maintenance in regulating the proliferation of activated human hepatic stellate cells (HSCs), to establish an immortal human HSC cell line. Human HSCs were isolated from surgical specimens of normal liver and infected with a retrovirus expressing hTERT. Ectopic expression of hTERT reconstituted telomerase activity and maintained telomere length in human HSCs. Control human HSCs, which were either not infected or infected with a retroviral vector containing only the neomycin resistance gene, showed no detectable telomerase activity and had slightly shortened telomeres. These telomerase-negative HSCs entered a nondividing state after about 9 to 15 passages and senesced. In contrast, telomerase-positive HSCs to date have undergone 69 passages. Telomerase-positive HSCs did not undergo oncogenic transformation and exhibit morphologic and functional characteristics of activated HSCs. Microarray and RT-PCR analysis showed that mRNA expression patterns in telomerase-positive HSCs are very similar to those in activated human HSCs. Plating telomerase-positive HSCs on a basement membrane-like matrix reverts them toward a more quiescent phenotype. In conclusion, introduction of hTERT into activated human HSCs immortalizes them and maintains their activated phenotype. This newly developed cell line will be a useful tool to study the cell biology of human HSCs in culture.
Prediction of seminal vesicle invasion in prostate cancer: incremental value of adding endorectal MR imaging to the Kattan nomogram.

Purpose: To retrospectively determine whether endorectal magnetic resonance (MR) imaging findings contribute incremental value to the Kattan nomogram for predicting seminal vesicle invasion (SVI) in patients with prostate cancer. Materials and Methods: The institutional review board issued a waiver of authorization, which included a waiver of informed consent, for this HIPAA-compliant study. From October 2000 through January 2005, 573 patients (mean age, 58.3 years; age range, 36–86 years) underwent endorectal MR imaging before prostate cancer surgery. The endorectal MR imaging results had been prospectively interpreted by seven radiologists, and the likelihood of SVI was retrospectively scored on the basis of radiologists' written reports. MR imaging findings, individual clinical variables (serum prostate-specific antigen [PSA] level, Gleason grade, clinical stage, greatest percentage of cancer in all biopsy cores, percentage of positive cores in all biopsy cores, and perineural invasion), and the Kattan...
Reliability of Continuous Non-Invasive Assessment of Hemoglobin and Fluid Responsiveness: Impact of Obesity and Abdominal Insufflation Pressures

During surgery, proper fluid resuscitation and hemostatic control is critical. Pleth variability index (PVI) is advocated as a reliable way of optimizing intraoperative fluid resuscitation. PVI is a measure of dynamic change in perfusion index during a complete respiratory cycle. Non-invasive monitoring of total hemoglobin could provide a reliable means to determine need for transfusion. We analyzed the impact of insufflation and obesity on non-invasive measurements of hemoglobin and PVI in laparoscopic procedures to validate reliability of fluid responsiveness and hemoglobin levels. A non-invasive hemoglobin and PVI monitoring device was prospectively analyzed in patients undergoing abdominal operations. Patients were stratified by open and laparoscopic approach and obesity (body mass index (BMI) ≥35). PVI and hemoglobin values were assessed before, during, and after insufflation and compared to control patients undergoing open surgery. Sixty-three patients were enrolled (mean age 42 years; 71 % male; mean BMI 36) with 24 patients laparoscopic non-obese (LNO), 20 laparoscopic obese (LO), and 19 undergoing open operations. There was no significant blood loss. Hemoglobin did not change significantly before or after insufflation. There was false elevation of PVI with insufflation and more pronounced in obese patients. Insufflation or obesity was not associated with significant variations in hemoglobin. Non-invasive monitoring of hemoglobin is useful in laparoscopic procedures in obese and non-obese patients. PVI values should be used cautiously during laparoscopic procedures, particularly in obese patients.
Actuator selection for desired dynamic performance

This article presents two methods for selecting actuators based on the dynamic loading criteria, which yield a manipulator with a desired level of dynamic performance. Here, dynamic performance is measured in terms of a robot's acceleration and force capabilities, which describe its ability to accelerate the end-effector and to apply forces to the environment, given the limitations on its actuator torques. The dynamic capability equations are used to model the relationship between actuator torque capacities and the acceleration and force capabilities, because they treat linear and angular quantities in a consistent and physically meaningful way. This article discusses actuator selection for a single configuration, as well as for multiple configurations.
How modeling and simulation have enhanced decision making in new drug development

The idea of model-based drug development championed by Lewis Sheiner, in which pharmacostatistical models of drug efficacy and safety are developed from preclinical and available clinical data, offers a quantitative approach to improving drug development and development decision-making. Examples are presented that support this paradigm. The first example describes a preclinical model of behavioral activity to predict potency and time-course of response in humans and assess the potential for differentiation between compounds. This example illustrates how modeling procedures expounded by Lewis Sheiner provided the means to differentiate potency and the lag time between drug exposure and response and allow for rapid decision making and dose selection. The second example involves planning a Phase 2a dose-ranging and proof of concept trial in Alzheimer's disease (AD). The issue was how to proceed with the study and what criteria to use for a go/no go decision. The combined knowledge of AD disease progression, and preclinical and clinical information about the drug were used to simulate various clinical trial scenarios to identify an efficient and effective Phase 2 study. A design was selected and carried out resulting in a number of important learning experiences as well as extensive financial savings. The motivation for this case in point was the "Learn-Confirm" paradigm described by Lewis Sheiner. The final example describes the use of Pharmacokinetic and Pharmacodynamic (PK/PD) modeling and simulation to confirm efficacy across doses. In the New Drug Application for gabapentin, data from two adequate and well-controlled clinical trials was submitted to the Food and Drug Administration (FDA) in support of the approval of the indication for the treatment of post-herpetic neuralgia. The clinical trial data was not replicated for each of the sought dose levels in the drug application presenting a regulatory dilemma. Exposure response analysis submitted in the New Drug Application was applied to confirm the evidence of efficacy across these dose levels. Modeling and simulation analyses showed that the two studies corroborate each other with respect to the pain relief profiles. The use of PK/PD information confirmed evidence of efficacy across the three studied doses, eliminating the need for additional clinical trials and thus supporting the approval of the product. It can be speculated that the work by Lewis Sheiner reflected in the FDA document titled "Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products" made this scientific approach to the drug approval process possible.
Position Paper of the American Council on Science and Health on Risk Factors for Breast Cancer: Established, Speculated, and Unsupported

: This article provides the position of the American Council on Science and Health regarding how breast cancer is defined and classified; the magnitude of the public health problem of breast cancer among women; the implications of variation in incidence of breast cancer internationally and with migration; access to health care as a factor in slight differences in incidence and mortality rates among African-American and white women; and the evidence concerning various proposed human-breast-cancer risk factors. The article classifies risk factors as either established, speculated, or unsupported on the basis of available evidence. Specific genes have been identified that may explain as much as 5–10% of new breast cancer cases. Inherited predispositions may be characterized by family history of breast or ovarian cancer, young age at diagnosis, breast cancer diagnosed in both breasts, and male breast cancer. Benign breast disease (BBD), particularly the subtypes of BBD involving atypical hyperplasia, and exposure early in life to ionizing radiation is an established risk factor for breast cancer. Several reproductive characteristics are established as risk factors for breast cancer: early age at menarche, first full-term pregnancy after age 35 years of late age, and late age of menopause. Obesity and low physical activity are established as risk factors for breast cancer and are modifiable. Speculated risk factors for breast cancer that are gaining scientific support include nulliparity, oral contraceptive use, and postmenopausal estrogen replacement therapy. Speculated risk factors for which there is conflicting or preliminary support include not breast feeding, postmenopausal estrogen/progestogen replacement therapy, prescribed diethylstilbestrol, low consumption of phytoestrogens, specific dietary practices, alcohol consumption, not using nonsteroidal antinflammatory drugs, abortion, and breast augmentation. Unsupported risk factors include higher than average consumption of phytoestrogens, premenopausal obesity, electromagnetic fields, and low-dose ionizing radiation after 40 years of age. There is only limited support for xenoestrogens and large breast size as risk factors for breast cancer.
Histone deacetylase activity is necessary for left-right patterning during vertebrate development

Consistent asymmetry of the left-right (LR) axis is a crucial aspect of vertebrate embryogenesis. Asymmetric gene expression of the TGFβ superfamily member Nodal related 1 (Nr1) in the left lateral mesoderm plate is a highly conserved step regulating the situs of the heart and viscera. In Xenopus, movement of maternal serotonin (5HT) through gap-junctional paths at cleavage stages dictates asymmetry upstream of Nr1. However, the mechanisms linking earlier biophysical asymmetries with this transcriptional control point are not known. To understand how an early physiological gradient is transduced into a late, stable pattern of Nr1 expression we investigated epigenetic regulation during LR patterning. Embryos injected with mRNA encoding a dominant-negative of Histone Deacetylase (HDAC) lacked Nr1 expression and exhibited randomized sidedness of the heart and viscera (heterotaxia) at stage 45. Timing analysis using pharmacological blockade of HDACs implicated cleavage stages as the active period. Inhibition during these early stages was correlated with an absence of Nr1 expression at stage 21, high levels of heterotaxia at stage 45, and the deposition of the epigenetic marker H3K4me2 on the Nr1 gene. To link the epigenetic machinery to the 5HT signaling pathway, we performed a high-throughput proteomic screen for novel cytoplasmic 5HT partners associated with the epigenetic machinery. The data identified the known HDAC partner protein Mad3 as a 5HT-binding regulator. While Mad3 overexpression led to an absence of Nr1 transcription and randomized the LR axis, a mutant form of Mad3 lacking 5HT binding sites was not able to induce heterotaxia, showing that Mad3's biological activity is dependent on 5HT binding. HDAC activity is a new LR determinant controlling the epigenetic state of Nr1 from early developmental stages. The HDAC binding partner Mad3 may be a new serotonin-dependent regulator of asymmetry linking early physiological asymmetries to stable changes in gene expression during organogenesis.
Hunger: The carrot and the stick

The distinction between feeding driven by homeostatic energy deficit versus non-homeostatic reward is a frequently heard dichotomy in the neurobiology of appetite. Although oversimplified, the underlying idea is that there are multiple appetitive systems. One important homeostatic system is mediated by Agouti related protein (Agrp)-expressing neurons, a hypothalamic cell type that is activated by conditions of homeostatic energy deficit. Optogenetic [1] or chemogenetic [2] activation of AGRP neurons rapidly elicits intense food intake, and transient inhibition of these neurons reduces appetite [2], [3]. Recently, this population has also been found to transmit a signal with negative valence, and this may serve as a motive for mice to consume food, which consequently reduces AGRP neuron activity [3]. In fact, 96% of AGRP neurons have been shown by in vivo calcium imaging to rapidly reduce activity upon just the sight of food, such that the neurons have low activity during food consumption [3]. This indicates that AGRP neurons are involved in food-seeking but not food consumption. However, sustained reduction of AGRP neuron activity requires food consumption, which is consistent with a homeostatic role [3]. Conversely, a population of inhibitory neurons in the lateral hypothalamus increases feeding, is active during food consumption, and shows rewarding characteristics [4]. These neurons preferentially elicit palatable food consumption and interact with the ventral tegmental area (VTA), a brain region associated with incentive (reward)-based learning [5]. Notably, lateral hypothalamic neurons and VTA dopamine neurons have also been demonstrated to have receptors for key homeostatic hormones such as ghrelin [6] or leptin, indicating that positive valence (i.e., ‘hedonic’) systems are also homeostatically sensitive. Taken together, these systems mediate appetite regulation by both the ‘carrot and the stick’, where the positive valence of lateral hypothalamic/dopamine circuits associated with food consumption or the expectation of consumption pulls an animal towards incentives, and the negative valence AGRP neurons push an animal to attend to physiological needs. Both positive and negative valence systems are homeostatically sensitive, but the positive valence system also operates in the absence of homeostatic need if the reward value of the food is high enough (Figure 1).
Private Health Insurance And Risk Protection: Changes In Out-Of-Pocket Medical Spending, 2001 And 2005

Changes in the cost-sharing provisions of employment-sponsored health insurance in the 2000s were designed to control U.S. health-care spending. However, such provisions may also increase the financial burden on families who need medical care and may differentially affect families according to their socioeconomic characteristics and the health status of family members. Additionally, changes in cost sharing may alter the entire shape of the out-of-pocket spending distribution. Using quantile regressions, I assess whether the distribution of out-of-pocket spending and hence the risk-protection function of private insurance has been affected by such changes. The empirical results reveal that families who are likely to incur higher health-care spending because of family members’ existing health conditions were most affected by changes in cost sharing, while families with older policyholders at higher percentiles of the out-of-pocket spending distribution experienced decreases in such spending.
Transition in Atmospheric Turbulence Structure from Neutral to Convective Stability States

The magnitude and structure of the turbulence eddies in the atmosphere surface layer directly impacts the operation of wind turbines through the temporal variabilities in shaft torque and in blade, shaft bending moments that alter power production and reduce reliability due to premature component failure. The scales, strengths and detailed structure of daytime atmospheric turbulence is strongly dependent on the relative contribution of buoyancy-driven vertical motions from surface heating to shear driven by a geostrophic wind at the mesoscale. In this study, we apply spectral LES at high resolution and low dissipation to describe and quantify the turbulence structure over the range of stability states that characterize the transition from the purely shear-driven neutral boundary layer to the moderately convective atmospheric boundary layer, driven by both shear and buoyancy. Whereas we anticipated a transition that is rapid but monotonic in the stability parameter –zi/L (zi is the boundary layer depth and L the Monin-Obukhov length scale), our simulations indicate a particular transitional state with extraordinarily strong streamwise coherence in streamwise and vertical velocity when the stability state is characterized by – zi/L  1. Visualizations indicate that this particular turbulence structure is quite differnet from slightly less or more unstable boundary layers. The degree of streamwise coherence decreases quantitatively more rapidly towards the neutral limit (-zi/L 1.5) states. We scrutinize these observations and hypothesise that the special stability state with abnormally strong coherence could create unusually strong variations in wind turbine loadings.
TEMPORAL DATA IN PHYLOGENETIC SYSTEMATICS: AN EXAMPLE FROM THE MAMMALIAN FOSSIL RECORD

ABsTRAcr-A method of phylogenetic inference is proposed for taxa that are known from large samples spaced closely in time. The method employs elements of cladistic and stratophenetic methods, and consists of four steps. 1) Morphologically homogeneous clusters are recognized within temporally and geographically constrained samples. 2) Temporally disjunct and geographically dispersed taxa are recognized, and their anagenetic evolution and geographic variation documented. 3) A character matrix is constructed for the taxa and analyzed cladistically. 4) Resulting cladograms are used to construct a phylogenetic tree with additional input from temporal, morphological, ecological, and geographical data. This method supplements the use of cladistically analyzed morphological data with data that are not suited for cladistic analysis, and thus reduces the amount of unused data.
Biogeographic gradients in ecosystem processes of the invasive ecosystem engineer Phragmites australis

Latitudinal gradients in ecosystem patterns arise from complex interactions between biotic and abiotic forces operating at a range of spatial and temporal scales. Widespread invasive species, particularly invasive ecosystem engineers with large effects on their environment, may alter these gradients. We sampled 3–5 stands of the invasive common reed, Phragmites australis, in eight coastal wetlands ranging from Massachusetts (42°N) to South Carolina (32°N) to document geographic variation in P. australis primary production, associated plant and animal species diversity, and sediment carbon storage and to examine how local-, regional-, and large-scale environmental factors contribute to these patterns. Latitude best explained variation in P. australis density, but contrary to expectations, density increased with increasing latitude across our sites. Latitude also predicted macroinvertebrate species richness, which increased with latitude in a manner similar to P. australis density. In addition to latitude, P. australis leaf carbon:nitrogen ratios, distance to the open coast, and sediment oxygen levels were most important for explaining variation in P. australis production, as well as community (plant or animal species richness) and ecosystem (carbon storage) variables. The percent of developed land was positively associated with P. australis density, yet this variable had relatively low predictive power in our study. Our study provides an important biogeographic perspective for documenting and understanding variation in invasive P. australis that is fundamental both for managing the invasion and for understanding latitudinal gradients in ecosystem structure and function.
An Assessment of the Impact of Uncertainty on Automatic Generation Control Systems

This paper proposes a framework to quantify the impact of uncertainty that arises from load variations, renewable-based generation, and noise in communication channels on the automatic generation control (AGC) system. To this end, we rely on a model of the power system that includes the synchronous generator dynamics, the network, and the AGC system dynamics, as well as the effect of various sources of uncertainty. Then, we develop a method to analytically propagate the uncertainty from the aforementioned sources to the system frequency and area control error (ACE), and obtain expressions that approximate their probability distribution functions. We make use of this framework to obtain probabilistic expressions for the frequency performance criteria developed by the North American Electric Reliability Corporation (NERC); such expressions may be used to determine the limiting values of uncertainty that the system may withstand. The proposed ideas are illustrated through the Western Electricity Coordination Council (WECC) 9-bus 3-machine system and a 140-bus 48-machine system.
Talimogene laherparepvec in advanced melanoma

ABSTRACTIntroduction: Melanoma is the most aggressive of the cutaneous malignancies. Treatment options for advanced melanoma have greatly expanded through the development of immune checkpoint inhibitors and small molecule targeting agents. The most recently approved therapy, talimogene laherparepvec (Imlygic™, OncoVEXGM-CSF, T-VEC), is a genetically modified herpes simplex virus type 1 that has demonstrated clinical activity in advanced melanoma. This first in class oncolytic virus immunotherapy represents a step forward for the promising class of oncolytic virus therapies.Areas covered: The article reviews melanoma treatment with a focus on the novel oncolytic virus therapy and the preclinical and clinical evidence for treatment of advanced melanoma with T-VEC. The focus for clinical evidence will be on a phase III study of T-VEC in patients with stage IIIB, IIIC or IV melanoma, as well as the phase I and II studies. We also explore the future use of T-VEC in combination with other immunotherapy agents. ...
Intrauterine growth restriction combined with a maternal high-fat diet increases hepatic cholesterol and low-density lipoprotein receptor activity in rats.

Intrauterine growth restriction (IUGR) and maternal consumption of a high‐saturated‐fat diet (HFD) increase the risk of hypercholesterolemia, a leading cause of morbidity and mortality. Many pregnant women eat a HFD, thus exposing the fetus to a HFD in utero. The cumulative effect of in utero exposure to IUGR and a HFD on offspring cholesterol levels remains unknown. Furthermore, little is known about the mechanism through which IUGR and maternal HFD consumption increase cholesterol. We hypothesize that IUGR combined with a maternal HFD would increase offspring serum and hepatic cholesterol accumulation via alteration in levels of key proteins involved in cholesterol metabolism. To test our hypothesis we used a rat model of surgically induced IUGR and fed the dams a regular diet or a HFD. HFD‐fed dams consumed the same kilocalories as regular diet‐fed dams, with no difference between surgical intervention groups. In the offspring, IUGR combined with a maternal HFD increased hepatic cholesterol levels, low‐density lipoprotein (LDL) receptor protein levels, and Ldlr activity in female rat offspring at birth and both sexes at postnatal day 14 relative to non‐IUGR offspring both from regular diet‐ and HFD‐fed dams. These findings suggest that IUGR combined with a maternal HFD increases hepatic cholesterol accumulation via increased LDL cholesterol uptake into the liver with resulting persistent increases in hepatic cholesterol accumulation.