cssi/SciSciGPT-SciSciNet huggingface dataset:
Lack of Refractoriness to Prolonged Thyrotropin Administration in Birds

SummaryIn the English sparrow, prolonged injection of sheep thyrotropic hormone does not lead to the development of refractoriness. The thyroids remain enlarged and hyperplastic, and the elevation in metabolic rate is maintained over periods up to 5 months.
Effects of college education on demonstrated happiness in the United States

Among the many documented benefits of a college education is a higher level of self-reported happiness. The present work considers instead the level of demonstrated happiness and unhappiness within groups, the latter proxied by the conditional probability of suicide within groups having a college education and those without. Those with college are not happier for it, in these terms, and actually have slightly higher rates of suicide than those without college, based on a recent US data.
Teacher influence on pupil cognitive performance

Probably the most widely accepted and frequently cited goal of formal education is to create independent thinkers capable of acquiring and utilizing knowledge in various productive ways. In establishing learning environments, behavioral objectives, and instructional modalities, teachers significantly determine whether pupils reached this goal. Abundant research reveals the unfortunate trend in current educational practices of emphasis on accumulation rather than on application of knowledge. A partial explanation for the limited thinking in our schools is that teachers may be ignorant of important theories of intellectual development and cognitive function. As a result, classroom implementation of these theories is inadequate. This review examines major cognitive theories and relates them to available information regarding teacher influence on pupil cognitive performance to help generate a practical body of information and direction for future teacher training. Jean Piaget contributes greatly to understanding intellectual development and mental processes of knowledge acquisition. Three elements of Piaget's work in child psychology concern us here: definition of intelligence, stages of intellectual development, and factors influencing development. Russell Stauffer describes Piaget's definition of intelligence as "an adaptation, an organizing activity whereby there occurs a progressive balancing of increasing complex forms under the impact of experience."1 The inherent tendency to adapt to the environment is composed of the complementary processes of assimilation and accommodation. In assimiliation, the child uses existing mental structures to understand and incorporate new elements. Accommodation or change in these existing structures as a response to environmental demands results from the assimilation process. Interaction with the world is the key to Piaget's definition of intelligence. As Ginsberg and Opper point out, "Piaget believes that knowledge is not given to a passive observer; rather knowledge of reality must be discovered and constructed by the activity of the child."2 Gorman succinctly explains this notion
Characterization of the antioxidant status of the heterozygous manganese superoxide dismutase knockout mouse.

Abstract The antioxidant status of several tissues (liver, kidney, lung, brain, heart, muscle, stomach, and spleen) from heterozygous manganese superoxide dismutase (MnSOD) mutant mice (Sod2−/+) was characterized. The activity of MnSOD was decreased (30 to 80%) in all tissues examined. The levels of mRNA coding for the major antioxidant enzymes (CuZnSOD, catalase, and glutathione peroxidase) were not significantly altered in liver, kidney, heart, lung, or brain in theSod2−/+mice. The activities of the enzymes were not altered in any of these tissues, with the exception of a decrease in glutathione peroxidase activity in muscle in theSod2−/+mice compared to theSod2+/+mice. Thus, there was no up-regulation of the activities of the major antioxidant enzymes to compensate for the decrease in MnSOD activity. Reduced glutathione levels were 30 to 50% lower in the lung, brain, and muscle of theSod2−/+mice compared to the wild-typeSod2+/+mice. In addition, the ratio of GSH/GSSG was decreased approximately 50% inSod2−/+muscle, indicating that the decrease in MnSOD activity in theSod2−/+mice results in some degree of oxidative stress in this tissue.
The combining of forecasts using recursive techniques with non‐stationary weights

This paper evaluates six optimal and four ad hoc recursive combination methods on five actual data sets. The performance of all methods is compared to the mean and recursive least squares. A modification to one method is proposed and evaluated. The recursive methods were found to be very effective from start-up on two of the data sets. Where the optimal methods worked well so did the ad hoc ones, suggesting that often combination methods allowing ‘local bias’ adjustment may be preferable to the mean forecast and comparable to the optimal methods.
Alteration Effects at Tuba Dike, Cameron, Arizona

Tuba dike is a monchiquite dike approximately 2 miles long which crops out in the lower Jurassic along the northern edge of the Painted Desert 12 miles northeast of the Cameron uranium mining district. The dike strikes almost due north and forms a low spinelike ridge rising out of the blow-sand-covered sedimentary strata. The dike has a porphyritic texture consisting of olivine and calcite- and chlorite-replaced olivine phenocrysts in a matrix of unterlocking augite blades. Fractures filled with calcite parallel and crosscut the dike. Two carbonate-filled pipes lie just west of the center of the dike. The sandstones of these vents have been heavily impregnated by introduced calcite which has also invaded a large part of the sediments between the dike and the vents. Argillic alteration of montmorillonite to illite, concentrated in the sediments immediately adjacent to the dike, has produced relatively resistant borders of a wall-like nature at the dike contact. Deuteric alteration, calcitic impregnation, and argillic alteration indicate considerable hydrothermal activity associated with the formation of the dike. The dike and accompanying alteration represent possible sources of hydrothermally introduced mineralization.
Altitudinal and latitudinal migration of Cryptomeria japonica for the past 20,000 years in Japan

Biostatistical analysis of modern pollen assemblages in 152 Japanese surface samples shows that Cryptomeria japonica can normally grow in areas with a mean January temperature of approximately −7° to 7°C, a mean August temperature of 19° to 27°C, and an effective precipitation (total precipitation during the growing season) of over 1000 mm. The full-glacial distribution of the species on both the Sea of Japan and the Pacific coasts (35–36°N lat) indicates that in these areas the maximum possible reduction of temperature was 8.7–10.2°C in January and 6.0–7.3°C in August, and that the effective precipitation was low, being 1000–1350 mm, or 40–55% below the modern level, provided that the species has not changed its physiological characteristics. Populations of C. japonica expanded northward and upslope from their full-glacial areas of distribution immediately after late-glacial climatic amelioration. This expansion appears to have been regulated mainly by the availability of effective precipitation which became high in northeastern Honshu about 4000 yr ago. After about 2500 yr B.P., C. japonica was planted extensively by humans in moist, temperate climatic regions (excluding Hokkaido), and now has its widest distribution since at least the last full-glacial interval.
Charge-Quantization Studies Using a Tunnel Capacitor

A tunnel capacitor is an array of microscopic resistance-capacitance circuits with the resistive element provided by a tunnel junction. Because of their small size, such microcircuits display special properties due to charge quantization. An array of such circuits shows an oscillatory behavior in its capacitance-versus-voltage measurements. A new type of memory effect is found.
Gender-Based Strategies on Candidate Websites

As a result of changes in the campaign landscape, candidates have several strategic options available to them, particularly when considering how to respond to voters’ gender stereotypes. The goal of this paper is to understand candidates’ use of strategies based on gender stereotypes by emphasizing either particular issues or particular traits that are commonly associated with one gender or the other. To do this, I developed hypotheses of why candidates might choose a trait or issues strategy based on gender stereotypes. I tested these hypotheses using a large-scale content analysis of candidate websites over four election cycles. I found that female candidates mostly pursued strategies that were consistent with gender stereotypes. Interestingly, female candidates were found to have different strategies on different pages of their websites. I discuss the implications of gender-based strategies for the election of female candidates and for representation.
"Spider bite" lesions are usually diagnosed as skin and soft-tissue infections.

Abstract Background: Many people seek medical attention for skin lesions and other conditions they attribute to spider bites. Prior experience suggests that many of these lesions have alternate causes, especially infections with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Objectives: This study determined the percentage of emergency department (ED) patients reporting a "spider bite" who received a clinical diagnosis of spider bite by their physician vs. other etiologies, and if the diagnoses correlated with demographic risk factors for developing CA-MRSA infections. Methods: ED patients who reported that their condition was caused by a "spider bite" were prospectively enrolled in an anonymous, voluntary survey regarding details of their illness and demographic information. Discharge diagnoses were also collected and categorized as: spider bite, bite from other animal (including unknown arthropod), infection, or other diagnosis. Results: There were 182 patients enrolled over 23 months. Seven patients (3.8%) were diagnosed with actual spider bites, 9 patients (4.9%) with bites from other animals, 156 patients (85.7%) with infections, and 6 patients (3.3%) were given other diagnoses. Four patients were given concurrent diagnoses in two categories, and 8 (4.4%) did not have the diagnosis recorded on the data collection instrument. No statistically significant associations were found between the patients' diagnostic categories and the demographic risk factors for CA-MRSA assessed. Conclusion: ED patients reporting a "spider bite" were most frequently diagnosed with skin and soft-tissue infections. Clinically confirmed spider bites were rare, and were caused by black widow spiders when the species could be identified.
Occupational and Physical Therapists' Perspective of the Perceived Benefits of a Therapeutic Home Visit Program

The purpose of this pilot study was to determine what occu ational and physical therapists in rehabilitation perceive as the benepts of a Therapeutic Home Visit (THV) to the patient, the W y and th...
Selectivity of Etching III–V Compounds by Laser-Induced Electrochemistry

The laser-induced electrochemical etching of III–V compounds is a demonstrated method for the spatially defined removal of materials from surfaces [1]. A critical feature of the etching process is its selectivity: for example, the relative etch rate of p-doped compared to n-doped material or of one compound compared to another compound. A second important feature is the etching mechanism near a heterojunction or a p-n junction. We have identified the controlling mechanisms of the etching process that elucidates these features. For illustrative purpose, we will present the analysis and data on the Ar+- laser-induced electrochemical etching of the compounds gallium arsenide and gallium phosphide with n and p dopants. Etching occurs in an aqueous solution of KOH. The analysis and description is also applicable to other III–V compound materials.
Mandibular myofibrosarcoma of childhood: surgical resection & reconstruction with fibula flap.

MD, FACS (Professor, Kansas University Medical Center, Department of Otolaryngology)Kansas University Medical CenterCorresponding author: Konstantinos Kourelis, Union Memorial Hospital, 201 E University Pkwy Suite 631, Baltimore, MD 21218, USAPaper submitted to the BJORL-SGP (Publishing Management System – Brazilian Journal of Otorhinolaryngology) on August 21, 2009; and accepted on October 17, 2010. cod. 7277
Analysis of Novel Soluble Chromate and Uranyl Reductases and Generation of an Improved Enzyme by Directed Evolution

Most polluted sites contain mixed waste. This is especially true of the U.S. Department of Energy (DOE) waste sites which hold a complex mixture of heavy metals, radionuclides, and organic solvents. In such environments enzymes that can remediate multiple pollutants are advantageous. We report here evolution of an enzyme, ChrR6 (formerly referred to as Y6), which shows a markedly enhanced capacity for remediating two of the most serious and prevalent DOE contaminants, chromate and uranyl. ChrR6 is a soluble enzyme and reduces chromate and uranyl intracellularly. Thus, the reduced product is at least partially sequestered and nucleated, minimizing the chances of reoxidation. Only one amino acid change, Tyr128Asn, was responsible for the observed improvement. We show here that ChrR6 makes Pseudomonas putida and Escherichia coli more efficient agents for bioremediation if the cellular permeability barrier to the metals is decreased.
A systematic model for teaching DSP

While many DSP topics are difficult for undergraduates to internalize, appropriate demonstrations and laboratory experiences have been shown to be very helpful. This paper describes a highly successful pedagogical model the authors have developed which includes theory, demos, lab exercises, and real-time DSP experience using MATLAB and the Texas Instruments C6711 digital signal processing starter kit.
Provisioning of Nestling Dickcissels in Native Warm-Season Grass Field Buffers

Abstract We used video cameras in 2008–2009 to record provisioning activities at Dickcissel (Spiza americana) nests in and around Conservation Reserve Program field buffers in north-central Mississippi, USA. We simultaneously observed foraging flight distances of parents. Provisioning rate (P = 0.412), biomass (P = 0.161), and foraging distance (P = 0.159) did not increase with nestling age. Parents delivered larger items to meet demand associated with older nestlings (P = 0.010–0.001). This suggests energetic costs of changes in prey selection were less than costs of increasing the number or distance of provisioning trips. Presence of male helpers increased provisioning rate (P < 0.001) but not biomass (P = 0.992) because males brought smaller prey items (P = 0.001–0.021). Presence of observers 30 m from the nest reduced provisioning rates (P = 0.005) and biomass delivered (P = 0.066). Lack of habitat effects for any aspect of provisioning suggests grass field buffers provided nestling fo...
Training New Technology: Automatic Teller Machines and Older Adults

The purpose of the present study was to assess the benefits of providing on-line training for an automatic teller machine (ATM). An ATM simulator was developed for the study, and older adults (65-80) served as the subjects. Subjects were assigned to one of two conditions. Half of the subjects were given a written description of how the ATM worked. The other half went through an on-line tutorial, which showed them how to perform transactions on the simulator. After performing 30 transactions on the simulator, subjects were transferred to a new ATM simulator that was topographically different. The subjects who received the on-line tutorial performed more transactions correctly during acquisition, and were better able to transfer their skills to a different ATM simulator and to novel transactions.
Routine screening mammography: how important is the radiation-risk side of the benefit-risk equation?

expected increase in biological e Vectiveness of these The potential radiation hazards associated with routine screening lower-energy X-rays is that they set in motion slower mammography, in terms of breast cancer induction, are discussed secondary electrons, with correspondingly higher in the context of the potential benee ts. The very low energy LET (Brenner and Amols 1989, Kellerer 2002). X-rays used in screening mammography (26‐ 30kVp) are In this regard, Frankenberg et al. (2002) reported expected to be more hazardous, per unit dose, than high-energy data on in vitro oncogenic transformations frequencies X- or c-rays, such as those to which A-bomb survivors (from which radiation risk estimates are derived) were exposed. Based induced by 29-kVp X-rays relative to ‘ conventional’ on in vitro studies using oncogenic transformation and chromo- 200-kVp X-rays suggesting that the low-energy X-rays some aberration end-points, as well as theoretical estimates, it used in screening mammography are considerably seems likely that low doses of low-energy X-rays produce an more biologically e Vective. This conclusion echoes increased risk per unit dose (compared with high energy photons) some earlier calculations on this subject (Brenner and of about a factor of 2. Because of the low doses involved in Amols 1989) and a variety of earlier experimental screening mammography, the benee t‐ risk ratio for older women would still be expected to be large, though for younger women data for chromosome aberration induction (see below). the increase in the estimated radiation risk suggests a somewhat An increase in the relative biological e Vectiveness later age than currently recommended— by about 5‐ 10 years— (RBE) of low-energy mammographic X-rays comat which to commence routine breast screening. pared with high-energy photons is of relevance in assessing the risk side of the benee t‐ risk equation for
Anticipatory perceptual simulation for human-robot joint practice: theory and application study

With the aim of fluency and efficiency in human-robot teams, we have developed a cognitive architecture based on the neuro-psychological principles of anticipation and perceptual simulation through top-down biasing. An instantiation of this architecture was implemented on a nonanthropomorphic robotic lamp, performing in a human-robot collaborative task. In a human-subject study, in which the robot works on a joint task with untrained subjects, we find our approach to be significantly more efficient and fluent than in a comparable system without anticipatory perceptual simulation. We also show the robot and the human to be increasingly contributing at a similar rate. Through self-report, we find significant differences between the two conditions in the sense of team fluency, the team's improvement over time, and the robot's contribution to the efficiency and fluency. We also find difference in verbal attitudes towards the robot: most notably, subjects working with the anticipatory robot attribute more positive and more human qualities to the robot, but display increased self-blame and self-deprecation.
A prospective study of alcohol use among middle-aged adults and marital partner influences on drinking.

Objective:The purpose of this three-wave longitudinal study was twofold. First, prevalence data on alcohol characteristics (e.g., drinks per day, heavy episodic drinking [HED]) were provided for a community sample of middle-aged adults. Aggregate (or group) and individual levels of stability of these characteristics across a 10-year interval were a major focus. Second, an actor–partner interdependence model (APIM) was used to test husbands’ and wives’ mutual influences on each other’s alcohol use.Method:Prospective data were collected from the middle-aged parents of a cohort study that originally targeted adolescents. Three measurement occasions occurred at baseline, 5 years later, and an additional 5 years later. Data from 597 men and 847 women were used to derive prevalence data on alcohol use, and 489 intact marital dyads were used to test spouses’ interdependence on alcohol use and HED in the APIMs.Results:The majority of men and women reported alcohol use at each measurement occasion, and the average...
Clinical profile of the overweight child in the new millennium.

Background In conjunction with the rising prevalence of obesity during the past several decades, the clinical profile of the obese child has changed. Hypothesis. Environmental influences and eating practices have had an impact on the presence of medical morbidities among obese children.Design Retrospective chart review of data collected from 90 children entering into a pediatric weight management program was performed. Fisher's exact tests and Wilcoxon rank sum tests were used to compare outcomes between subpopulations.Results There was greater elevation in systolic blood pressure among children who ate in front of the television (P = .03) and a greater degree of fast-food consumption among children with more than 3 medical morbidities (P = .02). Breast-feeding did not have a protective effect on the degree of obesity (P = .02).Conclusion Aggressive assessment for symptoms should be an important part of evaluating the overweight child. Environmental influences and social feeding practices can counteract t...
Properties of nanocrystalline diamond thin films grown by MPCVD for biomedical implant purposes

Abstract Nanocrystalline diamond (NCD) thin films have been grown by microwave plasma chemical vapor deposition (MPCVD) and investigated to determine their suitability for biomedical applications. Growth conditions were chosen to produce very uniform films over the surface of curved temporomandibular joint implants. These parameters include methane flow rates exceeding 20% of the hydrogen gas flow rate, and chamber pressure and microwave power were maintained at 30 Torr and 0.73 kW, respectively, in a Wavemat 6 kW MPCVD device. Films (3 μm thick) that completely coated 2.54-cm-diameter Ti–6Al–4V disks under these conditions exhibit mean grain size of 30.4 nm as determined by XRD peak broadening, hardness of 80 GPa as determined by nanoindentation, RMS mean roughness of 15.3±5.3 nm as determined by stylus profilometry, and film adhesion toughness (ΓC) of 158 J/m2 as determined by a Rockwell indentation method. Similar deposition performed on small Ti–6Al–4V hemispheres produce films with smaller mean grain size of 21.1 nm and correspondingly lower hardness and roughness. Overall, these films exhibit properties well suited for use in biomedical applications.
Peroneal palsy in depressed patients. Weight loss, psychomotor retardation predispose patients to this complication.

Abstract Twenty-one of 181 depressed psychiatric inpatients receiving neurologic consultations were found to have clinical indications of peroneal palsy. Weight loss was universal but not excessive. Electromyography and nerve conduction studies were performed on 15 patients and were diagnostic in 12 of them. In all cases a causative factor was leg crossing, related to excessive sitting during depressive illnesses, although two patients also had diabetes mellitus. Thin individuals and women are more susceptible.
Data requested from the subgroups studied in the APL93 trial.

To the Editor: The recent article by Fenaux et al in Blood continues the interesting and exciting work being conducted in the treatment of acute promyelocytic leukemia.[1][1] Given the 2 randomization points (induction regimen and maintenance regimen) designed in the APL93 trial, data presented on
Asymptotic independence of servers' activity in queueing systems with limited resource pooling

We consider multi-class multi-server queuing systems where a subset of servers, called a server pool, may collaborate in serving jobs of a given class. The pools of servers associated with different classes may overlap, so the sharing of server resources across classes is done via a dynamic allocation policy based on a fairness criterion. We consider an asymptotic regime where the total load increases proportionally with the system size. We show that under limited scaling in size of server pools the stationary distribution for activity of a fixed finite subset of servers has asymptotically a product form, which in turn implies a concentration result for server activity. In particular, we establish a clear connection between the scaling of server pools' size and asymptotic independence. Further, these results are robust to the service requirement distribution of jobs. For large-scale cloud systems where heterogeneous pools of servers collaborate in serving jobs of diverse classes, a concentration in server activity indicates that the overall power and network capacity that need to be provisioned may be substantially lower than the worst case, thus reducing costs.
Chat spaces

Chat Spaces are rich persistent chats that provide light-weight shared workspaces for small to medium-scale group activities. Chat Spaces can accommodate brief, informal interactions (similar to Instant Messaging), and can also support longer-term complex threaded conversations including large numbers of people and shared resources. Our design maps a hierarchical thread representation onto a time-ordered two-column user interface. This mapping allows a user to follow the global dynamics of the entire thread in the chronological column on the left while being able to participate in a selected topical branch in a second column on the right. We also present a dynamic thread map that provides an overview of the entire conversation and supports quick navigation of topical branches in the thread.
Transthoracic echocardiography in rats. Evalution of commonly used indices of left ventricular dimensions, contractile performance, and hypertrophy in a genetic model of hypertrophic heart failure (SHHF-Mcc-facp-Rats) in comparison with Wistar rats during aging.

Two-weekly echocardiographic examinations were conducted in nine SHHF-Mc-facp rats in comparison with eight age-matched Wistar rats. In the SHHF-rats, characterized by progressive LV-dilation and decreasing contractile function between 77–87 weeks of age, left ventricular (LV) hypertrophy was most sensitively demonstrated by increased LV-mass-index (p < 0.001). LV-areas and area-ejection fraction (EF) (2D-images) discriminated more sensitively in the early stages than M-mode-derived diameters and fractional shortening (FS); midwall shortening was the most sensitive parameter of reduced systolic function. Post-mortem measurements showed an excellent correlation with calculated LV-mass (r = 0.91). Post-mortem LV-volumes correlated signiﬁcantly with diastolic LV-diameters, LV-areas, and calculated LV-volumes (r = 0.56–0.59). Mean within-subject standard deviations in controls were 0.5–0.6 mm (LV-diameters), 3.1–4.6 mm2 (LV-areas), ~10% of the mean for FS, area-EF and midwall shortening, and ~20% for wall thickness and LV-mass. The data might be used to choose the most sensitive parameters, and to estimate sample size for echocardiographic investigations in rats.
Imaging deep brain hemodynamics and metabolism with Optical Coherence Tomography

We present advances in deep rodent brain imaging using Optical Coherence Tomography: including dynamic contrast, ~1700 nm for deeper penetration to subcortical layers, and visible light for hemoglobin concentrations and cortical metabolism.
180 EFFECTS OF MECHANICAL VENTILATION ON GENES THAT REGULATE LUNG DEVELOPMENT IN NEWBORN MICE

Failed formation of alveoli and lung capillaries is a key histological feature of neonatal chronic lung disease (CLD). CLD typically afflicts preterm infants with incompletely developed lungs that have been exposed to prolonged mechanical ventilation with O 2 -enriched gas. As lung septation and angiogenesis occur mainly after term birth in mice, we did studies to see if positive-pressure mechanical ventilation, with or without added O 2 , would alter lung expression of genes that regulate alveolar and lung vascular development in newborn mice. We studied 4 groups of 6-8 pups that were 2-4d old and weighed 2.8±0.7g. Group 1 (MV-O 2 ) had a tracheotomy with ketamine-xylazine anesthesia, followed by mechanical ventilation with 40% O 2 for 8h at 60 breaths/min (bpm), peak inflation pressure (PIP) 17±1 cmH2O, end-expiratory pressure (PEEP) 1 cmH2O. Group 2 (Control-O 2 ) had sham surgery and then breathed spontaneously in 40% O 2 for 8h. Group 3 (MV-air) had a tracheotomy followed by mechanical ventilation with air for 8h at 60 bpm, PIP 16 ± 1 and PEEP 1 cmH2O. Group 4 (Control-air) had sham surgery and then breathed room air for 8h. Lungs from 4-6 pups/group were frozen in liquid N2 and stored at -80(C for later gene microarray analysis and quantitative RT-PCR to measure mRNA for genes considered important in lung development (Vascular Endothelial Growth Factor A, VEGF-A, and its receptor, VEGF-R2; Tenascin-C, TN-C; and Lysyl Oxidase, LO). Lungs from some pups in each group were fixed by tracheal instillation of 10% formalin for histology, which showed no structural differences or evidence of injury among the 4 groups of mice. Gene microarrays and qRT-PCR showed significantly less lung expression of VEGF, VEGF-R2 and TN-C, and more LO in Group 1 (MV-O 2 ) compared to Group 2 (Control-O 2 ). Parallel studies on lungs of pups that breathed air showed significantly less VEGF, but not VEGF-R2 or TN-C, and more LO in Group 3 (MV-air) compared to Group 4 (Control-air). These findings indicate that a prolonged period of cyclic lung inflation with O 2 -enriched gas at a critical stage of development, even without apparent lung injury, may adversely affect pulmonary expression of genes that are known to be important in regulating formation of alveoli and lung blood vessels. This work has important implications for studying mechanisms involved in the pathogenesis of CLD.
Calculating binding free energies of host–guest systems using the AMOEBA polarizable force field

Molecular recognition is of paramount interest in many applications. Here we investigate a series of host–guest systems previously used in the SAMPL4 blind challenge by using molecular simulations and the AMOEBA polarizable force field. The free energy results computed by Bennett's acceptance ratio (BAR) method using the AMOEBA polarizable force field ranked favorably among the entries submitted to the SAMPL4 host–guest competition [Muddana, et al., J. Comput.-Aided Mol. Des., 2014, 28, 305–317]. In this work we conduct an in-depth analysis of the AMOEBA force field host–guest binding thermodynamics by using both BAR and the orthogonal space random walk (OSRW) methods. The binding entropy–enthalpy contributions are analyzed for each host–guest system. For systems of inordinate binding entropy–enthalpy values, we further examine the hydrogen bonding patterns and configurational entropy contribution. The binding mechanism of this series of host–guest systems varies from ligand to ligand, driven by enthalpy and/or entropy changes. Convergence of BAR and OSRW binding free energy methods is discussed. Ultimately, this work illustrates the value of molecular modelling and advanced force fields for the exploration and interpretation of binding thermodynamics.
SETD2 Heterozygous Loss in Leukemia Leads to Chemotherapy Resistance through Attenuation of the DNA Damage Response

Abstract Relapsed leukemia is chemotherapy resistant and survival is poor. We recently found that mutations in epigenetic regulators are enriched in relapsed pediatric B-cell acute lymphoblastic leukemia (B-ALL), suggesting that they are associated with clonal survival and chemotherapy resistance. The mutations included loss of function mutations in the epigenetic regulator SETD2, which had not before been described in B-ALL. SETD2 is the only known mammalian Histone 3 Lysine 36 (H3K36) trimethyltransferase and one or two copy loss leads to a global decrease or elimination, respectively, of its chromatin mark, H3K36me3. Using CRISPR/Cas9 to engineer isogenic human and murine leukemia cells, we have demonstrated that SETD2 loss leads to resistance to DNA damaging chemotherapy used in standard ALL therapy, consistent with the gain of SETD2 mutations at relapse. Leukemia cells with SETD2 heterozygous deletion demonstrated a significant increase in IC50 to the DNA damaging anti-metabolites 6-thioguanine (6TG) and cytarabine (AraC), but not the protein synthesis inhibitor L-Asparaginase (Asp). To model the enrichment of SETD2 mutations at relapse, we competed a small population of SETD2 heterozygous cells with isogenic control leukemia cells. Within 3 weeks, treatment with 6TG and AraC, but not Asp or vehicle, led to a dramatic selection of SETD2 heterozygous cells, mimicking the selective pressure of SETD2 clones in patients. Recent reports have shown that H3K36me3is important in the DNA damage response (DDR). Consistent with this, we find that heterozygous SETD2 loss impairs the DDR signaling pathway with attenuated phosphorylation of multiple DDR components, including Chk1 and Chk2, in response to chemotherapy. Consequently, SETD2 heterozygous cells showed an abrogation of the apoptotic response to the DNA damaging chemotherapy agents 6TG and AraC, despite a normal apoptotic response to Asp. In summary, we have demonstrated that SETD2 loss leads to resistance to DNA damaging chemotherapy. The resistance is caused by a failure to trigger DDR signaling and apoptosis after chemotherapy induced DNA damage. These findings identify heterozygous SETD2 lossas a novel mechanism of chemotherapy resistance in leukemia and have implications for therapy selection and novel therapeutic interventions. Disclosures No relevant conflicts of interest to declare.
CALMing Down Arrhythmogenic Calmodulinopathies via a Precision Medicine Approach.

In this issue, Limpitikul et al1 used the novel CRISPR interference (CRSPRi) strategy to suppress the expression of an arrhythmogenic mutant calmodulin (CaM) gene in human induced pluripotent cell-derived cardiomyocytes (iPSC-CM). This mutant CaM (D130G) is linked with long-QT syndrome (LQTS).2 The main LQTS mechanism is via a loss in Ca2+ affinity of CaM, resulting in a loss of Ca-dependent inactivation of L-type Ca current (ICa) and hence prolongation of the ventricular action potential duration (Figure).2–4 Several other human CaM mutations have been linked with LQTS and seem likely to function at ICa in the same way (D96V, N98I, A103V, D130V, D134H, E141G, F142L).5 Indeed, all of these mutations are in the third and fourth Ca2+ binding domains of CaM, which are known to be critical in ICa inactivation.6 Human CaM mutations have also been linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), a phenotype that is mediated by inappropriate diastolic SR Ca release channel (ryanodine receptor 2 [RyR2]) activity (CaM-N54I, N98S, and A103V)7–9 and also by the promotion of late Na current (INaL; CaM-141G)5 and some degree of target overlap exists. For example, N98S and A103V promote both ICa and RyR2-mediated Ca leak, and E141G has effects on both ICa and INaL. Given the ubiquitous role of CaM in cellular Ca2+-dependent signaling, this is likely to be only the tip of the iceberg for CaM mutant effects, albeit highly apparent because of the strong arrhythmogenic …
A review of the Neotropical genus Bidessodes Régimbart, 1895 including description of four new species (Coleoptera, Adephaga, Dytiscidae, Hydroporinae, Bidessini)

The Neotropical genus Bidessodes Regimbart, 1895 is reviewed. Four new species are described, Bidessodes chlorus Miller, sp. n., Bidessodes erythros Miller, sp. n., Bidessodes leukus Miller, sp. n., and Bidessodes melas Miller, sp. n., bringing the total number of species in the genus to 20. A key to species is provided. Important diagnostic features are illustrated and described and distributions of all species based on examined specimens and published records are provided. Recognition of the subgenera of Bidessodes is not justified, and the two names Hughbosdineus Spangler, 1981 syn. n. and Youngulus Spangler, 1981 syn. n., described at the genus rank, are placed in synonymy with Bidessodes.
Subsidies for Oral Chemotherapy and Use of Immunomodulatory Drugs Among Medicare Beneficiaries With Myeloma

Purpose The low-income subsidy (LIS) substantially lowers out-of-pocket costs for qualifying Medicare Part D beneficiaries who receive orally administered chemotherapy. We examined the association of LIS with the use of novel oral immunomodulatory drugs (IMiDs; lenalidomide and thalidomide) among beneficiaries with myeloma, who can receive either orally administered or parenteral (bortezomib-based) therapy. Methods Using SEER-Medicare data, we identified Part D beneficiaries diagnosed with myeloma in 2007 to 2011. In multivariable models adjusted for sociodemographic and clinical characteristics, we analyzed associations between the LIS and use of IMiD-based therapy, delays between IMiD refills, and select health outcomes during the first year of therapy. Results Among 3,038 beneficiaries, 41% received first-line IMiDs. Median out-of-pocket cost for the first IMiD prescription was $3,178 for LIS nonrecipients and $3 for LIS recipients, whereas the respective median costs for the first year of therapy were $5,623 and $6, respectively. Receipt of the LIS was associated with a 32% higher (95% CI, 16% to 47%) probability of receiving IMiDs among beneficiaries age 75 to 84 years and a significantly lower risk of delays between refills in all age groups (adjusted relative risk, 0.54; 95% CI, 0.32 to 0.92). Duration of therapy did not significantly differ between LIS recipients and nonrecipients (median, 7.6 months). Patients treated with IMiDs had significantly fewer emergency department visits and hospitalizations compared with patients receiving bortezomib (without IMiDs), but 1-year overall survival and cumulative Medicare costs were similar. Conclusion Medicare beneficiaries with myeloma who do not receive LISs face a substantial financial barrier to accessing orally administered anticancer therapy, warranting urgent attention from policymakers. Limiting out-of-pocket costs for expensive anticancer drugs like the IMiDs may improve access to oral therapy for patients with myeloma.
Arthroscopic Meniscal Surgery Is Equivalent to Nonoperative Management.

The existing research base, with biases that typically make interventions look better, is unable to demonstrate that arthroscopy for meniscal injuries is any better than nonoperative approaches. Because this is a costly intervention and is being used more often, perhaps insurance companies should reevaluate whether to continue paying for it.
Methodology for Probabilistic Modeling of Highway Bridge Infrastructure Condition: Accounting for Improvement Effectiveness and Incorporating Random Effects

AbstractThe peculiar nature of bridge infrastructure condition data persistently poses challenges in predicting bridge component deterioration that necessitate the continued investigation of probab...
Using and Combining Learning Theories in Medical Education

Medical education needs to be well informed by learning theories, and preferably more than one theory. Medical teachers need to be familiar with a range of learning theories and should be able to critique them in ways that allow us to combine good ideas from one theory with good ideas from other theories. This can give our teaching real depth and help us avoid common pitfalls that arise from misapplying a theory due to a superficial understanding. We provide an example where a number of learning theories were usefully combined.
Island Archaeology, Model Systems, the Anthropocene, and How the Past Informs the Future

The use of islands as ‘model systems’ has become particularly relevant for examining a host of important issues in archaeology and other disciplines. As papers in this special issue of the Journal ...
Olfaction in Invertebrates: Drosophila

Olfactory neurons in Drosophila are organized in sensilla in the antennae and maxillary palps. Odorants interact with soluble odorant-binding proteins and activate membrane-associated odorant receptors. Each neuron expresses one of 56 odorant receptors and the common Or83b receptor, which transports odorant receptors to the chemosensory membrane. Axons from olfactory neurons that express the same receptors converge onto output neurons within glomeruli in the antennal lobes, where distinct glomerular activation patterns encode odorant quality and concentration. Projection neurons transfer this information to the central brain, where neuronal integration is transformed into an olfactory perception that elicits an appropriate behavioral response.
Protein crosslinkages. I. Effect of iodination on the time-dependent solubility changes of reconstituted collagen fibrils.

It has been shown that the iodination of tropocollagen leads to a more rapid formation of intermoleoular crosslinks of the reconstituted fibrils as judged by the inability to dissolve the fibrils in urea-HOAc solution. Iodination of the tropocollagen without subsequent fibril formation results in the formation of some intramolecular crosslinks as determined by ultracentrifugation at 40° and acrylamide gel electrophoresis and by the melting point and formation of segmented-long-spaced structures of the cooled gelatins derived therefrom. Control experiments and aminoacid analyses have shown that possible oxidation reactions cannot account for the changes. It is postulated that the iodination of histidine and/or tyrosine residues increases the rate of a normally occurring crosslinking reaction.
The role of lysosomes in immune responses.

Publisher Summary This chapter discusses the role of lysosomes in immune responses. Lysosomes are the central part of many studies related to the tissue injury, inflammation, and immunity. Lysosomes can also be considered as the important part of a vacuolar system or an “exoplasmic reticulum” concerned with the digestion of heterologous and autologous material. Although there is a considerable body of evidence implicating macrophages in the afferent limb of the immune response, their exact role is not clear. Macrophages may prevent excess antigen from paralyzing lymphocytes that act as convenient carriers of antigen throughout the body, concentrate and retain antigen over longer periods of time, present antigen to responsive cells, degrade antigen into active subunits, convert crude antigen into a better immunogen, translate antigen into specific information, or exert some nonspecific effect on antigen-reactive cells that allow them to perform properly. Trapping of antigens by reticular cells may not be the only mechanism responsible for their localization in follicles. Recently, there is a new subpopulation of lymphocytes that binds antigen–antibody complexes in the presence of modified complement. Because the bulk of this subpopulation, termed “complement receptor lymphocytes,” resides in the follicular areas of peripheral lymphoid tissue, it may seem that the lymphocytes contribute to antibody mediated retention of antigens by lymphoid follicles.
Care Ethics, Dependency, and Vulnerability

Vulnerability has emerged as a fruitful concept in recent political discourse. Although care theorists have sometimes framed care ethics in terms of vulnerability, they have most often oriented it ...
Foundations of Criminal Justice eory Snipes and Maguire defi ne scientifi c theory and explain how it diff ers from common conceptions about the meaning of the word “theory.” Th ey

INTRODUCTION Criminal justice has been developing as an academic fi eld since the appearance of several infl uential studies and the inception of its fi rst doctoral program in the 1960s at the University at Albany. Th ere are now about three dozen programs in the United States and Canada. As the fi eld continues to grow, there is a need to monitor its evolution and identify any shortcomings, inconsistencies, or other constraints that might inhibit its development. We argue that the academic study of criminal justice must overcome a major hurdle that will otherwise limit its growth and vitality: Th ere is no common understanding or teaching of theory. Instead, academic programs consist of scattergun approaches to study, with little eff ort toward unity and coherence beyond very basic organizational divisions such as police, courts, and corrections.
Progress in Understanding and Treating Idiopathic Pulmonary Fibrosis

This is a time of substantial progress in the evaluation and care of patients with idiopathic pulmonary fibrosis (IPF). In addition to the approval and widespread availability of the first IPF-specific therapies, there have been improvements in imaging interpretation and lung biopsy methods to enable more expeditious and more accurate diagnosis. Recent advances in identifying genetic factors that underlie susceptibility to IPF and affect prognosis have raised the possibility of personalized therapeutic approaches in the future. Further, evolving work is elucidating novel mechanisms influencing epithelial, mesenchymal, and inflammatory cell responses during the injury-repair process, thus advancing understanding of disease pathogenesis. As analytic approaches mature, the field is now poised to harness the power of rapidly advancing "omics" technologies to further accelerate progress.
Exact Solutions of Some Functional Differential Equations

Publisher Summary This chapter describes the exact solutions of some functional differential equations. The Green's function of a linear autonomous retarded functional differential equation satisfies an integrodifferential equation of convolution type with kernel of compact support. It is preferable to compute the convolution of functions and distributions rather than of measures. In computing the Green's function Φ ( t ), if one assumes be the zero-order distribution, then n ( t ) is also a zero-order distribution corresponding to the nth convolution of the measure. The Green's function corresponding to a nonautonomous functional differential equation satisfies an integrodifferential equation not of convolution type.
Respiratory exacerbations in post infectious obliterative bronchiolitis

Post infectious obliterative bronchiolitis (PIBO) is an unusual and rare complication of lower respiratory tract infections in children, with Adenovirus being the most common cause. The condition is non progressive and treatments mostly supportive. Little is known about the respiratory morbidity from frequent exacerbations of respiratory symptoms. Methods: We describe the frequency and symptoms during exacerbation in a cohort of 12 patients for a mean 2.6 years after diagnosis. Diagnosis of PIBO was based on CT findings together with a suggestive clinical course. The exacerbations were classified as wheezy or infective based on the predominant symptom. Data on the types of symptoms and treatments given were collected. Results: Median age at diagnosis was 2 yrs 4 months. Most cases were post infective (80%) and the most common aetiologic agents were Adenovirus (60%), Rhinovirus (40%) and RSV (30%). Most patients were managed on long term anti-inflammatory therapy with Azithromycin and inhaled steroids. 5 patients were on home oxygen. The mean time between outpatient follow-up was 3 months. There was significant variability in the number of exacerbations ranging between 0 to 4 per year. Most children had infective exacerbations which did not usually lead to hospitalisation. Most were treated with oral antibiotics usually Co-amoxiclav. In the same individual the exacerbations are usually of the same types. Conclusion: There is considerable heterogeneity in the presentation of children with exacerbations. These may correlate with the extent of bronchiectasis radiologically. Outcomes could be improved by proactive antibiotic treatment if such a correlation can be studied in a larger cohort using a national database.