cssi/SciSciGPT-SciSciNet huggingface dataset:
The Distribution of Sales Revenues from Pharmaceutical Innovation

Objective: This report updates our earlier work on the returns to pharmaceutical research and development (R&D) in the US (1980 to 1984), which showed that the returns distributions are highly skewed. It evaluates a more recent cohort of new drug introductions in the US (1988 to 1992) and examines how the returns distribution is emerging for drugs with life cycles concentrated in the 1990s versus the 1980s. Design and setting: Methods were described in detail in our earlier reports. The current sample included 110 new drug entities (including 28 orphan drugs), and sales data were obtained for the period 1988 to 1998, which represented between 7 and 11 years of sales for the drugs included. 20 years was chosen as the expected market life for this cohort, and a 2-step procedure was used to project future sales for the drugs — during the period until patent expiry and then beyond patent expiry until the 20-year time-horizon was completed. Thus, the values in the first half of the life cycle are essentially based on realised sales, while those in the second half are projected using information on patent expiry and other inputs. Main outcome measures and results: Peak annual sales for the top decile of drugs introduced between 1988 and 1992 in the US amounted to almost $US1.1 billion compared with peak sales of less than $US175 million (1992 values) for the mean compound. In particular, the top decile accounted for 56% of overall sales revenue. Although the sales distributions were skewed in both our earlier and current analysis, the top decile in the later time-period exhibited more rapid rates of growth after launch, a peak that was more than 50% greater in real terms than for the 1980 to 1984 cohort, and a faster rate of expected decline in sales after patent expiry. One factor contributing to the distribution of sales revenues becoming more skewed over time is the orphan drug phenomenon (i.e. most of the orphan drugs are concentrated at the bottom of the distribution). Conclusion: The distribution of sales revenues for new drug compounds is highly skewed in nature. In this regard, the top decile of new drugs accounts for more than half of the total sales generated by the 1988 to 1992 cohort analysed. Furthermore, the distribution of sales revenues for this cohort is more skewed than that of the 1980 to 1984 cohort we analysed in previous research.
Asymmetric Effect of Mechanical Stress on the Forward and Reverse Reaction Catalyzed by an Enzyme

The concept of modulating enzymatic activity by exerting a mechanical stress on the enzyme has been established in previous work. Mechanical perturbation is also a tool for probing conformational motion accompanying the enzymatic cycle. Here we report measurements of the forward and reverse kinetics of the enzyme Guanylate Kinase from yeast (Saccharomyces cerevisiae). The enzyme is held in a state of stress using the DNA spring method. The observation that mechanical stress has different effects on the forward and reverse reaction kinetics suggests that forward and reverse reactions follow different paths, on average, in the enzyme's conformational space. Comparing the kinetics of the stressed and unstressed enzyme we also show that the maximum speed of the enzyme is comparable to the predictions of the relaxation model of enzyme action, where we use the independently determined dissipation coefficient for the enzyme's conformational motion. The present experiments provide a mean to explore enzyme kinetics beyond the static energy landscape picture of transition state theory.
The Crises Of The Uncontrolled And Un-understood Numbers Of Health Care Costs

Innovative technologies have dramatically reduced the risk/benefit ratios of health care. These reductions have led to marked growths in health care utilization resulting in the spiraling increases in health care costs. With minimal risks, when health me becomes necessary is not obvious. With innovative technologies, the question regarding health care delivery has changed from "Can it be done?" to "Should it be done?" Physicians do not currently have the information necessary to answer this question. Quality of care issues must replace risk/benefit ratios as the new paradigm for a physician's ordering of health care delivery. Quality of care issues include: medical indication, minimizing risks, cost efficiency and patient satisfaction. Much of health care delivered today lacks the warraritedness and efficacy components of medical indication making it unnecessary. New and, as yet, undeveloped information systems must provide information on all quality of care issues to physicians so appropriate decisions regarding health care delivery can be made. With this information, quality of care will improve and large portions of current health care delivery will be found unnecessary or nonessential. Consequently, information systems can serve to control health care costs and to improve quality of health care.
Using Google Dengue Trends to Estimate Climate Effects in Mexico

The incidence of dengue fever (DF) has increased 30 fold between 1960 and 2011. The literature suggests that temperature plays a major role in the life cycle of the mosquito vector and in turn, the timing of DF outbreaks. We use real-time data from GDT and real-time temperature estimates from NASA Earth observing systems to examine the relationship between dengue and climate in 17 Mexican states from 2003-2011. For the majority of states, we predict that a warming climate will increase the number of days the minimum temperature is within the risk range for dengue.
Ritual coordination of medical pluralism in highland Nepal: Implications for policy

In highland Nepal, just as in many other regions of South Asia, multiple indigenous healing traditions and a variety of traditional curing specialists co-exist in a pluralistic cultural environment. It is argued that the interaction of diverse medical traditions is a particular aspect of the more general tendency toward the accretion and super-imposition of cultural traits which has been a common feature of Hindu-influenced social systems. Allopathic medicine and its practitioners, therefore, are less likely to displace traditional curing practices than to become integrated into a network characterized by continued pluralism. To insure that allopathy is properly understood and utilized within the pluralistic context, the identification and training of coordinating personnel who may specialize in diagnosis or referral demonstrates promise. The traditional curing network of the Thakali people of Northwest Nepal is described, with particular attention to the mu tu ceremony of divination, as an example of an indigenous agency of medical referral. It is suggested that referral specialists such as the Buddhist monks who perform mu tu are particularly appropriate targets for health education initiatives aimed at familiarizing village populations with the role and proper usage of modern medicine.
Direct imaging of single UvrD helicase dynamics on long single-stranded DNA

Fluorescence imaging of single-protein dynamics on DNA has been largely limited to double-stranded DNA or short single-stranded DNA. We have developed a hybrid approach for observing single proteins moving on laterally stretched kilobase-sized ssDNA. Here we probed the single-stranded DNA translocase activity of Escherichia coli UvrD by single fluorophore tracking, while monitoring DNA unwinding activity with optical tweezers to capture the entire sequence of protein binding, single-stranded DNA translocation and multiple pathways of unwinding initiation. The results directly demonstrate that the UvrD monomer is a highly processive single-stranded DNA translocase that is stopped by a double-stranded DNA, whereas two monomers are required to unwind DNA to a detectable degree. The single-stranded DNA translocation rate does not depend on the force applied and displays a remarkable homogeneity, whereas the unwinding rate shows significant heterogeneity. These findings demonstrate that UvrD assembly state regulates its DNA helicase activity with functional implications for its stepping mechanism, and also reveal a previously unappreciated complexity in the active species during unwinding.
Acceptance, Mindfulness, and Science

The inclusion of technologies drawn from spiritual and religious traditions into empirical clinical psychology is a positive step forward, but it also helps reveal problems in the technological model of treatment development. The technological model does not necessarily lead to a more coherent, innovative, and progressive discipline, which requires the development of more adequate theory, not merely more adequate technology. If technologies drawn from spiritual and religious traditions are to be included in modern scientific psychology, the field must be free to interpret and transform them theoretically, without being limited by their religious and spiritual past.
Education: Keystone of Apartheid.

We must strive to win the fight against the non-White in the classroom instead of losing it on the battlefield. Administrator of the Transvaal, 19612 In all societies education fulfills some of the same basic functions. It transmits culture, trains people for specialized roles, and is simultaneously a force of continuity and change. How these functions are fulfilled varies from society to society and even at different times within the same society depending upon the character of the economy, the family, the political organization, and the religion. The literature discusses the principal functions of education in processes of social stratification. It establishes that access to education is often a status reward that is distributed differentially and that education can be a mechanism of social control. But the literature mainly provides ethnography on the role of education in class stratification. This paper describes the role of education in South Africa, a society stratified on the basis of ethnicity. Schooling in this country is divided into four component systems, each serving members of a separate "racial" category: African, Colored, Indian, and White. Moreover, within the "racial" categories, the various "ethnic" groups are also segregated. Thus, among the Africans, Zulu, Tswana, Xhosa, and so on, attend separate schools, as do the Afrikaners and English among the whites. Each system consists of primary, secondary, university, technical, and teacher training institutions. For purposes of highlighting the role of education in social stratification, however, only white and African primary and secondary education are contrasted here. The analysis demonstrates how education is being manipulated for stratification purposes, that is, how it is being used as an instrument of social engineering. The first section describes the historical relationship of education to some of the major political and economic events in South Africa. The
Strong termination for the epsilon substitution method

Ackermann proved termination for a special order of reductions in Hilbert's epsilon substitution method for the first order arithmetic. We establish termination for arbitrary order of reductions. ?
Model (in) validation of switched ARX systems with unknown switches and its application to activity monitoring

Identification of switched linear systems has received considerable attention during the past few years. Since the problem is generically NP-Hard, the majority of existing algorithms are based on heuristics or relaxations. Therefore, it is crucial to check the validity of the identified models against additional experimental data. This paper addresses the problem of model (in)validation for multi-input multi-output switched affine autoregressive exogenous systems with unknown switches. Our main result provides necessary and sufficient conditions for a given model to be (in) validated by the experimental data. In principle, checking these conditions requires solving a sequence of convex optimization problems involving increasingly large matrices. However, as we show in the paper, if in the process of solving these problems either a positive solution is found or the so-called flat extension property holds, then the process terminates with a certificate that either the model has been invalidated or that the experimental data is indeed consistent with the model and a-priori information. By using duality, the proposed approach exploits the inherently sparse structure of the optimization problem to substantially reduce its computational complexity. The effectiveness of the proposed method is illustrated using both academic examples and a non-trivial problem arising in computer vision: activity monitoring.
Desiccation resistance in arboreal and terrestrial ants.

Arboreal and terrestrial ants were exposed to 0, 25, 50, 75 and 100 (control)% r.h., at 30oC. Desiccation resistance increased with body size (as dry weight0.55), but not as quickly as expected from the consequences of the surface area and volume relationship (as dry weight0.67). Arboreal ants took 8 times longer to die than terrestrial ants of comparable size. Even after size effects were removed, desiccation resistance differed between various terrestrial species and showed a correlation with foraging patterns. Arboreal and terrestrial ants whose waterproofing epicuticular lipids were removed by chloroform: methanol extraction had equally high water loss rates at 0% r.h. Unextracted arboreal ants had water loss rates half those of unextracted terrestrial ants, suggesting that differences between them were based on differences in epicuticular lipids. The lower water loss rates of arboreal ants contributed significantly to their longer survival under desiccation. Arboreal ants also had greater total rectal pad area than terrestrial ants, suggesting that they may be able to reclaim faecal water more effectively. There were no differences in the minimum viable water content between the two groups of ants. Both had water loss tolerances comparable with those of arthropods adapted to xeric environments. Initial water loss rates could not account for all of the differences in desiccation resistance between arboreal and terrestrial ants. Other adaptations to desiccation stress by arboreal ants are likely. Comparisons of water loss rates and desiccation resistance between arboreal and desert ants suggest that the arboreal habitat is at least as stressful as the desert habitat.
Making the Case for Contract Theory

Economics has changed a great deal in the last thirty years and there is every reason to think that the changes in the next twenty to thirty years will be at least as great. Although theory may not be as prominent as it once was, it remains essential for understanding the (increasingly) complex world we live in. One cannot analyze the bewildering amount of data now available, or make sensible policy recommendations, without the organizing framework that theory provides. Contract theory is a good example of an area where great progress has been made in the last thirty years, and yet where much remains to be done. In this short essay I will discuss some of the major themes of contract theory and also issues that are still not well understood.
Effects of Extreme Hemodilution during Cardiac Surgery on Cognitive Function in the Elderly

Background Strategies for neuroprotection including hypothermia and hemodilution have been routinely practiced since the inception of cardiopulmonary bypass. Yet postoperative neurocognitive deficits that diminish the quality of life of cardiac surgery patients are frequent. Because there is uncertainty regarding the impact of hemodilution on perioperative organ function, the authors hypothesized that extreme hemodilution during cardiac surgery would increase the frequency and severity of postoperative neurocognitive deficits. Methods Patients undergoing coronary artery bypass grafting surgery were randomly assigned to either moderate hemodilution (hematocrit on cardiopulmonary bypass >or=27%) or profound hemodilution (hematocrit on cardiopulmonary bypass of 15-18%). Cognitive function was measured preoperatively and 6 weeks postoperatively. The effect of hemodilution on postoperative cognition was tested using multivariable modeling accounting for age, years of education, and baseline levels of cognition. Results After randomization of 108 patients, the trial was terminated by the Data Safety and Monitoring Board due to the significant occurrence of adverse events, which primarily involved pulmonary complications in the moderate hemodilution group. Multivariable analysis revealed an interaction between hemodilution and age wherein older patients in the profound hemodilution group experienced greater neurocognitive decline (P = 0.03). Conclusions In this prospective, randomized study of hemodilution during cardiac surgery with cardiopulmonary bypass in adults, the authors report an early termination of the study because of an increase in adverse events. They also observed greater neurocognitive impairment among older patients receiving extreme hemodilution.
Online traveling salesman problems with service flexibility

The traveling salesman problem is a well-known combinatorial optimization problem. We are concerned here with online versions of this problem defined on metric spaces. One novel aspect in this article is the introduction of a sound theoretical model to incorporate “yes-no” decisions on which requests to serve, together with an online strategy to visit the accepted requests. To do so, we assume that there is a penalty for not serving a request. Requests for visit of points in the metric space are revealed over time to a server, initially at a given origin, who must decide in an online fashion which requests to serve to minimize the time to serve all accepted requests plus the sum of the penalties associated with the rejected requests. We first look at the special case of the non-negative real line. After providing a polynomial time algorithm for the offline version of the problem, we propose and prove the optimality of a 2-competitive polynomial time online algorithm based on reoptimization approaches. We also consider the impact of advanced information (lookahead) on this optimal competitive ratio. We then consider the generalizations of these results to the case of the real line. We show that the previous algorithm can be extended to an optimal 2-competitive online algorithm. Finally we consider the case of a general metric space and propose an original c -competitive online algorithm, where \documentclass{article}\usepackage{mathrsfs, amsmath, amsfonts, amssymb}\pagestyle{empty}\begin{document} $c = \sqrt{({17+5})}/{4} \approx 2.28$ \end{document} **image** . We also give a polynomial-time (1.5ρ + 1) -competitive online algorithm which uses a polynomial-time ρ -approximation for the offline problem. © 2011 Wiley Periodicals, Inc. NETWORKS, 2011 © 2011 Wiley Periodicals, Inc.
AIDS and the Elderly

Individuals 50 years of age or older continue to account for at least 10% of AIDS cases reported to the Centers for Disease Control and Prevention in recent years. Little research is devoted to addressing the specific issues affecting diagnosis, treatment, and prevention of AIDS in older Americans. Survival rates among elderly individuals infected with human immunodeficiency virus (HIV) are consistently decreased in comparison with those for younger patients. Elderly individuals also are less likely to use a condom during sexual intercourse or to participate in routine HIV testing. This article reviews the current literature concerning the changing epidemiology of AIDS among older Americans. The article also addresses AIDS-related morbidity and mortality, treatment issues, and HIV-prevention behaviors among the elderly. Enhanced clinician awareness of HIV in the elderly, along with further research concerning HIV treatment and prevention, is necessary to improve survival and outcome for those patients.
A Small Molecule Inhibitor of Redox-Regulated Protein Translocation into Mitochondria

The mitochondrial disulfide relay system of Mia40 and Erv1/ALR facilitates import of the small translocase of the inner membrane (Tim) proteins and cysteine-rich proteins. A chemical screen identified small molecules that inhibit Erv1 oxidase activity, thereby facilitating dissection of the disulfide relay system in yeast and vertebrate mitochondria. One molecule, mitochondrial protein import blockers from the Carla Koehler laboratory (MitoBloCK-6), attenuated the import of Erv1 substrates into yeast mitochondria and inhibited oxidation of Tim13 and Cmc1 in in vitro reconstitution assays. In addition, MitoBloCK-6 revealed an unexpected role for Erv1 in the carrier import pathway, namely transferring substrates from the translocase of the outer membrane complex onto the small Tim complexes. Cardiac development was impaired in MitoBloCK-6-exposed zebrafish embryos. Finally, MitoBloCK-6 induced apoptosis via cytochrome c release in human embryonic stem cells (hESCs) but not in differentiated cells, suggesting an important role for ALR in hESC homeostasis.
Massive and massless monopoles with non-Abelian magnetic charges.

We use the multimonopole moduli space as a tool for studying the properties of BPS monopoles carrying non-Abelian magnetic charges. For configurations whose total magnetic charge is purely Abelian, the moduli space for non-Abelian breaking can be obtained as a smooth limit of that for a purely Abelian breaking. As the asymptotic Higgs field is varied toward one of the special values for which the unbroken symmetry is enlarged to a non-Abelian group, some of the fundamental monopoles of unit topological charge remain massive but acquire non-Abelian magnetic charges. The BPS mass formula indicates that others should become massless in this limit. We find that these do not correspond to distinct solitons but instead manifest themselves as {open_quote}{open_quote}non-Abelian clouds{close_quote}{close_quote} surrounding the massive monopoles. The moduli space coordinates describing the position and U(1) phase of these massless monopoles are transformed into an equal number of non-Abelian global gauge orientation and gauge-invariant structure parameters characterizing the non-Abelian cloud. We illustrate this explicitly in a class of Sp(2{ital N}) examples for which the full family of monopole solutions is known. We show in detail how the unbroken symmetries of the theory are manifested as isometries of the moduli space metric. We discuss themore » connection of these results to the Montonen-Olive duality conjecture, arguing in particular that the massless monopoles should be understood as the duals to the massless gauge bosons that appear as the mediators of the non-Abelian forces in the perturbative sector. {copyright} {ital 1996 The American Physical Society.}« less
200mm Fab AMHS improvement during aggressive ramp

The semiconductor industry experienced increased requirements during the period 2008–2010. These requirements were followed by more wafer starts (loading upside). Micron Israel's 200mm factory capacity increased by more than 40% within one year. The automated material handling system (AMHS) was not originally intended to support a 40% load increase. Prior to the load increase, the 200mm AMHS was not considered a factory constraint. However, after the increase, with the AMHS capacity gap at about 40% of the expected loading, a capacity improvement roadmap was implemented for all toolsets, including the AMHS. This roadmap, among other things, included: optimization of the lot destination, stocker capacity increase, stocker cleaning, and leading parameter definition to prioritize manual handling of lots and route changes. Roadmap action plan priorities were set through simulation gain analysis. All of the AMHS improvements resulted in a system capability increase of more than 20% over the original planned capability. This paper presents a review of the AMHS improvement roadmap actions that led to the system capability increase.
Myelopoiesis in the zebrafish, Danio rerio

Genome-wide chemical mutagenesis screens in the zebrafish (Danio rerio) have led to the identification of novel genes affecting vertebrate erythropoiesis. In determining if this approach could also be used to clarify the molecular genetics of myelopoiesis, it was found that the developmental hierarchy of myeloid precursors in the zebrafish kidney is similar to that in human bone marrow. Zebrafish neutrophils resembled human neutrophils, possessing segmented nuclei and myeloperoxidase-positive cytoplasmic granules. The zebrafish homologue of the human myeloperoxidase (MPO) gene, which is specific to cells of the neutrophil lineage, was cloned and used to synthesize antisense RNA probes for in situ hybridization analyses of zebrafish embryos. Granulocytic cells expressing zebrafish mpo were first evident at 18 hours after fertilization (hpf) in the posterior intermediate cell mass (ICM) and on the anterior yolk sac by 20 hpf. By 24 hpf, mpo-expressing cells were observed along the ICM and within the developing vascular system. Thus, the mpo gene should provide a useful molecular probe for identifying zebrafish mutants with defects in granulopoiesis. The expression of zebrafish homologues was also examined in 2 other mammalian hematopoietic genes, Pu.1, which appears to initiate a commitment step in normal mammalian myeloid development, and L-Plastin, a gene expressed by human monocytes and macrophages. The results demonstrate a high level of conservation of the spatio-temporal expression patterns of these genes between zebrafish and mammals. The morphologic and molecular genetic evidence presented here supports the zebrafish as an informative model system for the study of normal and aberrant human myelopoiesis. (Blood. 2001;98:643-651)
Positive Temperature Coefficient of Resistance and Bistable Conduction in Lead Selenide Quantum Dot Thin Films

We report the observation of a positive temperature coefficient of resistance in strongly coupled quantum dot (QD) arrays. Conductivities of lead selenide (PbSe) QD thin films treated with 1,2-ethanedithiol increase when cooled from room temperature to 78 K, consistent with bulk PbSe crystals and indicating bandlike transport. Small angle X-ray scattering and infrared absorption spectroscopy results confirm a very strong electronic coupling among QDs. These QD thin films also exhibit bistable conduction above 160 K. As the electric field reaches a threshold, on the order of 0.1 V/μm, the film conductance increases abruptly by up to 10 orders of magnitude and remains high until the bias voltage is reduced to about zero volts. This bistability is likely induced either by filament formation or by a trap-related electronic switching.
Piperidinium tethered nanoparticle-hybrid electrolyte for lithium metal batteries

We report on the synthesis of novel piperidinium-based ionic liquid tethered nanoparticle hybrid electrolytes and investigate their physical and electrochemical properties. Hybrid electrolytes based on the ionic liquid 1-methyl-1-propylpiperidinium bis(trifluoromethanesulfone) imide covalently tethered to silica nanoparticles (SiO2–PP–TFSI) were blended with propylene carbonate–1 M lithium bis(trifluoromethanesulfone) imide (LiTFSI). We employed NMR analysis to confirm the successful creation of the hybrid material. Dielectric and rheological measurements show that these electrolytes exhibit exceptional room-temperature DC ionic conductivity (10−2 to 10−3 S cm−1) as well as high shear mechanical moduli (105 to 106 Pa). Lithium transference numbers were found to increase with particle loading and to reach values as high as 0.22 at high particle loadings where the particle jam to form a soft glassy elastic medium. Analysis of lithium electrodeposits obtained in the hybrid electrolytes using SEM and EDX spectra show that the SiO2–PP–TFSI nanoparticles are able to smooth lithium deposition and inhibit lithium dendrite proliferation in Li metal batteries. LTO|SiO2–PP–TFSI/PC in 1 M LiTFSI|Li half-cells based on the SiO2–PP–TFSI hybrid electrolytes exhibit attractive voltage profiles and trouble-free extended cycling behavior over more than 1000 cycles of charge and discharge.
Plumage color and reproduction in the red-backed fairy-wren: Why be a dull breeder?

Males of many species can breed in distinct alternative phenotypes; for example, in many birds some males breed in dull plumage while others breed in bright plumage. Because females often appear to prefer brighter males, it is unclear why some males breed in dull plumage. Males in dull plumage might enjoy enhanced within-pair reproductive success if they can gain access to better breeding territories, or they might have relatively high extrapair reproductive success if they are better able to intrude on the territories of other males. To test these possibilities, we examined the reproductive consequences of plumage color in the red-backed fairy-wren (Malurus melanocephalus), a species in which males can breed in either bright plumage or dull plumage or serve as nonbreeding auxiliaries. Male plumage color was distributed bimodally and was loosely associated with age, such that some males molted into bright plumage a year or more earlier than others. Both male phenotypes were cuckolded at similar rates, but bright males sired significantly more extrapair young than did dull males, and this effect was independent of age. Thus, 1-year-old males who bred in dull plumage had low seasonal reproductive success compared with same-aged males who bred in bright plumage. These results suggest that males may not reap any fitness benefits by breeding in dull coloration, compared with breeding in bright plumage, but rather may be constrained to breed in suboptimal plumage by the timing of plumage acquisition.
The role of academic inventors in entrepreneurial firms: sharing the laboratory life

While science-based entrepreneurial firms are a key feature of the modern economy, our insights into their organization and productivity remain limited. In particular, our understanding of the mechanisms through which academic inventors shape entrepreneurial firms established to commercialize their scientific ideas is based upon a traditional perspective that highlights the importance of human capital. Based on a study of biotechnology firms and their academic inventors, this paper examines the extent and mechanisms through which academic scientists contribute not only human capital but also social capital to entrepreneurial firms. The paper makes two contributions to our understanding of the academic–firm interface: First, it establishes that the social capital of academic scientists is critical to firms because it can be transformed into scientific networks that embed the firm in the scientific community through a variety of mechanisms. Second, the paper argues that an academic inventor’s career plays a critical role in shaping his social capital, thus scientific careers mediate the networks and potential for embeddedness that an academic inventor brings to a firm. Specifically, the foundations of an academic’s social capital can be traced to two sources: The first element that the firm may leverage is the academic’s local laboratory network—a network to current and former students and advisors established by the inventor through his laboratory life. The second form of social capital is a wider, cosmopolitan network of colleagues and co-authors established through the social patterns of collaboration, collegiality and competition that exemplify scientific careers. These findings suggest that scientific careers are central in shaping an academic’s social capital which can be translated into critical scientific networks in which entrepreneurial firms become embedded.
Thermal processing of hydroxyapatite for coating production

Thermally processed hydroxyapatite coatings used on dental implants and hip prostheses for enhanced fixation may typically consist of a number of chemical and structural phases. These phases affect coating performance and tissue attachment. Hydroxyapatite was plasma sprayed to examine the phase evolution during processing. Coatings were examined with X-ray diffraction and elemental analysis. Results indicate that phase transformations are produced by (a) preferential removal of hydroxyl and phosphate leading to a change in melt composition, and (b) the high cooling rate due to the thermal spray process. Hydroxyl group removal promotes the amorphous phase and oxyapatite. Further heating produces a less viscous melt facilitating decomposition of hydroxyapatite to tricalcium and tetracalcium phosphate. Phosphate removal during flight produces a more calcium-rich melt preferring tetracalcium phosphate and calcium oxide formation. A proposed model shows the phase location within the lamellae of these coatings. Coating processes must thus prevent removal of hydroxide and phosphate during processing to maximize the hydroxyapatite content.
Computational Analysis of DNA Gyrase Action

DNA gyrase introduces negative supercoiling into circular DNA by catalyzing the passage of one DNA segment through another. The efficiency of the reaction is many times higher than that of other topological transformations. We analyze, by a computer simulation, the reaction selectivity for a model of DNA gyrase action that assumes existence of a free loop between the G- and T- DNA segments participating in the reaction. A popular model of this type assumed that the selectivity can be provided by the conformation of the DNA segment wrapped around the enzyme into the right-handed helix turn (G-segment). We simulated the distribution of the reaction products for this model. Equilibrium sets of DNA conformations with one segment of the double helix wrapped around the enzyme were constructed. From these sets we selected conformations that had a second segment properly juxtaposed with the first one. Assuming that the juxtapositions result in the strand-passing reaction, we calculated the reaction products for all these conformations. The results show that different products have to be formed if the enzyme acts according to the model. This conclusion can be extended for any model with a free loop between the G- and T-segments. An alternative model that is consistent with the major experimental observations and the computational analysis, is suggested.
The Memorial Symptom Assessment Scale: an instrument for the evaluation of symptom prevalence, characteristics and distress

The Memorial Symptom Assessment Scale (MSAS) is a new patient-rated instrument that was developed to provide multidimensional information about a diverse group of common symptoms. This study evaluated the reliability and validity of the MSAS in the cancer population. Randomly selected inpatients and outpatients (n = 246) with prostate, colon, breast or ovarian cancer were assessed using the MSAS and a battery of measures that independently evaluate phenomena related to quality of life. Symptom prevalence in the 218 evaluable patients ranged from 73.9% for lack of energy to 10.6% for difficulty swallowing. Based on a content analysis, three symptoms were deleted and two were added; the revised scale evaluates 32 physical and psychological symptoms. A factor analysis of variance yielded two factors that distinguished three major symptom groups and several subgroups. The major groups comprised psychological symptoms (PSYCH), high prevalence physical symptoms (PHYS H), and low prevalence physical symptoms (PHYS L). Internal consistency was high in the PHYS H and PSYCH groups (Cronback alpha coefficients of 0.88 and 0.83, respectively), and moderate in the PHYS L group (alpha = 0.58). Although the severity, frequency and distress dimensions were highly intercorrelated, canonical correlations and other analyses demonstrated that multidimensional assessment (frequency and distress) augments information about the impact of symptoms. High correlations with clinical status and quality of life measures support the validity of the MSAS and indicate the utility of several subscale scores, including PSYCH, PHYS, and a brief Global Distress Index. The MSAS is a reliable and valid instrument for the assessment of symptom prevalence, characteristics and distress. It provides a method for comprehensive symptom assessment that may be useful when information about symptoms is desirable, such as clinical trials that incorporate quality of life measures or studies of symptom epidemiology.
A Model of the Nature of Family-Therapist Relationships: Implications for Education

Objectives The family play an important role in rehabilitation of persons with chronic disabilities and in supporting their reintegration into the community. To be prepared for family-centered intervention, educators need to frame the content that occupational therapy students must master. The purpose of this study was to develop a hierarchy of occupational therapists' attitudes about the family's involvement in services for a family member with special needs. Method Participants were 302 occupational therapists who reported some contact with families of clients. Through an open-ended question, participants were asked to indicate the most important outcome of their interactions with their clients' families. Results Analysis of participant responses led to the development of a seven-level hierarchy of family-therapist interactions. The levels are based on the participants' views of the outcome of family involvement as suggested by their attitudes about a family's role and abilities. Knowledge and skills needed to work at different levels of the hierarchy are identified. Conclusion Recommendations for preparation of entry-level practitioners to work at all levels of the model are discussed.
Rate Effect, Size Effect and Nonlocal Concepts for Fracture of Concrete and Other Quasi-Brittle Materials

The lecture reviews several recent results achieved at Northwestern University in the problem of size effects and nonlocal concepts for concrete and other brittle heterogeneous materials, and presents a new method for calculating the load-deflection curves of fracture specimens or structures with time-dependent crack growth and viscoelastic material behavior. The results reviewed deal with the size effect law in fracture and its exploitation for determining material fracture characteristics, statistical generalization of the size effect law with a nonlinear reformulation of Weibull’s weakest-link theory, determination of the size dependence of the fracture energy determined by work-of-fracture method, nonlocal models for smeared cracking and damage, microstructural determination of the nonlocal material properties and fracture process zone behavior, size effect in fatigue fracture of concrete, and use of the size effect for determining the fracture properties of high-strength concrete.
Reengineering: Internal Controls Are More Important Than Ever Before

Companies are reengineering their fundamental business processes to improve quality, service, and efficiency. When vital business processes are reengineered, new ways of managing and controlling the processes are required. A reengineered accounts payable system and the controls that should be included in the system are described. Through training and support of those who will perform the new processes and the appropriate use of internal controls, companies will maximize their benefits from business reengineering.
Interactive Scalar Quantization for Distributed Resource Allocation

In many resource allocation problems, a centralized controller needs to award some resource to a user selected from a collection of distributed users with the goal of maximizing the utility the user would receive from the resource. This can be modeled as the controller computing an extremum of the distributed users’ utilities. The overhead rate necessary to enable the controller to reproduce the users’ local state can be prohibitively high. An approach to reduce this overhead is interactive communication wherein rate savings are achieved by tolerating an increase in delay. In this paper, we consider the design of a simple achievable scheme based on successive refinements of scalar quantization at each user. The optimal quantization policy is computed via a dynamic program and we demonstrate that tolerating a small increase in delay can yield significant rate savings. We then consider two simpler quantization policies to investigate the scaling properties of the rate-delay tradeoffs. Using a combination of these simpler policies, the performance of the optimal policy can be closely approximated with lower computational costs.
Design of a series elastic humanoid for the DARPA Robotics Challenge

This paper describes the mechanical design of ESCHER, a series elastic humanoid developed to compete in the DARPA Robotics Challenge (DRC). The design methodology was informed by preliminary experimental results obtained using the THOR humanoid, a prototype platform developed for the DRC Trials, relying heavily on an accurate model of the torque-controlled robot in the Gazebo simulation environment. The redesigned lower body features a unique double actuated knee; by driving the single degree of freedom joint with two identical linear series elastic actuators (SEAs), the lower body is able to meet the necessary speed and torque requirements for locomotion on rough terrain. Experimental results demonstrating ESCHER's ability to step onto a 23 cm block, representative of the stairs task at the DRC Finals, validating the proposed approach. Joint torques measured on the hardware platform approximate those in simulation, validating the proposed design methodology.
Cofactor-Mediated Conformational Dynamics Promote Product Release From Escherichia coli Dihydrofolate Reductase via an Allosteric Pathway

The enzyme dihydrofolate reductase (DHFR, E) from Escherichia coli is a paradigm for the role of protein dynamics in enzyme catalysis. Previous studies have shown that the enzyme progresses through the kinetic cycle by modulating the dynamic conformational landscape in the presence of substrate dihydrofolate (DHF), product tetrahydrofolate (THF), and cofactor (NADPH or NADP(+)). This study focuses on the quantitative description of the relationship between protein fluctuations and product release, the rate-limiting step of DHFR catalysis. NMR relaxation dispersion measurements of millisecond time scale motions for the E:THF:NADP(+) and E:THF:NADPH complexes of wild-type and the Leu28Phe (L28F) point mutant reveal conformational exchange between an occluded ground state and a low population of a closed state. The backbone structures of the occluded ground states of the wild-type and mutant proteins are very similar, but the rates of exchange with the closed excited states are very different. Integrated analysis of relaxation dispersion data and THF dissociation rates measured by stopped-flow spectroscopy shows that product release can occur by two pathways. The intrinsic pathway consists of spontaneous product dissociation and occurs for all THF-bound complexes of DHFR. The allosteric pathway features cofactor-assisted product release from the closed excited state and is utilized only in the E:THF:NADPH complexes. The L28F mutation alters the partitioning between the pathways and results in increased flux through the intrinsic pathway relative to the wild-type enzyme. This repartitioning could represent a general mechanism to explain changes in product release rates in other E. coli DHFR mutants.
IR Theory's 21st Century Experiential Evolution

Twenty-first century scholarship within international relations illuminates a sea-change away from the primacy of the state and second order analyses toward the relationship that individuals have within the international system, linking first- and third-order analyses together. This intellectual movement reflects experiences in international history that diminish the role of the state and reinforce the humans and humanity into the heart of a discipline whose origins lie not only in what has been done (international history) but also in the motivation for action. This change is a 21st century phenomenon with experiential roots in the terror attacks of 9/11, the Global Financial Crisis, the resultant uprisings such as Arab Spring and Occupy, and the rise of hacktivism. These global, historical experiences are fostering the rise of cutting-edge and revolutionary IR theory that embraces complexity and multidisciplinarity rather than paying homage to self-absorbed philosophical traditions.
Sulfation pathway of thyroid hormone metabolism in selenium-deficient male rats.

Male Sprague-Dawley rats were fed a selenium-deficient yeast-based laboratory diet or a control diet for 6 wk. The tissue type I 5'-monodeiodinase (5'-MDI) activity and the immunoassayable 5'-MDI w...
Withholding anticoagulation following a single negative whole-leg ultrasound in patients at high pretest probability for deep vein thrombosis.

Prompt, accurate diagnosis of deep vein thrombosis (DVT) is essential. A single, whole-leg ultrasound (whole-leg US) has been used to exclude DVT, but limited data exist for patients with high pretest probability (PTP) for DVT. This diagnostic management study tested the rate of venous thromboembolism (VTE) in patients with a PTP of “DVT likely” per the simplified Wells score when anticoagulation is withheld based on a single, negative whole-leg US. Consecutive patients presenting during coordinator shifts with a PTP of DVT likely were enrolled. Anticoagulation was withheld after a single, negative whole-leg US. The outcome was objectively confirmed VTE in 3 months. All 167 patients completed the follow-up. A single patient death was adjudicated as possibly caused by VTE, resulting in a VTE rate of 0.60% (95% confidence interval: 0.02%-3.29%). Whole-leg US should be further studied in diagnostic algorithms that utilize PTP scoring and d-dimer testing.
Modification of Herbivore and Parasitoid Behavior Over Three Trophic Levels by the Entomopathogen Nosema pyrausta (Microsporida: Nosematidae)

Effects of the microsporidian Nosema pyrausta Paillot on behavior of the European corn borer, Ostrinia nubilalis (Hubner), and its parasitoid, Macrocentrus grandii Goidanich, were examined in the laboratory. Silk produced by O. nubilalis larvae around feeding and pupation sites was more frequently diffuse (cobweblike, unstructured) in diet cups containing N. pyrausta -infected larvae; however, frequency of diffuse silk production by O. nubilalis larvae was not influenced by M. grandii parasitism. We found no evidence of N. pyrausta spores in the silk produced by infected O. nubilalis larvae. Three O. nubilalis cocoon statuses were identified as follows: (1) complete cocoon, in which thick silk cocoon completely surrounded larvae or larval remains at O. nubilalis or M. grandii pupation; (2) incomplete cocoon, which was open on one or more sides at pupation; and (3) no cocoon at pupation. The percentage of O. nubilalis larvae that formed a complete cocoon or no cocoon was significantly influenced by both infection by N. pyrausta and parasitism by M. grandii. O. nubilalis larvae that had been either infected or parasitized displayed ≈7.2- and 12.3-fold increases in activity, respectively. Larvae that had been both infected and parasitized displayed a 45-fold increase in level of activity. Sixty-two to 80% of parasitoids emerging from hosts with an incomplete cocoon, and >91% emerging from no cocoon, were unable to spin their own cocoons, wandered from host carcasses, and did not pupate. The incidence of M. grandii spinning and wandering, and distance wandered, were independent of N. pyrausta dosage to which host larvae were exposed. Fully fed M. grandii larvae, which emerged from hosts that had not spun cocoons and were placed in complete cocoons, were able to pupate successfully and to emerge, regardless of infection status.
¡Oye Loca!: From the Mariel Boatlift to Gay Cuban Miami . By Susana Peña.

Given the heightened public visibility of the gay movement in Cuba over the last several years and the recent series of setbacks in LGBTQ civil rights in the United States, iOye Loca! is exactly th...