University of Illinois at Springfield

Identification and size characterization of surface pockets and occluded cavities are initial steps in protein structure-based ligand design. A new program, CAST, for automatically locating and measuring protein pockets and cavities, is based on precise computational geometry methods, including alpha shape and discrete flow theory. CAST identifies and measures pockets and pocket mouth openings, as well as cavities. The program specifies the atoms lining pockets, pocket openings, and buried cavities; the volume and area of pockets and cavities; and the area and circumference of mouth openings. CAST analysis of over 100 proteins has been carried out; proteins examined include a set of 51 monomeric enzyme-ligand structures, several elastase-inhibitor complexes, the FK506 binding protein, 30 HIV-1 protease-inhibitor complexes, and a number of small and large protein inhibitors. Medium-sized globular proteins typically have 10-20 pockets/cavities. Most often, binding sites are pockets with 1-2 mouth openings; much less frequently they are cavities. Ligand binding pockets vary widely in size, most within the range 10(2)-10(3)A3. Statistical analysis reveals that the number of pockets and cavities is correlated with protein size, but there is no correlation between the size of the protein and the size of binding sites. Most frequently, the largest pocket/cavity is the active site, but there are a number of instructive exceptions. Ligand volume and binding site volume are somewhat correlated when binding site volume is < or =700 A3, but the ligand seldom occupies the entire site. Auxiliary pockets near the active site have been suggested as additional binding surface for designed ligands (Mattos C et al., 1994, Nat Struct Biol 1:55-58). Analysis of elastase-inhibitor complexes suggests that CAST can identify ancillary pockets suitable for recruitment in ligand design strategies. Analysis of the FK506 binding protein, and of compounds developed in SAR by NMR (Shuker SB et al., 1996, Science 274:1531-1534), indicates that CAST pocket computation may provide a priori identification of target proteins for linked-fragment design. CAST analysis of 30 HIV-1 protease-inhibitor complexes shows that the flexible active site pocket can vary over a range of 853-1,566 A3, and that there are two pockets near or adjoining the active site that may be recruited for ligand design.

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Clinical questions regarding the treatment and management of AAV were developed in the population, intervention, comparator, and outcome (PICO) format (47 for GPA/MPA, 34 for EGPA). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 26 recommendations and 5 ungraded position statements for GPA/MPA, and 15 recommendations and 5 ungraded position statements for EGPA. This guideline provides recommendations for remission induction and maintenance therapy as well as adjunctive treatment strategies in GPA, MPA, and EGPA. These recommendations include the use of rituximab for remission induction and maintenance in severe GPA and MPA and the use of mepolizumab in nonsevere EGPA. All recommendations are conditional due in part to the lack of multiple randomized controlled trials and/or low-quality evidence supporting the recommendations. CONCLUSION: This guideline presents the first recommendations endorsed by the American College of Rheumatology and the Vasculitis Foundation for the management of AAV and provides guidance to health care professionals on how to treat these diseases.

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis. METHODS: Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions. CONCLUSION: These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions.

Abstract Traditional expectations for how widely and how often freshwater invertebrates disperse differ from empirical data. Freshwater invertebrates have been characterized as frequent, widespread dispersers, particularly those that are transported passively. Our review finds that this characterization may describe the potential for dispersal in some taxa, but it is not an accurate generalization for actual dispersal rates. High variance among habitats and taxonomic groups is a consistent theme. Advances in population genetics may help resolve these issues, but underlying assumptions should be carefully tested. Further, even unbiased estimates of gene flow may not equate with individual movement, because not all dispersers survive and reproduce. Some freshwater invertebrates may exist in classic Levins metapopulations. However, other species fit into a broader metapopulation definition, where temporal dispersal via diapause is functionally equivalent to spatial dispersal. In the latter case, local extinctions and rescue effects may be rare or absent. Finally, limited dispersal rates in many taxa suggest that theories of freshwater community assembly and structure can be made more robust by integrating dispersal and local processes as joint, contingent regulators. Recent research on freshwater invertebrate dispersal has substantially advanced our basic and applied understanding of freshwaters, as well as evolutionary ecology in general.

BACKGROUND: The Delphi method is a research approach that is beneficial when wanting to solve real-world problems, and expert opinions are needed. OBJECTIVES: The purpose of this study was to describe the Delphi method as a qualitative research approach and provide a case study example of a study using the Delphi method to demonstrate the advantages and challenges of this methodological approach. METHODS: A literature search was conducted to understand the Delphi method and examine its use in nursing. RESULTS: The literature search revealed what the Delphi method was and how it could be used. To better help explain the method, a case study from the literature is presented. DISCUSSION: Using the Delphi method in nursing research is becoming easier. With emerging technology, communication with geographically diverse experts may be easily and affordably achieved. With updated software, results can be interpreted almost immediately, and additional rounds of the Delphi occur in a timely manner, increasing participation and decreasing attrition rates. The Delphi method is a viable option for nurse researchers looking for expert opinion.

Job segregation—the tendency for men and women to work in different occupations—is often cited as the reason that women's wages lag men's. But this begs the question: What is it about women's jobs that causes them to pay less? We argue that emotional labor offers the missing link in the explanation. Tasks that require the emotive work thought natural for women, such as caring, negotiating, empathizing, smoothing troubled relationships, and working behind the scenes to enable cooperation, are required components of many women's jobs. Excluded from job descriptions and performance evaluations, the work is invisible and uncompensated. Public service relies heavily on such skills, yet civil service systems, which are designed on the assumptions of a bygone era, fail to acknowledge and compensate emotional labor.

The properties and most successful methods for producing CuInSe2 films for solar-cell applications are reviewed and the production, analysis, and performance of photovoltaic devices based on CuInSe2 are discussed. The most successful methods for depositing thin CuInSe2 films for high-efficiency solar cells are three-source elemental evaporation and selenization of Cu/In layers in H2Se atmospheres. Devices based on CuInSe2 have achieved the highest conversion efficiencies for any nonepitaxial thin-film solar cell, 14.1% for a small cell and 10.4% (aperture efficiency) for a 3916-cm2 (4 sq. ft) device. Furthermore, high-efficiency devices have been produced by several groups and have shown no evidence of degradation of performance with time. The internal quantum efficiency is remarkably close to 100%, although various losses prevent making use of all of the generated carriers. The high performance results, in part, from the very-high-absorption coefficient of CuInSe2, which is of the order of 105 cm−1 for photons with energies slightly above 1 eV. Models of the operation of CuInSe2/CdS heterojunctions have begun to explain the processes limiting the device performance. The success of the models is based, in part, on the large amount of data which has accumulated on CuInSe2 in spite of the relatively short time it has been extensively studied.

Abstract Rationale This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months. Objectives To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe. Methods Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the ΔEBV–SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George’s Respiratory Questionnaire scores. Measurements and Main Results A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a ΔFEV1 greater than or equal to 15% (P &amp;lt; 0.001). ΔEBV–SoC at 12 months was statistically and clinically significant: for FEV1, 0.106 L (P &amp;lt; 0.001); 6-minute-walk distance, +39.31 m (P = 0.002); and St. George’s Respiratory Questionnaire, −7.05 points (P = 0.004). Significant ΔEBV–SoC were also observed in hyperinflation (residual volume, −522 ml; P &amp;lt; 0.001), modified Medical Research Council Dyspnea Scale (−0.8 points; P &amp;lt; 0.001), and the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index (−1.2 points). Pneumothorax was the most common serious adverse event in the treatment period (procedure to 45 d), in 34/128 (26.6%) of EBV subjects. Four deaths occurred in the EBV group during this phase, and one each in the EBV and SoC groups between 46 days and 12 months. Conclusions Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe. Clinical trial registered with www.clinicaltrials.gov (NCT 01796392).

The apparent decline in voter participation in national elections since 1972 is an illusion created by using the Bureau of the Census estimate of the voting-age population as the denominator of the turnout rate. We construct a more accurate estimate of those eligible to vote, from 1948–2000, using government statistical series to adjust for ineligible but included groups, such as noncitizens and felons, and eligible but excluded groups, such as overseas citizens. We show that the ineligible population, not the nonvoting, has been increasing since 1972. During the 1960s the turnout rate trended downward both nationally and outside the South. Although the average turnout rates for presidential and congressional elections are lower since 1972 than during 1948–70, the only pattern since 1972 is an increased turnout rate in southern congressional elections. While the voting age was lowered to 18 in 1971, the lower turnout rate of young voters accounts for less than one-fourth of reduced voter participation.

Temperature-dependent Hall-effect measurements were carried out both in dark and in ambient light on Si-doped ${\mathrm{Al}}_{x}{\mathrm{Ga}}_{1\ensuremath{-}x}\mathrm{As}$ layers grown by molecular-beam epitaxy over the entire composition range. Above 150 K, the measured Hall carrier densities (different from actual electron densities near the direct-indirect transition) show an exponential dependence on temperature. A shallow donor (\ensuremath{\le}15 meV) tied to the $\ensuremath{\Gamma}$ band and a deep donor level tied to the $L$ band were observed. The deep donor is dominant for $x&gt;0.2$, and its activation energy ${E}_{d}$ rises dramatically up to the direct-indirect band-gap crossover and peaks at 160 meV for $x\ensuremath{\sim}0.48$. As the A1 fraction increases further, ${E}_{d}$ decreases, reaching 57 meV for AlAs. The error due to multivalley conduction on the measured values of ${E}_{d}$ is shown to be negligible. The variation in ${E}_{d}$ of the dominant donor level with $x$ is accounted for by our theoretical calculations using a multivalley effective-mass model. A decrease of ${E}_{d}$ with increasing doping densities is also observed. At high substrate-growth temperature, the incorporation of Si atoms was found to decrease. The persistent-photoconductivity (PPC) effect was observed with an increase in mobilities over the dark values in the entire composition range. The effect was most pronounced in the range $0.20\ensuremath{\le}x\ensuremath{\le}0.40$. Traps related to the Si-doping density appear to be responsible for the observed photoconductivity effect. The ratio of the PCC traps and the Si atomic density is maximum at $x\ensuremath{\sim}0.32$ and is minimum in the direct-indirect band-gap crossover region.

This paper presents a cache coherence solu-tion for multiprocessors organized around a single time-shared bus. The solution aims at reducing bus traffic and hence bus wait time. This in turn increases the overall processor utilization. Unlike most traditional high-performance coherence solutions, this solution does not use any global tables. Furthermore, this coherence scheme is modular and easily extensible, requiring no modif-ication of cache modules to add more processors to a system. The performance of this scheme is evaluated by using an approximate analysis method. It is shown that the performance of this scheme is closely tied with the miss ratio and the amount of sharing between processors. I.

Generations of state politics scholars have believed that a U.S. state is more likely to adopt a law if its neighboring states have already done so, that is, that there is a positive regional effect on policy diffusion. But rarely has the social learning process, the theoretical underpinning of this effect, been examined critically Furthermore, the statistical models used to assess this effect have been fundamentally flawed. In this article, I consider more fully the potential impacts of social learning on policy diffusion, and develop a simple approach to modeling these impacts more flexibly. Using this approach, I take a fresh look at data from two classic studies of state policy diffusion and demonstrate that the regional effect is more complex than previously believed.

ABSTRACT Aim To examine the global pattern of the net primary production (NPP)/gross primary production (GPP) ratio of the Earth's land area along geographical and climatic gradients. Location The global planetary ecosystem. Methods The 4‐year average annual NPP/GPP ratio of the Earth's land area was calculated using 2000–03 Moderate Resolution Imaging Spectroradiometer (MODIS) data. The global pattern of the NPP/GPP ratio was investigated by comparing it among each typical terrestrial ecosystem and plotting it along a geographical and climatic gradient, including latitude, altitude, temperature and precipitation. Results The global terrestrial ecosystem had an average NPP/GPP ratio value of 0.52 with minor variation from 2000 to 2003. However, the NPP/GPP ratio showed considerable spatial variation associated with ecosystem type, geographical location and climate. Densely vegetated ecosystems had a lower NPP/GPP ratio than sparsely vegetated ecosystems. Forest ecosystems had a lower NPP/GPP ratio than shrub and herbaceous ecosystems. Geographically, the NPP/GPP ratio increased with altitude. In the Southern Hemisphere, the NPP/GPP ratio decreased along latitude from 30° to 10° and it exhibited high fluctuation in the Northern Hemisphere. Climatically, the NPP/GPP ratio exhibited a decreasing trend along enhanced precipitation when it was less than 2300 mm year −1 and a static trend when the annual precipitation was over 2300 mm. The NPP/GPP ratio showed a decreasing trend along temperature when it was between –20 °C and 10 °C, and showed an increasing trend along rising temperature when it was between –10 °C and 20 °C. Within each ecosystem, the NPP/GPP ratio revealed a similar trend to the global trend along temperature and precipitation. Conclusions The NPP/GPP ratio exhibited a pattern depending on the main climatic characteristics such as temperature and precipitation and geographical factors such as latitude and altitude. The findings of this research challenge the widely held assumption that the NPP/GPP ratio is consistent regardless of ecosystem type.

Most verification is concerned with finding incorrect code. Instead, this view looks at the probability that the code will fail if it is faulty. The authors present the benefits of their approach, describe how to design for it, and show how to measure testability through sensitivity analysis.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

INTRODUCTION: Penile prosthesis implantation has emerged as a definitive treatment to restore sexual function to the motivated man with erectile dysfunction. Substantial improvements in the design of inflatable devices have been made since they first became available more than four decades ago. AIM: To review the history of the penile prosthesis, the indications, preoperative evaluation, and patient and partner satisfaction. The current approaches to addressing intra- and postoperative complications, provide an understanding of prosthesis infection, and placement of these devices will be reviewed. METHODS: A committee of worldwide experts in this field was assembled during the 2015 International Consultation on Sexual Medicine (ICSM) and performed a systematic review of the peer-reviewed published medical literature pertaining to penile prosthesis. Particular attention was given to higher level trials when available. Recommendations are based upon the Oxford Criteria. MAIN OUTCOME MEASURES: Unfortunately there is limited level 1 and 2 evidence, and where expert opinion was utilized, the decision was unanimous within the committee with a goal of presenting a clinically relevant guideline pertaining to penile prostheses. RESULTS: Penile prosthesis has undergone an evolution over the past 40 years resulting in a more effective and reliable treatment for advanced erectile dysfunction not responding to less invasive methods including oral treatment with PDE5 inhibitors, vacuum erection device, and intracorporal injection therapy. It should be considered an appropriate treatment option for the man who wishes to restore erectile function and who understands the potential risk of mechanical failure and infection, both of which are less common now as a result of improvements made in device design as well as surgical protocols adhered to in the operating room. Patients must be clearly informed of the risks associated with penile prosthesis including mechanical failure, infection, shortening of the penis, change in sensation and configuration of the penis, as well as injury to local structures. Intraoperative complications are unusual but do occur and can usually be addressed intraoperatively to allow placement of the device at the time of initial surgery. Postoperative complications may also be addressed when they occur but may require more advanced reconstructive surgical techniques. Men with Peyronie's disease, corporal fibrosis due to infection, trauma, prior prosthesis explantation, priapism, and men who have undergone construction of a neophallus may require additional advanced maneuvers to obtain optimum results with a penile prosthesis. CONCLUSION: Penile prosthesis remains as an important, viable, and effective treatment for male erectile dysfunction that does not respond to other less invasive approaches or when these approaches are contraindicated or not acceptable to the patient. These devices provide the patient with the ability to engage in penetrative sexual activity without interfering with urination, ejaculation, sensation, or orgasm. Although mechanical failure can occur, the current devices are more reliable as a result of design modifications. Infection remains the most dreaded complication but since the introduction of antibiotic and hydrophilic coatings, infection is less common. Overall, patient and partner satisfaction appear to be reasonably high when a penile prosthesis is used to restore erectile function.

What makes a house beautiful? Is it serious to spend your time thinking about home decoration? Why do people disagree about taste? And can buildings make us happy? In The Architecture of Happiness, Alain de Botton tackles a relationship central to our lives. Our buildings - and the objects we fill them with - affect us more profoundly than we might think. To take architecture seriously is to accept that we are, for better and for worse, different people in different places. De Botton suggests that it is architecture's task to render vivid to us who we might ideally be. Turning the spotlight from the humble terraced house to some of the world's most renowned buildings, de Botton considers how our private homes and public edifices - from those of Christopher Wren to those of Le Corbusier and Norman Foster - influence how we feel, as well as how we could learn to build in ways that would increase our chances of happiness. The Architecture of Happiness amounts to a beguiling tour through the philosophy and psychology of architecture.

The sequence with nth term defined by [(n + 1)p] − [np] is an extremal zero-one valued sequence of asymptotic mean p in the following sense (for example): if a fraction p of customers from a point process with iid interarrival times is sent to an exponential server queue according to a prespecified splitting sequence, then the long-term average queue size is minimized when the above sequence is used. The proof involves consideration of the lower convex envelope J (which is a function on R m ) of a function J on Z m . An explicit representation is given for J in terms of J, for J in a broad class of functions, which we call “multimodular.” The expected queue size just before an arrival, considered as a function of the zero-one splitting sequence, is shown to belong to this class.

This paper extends the dynamic capability perspective into the study of innovation by entrepreneurial firms. Drawing from both the resource-based view and the dynamic capability perspective, this paper explores theoretically and examines empirically the different roles played by a firm's resource stock (endowment of resources and capabilities) and its integrative capabilities (ability to recognize opportunities as well as to configure and deploy resources) in the process of firm innovation. Our structural equation modeling results, based on a sample of 120 Internet-based companies, indicate that both the firm's resource stock and integrative capabilities affect its innovation. Additionally, we also found that the relationship between resource stock and innovation is mediated by integrative capabilities. That is, merely possessing well-endowed resource stock per se is not sufficient for innovation. Thus, it is the firm's ability to mobilize its resources and capabilities and align them dynamically with the changing opportunities in the environment that is of vital importance as the firm constantly innovates to survive and create its own competitive advantage. In the hypercompetitive and fast changing Internet-based environment, such a need for dynamic capabilities is especially accentuated. Implications and suggestions for future research are provided.

Modern metagenomic environmental DNA studies are almost completely reliant on next-generation sequencing, making evaluations of these methods critical. We compare two next-generation sequencing techniques - amplicon and shotgun - on water samples across four of Brazil's major river floodplain systems (Amazon, Araguaia, Paraná, and Pantanal). Less than 50% of phyla identified via amplicon sequencing were recovered from shotgun sequencing, clearly challenging the dogma that mid-depth shotgun recovers more diversity than amplicon-based approaches. Amplicon sequencing also revealed ~27% more families. Overall the amplicon data were more robust across both biodiversity and community ecology analyses at different taxonomic scales. Our work doubles the sampling size in similar environmental studies, and novelly integrates environmental data (e.g., pH, temperature, nutrients) from each site, revealing divergent correlations depending on which data are used. While myriad variants on NGS techniques and bioinformatic pipelines are available, our results point to core differences that have not been highlighted in any studies to date. Given the low number of taxa identified when coupling shotgun data with clade-based taxonomic algorithms, previous studies that quantified biodiversity using such bioinformatic tools should be viewed cautiously or re-analyzed. Nonetheless, shotgun has complementary advantages that should be weighed when designing projects.

Americanae nace como un proyecto conjunto que surge dentro de la Red Europea de Información y Documentación sobre América Latina (REDIAL), y que ha afrontado la Biblioteca de la Agencia Española de Cooperación Internacional para el Desarrollo (AECID). Esta nueva biblioteca virtual hace más accesibles los libros digitales de tema americanista a los investigadores y usuarios interesados de cualquier parte del mundo.