cssi/SciSciGPT-SciSciNet huggingface dataset:
Antisense oligonucleotide inhibition of cholesteryl ester transfer protein enhances RCT in hyperlipidemic, CETP transgenic, LDLr−/− mice

Due to their ability to promote positive effects across all of the lipoprotein classes, cholesteryl ester transfer protein (CETP) inhibitors are currently being developed as therapeutic agents for cardiovascular disease. In these studies, we compared an antisense oligonucleotide (ASO) inhibitor of CETP to the CETP small molecule inhibitor anacetrapib. In hyperlipidemic CETP transgenic (tg) mice, both drugs provided comparable reductions in total plasma cholesterol, decreases in CETP activity, and increases in HDL cholesterol. However, only mice treated with the antisense inhibitor showed an enhanced effect on macrophage reverse cholesterol transport, presumably due to differences in HDL apolipoprotein composition and decreases in plasma triglyceride. Additionally, the ASO-mediated reductions in CETP mRNA were associated with less accumulation of aortic cholesterol. These preliminary findings suggest that CETP ASOs may represent an alternative means to inhibit that target and to support their continued development as a treatment for cardiovascular disease in man.
The good organization speaking well: A paradigm case for religious institutional crisis management

Abstract Arguing that too much organizational apologia research focuses on the mistakes of big, for-profit corporations, this study examines the discourse of a religious institution that faced allegations of wrongdoing and cover-up. Specifically, this essay analyzes the discourse that surrounded the disclosure by the Christian and Missionary Alliance (C&MA) that a number of students at Mamou Alliance Academy in Guinea, West Africa, had been abused over a period of time (1950–1971) while their parents served as missionaries. The authors argue that the C&MA is engaged in ethical crisis management and is paradigmatic of what George Cheney has called “the good organization speaking well.” 1
Science, Government, and Citizen Feedback

This paper is based on the keynote address given at the 36th National Meeting of the Operations Research Society of America in Miami Beach, Florida; the theme of the meeting was "Operations Research in the Development of Emerging Countries."
Putative Surface Proteins Encoded within a Novel Transferable Locus Confer a High-Biofilm Phenotype to Enterococcus faecalis

Enterococci are opportunistic pathogens and among the leading causes of nosocomial infections. Enterococcus faecalis, the dominant species among infection-derived isolates, has recently been recognized as capable of forming biofilms on abiotic surfaces in vitro as well as on indwelling medical devices. A few bacterial factors known to contribute to biofilm formation in E. faecalis have been characterized. To identify additional factors which may be important to this process, we utilized a Tn917-based insertional mutagenesis strategy to generate a mutant bank in a high-biofilm-forming E. faecalis strain, E99. The resulting mutant bank was screened for mutants exhibiting a significantly reduced ability to form biofilms. One mutant, P101D12, which showed greater than 70% reduction in its ability to form biofilms compared to the wild-type parent, was further characterized. The single Tn917 insertion in P101D12 was mapped to a gene, bee-2, encoding a probable cell wall-anchored protein. Sequence information for the region flanking bee-2 revealed that this gene was a member of a locus (termed the bee locus for biofilm enhancer in enterococcus) comprised of five genes encoding three putative cell wall-anchored proteins and two probable sortases. Contour-clamped homogeneous electric field gel and Southern hybridization analyses suggested that the bee locus is likely harbored on a large conjugative plasmid. Filter mating assays using wild-type E99 or mutant P101D12 as a donor confirmed that the bee locus could transfer conjugally at high frequency to recipient E. faecalis strains. This represents the first instance of the identification of a mobile genetic element conferring biofilm-forming property in E. faecalis.
One-loop amplitudes of gluons in supersymmetric QCD

One-loop amplitudes of gluons in supersymmetric Yang-Mills are four-dimensional cut-constructible. This means that they can be determined from their unitarity cuts. We present a new systematic procedure to explicitly carry out any finite unitarity cut integral. The procedure naturally separates the contributions from bubble, triangle and box scalar integrals. This technique allows the systematic calculation of $\mathcal{N}=1$ amplitudes of gluons. As an application we compute all next-to-MHV six-gluon amplitudes in $\mathcal{N}=1$ super-Yang-Mills.
Method of moments learning for left-to-right Hidden Markov models

We propose a method-of-moments algorithm for parameter learning in Left-to-Right Hidden Markov Models. Compared to the conventional Expectation Maximization approach, the proposed algorithm is computationally more efficient, and hence more appropriate for large datasets. It is also asymptotically guaranteed to estimate the correct parameters. We show the validity of our approach with a synthetic data experiment and a word utterance onset detection experiment.
Climate Variability and Weather Extremes: Model-Simulated and Historical Data

The climate community is being challenged to provide increasingly more comprehensive societally-relevant information about the impacts of climate change that go well beyond broad statements about how much the global mean temperature will change. This in turn requires increasingly more comprehensive assessments of the quality of climate models to reproduce past regional climate impacts as well as the full spectrum of observed climate variability including those aspects (such as weather extremes) that are likely to have the greatest impact on society. This chapter examines the simulated and observed short-term climate variability and weather extremes that have occurred over the last three decades with a focus on the winter hemispheres.
Hydrogen doping in HfO2 resistance change random access memory

The structures and energies of hydrogen-doped monoclinic hafnium dioxide were calculated using density-functional theory. The electronic interactions are described within the LDA + U formalism, where on-site Coulomb corrections are applied to the 5d orbital electrons of Hf atoms and 2p orbital electrons of the O atoms. The effects of charge state, defect-defect interactions, and hydrogenation are investigated and compared with experiment. It is found that hydrogenation of HfO2 resistance-change random access memory devices energetically stabilizes the formation of oxygen vacancies and conductive vacancy filaments through multiple mechanisms, leading to improved switching characteristic and device yield.
Presumed Guilty: Innocence and the Death Penalty

DNA has really changed the way that defense lawyers and prosecutors think about wrongful convictions and about the criminal justice process. But it has not changed it enough. There are two distinct sets of prisoners who have been declared innocent and released from prison. One consists of DNA exonerees that was developed through the efforts of the innocence projects. The other consists of people who have been on death row who have been exonerated. Only relatively few of the death row exonerations were accomplished with DNA technology. This article examines both lists and discusses a few lessons that we are learning from DNA. By studying the factors that contributed to the convictions of innocent people, we can see the need for reforms in criminal justice system, including the areas of eye-witness identification, interrogation procedures which produce false confessions, reliance upon informant testimony, junk science and other factors. The fact that DNA was responsible for only fifteen of the 123 death row exonerations at the time of this presentation suggests that capital defendants are at greater risk of wrongful conviction than other defendants, and that DNA is of limited use in preventing the execution of the innocent.
Adaptive Transcutaneous Power Transfer to Implantable Devices: A State of the Art Review

Wireless energy transfer is a broad research area that has recently become applicable to implantable medical devices. Wireless powering of and communication with implanted devices is possible through wireless transcutaneous energy transfer. However, designing wireless transcutaneous systems is complicated due to the variability of the environment. The focus of this review is on strategies to sense and adapt to environmental variations in wireless transcutaneous systems. Adaptive systems provide the ability to maintain performance in the face of both unpredictability (variation from expected parameters) and variability (changes over time). Current strategies in adaptive (or tunable) systems include sensing relevant metrics to evaluate the function of the system in its environment and adjusting control parameters according to sensed values through the use of tunable components. Some challenges of applying adaptive designs to implantable devices are challenges common to all implantable devices, including size and power reduction on the implant, efficiency of power transfer and safety related to energy absorption in tissue. Challenges specifically associated with adaptation include choosing relevant and accessible parameters to sense and adjust, minimizing the tuning time and complexity of control, utilizing feedback from the implanted device and coordinating adaptation at the transmitter and receiver.
Diel variations in the nutritional physiology of Calanus glacialis from lat. 78° N in the summer

Calanus glacialis (Jaschnov) from Isfjord, western Spitzbergen, showed no tendency to pronounced diurnal vertical migration or cyclic variations in feeding activity. The samples, taken regularly over a 24-h period and at three different depths in the beginning of August, did however show considerable individual variations in feeding activity. These variations, reflected in the results of gut analyses, were not related to variations in the concentrations of particulate protein, carbohydrate or algal pigments in the water. Analyses of the activities of two digestive enzymes and the electron-transport system (ETS) indicated that those few individuals always present below the photic zone were there temporarily, and showed no signs of slowing down their metabolism. The results suggest that the population of C. glacialis, during the Arctic summer, feeds continuously in the upper water layer, but that intermittent, non-synchronous individual feeding rhythms are the rule.
Design and Characterization of Hover Nano Air Vehicle Propulsion System

A propulsion system for a Nano-Air Vehicle (NAV), defined as an air vehicle smaller than 7.5 cm and weighing about 10 grams, has been designed, fabricated, and tested. The design features a novel gearless torque-canceling propeller mechanism, with a tightly-integrated counter-rotating electric drive motor. A design procedure that strongly couples the design tradeoff for the electrical motor and the propellers was developed and used to obtain an optimum design minimizing the power consumption at hover thrust. From the test results, the prototype: demonstrated maximum thrust of 17.28 g; provided hover thrust at a power consumption of 1.26 Watts and input voltage of 3.3 Volts, which translates to 20 minutes of hovering endurance; and provided a torque-canceling mechanism capable of canceling up to 99% of torque generated in the motor. Using a combination of 5-bladed and 3-bladed propellers with an operating motor speed of 9,000 rpm, this propulsion system had a noise footprint of 42.55 dBA 1m away from the vehicle, quieter than typical indoor background noise during the day. It is concluded that the propulsion system developed was capable of meeting all the requirements imposed by DARPA.
Observations on Freshwater Dolphins in the Upper Amazon

Although freshwater dolphins of the families Platanistidae and Delphinidae are among the more interesting and conspicuous members of the Amazon River fauna of South America, relatively little is known of their habits. The Amazon dolphin or bouto, Inia geoffrensis (Blainville), occurs throughout much of the Amazon and its principal affluents and in the Orinoco as well. River dolphins of the genus Sotalia also inhabit a considerable portion of the Amazon system, their range extending to over 1,600 miles above the mouth of the river. In February, 1956, an expedition sponsored by Florida's Silver Springs was made to the upper Amazon at Leticia in the Commissary of Amazonas in southern Columbia to collect living freshwater dolphins for exhibition purposes. Both Inia and Sotalia were present in some numbers in the region visited, and four Amazon dolphins, which had been harpooned and captured alive, were obtained from natives and flown from Leticia to Florida. Of the four, one young female died en route and a young male succumbed shortly after arrival. The two surviving dolphins, both males, were kept at Silver Springs near Ocala, Florida. As a member of this party, the writer had excellent opportunities to study Inia and Sotalia in their natural surroundings over a 15-day period from February 19 to March 2. Observations were largely confined to the environs of Leticia, although some data were obtained at the settlement of Ramon Castilho, Peru, directly across the river from Leticia, and in the vicinity of Benjamin Constant, Brazil (Fig. 1). The dolphins were watched daily for periods ranging from an hour or two to nearly the entire day. In addition, several night trips were made to investigate the extent of their nocturnal activity. The majority of observations were made from a 16-foot aluminum boat equipped with an outboard motor or …
Transport coefficients of graphene: Interplay of impurity scattering, Coulomb interaction, and optical phonons

We study the electric and thermal transport of the Dirac carriers in monolayer graphene using the Boltzmann-equation approach. Motivated by recent thermopower measurements [F. Ghahari, H.-Y. Xie, T. Taniguchi, K. Watanabe, M. S. Foster, and P. Kim, Phys. Rev. Lett. 116, 136802 (2016)], we consider the effects of quenched disorder, Coulomb interactions, and electron--optical-phonon scattering. Via an unbiased numerical solution to the Boltzmann equation we calculate the electrical conductivity, thermopower, and electronic component of the thermal conductivity, and discuss the validity of Mott's formula and of the Wiedemann-Franz law. An analytical solution for the disorder-only case shows that screened Coulomb impurity scattering, although elastic, violates the Wiedemann-Franz law even at low temperature. For the combination of carrier-carrier Coulomb and short-ranged impurity scattering, we observe the crossover from the interaction-limited (hydrodynamic) regime to the disorder-limited (Fermi-liquid) regime. In the former, the thermopower and the thermal conductivity follow the results anticipated by the relativistic hydrodynamic theory. On the other hand, we find that optical phonons become non-negligible at relatively low temperatures and that the induced electron thermopower violates Mott's formula. Combining all of these scattering mechanisms, we obtain the thermopower that quantitatively coincides with the experimental data.
An integrated platform for assessing biologics(Conference Presentation)

Protein therapeutics are a rapidly growing portion of the pharmaceuticals market and have many significant advantages over traditional small molecule drugs. As this market expands, however, critical regulatory and quality control issues remain, most notably the problem of protein aggregation. Individual target proteins often aggregate into larger masses which trigger an immune response in the body, which can reduce the efficacy of the drug for its intended purpose, or cause serious anaphylactic side-effects. Although detecting and minimizing aggregate formation is critical to ensure an effective product, aggregation dynamics are often highly complicated and there is little hope of reliable prediction and prevention from first principles. This problem is compounded for aggregates in the subvisible range of 100 nm to 10 micrometers where traditional techniques for detecting aggregates have significant limitations. Here, we present an integrated optofluidic platform for detecting nanoscale protein aggregates and characterizing interactions between these aggregates and a reference surface. By delivering light to a solution of proteins with an optical waveguide, scattered light from individual protein aggregates can be detected and analyzed to determine the force profile between each particle and the waveguide surface. Unlike existing methods which only determine size or charge, our label-free screening technique can directly measure the surface interaction forces between single aggregates and the glass substrate. This direct measurement capability may allow for better empirical predictions of the stability of protein aggregates during drug manufacturing and storage.
Embrace WetBond Resin Cement save repair jackkniifing dental clinical application and curative effect

Objective Through the research Embrace WetBond Resin Cement used for resin bond jackknifing dental clinical curative effect,so as to save repair jackknifing tooth set up a set of practicul and simple treatment mode to improve the conserve with teeth.Methods Choose 35 cases of 36 a jackknifing teeth as the research object,the first open the teeth with nearly far in the contact point,with the ring fixed to decrease in the height,in the fissure two side preparation double dovetail hole type,will Embrace WetBond Resin Cement injection jackknifing surface and timely reset,lighting,filling,observe for 2weeks later,to ring do full crown restoration.Results After 6 to 12 months above review: 3 cases jackknifing tooth for recurrent episodes appeared periodontal abscess pull out,2 cases chewing have not comfortable feeling the success rate was 91%.Conclusion Use Embrace WetBond Resin Cement save repair jackknifing teeth,make up for the defects of the traditional bonding method,make a tooth has been preserved and simple clinical doctor's operation.
Immunologic Glomerular Injury

Glomerulonephritis appears to begin with an immunologic process in at least four out of five cases. Either antibodies specific for antigens in the glomerular basement membrane or antibodies reacting with circulating, nonglomerular antigens can trigger the injury. The two mechanisms are distinguishable by immunofluorescence.
Positive Psychology as the Evenhanded Positive Psychologist Views It.

Matthews, G., & Zeidner, M. (2000). Emotional intelligence, adaptation to stressful encounters, and health outcomes. In R. Bar-On & J. M. Parker (Eds.), Handbook of emotional intelligence (pp. 459-489). San Francisco: Jossey-Bass. Matthews, G., Zeidner, M., & Roberts, R. (2002). Emnotional intelligence: Science or myth? Cambridge, MA: MIT Press. Mayer, J. D., Salovey, P., & Caruso, D. R. (2000). Models of emotional intelligence. In R. J. Sternberg (Ed.), Hantdbook of human intelligence (2nd ed.). New York: Cambridge University Press. Newell, A. (1982). The knowledge level. Artifcial Intelligence, 18, 87-127. Schimmack, U., & Grob, A. (2000). Dimensional models of core affect: A quantitative comparison by means of structural equation modeling. European Journal of Personality, 14, 325-345. Seligman, M. E. P., & Csikszentmihalyi, M. (2000). Positive psychology: An introduction. American Psychologist, 55, 5-14. Stroop, J. R. (1992). Studies of interference in verbal reactions. Journal of Experitmental Pvychology: General, 121. 15-23. W tson, D. (2000). Mood and tenmperament. New York: Guilford. Zeidner, M., & Endler, N. (Eds.). (1996). Handbook of coping: Theory, research, applications. New York: Wiley. Zeidner, M., & Matthews, G. (2000). Intelligence and Personality. In R. J. Stemnberg (Ed.), Handbook of intelligence (2nd ed., pp. 581-610). New York: Cambridge University Press. Zeidner, M., Matthews, G., & Roberts, R. (2001). Slow down, you move too fast: Emotional intelligence remains an "elusive" intelligence. Em1otions, 1, 265-275. Zeidner, M., Matthews, G.. & Roberts, R. (in press). Emotional intelligence at work: A critical review. Applied Psychology: An International Review. Zeidner, M., Roberts, R., & Matthews, G. (2002). Can emotional intelligence be schooled? A critical review. Educational Psychologist, 37, 215-231. Zeidner, M., & Saklofske, D. (1996). Adaptive and maladaptive coping. In M. Zeidner & N. Endler (Eds.), Hfandbook ofXcoping (pp. 505-53 1). New York: Wiley.
Pano: Slave Trade, Dress, and Fashion in Cape Verde, 1600-1800s

A vibrant trade in slaves and other goods between the Cape Verde islands and mainland, known as Upper Guinea, enabled a back and forth movement of goods, ideas and peoples. This allowed for the forging of one broad region culturally, between the islands and coast. This paper explores the development of cotton cloth (pano) as fashion in Cape Verde and how gender and class influenced this process. The manner and the type of pano worn varied among the social classes, because people with means, such as some manumitted slaves, particularly freed African women, used silk, damask, and other type of finery. The rise of an Afro-Atlantic feminine aesthetic in Cape Verde, I argue was the continuation of Guinean “cultural core” rather than creolization. During this period, people expressed their identities in a number of ways, and importantly through the clothes they wore. Cultural brokers changed identities as quickly as they changed shirts, demonstrating who they were through dress as well as language and professions of religious affiliation. This flexibility of identity led to cross-cultural exchange that cannot be summed up under the often-used term “creolization.”
On the involvement of multiple muscarinic receptor subtypes in the activation of phosphoinositide metabolism in rat cerebral cortex

We have examined the activation of phosphoinositide metabolism by muscarinic agonists in rat cerebral cortex, in an attempt to delineate the mechanisms by means of which some selective antagonists inhibit this response in a manner that deviates from simple mass action law. The accumulation of [3H]inositol phosphates induced by the full agonist carbamylcholine in cell aggregates preparations was inhibited by muscarinic antagonists with the following order of potency: telenzepine greater than atropine greater than 4-diphenylacetoxy-N-methyl-piperidine methbromide greater than pirenzepine greater than hexahydro-sila-difenidol greater than AF-DX 116. The same order of potency was found for the competition of these antagonists with [3H]telenzepine binding to M1 muscarinic receptors. The inhibition of the formation of [3H]inositol phosphates activated by acetylcholine, carbamylcholine, and oxotremorine-M by pirenzepine and telenzepine showed biphasic curves, with 62-73% of the response being inhibited with high affinity. Atropine, AF-DX 116, and pirenzepine shifted the concentration-response curves of oxotremorine-M to the right in a parallel manner. However, pirenzepine at micromolar concentrations showed deviation from linearity of the Schild regression. The blockade by high concentrations of pirenzepine and telenzepine showed less than additive dose ratios when assayed in the presence of atropine, suggesting deviation of their antagonism from simple competition. However, after alkylation with propylbenzilylcholine mustard in the presence of low concentrations of pirenzepine, the response to carbamylcholine and oxotremorine-M showed monophasic inhibition curves by pirenzepine and linear Schild regression for this antagonist. These results support the interpretation that the formation of [3H]inositol phosphates is activated by multiple muscarinic receptor subtypes in rat cerebral cortex. The profile of affinities of muscarinic antagonists indicates that a major component of the response is activated by an M1 receptor subtype and a minor component is probably mediated by M3 muscarinic receptors when acetylcholine, carbamylcholine, or oxotremorine-M are used to stimulate the response. Conversely, pirenzepine inhibited the response induced by methacholine and bethanechol in a monophasic manner with high affinity (Ki = 13 nM), suggesting that these agonists can selectively stimulate phosphoinositide metabolism through activation of M1 muscarinic receptors in rat cerebral cortex.
New Insights into Second-Order Goods Retailing

The retailing of second-order goods by profit-seeking organizations has been growing dramatically in the United States. Previous studies of second-order goods retailing have focused exclusively on the not-for-profit or personal sales sectors. Moreover, most studies have used student samples or a case format, thereby limiting the generalizability of previous research findings. This study attempts to provide information from a more generalizable research format and addresses, for the first time, the for-profit segment of the second-order goods market, at the same time providing sound validation for previous research finding.
The Cold War World Turned Upside Down

Addressing the problems that led to the attacks on September 11, 2001 requires a perspective that looks beyond the Middle East or the Western and Muslim “civilizations” to the entire post-Cold War global configuration. A series of contingencies following the end of the Cold War affected the status of nations in the international society of states. These changes prompted a devaluation of collective identities for certain individuals; the failure of collective identity, in turn, affected their personal sense of worth. Acts of violence by state and non-state actors (sometimes referred to as “terrorists”) are, therefore, not disparate events. Rather, they represent attempts to assert identities in a local or global context and to reclaim a status that specific nations or peoples feel they have lost.
Organizational Connections: The Moderation of Subordinate POS in the Relationship between LMX and Work Outcomes

Previous research on leader-member exchange (LMX) has often viewed the supervisor as the primary recipient of organizational resources. These resources often serve as incentives or catalysts for the subordinates to enter a dyadic relationship with the supervisor. However, this research has overlooked the salient role that subordinates play in the initiation of these relationships and their contributions to the organization. The aim of the present study was to examine LMX and perceived organizational support (POS) simultaneously from the subordinate’s perspective and its impact in the development of LMX and work outcomes. Hayes’ process macro (2013) was used to test the moderation model using a sample of 111 subordinates. Results confirm that subordinate POS moderates the relationship between (LMX) and various work outcomes (job satisfaction, organizational commitment, and organizational citizenship behavior (OCB)). Furthermore, the relationship between LMX and work outcomes was stronger when subordinates had high POS. The implications, limitations, and direction for future research are discussed.
Kleinian Groups; Eichler Cohomology and the Complex Theory

In this expanded version of an expository lecture delivered at the University of Michigan in honor of Fred Gehring’s seventieth birthday, I discuss the complex analytic theory of finitely generated Kleinian groups. The common theme, for all but the last section, is Eichler cohomology as developed in [29] and [30]1. We follow, however, the notation established in [35]. Our aim is to illustrate the general picture, especially by good examples that can be generalized. Full proofs are found in the articles listed in the bibliography. In order to help the reader2an appendix with some standard definitions and elementary properties has been included.
TIME IN THERAPEUTIC RANGE PREDICTS MORTALITY AND CEREBROVASCULAR EVENTS IN ATRIAL FIBRILLATION PATIENTS TREATED WITH WARFARIN

Background: Time in therapeutic range (TTR) (INR 2 – 3) indicates efficacy of warfarin anticoagulation in atrial fibrillation (AF) patients. Whether it predicts outcomes in the community is not known. Methods: A community-based cohort of incident AF in Olmsted County, MN residents ≥18 y between
Assessment of sarcopenia as predictor of response and outcome after neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC).

e15512 Background: Sarcopenia (loss of skeletal muscle mass) at the time of RC has been associated with lower cancer-specific and overall survival (OS) in bladder cancer patients. Change in muscle ...
Fume emissions from a low-cost 3-D printer with various filaments

ABSTRACT3-D printing is an additive manufacturing process involving the injection of melted thermoplastic polymers, which are then laid down in layers to achieve a pre-designed shape. The heated deposition process raises concerns of potential aerosol and volatile organic compounds (VOC) emission and exposure. The decreasing cost of desktop 3-D printers has made the use of 3-D printers more acceptable in non-industrial workplaces lacking sufficient ventilation. Meanwhile, little is known about the characteristics of 3-D printing fume emission. The objective of this study was to characterize aerosols and VOC emissions generated from various filaments used with a low-cost 3-D printer in an environmental testing chamber. A pre-designed object was printed in 1.25 hours using eight types of filaments. A scanning mobility particle sizer and an aerodynamic particle sizer were employed to measure the particle size distribution in sub-half-micron fraction (<0.5 µm) and super-half-micron fraction (0.5–20 µm), respec...
Allosteric Inhibitors, Crystallography, and Comparative Analysis Reveal Network of Coordinated Movement across Human Herpesvirus Proteases.

Targeting of cryptic binding sites represents an attractive but underexplored approach to modulating protein function with small molecules. Using the dimeric protease (Pr) from Kaposi’s sarcoma-associated herpesvirus (KSHV) as a model system, we sought to dissect a putative allosteric network linking a cryptic site at the dimerization interface to enzyme function. Five cryogenic X-ray structures were solved of the monomeric protease with allosteric inhibitors bound to the dimer interface site. Distinct coordinated movements captured by the allosteric inhibitors were also revealed as alternative states in room-temperature X-ray data and comparative analyses of other dimeric herpesvirus proteases. A two-step mechanism was elucidated through detailed kinetic analyses and suggests an enzyme isomerization model of inhibition. Finally, a representative allosteric inhibitor from this class was shown to be efficacious in a cellular model of viral infectivity. These studies reveal a coordinated dynamic network of ...
The crisis of virtue: arming for the cultural wars and Pellegrino at the limes.

Edmund Pellegrino’s work has been crucial to the renaissance of interest in the philosophy of medicine and the philosophical grounding of medical ethics that has framed the contemporary field of bioethics in the expectation, of the rational justification of a universal content-full morality. However, this attempt at rational justification has failed, leaving a plurality of bioethics and the inability to secure the canonical account of virtue and character which Pellegrino has sought. This failure is integral to a Western Christian error regarding the nature of virtue.
Prospective longitudinal quality of life and survival outcomes in patients with advanced infiltrative hepatocellular carcinoma and portal vein thrombosis treated with Yttrium-90 radioembolization.

To determine the effect of Yttrium-90 (Y90) radioembolization on health-related quality of life (HRQOL) and its effect on overall survival advanced, unresectable infiltrative hepatocellular carcinoma (HCC) patients with concurrent portal vein thrombosis (PVT). Consecutive patients with unresectable infiltrative HCC and PVT were recruited. The Short-Form 36 (SF-36) questionnaire was used to assess HRQOL for consecutive patients treated with glass-based Y90 based on a prospective phase II trial. MR imaging was used to determine tumor progression every 3 months post-treatment. Overall survival (OS) from treatment and time to progression (TTP) was analyzed using Kaplan-Meier estimation and log-rank test. Thirty patients were treated and followed for 17.4 months; physical and mental component summary scores (PCS & MCS) remained unchanged at one, three, and six months. While no difference was observed in baseline SF-36 scores for patients with prolonged TTP (≥4 months) and OS (≥ 6 months), corresponding 1-month PCS were significantly higher than those with TTP < 4 months and OS < 6 months. At 1 month, patients with normalized Physical Function (PF), Role Physical (RP) and PCS within 2 standard deviations (SD) of US normalized baseline scores had a significantly prolonged median OS (15.7 vs. 3.7 months; p < 0.001) and TTP (12.4 vs. 1.8 mo; p < 0.001) compared those with physical component scores greater than 2SD below normalized US population values. Y90 radioembolization for HCC demonstrated long-term preservation of HRQOL. Lower baseline HRQOL scores were predictive of poorer OS. Early (1 month post-treatment) significant decreases in PCS were independent predictors of poorer OS and TTP. ClinicalTrials.gov identifier NCT01556282 , registered March 16, 2012.
Affine Group Schemes: Examples

A homomorphism of affine group schemes is a natural map G → H for which each G(R) → H(R) is a homomorphism. We have already seen the example det: GL n → G m . The Yoneda lemma shows as expected that such maps correspond to Hopf algebra homomorphisms. But since any map between groups preserving multiplication also preserves units and inverses, we need to check only that Δ is preserved. An algebra homomorphism between Hopf algebras which preserves Δ must automatically preserve S and e.
Low Self-Control, Parental Intervention, and Delinquency Among Native American Youth:

Researchers in criminal justice literature have relatively underexamined the delinquency among Native American (NA) youth. Using data from the Drug Use Among Young Indians: Epidemiology and Predict...
Genetic immunization: Applying recombinant DNA technology in the immune system to develop new vaccines

Genetic immunization is a new method for vaccine development where the gene for an antigen is introduced into the host, such that the host cells produce vaccine antigens in vivo. By producing antigens intracellularly, genetic immunization is able to produce protective cellular immune responses as well as antibody responses to combat pathogens and cancer. Because genetic vaccines consist of plasmid DNA, the fundamental character of this vaccine can be manipulated at will by simple recombinant DNA techniques. This ability to easily modify and test novel vaccines combined with the power to drive both arms of the immune system, gives this technology a unique potential unavailable to other vaccines to combat the most difficult of disease targets. This review will discuss the current and future applications of this technology.
A multi-component based volumetric directional pattern for texture feature extraction from hyperspectral imagery

Texture information has shown a significant contribution to pattern recognition in hyperspectral image (HSI) analysis. In this paper, a multi-component based the volumetric directional pattern (MC-VDP) is proposed for HSI classification. The original VDP operator extracts a three-dimensional texture feature from three consecutive bands by applying eight directional Kirsch filters to the raw intensity values. However, the local sign and local magnitude components, that are generated by a local difference sign-magnitude transform, are not incorporated before Kirsch masking. In this work, we first compute the local sign and local magnitude components followed by VDP operator and then combine them with the original VDP feature to form MC-VDP. By analyzing the local sign and local magnitude components, two volumetric texture features are obtained, namely VDP-Sign (VDP-S) and VDP-Magnitude (VDP-M). Thus MC-VDP operator is constituted of VDP-S, VDP-M, and the original VDP features. In details, VDP-S and VDP-M preserve additional discriminant information to describe the volumetric local structures in HSI, and they can be readily fused since their scheme are constructed in the same fashion. From experimental results, it is observed that a fusion of VDP-S, VDP-M, and the original VDP coded maps provides more discriminant information and thus better classification accuracy compared to the other popular spatial feature extraction methods.
Funding Support and Principal Investigator Leadership of Oncology Clinical Trials Using Radiation Therapy.

Purpose Sources of funding and principal investigator (PI) leadership for clinical trials using radiation therapy (RT) are not well characterized but are important mediators of innovation, particularly because funding for trials from the National Institutes of Health (NIH) has decreased and industry funding has increased. We sought to determine characteristics of trials using RT that are associated with industry funding, NIH funding, and radiation oncologist (RO) PI leadership. Methods and Materials www.ClinicalTrials.gov was queried for all open, interventional trials that administered RT. Logistic regression was used to identify associations between trial characteristics, receipt of funding type (NIH, industry, or other), and PI leadership. Results The authors identified 1469 oncology trials, of which 41% were based in the United States, 56% were based internationally, and 3% were based in the United States and internationally. Of these, 22% were RT monotherapy, 53% were bimodality (40% RT + drug, 13% RT + surgery), and 24% were trimodality. Although ROs led 60% of all trials, industry-sponsored trials were significantly less likely to have RO PIs (35% RO vs 65% non-RO PI; adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.28-0.73), to fund trials that did not incorporate drug therapy (aOR, 0.19; 95% CI, 0.10-0.35), or to fund phase III trials (aOR, 0.25; 95% CI, 0.11-0.60) because industry-sponsored trials favored smaller phase I trials. NIH-funded trials were not associated with PI type and, although not statistically significant, favored larger phase III trials (unadjusted OR, 2.06; 95% CI, 0.99-4.29). ROs were less likely to lead trials incorporating drug therapy (aOR, 0.30; 95% CI, 0.22-0.41). Conclusions ROs are less likely than other specialties to lead trials that use RT in combination with drug therapy or surgery and more likely to lead trials supported by nonindustry, non-NIH funding. This suggests a need for ROs to lead multimodality trials and to consider opportunities to interact with industry. As NIH resources decrease, alternative funding is needed to support innovation, particularly in in RT-alone trials.
Land Expectation Value to Profit Maximization: Re-Examination of the Faustmann Formula

By comparing the use of land expectation value (LEV), internal rate of return (IRR), labor wage expectation value (WEV), and profit (PF) in finding optimum rotation age in forest management, it is argued that the four approaches are essentially similar in maximizing the residual value but different in sharing the value from production. In the long run, the residual (loss) is created by all four factors and are shared depending on relative factor markets. Profit maximization is the most general approach as the scale of land, capital, labor and time are considered. If time value of capital becomes more costly, more land will be applied to substitute the time (shortening rotation); if land becomes more costly, longer rotation will be applied to substitute the land (shrinking land holding). If labor is more costly, more land and longer rotation will be applied. Considering the fact that timberland market is becoming active, and the role of entrepreneurs and investors who pay more attention to the scale of land than the rotation issue in land management, LEV approach which treats the scale of land as fixed is no longer appropriate. This chapter argues that PF maximization would be a more general and suitable approach as it can incorporate both scale of land and capital (management input) and time simultaneously.
New MR Technologies for Diagnosis of Acute Ischemic Stroke: MR Angiography, Diffusion, and Perfusion Imaging

Technological advances in magnetic resonance imaging (MRI) continue at a rapid pace. To those familiar with recent advances in what are broadly termed functional MRI techniques, techniques that measure physiological rather than anatomical aspects of the brain, their routine use in acute stroke diagnosis and clinical trials seems inevitable. I limit my remarks here to aspects of these new techniques that are relevant to thrombolytic therapies and therapeutic trials.
Plotting the Black Commons

This article examines Black communities’ engagement with practices of place and alternative figurations of land and water in the antebellum and post-emancipation periods around the lower–Chesapeake...
Measuring the Direct and Spillover Effects of Body Worn Cameras on the Civility of Police–Citizen Encounters and Police Work Activities

Existing research on the effects of body-worn cameras (BWCs) have found largely consistent results regarding direct significant reductions in citizen complaints and often also report reductions in use of force reports. However, few studies have examined possible spillover effects onto untreated officers. This study explicitly tests for direct and spillover effects of BWCs on the civility of police-citizen encounters and police work activities. This study assesses the direct effects of BWCs on citizen complaints, police use of force, and police proactivity and discretion during a 1-year randomized controlled trial in the Boston Police Department. Through a simultaneous quasi-experimental design, this study also investigates whether BWC deployment results in spillover effects onto control officers in treated districts as compared to comparison officers in untreated districts. Findings indicate that the use of BWCs reduces citizen complaints and police use of force but has no appreciable impact on officer activity or discretion. Furthermore, results indicate significant spillover reductions in citizen complaints for control officers in treated districts. The results of this study suggest that a limited BWC adoption may generate spillover deterrent impacts as officers and citizens perceive an increased threat that inappropriate and illegal behaviors will be captured on video even when BWCs are not actually present during an encounter. Partial BWC implementation seems like a cost-effective alternative to full implementation. However, police executives and policy makers need to think carefully about possible negative externalities generated by uneven BWC coverage.
Urinary prostaglandin E2 is a biomarker of early adaptive hyperfiltration in solitary functioning kidney

Abstract Introduction Hyperfiltration is a major contributor to progression of chronic kidney disease (CKD) in diabetes, obesity and in individuals with solitary functioning kidney (SFK). We have proposed hyperfiltration-induced injury as a continuum of overlapping glomerular changes caused by increased biomechanical forces namely, fluid flow shear stress (FFSS) and tensile stress. We have shown that FFSS is elevated in animals with SFK and, it upregulates prostaglandin E2 (PGE2), cyclooxygenase-2 and PGE2 receptor EP2 in cultured podocytes and in uninephrectomized mice. We conceptualized urinary PGE2 as a biomarker of early effects of hyperfiltration-induced injury preceding microalbuminuria in individuals with SFK. We studied children with SFK to validate our hypothesis. Methods Urine samples from children with SFK and controls were analyzed for PGE2, albumin (glomerular injury biomarker) and epidermal growth factor (EGF, tubular injury biomarker). Age, gender, and Z-scores for height, weight, BMI, and blood pressure were obtained. Results Children with SFK were comparable to controls except for lower BMI Z-scores. The median values were elevated in SFK compared to control for urine PGE2 [9.1 (n = 57) vs. 5.7 (n = 72), p = 0.009] ng/mgCr and albumin [7.6 (n = 40) vs. 7.0 (n = 41), p = 0.085] μg/mgCr, but not for EGF [20098 (n = 44) vs. 18637 (n = 44), p = 0.746] pg/mgCr. Significant increase in urinary PGE2 (p = 0.024) and albumin (p = 0.019) but not EGF (p = 0.412) was observed using additional regression modeling. These three urinary analytes were independent of each other. Conclusion Increased urinary PGE2 from elevated SNGFR and consequently increased FFSS during early stage of CKD precedes overt microalbuminuria and is a biomarker for early hyperfiltration-induced injury in individuals with SFK.
Chapter 9 – Greenhouse Gases

A greenhouse gas is a gas that absorbs and emits infrared radiation. The primary greenhouse gases in the atmosphere are water vapor, carbon dioxide, methane, nitrous oxide, and ozone. Atmospheric carbon dioxide (CO2) is a nontoxic, colorless, odorless gas. Water vapor accounts for by far the largest greenhouse effect (90–85%) because water vapor emits and absorbs infrared radiation at many more wavelengths than any of the other greenhouse gases, and there is much more water vapor in the atmosphere than any of the other greenhouse gases. CO2 makes up only a tiny portion of the atmosphere (0.040%) and constitutes only 3.6% of the greenhouse effect. The atmospheric content of CO2 has increased only 0.008% since emissions began to soar after 1945. Such a tiny increment of increase in CO2 cannot cause the 10°F increase in temperature predicted by CO2 advocates. Computer climate modelers build into their models a high water vapor component, which they claim is due to increased atmospheric water vapor caused by very small warming from CO2, and since water vapor makes up 90–95% of the greenhouse effect, they claim the result will be warming. The problem is that atmospheric water vapor has actually declined since 1948, not increased as demanded by climate models. If CO2 causes global warming, then CO2 should always precede warming when the Earth's climate warms up after an ice age. However, in all cases, CO2 lags warming by ∼800 years. Shorter time spans show the same thing—warming always precedes an increase in CO2 and therefore it cannot be the cause of the warming.
Challenges and opportunities for the next decade of XFELs

The first decade of X-ray free-electron lasers (XFELs) has led to technological advances and scientific discoveries, but has also highlighted several facility-level challenges. Chi-Chang Kao, Director of SLAC, discusses the lessons to be learned from the first 10 years of operation and shares his thoughts on how facilities can overcome challenges facing XFEL development.