cssi/SciSciGPT-SciSciNet huggingface dataset:
Locostatin Disrupts Association of Raf Kinase Inhibitor Protein With Binding Proteins by Modifying a Conserved Histidine Residue in the Ligand-Binding Pocket

Raf kinase inhibitor protein (RKIP) interacts with a number of different proteins and regulates multiple signaling pathways. Here, we show that locostatin, a small molecule that covalently binds RKIP, not only disrupts interactions of RKIP with Raf-1 kinase, but also with G protein-coupled receptor kinase 2. In contrast, we found that locostatin does not disrupt binding of RKIP to two other proteins: inhibitor of κB kinase α and transforming growth factor β-activated kinase 1. These results thus imply that different proteins interact with different regions of RKIP. Locostatin's mechanism of action involves modification of a nucleophilic residue on RKIP. We observed that after binding RKIP, part of locostatin is slowly hydrolyzed, leaving a smaller RKIP-butyrate adduct. We identified the residue alkylated by locostatin as His86, a highly conserved residue in RKIP's ligand-binding pocket. Computational modeling of the binding of locostatin to RKIP suggested that the recognition interaction between small molecule and protein ensures that locostatin's electrophilic site is poised to react with His86. Furthermore, binding of locostatin would sterically hinder binding of other ligands in the pocket. These data provide a basis for understanding how locostatin disrupts particular interactions of RKIP with RKIP-binding proteins and demonstrate its utility as a probe of specific RKIP interactions and functions.
On the Madden–Julian Oscillation–Atlantic Hurricane Relationship

Abstract The large-scale equatorial circulation known as the Madden–Julian oscillation (MJO) has been shown to impact tropical cyclone activity in several basins around the globe. In this paper, the author utilizes an MJO index created by Wheeler and Hendon to examine its impacts on tropical genesis and intensification in the Atlantic. Large differences in frequency and intensity of tropical cyclone activity are seen, both in the tropical Atlantic as well as in the northwest Caribbean and Gulf of Mexico depending on the MJO phase. Coherent changes in upper- and lower-level winds and relative humidity are likely responsible for these differences. Since the MJO shows potential predictability out to about two weeks, the relationships discussed in this paper may be useful for short-term predictions of the probability of tropical cyclone activity in the Atlantic as a complement to the already available longer-term seasonal predictions.
Biological Research in Child Psychiatry

Three areas of biological research pertinent to child psychiatry are reviewed: pediatric psychopharmacology, neuroradiological diagnostic techniques, and psychogenetics. Eventually, these areas of research may help refine diagnosis, predict the efficacy of treatments and give hints as to etiology. At present, however, such research is in early stages. The review suggests important new areas for clinicians to follow.
Scattering of a light beam from waves at an air–sea interface

The authors report a new theory that describes the scattering of an upward propagating laser beam from the sea through the air-sea interface in the presence of sea waves. The sea is assumed to be a uniform dielectric and conventional scattering theory is employed by using a modification to the first Born approximation that permits treatment of surface refraction phenomena. Methods of statistical radiometry are also used in a new manner by assuming that the surface scattering function for the sea waves can be treated by a quasi-homogeneous source model to calculate the second-order correlation functions for the partially coherent scattered field. These correlation functions yield a simple expression for the radiant intensity of the scattered field as the convolution of the Fourier transform of the complex degree of spectral coherence for the sea waves with the squared modulus of the angular spectrum of plane waves for the incident laser beam. We believe that this theory is a significant improvement over the models that are usually used for modeling this phenomenon.
Functional requirements and design criteria for the design of high hazard containment laboratories

A brief overview of the design process which has been successfully utilized in planning a high hazard containment laboratory.
Geometry-Assisted Three-Dimensional Superlocalization Imaging of Single-Molecule Catalysis on Modular Multilayer Nanocatalysts

To establish the structure–catalytic property relationships of heterogeneous catalysts, a detailed characterization of the three-dimensional (3D) distribution of active sites on a single catalyst is essential. Single-particle catalysis of a modular multilayer catalytic platform that consists of a solid silica core, a mesoporous silica shell, and uniformly distributed Pt nanoparticles sandwiched in between these layers is presented. The first 3D high-resolution super-localization imaging of single fluorescent molecules produced at active sites on the core-shell model nanocatalysts is demonstrated. The 3D mapping is aided by the well-defined geometry and a correlation study in scanning electron microscopy and total internal reflection fluorescence and scattering microscopy. This approach can be generalized to study other nano- and mesoscale structures.
Membership and Behavior of Ultra-Low-Diversity Pathogen Communities Present in the Gut of Humans during Prolonged Critical Illness

ABSTRACT We analyzed the 16S rRNA amplicon composition in fecal samples of selected patients during their prolonged stay in an intensive care unit (ICU) and observed the emergence of ultra-low-diversity communities (1 to 4 bacterial taxa) in 30% of the patients. Bacteria associated with the genera Enterococcus and Staphylococcus and the family Enterobacteriaceae comprised the majority of these communities. The composition of cultured species from stool samples correlated to the 16S rRNA analysis and additionally revealed the emergence of Candida albicans and Candida glabrata in ~75% of cases. Four of 14 ICU patients harbored 2-member pathogen communities consisting of one Candida taxon and one bacterial taxon. Bacterial members displayed a high degree of resistance to multiple antibiotics. The virulence potential of the 2-member communities was examined in C. elegans during nutrient deprivation and exposure to opioids in order to mimic local conditions in the gut during critical illness. Under conditions of nutrient deprivation, the bacterial members attenuated the virulence of fungal members, leading to a “commensal lifestyle.” However, exposure to opioids led to a breakdown in this commensalism in 2 of the ultra-low-diversity communities. Application of a novel antivirulence agent (phosphate-polyethylene glycol [Pi-PEG]) that creates local phosphate abundance prevented opioid-induced virulence among these pathogen communities, thus rescuing the commensal lifestyle. To conclude, the gut microflora in critically ill patients can consist of ultra-low-diversity communities of multidrug-resistant pathogenic microbes. Local environmental conditions in gut may direct pathogen communities to adapt to either a commensal style or a pathogenic style. IMPORTANCE During critical illness, the normal gut microbiota becomes disrupted in response to host physiologic stress and antibiotic treatment. Here we demonstrate that the community structure of the gut microbiota during prolonged critical illness is dramatically changed such that in many cases only two-member pathogen communities remain. Most of these ultra-low-membership communities display low virulence when grouped together (i.e., a commensal lifestyle); individually, however, they can express highly harmful behaviors (i.e., a pathogenic lifestyle). The commensal lifestyle of the whole community can be shifted to a pathogenic one in response to host factors such as opioids that are released during physiologic stress and critical illness. This shift can be prevented by using compounds such as Pi-PEG15-20 that interrupt bacterial virulence expression. Taking the data together, this report characterizes the plasticity seen with respect to the choice between a commensal lifestyle and a pathogenic lifestyle among ultra-low-diversity pathogen communities that predominate in the gut during critical illness and offers novel strategies for prevention of sepsis.
The Anderson nomograms for permanent interstitial prostate implants: a briefing for practitioners.

Abstract Purpose: The objective of this report is to re-evaluate the role of the Anderson nomograms in treatment planning for permanent prostate implants. The incentive for revisiting this topic concerns three issues: ( 1 ) Although nomograms continue to be used in many centers for ordering seeds, few centers use them during treatment planning; ( 2 ) Whereas nomograms were designed to deliver a minimum peripheral dose for a uniform distribution of seeds in the gland, many practitioners use peripheral seed loading patterns to reduce urethral toxicity; and ( 3 ) As preoperative and intraoperative treatment planning is becoming standard, the apparent role of nomograms is diminished. The nomogram method is reviewed in terms of: ( 1 ) total activity predicted, ( 2 ) target coverage (as planned in the operating room and as calculated from postimplant computed tomography studies), and ( 3 ) reproducibility (i.e., patient-to-patient and planner-to-planner variability). In each case, the computer-optimization system for intraoperative planning currently in use at our institution was taken as the "gold standard." Methods and Materials: We compared for the same patient the results of nomogram planning to those yielded by genetic algorithm (GA) optimization in terms of total activity predicted ( n = 20 cases) and percent target coverage ( n = 5 cases). Furthermore, we examined retrospectively the dosimetry of 61 prostate implants planned with the GA ( n = 27) and the current implementation of Anderson nomograms ( n = 34). Results: Nomogram predictions of the total activity required are in good agreement (within 10%) with the GA-planned activity. However, computer-optimized plans consistently yield superior plans, as reflected in both pre- and postimplant analyses. We find also that user (specifically, treatment planner) implementation of the nomograms may be a major source of variability in nomogram planning—a difficulty to which robust computer optimization is less prone. Conclusions: Nomograms continue to be useful tools for predicting the total required activity for volume implants, and thus for performing an independent check of this quantity. Not unexpectedly, computer optimization remains the preferred planning method. Generally, nomogram-guided implants do not incorporate structures other than the treatment volume into the planning process. Further yet, they deliver a lower dose than that prescribed and result in greater variability among plans than computer-optimized treatments. In summary, nomograms ( 1 ) remain an efficient quality assurance tool for computer-generated plans, ( 2 ) serve as a good predictor of the number of seeds required for ordering purposes, and ( 3 ) provide a simple and dependable backup planning method in case the intraoperative planning system fails.
Efficacy of PLD-118, a Novel Inhibitor of Candida Isoleucyl-tRNA Synthetase, against Experimental Oropharyngeal and Esophageal Candidiasis Caused by Fluconazole-Resistant C. albicans

PLD-118, formerly BAY 10-8888, is a synthetic antifungal derivative of the naturally occurring beta-amino acid cispentacin. We studied the activity of PLD-118 in escalating dosages against experimental oropharyngeal and esophageal candidiasis (OPEC) caused by fluconazole (FLC)-resistant Candida albicans in immunocompromised rabbits. Infection was established by fluconazole-resistant (MIC > 64 microg/ml) clinical isolates from patients with refractory esophageal candidiasis. Antifungal therapy was administered for 7 days. Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v. BID injections; and animals receiving desoxycholate amphotericin B (DAMB) i.v. at 0.5 mg/kg/day. PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P </= 0.05, P </= 0.01, P </= 0.001, respectively), while FLC had no significant activity. PLD-118 demonstrated nonlinear plasma pharmacokinetics across the investigated dosage range, as was evident from a dose-dependent increase in plasma clearance and a dose-dependent decrease in the area under the plasma concentration-time curve. The biochemical safety profile was similar to that of FLC. In summary, PLD-118 demonstrated dosage-dependent antifungal activity and nonlinear plasma pharmacokinetics in treatment of experimental FLC-resistant oropharyngeal and esophageal candidiasis.
The sink tree paradigm: connectionless traffic support on ATM LAN's

Asynchronous transfer mode (ATM) is a connection-oriented technology in which all communication is based on virtual connections established prior to the transfer of data. It is expected that the bulk of traffic carried by the ATM network will be data traffic, e.g., local area network (LAN) internetwork traffic. Hence, a major issue regarding ATM is the support for connectionless (datagram) traffic. A scheme for the efficient support for connectionless traffic in ATM LANs based on trees of virtual connections is proposed. In this scheme, a sink tree is built for every switch in the LAN. Each tree provides an efficient means of routing connectionless traffic from any switch in the network to the sink switch (root) of the tree. The sink tree solution may also be used to broadcast connectionless messages in the reverse direction. The trees can easily be updated to adapt to topological changes or congestion in the network. A protocol for refreshing the tree structure using the ATM switch routing tables is described. An adaptive rate control solution, in conjunction with fast back pressure at the ATM layer, is presented. It is shown that this scheme achieves high utilization of available bandwidth for connectionless traffic, has low cell loss probability, and small overhead.
The Capstone Strategy Course: What Might Real Integration Look Like?:

The traditional master of business administration (MBA) capstone strategy course is intended to integrate the prior course work of the MBA program but is doing this less and less well in today's high-velocity and complex business environment. The traditional strategy course structures, emphasizing formulation— implementation and the internal—external environments, do relatively well at developing theoretical and applied integration skills but do poorly in developing practical integration skills—the very skills increasingly demanded by employers. The authors do not believe that the traditional organization of and pedagogies for the capstone strategy course develop the level of integrated thinking necessary for managers to make good decisions in today's business environment. They suggest reorganizing the strategy capstone course along the levels of managerial decision making and emphasizing pedagogies that employ rich-enough cases and business simulations to better develop integration skills—particularly pr...
Towards Synthesizing Realistic Workload Traces for Studying the Hadoop Ecosystem

Designing cloud computing setups is a challenging task. It involves understanding the impact of a plethora of parameters ranging from cluster configuration, partitioning, networking characteristics, and the targeted applications' behavior. The design space, and the scale of the clusters, make it cumbersome and error-prone to test different cluster configurations using real setups. Thus, the community is increasingly relying on simulations and models of cloud setups to infer system behavior and the impact of design choices. The accuracy of the results from such approaches depends on the accuracy and realistic nature of the workload traces employed. Unfortunately, few cloud workload traces are available (in the public domain). In this paper, we present the key steps towards analyzing the traces that have been made public, e.g., from Google, and inferring lessons that can be used to design realistic cloud workloads as well as enable thorough quantitative studies of Hadoop design. Moreover, we leverage the lessons learned from the traces to undertake two case studies: (i) Evaluating Hadoop job schedulers, and (ii) Quantifying the impact of shared storage on Hadoop system performance.
Measurement of endosome pH following folate receptor-mediated endocytosis.

Abstract Free folic acid is believed to enter some cells by folate receptor-mediated endocytosis at membrane invaginations termed caveolae. Folate conjugated macromolecules also enter cells by folate receptor-mediated endocytosis, but their site of entry has never been conclusively identified. In this paper, we show that internalization of folate-macromolecule conjugates by receptor-bearing KB cells can be blocked by agents that specifically inhibit caveolae assembly or internalization such as nystatin and phorbol-12-myristate acetate (PMA). To characterize the intracellular conditions to which the macromolecule-folate conjugates are subsequently exposed, we have measured the pH of the major compartments of the folate endocytosis pathway. pH values of individual endosomal compartments in KB cells were determined by dual-excitation laser-scanning confocal microscopy, where the fluorescence ratio of folate-DM-NERF-dextran (pH-sensitive) and Texas Red-dextran (pH-insensitive) was used to calculate pH. These studies revealed that the pH of folate conjugate-containing endosomes commonly varies between 4.7 and 5.8, with the pH in some endosomes as low as 4.3. The most frequent pH value in these compartments was ≈ 5.0.
Erythropoietin Attenuates Inflammatory Factors and Cell Death in Neonatal Rats with Intracerebral Hemorrhage

Stroke affects infants at a rate of 26/100,000 live births each year. Of these strokes, approximately 6.7 are hemorrhagic strokes. Erythropoietin (EPO) is an anti-apoptotic and neuroprotective hormone. In adult rodents, EPO attenuates inflammatory factor expression and blood–brain barrier damage after intracerebral hemorrhage (ICH). However, the effect of EPO in neonatal ICH stroke remains unexplored. This investigation aimed to elucidate the underpinnings of inflammation after ICH in postnatal day 7 (P7) rats and the effect of human recombinant EPO (hrEPO) treatment on ICH-induced inflammation. The P7 rat pups were pretreated with hrEPO (5,000 U/kg i.p.) or saline vehicle 4 h prior to the induction of ICH by blood injection into the right cerebral cortex and basal ganglia. Supplemental half doses of hrEPO treatment or saline injections were subsequently given 16 h after ICH induction. Real-time PCR done 24 h after ICH showed reductions in interleukin1-β (IL1-β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) mRNA expression in the basal ganglia of the hrEPO-treated rats compared to saline-treated rats. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining indicated fewer dying cells in the hrEPO-treated brain. Our data suggest that hrEPO has an anti-inflammatory action in neonates after ICH. The suppression of inflammatory cascades likely contributes to hrEPO’s neuroprotective effect, which may be explored as a therapeutic treatment for ICH.
Emergency department presentation of bilateral carotid artery dissections in a postpartum patient

Spontaneous unilateral postpartum carotid arterial dissection is a rarely reported event. This is the first reported case of bilateral carotid artery dissection. A 35-year-old gravida 4, para 3 woman presented to our emergency department with complaint of headache for 3 days. Medical history included delivery of a full-term infant by cesarean section 9 days before presentation because of arrest of descent after 3 hours of pushing. Symptoms were later attributed to a parietal lobe cerebral vascular accident and bilateral internal carotid artery dissection. Physicians should consider the possibility of arterial dissection in any postpartum patient with unremitting headache when evaluation of typical causes fails to lead to a diagnosis. Appropriate diagnostic evaluation and treatment should be actively pursued in this population.
Impending extinction of salmon, steelhead, and trout (Salmonidae) in California

California contains the southernmost native populations of most Pacific Coast salmon and trout, many of which appear to be rapidly headed toward extinction. A quantitative protocol was developed to determine conservation status of all salmonids native to the state. Results indicate that if present trends continue, 25 (78%) of the 32 taxa native to California will likely be extinct or extirpated within the next century,followingthebulltrout(Salvelinus confluentus), which was extirpated in the 1970s. California's salmo- nids are adapted to living in a topographically diverse region with a Mediterranean climate, characterized by extreme seasonal and inter-annual variability in streamflow. Consequently, California salmonids have evolved extraordinary life history diversity to persist in the face of stressful conditions that often approach physiological limits. The spatial distributions of California salmonids vary from wide-ranging anadro- mous forms to endemic inland forms persisting in only a few kilometers of stream. Eighty-one percent of anadromous taxa are threatened with extinction and 73% inland taxa are either threatened or already extinct. Although specific drivers of decline differ across species, major causes of decline are related to increasing competition with humans for water, human degradation of watersheds, and adverse effects of hatchery propagation. Climate change, interacting with the other causes of decline, is increasing the trajectory towards extinction for most populations. Bringing all of California's salmonid fishes back from the brink of extinction may not be possible. If there are bold changes to management policy, however, self-sustaining populations of many species may be possible due to their inherent ability to adapt to changing conditions.
Problem solving using cultural algorithms

In this paper an approach to evolutionary learning based upon principles of cultural evolution is developed. In this dual-inheritance system, there is an evolving population of trait sequences as well as an associated belief space. The belief space is derived from the behavior of individuals and is used to actively constrain the traits acquired in future populations. Shifts in the representation of the belief space and the population is supported. The approach is used to solve several versions of the BOOLE problem; F6, F11, and F20. The results are compared with other approaches and the advantages of a dual inheritance approach using cultural algorithms is discussed. >
Sequence Homology Among Sperm Antigens Involved in Mammalian Fertilization: Search for a Common Epitope for Immunocontraception

Sequence homology was searched among the nine cDNAs/deduced amino acid sequences encoding for the eight fertilization-related sperm antigens: namely, lactate dehydrogenase (LDH-C4), galacto-syltransferase (GT), SP-10, rabbit sperm autoantigen (RSA), guinea pig (g)PH-20, cleavage signal protein (CS-1), HSA-63, human (h)PH-20, and AgX-1, respectively. Most significant identity (>50%) was found between HSA-63 and SP-10 (59.8%), and between gPH-20 and hPH-20 (61.1%); followed by identity between SP-10 and GT (34.7%); and then between AgX-1 and hPH-20 (39.4%). All others had identity <25%. The significance of these sequence homologies among the sperm antigens in the development of an antisperm contraceptive vaccine is discussed.
Parallelism-centric optimization and performance study of a finance aggregation engine on modern NUMA systems

Mark-to-future aggregation is a key component of counterparty credit risk analysis in the IBM Algorithmics software. Its computation exhibits complex memory access and control flow patterns, and is hard to accelerate. The prior effort to improve performance takes a "pre-compiled" approach that aims to reduce the overhead and inefficiencies primarily through compiler techniques. While combined with other optimizations, the performance is improved by 3 to 5 times, many extra lines of code are dynamically generated. Maintenance and testing become a challenge. In our study we take a parallelism centric approach guided by hardware counter based profiling. Minimal modifications are made to the code and about 10 times speedup is achieved.We also study the behavior of mark-to-future aggregation on a NUMA platform. We evaluate the impact of architectural choices on the performance. Our study sheds some light on accelerating mark-to-future aggregation on current and emerging architectures.
Biodegradation of biodiesel and microbiologically induced corrosion of 1018 steel by Moniliella wahieum Y12

Abstract A putatively novel basidiomycetous fungus termed Moniliella wahieum Y12T was isolated from a 20% biodiesel blend. The strain maximally degraded biodiesel at a rate of 3.56 × 10−2 mg/h during log phase growth. Induction of metal corrosion by the strain in a mass loss procedure using 1018 metal coupons showed total mass reduction exceeded that in controls by 70% through 30 days. Enhanced corrosion was observed at the pellicle and due to medium acidification. This is the first investigation of a Moniliella sp. and its impact on biodiesel stability and 1018 steel corrosion. (M. wahieum Y12T = ATCC MYA-4962).
Memories and Social Change: Creative Knowledge Society versus Global Crisis

This study is focused on (re)searching an answer to the question: * WHY DOES NOT THE RATIO POVERTY/WELFARE WORK as a dynamically pro-market reform indicator, into the contemporary MARKET and ECONOMY? A two stage answering-approach (as below # and ## paragraphs show) is proposed:# If (a) [simple and/or complex] answer(s) exist(s), then it would operatively result, at least, from the construct CREATIVE PARTNERSHIP. This construct would “mean” the existence of a flow of the proposed (re)search: to complete a Charta I of GENEROSITY-CREATIVITY-SOLIDARITY WITHIN CREATIVE PARTNERSHIP, to largely diffuse the Charta I and to elicit the creative partnership onto a minimal case study on conflict-consensus on high school teenagers issues, to amend – to adapt – to negotiate the (numerical) parameters of the Charta I, to complete the extensions of the addenda as research co-themes, to gather the knowledge and the societal praxis in order to elicit the constructs: CREATIVE PARTNER, INTERNATIONALLY CIVIL SOCIETY, SUBTLE WORLD, SUBTLE INDICATORS, ECO-CONSCIOUSNESS till to construct a self-sustained Center for Creative Partnership, a Moral Market, at all. ## If (a) [simple and/or complex] answer(s) exist(s), then it would operatively result, at least, from the construct CREATIVE KNOWLEDGE SOCIETY WITHIN A NEGOTIATION NEXUS ONTO THE COMPLEXITY OF HUMANKIND, SCENARIOS ON TH WORLD NEAR FUTURE, SCIENCE-RELIGION DIALOGUE. This construct would “mean” the existence of a flow of the proposed (re)search: to complete a Charta II of OPENING (at least) SCIENCE-RELIGION DIALOGUE, to largely diffuse the Charta II and to elicit the creative dialogues versus negotiations on Science-Religion matter, at least within a minimal partnership onto a contemporary educational case study on high school issues, to amend – to adapt – to (re)negotiate the (numerical) parameters of the Charta II, to complete the extensions of the addenda as research co-themes, to gather the knowledge and the societal praxis in order to elicit the constructs: SCIENCE-RELIGION PARTNER, INTERNATIONALLY SCIENCE-RELIGION SOCIETY, SUBTLE WORLD, SUBTLE INDICATORS, ECO-CONSCIOUSNESS till to construct a self-sustained Center for a Creative Negotiation Nexus onto the Science-Religion Dialogue, an inquiry into the deepness of the actual globalised crisis, a Moral Knowledge Society, a Consciousness Society, a Science-Religion Partnership market of information and knowledge, at all. This study is a re-formulation of the “Memories and Social Change: Creative Knowledge Society” – submitted to SSRN on 01/06/2011 ID: http://ssrn.com/abstract=1736244 This re-formulation as “Memories and social change: creative knowledge society versus global crisis” was presented and included into the printed abstracts and proceedings of the United Kingdom Systems Society (UKSS) International Conference, St Anne’s College Oxford, August 30-31, 2012 - Global Crises: Exploring the Systems Perspective - Papers Stream 2, Seminar Room 1, August 31, 2012 1:15-3:15; abstract printed at the pp. 6-7 of the UKSS/2012.
Cytotaxonomic studies of the harvest mice of the San Francisco Bay region.

The karyotypes of Reithrodontomys megalotis longicaudus, R. raviventris halicoetes and R. r. raviventris in the San Francisco Bay region were studied to understand better the taxonomic relationships of the three taxa. Reithrodontomys megalotis has 44 chromosomes whereas the two endemic suspecies of raviventris have 38. The karyotypes of R. r. halicoetes and R. r. raviventris are different enough to suggest that the two are in the terminal stages of speciation.
Numerical simulations of hypersonic boundary-layer instability with wall blowing

We perform a Navier-Stokes simulation as well as a linear stability analysis of a hypersonic flat plate boundary-layer with wall blowing. We observe that as blowing increases, the maximum amplification rate of the disturbance instability grows and moves toward lower frequencies. Disturbance beating diminishes with the unstable second-mode dominating the stable mode. We present the results from the Navier-Stokes simulations and the linear stability theory showing good agreement.
Abstract 511: Thioredoxin Interacting Protein Ablation Protects Vascular Smooth Muscle Cells from Oxidative Stress

Vascular smooth muscle cells (SMC) play an important role in atherosclerosis. In response to increased oxidative stress, SMC secrete cytokines and express cell adhesion molecules which in turns, regulate monocyte/macrophage adhesion and other processes during atherosclerosis. Thioredoxin interacting protein (Txnip), an endogenous inhibitor of thioredoxin, is a key regulator of cellular sulfhydryl redox status. Recent studies also showed that Txnip is a key modulator of cellular glucose metabolism and insulin resistance. In addition, Txnip serves as a critical sensor linking inflammasome to inflammation associated oxidative stress. We hypothesized that Txnip ablation would lead to decreased inflammatory responses in SMC by limiting cellular oxidative stress. To examine this hypothesis, we isolated primary SMC from the thoracic aorta of Txnip knockout (TKO) mice. Comparing to SMC from wild type (WT) control mice, SMC from TKO mice have reduced levels of reactive oxygen species (ROS), as assessed by dihydroethidium (DHE) staining. Furthermore, Txnip ablation protected cells from oxidative stress when challenged with OxPAPC and hydrogen peroxide. Inflammatory markers (ICAM-1 and MCP-1) were down-regulated in Txnip-null SMC whereas oxidative stress-induced expression of inflammatory markers was inhibited by Txnip-deficiency. Interestingly, we found that macrophage adhesion to SMC was markedly reduced in Txnip-null cells. This is associated with a reduction in adhesion molecule and inflammatory marker expression in both SMC and macrophages from TKO mice. SMC from TKO mice exhibited an increased expression of KLF2 and decreased NF-κB (p65) activity, comparing to WT SMC. Taken together, our data demonstrate a critical role of Txnip-deficiency in inflammatory responses in SMC and suggest Txnip inhibition in SMC may represent a potential target for intervention of atherosclerosis.
Total Shoulder Arthroplasty Demographics, Incidence, and Complications-A Nationwide Inpatient Sample Database Study.

Introduction Total shoulder arthroplasty (TSA) has become a popular and successful surgery to treat advanced glenohumeral arthritis, rotator cuff arthropathy, and proximal humerus fractures. Historical data is available investigating the epidemiology of total shoulder arthroplasty with regard to patient characteristics, outcomes, and complications; however, there is a lack of studies investigating the most recent and up to date national trends related to shoulder replacement. The purpose of this study was to evaluate changes in the annual incidence, various demographics, and complications of TSA in America. Materials and methods The Nationwide Inpatient Sample (NIS) was assessed to identify all patients who were admitted for TSA in the United States between 1998 and 2010. National trends in patient demographics, incidence, and length-of-stay (LOS) were analyzed for correlations. The impacts of contributing factors to each outcome were assessed using adjusted multivariable regression analysis. These were used to calculate odds ratios of cohort demographics and their association with complications and LOS. Results Admissions for TSA have risen (8,041 to 39,072 admissions). The majority of the cohort consisted of Caucasian men between the ages of 64 and 79 years. The incidence rate of complications has remained consistent. Female gender, age > 80 years, and higher Deyo Comorbidity scores were risk factors for higher complications. The LOS has decreased (2.96 to 2.21 days) during the study time period. Female gender, African-American race, Medicaid insurance, and higher Deyo Comorbidity scores were associated with longer stays. Discussion Our study demonstrates a rapid increase in incidence rates of TSAs within the 13-year period in the United States. An increased risk of complications was noted with older age, female gender, and increased Deyo score. Conclusion Our findings may help health care providers identify ways to better manage this procedure and select patients.
An Architectural Characterization Study of Data Mining and Bioinformatics Workloads

Data mining is the process of automatically finding implicit, previously unknown, and potentially useful information from large volumes of data. Recent advances in data extraction techniques have resulted in tremendous increase in the input data size of data mining applications. Data mining systems, on the other hand, have been unable to maintain the same rate of growth. Therefore, there is an increasing need to understand the bottlenecks associated with the execution of these applications in modern architectures. In this paper, we present MineBench, a publicly available benchmark suite containing fifteen representative data mining applications belonging to various categories: classification, clustering, association rule mining and optimization. First, we highlight the uniqueness of data mining applications. Subsequently, we evaluate the MineBench applications on an 8-way shared memory (SMP) machine and analyze important performance characteristics such as L1 and L2 cache miss rates, branch misprediction rates.
Chronic Deferasirox Administration Decreases Hepatic Oxidative Stress and Apoptosis in the Iron Overloaded Gerbil.

Abstract 1996 Poster Board I-1018 Background: Iron overload occurs under conditions such as primary (hereditary) hemochromatosis and secondary iron overload (hemosiderosis) and is associated with an increased risk of developing liver fibrosis, cirrhosis, and hepatocellular carcinoma. Deferasirox is a novel oral chelator with high iron-binding potency and selectivity. Here we investigate the ability of deferasirox to remove excessive hepatic iron and prevent or reverse iron induced hepatic injury. Methods: Adult male Mongolian Gerbils were randomly divided into three groups: control, iron overload, and iron overload + deferasirox treatment (n = 8 / group). Iron overload animals received iron dextran 100mg/kg i.p /5d for 10 wks while deferasirox was given 100mg/kg/d p.o for 1-,3-, or 9- months. Hepatic iron levels were determined by inductively coupled plasma atomic emission spectrometry and Prussian blue staining was performed to examine iron deposition in the corresponding tissues. Immunoblot and immunohistochemical analyses for markers of oxidative stress were employed to assess effects of deferasirox treatment on hepatic protein oxidation and superoxide levels. TUNEL assay was employed to examine the extent of hepatic apoptosis. Results: Compared to the non-treated iron overload group, deferasirox treatment reduced hepatic iron levels by 21.3%, 43.5%, and 47.4% after 1, 3, and 9 months of treatment, respectively (p<0.05). Prussian blue staining and histological analysis detected frequent iron deposition, evidence of hepatic damage, and lipid accumulation in hepatic tissue of the iron overloaded group. Iron deposition was significantly diminished with deferasirox treatment and no evidence of lipid accumulation was observed. Immunoblotting demonstrated that iron overload caused 2- fold increase in hepatic ferritin expression (p< 0.05) which was reduced by 47.5% following three months of deferasirox treatment (p< 0.05). In addition, deferasirox significantly reduced hepatic protein oxidation and superoxide abundance. The percentage of TUNEL-positive nuclei in the deferasirox treated livers was 41.0% lower than that of iron overloaded group (p<0.05). Conclusions: These findings suggest that chronic deferasirox treatment may decrease iron-induced hepatic oxidative stress and apoptosis. Decrease in ROS accumulation in the liver may be the possible mechanism of this protective effect. Further studies are underway to delineate specific mechanisms. Disclosures: No relevant conflicts of interest to declare.
BCR-ABL1 Disrupts SDF-1-Dependent Hematopoietic Cell Migration and Adhesion through the LFA-1 Integrin-Mediated Mechanism.

Abstract Stromal-derived factor-1 (SDF-1) and its receptor, CXCR4, are essential for normal stem/progenitor cell movement, adherence, and retention within the bone marrow environment. Two mechanisms through which BCR-ABL1 are thought to disrupt CXCR4-mediated chemotactic responses have been described in leukemia: 1. the inhibition of CXCR4 expression (Geay et al. 2005, Cancer Res.) and 2. intra-cellular signaling defects without modification of CXCR4 expression (Salgia et al. 1999, Blood; Ptasznik et al. 2002, J. Exp. Med.). These opposing mechanisms suggest that the actual situation is more complex and that new signaling paradigms are needed. To address this, we studied the effects of BCR-ABL1 on SDF-1-dependent, integrin-mediated, migration and adhesion of hematopoietic precursors. Stimulation of BCR-ABL1(−) hematopoietic cells with SDF-1 showed reduced cell adherence to surfaces coated with ICAM-1 (a ligand for the LFA-1 integrin), which was associated with down-regulated expression of activation-dependent epitopes of the β2 integrin, LFA-1, on hematopoietic cells. Inhibition of Lyn expression with siRNA prevented the SDF-1-triggered down-regulation of LFA-1 and cell adherence, indicating that CXCR4 inhibited the function of LFA-1 through Lyn. Expression of BCR-ABL1 in these cells resulted in increased expression of activation-dependent epitopes of LFA-1 and prevented SDF-1-dependent regulatory effects on both LFA-1 affinity and ICAM-1 adherence. Also, expression of BCR-ABL1 prevented Lyn-mediated regulation of cell adhesion to ICAM-1 as well as Lyn-mediated regulation of LFA-1 affinity. These results indicate that BCR-ABL1 constitutively increases the affinity of the LFA-1 integrin to its ligand ICAM-1, locking the integrin into an “active” conformation. The net result is the loss of responsiveness of LFA-1 to SDF-1-induced ‘inside-out' signaling involving CXCR4 and Lyn kinase. Because in our experiments BCR-ABL1 had no significant effect on the expression of CXCR4 in Mo7e cells, transfected with low and high amounts of p210-BCR-ABL, or in primary BCR-ABL(+) cells from CML blast crisis patients (n=3), we conclude that BCR-ABL1 inhibits CXCR4-triggered ‘inside-out' integrin signaling rather than CXCR4 expression. Taken together, we propose that BCR-ABL1 disrupts the signaling link between the chemokine receptor, CXCR4 and the β2 integrin LFA-1 so as to inhibit normal SDF-1-mediated chemotaxis and adhesion in hematopoietic cells.
Expression of Ifnlr1 on Intestinal Epithelial Cells Is Critical to the Antiviral Effects of Interferon Lambda against Norovirus and Reovirus

Lambda interferon (IFN-λ) has potent antiviral effects against multiple enteric viral pathogens, including norovirus and rotavirus, in both preventing and curing infection. Because the intestine includes a diverse array of cell types, however, the cell(s) upon which IFN-λ acts to exert its antiviral effects is unclear. Here, we sought to identify IFN-λ-responsive cells by generation of mice with lineage-specific deletion of the receptor for IFN-λ, Ifnlr1 We found that expression of IFNLR1 on intestinal epithelial cells (IECs) in the small intestine and colon is required for enteric IFN-λ antiviral activity. IEC Ifnlr1 expression also determines the efficacy of IFN-λ in resolving persistent murine norovirus (MNoV) infection and regulates fecal shedding and viral titers in tissue. Thus, the expression of Ifnlr1 by IECs is necessary for the response to both endogenous and exogenous IFN-λ. We further demonstrate that IEC Ifnlr1 expression is required for the sterilizing innate immune effects of IFN-λ by extending these findings in Rag1-deficient mice. Finally, we assessed whether our findings pertained to multiple viral pathogens by infecting mice specifically lacking IEC Ifnlr1 expression with reovirus. These mice phenocopied Ifnlr1-null animals, exhibiting increased intestinal tissue titers and enhanced reovirus fecal shedding. Thus, IECs are the critical cell type responding to IFN-λ to control multiple enteric viruses. This is the first genetic evidence that supports an essential role for IECs in IFN-λ-mediated control of enteric viral infection, and these findings provide insight into the mechanism of IFN-λ-mediated antiviral activity.IMPORTANCE Human noroviruses (HNoVs) are the leading cause of epidemic gastroenteritis worldwide. Type III interferons (IFN-λ) control enteric viral infections in the gut and have been shown to cure mouse norovirus, a small-animal model for HNoVs. Using a genetic approach with conditional knockout mice, we identified IECs as the dominant IFN-λ-responsive cells in control of enteric virus infection in vivo Upon murine norovirus or reovirus infection, Ifnlr1 depletion in IECs largely recapitulated the phenotype seen in Ifnlr1-/- mice of higher intestinal tissue viral titers and increased viral shedding in the stool. Moreover, IFN-λ-mediated sterilizing immunity against murine norovirus requires the capacity of IECs to respond to IFN-λ. These findings clarify the mechanism of action of this cytokine and emphasize the therapeutic potential of IFN-λ for treating mucosal viral infections.
Church and State in Bourbon Mexico: The Diocese of Michoacán, 1749-1810

Preface Part I. The Religious Orders: 1. Jesuit expulsion 2. Mendicant chronicles 3. Oratorians 4. Secularisation 5. Nuns Part II. Priests and Laity: 6. Priests 7. Confraternities and parochial income 8. Devotion and deviance Part III. Bishops and Chapter: 9. Cathedral and chapter 10. A bishop and his canons 11. Tithes and chantries 12. Liberal prelate Appendices Notes Bibliography Index.
Significant Discrepancy Between Estimated and Actual Longevity in St. Jude Medical Implantable Cardioverter-Defibrillators.

Discrepancy in Longevity Estimation in SJM ICDsBackground Real-time estimated longevity has been reported in pacemakers for several years, and was recently introduced in implantable cardioverter-defibrillators (ICDs). Objective We sought to evaluate the accuracy of this longevity estimate in St. Jude Medical (SJM) ICDs, especially as the device battery approaches depletion. Methods Among patients with SJM ICDs who underwent generator replacements due to reaching elective replacement indicator (ERI) at our institution, we identified those with devices that provided longevity estimates and reviewed their device interrogations in the 18 months prior to ERI. Significant discrepancy was defined as a difference of more than 12 months between estimated and actual longevity at any point during this period. Results Forty-six patients with Current/Promote devices formed the study group (40 cardiac resynchronization therapy [CRT] and 6 single/dual chamber). Of these, 34 (74%) had significant discrepancy between estimated and actual longevity (28 CRT and all single/dual). Longevity was significantly overestimated by the device algorithm (mean maximum discrepancy of 18.8 months), more in single/dual than CRT devices (30.5 vs. 17.1 months). Marked discrepancy was seen at voltages ≥2.57 volts, with maximum discrepancy at 2.57 volts (23 months). The overall longevity was higher in the discrepant group of CRT devices than in the nondiscrepant group (67 vs. 61 months, log-rank P = 0.03). Conclusions There was significant overestimation of longevity in nearly three-fourths of Current/Promote SJM ICDs in the last 18 months prior to ERI. Longevity estimates of SJM ICDs may not be reliable for making clinical decisions on frequency of follow-up, as the battery approaches depletion.
Cultural Insensitivity in the Classroom: Should It Be a Concern?

The imbalance between student-teacher cultural demographics creates conditions that are not conducive to developing and maintaining a culturally sensitive school environment or implementing culturally relevant instruction. The teachersâ€™ lack of knowledge about culturally-based factors that impact student learning, the differential power and status between teacher and student, and policies/practices requiring American cultural values as prerequisites to school success are proposed components of a culturally insensitivity environment. Examples of negative outcomes stemming from cultural insensitivityâ€™s are enumerated. Suggestions for offsetting cultural insensitivity in the schools are offered.
Debt spikes and stock flow adjustments: Emerging economies in perspective

What explains public debt spikes? Are debt spikes different in emerging economies than in advanced countries? Analysis of 179 episodes from 1945 to 2014 shows that debt spikes are not rare events and their probability increases with time. Large debt spikes in advanced and emerging countries are neither driven by high primary deficits nor by output declines but instead by sizable stock-flow adjustments (SFAs). Higher SFA accumulation is associated with a higher probability of suffering non-declining debt paths in the aftermath of public debt spikes. Importantly, despite their sizeable impact on debt accumulation, SFAs have been largely ignored in debt sustainability analyses.
Plant-Derived Natural Products as Anticancer Agents

Nature has provided the oncologist with many valuable agents for cancer treatment, including the podophyllotoxin analogs etoposide, teniposide, and etopophos, the taxanes paclitaxel and docetaxel, and the camptothecin derivatives topotecan and irinotecan. The discovery, chemistry, and clinical applications of these compounds are described.