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The complexity of modern systems of systems (SoS) requires the ability to quickly and effectively evaluate robustness in architecture alternatives. This article presents a framework for rapid, quantitative comparisons of robustness in SoS architectures that leverages complex network methods for assessing robustness and design of experiments (DoE) techniques for validating their use in the scenario of interest. We consider both single-layer and multilayer network representations of SoS and focus on algebraic connectivity, inverse average path length, and largest connected component size as measures of robustness. Two case studies are used to illustrate our framework and assess its utility: a command, control, communications, computer, intelligence, surveillance, and reconnaissance (C4ISR) simulation and a multilayer message-passing network simulation. We find that most of the considered network metrics capture expected robustness trends, though their ability to capture these trends is often affected by the scenario of interest. These results demonstrate the potential value of complex network methods for lightweight analysis of robustness in SoS architecture alternatives, when appropriately supported by DoE methods for understanding their limitations.

Systolic blood pressure of more than 185 mm Hg is a contraindication to thrombolytic treatment with intravenous alteplase in patients with acute ischaemic stroke, but the target systolic blood pressure for optimal outcome is uncertain. We assessed intensive blood pressure lowering compared with guideline-recommended blood pressure lowering in patients treated with alteplase for acute ischaemic stroke.

Immune thrombocytopenia (ITP) is an acquired thrombocytopenia resulting from immune-mediated platelet destruction via antiplatelet antibodies and T cells. Medical management of ITP includes corticosteroids and multiple other adjunct therapies, with splenectomy generally being reserved for severe, refractory cases. In this clinical case report, we describe the evaluation of a 35-year-old male with a history of prior traumatic splenic injury who presented to the emergency department endorsing easy bruising and a petechial rash, ultimately found to have severe thrombocytopenia. The patient was diagnosed with primary ITP that proved to be refractory to a number of first- and second-line medical therapies. His course was complicated by the presence of abdominal splenosis discovered at the time of planned splenectomy and intra-abdominal hemorrhage requiring splenic artery embolization thereafter. To our knowledge, this is one of few published cases of ITP complicated by abdominal splenosis, highlighting the need to consider splenosis and the presence of accessory splenic tissue in cases of refractory ITP.

Recent experiments on thin films and hetero-structures of ionically conducting oxides have indicated to an enhancement of oxygen ion conduction typically ascribed to strain-related effects. We performed first-principles calculations to investigate the effects of biaxial lattice strain on the oxygen anion diffusivity in Sm2O3 doped CeO2 (SDC). The oxygen ion migration paths and barriers in SDC as functions of lattice strain were assessed computationally using density functional theory (DFT) with U correction and climbing image nudged elastic band (CI-NEB) method. Our current results indicate that both expansive and compressive strains lead to decreases in the ionic migration barriers.

Recently, magnetic-based theranostic nanoparticle (MBTN) systems have been studied, researched, and applied extensively to detect and treat various diseases including cancer. Theranostic nanoparticles are advantageous in that the diagnosis and treatment of a disease can be performed in a single setting using combinational strategies of targeting, imaging, and/or therapy. Of these theranostic strategies, magnetic-based systems containing magnetic nanoparticles (MNPs) have gained popularity because of their unique ability to be used in magnetic resonance imaging, magnetic targeting, hyperthermia, and controlled drug release. To increase their effectiveness, MNPs have been decorated with a wide variety of materials to improve their biocompatibility, carry therapeutic payloads, encapsulate/bind imaging agents, and provide functional groups for conjugation of biomolecules that provide receptor-mediated targeting of the disease. This review summarizes recent patents involving various polymer coatings, imaging agents, therapeutic agents, targeting mechanisms, and applications along with the major requirements and challenges faced in using MBTN for disease management.

An updated and practical approach to the synthesis of dithymoquinone via one-step photoirradiation of thymoquinone (2-methyl-5-isopropyl-1,4-benzoquinone) is described. Synthesis resulted in a 55 yield of one structural isomer (trans-anti derivative), as confirmed by HPLC, NMR spectroscopy and first ever single-crystal X-ray diffraction analyses.

Prostate cancer is the most common cancer and second leading cause of cancer deaths among men in the United States. Most men have localized disease diagnosed following an elevated serum prostate specific antigen test for cancer screening purposes. Standard treatment options consist of surgery or definitive radiation therapy directed by clinical factors that are organized into risk stratification groups. Current clinical risk stratification systems are still insufficient to differentiate lethal from indolent disease. Similarly, a subset of men in poor risk groups need to be identified for more aggressive treatment and enrollment into clinical trials. Furthermore, these clinical tools are very limited in revealing information about the biologic pathways driving these different disease phenotypes and do not offer insights for novel treatments which are needed in men with poor-risk disease. We believe molecular biomarkers may serve to bridge these inadequacies of traditional clinical factors opening the door for personalized treatment approaches that would allow tailoring of treatment options to maximize therapeutic outcome. We review the current state of prognostic and predictive tissuebased molecular biomarkers which can be used to direct localized prostate cancer treatment decisions, specifically those implicated with definitive and salvage radiation therapy.

As an important aspect of computer-aided drug design, structure-based drug design brought a new horizon to pharmaceutical development. This in silico method permeates all aspects of drug discovery today, including lead identification, lead optimization, ADMET prediction and drug repurposing. Structure-based drug design has resulted in fruitful successes drug discovery targeting proteinligand and protein-protein interactions. Meanwhile, challenges, noted by low accuracy and combinatoric issues, may also cause failures. In this review, state-of-the-art techniques for protein modeling (e.g. structure prediction, modeling protein flexibility, etc.), hit identification/ optimization (e.g. molecular docking, focused library design, fragment-based design, molecular dynamic, etc.), and polypharmacology design will be discussed. We will explore how structure-based techniques can facilitate the drug discovery process and interplay with other experimental approaches.

As an important aspect of computer-aided drug design, structure-based drug design brought a new horizon to pharmaceutical development. This in silico method permeates all aspects of drug discovery today, including lead identification, lead optimization, ADMET prediction and drug repurposing. Structure-based drug design has resulted in fruitful successes drug discovery targeting proteinligand and protein-protein interactions. Meanwhile, challenges, noted by low accuracy and combinatoric issues, may also cause failures. In this review, state-of-the-art techniques for protein modeling (e.g. structure prediction, modeling protein flexibility, etc.), hit identification/ optimization (e.g. molecular docking, focused library design, fragment-based design, molecular dynamic, etc.), and polypharmacology design will be discussed. We will explore how structure-based techniques can facilitate the drug discovery process and interplay with other experimental approaches.

As an important aspect of computer-aided drug design, structure-based drug design brought a new horizon to pharmaceutical development. This in silico method permeates all aspects of drug discovery today, including lead identification, lead optimization, ADMET prediction and drug repurposing. Structure-based drug design has resulted in fruitful successes drug discovery targeting proteinligand and protein-protein interactions. Meanwhile, challenges, noted by low accuracy and combinatoric issues, may also cause failures. In this review, state-of-the-art techniques for protein modeling (e.g. structure prediction, modeling protein flexibility, etc.), hit identification/ optimization (e.g. molecular docking, focused library design, fragment-based design, molecular dynamic, etc.), and polypharmacology design will be discussed. We will explore how structure-based techniques can facilitate the drug discovery process and interplay with other experimental approaches.

Alzheimers disease (AD) is a degenerative disorder that leads to progressive, irreversible cognitive decline. It develops as a result of over-production and aggregation of -amyloid (A) peptides in the brain. We have recently shown that stress exacerbates, while nicotine prevents long-term memory impairment induced by -Amyloid. In this study, we evaluated the effect of chronic psychosocial stress on synaptic plasticity (Late-phase long-term potentiation; L-LTP, and long-term depression; LTD) in the -Amyloid rat model of AD, and the positive impact of chronic nicotine treatment. Chronic psychosocial stress was induced by an intruder method. The Rat AD model was induced by 14-day i.c.v. osmotic pump infusion of a 1:1 mixture of 300 pmol/day A1-40/A1-42. The rats were treated with nicotine (2 mg/kg/day) for 6 weeks. In vivo electrophysiological recordings of L-LTP, and LTD in hippocampal area CA1 showed that chronic stress by itself did not affect L-LTP. However, it markedly aggravated the impairment of this response as well as LTD in A- treated rats. The effects of A and the combination of stress and A were totally prevented by chronic nicotine treatment. Immunoblot analysis revealed that stress and/or A significantly increased the basal levels of calcineurin and prevented the expected L-LTP-induced increase in CREB phosphorylation, and CaMKIV levels. These effects were not seen in A- infused rats chronically treated with nicotine. The changes in synaptic plasticity-related molecules may explain the effects of stress and/or chronic nicotine on L-LTP in A animals.

Basal synaptic transmission and activity-dependent synaptic plasticity were evaluated in superior cervical sympathetic ganglia (SCG) of amyloid- rat model of Alzheimers disease (A rat) using electrophysiological and molecular techniques. Rats were administered A peptides (a mixture of 1:1 A1-40 and A1-42) by chronic intracerebroventricular infusion via 14-day mini-osmotic pumps (300 pmol/day). Control rats received A40-1 (inactive reverse peptide: 300 pmol/day). Ganglionic compound action potentials were recorded before (basal) and after repetitive stimulation. In isolated SCG, ganglionic long-term potentiation (gLTP) was generated by a brief train of stimuli (20Hz for 20s) and ganglionic long-term depression (gLTD) was produced with trains of paired pulses. The input/output (I/O) curves of ganglia from A rats showed a marked downward shift along all stimulus intensities, compared to those of ganglia from control animals, indicating impaired basal synaptic transmission. In addition, repetitive stimulation induced robust gLTP and gLTD in ganglia isolated from control animals, but, the same protocols failed to induce gLTP or gLTD in ganglia from A rats indicating impairment of activity-dependent synaptic plasticity in these animals. Western blotting of SCG homogenate from A rats revealed reduction in the ratio of phosphorylated-/total-CaMKII and in calcineurin protein levels. Although other mechanisms could be involved, these changes in signaling molecules could represent an important molecular mechanism linked to the failure to express synaptic plasticity in A rat ganglia. Results of the current study could explain some of the peripheral nervous system manifestations of Alzheimers disease.

Soil degradation and water pollution are widespread land degradation problems in Southeast Asia. Policy makers are currently faced with the challenge of designing and implementing strategies to maintain soil fertility and avoid off-site effects. The aim of this study was to determine the effect of organic substrate amendments on soil properties, nutrient leaching and the growth of Ipomea aquaticain an acidic degraded soil from northern Vietnam. Plants were grown in an Acrisol in buckets under natural weather conditions for two months. The same amount of nutrients was applied either in a purely synthetic form (mineral fertilizers) or as two alternative organic substrates (three month old compost or vermicompost from buffalo dung) plus additional amounts of synthetic mineral nutrients to ensure the same quantity of NPK. The influence of these respective substrates on the soil's physical and chemical properties as well as plant growth was examined. Both compost and vermicompost led to an improvement in soil properties with an increase in the pH, soil organic matter and nutrient content, compared to soil fertilized with synthetic mineral products. The highest plant productivity was obtained with vermicompost and synthetic fertilizers, with no significant difference between these two treatments. Chemical fertilization, however, is the least effective practice based on the amount of nutrients leached from the soil (about 38% of N and 22% of K, compared to less than 10 and 5% of N and K with organic amendments). P leaching was not influenced by the fertilizer treatments. In conclusion, vermicompost does appear to be a relevant alternative to chemical fertilizers because it leads to similar enhancements in plant growth, at the same time as increasing soil quality and decreasing nutrient leaching.

With the expansion of the Internet and World Wide Web (or the Web), research environments have changed dramatically. As a result, the need to be able to efficiently and securely access information and resources from remote computer systems is becoming even more critical. This paper describes the development of an extendable integrated Web-accessible simulation environment for computational science and engineering called Computational Science and Engineering Online (CSE-Online; http://cse-online.net). CSE-Online is based on a unique client−server software architecture that can distribute the workload between the client and server computers in such a way as to minimize the communication between the client and server, thus making the environment less-sensitive to network instability. Furthermore, the new software architecture allows the user to access data and resources on one or more remote servers as well as on the computing grid while having the full capability of the Web-services collaborative environment. It can be accessed anytime and anywhere from a Web browser connected to the network by either a wired or wireless connection. It has different modes of operations to support different working environments and styles. CSE-Online is evolving into middleware that can provide a framework for accessing and managing remote data and resources including the computing grid for any domain, not necessarily just within computational science and engineering.

Proper microtubule organization is essential for cellular processes such as organelle positioning during interphase and spindle formation during mitosis. The fission yeast Schizosaccharomyces pombe presents a good model for understanding microtubule organization. We identify fission yeast ase1p, a member of the conserved ASE1/PRC1/MAP65 family of microtubule bundling proteins, which functions in organizing the spindle midzone during mitosis. Using fluorescence live cell imaging, we show that ase1p localizes to sites of microtubule overlaps associated with microtubule organizing centers at both interphase and mitosis. ase1Delta mutants fail to form overlapping antiparallel microtubule bundles, leading to interphase nuclear positioning defects, and premature mitotic spindle collapse. FRAP analysis revealed that interphase ase1p at overlapping microtubule minus ends is highly dynamic. In contrast, mitotic ase1p at microtubule plus ends at the spindle midzone is more stable. We propose that ase1p functions to organize microtubules into overlapping antiparallel bundles both in interphase and mitosis and that ase1p may be differentially regulated through the cell cycle.

XMAP215 is a microtubule associated protein that speeds microtubule plus end growth by seven- to tenfold and protects these ends from destabilization by the Kin I kinesin, XKCM1. To understand the mechanisms responsible for these activities, it is necessary to know the structure of XMAP215. By unidirectional shadowing and electron microscopy, XMAP215 appeared as an elongate molecule of 60+/-18 nm, suggesting that XMAP215 could span up to seven to eight tubulin dimers along a protofilament. Most XMAP215 molecules were straight but a subset were bent suggesting that XMAP215 is flexible. Antibodies to the C terminus labeled one end of XMAP215 with no evidence for XMAP215 dimerization. Incubation of XMAP215 and tubulin at 4 degrees C resulted in assembly of curved protofilaments, which appeared to be incomplete tubulin rings. Measurements from rotary shadowed samples showed that tubulin/XMAP215 partial rings had an average width of 8.8+/-1.8 nm compared with 5.6+/-1.1 nm for rings assembled from tubulin dimers alone, suggesting that XMAP215 adds a width of approximately 3.2 nm to the curved tubulin protofilament. XMAP215 did not change the radius of curvature of these partial tubulin rings. Measurements of microtubule flexural rigidity by thermal fluctuations showed that XMAP215 did not change microtubule rigidity. Finally, sequence analysis shows that the N-terminal half of XMAP215 contains four repeats, each composed of multiple HEAT repeats.

The action of several dopamine agonists on blood pressure was investigated. In dogs, apomorphine induced a decrease in blood pressure and an increase in heart rate. These effects were suppressed by intravenous haloperidol or phentolamine. Intravenous but not intracisternal domperidone suppressed the hypotensive responses elicited by intravenous or intracisternal apomorphine. Furthermore, the hypotensive effect of bromocriptine or apomorphine was abolished in adrenal demedullated dogs. Apomorphine and bromocriptine decreased adrenal catecholamine levels. In men, the acute hypotensive property of apomorphine (but not the long term effect of bromocriptine) was suppressed by pretreatment with domperidone. In hypertensive Parkinsonians, bromocriptine reduced blood pressure, induced an increase in inulin clearance, a decrease in plasma creatinine concentration and in renal vascular resistances. These results suggest that dopamine agonists (like apomorphine or bromocriptine) reduce blood pressure through both a decrease in sympathetic tone and an improvement in renal function. However, the mechanism of the acute and long term hypotensive effects could be different only involving peripheral mechanisms after acute

This research work demonstrates a novel hybrid electrolyte based on a deep eutectic solvent (DES) combined with organic solvents for high-performance supercapacitors. DES was formed between ethylene glycol (EG) and lithium bis((trifluoromethyl)sulfonyl) imide (LiTFSI) and diluted by ethylene carbonate (EC) or acetonitrile (AN) with different amounts (10–50% wt.). Such a combination gives superior properties for hybrid electrolytes compared to pure DESs and reduces the volatility of mixed organic solvents. Regarding the electrochemical properties, DES-AN mixtures exhibited a better performance under high applied voltage and more reversible behavior than DES-EC ones, which suffered from the increasing distance in the electrical double layer. DES 1 : 4 + 20% wt. AN exhibited favorable electrolyte properties such as high ionic conductivity (3.1 mS·cm−1 at 30oC), relatively lower viscosity (14.28 mPa s at 30oC, approximately 2 times lower thanDES pure), and quite large electrochemical stability window up to 3.4 V (at 20–30% wt. AN) compared to the baseline electrolyte (LiTFSI/TBABF4 in AN). With these interesting properties, selected hybrid electrolyte (DES 1 : 4 + 20% wt. AN) tested in the symmetric capacitor using the activated carbon offered decent capacitance (15 F·g−1 at 3.4 V with a scanning rate of 1 A·g−1 and remains around 95% after 100 cycles) and good charge-discharge durability (>80% retention after 2000 cycles), especially the EDLC with DES 1 : 4 + 20% wt. AN shows good rate capacity (13.2 F·g−1 at 2 A·g−1, remaining 6 F·g−1 at 10 A·g−1).

The aim of this study was to examine the reliability and validity of the Job Content Questionnaire (JCQ) in Vietnamese among hospital nursing staff. The 22‐items version of the JCQ was used. This includes four scales: (a) psychological demands (5 items); (b) job control (9 items); (c) supervisor support (4 items); and (d) coworker support (4 items). All 1258 nurses in a general hospital in Vietnam, excluding 11 who were due to retire, were invited to complete the cross‐sectional survey. The internal consistency reliability was estimated using Cronbach's α. Construct validity was examined using exploratory factor analysis (EFA). Convergent validity was evaluated by calculating correlations between the JCQ scores and DASS 21 and overtime work. In total, 949 (75%) of the 1258 eligible nurses completed the survey. Cronbach's α values demonstrated acceptable internal consistency in two scales (supervisor support α = .87; coworker support α = .86), while Cronbach's α was below the acceptable threshold of 0.70 for job control (α = .45) and job demand (α = .50). EFA assuming a four‐factor structure showed a factor structure that was almost identical to the original JCQ, with two items loading on other scales. The subscales of depression, anxiety, and stress response of DASS 21 and the subscales of JCQ were significantly correlated, as expected. The results suggest that the JCQ in Vietnamese can be used with some reliability and validity for examining psychosocial work environment among nurses. Further studies should be done to confirm and expand our findings in a variety of occupational groups and in other Asian low‐ and middle‐income countries.

A transition metal complex covalently bound to an organic salt offers a unique opportunity to explore issues of catalysis in an ionic liquid medium. Ligand exchange of acetate with an imidazolium functionality tethered to a carboxylic acid afforded the desired metal-conjugate. The modified dirhodium(II) dimer was found to be an effective catalyst in the intermolecular cyclopropanation reaction of styrene using ethyl diazoacetate.

The rf design of a stabilized tunable high current RFQ was accomplished while remaining compatible with extreme pumping and cooling requirements. Several design innovations were introduced, including distributed pumping, compensated straps, dual dynamic balanced tuners and a tuner compensated drive loop. The code RFQ3D was demonstrated to be quantitatively useful for predicting design characteristics.

Two pairs of ceftolozane/tazobactam susceptible/resistant P. aeruginosa were isolated from 2 patients after exposure to β-lactams. The genetic basis of ceftolozane/tazobactam resistance was evaluated, and β-lactam-resistant mechanisms were assessed by phenotypic assays. Whole genome sequencing identified mutations in AmpC including the mutation (V213A) and a deletion of 7 amino acids (P210–G216) in the Ω-loop. Phenotypic assays showed that ceftolozane/tazobactam resistance in the strain with AmpCV213A variant was associated with increased β-lactamase hydrolysis activity. On the other hand, the deletion of 7 amino acids in the Ω-loop of AmpC did not display enhanced β-lactamase activity. Resistance to ceftolozane/tazobactam in P. aeruginosa is associated with changes in AmpC; however, the apparent loss of β-lactamase activity in AmpC∆7 suggests that non-AmpC mechanisms could play an important role in resistance to β-lactam/β-lactamase inhibitor combinations.

Using Transition-State Theory, experimental rate constants, determined over a range of temperatures, for reactions of vitamin E type antioxidants are analysed in terms of their enthalpies and entropies of activation. It is further shown that computational methods may be employed to calculate enthalpies and entropies, and hence Gibbs Free Energies, for the overall reactions. Within the Linear Free Energy Relationship (LFER) assumption, that the Gibbs Free Energy of activation is proportional to the overall Gibbs Free Energy change for the reaction, it is possible to rationalise, and even to predict, the relative contributions of enthalpy and entropy for reactions of interest, involving potential antioxidants.

Implantable cardioverter defibrillator (ICD) placements can be associated with serious complications. This paper reports a patient in whom percutaneous placement of an ICD resulted in a hemopneumothorax. This was due to an active fixation lead that perforated the right atrial wall and injured the adjacent lung parenchyma. The hemothorax was drained thoracoscopically, and the atrial injury was covered with fibrin glue.

The approach to patients with indeterminate pulmonary nodules is poorly defined. Should every pulmonary nodule be biopsied, is needle biopsy adequate, and other questions are challenges. Video assisted thoracic surgery or thoracoscopy has added a new diagnostic possibility which is evaluated in this paper. Fifty-five patients underwent thoracoscopy for diagnosis of a solitary pulmonary nodule. There were few complications and mortality was zero. A definitive diagnosis was obtained in all patients, although one required a second thoracoscopic wedge resection and 10 required conversion to an open thoracotomy.