The Influence of Website Quality on Online Purchase Intentions on Agoda.Com with E-Trust as a Mediator

In e-commerce market, there is no physical interaction between buyers, sellers, and payments. The confidence to buy online e-trust can raise or lower the perceived risk and security issues, so e-trust is crucial for the success of e-commerce companies, such as Agoda.com. The sorting of online businesses is vital to avoid losses when doing the online business transaction, such as by looking at the quality of the website and the company's ability to provide e-trust. The methods used in this research were quantitative and causal. The research sample was collected using non-probability sampling method which was purposive sampling by taking 200 respondents. Data analysis techniques used SEM (Structural Equation Modeling).The conclusion shows the existence of a significant influence on the website's quality towards e-trust, and e-trust on the online purchase intentions. Moreover, there is an insignificant impact on the quality of the site towards online purchase intentions

Missileborne Artificial Vision System (MAVIS)

Several years ago when INTEL and China Lake designed the ETANN chip, analog VLSI appeared to be the only way to do high density neural computing. In the last five years, however, digital parallel processing chips capable of performing neural computation functions have evolved to the point of rough equality with analog chips in system level computational density. The Naval Air Warfare Center, China Lake, has developed a real time, hardware and software system designed to implement and evaluate biologically inspired retinal and cortical models. The hardware is based on the Adaptive Solutions Inc. massively parallel CNAPS system COHO boards. Each COHO board is a standard size 6U VME card featuring 256 fixed point, RISC processors running at 20 MHz in a SIMD configuration. Each COHO board has a companion board built to support a real time VSB interface to an imaging seeker, a NTSC camera, and to other COHO boards. The system is designed to have multiple SIMD machines each performing different corticomorphic functions. The system level software has been developed which allows a high level description of corticomorphic structures to be translated into the native microcode of the CNAPS chips. Corticomorphic structures are those neural structures with a form similar to that of the retina, the lateral geniculate nucleus, or the visual cortex. This real time hardware system is designed to be shrunk into a volume compatible with air launched tactical missiles. Initial versions of the software and hardware have been completed and are in the early stages of integration with a missile seeker

Automated Propulsion Data Screening demonstration system

A fully-instrumented firing of a propulsion system typically generates a very large quantity of data. In the case of the Space Shuttle Main Engine (SSME), data analysis from ground tests and flights is currently a labor-intensive process. Human experts spend a great deal of time examining the large volume of sensor data generated by each engine firing. These experts look for any anomalies in the data which might indicate engine conditions warranting further investigation. The contract effort was to develop a 'first-cut' screening system for application to SSME engine firings that would identify the relatively small volume of data which is unusual or anomalous in some way. With such a system, limited and expensive human resources could focus on this small volume of unusual data for thorough analysis. The overall project objective was to develop a fully operational Automated Propulsion Data Screening (APDS) system with the capability of detecting significant trends and anomalies in transient and steady-state data. However, the effort limited screening of transient data to ground test data for throttle-down cases typical of the 3-g acceleration, and for engine throttling required to reach the maximum dynamic pressure limits imposed on the Space Shuttle. This APDS is based on neural networks designed to detect anomalies in propulsion system data that are not part of the data used for neural network training. The delivered system allows engineers to build their own screening sets for application to completed or planned firings of the SSME. ERC developers also built some generic screening sets that NASA engineers could apply immediately to their data analysis efforts

Neutropenia induced in outbred mice by a simplified low-dose cyclophosphamide regimen: characterization and applicability to diverse experimental models of infectious diseases

BACKGROUND: For its low cost and ease of handling, the mouse remains the preferred experimental animal for preclinical tests. To avoid the interaction of the animal immune system, in vivo antibiotic pharmacodynamic studies often employ cyclophosphamide (CPM) to induce neutropenia. Although high doses (350–450 mg/kg) are still used and their effects on mouse leukocytes have been described, a lower dose (250 mg/kg) is widely preferred today, but the characteristics and applicability of this approach in outbred mice have not been determined. METHODS: Fifteen female ICR mice were injected intraperitoneally with 150 and 100 mg/kg of CPM on days 1 and 4, respectively. Blood samples (~160 μL) were drawn from the retro-orbital sinus of each mouse on days 1, 4, 5, 6, 7 and 11. Leukocytes were counted manually and the number of granulocytes was based on microscopic examination of Wright-stained smears. The impact of neutropenia induced by this method was then determined with a variety of pathogens in three different murine models of human infections: pneumonia (Klebsiella pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus), meningoencephalitis (S. pneumoniae), and the thigh model (S. aureus, Escherichia coli, Bacteroides fragilis). RESULTS: The basal count of leukocytes was within the normal range for outbred mice. On day 4, there was an 84% reduction in total white blood cells, and by day 5 the leukopenia reached its nadir (370 ± 84 cells/mm(3)). Profound neutropenia (≤10 neutrophils/mm(3)) was demonstrated at day 4 and persisted through days 5 and 6. Lymphocytes and monocytes had a 92% and 96% decline between days 1 and 5, respectively. Leukocytes recovered completely by day 11. Mice immunosupressed under this protocol displayed clinical and microbiological patterns of progressive and lethal infectious diseases after inoculation in different organs with diverse human pathogens. CONCLUSION: A CPM total dose of 250 mg/kg is sufficient to induce profound and sustained neutropenia (<10 neutrophils/mm(3)) at least during 3 days in outbred mice, is simpler than previously described methods, and allows successful induction of infection in a variety of experimental models

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

Combinations of β-lactam or aminoglycoside antibiotics with plectasin are synergistic against methicillin-sensitive and methicillin-resistant Staphylococcus aureus.

Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and the latter can be difficult to treat. The traditional strategy of novel therapeutic drug development inevitably leads to emergence of resistant strains, rendering the new drugs ineffective. Therefore, rejuvenating the therapeutic potentials of existing antibiotics offers an attractive novel strategy. Plectasin, a defensin antimicrobial peptide, potentiates the activities of other antibiotics such as β-lactams, aminoglycosides and glycopeptides against MSSA and MRSA. We performed in vitro and in vivo investigations to test against genetically diverse clinical isolates of MSSA (n = 101) and MRSA (n = 115). Minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The effects of combining plectasin with β-lactams, aminoglycosides and glycopeptides were examined using the chequerboard method and time kill curves. A murine neutropenic thigh model and a murine peritoneal infection model were used to test the effect of combination in vivo. Determined by factional inhibitory concentration index (FICI), plectasin in combination with aminoglycosides (gentamicin, neomycin or amikacin) displayed synergistic effects in 76-78% of MSSA and MRSA. A similar synergistic response was observed when plectasin was combined with β-lactams (penicillin, amoxicillin or flucloxacillin) in 87-89% of MSSA and MRSA. Interestingly, no such interaction was observed when plectasin was paired with vancomycin. Time kill analysis also demonstrated significant synergistic activities when plectasin was combined with amoxicillin, gentamicin or neomycin. In the murine models, plectasin at doses as low as 8 mg/kg augmented the activities of amoxicillin and gentamicin in successful treatment of MSSA and MRSA infections. We demonstrated that plectasin strongly rejuvenates the therapeutic potencies of existing antibiotics in vitro and in vivo. This is a novel strategy that can have major clinical implications in our fight against bacterial infections

Clinical Practice Guidelines for the Management Candidiasis: 2009 Update by the Infectious Diseases Society of America

Guidelines for the management of patients with invasive candidiasis and mucosal candidiasis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections. Since 2004, several new antifungal agents have become available, and several new studies have been published relating to the treatment of candidemia, other forms of invasive candidiasis, and mucosal disease, including oropharyngeal and esophageal candidiasis. There are also recent prospective data on the prevention of invasive candidiasis in high-risk neonates and adults and on the empiric treatment of suspected invasive candidiasis in adults. This new information is incorporated into this revised documen

Dual action antifungal small molecule modulates multidrug efflux and TOR signaling.

There is an urgent need for new strategies to treat invasive fungal infections, which are a leading cause of human mortality. Here, we establish two activities of the natural product beauvericin, which potentiates the activity of the most widely deployed class of antifungal against the leading human fungal pathogens, blocks the emergence of drug resistance, and renders antifungal-resistant pathogens responsive to treatment in mammalian infection models. Harnessing genome sequencing of beauvericin-resistant mutants, affinity purification of a biotinylated beauvericin analog, and biochemical and genetic assays reveals that beauvericin blocks multidrug efflux and inhibits the global regulator TORC1 kinase, thereby activating the protein kinase CK2 and inhibiting the molecular chaperone Hsp90. Substitutions in the multidrug transporter Pdr5 that enable beauvericin efflux impair antifungal efflux, thereby impeding resistance to the drug combination. Thus, dual targeting of multidrug efflux and TOR signaling provides a powerful, broadly effective therapeutic strategy for treating fungal infectious disease that evades resistance