Funnels in Energy Landscapes

Local minima and the saddle points separating them in the energy landscape are known to dominate the dynamics of biopolymer folding. Here we introduce a notion of a "folding funnel" that is concisely defined in terms of energy minima and saddle points, while at the same time conforming to a notion of a "folding funnel" as it is discussed in the protein folding literature.Comment: 6 pages, 3 figures, submitted to European Conference on Complex Systems 200

Determination of MIC and Disk Diffusion Quality Control Guidelines for Meropenem–Vaborbactam, a Novel Carbapenem/Boronic Acid β-Lactamase Inhibitor Combination

Meropenem–vaborbactam is a carbapenem/cyclic boronic acid β-lactamase inhibitor combination primarily active against Gram-negative bacilli, including those harboring class A serine carbapenemases such as Klebsiella pneumoniae carbapenemase (KPC). A Clinical and Laboratory Standards Institute M23-A4 (Tier 2) quality control study established broth microdilution and disk diffusion ranges for reference strains. Two KPC-producing K. pneumoniae ATCC strains are recommended for quality control testing

Brans-Dicke cylindrical wormholes

Static axisymmetric thin-shell wormholes are constructed within the framework of the Brans-Dicke scalar-tensor theory of gravity. Examples of wormholes associated with vacuum and electromagnetic fields are studied. All constructions must be threaded by exotic matter, except in the case of geometries with a singularity of finite radius, associated with an electric field, which can have a throat supported by ordinary matter. These results are achieved with any of the two definitions of the flare-out condition considered.Comment: 11 pages, 3 figures; v3: corrected version, conclusions unchange

Ceftaroline activity tested against contemporary Latin American bacterial pathogens (2011)

AbstractA total of 2484 target bacterial pathogens were collected (one per patient episode) from patients in 16 Latin American medical centers located in seven nations during 2011. Isolate identity was confirmed at a coordinating laboratory and susceptibility testing was performed for ceftaroline and comparator agents according to reference broth microdilution methods. A total of 30.0% of isolates were from respiratory tract, 29.4% from skin and skin structure, 21.4% from blood stream, 7.9% from urinary tract and 11.3% from other sites. Ceftaroline was active against Staphylococcus aureus (42.8% MRSA) with 83.6% of the isolates at ≤1mg/L and all isolates at ≤2mg/L (MIC5090, 0.25/2mg/L). National MRSA rates ranged from a low of 28.8% in Colombia to a high of 68.1% in Chile. All Streptococcus pyogenes and Streptococcus agalactiae were susceptible to ceftaroline (MIC50/90 values were at ≤0.015/≤0.015mg/L for both). All Streptococcus pneumoniae were susceptible to ceftaroline, linezolid, tigecycline and vancomycin. Susceptibility to ceftriaxone was at 88.4% (CLSI non-meningitis interpretive criteria) and 73.9% (CLSI meningitis interpretive criteria) for all S. pneumoniae. Ceftriaxone susceptibility was only at 33.3% (CLSI non-meningitis interpretive criteria) and 0.0% (CLSI meningitis interpretive criteria) for penicillin-intermediate (penicillin MIC, 4mg/L) strains. All Haemophilus influenzae (29.4% β-lactamase-positive) isolates were susceptible to ceftaroline, amoxicillin–clavulanate, ceftriaxone, and levofloxacin. For the Latin American region, the ESBL-phenotype rate was 37.6% for Escherichia coli and 53.3% for Klebsiella pneumoniae. Ceftaroline was not active against ESBL-phenotype strains but was active against >90.0% of the non-ESBL-phenotype. The spectrum of activity of ceftaroline against pathogens from Latin America indicates that it merits further study for its potential use in the Latin American region

Energetics in Condensate Star and Wormholes

It is known that the total gravitational energy in localized sources having static spherical symmetry and satisfying energy conditions is negative (attractive gravity). A natural query is how the gravitational energy behaves under circumstances where energy conditions are violated. To answer this, the known expression for the gravitational energy is suitably modified to account for situations like the ones occurring in wormhole spacetime. It is then exemplified that in many cases the modified expression yields desirable answers. The implications are discussed.Comment: 16 pages, 1 figure, references added, To appear in PR

Wormholes, Gamma Ray Bursts and the Amount of Negative Mass in the Universe

In this essay, we assume that negative mass objects can exist in the extragalactic space and analyze the consequences of their microlensing on light from distant Active Galactic Nuclei. We find that such events have very similar features to some observed Gamma Ray Bursts and use recent satellite data to set an upper bound to the amount of negative mass in the universe.Comment: Essay awarded ``Honorable Mention'' in the Gravity Foundation Research Awards, 199

Computational Study of an Axisymmetric Dual Throat Fluidic Thrust Vectoring Nozzle for a Supersonic Aircraft Application

A computational investigation of an axisymmetric Dual Throat Nozzle concept has been conducted. This fluidic thrust-vectoring nozzle was designed with a recessed cavity to enhance the throat shifting technique for improved thrust vectoring. The structured-grid, unsteady Reynolds- Averaged Navier-Stokes flow solver PAB3D was used to guide the nozzle design and analyze performance. Nozzle design variables included extent of circumferential injection, cavity divergence angle, cavity length, and cavity convergence angle. Internal nozzle performance (wind-off conditions) and thrust vector angles were computed for several configurations over a range of nozzle pressure ratios from 1.89 to 10, with the fluidic injection flow rate equal to zero and up to 4 percent of the primary flow rate. The effect of a variable expansion ratio on nozzle performance over a range of freestream Mach numbers up to 2 was investigated. Results indicated that a 60 circumferential injection was a good compromise between large thrust vector angles and efficient internal nozzle performance. A cavity divergence angle greater than 10 was detrimental to thrust vector angle. Shortening the cavity length improved internal nozzle performance with a small penalty to thrust vector angle. Contrary to expectations, a variable expansion ratio did not improve thrust efficiency at the flight conditions investigated

Ceftobiprole Activity against over 60,000 Clinical Bacterial Pathogens Isolated in Europe, Turkey, and Israel from 2005 to 2010

Ceftobiprole medocaril is a newly approved drug in Europe for the treatment of hospital-acquired pneumonia (HAP) (excluding patients with ventilator-associated pneumonia but including ventilated HAP patients) and community-acquired pneumonia in adults. the aim of this study was to evaluate the in vitro antimicrobial activity of ceftobiprole against prevalent Gram-positive and -negative pathogens isolated in Europe, Turkey, and Israel during 2005 through 2010. A total of 60,084 consecutive, nonduplicate isolates from a wide variety of infections were collected from 33 medical centers. Species identification was confirmed, and all isolates were susceptibility tested using reference broth microdilution methods. Ceftobiprole had high activity against methicillin-susceptible Staphylococcus aureus (MSSA) (100.0% susceptible), methicillin-susceptible coagulase-negative staphylococci (CoNS), beta-hemolytic streptococci, and Streptococcus pneumoniae (99.3% susceptible), with MIC90 values of 0.25, 0.12, 80% inhibited at 8 mu g/ml; 64.6% at MIC values of 16 mu g/ml; 75.4% susceptible), but limited activity was observed against Acinetobacter spp. and Stenotrophomonas maltophilia. High activity was also observed against all Haemophilus influenzae (MIC90, <= 0.06 mu g/ml) and Moraxella catarrhalis (MIC50/90, <= 0.06/0.25 mu g/ml) isolates. Ceftobiprole demonstrated a wide spectrum of antimicrobial activity against this very large longitudinal sample of contemporary pathogens.Basilea Pharmaceutica International AG (Basel, Switzerland)AchaogenAiresAmerican Proficiency Institute (API)AnacorAstellasAstraZenecaBayerbioMerieuxCempraCerexaContrafectCubist PharmaceuticalsDaiichiDipexiumEnantaFuriexGlaxoSmithKlineJohnson JohnsonLegoChem Biosciences Inc.Meiji Seika KaishaMerckNabrivaNovartisParatekPfizerPPD TherapeuticsPremier Research GroupRempexRib-X PharmaceuticalsSeachaidShionogiThe Medicines Co.TheravanceThermo FisherJMI Labs, North Liberty, IA 52317 USAUniv Toronto, Dept Lab Med & Pathobiol, Toronto, ON, CanadaUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilTufts Univ, Sch Med, Boston, MA 02111 USAUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilWeb of Scienc