509 research outputs found
Energy landscapes, ideal glasses, and their equation of state
Using the inherent structure formalism originally proposed by Stillinger and
Weber [Phys. Rev. A 25, 978 (1982)], we generalize the thermodynamics of an
energy landscape that has an ideal glass transition and derive the consequences
for its equation of state. In doing so, we identify a separation of
configurational and vibrational contributions to the pressure that corresponds
with simulation studies performed in the inherent structure formalism. We
develop an elementary model of landscapes appropriate to simple liquids which
is based on the scaling properties of the soft-sphere potential complemented
with a mean-field attraction. The resulting equation of state provides an
accurate representation of simulation data for the Lennard-Jones fluid,
suggesting the usefulness of a landscape-based formulation of supercooled
liquid thermodynamics. Finally, we consider the implications of both the
general theory and the model with respect to the so-called Sastry density and
the ideal glass transition. Our analysis shows that a quantitative connection
can be made between properties of the landscape and a simulation-determined
Sastry density, and it emphasizes the distinction between an ideal glass
transition and a Kauzmann equal-entropy condition.Comment: 11 pages, 3 figure
Variant O89 O-Antigen of E. coli Is Associated With Group 1 Capsule Loci and Multidrug Resistance
<p>Bacterial surface polysaccharides play significant roles in fitness and virulence. In Gram-negative bacteria such as Escherichia coli, major surface polysaccharides are lipopolysaccharide (LPS) and capsule, representing O- and K-antigens, respectively. There are multiple combinations of O:K types, many of which are well-characterized and can be related to ecotype or pathotype. In this investigation, we have identified a novel O:K permutation resulting through a process of major genome reorganization in a clade of E. coli. A multidrug-resistant, extended-spectrum β-lactamase (ESBL)-producing strain – E. coli 26561 – represented a prototype of strains combining a locus variant of O89 and group 1 capsular polysaccharide. Specifically, the variant O89 locus in this strain was truncated at gnd, flanked by insertion sequences and located between nfsB and ybdK and we apply the term O89m for this variant. The prototype lacked colanic acid and O-antigen loci between yegH and hisI with this tandem polysaccharide locus being replaced with a group 1 capsule (G1C) which, rather than being a recognized E. coli capsule type, this locus matched to Klebsiella K10 capsule type. A genomic survey identified more than 200 E. coli strains which possessed the O89m locus variant with one of a variety of G1C types. Isolates from our collection with the combination of O89m and G1C all displayed a mucoid phenotype and E. coli 26561 was unusual in exhibiting a mucoviscous phenotype more recognized as a characteristic among Klebsiella strains. Despite the locus truncation and novel location, all O89m:G1C strains examined showed a ladder pattern typifying smooth LPS and also showed high molecular weight, alcian blue-staining polysaccharide in cellular and/or extra-cellular fractions. Expression of both O-antigen and capsule biosynthesis loci were confirmed in prototype strain 26561 through quantitative proteome analysis. Further in silico exploration of more than 200 E. coli strains possessing the O89m:G1C combination identified a very high prevalence of multidrug resistance (MDR) – 85% possessed resistance to three or more antibiotic classes and a high proportion (58%) of these carried ESBL and/or carbapenemase. The increasing isolation of O89m:G1C isolates from extra-intestinal infection sites suggests that these represents an emergent clade of invasive, MDR E. coli.</p
А. С. Макаренко о «педагогической системе хозяйства», или еще раз о «параллельности» производительного труда и воспитания
Biofilms represent the predominant mode of microbial growth in the natural environment. Bacillus subtilis is a ubiquitous Gram-positive soil bacterium that functions as an effective plant growth-promoting agent. The biofilm matrix is composed of an exopolysaccharide and an amyloid fiber-forming protein, TasA, and assembles with the aid of a small secreted protein, BslA. Here we show that natively synthesized and secreted BslA forms surface layers around the biofilm. Biophysical analysis demonstrates that BslA can self-assemble at interfaces, forming an elastic film. Molecular function is revealed from analysis of the crystal structure of BslA, which consists of an Ig-type fold with the addition of an unusual, extremely hydrophobic “cap” region. A combination of in vivo biofilm formation and in vitro biophysical analysis demonstrates that the central hydrophobic residues of the cap are essential to allow a hydrophobic, nonwetting biofilm to form as they control the surface activity of the BslA protein. The hydrophobic cap exhibits physiochemical properties remarkably similar to the hydrophobic surface found in fungal hydrophobins; thus, BslA is a structurally defined bacterial hydrophobin. We suggest that biofilms formed by other species of bacteria may have evolved similar mechanisms to provide protection to the resident bacterial community
Molecular patterns in acute pancreatitis reflect generalisable endotypes of the host response to systemic injury in humans
Images of the Early Universe from the BOOMERanG experiment
The CMB is the fundamental tool to study the properties of the early universe and of the
universe at large scales. In the framework of the Hot Big Bang model, when we look to
the CMB we look back in time to the end of the plasma era, at a redshift ~ 1000, when
the universe was ~ 50000 times younger, ~ 1000 times hotter and ~ 10^9 times denser
than today. The image of the CMB can be used to study the physical processes there, to
infer what happened before, and also to study the background geometry of our Universe
The DLV System for Knowledge Representation and Reasoning
This paper presents the DLV system, which is widely considered the
state-of-the-art implementation of disjunctive logic programming, and addresses
several aspects. As for problem solving, we provide a formal definition of its
kernel language, function-free disjunctive logic programs (also known as
disjunctive datalog), extended by weak constraints, which are a powerful tool
to express optimization problems. We then illustrate the usage of DLV as a tool
for knowledge representation and reasoning, describing a new declarative
programming methodology which allows one to encode complex problems (up to
-complete problems) in a declarative fashion. On the foundational
side, we provide a detailed analysis of the computational complexity of the
language of DLV, and by deriving new complexity results we chart a complete
picture of the complexity of this language and important fragments thereof.
Furthermore, we illustrate the general architecture of the DLV system which
has been influenced by these results. As for applications, we overview
application front-ends which have been developed on top of DLV to solve
specific knowledge representation tasks, and we briefly describe the main
international projects investigating the potential of the system for industrial
exploitation. Finally, we report about thorough experimentation and
benchmarking, which has been carried out to assess the efficiency of the
system. The experimental results confirm the solidity of DLV and highlight its
potential for emerging application areas like knowledge management and
information integration.Comment: 56 pages, 9 figures, 6 table
Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells
Glyphosate (N-phosphonomethyl glycine) and its commercial herbicide formulations have been shown to exert toxicity via various mechanisms. It has been asserted that glyphosate substitutes for glycine in polypeptide chains leading to protein misfolding and toxicity. However, as no direct evidence exists for glycine to glyphosate substitution in proteins, including in mammalian organisms, we tested this claim by conducting a proteomics analysis of MDA-MB-231 human breast cancer cells grown in the presence of 100 mg/L glyphosate for 6 days. Protein extracts from three treated and three untreated cell cultures were analysed as one TMT-6plex labelled sample, to highlight a specific pattern (+/+/+/−/−/−) of reporter intensities for peptides bearing true glyphosate treatment induced-post translational modifications as well as allowing an investigation of the total proteome
Pneumococcal conjugate vaccine use during humanitarian crises.
Streptococcus pneumoniae is a common human commensal that causes a sizeable part of the overall childhood mortality in low income settings. Populations affected by humanitarian crises are at especially high risk, because a multitude of risk factors that are enhanced during crises increase pneumococcal transmission and disease severity. Pneumococcal conjugate vaccines (PCVs) provide effective protection and have been introduced into the majority of routine childhood immunisation programmes globally, though several barriers have hitherto limited their uptake during humanitarian crises. When PCV coverage cannot be sustained during crises or when PCV has not been part of routine programmes, mass vaccination campaigns offer a quick acting and programmatically feasible bridging solution until services can be restored. However, we currently face a paucity of evidence on which to base the structure of such campaigns. We believe that, now that PCV can be procured at a substantially reduced price through the Humanitarian Mechanism, this lack of information is a remaining hurdle to PCV use in humanitarian crises. Considering the difficulties in conducting research in crises, we propose an evidence generation pathway consisting of primary data collection in combination with mathematical modelling followed by quasi-experimental evaluation of a PCV intervention, which can inform on optimal vaccination strategies that consider age targeting, dosing regimens and impact duration
Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort
BACKGROUND:
Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice.
METHODS:
A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively.
RESULTS:
SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655.
CONCLUSIONS:
In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin
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