68 research outputs found
Out-of-equilibrium states as statistical equilibria of an effective dynamics
We study the formation of coherent structures in a system with long-range
interactions where particles moving on a circle interact through a repulsive
cosine potential. Non equilibrium structures are shown to correspond to
statistical equilibria of an effective dynamics, which is derived using
averaging techniques. This simple behavior might be a prototype of others
observed in more complicated systems with long-range interactions, like
two-dimensional incompressible fluids or self-gravitating systems.Comment: 4 figure
Space-time Phase Transitions in Driven Kinetically Constrained Lattice Models
Kinetically constrained models (KCMs) have been used to study and understand
the origin of glassy dynamics. Despite having trivial thermodynamic properties,
their dynamics slows down dramatically at low temperatures while displaying
dynamical heterogeneity as seen in glass forming supercooled liquids. This
dynamics has its origin in an ergodic-nonergodic first-order phase transition
between phases of distinct dynamical "activity". This is a "space-time"
transition as it corresponds to a singular change in ensembles of trajectories
of the dynamics rather than ensembles of configurations. Here we extend these
ideas to driven glassy systems by considering KCMs driven into non-equilibrium
steady states through non-conservative forces. By classifying trajectories
through their entropy production we prove that driven KCMs also display an
analogous first-order space-time transition between dynamical phases of finite
and vanishing entropy production. We also discuss how trajectories with rare
values of entropy production can be realized as typical trajectories of a
mapped system with modified forces
Non-Equilibrium Statistical Physics of Currents in Queuing Networks
We consider a stable open queuing network as a steady non-equilibrium system
of interacting particles. The network is completely specified by its underlying
graphical structure, type of interaction at each node, and the Markovian
transition rates between nodes. For such systems, we ask the question ``What is
the most likely way for large currents to accumulate over time in a network
?'', where time is large compared to the system correlation time scale. We
identify two interesting regimes. In the first regime, in which the
accumulation of currents over time exceeds the expected value by a small to
moderate amount (moderate large deviation), we find that the large-deviation
distribution of currents is universal (independent of the interaction details),
and there is no long-time and averaged over time accumulation of particles
(condensation) at any nodes. In the second regime, in which the accumulation of
currents over time exceeds the expected value by a large amount (severe large
deviation), we find that the large-deviation current distribution is sensitive
to interaction details, and there is a long-time accumulation of particles
(condensation) at some nodes. The transition between the two regimes can be
described as a dynamical second order phase transition. We illustrate these
ideas using the simple, yet non-trivial, example of a single node with
feedback.Comment: 26 pages, 5 figure
The STF2p Hydrophilin from Saccharomyces cerevisiae Is Required for Dehydration Stress Tolerance
The yeast Saccharomyces cerevisiae is able to overcome cell dehydration; cell metabolic activity is arrested during this period but restarts after rehydration. The yeast genes encoding hydrophilin proteins were characterised to determine their roles in the dehydration-resistant phenotype, and STF2p was found to be a hydrophilin that is essential for survival after the desiccation-rehydration process. Deletion of STF2 promotes the production of reactive oxygen species and apoptotic cell death during stress conditions, whereas the overexpression of STF2, whose gene product localises to the cytoplasm, results in a reduction in ROS production upon oxidative stress as the result of the antioxidant capacity of the STF2p protein
Assessment and Management of Anti-insulin Autoantibodies in Varying Presentations of Insulin Autoimmune Syndrome
Context: Insulin autoimmune syndrome (IAS), spontaneous hyperinsulinemic hypoglycemia due to insulin-binding autoantibodies, may be difficult to distinguish from tumoral or other forms of hyperinsulinemic hypoglycemia including surreptitious insulin administration. No standardized treatment regimen exists. Objectives: To evaluate an analytic approach to IAS and responses to different treatments. Design and Setting: Observational study in the UK Severe Insulin Resistance Service. Patients: 6 patients with hyperinsulinemic hypoglycemia and detectable circulating anti-insulin antibody (IA). Main outcome measures: Glycemia, plasma insulin and C-peptide concentrations by immunoassay or mass spectrometry (MS). Immunoreactive insulin was determined in the context of polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC). IA quantification using enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA), and IA were further characterized using radioligand binding studies. Results: All patients were diagnosed with IAS (5 IgG, 1 IgA) based on high insulin:C-peptide ratio, low insulin recovery after PEG precipitation, and GFC evidence of antibody-bound insulin. Neither ELISA nor RIA result proved diagnostic for every case. MS provided a more robust quantification of insulin in the context of IA. 1 patient was managed conservatively, 4 were treated with diazoxide without sustained benefit, and 4 were treated with immunosuppression with highly variable responses. IA affinity did not appear to influence presentation or prognosis. Conclusions: IAS should be considered in patients with hyperinsulinemic hypoglycemia and a high insulin:C-peptide ratio. Low insulin recovery on PEG precipitation supports the presence of insulin-binding antibodies, with GFC providing definitive confirmation. Immunomodulatory therapy should be customized according to individual needs and clinical response
A family of dual-activity glycosyltransferasesphosphorylases mediates mannogen turnover and virulence in Leishmania parasites
Parasitic protists belonging to the genus Leishmania synthesize the non-canonical carbohydrate reserve, mannogen, which is composed of β-1,2-mannan oligosaccharides. Here, we identify a class of dual-activity mannosyltransferase/phosphorylases (MTPs) that catalyze both the sugar nucleotide-dependent biosynthesis and phosphorolytic turnover of mannogen. Structural and phylogenic analysis shows that while the MTPs are structurally related to bacterial mannan phosphorylases, they constitute a distinct family of glycosyltransferases (GT108) that have likely been acquired by horizontal gene transfer from gram-positive bacteria. The seven MTPs catalyze the constitutive synthesis and turnover of mannogen. This metabolic rheostat protects obligate intracellular parasite stages from nutrient excess, and is essential for thermotolerance and parasite infectivity in the mammalian host. Our results suggest that the acquisition and expansion of the MTP family in Leishmania increased the metabolic flexibility of these protists and contributed to their capacity to colonize new host niches
Structures of the Signal Recognition Particle Receptor from the Archaeon Pyrococcus furiosus: Implications for the Targeting Step at the Membrane
In all organisms, a ribonucleoprotein called the signal recognition particle (SRP) and its receptor (SR) target nascent proteins from the ribosome to the translocon for secretion or membrane insertion. We present the first X-ray structures of an archeal FtsY, the receptor from the hyper-thermophile Pyrococcus furiosus (Pfu), in its free and GDP•magnesium-bound forms. The highly charged N-terminal domain of Pfu-FtsY is distinguished by a long N-terminal helix. The basic charges on the surface of this helix are likely to regulate interactions at the membrane. A peripheral GDP bound near a regulatory motif could indicate a site of interaction between the receptor and ribosomal or SRP RNAs. Small angle X-ray scattering and analytical ultracentrifugation indicate that the crystal structure of Pfu-FtsY correlates well with the average conformation in solution. Based on previous structures of two sub-complexes, we propose a model of the core of archeal and eukaryotic SRP•SR targeting complexes
What Do We Know About Neuropsychological Aspects Of Schizophrenia?
Application of a neuropsychological perspective to the study of schizophrenia has established a number of important facts about this disorder. Some of the key findings from the existing literature are that, while neurocognitive impairment is present in most, if not all, persons with schizophrenia, there is both substantial interpatient heterogeneity and remarkable within-patient stability of cognitive function over the long-term course of the illness. Such findings have contributed to the firm establishment of neurobiologic models of schizophrenia, and thereby help to reduce the social stigma that was sometimes associated with purely psychogenic models popular during parts of the 20th century. Neuropsychological studies in recent decades have established the primacy of cognitive functions over psychopathologic symptoms as determinants of functional capacity and independence in everyday functioning. Although the cognitive benefits of both conventional and even second generation antipsychotic medications appear marginal at best, recognition of the primacy of cognitive deficits as determinants of functional disability in schizophrenia has catalyzed recent efforts to develop targeted treatments for the cognitive deficits of this disorder. Despite these accomplishments, however, some issues remain to be resolved. Efforts to firmly establish the specific neurocognitive/neuropathologic systems responsible for schizophrenia remain elusive, as do efforts to definitively demonstrate the specific cognitive deficits underlying specific forms of functional impairment. Further progress may be fostered by recent initiatives to integrate neuropsychological studies with experimental neuroscience, perhaps leading to measures of deficits in cognitive processes more clearly associated with specific, identifiable brain systems
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