4,771 research outputs found
To Thine Ownself Be True: IMF Conditionality and Erosion of Economic Sovereignty in the Asian Financial Crisis
High-Energy String Scattering Amplitudes and Signless Stirling Number Identity
We give a complete proof of a set of identities (7) proposed recently from
calculation of high-energy string scattering amplitudes. These identities allow
one to extract ratios among high-energy string scattering amplitudes in the
fixed angle regime from high-energy amplitudes in the Regge regime. The proof
is based on a signless Stirling number identity in combinatorial theory. The
results are valid for arbitrary real values rather than only for
proved previously. The identities for non-integer real value were recently
shown to be realized in high-energy compactified string scattering amplitudes
[He S., Lee J.C., Yang Y., arXiv:1012.3158]. The parameter is related to
the mass level of an excited string state and can take non-integer values for
Kaluza-Klein modes
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Antibiotic Treatment Expands the Resistance Reservoir and Ecological Network of the Phage Metagenome
The mammalian gut ecosystem has significant influence on host physiology1–4, but the mechanisms that sustain this complex environment in the face of different stresses remain obscure. Perturbations to this ecosystem, such as through antibiotic treatment or diet, are currently interpreted at the level of bacterial phylogeny5–7. Less is known about the contributions of the abundant population of phage to this ecological network. Here, we explore the phageome as a potential genetic reservoir for bacterial adaptation by sequencing murine fecal phage populations following antibiotic perturbation. We show that antibiotic treatment leads to the enrichment of phage-encoded genes that confer resistance via disparate mechanisms to the administered drug as well as genes that confer resistance to antibiotics unrelated to the administered drug, and we demonstrate experimentally that phage from treated mice afford aerobically cultured naïve microbiota increased resistance. Systems-wide analyses uncover post-treatment phage-encoded processes related to host colonization and growth adaptation, indicating that the phageome broadly enriches for functionally beneficial genes under stress-related conditions. We also show that antibiotic treatment expands the interactions between phage and bacterial species, leading to a more highly connected phage-bacterial network for gene exchange. Our work implicates the phageome in the emergence of multidrug resistance and indicates that the adaptive capacity of the phageome may represent a community-based mechanism for protecting the gut microflora, preserving its functional robustness during antibiotic stress
Neighborhood conditions matter for the employment of young people who have been involved in the justice system
Young people who have been involved with the criminal justice system are much more likely to be unemployed than those who have not. In new research, Lewis H. Lee, Minseop Kim, Catherine Carlson, Taylor Ellis, Karen Johnson, and Angela Pretz examined the role of neighborhoods in the employment of justice-involved young adults. They find that young adults who perceive worsening neighborhood conditions tend to work less for formal jobs, whereas a justice-involved young adult who has the same perception is more likely to work more for informal or under-the-table jobs
Apolipoprotein E mediates evasion from hepatitis C virus−neutralizing antibodies
Background & Aims
Efforts to develop an effective vaccine against hepatitis C virus (HCV) have been hindered by the propensity of the virus to evade host immune responses. HCV particles in serum and in cell culture associate with lipoproteins, which contribute to viral entry. Lipoprotein association has also been proposed to mediate viral evasion of the humoral immune response, though the mechanisms are poorly defined.
Methods
We used small interfering RNAs to reduce levels of apolipoprotein E (apoE) in cell culture−derived HCV−producing Huh7.5-derived hepatoma cells and confirmed its depletion by immunoblot analyses of purified viral particles. Before infection of naïve hepatoma cells, we exposed cell culture−derived HCV strains of different genotypes, subtypes, and variants to serum and polyclonal and monoclonal antibodies isolated from patients with chronic HCV infection. We analyzed the interaction of apoE with viral envelope glycoprotein E2 and HCV virions by immunoprecipitation.
Results
Through loss-of-function studies on patient-derived HCV variants of several genotypes and subtypes, we found that the HCV particle apoE allows the virus to avoid neutralization by patient-derived antibodies. Functional studies with human monoclonal antiviral antibodies showed that conformational epitopes of envelope glycoprotein E2 domains B and C were exposed after depletion of apoE. The level and conformation of virion-associated apoE affected the ability of the virus to escape neutralization by antibodies.
Conclusions
In cell-infection studies, we found that HCV-associated apoE helps the virus avoid neutralization by antibodies against HCV isolated from chronically infected patients. This method of immune evasion poses a challenge for the development of HCV vaccines
The effects of attractive vs. repulsive instructional cuing on balance performance
Abstract
Background
Torso-based vibrotactile feedback has been shown to improve postural performance during quiet and perturbed stance in healthy young and older adults and individuals with balance impairments. These systems typically include tactors distributed around the torso that are activated when body motion exceeds a predefined threshold. Users are instructed to “move away from the vibration”. However, recent studies have shown that in the absence of instructions, vibrotactile stimulation induces small (~1°) non-volitional responses in the direction of its application location. It was hypothesized that an attractive cuing strategy (i.e., “move toward the vibration”) could improve postural performance by leveraging this natural tendency.
Findings
Eight healthy older adults participated in two non-consecutive days of computerized dynamic posturography testing while wearing a vibrotactile feedback system comprised of an inertial measurement unit and four tactors that were activated in pairs when body motion exceeded 1° anteriorly or posteriorly. A crossover design was used. On each day participants performed 24 repetitions of Sensory Organization Test condition 5 (SOT5), three repetitions each of SOT 1–6, three repetitions of the Motor Control Test, and five repetitions of the Adaptation Test. Performance metrics included A/P RMS, Time-in-zone and 95 % CI Ellipse. Performance improved with both cuing strategies but participants performed better when using repulsive cues. However, the rate of improvement was greater for attractive versus repulsive cuing.
Conclusions
The results suggest that when the cutaneous signal is interpreted as an alarm, cognition overrides sensory information. Furthermore, although repulsive cues resulted in better performance, attractive cues may be as good, if not better, than repulsive cues following extended training.http://deepblue.lib.umich.edu/bitstream/2027.42/134532/1/12984_2016_Article_131.pd
In Silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem Cell Transplant Donors and Recipients: Understanding the Quantitative Immuno-biology of Allogeneic Transplantation
Donor T cell mediated graft vs. host effects may result from the aggregate
alloreactivity to minor histocompatibility antigens (mHA) presented by the HLA
in each donor-recipient pair (DRP) undergoing stem cell transplantation (SCT).
Whole exome sequencing has demonstrated extensive nucleotide sequence variation
in HLA-matched DRP. Non-synonymous single nucleotide polymorphisms (nsSNPs) in
the GVH direction (polymorphisms present in recipient and absent in donor) were
identified in 4 HLA-matched related and 5 unrelated DRP. The nucleotide
sequence flanking each SNP was obtained utilizing the ANNOVAR software package.
All possible nonameric-peptides encoded by the non-synonymous SNP were then
interrogated in-silico for their likelihood to be presented by the HLA class I
molecules in individual DRP, using the Immune-Epitope Database (IEDB) SMM
algorithm. The IEDB-SMM algorithm predicted a median 18,396 peptides/DRP which
bound HLA with an IC50 of <500nM, and 2254 peptides/DRP with an IC50 of <50nM.
Unrelated donors generally had higher numbers of peptides presented by the HLA.
A similarly large library of presented peptides was identified when the data
was interrogated using the Net MHCPan algorithm. These peptides were uniformly
distributed in the various organ systems. The bioinformatic algorithm presented
here demonstrates that there may be a high level of minor histocompatibility
antigen variation in HLA-matched individuals, constituting an HLA-specific
alloreactivity potential. These data provide a possible explanation for how
relatively minor adjustments in GVHD prophylaxis yield relatively similar
outcomes in HLA matched and mismatched SCT recipients.Comment: Abstract: 235, Words: 6422, Figures: 7, Tables: 3, Supplementary
figures: 2, Supplementary tables:
ETDB-Caltech: a blockchain-based distributed public database for electron tomography
Three-dimensional electron microscopy techniques like electron tomography provide valuable insights into cellular structures, and present significant challenges for data storage and dissemination. Here we explored a novel method to publicly release more than 11,000 such datasets, more than 30 TB in total, collected by our group. Our method, based on a peer-to-peer file sharing network built around a blockchain ledger, offers a distributed solution to data storage. In addition, we offer a user-friendly browser-based interface, https://etdb.caltech.edu, for anyone interested to explore and download our data. We discuss the relative advantages and disadvantages of this system and provide tools for other groups to mine our data and/or use the same approach to share their own imaging datasets
Invasive Haemophilus influenzae Disease in Adults ≥65 Years, United States, 2011.
BackgroundSince the introduction of the Haemophilus influenzae serotype b vaccine, H influenzae epidemiology has shifted. In the United States, the largest burden of disease is now in adults aged ≥65 years. However, few data exist on risk factors for disease severity and outcome in this age group.MethodsA retrospective case-series review of invasive H influenzae infections in patients aged ≥65 years was conducted for hospitalized cases reported to Active Bacterial Core surveillance in 2011.ResultsThere were 299 hospitalized cases included in the analysis. The majority of cases were caused by nontypeable H influenzae, and the overall case fatality ratio (CFR) was 19.5%. Three or more underlying conditions were present in 63% of cases; 94% of cases had at least 1. Patients with chronic heart conditions (congestive heart failure, coronary artery disease, and/or atrial fibrillation) (odds ratio [OR], 3.27; 95% confidence interval [CI], 1.65-6.46), patients from private residences (OR, 8.75; 95% CI, 2.13-35.95), and patients who were not resuscitate status (OR, 2.72; 95% CI, 1.31-5.66) were more likely to be admitted to the intensive care unit (ICU). Intensive care unit admission (OR, 3.75; 95% CI, 1.71-8.22) and do not resuscitate status (OR, 12.94; 95% CI, 4.84-34.55) were significantly associated with death.ConclusionsWithin this age group, burden of disease and CFR both increased significantly as age increased. Using ICU admission as a proxy for disease severity, our findings suggest several conditions increased risk of disease severity and patients with severe disease were more likely to die. Further research is needed to determine the most effective approach to prevent H influenzae disease and mortality in older adults
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