106 research outputs found
Geometrical and spectral study of beta-skeleton graphs
We perform an extensive numerical analysis of beta-skeleton graphs, a particular type of proximity graphs. In beta-skeleton graph (BSG) two vertices are connected if a proximity rule, that depends of the parameter beta is an element of (0, infinity), is satisfied. Moreover, for beta > 1 there exist two different proximity rules, leading to lune-based and circle-based BSGs. First, by computing the average degree of large ensembles of BSGs we detect differences, which increase with the increase of beta, between lune-based and circle-based BSGs. Then, within a random matrix theory (RMT) approach, we explore spectral and eigenvector properties of random BSGs by the use of the nearest-neighbor energy-level spacing distribution and the entropic eigenvector localization length, respectively. The RMT analysis allows us to conclude that a localization transition occurs at beta = 1
Scaling properties of the action in the Riemann-Liouville fractional standard map
The Riemann-Liouville fractional standard map (RL-fSM) is a two-dimensional
nonlinear map with memory given in action-angle variables . The
RL-fSM is parameterized by and which control the strength
of nonlinearity and the fractional order of the Riemann-Liouville derivative,
respectively. In this work, we present a scaling study of the average squared
action \left of the RL-fSM along strongly chaotic orbits, i.e.
for . We observe two scenarios depending on the initial action ,
or . However, we can show that \left/I_0^2
is a universal function of the scaled discrete time ( being the
th iteration of the RL-fSM). In addition, we note that \left
is independent of for . Analytical estimations support our
numerical results.Comment: 5 pages, 3 figure
Statistics of Resonances and Delay Times in Random Media: Beyond Random Matrix Theory
We review recent developments on quantum scattering from mesoscopic systems.
Various spatial geometries whose closed analogs shows diffusive, localized or
critical behavior are considered. These are features that cannot be described
by the universal Random Matrix Theory results. Instead one has to go beyond
this approximation and incorporate them in a non-perturbative way. Here, we pay
particular emphasis to the traces of these non-universal characteristics, in
the distribution of the Wigner delay times and resonance widths. The former
quantity captures time dependent aspects of quantum scattering while the latter
is associated with the poles of the scattering matrix.Comment: 30 pages, 15 figures (submitted to Journal of Phys. A: Math. and
General, special issue on "Aspects of Quantum Chaotic Scattering"
The Boston Puerto Rican Health Study, a longitudinal cohort study on health disparities in Puerto Rican adults: challenges and opportunities
BACKGROUND: The Boston Puerto Rican Health Study is an ongoing longitudinal cohort study designed to examine the role of psychosocial stress on presence and development of allostatic load and health outcomes in Puerto Ricans, and potential modification by nutritional status, genetic variation, and social support.
METHODS: Self-identified Puerto Ricans, aged 45-75 years and residing in the Boston, MA metro area, were recruited through door-to-door enumeration and community approaches. Participants completed a comprehensive set of questionnaires and tests. Blood, urine and salivary samples were extracted for biomarker and genetic analysis. Measurements are repeated at a two-year follow-up.
RESULTS: A total of 1500 eligible participants completed baseline measurements, with nearly 80% two-year follow-up retention. The majority of the cohort is female (70%), and many have less than 8th grade education (48%), and fall below the poverty level (59%). Baseline prevalence of health conditions is high for this age range: considerable physical (26%) and cognitive (7%) impairment, obesity (57%), type 2 diabetes (40%), hypertension (69%), arthritis (50%) and depressive symptomatology (60%).
CONCLUSIONS: The enrollment of minority groups presents unique challenges. This report highlights approaches to working with difficult to reach populations, and describes some of the health issues and needs of Puerto Rican older adults. These results may inform future studies and interventions aiming to improve the health of this and similar communities
Human telomeres that carry an integrated copy of human herpesvirus 6 are often short and unstable, facilitating release of the viral genome from the chromosome
Linear chromosomes are stabilized by telomeres, but the presence of short dysfunctional telomeres triggers cellular senescence in human somatic tissues, thus contributing to ageing. Approximately 1% of the population inherits a chromosomally integrated copy of human herpesvirus 6 (CI-HHV-6), but the consequences of integration for the virus and for the telomere with the insertion are unknown. Here we show that the telomere on the distal end of the integrated virus is frequently the shortest measured in somatic cells but not the germline. The telomere carrying the CI-HHV-6 is also prone to truncations that result in the formation of a short telomere at a novel location within the viral genome. We detected extra-chromosomal circular HHV-6 molecules, some surprisingly comprising the entire viral genome with a single fully reconstituted direct repeat region (DR) with both terminal cleavage and packaging elements (PAC1 and PAC2). Truncated CI-HHV-6 and extra-chromosomal circular molecules are likely reciprocal products that arise through excision of a telomere-loop (t-loop) formed within the CI-HHV-6 genome. In summary, we show that the CI-HHV-6 genome disrupts stability of the associated telomere and this facilitates the release of viral sequences as circular molecules, some of which have the potential to become fully functioning viruses
Inherited chromosomally integrated human herpesvirus 6 genomes are ancient, intact and potentially able to reactivate from telomeres
The genomes of human herpesviruses 6A and 6B (HHV-6A and HHV-6B) have the capacity to integrate into telomeres, the essential capping structures of chromosomes that play roles in cancer and ageing. About 1% of people worldwide are carriers of chromosomally integrated HHV-6 (ciHHV-6), which is inherited as a genetic trait. Understanding the consequences of integration for the evolution of the viral genome, for the telomere and for the risk of disease associated with carrier status is hampered by a lack of knowledge about ciHHV-6 genomes. Here, we report an analysis of 28 ciHHV-6 genomes and show that they are significantly divergent from the few modern non-integrated HHV-6 strains for which complete sequences are currently available. In addition ciHHV-6B genomes in Europeans are more closely related to each other than to ciHHV-6B genomes from China and Pakistan, suggesting regional variation of the trait. Remarkably, at least one group of European ciHHV-6B carriers has inherited the same ciHHV-6B genome, integrated in the same telomere allele, from a common ancestor estimated to have existed 24,500 ±10,600 years ago. Despite the antiquity of some, and possibly most, germline HHV-6 integrations, the majority of ciHHV-6B (95%) and ciHHV-6A (72%) genomes contain a full set of intact viral genes and therefore appear to have the capacity for viral gene expression and full reactivation. IMPORTANCE: Inheritance of HHV-6A or HHV-6B integrated into a telomere occurs at a low frequency in most populations studied to date but its characteristics are poorly understood. However, stratification of ciHHV-6 carriers in modern populations due to common ancestry is an important consideration for genome-wide association studies that aim to identify disease risks for these people. Here we present full sequence analysis of 28 ciHHV-6 genomes and show that ciHHV-6B in many carriers with European ancestry most likely originated from ancient integration events in a small number of ancestors. We propose that ancient ancestral origins for ciHHV-6A and ciHHV-6B are also likely in other populations. Moreover, despite their antiquity, all of the ciHHV-6 genomes appear to retain the capacity to express viral genes, and most are predicted to be capable of full viral reactivation. These discoveries represent potentially important considerations in immune-compromised patients, in particular in organ transplantation and in stem cell therapy
Multimeric single-domain antibody complexes protect against bunyavirus infections
The World Health Organization has included three bunyaviruses posing an increasing
threat to human health on the Blueprint list of viruses likely to cause major epidemics and for which
no, or insufficient countermeasures exist. Here, we describe a broadly applicable strategy, based
on llama-derived single-domain antibodies (VHHs), for the development of bunyavirus
biotherapeutics. The method was validated using the zoonotic Rift Valley fever virus (RVFV) and
Schmallenberg virus (SBV), an emerging pathogen of ruminants, as model pathogens. VHH building
blocks were assembled into highly potent neutralizing complexes using bacterial superglue
technology. The multimeric complexes were shown to reduce and prevent virus-induced morbidity
and mortality in mice upon prophylactic administration. Bispecific molecules engineered to present
two different VHHs fused to an Fc domain were further shown to be effective upon therapeutic
administration. The presented VHH-based technology holds great promise for the development of
bunyavirus antiviral therapies
Adjuvant interferon gamma in patients with drug – resistant pulmonary tuberculosis: a pilot study
BACKGROUND: Tuberculosis (TB) is increasing in the world and drug-resistant (DR) disease beckons new treatments. METHODS: To evaluate the action of interferon (IFN) gamma as immunoadjuvant to chemotherapy on pulmonary DR-TB patients, a pilot, open label clinical trial was carried out in the Cuban reference ward for the management of this disease. The eight subjects existing in the country at the moment received, as in-patients, 1 × 10(6 )IU of recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to the indicated chemotherapy, according to their antibiograms and WHO guidelines. Sputum samples collection for direct smear observation and culture as well as routine clinical and thorax radiography assessments were done monthly. RESULTS: Sputum smears and cultures became negative for acid-fast-bacilli before three months of treatment in all patients. Lesion size was reduced at the end of 6 months treatment; the lesions disappeared in one case. Clinical improvement was also evident; body mass index increased in general. Interferon gamma was well tolerated. Few adverse events were registered, mostly mild; fever and arthralgias prevailed. CONCLUSIONS: These data suggest that IFN gamma is useful and well tolerated as adjunctive therapy in patients with DR-TB. Further controlled clinical trials are encouraged
The Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins
Snakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually. High-quality, genome-enabled comprehensive characterization of toxin genes will facilitate development of effective humanized recombinant antivenom. We report a de novo near-chromosomal genome assembly of Naja naja, the Indian cobra, a highly venomous, medically important snake. Our assembly has a scaffold N50 of 223.35 Mb, with 19 scaffolds containing 95% of the genome. Of the 23,248 predicted protein-coding genes, 12,346 venom-gland-expressed genes constitute the \u27venom-ome\u27 and this included 139 genes from 33 toxin families. Among the 139 toxin genes were 19 \u27venom-ome-specific toxins\u27 (VSTs) that showed venom-gland-specific expression, and these probably encode the minimal core venom effector proteins. Synthetic venom reconstituted through recombinant VST expression will aid in the rapid development of safe and effective synthetic antivenom. Additionally, our genome could serve as a reference for snake genomes, support evolutionary studies and enable venom-driven drug discovery
- …