457 research outputs found
In Vivo insulin-dependent glucose uptake of specific tissues is decreased during aging of mature wistar rats
Copyright (1997) The Endocrine Society .The paper can be found at the following URL on the website http://endo.endojournals.org
Leveraging phylogenetics to understand HIV transmission and partner notification networks
Background: Partner notification is an important component of public health test and treat interventions. To enhance this essential function, we assessed the potential for molecular methods to supplement routine partner notification and corroborate HIV networks. Methods: All persons diagnosed with HIV infection in Wake County, NC, during 2012-2013 and their disclosed sexual partners were included in a sexual network. A data set containing HIV-1 pol sequences collected in NC during 1997-2014 from 15,246 persons was matched to HIV-positive persons in the network and used to identify putative transmission clusters. Both networks were compared. Results: The partner notification network comprised 280 index cases and 383 sexual partners and high-risk social contacts (n = 131 HIVpositive). Of the 411 HIV-positive persons in the partner notification network, 181 (44%) did not match to a HIV sequence, 61 (15%) had sequences but were not identified in a transmission cluster, and 169 (41%) were identified in a transmission cluster. More than half (59%) of transmission clusters bridged sexual network partnerships that were not recognized in the partner notification; most of these clusters were dominated by men who have sex with men. Conclusions: Partner notification and HIV sequence analysis provide complementary representations of the existent partnerships underlying the HIV transmission network. The partner notification network components were bridged by transmission clusters, particularly among components dominated by men who have sex with men. Supplementing the partner notification network with phylogenetic data highlighted avenues for intervention
Driver mutations (JAK2V617F, MPLW515L/K or CALR), pentraxin-3 and C-reactive protein in essential thrombocythemia and polycythemia vera
Background: The driver mutations JAK2V617F, MPLW515L/K and CALR influence disease phenotype of myeloproliferative neoplasms (MPNs) and might sustain a condition of chronic inflammation. Pentraxin 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) are inflammatory biomarkers potentially useful for refining prognostic classification of MPNs.
Methods: We evaluated 305 with essential thrombocythemia (ET) and 172 polycythemia vera (PV) patients diagnosed according to the 2016 WHO criteria and with full molecular characterization for driver mutations.
Results: PTX3 levels were significantly increased in carriers of homozygous JAK2V617F mutation compared to all the other genotypes and triple negative ET patients, while hs-CRP levels were independent of the mutational profile. The risk of haematological evolution and death from any cause was about 2- and 1.5-fold increased in individuals with high PTX-3 levels, while the thrombosis rate tended to be lower. High hs-CRP levels were associated with risk of haematological evolution, death and also major thrombosis. After sequential adjustment for potential confounders (age, gender, diagnosis and treatments) and the presence of JAK2V617F homozygous status, high hs-CRP levels remained significant for all outcomes, while JAK2V617F homozygous status as well as treatments were the factors independently accounting for adverse outcomes among patients with high PTX3 levels.
Conclusions: These results provide evidence that JAK2V617F mutation influences MPN-associated inflammation with a strong correlation between allele burden and PTX3 levels. Plasma levels of hs-CRP and PTX3 might be of prognostic value for patients with ET and PV, but their validation in future prospective studies is needed
Probing the DeltaNN component of 3He
The 3He(gamma,pi^+/- p) reactions were measured simultaneously over a tagged
photon energy range of 800<E_gamma<1120 MeV, well above the Delta resonance
region. An analysis was performed to kinematically isolate Delta knockout
events from conventional Delta photoproduction events, and a statistically
significant excess of pi+p events was identified, consistent with Delta++
knockout. Two methods were used to estimate the DeltaNN probability in the 3He
ground state, corresponding to the observed knockout cross section. The first
gave a lower probability limit of 1.5+/-0.6+/-0.5%; the second yielded an upper
limit of about 2.6%.Comment: 14 page
Comparing the artificial neural network with parcial least squares for prediction of soil organic carbon and pH at different moisture content levels using visible and near-infrared spectroscopy
Examination and prognostic implications of the unique microenvironment of breast cancer brain metastases
Purpose: Brain metastases (BM) are a complication of advanced breast cancer (BC). Histology of melanoma BM offers prognostic value; however, understanding the microenvironment of breast cancer brain metastases (BCBM) is less characterized. This study reports on four histological biomarkers, gliosis, immune infiltrate, hemorrhage, necrosis, and their prognostic significance in BCBM. Methods: A biobank of 203 human tissues from patients who underwent craniotomy for BCBM was created across four academic institutions. Degree of gliosis, immune infiltrate, hemorrhage, and necrosis were identified and scored via representative H&E stain (0–3+). Overall survival (OS) was estimated using the Kaplan–Meier method. Cox proportional hazards regression evaluated prognostic value of the biomarkers in the context of standard clinical characteristics. Results: BCBM subtype (available for n = 158) was 36% Her2+, 26% hormone receptor (HR)+/Her2− 38% HR−/Her2− (triple negative, TN). Gliosis was observed in 82% (116/141) of BCBM, with immune infiltrate 44% (90/201), hemorrhage 82% (166/141), and necrosis 87% (176/201). Necrosis was significantly higher in TNBC (p < 0.01). Presence of gliosis, immune infiltrate, and hemorrhage correlated with improved OS (p = 0.03, p = 0.03, p = 0.1), while necrosis correlated with inferior OS (p = 0.01). Improved OS was associated with gliosis in TN (p = 0.02), and immune infiltrate (p = 0.001) and hemorrhage (p = 0.07) in HER2+. In a multivariable model for OS, incorporating these biomarkers with traditional clinical variables improved the model fit (p < 0.001). Conclusion: Gliosis confers superior prognosis in TNBC BM; immune infiltrate and hemorrhage correlate with superior prognosis in HER2+ BCBM. Understanding the metastatic microenvironment of BCBM refines prognostic considerations and may unveil novel therapeutic strategies
Clustering Algorithms: Their Application to Gene Expression Data
Gene expression data hide vital information required to understand the biological process that takes place in a particular organism in relation to its environment. Deciphering the hidden patterns in gene expression data proffers a prodigious preference to strengthen the understanding of functional genomics. The complexity of biological networks and the volume of genes present increase the challenges of comprehending and interpretation of the resulting mass of data, which consists of millions of measurements; these data also inhibit vagueness, imprecision, and noise. Therefore, the use of clustering techniques is a first step toward addressing these challenges, which is essential in the data mining process to reveal natural structures and iden-tify interesting patterns in the underlying data. The clustering of gene expression data has been proven to be useful in making known the natural structure inherent in gene expression data, understanding gene functions, cellular processes, and subtypes of cells, mining useful information from noisy data, and understanding gene regulation. The other benefit of clustering gene expression data is the identification of homology, which is very important in vaccine design. This review examines the various clustering algorithms applicable to the gene expression data in order to discover and provide useful knowledge of the appropriate clustering technique that will guarantee stability and high degree of accuracy in its analysis procedure
gSeaGen: The KM3NeT GENIE-based code for neutrino telescopes
Program summary
Program Title: gSeaGen
CPC Library link to program files: http://dx.doi.org/10.17632/ymgxvy2br4.1
Licensing provisions: GPLv3
Programming language: C++
External routines/libraries: GENIE [1] and its external dependencies. Linkable to MUSIC [2] and PROPOSAL
[3].
Nature of problem: Development of a code to generate detectable events in neutrino telescopes, using
modern and maintained neutrino interaction simulation libraries which include the state-of-the-art
physics models. The default application is the simulation of neutrino interactions within KM3NeT [4].
Solution method: Neutrino interactions are simulated using GENIE, a modern framework for Monte
Carlo event generators. The GENIE framework, used by nearly all modern neutrino experiments, is
considered as a reference code within the neutrino community.
Additional comments including restrictions and unusual features: The code was tested with GENIE version
2.12.10 and it is linkable with release series 3. Presently valid up to 5 TeV. This limitation is not intrinsic
to the code but due to the present GENIE valid energy range.
References:
[1] C. Andreopoulos at al., Nucl. Instrum. Meth. A614 (2010) 87.
[2] P. Antonioli et al., Astropart. Phys. 7 (1997) 357.
[3] J. H. Koehne et al., Comput. Phys. Commun. 184 (2013) 2070.
[4] S. Adrián-Martínez et al., J. Phys. G: Nucl. Part. Phys. 43 (2016) 084001.The gSeaGen code is a GENIE-based application developed to efficiently generate high statistics samples
of events, induced by neutrino interactions, detectable in a neutrino telescope. The gSeaGen code is able
to generate events induced by all neutrino flavours, considering topological differences between tracktype
and shower-like events. Neutrino interactions are simulated taking into account the density and
the composition of the media surrounding the detector. The main features of gSeaGen are presented
together with some examples of its application within the KM3NeT project.French National Research Agency (ANR)
ANR-15-CE31-0020Centre National de la Recherche Scientifique (CNRS)European Union (EU)Institut Universitaire de France (IUF), FranceIdEx program, FranceUnivEarthS Labex program at Sorbonne Paris Cite
ANR-10-LABX-0023
ANR-11-IDEX-000502Paris Ile-de-France Region, FranceShota Rustaveli National Science Foundation of Georgia (SRNSFG), Georgia
FR-18-1268German Research Foundation (DFG)Greek Ministry of Development-GSRTIstituto Nazionale di Fisica Nucleare (INFN)Ministry of Education, Universities and Research (MIUR)PRIN 2017 program Italy
NAT-NET 2017W4HA7SMinistry of Higher Education, Scientific Research and Professional Training, MoroccoNetherlands Organization for Scientific Research (NWO)
Netherlands GovernmentNational Science Centre, Poland
2015/18/E/ST2/00758National Authority for Scientific Research (ANCS), RomaniaMinisterio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento, Spain (MCIU/FEDER)
PGC2018-096663-B-C41
PGC2018-096663-A-C42
PGC2018-096663-BC43
PGC2018-096663-B-C44Severo Ochoa Centre of Excellence and MultiDark Consolider (MCIU), Junta de Andalucia, Spain
SOMM17/6104/UGRGeneralitat Valenciana: Grisolia, Spain
GRISOLIA/2018/119GenT, Spain
CIDEGENT/2018/034La Caixa Foundation
LCF/BQ/IN17/11620019EU: MSC program, Spain
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Saethre-Chotzen syndrome : cranofacial anomalies caused by genetic changes in the TWIST gene
In this thesis, one of the most frequently occurring and most variable craniosynostosis
syndromes was investigated; Saethre-Chotzen syndrome. Craniosynostosis is the premature
obliteration of cranial sutures in the developing embryo. It can also occur in the first few
months of life. Saethre-Chotzen syndrome is, besides craniosynostosis, characterized by
specific facial and limb abnormalities, of which the most frequently reported are ptosis,
prominent crus helicis, cutaneous syndactyly of digit 2 and 3 on both hands and feet, and
broad halluces. Saethre-Chotzen syndrome has been linked to the TWIST gene on
chromosome 7p21.1. Mutations in and variably sized deletions of this gene can be found in
patients with clinical features of Saethre-Chotzen syndrome. The latter, TWIST deletions,
often also include part of the surrounding chromosome 7p and are reported to be associated
with mental retardation. In Saethre-Chotzen patients, in whom neither a mutation nor a
deletion of TWIST had been found, the FGFR3 P250R mutation was in some cases detected.
This mutation has specifically been linked to Muenke syndrome that is characterized by unior
bicoronal synostosis and slight facial dysmorphology. However, a Saethre-Chotzen like
phenotype can also result from this mutation.
Because of the possible overlap of Saethre-Chotzen with Muenke syndrome, these syndromes
were studied in order to provide clinical criteria that discriminate between the two (chapter 4).
Many phenotypic features occur in both syndromes. In addition, although unicoronal
synostosis occurs slightly more frequently in Muenke syndrome, unicoronal and bicoronal
synostosis are seen in both syndromes. The discrimination between Saethre-Chotzen and
Muenke is often not made easily and the associated genes, TWIST and FGFR3, respectively,
are simultaneously tested for pathogenic m
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