The significance of local thermal non-equilibrium in simulations of enhanced geothermal recovery

International audienceAccessing the thermo-mechanical response of large deep hot dry rock (HDR) reservoirs during geothermal extraction remains a challenging task that can be comprehended with numerical tools. Of crucial im-portance to the economic viability of these HDR reservoirs is the knowledge of thermal output evolution, fluid excessive pressure and induced thermal stress, at various steps of the circulation tests. Thermal recovery from a HDR reservoir, viewed as a deformable fractured medium, is investigated with a focus on the assumption of lo-cal thermal non-equilibrium (LTNE). To this end, a fully coupled finite element formulation for a thermo-elastic fractured medium in LTNE is developed (Gelet et al. 2013). Hydraulic diffusion, thermal diffusion, forced con-vection and deformation are considered in a two-phase framework, the solid phase being made by impermeable solid blocks separated by saturated fractures. Each of the two phases is endowed with its own temperature. The resulting system of equations is used to address a generic HDR reservoir subjected to temperature and pressure gradients. A change of time profile of the outlet fluid temperature is observed as the fracture spacing increases, switching from a single-step pattern to a double-step pattern, a feature which is viewed as characteristic of established LTNE. A dimensionless number is proposed to delineate between local thermal equilibrium (LTE) and non-equilibrium. This number embodies local physical properties of the mixture, elements of the geometry of the reservoir and the production flow rate. All the above properties being fixed, the resulting fracture spacing threshold between LTNE and LTE is found to decrease with increasing porosity. The thermally induced effec-tive stress is tensile near the injection well, illustrating the thermal contraction of the rock, while the pressure contribution of the fracture fluid is negligible during the late period

Measure Twice: Promise of Liquid Biopsy in Pediatric High-Grade Gliomas

Purpose To review and critique the current state of liquid biopsy in pHGG. Materials and Methods Published literature was reviewed for articles related to liquid biopsy in pediatric glioma and adult glioma with a focus on high-grade gliomas. Results This review discusses the current state of liquid biomarkers of pHGG and their potential applications for liquid biopsy development. Conclusions While nascent, the progress toward identifying circulating analytes of pHGG primes the field of neuro-oncoogy for liquid biopsy development

Excess risk of adverse pregnancy outcomes in women with porphyria: a population-based cohort study

The porphyrias comprise a heterogeneous group of rare, primarily hereditary, metabolic diseases caused by a partial deficiency in one of the eight enzymes involved in the heme biosynthesis. Our aim was to assess whether acute or cutaneous porphyria has been associated with excess risks of adverse pregnancy outcomes. A population-based cohort study was designed by record linkage between the Norwegian Porphyria Register, covering 70% of all known porphyria patients in Norway, and the Medical Birth Registry of Norway, based on all births in Norway during 1967–2006. The risks of the adverse pregnancy outcomes preeclampsia, delivery by caesarean section, low birth weight, premature delivery, small for gestational age (SGA), perinatal death, and congenital malformations were compared between porphyric mothers and the rest of the population. The 200 mothers with porphyria had 398 singletons during the study period, whereas the 1,100,391 mothers without porphyria had 2,275,317 singletons. First-time mothers with active acute porphyria had an excess risk of perinatal death [adjusted odds ratio (OR) 4.9, 95% confidence interval (CI) 1.5–16.0], as did mothers with the hereditable form of porphyria cutanea tarda (PCT) (3.0, 1.2–7.7). Sporadic PCT was associated with an excess risk of SGA [adjusted relative risk (RR) 2.0, 1.2–3.4], and for first-time mothers, low birth weight (adjusted OR 3.4, 1.2–10.0) and premature delivery (3.5, 1.2–10.5) in addition. The findings suggest women with porphyria should be monitored closely during pregnancy

What does the structure-function relationship of the HIV-1 Tat protein teach us about developing an AIDS vaccine?

The human immunodeficiency virus type 1 (HIV-1) trans-activator of transcription protein Tat is an important factor in viral pathogenesis. In addition to its function as the key trans-activator of viral transcription, Tat is also secreted by the infected cell and taken up by neighboring cells where it has an effect both on infected and uninfected cells. In this review we will focus on the relationship between the structure of the Tat protein and its function as a secreted factor. To this end we will summarize some of the exogenous functions of Tat that have been implicated in HIV-1 pathogenesis and the impact of structural variations and viral subtype variants of Tat on those functions. Finally, since in some patients the presence of Tat-specific antibodies or CTL frequencies are associated with slow or non-progression to AIDS, we will also discuss the role of Tat as a potential vaccine candidate, the advances made in this field, and the importance of using a Tat protein capable of eliciting a protective or therapeutic immune response to viral challenge

Identification and Phylogenetic Analysis of Tityus pachyurus and Tityus obscurus Novel Putative Na+-Channel Scorpion Toxins

Background: Colombia and Brazil are affected by severe cases of scorpionism. In Colombia the most dangerous accidents are caused by Tityus pachyurus that is widely distributed around this country. In the Brazilian Amazonian region scorpion stings are a common event caused by Tityus obscurus. The main objective of this work was to perform the molecular cloning of the putative Na+-channel scorpion toxins (NaScTxs) from T. pachyurus and T. obscurus venom glands and to analyze their phylogenetic relationship with other known NaScTxs from Tityus species. Methodology/Principal Findings: cDNA libraries from venom glands of these two species were constructed and five nucleotide sequences from T. pachyurus were identified as putative modulators of Na+-channels, and were named Tpa4, Tpa5, Tpa6, Tpa7 and Tpa8; the latter being the first anti-insect excitatory b-class NaScTx in Tityus scorpion venom to be described. Fifteen sequences from T. obscurus were identified as putative NaScTxs, among which three had been previously described, and the others were named To4 to To15. The peptides Tpa4, Tpa5, Tpa6, To6, To7, To9, To10 and To14 are closely related to the a-class NaScTxs, whereas Tpa7, Tpa8, To4, To8, To12 and To15 sequences are more related to the b-class NaScTxs. To5 is possibly an arthropod specific toxin. To11 and To13 share sequence similarities with both a and b NaScTxs. By means of phylogenetic analysis using the Maximum Parsimony method and the known NaScTxs from Tityus species, these toxins were clustered into 14 distinct groups. Conclusions/Significance: This communication describes new putative NaScTxs from T. pachyurus and T. obscurus and their phylogenetic analysis. The results indicate clear geographic separation between scorpions of Tityus genus inhabiting the Amazonian and Mountain Andes regions and those distributed over the Southern of the Amazonian rainforest. Based on the consensus sequences for the different clusters, a new nomenclature for the NaScTxs is proposed

Plus- and Minus-End Directed Microtubule Motors Bind Simultaneously to Herpes Simplex Virus Capsids Using Different Inner Tegument Structures

Many viruses depend on host microtubule motors to reach their destined intracellular location. Viral particles of neurotropic alphaherpesviruses such as herpes simplex virus 1 (HSV1) show bidirectional transport towards the cell center as well as the periphery, indicating that they utilize microtubule motors of opposing directionality. To understand the mechanisms of specific motor recruitment, it is necessary to characterize the molecular composition of such motile viral structures. We have generated HSV1 capsids with different surface features without impairing their overall architecture, and show that in a mammalian cell-free system the microtubule motors dynein and kinesin-1 and the dynein cofactor dynactin could interact directly with capsids independent of other host factors. The capsid composition and surface was analyzed with respect to 23 structural proteins that are potentially exposed to the cytosol during virus assembly or cell entry. Many of these proteins belong to the tegument, the hallmark of all herpesviruses located between the capsid and the viral envelope. Using immunoblots, quantitative mass spectrometry and quantitative immunoelectron microscopy, we show that capsids exposing inner tegument proteins such as pUS3, pUL36, pUL37, ICP0, pUL14, pUL16, and pUL21 recruited dynein, dynactin, kinesin-1 and kinesin-2. In contrast, neither untegumented capsids exposing VP5, VP26, pUL17 and pUL25 nor capsids covered by outer tegument proteins such as vhs, pUL11, ICP4, ICP34.5, VP11/12, VP13/14, VP16, VP22 or pUS11 bound microtubule motors. Our data suggest that HSV1 uses different structural features of the inner tegument to recruit dynein or kinesin-1. Individual capsids simultaneously accommodated motors of opposing directionality as well as several copies of the same motor. Thus, these associated motors either engage in a tug-of-war or their activities are coordinately regulated to achieve net transport either to the nucleus during cell entry or to cytoplasmic membranes for envelopment during assembly