Specific Heat Study of the Magnetic Superconductor HoNi2B2C

The complex magnetic transitions and superconductivity of HoNi2B2C were studied via the dependence of the heat capacity on temperature and in-plane field angle. We provide an extended, comprehensive magnetic phase diagram for B // [100] and B // [110] based on the thermodynamic measurements. Three magnetic transitions and the superconducting transition were clearly observed. The 5.2 K transition (T_{N}) shows a hysteresis with temperature, indicating the first order nature of the transition at B=0 T. The 6 K transition (T_{M}), namely the onset of the long-range ordering, displays a dramatic in-plane anisotropy: T_{M} increases with increasing magnetic field for B // [100] while it decreases with increasing field for B // [110]. The anomalous anisotropy in T_{M} indicates that the transition is related to the a-axis spiral structure. The 5.5 K transition (T^{*}) shows similar behavior to the 5.2 K transition, i.e., a small in-plane anisotropy and scaling with Ising model. This last transition is ascribed to the change from a^{*} dominant phase to c^{*} dominant phase.Comment: 9 pages, 11 figure

Persistent HIV-infected cells in cerebrospinal fluid are associated with poorer neurocognitive performance

BACKGROUND. Persistence of HIV in sanctuary sites despite antiretroviral therapy (ART) presents a barrier to HIV remission and may affect neurocognitive function. We assessed HIV persistence in cerebrospinal fluid (CSF) and associations with inflammation and neurocognitive performance during long-term ART. METHODS. Participants enrolled in the AIDS Clinical Trials Group (ACTG) HIV Reservoirs Cohort Study (A5321) underwent concurrent lumbar puncture, phlebotomy, and neurocognitive assessment. Cell-associated HIV DNA and HIV RNA (CA-DNA, CA-RNA) were measured by quantitative PCR (qPCR). in peripheral blood mononuclear cells (PBMCs) and in cell pellets from CSF. In CSF supernatant and blood plasma, cell-free HIV RNA was quantified by qPCR with single copy sensitivity, and inflammatory biomarkers were measured by enzyme immunoassay. RESULTS. Sixty-nine participants (97% male, median age 50 years, CD4 696 cells/mm3, plasma HIV RNA <100 copies/mL) were assessed after a median 8.6 years of ART. In CSF, cell-free RNA was detected in 4%, CA-RNA in 9%, and CA-DNA in 48% of participants (median level 2.1 copies/103 cells). Detection of cell-free CSF HIV RNA was associated with higher plasma HIV RNA (P = 0.007). CSF inflammatory biomarkers did not correlate with HIV persistence measures. Detection of CSF CA-DNA HIV was associated with worse neurocognitive outcomes including global deficit score (P = 0.005), even after adjusting for age and nadir CD4 count. CONCLUSION. HIV-infected cells persist in CSF in almost half of individuals on long-term ART, and their detection is associated with poorer neurocognitive performance

Validation of the BOADICEA model and a 313-variant polygenic risk score for breast cancer risk prediction in a Dutch prospective cohort

Purpose: We evaluated the performance of the recently extended Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA version 5) in a Dutch prospective cohort, using a polygenic risk score (PRS) based on 313 breast cancer (BC)–associated variants (PRS313) and other, nongenetic risk factors. Methods: Since 1989, 6522 women without BC aged 45 or older of European descent have been included in the Rotterdam Study. The PRS313 was calculated per 1 SD in controls from the Breast Cancer Association Consortium (BCAC). Cox regression analysis was performed to estimate the association between the PRS313 and incident BC risk. Cumulative 10-year risks were calculated with BOADICEA including different sets of variables (age, risk factors and PRS313). C-statistics were used to evaluate discriminative ability. Results: In total, 320 women developed BC. The PRS313 was significantly associated with BC (hazard ratio [HR] per SD of 1.56, 95% confidence interval [CI] [1.40–1.73]). Using 10-year risk estimates including age and the PRS313, other risk factors improved the discriminatory ability of the BOADICEA model marginally, from a C-statistic of 0.636 to 0.653. Conclusions: The effect size of the PRS313 is highly reproducible in the Dutch population. Our results validate the BOADICEA v5 model for BC risk assessment in the Dutch general population

Ivermectin, ‘Wonder drug’ from Japan: the human use perspective

Discovered in the late-1970s, the pioneering drug ivermectin, a dihydro derivative of avermectin—originating solely from a single microorganism isolated at the Kitasato Intitute, Tokyo, Japan from Japanese soil—has had an immeasurably beneficial impact in improving the lives and welfare of billions of people throughout the world. Originally introduced as a veterinary drug, it kills a wide range of internal and external parasites in commercial livestock and companion animals. It was quickly discovered to be ideal in combating two of the world’s most devastating and disfiguring diseases which have plagued the world’s poor throughout the tropics for centuries. It is now being used free-of-charge as the sole tool in campaigns to eliminate both diseases globally. It has also been used to successfully overcome several other human diseases and new uses for it are continually being found. This paper looks in depth at the events surrounding ivermectin’s passage from being a huge success in Animal Health into its widespread use in humans, a development which has led many to describe it as a “wonder” drug

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

Elliptic flow of identified hadrons in Pb-Pb collisions at 1asNN = 2.76 TeV

The elliptic flow coefficient (v2) of identified particles in Pb-Pb collisions at 1asNN = 2.76 TeV was measured with the ALICE detector at the Large Hadron Collider (LHC). The results were obtained with the Scalar Product method, a two-particle corre- lation technique, using a pseudo-rapidity gap of | 06\u3b7| > 0.9 between the identified hadron under study and the reference particles. The v2 is reported for \u3c0\ub1, K\ub1, K0S, p+p, \u3c6, \u39b+\u39b, \u39e 12+\u39e+ and \u3a9 12+\u3a9+ in several collision centralities. In the low transverse momentum (pT) region, pT 3 GeV/c

Centrality dependence of inclusive J/\u3c8 production in p-Pb collisions at 1asNN = 5.02 TeV

We present a measurement of inclusive J/\u3c8 production in p-Pb collisions at 1asNN = 5.02TeV as a function of the centrality of the collision, as estimated from the energy deposited in the Zero Degree Calorimeters. The measurement is performed with the ALICE detector down to zero transverse momentum, pT, in the backward ( 124.46 < ycms < 122.96) and forward (2.03 < ycms < 3.53) rapidity intervals in the dimuon decay channel and in the mid-rapidity region ( 121.37 < ycms < 0.43) in the dielectron decay channel. The backward and forward rapidity intervals correspond to the Pb-going and p-going direction, respectively. The pT-differential J/\u3c8 production cross section at backward and forward rapidity is measured for several centrality classes, together with the corresponding average pT and pT2 values. The nuclear modification factor is presented as a function of centrality for the three rapidity intervals, and as a function of pT for several centrality classes at backward and forward rapidity. At mid- and forward rapidity, the J/\u3c8 yield is suppressed up to 40% compared to that in pp interactions scaled by the number of binary collisions. The degree of suppression increases towards central p-Pb collisions at forward rapidity, and with decreasing pT of the J/\u3c8. At backward rapidity, the nuclear modification factor is compatible with unity within the total uncertainties, with an increasing trend from peripheral to central p-Pb collisions

Centrality dependence of high-pT D meson suppression in Pb-Pb collisions at 1asNN = 2.76 TeV

The nuclear modification factor, RAA, of the prompt charmed mesons D0, D+ and D 17+, and their antiparticles, was measured with the ALICE detector in Pb-Pb collisions at a centre-of-mass energy 1asNN = 2.76 TeV in two transverse momentum intervals, 5 < pT < 8GeV/c and 8 < pT < 16GeV/c, and in six collision centrality classes. The RAA shows a maximum suppression of a factor of 5\u20136 in the 10% most central collisions. The suppression and its centrality dependence are compatible within uncertainties with those of charged pions. A comparison with the RAA of non-prompt J/\u3c8 from B meson decays, measured by the CMS Collaboration, hints at a larger suppression of D mesons in the most central collisions