Posttransplant lymphoproliferative disorders in neuronal xenotransplanted macaques

Posttransplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoid proliferations that occur in the setting of depressed T-cell function due to immunosuppressive therapy used following solid organ transplantation, hematopoietic stem cell transplantation, and also xenotransplantation. In the present study, 28 immunosuppressed parkinsonian Macaca fascicularis were intracerebrally injected with wild-type or CTLA4-Ig transgenic porcine xenografts to identify a suitable strategy to enable long-term cell survival, maturation, and differentiation. Nine of 28 (32%) immunosuppressed primates developed masses compatible with PTLD, located mainly in the gastrointestinal tract and/or nasal cavity. The masses were classified as monomorphic PTLD according to the World Health Organization classification. Immunohistochemistry and polymerase chain reaction (PCR) analyses revealed that the PTLDs were associated with macaca lymphocryptovirus as confirmed by double-labeling immunohistochemistry for CD20 and Epstein-Barr nuclear antigen 2 (EBNA-2), where the viral protein was located within the CD20+ neoplastic B cells. In sera from 3 distinct phases of the experimental life of the primates, testing by quantitative PCR revealed a progression of the viral load that paralleled the PTLD progression and no evidence of zoonotic transmission of porcine lymphotropic herpesvirus through xenoneuronal grafts. These data suggest that monitoring the variation of macaca lymphocryptovirus DNA in primates could be used as a possible early diagnostic tool for PTLD progression, allowing preemptive treatment such as immunosuppression therapy reduction

On asymptotic continuity of functions of quantum states

A useful kind of continuity of quantum states functions in asymptotic regime is so-called asymptotic continuity. In this paper we provide general tools for checking if a function possesses this property. First we prove equivalence of asymptotic continuity with so-called it robustness under admixture. This allows us to show that relative entropy distance from a convex set including maximally mixed state is asymptotically continuous. Subsequently, we consider it arrowing - a way of building a new function out of a given one. The procedure originates from constructions of intrinsic information and entanglement of formation. We show that arrowing preserves asymptotic continuity for a class of functions (so-called subextensive ones). The result is illustrated by means of several examples.Comment: Minor corrections, version submitted for publicatio

Registrar wellness in Botswana: Measuring burnout and identifying ways to improve wellness

Background. Burnout during registrar training is high, especially in resource-limited settings where stressors are intensified. Burnout leads to decreased quality of life for doctors, poor job and patient satisfaction, and difficulty retaining doctors.Objectives. Primary: to measure burnout among registrars working at Princess Marina Hospital in Gaborone, Botswana. Secondary: to determine factors contributing to burnout and identify potential wellness interventions.Methods. The validated Maslach Burnout Inventory was used to measure the degree of emotional exhaustion, depersonalisation and personal accomplishment. Work-related difficulties and potential wellness interventions were explored through multiple-choice and open-ended questions.Results. Of 40 eligible registrars, 20 (50%) completed the survey. High levels of burnout were reported for emotional exhaustion in 65% (13/20), depersonalisation in 45% (9/20), and personal accomplishment in 35% (7/20) of registrars. A high degree of burnout was reported by 75% (15/20) of registrars in one or more domains. In the previous 7 days, registrars worked an average of 77 hours, took 1.5 overnight calls, slept 5.7 hours per night, and 53% (10/19) had ≥1 of their patients die. Five (25%) registrars considered leaving Botswana to work in another country, which correlated with those with the highest degree of burnout. The most common frustrations included insufficient salary and limited medical resources. Suggested interventions included improved mentorship and wellness lectures.Conclusions. There is a high degree of burnout, especially emotional exhaustion, among registrars. Encouragingly, most registrars have a desire to work in Botswana after training. Future research on improving registrar wellness in low-resource settings is urgently needed

Additivity and non-additivity of multipartite entanglement measures

We study the additivity property of three multipartite entanglement measures, i.e. the geometric measure of entanglement (GM), the relative entropy of entanglement and the logarithmic global robustness. First, we show the additivity of GM of multipartite states with real and non-negative entries in the computational basis. Many states of experimental and theoretical interests have this property, e.g. Bell diagonal states, maximally correlated generalized Bell diagonal states, generalized Dicke states, the Smolin state, and the generalization of D\"{u}r's multipartite bound entangled states. We also prove the additivity of other two measures for some of these examples. Second, we show the non-additivity of GM of all antisymmetric states of three or more parties, and provide a unified explanation of the non-additivity of the three measures of the antisymmetric projector states. In particular, we derive analytical formulae of the three measures of one copy and two copies of the antisymmetric projector states respectively. Third, we show, with a statistical approach, that almost all multipartite pure states with sufficiently large number of parties are nearly maximally entangled with respect to GM and relative entropy of entanglement. However, their GM is not strong additive; what's more surprising, for generic pure states with real entries in the computational basis, GM of one copy and two copies, respectively, are almost equal. Hence, more states may be suitable for universal quantum computation, if measurements can be performed on two copies of the resource states. We also show that almost all multipartite pure states cannot be produced reversibly with the combination multipartite GHZ states under asymptotic LOCC, unless relative entropy of entanglement is non-additive for generic multipartite pure states.Comment: 45 pages, 4 figures. Proposition 23 and Theorem 24 are revised by correcting a minor error from Eq. (A.2), (A.3) and (A.4) in the published version. The abstract, introduction, and summary are also revised. All other conclusions are unchange

Spin and Rotations in Galois Field Quantum Mechanics

We discuss the properties of Galois Field Quantum Mechanics constructed on a vector space over the finite Galois field GF(q). In particular, we look at 2-level systems analogous to spin, and discuss how SO(3) rotations could be embodied in such a system. We also consider two-particle `spin' correlations and show that the Clauser-Horne-Shimony-Holt (CHSH) inequality is nonetheless not violated in this model.Comment: 21 pages, 11 pdf figures, LaTeX. Uses iopart.cls. Revised introduction. Additional reference

The PolyA tail length of yeast histone mRNAs varies during the cell cycle and is influenced by Sen1p and Rrp6p

Yeast histone mRNAs are polyadenylated, yet factors such as Rrp6p and Trf4p, required for the 3′-end processing of non-polyadenylated RNAs, contribute to the cell cycle regulation of these transcripts. Here, we investigated the role of other known 3′-end processing/transcription termination factors of non-polyadenylated RNA in the biogenesis of histone mRNAs, specifically the Nab3p/Nrd1p/Sen1p complex. We also re-evaluated the polyadenylation status of these mRNAs during the cell cycle. Our analysis reveals that yeast histone mRNAs have shorter than average PolyA tails and the length of the PolyA tail varies during the cell cycle; S-phase histone mRNAs possess very short PolyA tails while in G1, the tail length is relatively longer. Inactivation of either Sen1p or Rrp6p leads to a decrease in the PolyA tail length of histone mRNAs. Our data also show that Sen1p contributes to 3′-end processing of histone primary transcripts. Thus, histone mRNAs are distinct from the general pool of yeast mRNAs and 3′-end processing and polyadenylation contribute to the cell cycle regulation of these transcripts

Ictal Behaviors During Nonepileptic Seizures Differ in Patients with Temporal Lobe Interictal Epileptiform EEG Activity and Patients Without Interictal Epileptiform EEG Abnormalities

Purpose: Ictal behaviors during psychogenic non-epileptic seizures (NES) vary considerably among individuals, and can closely resemble common semiologies of epileptic seizures (ES). We tested the hypothesis that behaviors during NES in patients who have temporal spikes would more closely resemble behaviors during ES in patients with temporal lobe epilepsy than would behaviors during NES in patients who do not have EEG spikes. Methods: We identified 20 patients who had interictal temporal EEG spikes and EEG-video recorded NES (Study Group), 133 patients with temporal EEG spikes and recorded ES, without NES (Epileptic Group), and 24 patients with recorded NES and no epileptiform EEG abnormalities, without ES (Nonepileptic Group). Results: The hypothesis was supported with regard to ictal motor behaviors. Motionless staring or complex automatisms occurred mainly during NES in the Study Group and during ES in the Epileptic Group. In contrast, convulsive movements or flaccid falls were most common during NES in the Nonepileptic Group. Duration of unresponsiveness was longer, and there were fewer postictal states in NES both in the Study and Non-epileptic Groups. Unresponsiveness was briefer and postictal states were more consistent in ES in the Epileptic Group, however. Conclusions: Stereotyped motor activities during NES presumably represent learned behaviors. Processes underlying acquisition of ictal behaviors of NES probably differ in patients with interictal epileptiform EEG abnormalities compared to those without. Prior experiences and temporal lobe dysfunctions that are associated with epilepsy, and psychological characteristics that are unrelated to interictal epileptic dysfunctions, may determine ictal behaviors during NES.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65913/1/j.1528-1157.1998.tb01355.x.pd

Analysis of health concerns not addressed by REACH for low tonnage chemicals and opportunities for new approach methodology

In Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) the criterion for deciding the studies that must be performed is the annual tonnage of the chemical manufactured or imported into the EU. The annual tonnage may be considered as a surrogate for levels of human exposure but this does not take into account the physico-chemical properties and use patterns that determine exposure. Chemicals are classified using data from REACH under areas of health concern covering effects on the skin and eye; sensitisation; acute, repeated and prolonged systemic exposure; effects on genetic material; carcinogenicity; and reproduction and development. We analysed the mandated study lists under REACH for each annual tonnage band in terms of the information they provide on each of the areas of health concern. Using the European Chemicals Agency (ECHA) REACH Registration data base of over 20,000 registered substances, we found that only 19% of registered substances have datasets on all areas of health concern. Information limited to acute exposure, sensitisation and genotoxicity was found for 62%. The analysis highlighted the shortfall of information mandated for substances in the lower tonnage bands. Deploying New Approach Methodologies (NAMs) at this lower tonnage band to assess health concerns which are currently not covered by REACH, such as repeat and extended exposure and carcinogenicity, would provide additional information and would be a way for registrants and regulators to gain experience in the use of NAMs. There are currently projects in Europe aiming to develop NAM-based assessment frameworks and they could find their first use in assessing low tonnage chemicals once confidence has been gained by their evaluation with data rich chemicals

Multiscale model approaches to the design of advanced permanent magnets

We describe the process of multiscale modelling of magnetic materials, based on atomistic models coupled parametrically to micromagnetic calculations. At the atomistic lengthscale we use Spin Dynamics (SD) to study switching mechanisms, using structures predicted by Molecular Dynamics. The process is completed using SD to calculate the cell size and temperature dependent parameters for micromagnetic calculations. We demonstrate an unusually strong cell size scaling for Nd2Fe14B, and demonstrate numerically the existence of atomic scale Barkhausen jumps during magnetization switching. Scaling of magnetic properties is shown to be important in micromagnetic calculations of hysteresis, especially considering variation in micromagnetic cell size

Cohesin Is Limiting for the Suppression of DNA Damage–Induced Recombination between Homologous Chromosomes

Double-strand break (DSB) repair through homologous recombination (HR) is an evolutionarily conserved process that is generally error-free. The risk to genome stability posed by nonallelic recombination or loss-of-heterozygosity could be reduced by confining HR to sister chromatids, thereby preventing recombination between homologous chromosomes. Here we show that the sister chromatid cohesion complex (cohesin) is a limiting factor in the control of DSB repair and genome stability and that it suppresses DNA damage–induced interactions between homologues. We developed a gene dosage system in tetraploid yeast to address limitations on various essential components in DSB repair and HR. Unlike RAD50 and RAD51, which play a direct role in HR, a 4-fold reduction in the number of essential MCD1 sister chromatid cohesion subunit genes affected survival of gamma-irradiated G2/M cells. The decreased survival reflected a reduction in DSB repair. Importantly, HR between homologous chromosomes was strongly increased by ionizing radiation in G2/M cells with a single copy of MCD1 or SMC3 even at radiation doses where survival was high and DSB repair was efficient. The increased recombination also extended to nonlethal doses of UV, which did not induce DSBs. The DNA damage–induced recombinants in G2/M cells included crossovers. Thus, the cohesin complex has a dual role in protecting chromosome integrity: it promotes DSB repair and recombination between sister chromatids, and it suppresses damage-induced recombination between homologues. The effects of limited amounts of Mcd1and Smc3 indicate that small changes in cohesin levels may increase the risk of genome instability, which may lead to genetic diseases and cancer