Miracle-dz/UniFAR-FTUs huggingface dataset:
Mycobacterial Membrane Vesicles Administered Systemically in Mice Induce a Protective Immune Response to Surface Compartments of Mycobacterium tuberculosis

ABSTRACT Pathogenic and nonpathogenic species of bacteria and fungi release membrane vesicles (MV), containing proteins, polysaccharides, and lipids, into the extracellular milieu. Previously, we demonstrated that several mycobacterial species, including bacillus Calmette-Guerin (BCG) and Mycobacterium tuberculosis, release MV containing lipids and proteins that subvert host immune response in a Toll-like receptor 2 (TLR2)-dependent manner (R. Prados-Rosales et al., J. Clin. Invest. 121:1471–1483, 2011, doi:10.1172/JCI44261). In this work, we analyzed the vaccine potential of MV in a mouse model and compared the effects of immunization with MV to those of standard BCG vaccination. Immunization with MV from BCG or M. tuberculosis elicited a mixed humoral and cellular response directed to both membrane and cell wall components, such as lipoproteins. However, only vaccination with M. tuberculosis MV was able to protect as well as live BCG immunization. M. tuberculosis MV boosted BCG vaccine efficacy. In summary, MV are highly immunogenic without adjuvants and elicit immune responses comparable to those achieved with BCG in protection against M. tuberculosis. IMPORTANCE This work offers a new vaccine approach against tuberculosis using mycobacterial MV. Mycobacterium MV are a naturally released product combining immunogenic antigens in the context of a lipid structure. The fact that MV do not need adjuvants and elicit protection comparable to that elicited by the BCG vaccine encourages vaccine approaches that combine protein antigens and lipids. Consequently, mycobacterium MV establish a new type of vaccine formulation. This work offers a new vaccine approach against tuberculosis using mycobacterial MV. Mycobacterium MV are a naturally released product combining immunogenic antigens in the context of a lipid structure. The fact that MV do not need adjuvants and elicit protection comparable to that elicited by the BCG vaccine encourages vaccine approaches that combine protein antigens and lipids. Consequently, mycobacterium MV establish a new type of vaccine formulation.
Determination and significance of femoral neck anteversion.

Femoral neck anteversion (FNA) describes the normal torsion or twist present in the femur. Femoral neck anteversion is defined as the angle between an imaginary transverse line that runs medially to laterally through the knee joint and an imaginary transverse line passing through the center of the femoral head and neck (Fig. 1). 1,2 In adults without pathology, the femur is twisted so the head and neck of the femur are angled forward between 15 and 20 degrees from the frontal plane of the body.1,2 In some instances, the FNA angle is directed forward or backward well beyond this angle. Some researchers3–8 suggest that FNA angles outside this 15- to 20-degree average are a contributing factor in many different orthopedic problems in the lower extremity that are commonly seen by physical therapists. The purpose of this Update is to describe how FNA is related to hip rotation, how hip rotation range of motion can be used to predict abnormal FNA, and how asymmetries in hip rotation may be used to identify patients who may be at risk for developing various orthopedic problems in the hip and lower extremity. Figure 1. Illustration of normal, increased, and decreased femoral neck anterversion (FNA) angle. Femoral neck anteversion sometimes is called “medial femoral torsion. ”2,3 It is thought to result from medial (internal) rotation of the limb bud in early intrauterine life.3 In postnatal development, a reduction of the FNA angle usually occurs during growth.2,3 In the newborn, the average FNA angle is 31 degrees.2 The average FNA angle is 26 degrees by 5 years of age, 21 degrees by 9 years of age, and 15 degrees by 16 years of age.2 The FNA angle, therefore, diminishes about 1.5 …
Teaching clinical examination using peer‐assisted learning amongst graduate‐entry students

Background: We ran a peer‐assisted learning programme for teaching clinical examination amongst graduate‐entry medical students. We had three objectives: (1) to provide a forum for using peer‐assisted learning to deliver the medical schools’ clinical examination curriculum using the techniques of deliberate practice; (2) to obtain feedback on the programme using the nominal group technique; (3) to use the feedback to provide a means of improving the programme in subsequent years.
Regional scale rain-forest height mapping using regression-kriging of spaceborne and airborne LiDAR data: Application on French Guiana

LiDAR remote sensing has been shown to be a good technique for the estimation of forest parameters such as canopy heights and aboveground biomass. Whilst airborne LiDAR data are in general very dense but only available over small areas due to the cost of their acquisition, spaceborne LiDAR data acquired from the Geoscience Laser Altimeter System (GLAS) have a coarser acquisition density associated with a global cover. It is therefore valuable to analyze the integration relevance of canopy heights estimated from LiDAR sensors with ancillary data such as geological, meteorological, and phenological variables in order to propose a forest canopy height map with good precision and high spatial resolution. In this study, canopy heights extracted from both airborne and spaceborne LiDAR, were first extrapolated from available environmental data. The estimated canopy height maps using random forest (RF) regression from the airborne or GLAS calibration datasets showed similar precisions (RMSE better than 6.5 m). In order to improve the precision of the canopy height estimates regression-kriging (kriging of RF regression residuals) was used. Results indicated an improvement in the RMSE (decrease from 6.5 to 4.2 m) for the regression-kriging maps from the GLAS dataset, and from 5.8 to 1.8 m for the regression-kriging map from the airborne LiDAR dataset.
The Antitumor Effect of Metformin Is Mediated by miR-26a in Breast Cancer

Metformin, a drug approved for diabetes type II treatment, has been associated with a reduction in the incidence of breast cancer and metastasis and increased survival in diabetic breast cancer patients. High levels of miR-26a expression have been proposed as one of the possible mechanisms for this effect; likewise, this miRNA has also been associated with survival/apoptosis processes in breast cancer. Our aim was to evaluate if miR-26a and some of its targets could mediate the effect of metformin in breast cancer. The viability of MDA-MB-231, MDA-MB-468, and MCF-7 breast cancer cell lines was evaluated with an MTT assay after ectopic overexpression and/or downregulation of miR-26a. Similarly, the expression levels of the miR-26a targets CASP3, CCNE2, ABL2, APAF1, XIAP, BCL-2, PTEN, p53, E2F3, CDC25A, BCL2L1, MCL-1, EZH2, and MTDH were assessed by quantitative polymerase chain reaction (PCR). The effect of metformin treatment on breast cancer cell viability and miR-26a, BCL-2, PTEN, MCL-1, EZH2, and MTDH modulation were evaluated. Wound healing experiments were performed to analyze the effect of miR-26a and metformin treatment on cell migration. MiR-26a overexpression resulted in a reduction in cell viability that was partially recovered by inhibiting it. E2F3, MCL-1, EZH2, MTDH, and PTEN were downregulated by miR-26a and the PTEN (phosphatase and tensin homolog) protein was also reduced after miR-26a overexpression. Metformin treatment reduced breast cancer cell viability, increased miR-26a expression, and led to a reduction in BCL-2, EZH2, and PTEN expression. miR-26a inhibition partly prevents the metformin viability effect and the PTEN and EZH2 expression reduction. Our results indicate that metformin effectively reduces breast cancer cell viability and suggests that the effects of the drug are mediated by an increase in miR-26a expression and a reduction of its targets, PTEN and EHZ2 Thus, the use of metformin in breast cancer treatment constitutes a promising potential breast cancer therapy.
A Spatial Data Infrastructure Approach for the Characterization of New Zealand's Groundwater Systems

The future information needs of stakeholders for hydrogeological and hydro‐climate data management and assessment in New Zealand may be met with an Open Geospatial Consortium (OGC) standards‐compliant publicly accessible web services framework which aims to provide integrated use of groundwater information and environmental observation data in general. The stages of the framework development described in this article are search and discovery as well as data collection and access with (meta)data services, which are developed in a community process. The concept and prototype implementation of OGC‐compliant web services for groundwater and hydro‐climate data include demonstration data services that present multiple distributed datasets of environmental observations. The results also iterate over the stakeholder community process and the refined profile of OGC services for environmental observation data sharing within the New Zealand Spatial Data Infrastructure (SDI) landscape, including datasets from the National Groundwater Monitoring Program and the New Zealand Climate Database along with datasets from affiliated regional councils at regional‐ and sub‐regional scales. With the definition of the New Zealand observation data profile we show that current state‐of‐the‐art standards do not necessarily need to be improved, but that the community has to agree upon how to use these standards in an iterative process.
Benign rolandic epilepsy: neuropsychological findings

Benign rolandic epilepsy (BRE) is a partial idiopathic epilepsy of childhood presenting with a nocturnal seizure and with a typical EEG showing centrotemporal spike and multifocal or generalized sharp slow waves. Although normal neurological and intellectual development are expected in BRE, it is not infrequent to detect subtle defects in neuropsychological functions and neuromotor development. This study included 20 cases of BRE diagnosed according to the criteria of ILAE. The patients underwent several tests of neuropsychological functions as well as detailed neurological examination and the results were compared statistically to normal controls. In the patient group, a family history of language delay or learning disability (P < 0.005), presence of consanguinity (P < 0. 05), dyspraxia in the lower extremities (to imitation) (P < 0.05), difficulties in go-no-go test (P < 0.001), as well as some problems related to language such as dysprosody (P = 0.05), minor motor deficits in the left (P < 0.05) and right upper extremity (P < 0.05) were significantly more frequent compared to the control group. One should be rather guarded against the prognosis in BRE with respect to the higher cortical functions and neurodevelopmental problems.
Black hole formation at the correspondence point

We study the process of bound state formation in a D-brane collision. We consider two mechanisms for bound state formation. The first, operative at weak coupling in the worldvolume gauge theory, is pair creation of W-bosons. The second, operative at strong coupling, corresponds to formation of a large black hole in the dual supergravity. These two processes agree qualitatively at intermediate coupling, in accord with the correspondence principle of Horowitz and Polchinski. We show that the size of the bound state and time scale for formation of a bound state agree at the correspondence point. The time scale involves matching a parametric resonance in the gauge theory to a quasinormal mode in supergravity.
Isoflurane Anesthesia Does Not Satisfy the Homeostatic Need for Rapid Eye Movement Sleep

BACKGROUND: Sleep and general anesthesia are distinct states of consciousness that share many traits. Prior studies suggest that propofol anesthesia facilitates recovery from rapid eye movement (REM) and non-REM (NREM) sleep deprivation, but the effects of inhaled anesthetics have not yet been studied. We tested the hypothesis that isoflurane anesthesia would also facilitate recovery from REM sleep deprivation. METHODS: Six rats were implanted with superficial cortical, deep hippocampal, and nuchal muscle electrodes. Animals were deprived of REM sleep for 24 hours and then (1) allowed to sleep ad libitum for 8 hours or (2) were immediately anesthetized with isoflurane for a 4-hour period followed by ad libitum sleep for 4 hours. The percentage of REM and NREM sleep after the protocols was compared with similar conditions without sleep deprivation. Hippocampal &thgr; activity during isoflurane anesthesia was also compared with &thgr; activity during REM sleep and active waking. RESULTS: Recovery after deprivation was associated with a 5.7-fold increase (P = 0.0005) in REM sleep in the first 2 hours and a 2.6-fold increase (P = 0.004) in the following 2 hours. Animals that underwent isoflurane anesthesia after deprivation demonstrated a 3.6-fold increase (P = 0.001) in REM sleep in the first 2 hours of recovery and a 2.2-fold increase (P = 0.003) in the second 2 hours. There were no significant differences in REM sleep rebound between the first 4 hours after deprivation and the first 4 hours after both deprivation and isoflurane anesthesia. Hippocampal &thgr; activity during isoflurane anesthesia was not affected by REM sleep deprivation, and the probability distribution of &thgr; events during anesthesia was more similar to that of waking than to REM sleep. CONCLUSION: Unlike propofol, isoflurane does not satisfy the homeostatic need for REM sleep. Furthermore, the regulation and organization of hippocampal &thgr; events during anesthesia are unlike sleep. We conclude that different anesthetics have distinct interfaces with sleep.
An Essential Role for Histone Deacetylase 4 in Synaptic Plasticity and Memory Formation

Histone deacetylases (HDACs), a family of enzymes involved in epigenetic regulation, have been implicated in the control of synaptic plasticity, as well as learning and memory. Previous work has demonstrated administration of pharmacological HDAC inhibitors, primarily those targeted to class I HDACs, enhance learning and memory as well as long-term potentiation. However, a detailed understanding of the role of class II HDACs in these processes remains elusive. Here, we show that selective loss of Hdac4 in brain results in impairments in hippocampal-dependent learning and memory and long-term synaptic plasticity. In contrast, loss of Hdac5 does not impact learning and memory demonstrating unique roles in brain for individual class II HDACs. These findings suggest that HDAC4 is a crucial positive regulator of learning and memory, both behaviorally and at the cellular level, and that inhibition of Hdac4 activity may have unexpected detrimental effects to these processes.
Learning arithmetic read-once formulas

A formula is read-once if each variable appears at most once in it. An arithmetic read-once formula is one in which the operators are addition, subtraction, multiplication, and division. We present polynomial time algorithm for exactly learning (or interpolating) arithmetic read-once formulas computing functions over a field. We present an algorithm that uses randomized membership queries (or substitutions) to identify such formulas over large finite fields and infinite fields. We also present a deterministic algorithm that uses equivalence queries as well as membership queries to identify arithmetic read-once formulas over small finite fields. We then non-constructively show the existence of deterministic membership query (interpolation) algorithms for arbitrary formulas over fields of characteristic 0 and for division-free formulas over large or infinite fields. Our algorithms assume we are able to efficiently perform arithmetic operations on field elements and compute square roots in the field. It is shown that the ability to compute square roots is necessary, in the sense that the problem of computing n – 1 square roots in a field can be reduced to the problem of identifying an arithmetic formula over n variables in that field. Our equivalence queries are of a slightly non-standard form, in which counterexamples are required to not be inputs on which the formula evaluates to 0/0. This assumption is shown to be necessary for fields of size o(n/log n), for which it is shown that there is no polynomial time identification algorithm that uses just membership and standard equivalence queries.
Theoretical Examination of the Lithium Depletion Boundary

We explore the sensitivity in open cluster ages obtained by the lithium depletion boundary (LDB) technique to the stellar model input physics. The LDB age technique is limited to open clusters with ages ranging from 20 to 200 Myr. Effective 1 σ errors in the LDB technique due to uncertain input physics are roughly 3% at the oldest age, increasing to 8% at the youngest age. Bolometric correction uncertainties add an additional 10% and 6% error to the LDB age technique for old and young clusters, respectively. Rotation rates matching the observed fastest rotators in the Pleiades affect LDB ages by less than 2%. The range of rotation rates in an open cluster is expected to "smear" the LDB location by only 0.02 mag for a Pleiades-age cluster, increasing to 0.06 mag for a 20 Myr old cluster. Thus, the observational error of locating the LDB (~7%-10%) and the bolometric correction uncertainty currently dominate the error in LDB ages. For our base case, we formally derive an LDB age of 148 ± 19 Myr for the Pleiades, where the error includes 8%, 3%, and 9% contributions from observational, theoretical, and bolometric correction sources, respectively. A maximally plausible 0.3 mag shift in the I-band bolometric correction to reconcile main-sequence isochrone fits with the observed V-I color for the low-mass Pleiades members results in an age of 126 ± 11 Myr, where the error includes observational and theoretical errors only. Upper main sequence-fitting ages that do not include convective core overshoot for the Pleiades (~75 Myr) are ruled out by the LDB age technique.
FOXA1 as a therapeutic target for breast cancer

Gene expression profiling studies have classified breast cancer into five intrinsic subtypes with distinct prognostic significance: luminal type A, luminal type B, normal-like, HER-2-positive and basal type. These studies have also uncovered novel diagnostic markers and molecular targets. FOXA1, a winged-helix transcription factor belonging to the forkhead family, is one among them as it is expressed predominantly in luminal type A breast cancer, which is characterized by the presence of estrogen receptor-α (ERα) with favorable prognosis. FOXA1 is a ‘pioneer’ factor that binds to chromatinized DNA, opens the chromatin and enhances binding of ERα to its target genes. It is essential for the expression of ∼ 50% of ERα:estrogen-regulated genes. Thus, a network comprising FOXA1, ERα and estrogen constitutes a major proliferation and survival signal for luminal type A breast cancer. However, by controlling differentiation and by regulating the expression of cell cycle inhibitor p27kip1 and the cell adhesion molecule E-cadherin, FOXA1 may prevent metastatic progression of luminal type A breast cancer. This article reviews possible roles of FOXA family transcription factors in breast cancer initiation, hormone dependency and speculates on the potential of FOXA1 as a therapeutic target.
STATUS OF THE RE-ENTRANT CAVITY BEAM POSITION MONITOR FOR THE EUROPEAN XFEL PROJECT

The European XFEL is a research facility, currently under construction in Germany. It is based on a superconducting electron linac including about 100 cryomodules based on the TESLA technology. Each cryomodule is equipped with a beam position monitor connected to a quadrupole at the high-energy end of the cavity string. Around one third of cold BPMs will be reentrant RF cavities. This contribution describes the present status of the cold re-entrant cavity BPM and presents the measurements performed with BPM pickup and electronics prototypes.
PET and MRI of Metastatic Peritoneal and Pulmonary Colorectal Cancer in Mice with Human Epidermal Growth Factor Receptor 1–Targeted 89Zr-Labeled Panitumumab

Human epidermal growth factor receptor 1 (HER1) plays an important role in the pathogenesis of colorectal cancer. Panitumumab is an anti-HER1 monoclonal antibody approved for use in colorectal cancer. However, few data exist regarding HER1 status in the corresponding distant metastases, and little corresponding information is available regarding the localization of panitumumab at primary and metastatic lesions. The utility of PET and MRI using 89Zr-panitumumab to assess the status of HER1 in distant metastases with different metastasis models is presented in this study. Methods: In vivo biodistribution and PET studies were performed in HER1-expressing LS-174T and HER1-negative A375 tumor xenografts. Additionally, studies were performed in different models of intraperitoneal and pulmonary metastases. MRI studies were performed for metastatic models to characterize the targeting potential of 89Zr-panitumumab at different lesion sites. Results: HER1-mediated targeting was achieved in all HER1-expressing models. The LS-174T tumor area under the curve (AUC) was 3.7-fold greater than the AUC for A375. The LS-174T tumor AUC of 204.13 ± 9.67 was significantly greater (P < 0.001) than the LS-174T tumor AUC of 36.45 ± 1.39 obtained from mice coinjected with 0.1 mg of panitumumab for blocking the target. Differences were observed in 2 intraperitoneal models; tumor uptake in mice with a 3-d tumor burden was more than 2-fold greater than the mice with a 7-d tumor burden. PET and MRI studies revealed HER1-mediated tumor targeting in all metastatic models. However, significant differences were observed between different LS-174T tumor models. Peak tumor uptake of approximately 40 percentage injected dose per gram (%ID/g) was observed at 3–4 d after injection for the subcutaneous tumor model, in contrast to approximately 75 %ID/g at 2 d after injection for the thoracic tumors and approximately 95 %ID/g at 1–2 d after injection for the intraperitoneal tumors. Conclusion: The potential utility of 89Zr-panitumumab in assessing HER1 status in distant metastases and understanding the variations in antibody uptake at different lesion sites is demonstrated in this study. 89Zr-panitumumab can play a vital role in patient stratification and immunotherapy and therefore warrants further investigation for clinical translation.