Miracle-dz/UniFAR-FTUs huggingface dataset:
Permanent Alteration of PCSK9 With In Vivo CRISPR-Cas9 Genome Editing

Rationale: Individuals with naturally occurring loss-of-function proprotein convertase subtilisin/kexin type 9 (PCSK9) mutations experience reduced low-density lipoprotein cholesterol levels and protection against cardiovascular disease. Objective: The goal of this study was to assess whether genome editing using a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system can efficiently introduce loss-of-function mutations into the endogenous PCSK9 gene in vivo. Methods and Results: We used adenovirus to express CRISPR-associated 9 and a CRISPR guide RNA targeting Pcsk9 in mouse liver, where the gene is specifically expressed. We found that <3 to 4 days of administration of the virus, the mutagenesis rate of Pcsk9 in the liver was as high as >50%. This resulted in decreased plasma PCSK9 levels, increased hepatic low-density lipoprotein receptor levels, and decreased plasma cholesterol levels (by 35–40%). No off-target mutagenesis was detected in 10 selected sites. Conclusions: Genome editing with the CRISPR–CRISPR-associated 9 system disrupts the Pcsk9 gene in vivo with high efficiency and reduces blood cholesterol levels in mice. This approach may have therapeutic potential for the prevention of cardiovascular disease in humans.
Minerals of the rhabdophane group and the alunite supergroup in microgranite: products of low-temperature alteration in a highly acidic environment from the Velence Hills, Hungary

ABSTRACT An assemblage of alunite-supergroup minerals (ASM), rhabdophane-group minerals (RGM), goethite and associated clay minerals occurs in Permian A-type porphyritic microgranite in the eastern part of the Velence Hills, Hungary. The secondary sulfates/phosphates include jarosite, Pb-rich jarosite and alunite, corkite, hinsdalite and rhabdophane-(Ce), -(La) and -(Nd). Detailed electron probe microanalysis and Raman spectroscopy reveal a wide miscibility among RGM end-members and show a rhabdophane–tristramite–brockite solid solution with extensive compositional variation. Moreover, ASM show heterogeneous composition and complex substitution mechanisms within the alunite, beudantite and plumbogummite groups. The formation of this rare mineral assemblage reveals extensive remobilization of rare-earth elements (REE), Th, U, P, S, Fe and Pb under supergene conditions. Compositional variations and substitution trends of the RGM investigated indicate that Th, U, Ca and Pb are incorporated into the rhabdophane structure by a (Ca, Pb)2+ + (Th, U)4+ ↔ 2REE3+ substitution mechanism. Consequently, we suggest the following end-member formulae for RGM containing divalent and tetravalent cations: (Ca0.5Th0.5)PO4·H2O for brockite, (Pb0.5Th0.5)PO4·H2O for grayite and (Ca0.5U0.5)PO4·2H2O for tristramite. The ASM and RGM originated from total leaching of the primary magmatic REE, Th, U and P minerals in the microgranite [most probably allanite-(Ce), fluorapatite and possibly also xenotime-(Y)], together with input of Pb and S in low-temperature, acid sulfate solutions, connected with an adjacent Palaeogene andesite–diorite intrusion and the accompanying hydrothermal sulfide mineralization.
UMTS coverage and capacity enhancement using repeaters and remote RF heads

For the evolving 3rd generation UMTS networks, there is a need for coverage and capacity enhancement with the flexibility of solutions. The target of this paper is to evaluate and propose a scheme for UMTS network upgrade, with the coexistence of repeaters and remote RF heads as solution to improve the network coverage and capacity. A step-by-step study of the UMTS network with repeaters and remote RF heads in a downlink limited system is presented. Results from dynamic system level simulations for circuit switched services under varying traffic distributions are evaluated. The simulation results indicate that, repeaters, in principle, are useful to enhance the network coverage. Proper tuning of repeater gain is essential. Nevertheless, additional gain on using repeaters in an already optimized pure macro network is limited. The results show that, at system level, networks enhanced with a mixture of repeaters and remote RF heads can carry significantly more traffic than the pure macro network. The antennas mounted below rooftops in such a network, yields considerable improvement in the signal-to-noise-plus-interference ratio (SNIR) of the common pilot channel (CPICH). Roughly 50% reduction in downlink power consumption was observed. Thus, during the initial UMTS network upgrade, repeaters could be added to the macro cells to enhance coverage. Further, some or all of the repeater locations can be reused and converted to remote RF heads when additional capacity requirement arises.
Optimal Low-Rank Tensor Recovery from Separable Measurements: Four Contractions Suffice

Tensors play a central role in many modern machine learning and signal processing applications. In such applications, the target tensor is usually of low rank, i.e., can be expressed as a sum of a small number of rank one tensors. This motivates us to consider the problem of low rank tensor recovery from a class of linear measurements called separable measurements. As specic examples, we focus on two distinct types of separable measurement mechanisms (a) Random projections, where each measurement corresponds to an inner product of the tensor with a suitable random tensor, and (b) the completion problem where measurements constitute revelation of a random set of entries. We present a computationally ecient algorithm, with rigorous and order-optimal sample complexity results (upto logarithmic factors) for tensor recovery. Our method is based on reduction to matrix completion sub-problems and adaptation of Leurgans’ method for tensor decomposition. We extend the methodology and sample complexity results to higher order tensors, and experimentally validate our theoretical results
Higher chronic stress is associated with a decrease in temporal sensitivity but not in subjective duration in healthy young men

Maintaining accurate and precise temporal perception under conditions of stress is important. Studies in animal models and clinic patients have suggested that time perception can change under chronic stress. Little is known, however, about the relationship between chronic stress and time perception in healthy individuals. Here, a sample of 62 healthy young men completed Cohen’s Perceived Stress Scale (PSS) as a measure of chronic stress levels, while time perception was measured using a temporal bisection task. This task used short (400 ms) and long (1600 ms) visual signals as anchor durations. Participants were presented with a range of intermediate probe durations and were required to judge whether the durations were more similar to the short or the long anchor. Results showed that chronic stress was negatively related to temporal sensitivity indexed by the Weber ratio. However, there was no significant correlation between chronic stress and subjective duration indexed by the bisection point. These results demonstrate that higher chronic stress is associated with lower temporal sensitivity and thus provide evidence for a link between chronic stress and time perception in healthy adults.
Functional compensation of motor function in pre-symptomatic Huntington's disease

Involuntary choreiform movements are a clinical hallmark of Huntington's disease. Studies in clinically affected patients suggest a shift of motor activations to parietal cortices in response to progressive neurodegeneration. Here, we studied pre-symptomatic gene carriers to examine the compensatory mechanisms that underlie the phenomenon of retained motor function in the presence of degenerative change. Fifteen pre-symptomatic gene carriers and 12 matched controls performed button presses paced by a metronome at either 0.5 or 2 Hz with four fingers of the right hand whilst being scanned with functional magnetic resonance imaging. Subjects pressed buttons either in the order of a previously learnt 10-item finger sequence, from left to right, or kept still. Error rates ranged from 2% to 7% in the pre-symptomatic gene carriers and from 0.5% to 4% in controls, depending on the condition. No significant difference in task performance was found between groups for any of the conditions. Activations in the supplementary motor area (SMA) and superior parietal lobe differed with gene status. Compared with healthy controls, gene carriers showed greater activations of left caudal SMA with all movement conditions. Activations correlated with increasing speed of movement were greater the closer the gene carriers were to estimated clinical diagnosis, defined by the onset of unequivocal motor signs. Activations associated with increased movement complexity (i.e. with the pre-learnt 10-item sequence) decreased in the rostral SMA with nearing diagnostic onset. The left superior parietal lobe showed reduced activation with increased movement complexity in gene carriers compared with controls, and in the right superior parietal lobe showed greater activations with all but the most demanding movements. We identified a complex pattern of motor compensation in pre-symptomatic gene carriers. The results show that preclinical compensation goes beyond a simple shift of activity from premotor to parietal regions involving multiple compensatory mechanisms in executive and cognitive motor areas. Critically, the pattern of motor compensation is flexible depending on the actual task demands on motor control.
Association of sirolimus adverse effects with m-TOR, p70S6K or Raptor polymorphisms in kidney transplant recipients

Background The mammalian target of rapamycin (m-TOR) inhibitor sirolimus is an immunosuppressive drug used in kidney transplantation. m-TOR binds with Raptor and phosphorylates p70S6 kinase, a protein involved in numerous cell signalling pathways. We examined the association of candidate polymorphisms in m-TOR, Raptor and p70S6K, sirolimus dose and exposure, and other time-independent as well as time-dependent covariates, with sirolimus-induced adverse events in kidney transplant recipients. Methods This study included a first group of 113 patients, switched from a calcineurin inhibitor to sirolimus, and a validation group of 66 patients from another clinical trial, with the same immunosuppressive regimen. The effects of gene polymorphisms and covariates on the total cholesterol, LDL cholesterol, triglycerides, haemoglobin, cutaneous adverse events, oedemas and infections were studied using multilinear regression, or logistic regression imbedded in linear mixed-effect models. Results An m-TOR variant haplotype was significantly associated with a decrease in haemoglobin levels in the two populations of patients (discovery group: &bgr;=−0.82 g/dl, P=0.0076; validation group: &bgr;=−1.58 g/dl, P=0.0308). Increased sirolimus trough levels were significantly associated with increased total cholesterol levels (discovery group: &bgr;=0.02 g/l, P<0.0001; validation group: &bgr;=0.02 g/l, P=0.0002) and triglyceride levels (discovery group: &bgr;=0.02 g/l, P=0.0059; validation group: &bgr;=0.05 g/l, P=0.0370). Sirolimus trough levels were also associated with an increased risk for cutaneous adverse events [odds ratio=1.97, 95% confidence interval (1.32–1.94), P=0.0009] and oedemas [odds ratio=1.16, 95% confidence interval (1.03–1.30), P=0.01342] in the discovery group, but this was not confirmed in the validation group. Conclusion These results provide evidence of an association between an m-TOR haplotype and a decrease in haemoglobin in renal transplant recipients.
Sigma Factors for Cyanobacterial Transcription

Cyanobacteria are photosynthesizing microorganisms that can be used as a model for analyzing gene expression. The expression of genes involves transcription and translation. Transcription is performed by the RNA polymerase (RNAP) holoenzyme, comprising a core enzyme and a sigma (σ) factor which confers promoter selectivity. The unique structure, expression, and function of cyanobacterial σ factors (and RNAP core subunits) are summarized here based on studies, reported previously. The types of promoter recognized by the σ factors are also discussed with regard to transcriptional regulation.
Two Distinct Coagulase-Dependent Barriers Protect Staphylococcus aureus from Neutrophils in a Three Dimensional in vitro Infection Model

Staphylococcus aureus is a pyogenic abscess-forming facultative pathogenic microorganism expressing a large set of virulence-associated factors. Among these, secreted proteins with binding capacity to plasma proteins (e.g. fibrinogen binding proteins Eap and Emp) and prothrombin activators such as Coagulase (Coa) and vWbp are involved in abscess formation. By using a three-dimensional collagen gel (3D-CoG) supplemented with fibrinogen (Fib) we studied the growth behavior of S. aureus strain Newman and a set of mutants as well as their interaction with mouse neutrophils by real-time confocal microscopy. In 3D-CoG/Fib, S. aureus forms microcolonies which are surrounded by an inner pseudocapsule and an extended outer dense microcolony-associated meshwork (MAM) containing fibrin. Coa is involved in formation of the pseudocapsule whereas MAM formation depends on vWbp. Moreover, agr-dependent dispersal of late stage microcolonies could be observed. Furthermore, we demonstrate that the pseudocapsule and the MAM act as mechanical barriers against neutrophils attracted to the microcolony. The thrombin inhibitor argatroban is able to prevent formation of both pseudocapsule and MAM and supports access of neutrophils to staphylococci. Taken together, this model can simulate specific stages of S. aureus abscess formation by temporal dissection of bacterial growth and recruitment of immune cells. It can complement established animal infection models in the development of new treatment options.
Levodopa Treatment Improves Functional Recovery After Experimental Stroke

Background and Purpose— Delayed treatment of patients with stroke with levodopa/benserazide contributes to enhanced functional recovery, but the mechanisms involved are poorly understood. The present study was designed to investigate if levodopa/benserazide treatment improves recovery of lost neurological function and contributes to tissue reorganization in the rat brain after stroke. Methods— Male Wistar rats were subjected to transient occlusion of the middle cerebral artery (120 minutes) and treated with levodopa (1, 5, and 20 mg/kg)/benserazide (15 mg/kg) or saline for 12 consecutive days starting on Day 2 after transient occlusion of the middle cerebral artery. Infarct volume was determined and sensorimotor function was assessed using the rotating pole test, a 28-point neuroscore, and a cylinder test on Days 2, 7, and 14 after transient occlusion of the middle cerebral artery. The spatiotemporal expression pattern of dopamine-1 and dopamine-2 receptors and the dopamine- and cAMP-regulated neuronal phosphoprotein in reactive astrocytes were analyzed in the ischemic hemisphere as well as in cultured astrocytes. Results— Treatment with levodopa/benserazide significantly improved the recovery of sensorimotor function after transient occlusion of the middle cerebral artery without affecting the infarct volume. In addition, we found that different subpopulations of glial fibrillary acidic protein-positive astrocytes in the peri-infarct area express dopamine-1 receptors and dopamine-2 receptors as well as dopamine- and cAMP-regulated neuronal phosphoprotein. Conclusions— Our results strongly corroborate the concept of recovery enhancing actions of levodopa treatment after stroke. Also, astrocytes in the peri-infarct area may contribute to the dopamine enhanced recovery mechanisms.
Remote Geophysical Observatory in Antarctica with HF Data Transmission: A Review

The geophysical observatory in the Antarctic Spanish Station, Juan Carlos I (ASJI), on Livingston Island, has been monitoring the magnetic field in the Antarctic region for more than fifteen years. In 2004, a vertical incidence ionospheric sounder completed the observatory, which brings a significant added value in a region with low density of geophysical data. Although the ASJI is only operative during the austral summer, the geomagnetic station records the data throughout the year. A High Frequency (HF) transmission system was installed in 2004 in order to have the geomagnetic data available during the whole year. As the power supply is very limited when the station is not operative, we had to design a low-power HF transceiver with a very simple antenna, due to environmental aspects. Moreover, the flow of information was unidirectional, so the modulation had to be extremely robust since there is no retransmission in case of error. This led us to study the main parameters of the ionospheric channel and to design new modulations specially adapted to very low signal to noise scenarios with high levels of interference. In this paper, a review of the results of our remote geophysical observatory and associated transmission system in Antarctica during the last decade is presented.
Impact of obesity, overweight and underweight on life expectancy and lifetime medical expenditures: the Ohsaki Cohort Study

Objectives People who are obese have higher demands for medical care than those of the normal weight people. However, in view of their shorter life expectancy, it is unclear whether obese people have higher lifetime medical expenditure. We examined the association between body mass index, life expectancy and lifetime medical expenditure. Design Prospective cohort study using individual data from the Ohsaki Cohort Study. Setting Miyagi Prefecture, northeastern Japan. Participants The 41 965 participants aged 40–79 years. Primary and secondary outcome measures The life expectancy and lifetime medical expenditure aged from 40 years. Results In spite of their shorter life expectancy, obese participants might require higher medical expenditure than normal weight participants. In men aged 40 years, multiadjusted life expectancy for those who were obese participants was 41.4 years (95% CI 38.28 to 44.70), which was 1.7 years non-significantly shorter than that for normal weight participants (p=0.3184). Multiadjusted lifetime medical expenditure for obese participants was £112 858.9 (94 954.1–131 840.9), being 14.7% non-significantly higher than that for normal weight participants (p=0.1141). In women aged 40 years, multiadjusted life expectancy for those who were obese participants was 49.2 years (46.14–52.59), which was 3.1 years non-significantly shorter than for normal weight participants (p=0.0724), and multiadjusted lifetime medical expenditure was £137 765.9 (123 672.9–152 970.2), being 21.6% significantly higher (p=0.0005). Conclusions According to the point estimate, lifetime medical expenditure might appear to be higher for obese participants, despite their short life expectancy. With weight control, more people would enjoy their longevity with lower demands for medical care.
Hydrographic survey in the dying Aral Sea

We report the results of a hydrographic survey conducted in November, 2002, in the Uzbekistan part of the western basin of the dying Aral Sea. There were very few hydrographic measurements in this region since at least early 1990s. The salinity in the western deep basin of the Aral Sea varied from about 82 psu at the surface to over 94 psu at the bottom. The absolute lake surface level was about 30.5 m. Hence, the observed salinity values were much higher, and the level much lower, than expected according to earlier predictions. The density in the western basin exhibited an extremely strong stratification of ∼11 kg/m3 per ∼20 m in the bottom layer. The picnocline was accompanied by a temperature inversion whose magnitude was ∼4°C. The observed density stratification effectively isolating the lower part of the water column from surface exchanges may be responsible for the increase of summer SSTs and evaporation rates reported in previous studies. We discovered the hydrogen sulphide contamination in the bottom layer whose upper limit was at the depth of approximately 22 m. Estimates suggest that the western basin salinization occurs not only because of the local evaporation, but also because of the assimilation of the saltier eastern basin water in the course of the interbasin exchange through the connecting channel. The satellite imagery analysis, in particular the Maximum Cross‐Correlation method, suggests that the circulation pattern in the Aral Sea in its present limits is cyclonic under the eastern winds that are predominant in the region throughout the year.
New infrared star clusters in the southern Milky Way with 2MASS

We carried out a 2MASS J, H and Ks survey of infrared star clusters in the Milky Way sector 230 <'< 350. This zone was the least studied in the literature, previously including only 12 infrared clusters or stellar groups withjbj< 10, according to the recent catalogue by Bica et al. (2003). We concentrated eorts on embedded clusters, which are those expected in the areas of known radio and optical nebulae. The present study provides 179 new infrared clusters and stellar groups, which are interesting targets for detailed future infrared studies. The sample of catalogued infrared clusters and stellar groups in the Galaxy is now increased by 63%.
Targeted prevention of excess weight gain and eating disorders in high-risk adolescent girls: a randomized controlled trial.

BACKGROUND The high prevalence and incidence of obesity and eating disorders in US adolescent girls are serious health problems. Because of the shared risk factors for obesity and eating disorders, a targeted prevention of both conditions is a priority. OBJECTIVE We determined whether an adapted interpersonal psychotherapy prevention program is more efficacious for reducing excess weight gain and worsening disordered eating than health education in adolescent girls at high risk of obesity and eating disorders. DESIGN A parallel-group, randomized controlled trial was conducted between September 2008 and January 2013 in a university-based laboratory and a federal research hospital. The study included 113 adolescent (12-17-y-old) girls deemed at high risk of adult obesity and eating disorders because of a body mass index (BMI) between the 75th and 97th percentiles and reports of episodes of a loss of control over their eating. Girls were randomly assigned to participate in an adapted interpersonal psychotherapy or a health-education group program for 12 weekly 90-min group sessions. Follow-up assessments occurred immediately after group programs and at 6 and 12 mo. RESULTS Participation in both conditions was associated with decreases in expected BMI gain, age-adjusted BMI metrics, the percentage of fat by using dual-energy X-ray absorptiometry, symptoms of depression and anxiety, and the frequency of loss-of-control eating over 12 mo of follow-up (Ps < 0.001) with no group difference. In follow-up analyses, interpersonal psychotherapy was more efficacious than health education at reducing objective binge eating at the 12-mo follow-up (P < 0.05). CONCLUSIONS The intervention with adolescent girls with loss-of-control eating is associated with lower age-adjusted BMI and percentage of adiposity as well as improved mood symptoms over 1 y. Interpersonal psychotherapy further reduced objective binge eating. Additional research is needed to elucidate the mechanisms by which physical and psychological improvements were observed. This trial was registered at clinicaltrials.gov as NCT00680979.