Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamics of back‐arc extension controlled by subducting slab retreat: Insights from 2D thermo‐mechanical modelling

Back‐arc regions, located in the overriding slabs and separated from fore‐arcs by magmatic extrusion, are closely coupled with subduction zones. The width of back‐arc extension is broadly varied in the world. Although the dynamics of the subducting slab is widely studied, the coupling between subducting slab dynamics and back‐arc extension development is still poorly understood. In this study, we aim to numerically analyse how subducting slab retreat influences back‐arc extension, with particular attention paid on the coupling between subducting slab dynamics and back‐arc extension dynamics. Geometry evolution of the subducting slab in the deep upper mantle is investigated. Furthermore, we investigate key parameters that may control back‐arc extension dynamic pattern and process. We perform systematically a set of numerical experiments with 2D high‐resolution thermo‐mechanical coupled oceanic–continental subduction models.
A Deep Sequencing Approach to Comparatively Analyze the Transcriptome of Lifecycle Stages of the Filarial Worm, Brugia malayi

Background Developing intervention strategies for the control of parasitic nematodes continues to be a significant challenge. Genomic and post-genomic approaches play an increasingly important role for providing fundamental molecular information about these parasites, thus enhancing basic as well as translational research. Here we report a comprehensive genome-wide survey of the developmental transcriptome of the human filarial parasite Brugia malayi. Methodology/Principal Findings Using deep sequencing, we profiled the transcriptome of eggs and embryos, immature (≤3 days of age) and mature microfilariae (MF), third- and fourth-stage larvae (L3 and L4), and adult male and female worms. Comparative analysis across these stages provided a detailed overview of the molecular repertoires that define and differentiate distinct lifecycle stages of the parasite. Genome-wide assessment of the overall transcriptional variability indicated that the cuticle collagen family and those implicated in molting exhibit noticeably dynamic stage-dependent patterns. Of particular interest was the identification of genes displaying sex-biased or germline-enriched profiles due to their potential involvement in reproductive processes. The study also revealed discrete transcriptional changes during larval development, namely those accompanying the maturation of MF and the L3 to L4 transition that are vital in establishing successful infection in mosquito vectors and vertebrate hosts, respectively. Conclusions/Significance Characterization of the transcriptional program of the parasite's lifecycle is an important step toward understanding the developmental processes required for the infectious cycle. We find that the transcriptional program has a number of stage-specific pathways activated during worm development. In addition to advancing our understanding of transcriptome dynamics, these data will aid in the study of genome structure and organization by facilitating the identification of novel transcribed elements and splice variants.
Risk factors associated with the development of overt nephropathy in type 2 diabetes patients: A 12 years observational study

Background & objectives: Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal disease in developing countries. Early detection and risk reduction measures can prevent DN. The aim of the study was to determine the risk factors for the development of proteinuria over a period of 12 years of follow up in normoalbuminuric type 2 diabetes patients attending a specialized centre. Methods: Of the 2630 type 2 diabetes subjects newly registered in 1996, 152 (M:F;92:60) normoalbuminuric subjects had baseline and subsequent measurements of anthropometric, haemodynamic and biochemical details spanning 12 years. The subjects were divided into 2 groups based on the renal status during follow up visits. Group 1 (non-progressors) had persistent normoalbuminuria and group 2 (progressors) had persistent proteinuria. Presence of other diabetic complications during follow up and details on antidiabetic and antihypertensive agents were noted. Results: During median follow up of 11 years in subjects with normal renal function at baseline, 44.1 per cent developed proteinuria at follow up. Glucose levels, HbA1c, systolic blood pressure (SBP), triglycerides, and urea levels were significantly higher at baseline among progressors than non-progressors. Progressors had a longer duration of diabetes and significant fall in estimated glomerular filtration rate (eGFR) levels at follow up. In Cox's regression analysis, baseline age, duration of diabetes, baseline HbA1c and mean values of HbA1c, triglycerides, SBP and presence of retinopathy showed significant association with the development of macroalbuminuria. Interpretation & conclusions: Type 2 diabetes patients with uncontrolled diabetes and increase in blood pressure are at high risk of developing nephropathy. Age, long duration of diabetes, elevated BP, poor glycaemic control and presence of retinopathy were significantly associated with the progression of diabetic nephropathy.
New generation antipsychotic drugs and compliance behaviour

Purpose of review Antipsychotic therapy has been eclipsed by high rates of noncompliance; the problem was attributed to a lack of efficacy and the burden of side effects of neuroleptics. This review sought to examine whether the arrival of second generation (atypical) antipsychotic drugs with low side-effect liability and improved efficacy has helped to positively reinforce compliance behaviour among people treated for schizophrenia. Recent findings The number of studies that systematically examined compliance behaviour and its determinants during antipsychotic drug therapy is disappointingly low. A review of relevant clinical trials, drug dispensation databases and observational studies yielded equivocal results. The data have failed to substantiate the notion that novel antipsychotic drug use leads to improved medication compliance and favourable clinical outcomes. Summary A decade of clinical experience and research indicates that compliance behaviour has only marginally improved since the introduction of second generation antipsychotic drugs. Noncompliance in schizophrenia is a complex maladaptive pattern of behaviour determined by personal beliefs, illness-related factors, social attributes and health system variables. The reinforcing value of antipsychotic drugs may be less relevant in enhancing treatment compliance and influencing the natural history of schizophrenia.
A Hysteresis Approach to Phase--eld Models

Phase-eld systems as mathematical models to forecast the evolution of processes involving phase transitions have drawn a considerable interest in recent years. However, while they are capable of capturing many of the experimentally observed phenomena, they are only of restricted value in modelling hysteresis eeects occuring during phase transition processes. To overcome this shortcoming, a new approach to phase-eld models is proposed in this paper which is based on the mathematical theory of hysteresis operators developed in the past fteen years. The approach taken here leads to highly nonlinearly coupled systems of diierential equations containing hysteretic nonlinearities at diierent places. For such a system, well-posedness and thermodynamic consistency are proved. Due to the lack of smoothness (hysteresis operators are, as a rule, non-diierentiable) in the system, the method of proof has to be diierent from those usually employed for classical phase-eld systems.
Failure Progress of 3D Reinforced GFRP Laminate during Static Bending, Evaluated by Means of Acoustic Emission and Vibrations Analysis

The work aimed to assess the failure progress in a glass fiber-reinforced polymer laminate with a 3D-woven and (as a comparison) plain-woven reinforcement, during static bending, using acoustic emission signals. The innovative method of the separation of the signal coming from the fiber fracture and the one coming from the matrix fracture with the use of the acoustic event’s energy as a criterion was applied. The failure progress during static bending was alternatively analyzed by evaluation of the vibration signal. It gave a possibility to validate the results of the acoustic emission. Acoustic emission, as well as vibration signal analysis proved to be good and effective tools for the registration of failure effects in composite laminates. Vibration analysis is more complicated methodologically, yet it is more precise. The failure progress of the 3D laminate is “safer” and more beneficial than that of the plain-woven laminate. It exhibits less rapid load capacity drops and a higher fiber effort contribution at the moment of the main laminate failure.
Diffusible retinal secretions regulate the expression of tight junctions and other diverse functions of the retinal pigment epithelium

Purpose The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier. It is unclear how culture conditions might alter barrier properties of isolated RPE. We examined whether retinal secretions that increase the barrier functions of tight junctions in vitro also make gene expression in general more in vivo-like. Methods Chick RPE from embryonic day 7 (E7) and E14 were cultured on filters. Media conditioned by organ culture of E14 neural retinas was added to the apical medium chamber. RNA was isolated to probe the chick genome on Affymetrix microarrays, and expression was compared to native E14 RPE. Expression was further analyzed by quantitative real-time PCR immunoblotting and immunocytochemistry. Results More than 86% of the genes expressed in vivo were expressed in basal culture conditions, including RPE-specific markers such as RPE65 and bestrophin. E14 retinal conditioned medium affected 15% of the transcriptome in E7 cultures (24% if serum was included), but only 1.9% in E14 cultures (12% with serum). Examination of 610 genes important for RPE function revealed that mRNAs for 17% were regulated by retinal conditioned medium alone in E7 cultures, compared to 6.2% for E14. For tight junctions, retinal conditioned medium had the most effect on members of the claudin family. Besides regulating mRNA levels, immunoblotting and immunocytochemistry suggested additional mechanisms whereby retinal secretions regulated protein expression and localization. Conclusions Gene expression in primary cultures of embryonic RPE resembled the native tissue, but differentiation and the levels of gene expression became more in vivo-like when elements of the retinal environment were introduced into the medium bathing the apical side of the cultures. Albeit insufficient, retinal secretions promoted differentiation of immature RPE and helped maintain the properties of more mature RPE.
Trait and state anxiety reduce the mere exposure effect

The mere exposure effect refers to an affective preference elicited by exposure to previously unfamiliar items. Although it is a well-established finding, its mechanism remains uncertain, with some positing that it reflects affective processes and others positing that it reflects perceptual or motor fluency with repeated items. Here we examined whether individual differences in trait and state anxiety, which have been associated with the experience of emotion, influence the mere exposure effect. Participants’ trait (Study 1) and state (Study 2) anxiety were characterized with the State-Trait Anxiety Inventory. Greater trait and state anxiety correlated with greater negative affect and lesser positive affect. In both experiments, greater anxiety was associated with a reduced mere exposure effect. Measures of fluency (response times at study and test) were unrelated to the mere exposure effect. These findings support the role of affective processes in the mere exposure effect, and offer a new insight into the nature of anxiety such that anxiety is associated with a reduced experience of positive affect typically associated with familiarity.
SEX-RELATED DIFFERENCES IN TIME ESTIMATION AND THE ROLE OF EXPECTANCY

In this study, using auditory sequences, the authors designed an examination with three phases of stimulus-driven attention that is based on the possibility that involuntarily time shifts of attention are caused by nonunique stimulus properties. The purpose was to investigate whether attending and temporal expectancies are influenced by stimulus's properties and by sex. In each phase, an auditory stimulus train was presented, and the participant was asked to tap rhythmically in order to anticipate every fifth stimulus (or, in the third phase, the lack of it). The time between button pressing and stimulus onset was measured using a computer. Time estimation was accepted as a false response if the subject responded before 150 ms or 150 ms later from onset stimulus time. Error numbers were greater in Phase 3 and there was no significant difference between the male and female subjects for any of the phases when error numbers were compared. On the other hand, males pressed the button more accurately than females. Time estimation performance was affected by sex and expectancy-related motor responses are very important for time estimation.
Alternate multiwavelength modelocked fiber laser

We demonstrate alternate mode-locking of three 30-ps pulse trains at three different wavelengths, each at a repetition rate of 3.8 GHz. The successive multiwavelength pulsed operation is reached in an actively mode-locked erbium-doped fiber laser in which an unbalanced Mach-Zehnder interferometer has been introduced. This component plays both the role of intensity modulator and tunable filter.
Comparison of tissue distribution, phrenic nerve involvement, and epidural spread in standard- vs low-volume ultrasound-guided interscalene plexus block using contrast magnetic resonance imaging: a randomized, controlled trial.

BACKGROUND Ultrasound guidance allows for the use of much lower volumes of local anaesthetics for nerve blocks, which may be associated with less aberrant spread and fewer complications. This randomized, controlled study used contrast magnetic resonance imaging to view the differential-volume local anaesthetic distribution, and compared analgesic efficacy and respiratory impairment. METHODS Thirty patients undergoing shoulder surgery were randomized to receive ultrasound-guided interscalene block by a single, blinded operator with injection of ropivacaine 0.75% (either 20 or 5 ml) plus the contrast dye gadopentetate dimeglumine, followed by magnetic resonance imaging. The primary outcome was epidural spread. Secondary outcomes were central non-epidural spread, contralateral epidural spread, spread to the phrenic nerve, spirometry, ultrasound investigation of the diaphragm, block duration, pain scores during the first 24 h, time to first analgesic consumption, and total analgesic consumption. RESULTS All blocks provided fast onset and adequate intra- and postoperative analgesia, with no significant differences in pain scores at any time point. Epidural spread occurred in two subjects of each group (13.3%); however, spread to the intervertebral foramen and phrenic nerve and extensive i.m. local anaesthetic deposition were significantly more frequent in the 20 ml group. Diaphragmatic paralysis occurred twice as frequently (n=8 vs 4), and changes from baseline peak respiratory flow rate were larger [Δ=-2.66 (1.99 sd) vs -1.69 (2.0 sd) l min(-1)] in the 20 ml group. CONCLUSIONS This study demonstrates that interscalene block is associated with epidural spread irrespective of injection volume; however, less central (foraminal) and aberrant spread after low-volume injection may be associated with a more favourable risk profile. CLINICAL TRIAL REGISTRATION This study was registered with the European Medicines Agency (Eudra-CT number 2013-004219-36) and with the US National Institutes' of Health registry and results base, clinicaltrials.gov (identifier NCT02175069).
Simultaneous Calibration of Odometry and Sensor Parameters for Mobile Robots

Consider a differential-drive mobile robot equipped with an on-board exteroceptive sensor that can estimate its own motion, e.g., a range-finder. Calibration of this robot involves estimating six parameters: three for the odometry (radii and distance between the wheels) and three for the pose of the sensor with respect to the robot. After analyzing the observability of this problem, this paper describes a method for calibrating all parameters at the same time, without the need for external sensors or devices, using only the measurement of the wheel velocities and the data from the exteroceptive sensor. The method does not require the robot to move along particular trajectories. Simultaneous calibration is formulated as a maximum-likelihood problem and the solution is found in a closed form. Experimental results show that the accuracy of the proposed calibration method is very close to the attainable limit given by the Cramér–Rao bound.
From ingestion to colonization: the influence of the host environment on regulation of the LEE encoded type III secretion system in enterohaemorrhagic Escherichia coli

Enterohaemorrhagic Escherichia coli (EHEC) binds to host tissue and intimately attaches to intestinal cells using a dedicated type III secretion system (T3SS). This complex multi-protein organelle is encoded within a large pathogenicity island called the locus of enterocyte effacement (LEE), which is subject to extensive regulatory control. Over the past 15 years we have gained a wealth of knowledge concerning how the LEE is regulated transcriptionally by specific, global and phage encoded regulators. More recently, significant advances have been made in our understanding of how specific signals, including host or microbiota derived metabolic products and various nutrient sources, can affect how the LEE-encoded T3SS is regulated. In this review we discuss regulation of the LEE, focusing on how these physiologically relevant signals are sensed and how they affect the expression of this major virulence factor. The implications for understanding the disease process by specific regulatory mechanisms are also discussed.
Identiﬁcation and characterization of a human mitochondrial NAD kinase

NAD kinase is the sole NADP þ biosynthetic enzyme. Despite the great signiﬁcance of NADP þ , to date no mitochondrial NAD kinase has been identiﬁed in human, and the source of human mitochondrial NADP þ remains elusive. Here we present evidence demonstrating that a human protein of unknown function, C5orf33, is a human mitochondrial NAD kinase; this protein likely represents the missing source of human mitochondrial NADP þ . The C5orf33 protein exhibits NAD kinase activity, utilizing ATP or inorganic polyphosphate, and is localized in the mitochondria of human HEK293A cells. C5orf33 mRNA is more abundant than human cytosolic NAD kinase mRNA in almost all tissues examined. We further show by database searches that some animals and protists carry C5orf33 homologues as their sole NADP þ biosynthetic enzyme, whereas plants and fungi possess no C5orf33 homologue. These observations provide insights into eukaryotic NADP þ biosynthesis, which has pivotal roles in cells and organelles.
Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series

The largest kindred with inherited prion disease P102L, historically Gerstmann-Sträussler-Scheinker syndrome, originates from central England, with émigrés now resident in various parts of the English-speaking world. We have collected data from 84 patients in the large UK kindred and numerous small unrelated pedigrees to investigate phenotypic heterogeneity and modifying factors. This collection represents by far the largest series of P102L patients so far reported. Microsatellite and genealogical analyses of eight separate European kindreds support multiple distinct mutational events at a cytosine-phosphate diester-guanidine dinucleotide mutation hot spot. All of the smaller P102L kindreds were linked to polymorphic human prion protein gene codon 129M and were not connected by genealogy or microsatellite haplotype background to the large kindred or each other. While many present with classical Gerstmann-Sträussler-Scheinker syndrome, a slowly progressive cerebellar ataxia with later onset cognitive impairment, there is remarkable heterogeneity. A subset of patients present with prominent cognitive and psychiatric features and some have met diagnostic criteria for sporadic Creutzfeldt-Jakob disease. We show that polymorphic human prion protein gene codon 129 modifies age at onset: the earliest eight clinical onsets were all MM homozygotes and overall age at onset was 7 years earlier for MM compared with MV heterozygotes (P = 0.02). Unexpectedly, apolipoprotein E4 carriers have a delayed age of onset by 10 years (P = 0.02). We found a preponderance of female patients compared with males (54 females versus 30 males, P = 0.01), which probably relates to ascertainment bias. However, these modifiers had no impact on a semi-quantitative pathological phenotype in 10 autopsied patients. These data allow an appreciation of the range of clinical phenotype, modern imaging and molecular investigation and should inform genetic counselling of at-risk individuals, with the identification of two genetic modifiers.
Acute endovascular recanalization: lessons from randomized controlled trials.

PURPOSE OF REVIEW The purpose is to review the results and impact of recent positive studies on endovascular stroke treatment in the context of previous negative trials. RECENT FINDINGS Since October 2014, the results of five randomized controlled multicenter trials on the endovascular stroke treatment as adjunct to conservative treatment (largely including intravenous tissue-type plasminogen activator) versus conservative treatment alone have been published. All of these trials largely used stent retrievers as endovascular device and included patients with proven large vessel occlusion (mostly distal internal carotid or proximal middle cerebral artery (M1), short time windows after stroke onset and mostly small infarctions on initial imaging. Over all there was an overwhelming beneficial effect on outcome measured as shift in the modified Rankin Scale score and independent survival, respectively. Moreover, the rate of adverse events, in particular hemorrhage rate, was not increased. These new findings contrast previous studies on endovascular stroke treatment using mostly first generation nonstent retriever devices, longer time windows and different imaging inclusion criteria, which were overall neutral for patient outcome. SUMMARY Endovascular stroke treatment with stent retrievers is the standard of care in large vessel occlusion. New randomized controlled trials should investigate safety and efficacy in extended indications as advanced time windows or more extensive signs of ischemia on initial imaging. The same applies for new devices apart from stent retrievers.