Miracle-dz/UniFAR-FTUs huggingface dataset:
Enantiopure C1-symmetric N-Heterocyclic Carbene Ligands from Desymmetrized meso-1,2-Diphenylethylenediamine: Application in Ruthenium-Catalyzed Olefin Metathesis

In order to design improved chiral ruthenium catalysts for asymmetric olefin metathesis, enantiomeric catalysts incorporating C1-symmetric N-Heterocyclic carbenes (NHC) ligands with syn-related substituents on the backbone were synthesized starting from meso-1,2-diphenylethylenediamine. The absolute configuration of the enantiomers of the desymmetrized meso diamine was assigned by optical rotation analysis and in silico calculations, and was found to be maintained in their respective ruthenium catalysts by comparison of the relative electronic circular dichroism (ECD) spectra. The catalytic behaviour of the enantiomeric ruthenium complexes was investigated in model asymmetric metathesis transformations and compared to that of analogous complexes bearing C1-symmetric NHC ligands with an anti backbone. Modest enantioselectivities were registered and different catalyst properties depending on the nature of stereochemical relationship of substituents on the backbone were observed.
A MDM2‐dependent positive‐feedback loop is involved in inhibition of miR‐375 and miR‐106b induced by Helicobacter pylori lipopolysaccharide

Dysregulation of microRNAs (miRNAs) has been linked to virulence factors of Helicobacter pylori and shown to contribute to the progression of gastric cancer. However, the mechanisms of these processes remain poorly understood. The aim of this study was to investigate the mechanisms by which lipopolysaccharide (LPS), a virulence factor of H. pylori, regulates miR‐375 and miR‐106b expression in gastric epithelial cells. The results show that LPS from H. pylori 26695 downregulated the expression of miR‐375 and miR‐106b in gastric epithelial cells, and low levels of Dicer were also observed. Downregulation of miR‐375 was found to increase expression of MDM2 with SP1 activation. Overexpression of MDM2 inhibited Dicer by repressing p63 to create a positive‐feedback loop involving SP1/MDM2/p63/Dicer that leads to inhibition of miR‐375 and miR‐106b expression. In addition, we demonstrated that JAK1 and STAT3 were downstream target genes of miR‐106b. H. pylori LPS also enhanced the tyrosine phosphorylation of JAK1, JAK2 and STAT3. Together, these results provide insight into the regulatory mechanisms of MDM2 on H. pylori LPS‐induced specific miRNAs, and furthermore, suggest that gastric epithelial cells treated with H. pylori LPS may be susceptible to JAK/STAT3 signal pathway activation via inhibition of miR‐375 and miR‐106b.
Sensitivity and selectivity of intraneural stimulation using a silicon electrode array

A multielectrode array in silicon technology, as well as experimental paradigms and model calculations for sensitivity and selectivity measures, have been developed. The array consists of twelve platinum electrode sites (10*50 mu m and 50 mu m interdistance) on a 45- mu m thick tip-shaped silicon substrate and a Si/sub 3/N/sub 4/ insulating glass cover layer. The tip is inserted in the peroneal nerve of a rat during acute experiments to stimulate alpha motor fibers or the extensor digitorum longus muscle. Sensitivity calculations and experiments show a cubic dependence of the number of stimulated motor units on current amplitude of the stimulatory pulse (recruitment curves), starting at single motor level. Selectivity was tested by a method based on the refractory properties of neurons. At the lowest stimulus levels (for one motor unit) selectivity is maximal when two electrodes are separated by 200-250 mu m, which was also estimated on theoretical grounds. The study provides clues for future designs of two- and three-dimensional devices. <<ETX>>
Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes.

BACKGROUND Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being treated with brentuximab. RESULTS No toxicities attributable to CD30.CAR-Ts were observed. Of 7 patients with relapsed HL, 1 entered complete response (CR) lasting more than 2.5 years after the second infusion of CD30.CAR-Ts, 1 remained in continued CR for almost 2 years, and 3 had transient stable disease. Of 2 patients with ALCL, 1 had a CR that persisted 9 months after the fourth infusion of CD30.CAR-Ts. CD30.CAR-T expansion in peripheral blood peaked 1 week after infusion, and CD30.CAR-Ts remained detectable for over 6 weeks. Although CD30 may also be expressed by normal activated T cells, no patients developed impaired virus-specific immunity. CONCLUSION CD30.CAR-Ts are safe and can lead to clinical responses in patients with HL and ALCL, indicating that further assessment of this therapy is warranted. TRIAL REGISTRATION ClinicalTrials.gov NCT01316146. FUNDING National Cancer Institute (3P50CA126752, R01CA131027 and P30CA125123), National Heart, Lung, and Blood Institute (R01HL114564), and Leukemia and Lymphoma Society (LLSTR 6227-08).
Modular Combination of Reasoners for Ontology Classification

Classification is a fundamental reasoning task in ontology design, and there is currently a wide range of reasoners highly optimised for classification of SROIQ ontologies. Existing reasoners, however, do not exploit the fact that most of the axioms in many realistic SROIQ ontologies are expressed in some lightweight DL, such as EL. In this paper, we propose a novel reasoning technique that allows us to completely classify a large subset of the signature of a SROIQ ontology by relying only on a reasoner for a given lightweight DL. We also show how this information can then be exploited by the fully-fledged SROIQ reasoner HermiT to complete the classification of the ontology.
Energy-aware optimization and mechanism design for cellular device-to-device local area networks

In a device-to-device (D2D) local area network (LAN), mobile users (MUs) must cooperate to download common real-time content from a wireless cellular network. However, sustaining such D2D LANs over cellular networks requires the introduction of mechanisms that will incentivize the MUs to cooperate. In this paper, the problem of energy-aware D2D LAN formation over cellular networks is studied. The problem is formulated using a game-theoretic framework in which each MU seeks to minimize its energy consumption while actively participating in the D2D LAN. To account for the selfish behavior of the MUs, a punishment and incentive protocol is proposed in order to ensure cooperation among MUs. Within this protocol, an estimation algorithm is proposed to simulate the process of D2D LAN formation and, then, adjust the mechanism parameters to maintain cooperation. Simulation results show that the proposed framework can improve energy efficiency up to 36% relative to the traditional multicast scenario.
The Impact of Intranasal Oxytocin on Attention to Social Emotional Stimuli in Patients with Anorexia Nervosa: A Double Blind within-Subject Cross-over Experiment

Background and aim Social factors may be of importance causally and act as maintenance factors in patients with anorexia nervosa. Oxytocin is a neuromodulatory hormone involved in social emotional processing associated with attentional processes. This study aimed to examine the impact of oxytocin on attentional processes to social faces representing anger, disgust, and happiness in patients with anorexia nervosa. Method A double-blind, placebo-controlled within-subject crossover design was used. Intranasal oxytocin or placebo followed by a visual probe detection task with faces depicting anger, disgust, and happiness was administered to 64 female subjects: 31 patients with anorexia nervosa and 33 control students. Results Attentional bias to the disgust stimuli was observed in both groups under the placebo condition. The attentional bias to disgust was reduced under the oxytocin condition (a moderate effect in the patient group). Avoidance of angry faces was observed in the patient group under the placebo condition and vigilance was observed in the healthy comparison group; both of these information processing responses were moderated by oxytocin producing an increase in vigilance in the patients. Happy/smiling faces did not elicit an attentional response in controls or the patients under either the placebo or oxytocin conditions. Conclusion Oxytocin attenuated attentional vigilance to disgust in patients with anorexia nervosa and healthy controls. On the other hand, oxytocin changed the response to angry faces from avoidance to vigilance in patients but reduced vigilance to anger in healthy controls. We conclude that patients with anorexia nervosa appear to use different strategies/circuits to emotionally process anger from their healthy counterparts.
Task Switching and Novelty Processing Activate a Common Neural Network for Cognitive Control

The abrupt onset of a novel event captures attention away from, and disrupts, ongoing task performance. Less obvious is that intentional task switching compares with novelty-induced behavioral distraction. Here we explore the hypothesis that intentional task switching and attentional capture by a novel distracter both activate a common neural network involved in processing contextual novelty [Barcelo, F. , Periez, J. A. , & Knight, R. T. Think differently: A brain orienting response to task novelty. NeuroReport, 13, 18871892, 2002. ]. Event-related potentials were recorded in two task-cueing paradigms while 16 subjects sorted cards following either two (color or shape; two-task condition) or three (color, shape, or number; three-task condition) rules of action. Each card was preceded by a familiar tone cueing the subject either to switch or to repeat the previous rule. Novel sound distracters were interspersed in one of two blocks of trials in each condition. Both novel sounds and task-switch cues impaired responses to the following visual target. Novel sounds elicited novelty P3 potentials with their usual peak latency and frontal-central scalp distribution. Familiar tonal switch cues in the three- and two-task conditions elicited brain potentials with a similar latency and morphology as the novelty P3, but with relatively smaller amplitudes over frontal scalp regions. Covariance and principal component analyses revealed a sustained frontal negative potential that was distorting concurrent novelty P3 activity to the tonal switch cues. When this frontal negativity was statistically removed, P3 potentials to novel sounds and task-switch cues showed similar scalp topographies. The degree of activation in the novelty P3 network seemed to be a function of the information (entropy) conveyed by the eliciting stimulus for response selection, over and above its relative novelty, probability of occurrence, task relevance, or feedback value. We conclude that novelty P3 reflects transient activation in a neural network involved in updating task set information for goal-directed action selection and might thus constitute one key element in a central bottleneck for attentional control.
Addressing domestic violence through maternity services: policy and practice.

OBJECTIVE to explore current policies and practices in maternity units that aim to identify, assess and support women experiencing domestic violence. DESIGN AND SETTING a postal survey, conducted between June and October 1999, of all NHS Trusts in England and Wales that provided maternity services. PARTICIPANTS Heads of Midwifery or the midwife with expertise or interest in domestic violence in each Trust. MAIN OUTCOME MEASURES use of written policies and agreed practices for identifying and referring women experiencing domestic violence, such as availability of information, routine questioning of all women and offering women an appointment without their partner. RESULTS 87% (183) of the 211 NHS Trusts providing maternity care participated in the survey. Twelve per cent of units had written policies for identifying women experiencing domestic violence, and a further 30% had some form of agreed practice. Less than half of maternity units routinely offered women an appointment without their partner, and just over half displayed material about domestic violence in places where women receive maternity care. Only three units had undertaken audit on their domestic violence practices. CONCLUSIONS there is considerable variability around England and Wales in policies and practices related to domestic violence. It is evident that clear guidelines for identification and referral, training, audit and the integration of domestic violence policies with child protection and other policies are necessary to fully address the issues.
Information-theoretical Complexity Metrics

Information-theoretical complexity metrics are auxiliary hypotheses that link theories of parsing and grammar to potentially observable measurements such as reading times and neural signals. This review article considers two such metrics, Surprisal and Entropy Reduction, which are respectively built upon the two most natural notions of ‘information value’ for an observed event (Blachman 1968). This review sketches their conceptual background and touches on their relationship to other theories in cognitive science. It characterizes them as ‘lenses’ through which theorists ‘see’ the information-processing consequences of linguistic grammars. While these metrics are not themselves parsing algorithms, the review identifies candidate mechanisms that have been proposed for both of them.
Human Dendritic Cells Activate Resting Natural Killer (NK) Cells and Are Recognized via the NKp30 Receptor by Activated NK Cells

During the innate response to many inflammatory and infectious stimuli, dendritic cells (DCs) undergo a differentiation process termed maturation. Mature DCs activate antigen-specific naive T cells. Here we show that both immature and mature DCs activate resting human natural killer (NK) cells. Within 1 wk the NK cells increase two– to fourfold in numbers, start secreting interferon (IFN)-γ, and acquire cytolytic activity against the classical NK target LCL721.221. The DC-activated NK cells then kill immature DCs efficiently, even though the latter express substantial levels of major histocompatibility complex (MHC) class I. Similar results are seen with interleukin (IL)-2–activated NK cell lines and clones, i.e., these NK cells kill and secrete IFN-γ in response to immature DCs. Mature DCs are protected from activated NK lysis, but lysis takes place if the NK inhibitory signal is blocked by a human histocompatibility leukocyte antigen (HLA)-A,B,C–specific antibody. The NK activating signal mainly involves the NKp30 natural cytotoxicity receptor, and not the NKp46 or NKp44 receptor. However, both immature and mature DCs seem to use a NKp30 independent mechanism to act as potent stimulators for resting NK cells. We suggest that DCs are able to control directly the expansion of NK cells and that the lysis of immature DCs can regulate the afferent limb of innate and adaptive immunity.
Microrheology to explore protein and cell dynamics

In this thesis, I explore the applications of optical tweezers and passive video particle tracking microrheology for bioanalytical applications. Microrheology is a branch of rheology that has the same principles as conventional bulk rheology, but which works on micron length scales. Microrheological techniques relate the free or the driven motion of micron-sized tracer particles suspended in the fluid under investigation to the ‘elastic’ and ‘viscous’ components of the material. These components can be related to the dynamics of the molecules that make up the fluid, and thus microrheology has the potential to reveal new information about the microscopic properties of complex materials. Optical tweezers are sensitive instruments that have been used to apply forces on the order of pN and to measure the displacements down to nm of objects ranging in size from 10 nm to over 100μm, making them an essential tool for microrheology. Here, we have developed a new set of analytical methods for microrheological measurements of biological and bio-analytical systems. In particular, we have developed two new self-consistent procedures for measuring the linear viscoelastic properties of materials across the widest frequency range achievable with optical tweezers (Phys.Review E. (2010) 81:2, and J. Optics (2011) 13:4). Furthermore, we present a straightforward procedure for measuring the in vivo linear viscoelastic properties of single cells via passive video particle tracking microrheology of single beads attached to the cells’ exterior. Notably, the procedure presented here represents an alternative methodology that can be extended to many experimental formats and provides a simple addition to existing cellular physiology studies. In addition, we introduce new methodologies for deriving the concentration scaling laws of polymer and biopolymer solutions from microrheological measurements carried out with optical tweezers. These methods have been adopted to investigate the concentration scaling laws of in vitro reconstituted actin solutions and actin/myosin solutions
Unscented Rauch-Tung-Striebel Smoother

This note considers the application of the unscented transform to optimal smoothing of nonlinear state-space models. In this note, a new Rauch-Tung-Striebel type form of the fixed-interval unscented Kalman smoother is derived. The new smoother differs from the previously proposed two-filter-formulation-based unscented Kalman smoother in the sense that it is not based on running two independent filters forward and backward in time. Instead, a separate backward smoothing pass is used, which recursively computes corrections to the forward filtering result. The smoother equations are derived as approximations to the formal Bayesian optimal smoothing equations. The performance of the new smoother is demonstrated with a simulation.
A new code transformation technique for nested loops

For good performance of every computer program, good cache utilization is crucial. In numerical linear algebra libraries, good cache utilization is achieved by explicit loop restructuring (mainly loop blocking), but it requires a complicated memory pattern behavior analysis. In this paper, we describe a new source code transformation called dynamic loop reversal that can increase temporal and spatial locality. We also describe a formal method for predicting cache behavior and evaluate results of the model accuracy by the measurements on a cache monitor. The comparisons of the numbers of measured cache misses and the numbers of cache misses estimated by the model indicate that the model is relatively accurate and can be used in practice.
The Spatial Limitations of Current Neutral Models of Biodiversity

The unified neutral theory of biodiversity and biogeography is increasingly accepted as an informative null model of community composition and dynamics. It has successfully produced macro-ecological patterns such as species-area relationships and species abundance distributions. However, the models employed make many unrealistic auxiliary assumptions. For example, the popular spatially implicit version assumes a local plot exchanging migrants with a large panmictic regional source pool. This simple structure allows rigorous testing of its fit to data. In contrast, spatially explicit models assume that offspring disperse only limited distances from their parents, but one cannot as yet test the significance of their fit to data. Here we compare the spatially explicit and the spatially implicit model, fitting the most-used implicit model (with two levels, local and regional) to data simulated by the most-used spatially explicit model (where offspring are distributed about their parent on a grid according to either a radially symmetric Gaussian or a ‘fat-tailed’ distribution). Based on these fits, we express spatially implicit parameters in terms of spatially explicit parameters. This suggests how we may obtain estimates of spatially explicit parameters from spatially implicit ones. The relationship between these parameters, however, makes no intuitive sense. Furthermore, the spatially implicit model usually fits observed species-abundance distributions better than those calculated from the spatially explicit model's simulated data. Current spatially explicit neutral models therefore have limited descriptive power. However, our results suggest that a fatter tail of the dispersal kernel seems to improve the fit, suggesting that dispersal kernels with even fatter tails should be studied in future. We conclude that more advanced spatially explicit models and tools to analyze them need to be developed.
Major Variation in Carotid Bifurcation Anatomy: A Possible Risk Factor for Plaque Development?

Background and Purpose— Why is carotid plaque often so strikingly asymmetrical within individuals, and why does the extent of disease vary so considerably between individuals with similar systemic risk factors? Variability of carotid bifurcation anatomy is a possible explanation. Flow models suggest that vessel anatomy, in particular vessel diameter and area ratios, affects plaque formation at arterial bifurcations. However, carotid bifurcation anatomy could only be a major risk factor for plaque formation if it was sufficiently variable. Since very few data exist on the extent of interindividual and intraindividual variability of bifurcation anatomy, we studied 5395 angiograms from the European Carotid Surgery Trial. Methods— To minimize changes in bifurcation anatomy secondary to atherosclerosis, we excluded vessels with ≥30% stenosis. We measured arterial diameters at disease-free points and calculated the following ratios: internal to common carotid (ICA/CCA), external to common carotid (ECA/CCA), external to internal carotid (ECA/ICA), and outflow/inflow area. For intraindividual asymmetry, we compared the ratios on both sides. Results— Each ratio varied markedly between individuals. The 95% ranges were as follows: ICA/CCA, 0.44 to 0.86; ECA/CCA, 0.34 to 0.80; ECA/ICA, 0.55 to 1.33; and outflow/inflow area, 0.38 to 1.28. The results were very similar in 407 bifurcations with no disease. Among the 755 patients with <30% stenosis bilaterally, side differences of ≥25% were present in 17% (95% CI, 15% to 20%) for the ICA/CCA ratio, 27% (95% CI, 24% to 30%) for the ECA/CCA ratio, 32% (95% CI, 28% to 35%) for the ECA/ICA ratio, and 42% (95% CI, 38% to 45%) for the outflow/inflow area ratio. Conclusions— We found large interindividual differences in carotid bifurcation anatomy. For example, there was 4-fold variation of the ratio of outflow to inflow area. Intraindividual variation was also considerable. These data highlight the potential importance of anatomic variation as a risk factor for atheroma and provide a firm basis for flow modeling studies.