Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantifying the bias in the estimated treatment effect in randomized trials having interim analyses and a rule for early stopping for futility

In this paper, we consider the potential bias in the estimated treatment effect obtained from clinical trials, the protocols of which include the possibility of interim analyses and an early termination of the study for reasons of futility. In particular, by considering the conditional power at an interim analysis, we derive analytic expressions for various parameters of interest: (i) the underestimation or overestimation of the treatment effect in studies that stop for futility; (ii) the impact of the interim analyses on the estimation of treatment effect in studies that are completed, i.e. that do not stop for futility; (iii) the overall estimation bias in the estimated treatment effect in a single study with such a stopping rule; and (iv) the probability of stopping at an interim analysis.
Sleep Slow-Wave Activity Reveals Developmental Changes in Experience-Dependent Plasticity

Experience-dependent plasticity, the ability of the brain to constantly adapt to an ever-changing environment, has been suggested to be highest during childhood and to decline thereafter. However, empirical evidence for this is rather scarce. Slow-wave activity (SWA; EEG activity of 1–4.5 Hz) during deep sleep can be used as a marker of experience-dependent plasticity. For example, performing a visuomotor adaptation task in adults increased SWA during subsequent sleep over a locally restricted region of the right parietal cortex, which is known to be involved in visuomotor adaptation. Here, we investigated whether local experience-dependent changes in SWA vary as a function of brain maturation. Three age groups (children, adolescents, and adults) participated in a high-density EEG study with two conditions (baseline and adaptation) of a visuomotor learning task. Compared with the baseline condition, sleep SWA was increased after visuomotor adaptation in a cluster of eight electrodes over the right parietal cortex. The local boost in SWA was highest in children. Baseline SWA in the parietal cluster and right parietal gray matter volume, which both indicate region-specific maturation, were significantly correlated with the local increase in SWA. Our findings indicate that processes of brain maturation favor experience-dependent plasticity and determine how sensitive a specific brain region is for learning experiences. Moreover, our data confirm that SWA is a highly sensitive tool to map maturational differences in experience-dependent plasticity.
Regulatory T cells (Tregs): A major immune checkpoint to consider in combinatorial therapeutic HIV-1 vaccines

ABSTRACT The field of immunotherapeutics is living an exceptional time as new antibodies that take brakes off T-cells and unleash them on tumours are being approved by the US-Food and Drug Administration (FDA). For the design and development of an HIV-1 therapeutic-vaccine, one would need preferably to shift the balance T-effectors/T-regulatory cells (Teff/Tregs) towards effectors to improve vaccine-specific immune-responses. Given the success with the new immune-checkpoint-blockers (ICB), it is an appropriate time for HIV-1 field to seize this opportunity and develop new therapeutic vaccine-strategies that take into consideration ICB and other immunomodulators such as cytokines. While the vaccine is important to stimulate HIV-1-specific T-cell responses, cytokines will support the expansion of the stimulated virus-specific T-cells and ICB will reverse exhaustion and unchain cytotoxic T-cells. In this commentary, we will spotlight Tregs as another major brake for T-cell immunity and address the main stumbling-blocks that often blurs HIV-1-specific-Tregs status with regards to their role (beneficial or detrimental) and we will recall some proof-of-concept studies where therapeutic immunization skewed the HIV-1-specific response from Tregs to Teffs which impacts on the magnitude of viral replication. We will also suggest some strategies to shift the balance towards Teffs and potentiate HIV-1-specific immune-responses.
Sparse-to-Dense: Depth Prediction from Sparse Depth Samples and a Single Image

We consider the problem of dense depth prediction from a sparse set of depth measurements and a single RGB image. Since depth estimation from monocular images alone is inherently ambiguous and unreliable, to attain a higher level of robustness and accuracy, we introduce additional sparse depth samples, which are either acquired with a low-resolution depth sensor or computed via visual Simultaneous Localization and Mapping (SLAM) algorithms. We propose the use of a single deep regression network to learn directly from the RGB-D raw data, and explore the impact of number of depth samples on prediction accuracy. Our experiments show that, compared to using only RGB images, the addition of 100 spatially random depth samples reduces the prediction root-mean-square error by 50% on the NYU-Depth-v2 indoor dataset. It also boosts the percentage of reliable prediction from 59 % to 92 % on the KITTI dataset. We demonstrate two applications of the proposed algorithm: a plug-in module in SLAM to convert sparse maps to dense maps, and super-resolution for LiDARs. Software22https://github.com/fangchangma/sparse-to-dense and video demonstration33https://www.youtube. com/watch? v=vNIIT_M7×7Y are publicly available.
Micrasterias as a Model System in Plant Cell Biology

The unicellular freshwater alga Micrasterias denticulata is an exceptional organism due to its complex star-shaped, highly symmetric morphology and has thus attracted the interest of researchers for many decades. As a member of the Streptophyta, Micrasterias is not only genetically closely related to higher land plants but shares common features with them in many physiological and cell biological aspects. These facts, together with its considerable cell size of about 200 μm, its modest cultivation conditions and the uncomplicated accessibility particularly to any microscopic techniques, make Micrasterias a very well suited cell biological plant model system. The review focuses particularly on cell wall formation and composition, dictyosomal structure and function, cytoskeleton control of growth and morphogenesis as well as on ionic regulation and signal transduction. It has been also shown in the recent years that Micrasterias is a highly sensitive indicator for environmental stress impact such as heavy metals, high salinity, oxidative stress or starvation. Stress induced organelle degradation, autophagy, adaption and detoxification mechanisms have moved in the center of interest and have been investigated with modern microscopic techniques such as 3-D- and analytical electron microscopy as well as with biochemical, physiological and molecular approaches. This review is intended to summarize and discuss the most important results obtained in Micrasterias in the last 20 years and to compare the results to similar processes in higher plant cells.
Beyond supervised learning: A multi-perspective approach to outpatient physical therapy mentoring

ABSTRACT Background: Novice physical therapists face multiple challenges as they transition to autonomous, efficient, and seasoned therapists. Mentoring is known to facilitate growth among novice therapists; however, formalized mentoring programs within the outpatient setting are scarce or management-centered. This study sought to explore the most desired components of a formal mentoring program from multiple perspectives. Methods: An inductive qualitative inquiry explored perceptions of participants (n = 35) from four populations. Interviews were conducted with students (n = 5) and novice therapists (n = 5), and survey data was collected from faculty (n = 7) and expert therapists (n = 18). Thematic content analysis was used for data analysis. Results: Three primary themes emerged as program emphasis: 1) Program function; 2) novice therapists’ needs; and 3) the making of a mentorship (including mentor/mentee characteristics and matching strategy). Conclusions: This study captured multiple perspectives as to the components of interest in development of a formalized mentoring program for novice therapists in the outpatient setting. As the profession continues to emphasize standards for guided learning, steps must be taken by individual employers to promote and facilitate the most effective practices. Findings provide depth and suggestions for developing an outpatient-mentoring program.
The use of chemogenetics in behavioural neuroscience: receptor variants, targeting approaches and caveats

The last decade has seen major advances in neuroscience tools allowing us to selectively modulate cellular pathways in freely moving animals. Chemogenetic approaches such as designer receptors exclusively activated by designer drugs (DREADDs) permit the remote control of neuronal function by systemic drug administration. These approaches have dramatically advanced our understanding of the neural control of behaviour. Here, we review the different techniques and genetic approaches available for the restriction of chemogenetic receptors to defined neuronal populations. We highlight the use of a dual virus approach to target specific circuitries and the effectiveness of different routes of administration of designer drugs. Finally, we discuss the potential caveats associated with DREADDs including off‐target effects of designer drugs, the effects of chronic chemogenetic receptor activation and the issue of collateral projections associated with DREADD activation and inhibition.
Synergistic Effects of Nanosecond Pulsed Electric Fields Combined with Low Concentration of Gemcitabine on Human Oral Squamous Cell Carcinoma In Vitro

Treatment of cancer often involves uses of multiple therapeutic strategies with different mechanisms of action. In this study we investigated combinations of nanosecond pulsed electric fields (nsPEF) with low concentrations of gemcitabine on human oral cancer cells. Cells (Cal-27) were treated with pulse parameters (20 pulses, 100 ns in duration, intensities of 10, 30 and 60 kV/cm) and then cultured in medium with 0.01 µg/ml gemcitabine. Proliferation, apoptosis/necrosis, invasion and morphology of those cells were examined using MTT, flow cytometry, clonogenics, transwell migration and TEM assay. Results show that combination treatments of gemcitabine and nsPEFs exhibited significant synergistic activities versus individual treatments for inhibiting oral cancer cell proliferation and inducing apoptosis and necrosis. However, there was no apparent synergism for cell invasion. By this we demonstrated synergistic inhibition of Cal-27 cells in vitro by nsPEFs and gemcitabine. Synergistic behavior indicates that these two treatments have different sites of action and combination treatment allows reduced doses of gemcitabine and lower nsPEF conditions, which may provide better treatment for patients than either treatment alone while reducing systemic toxicities.
Video Scene Parsing with Predictive Feature Learning

Video scene parsing is challenging due to the following two reasons: firstly, it is non-trivial to learn meaningful video representations for producing the temporally consistent labeling map; secondly, such a learning process becomes more difficult with insufficient labeled video training data. In this work, we propose a unified framework to address the above two problems, which is to our knowledge the first model to employ predictive feature learning in the video scene parsing. The predictive feature learning is carried out in two predictive tasks: frame prediction and predictive parsing. It is experimentally proved that the learned predictive features in our model are able to significantly enhance the video parsing performance by combining with the standard image parsing network. Interestingly, the performance gain brought by the predictive learning is almost costless as the features are learned from a large amount of unlabeled video data in an unsupervised way. Extensive experiments over two challenging datasets, Cityscapes and Camvid, have demonstrated the effectiveness of our model by showing remarkable improvement over well-established baselines.
Spatial variation in otolith chemistry of Atlantic croaker larvae in the Mid-Atlantic Bight

Larval Atlantic croaker Micropogonias undulatus (1 to 7 mm in standard length) were collected on the east coast of the United States from North Carolina to Delaware during 2000. We defined 3 water-mass boundaries for potential groups of spawning Atlantic croaker using tempera- ture and salinity measured at each sampling station. We tested the hypothesis that distinct otolith chemistries existed among 3 groups of larval Atlantic croaker collected from these water masses using solution-based inductively coupled plasma-mass spectrometry. Multivariate analysis of vari- ance indicated that otolith chemistry differed significantly among water masses. Using a quadratic discriminant function, we were able to correctly classify fish from the Mid-Atlantic Bight (MAB) 73% of the time, South Atlantic Bight (SAB) 53% of the time, and Chesapeake Bay plume 36% of the time. The correct reclassification rates observed were significantly better than random. Results from this study indicate that it is possible to obtain measurable elemental concentrations from otoliths much smaller than previously analyzed (weight 0.015 to 1.976 µg). Moreover, contrary to previous studies, our results indicate that it is possible to distinguish natal signatures among larvae on different spawn- ing grounds in the MAB and SAB. Further, this new information could benefit investigations of dis- persal from offshore spawning grounds to estuaries or other nursery habitats.
Persistent suicide risk in clinically improved schizophrenia patients: challenge of the suicidal dimension

Background Suicide is a major problem in schizophrenia, estimated to affect 9%–13% of patients. About 25% of schizophrenic patients make at least one suicide attempt in their lifetime. Current outcome measures do not address this problem, even though it affects quality of life and patient safety. The aim of this study was to assess suicidality in long-term clinically improved schizophrenia patients who were treated in a nongovernmental psychiatric treatment centre in Mumbai, India. Method Participants were 61 patients out of 200 consecutive hospitalized first-episode patients with schizophrenia diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders who were much improved on the Clinical Global Impression Scale-Improvement (CGI-I) scale at the endpoint of a 10-year follow-up. Clinical assessment tools included the Positive and Negative Syndrome Scale for Schizophrenia, CGI-I, Global Assessment of Functioning, and suicidality. Results Many of the patients, although clinically improved, experienced emerging suicidality during the 10-year follow-up period. All of the patients reported significant suicidality (ie, suicide attempts, suicidal crises, or suicidal ideation) at the end of the study, whereas only 83% had reported previous significant suicidality at baseline. No sociodemographic and clinical variables at baseline were predictive of suicidal status at the end of the 10-year follow-up. Conclusion Schizophrenia is a complex neurobehavioral disorder that appears to be closely associated with suicidal behavior. Adequate assessment and management of suicidality needs to be a continual process, even in patients who respond well to treatment.
Multiple stable reference points in oyster populations: biological relationships for the eastern oyster (Crassostrea virginica)in Delaware Bay

Abstract—In the first of two companion papers, a 54-yr time series for the oyster population in the New Jersey waters of Delaware Bay was analyzed to develop biological relationships necessary to evaluate maximum sustainable yield (MSY) reference points and to consider how multiple stable points affect reference point-based management. The time series encompassed two regime shifts, one circa 1970 that ushered in a 15-yr period of high abundance, and a second in 1985 that ushered in a 20-yr period of low abundance. The intervening and succeeding periods have the attributes of alternate stable states. The biological relationships between abundance, recruitment, and mortality were unusual in four ways. First, the broodstock–recruitment relationship at low abundance may have been driven more by the provision of settlement sites for larvae by the adults than by fecundity. Second, the natural mortality rate was temporally unstable and bore a nonlinear relationship to abundance. Third, combined high abundance and low mortality, though likely requiring favorable environmental conditions, seemed also to be a self-reinforcing phenomenon. As a consequence, the abundance –mortality relationship exhibited both compensatory and depensatory components. Fourth, the geographic distribution of the stock was intertwined with abundance and mortality, such that interrelationships were functions both of spatial organization and inherent populatio
Ossification Pattern in Forelimbs of the Siamese Crocodile (Crocodylus siamensis): Similarity in Ontogeny of Carpus Among Crocodylian Species

Crocodylians have highly derived elongated carpus, which is related to their use of forelimbs in many types of gaits as well as in burrowing. The objective of present study was to describe the ossification of the forelimb in five stages of Siamese crocodile (Crocodylus siamensis). The ossification begins approximately at stage 20 in arm and forearm bones moving sequentially to the metacarpal elements. The first carpal elements with ossification centers are radiale + intermedium and ulnare (stage 22–23), and their ossification mode is typical of long bones. Between stages 22 and 24 distal carpals 3, 4, and 5 fuse together to a single formation. In the stage 25, the ossification proceeds to the pisiform, which starts ossifying late during the embryogenesis. The phalangeal formula of the digits is 2,3,4,5,3. Although there are some interspecific differences, it appears that all crocodylians have similarly uniform skeletal pattern, the process of ossification, number of carpal elements and phalangeal formulas probably due to their similar lifestyles. Anat Rec, 301:1159–1168, 2018. © 2018 Wiley Periodicals, Inc.
Reduction of false positives in prokaryotic mRNA differential display.

inverse PCR primers, P1 and P2, can be used to delete the same internal region from a series of DNA constructs containing the target region. Similarly, an internal deletion can be made by a PCR-ligation-PCR approach as described by Ali and Steinkasserer (1). According to this method, for example, the first-round PCR can be performed in two seperate reactions by primers V1/P2 and P1/V2, followed by ligation of the two PCR products and reamplification of the desired PCR product from the ligation mixture by primers V1/V2. The final PCR product will be equivalent to our PCR product after the second round of PCR. Compared with the method of Ali and Steinkasserer, our method has the following advantages. First, our procedure is completed by merely two PCRs instead of three. Second, our ligation is mostly a self-ligation with only a single ligated product with one orientation, while the method of Ali and Steinkasserer generates multiple products with different orientations, which can cause difficulty with identifying the correct PCR product in the end. Thus, our two-step PCR method is a useful alternative for generating an internal deletion.
A Theory of Mutual Funds: Optimal Fund Objectives and Industry Organization

This paper presents a model in which investors cannot remain in the market to trade at all times. As a result, they have an incentive to set up trading firms or financial market intermediaries (FMI's) to take over their portfolio while they engage in other activities. Previous research has assumed that such firms act like individuals endowed with a utility function. Here, as in reality, they are firms that simply take orders from their investors. From this setting emerges a theory of mutual funds and other FMI's (such as investment houses, banks, and insurance companies) with implications for their trading styles, as well as for their effects on asset prices. The model provides theoretical support for past empirical findings, and provides new empirical predictions which are tested in this paper.
Creep of Sylramic-iBN Fiber Tows at Elevated Temperature in Air and in Silicic Acid-Saturated Steam

Abstract : Stressed oxidation experiments on Sylramic-iBN fiber tows were performed to evaluate the novel fiber's mechanical performance, creep behavior, and creep mechanisms. This research effort investigated creep response of Sylramic-iBN fiber tows at elevated temperatures in both air and in silicic acid-saturated steam environments. Creep experiments were conducted at creep stresses ranging from 127 to 762 MPa at 400 deg C and 500 deg C in order to examine the mechanical behavior of the Sylramic-iBN fiber tows at temperatures below and above the melting point of boria (450 deg C). Sylramic-iBN fibers are known to have excellent creep resistance, better than most other non-oxide fibers and significantly better than oxide fibers. These fibers have a near-stoichiometric SiC composition, so they are a strong candidate for use in advanced aerospace CMCs. This research effort is a pilot program on the study of the effects of steam on Sylramic-iBN fibers. Previous attempts to study creep of SiC fiber tows in steam at elevated temperatures at the Air Force Institute of Technology's (AFIT) Mechanics of Advanced Aerospace Materials Research Laboratory have yielded inconclusive results. Prior work at AFIT showed that the steam extracted silicon from the fiber tow and became saturated with silicic acid (Si[OH]4) . As the steam traveled along the SiC fiber, it also chemically altered the fiber surface producing inconsistent chemical compositions along the length of the fiber tow specimen. Along the fiber portion exposed to the unsaturated steam, the fiber experienced a chemical change leading to material loss, while the fiber portion exposed to the saturated steam experienced a silica scale growth along the fiber surface. A new test facility had to be designed to accurately evaluate the effects of steam on SiC fibers. The facility design incorporated an apparatus for saturating steam with silicic acid prior to entering the test chamber.
Performance of a high-resolution depth-encoding PET detector module using linearly-graded SiPM arrays

The goal of this study was to exploit the excellent spatial resolution characteristics of a position-sensitive silicon photomultiplier (SiPM) and develop a high-resolution depth-of-interaction (DOI) encoding positron emission tomography (PET) detector module. The detector consists of a 30 × 30 array of 0.445 × 0.445 × 20 mm3 polished LYSO crystals coupled to two 15.5 × 15.5 mm2 linearly-graded SiPM (LG-SiPM) arrays at both ends. The flood histograms show that all the crystals in the LYSO array can be resolved. The energy resolution, the coincidence timing resolution and the DOI resolution were 21.8 ± 5.8%, 1.23 ± 0.10 ns and 3.8 ± 1.2 mm, respectively, at a temperature of −10 °C and a bias voltage of 35.0 V. The performance did not degrade significantly for event rates of up to 130 000 counts s−1. This detector represents an attractive option for small-bore PET scanner designs that simultaneously emphasize high spatial resolution and high detection efficiency, important, for example, in preclinical imaging of the rodent brain with neuroreceptor ligands.