Miracle-dz/UniFAR-FTUs huggingface dataset:
Separating Lentiviral Vector Injection and Induction of Gene Expression in Time, Does Not Prevent an Immune Response to rtTA in Rats

Background Lentiviral gene transfer can provide long-term expression of therapeutic genes such as erythropoietin. Because overexpression of erythropoietin can be toxic, regulated expression is needed. Doxycycline inducible vectors can regulate expression of therapeutic transgenes efficiently. However, because they express an immunogenic transactivator (rtTA), their utility for gene therapy is limited. In addition to immunogenic proteins that are expressed from inducible vectors, injection of the vector itself is likely to elicit an immune response because viral capsid proteins will induce “danger signals” that trigger an innate response and recruit inflammatory cells. Methodology and Principal Findings We have developed an autoregulatory lentiviral vector in which basal expression of rtTA is very low. This enabled us to temporally separate the injection of virus and the expression of the therapeutic gene and rtTA. Wistar rats were injected with an autoregulatory rat erythropoietin expression vector. Two or six weeks after injection, erythropoietin expression was induced by doxycycline. This resulted in an increase of the hematocrit, irrespective of the timing of the induction. However, most rats only responded once to doxycycline administration. Antibodies against rtTA were detected in the early and late induction groups. Conclusions Our results suggest that, even when viral vector capsid proteins have disappeared, expression of foreign proteins in muscle will lead to an immune response.
Central Haemodynamics during Induction of Neurolept Anaesthesia in Patients with Arteriosclerotic Heart Disease

The haemodynamic changes occurring during induction of neurolept anaesthesia and intubation in patients with reduced cardiac reserve were compared with the haemodynamic changes observed prior to operation during the stress of moderate physical exercise in the same patients. Anaesthesia consisted of droperidolum NFN (Dehydrobenzperidol®), fentanyli citras NFN (Haldid®) and nitrous oxide‐oxygen with suxamethonium for intubation. The haemodynamic parameters measured were mean arterial blood pressure, central venous pressure, pulmonary artery mean pressure, pulmonary capillary wedge pressure and cardiac output. Blood volume was also measured, as were arterial blood‐gas tensions and pH. The haemodynamic changes observed during induction with intubation were significantly smaller than those observed preoperatively during exercise.
Computing the Bidiagonal SVD Using Multiple Relatively Robust Representations

We describe the design and implementation of a new algorithm for computing the singular value decomposition (SVD) of a real bidiagonal matrix. This algorithm uses ideas developed by Grosser and Lang that extend Parlett’s and Dhillon’s multiple relatively robust representations (MRRR) algorithm for the tridiagonal symmetric eigenproblem. One key feature of our new implementation is that $k$ singular triplets can be computed using only $\mathcal{O}(nk)$ storage units and floating point operations, where $n$ is the dimension of the matrix. The algorithm will be made available as routine xBDSCR in the upcoming new release of the LAPACK library.
Approval Summary: Azacitidine for Treatment of Myelodysplastic Syndrome Subtypes

Purpose: This article summarizes data submitted to the U.S. Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome. Experimental Design: In one phase 3 controlled trial, 191 study subjects were randomized to treatment with azacitidine or to observation; an additional 120 patients were treated with azacitidine in two phase 2 single arm studies. The primary efficacy end point was the overall response rate, defined as complete or partial normalization of peripheral blood counts and bone marrow blast percentages for at least 4 weeks. Results: In the controlled trial, the overall response rate was 15.7% in the azacitidine treatment group; there were no responders in the observation group (P < 0.0001). Response rates were similar in the two single arm studies. During response patients stopped being red cell or platelet transfusion dependent. Median duration of responses was at least 9 months. An additional 19% of azacitidine-treated patients had less than partial responses, most becoming transfusion independent. The most common adverse events attributed to azacitidine were gastrointestinal, hematologic, local (injection site), and constitutional. There were no azacitidine-related deaths. Conclusions: On May 19, 2004 the U.S. Food and Drug Administration approved azacitidine as injectable suspension for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Full prescribing information is available at http://www.fda. gov/cder/foi/label/2004/050794lbl.pdf. Azacitidine is the first agent approved for treatment of myelodysplastic syndrome.
Dynamic 3D avatar creation from hand-held video input

We present a complete pipeline for creating fully rigged, personalized 3D facial avatars from hand-held video. Our system faithfully recovers facial expression dynamics of the user by adapting a blendshape template to an image sequence of recorded expressions using an optimization that integrates feature tracking, optical flow, and shape from shading. Fine-scale details such as wrinkles are captured separately in normal maps and ambient occlusion maps. From this user- and expression-specific data, we learn a regressor for on-the-fly detail synthesis during animation to enhance the perceptual realism of the avatars. Our system demonstrates that the use of appropriate reconstruction priors yields compelling face rigs even with a minimalistic acquisition system and limited user assistance. This facilitates a range of new applications in computer animation and consumer-level online communication based on personalized avatars. We present realtime application demos to validate our method.
Coevolving programs and unit tests from their specification

Writing a formal specification before implementing a program helps to find problems with the system requirements. The requirements might be for example incomplete and ambiguous. Fixing these types of errors is very difficult and expensive during the implementation phase of the software development cycle. Although writing a formal specification is usually easier than implementing the actual code, writing a specification requires time, and often it is preferred, instead, to use this time on the implementation. In this paper we introduce for the first time a framework that might evolve any possible generic program from its specification. We use the Genetic Programming to evolve the programs, and at the same time we exploit the specifications to coevolve sets of unit tests. Programs are rewarded on how many tests they do not fail, whereas the unit tests are rewarded on how many programs they make fail. We present and analyse four different problems on which this novel technique is successfully applied.
Circadian dysfunction in P23H rhodopsin transgenic rats: effects of exogenous melatonin

Abstract: This study focuses on the effects of retinal degeneration on the circadian patterns of P23H rats, as well as on the effect of exogenous melatonin administration. To this end, the body temperature of P23H and Sprague–Dawley rats was continuously monitored and their retinas examined at different stages of degeneration, by means of histological labeling and electroretinogram recordings. Melatonin (2 mg/kg BW/day) was supplied ad libitum throughout the experiment to a subset of animals. The body temperature recordings from wild‐type and mutant animals showed no differences in the periodogram and the pattern of the mean waveform. However, a progressive decrease in the relative amplitude of the rhythm (RA), a decline in the coupling strength of the rhythm to environmental zeitgebers (interdaily stability, IS) and increased rhythm fragmentation (intradaily variability, IV) were observed in P23H rats, when compared to wild‐type animals. The P23H animals showed a progressive decrease in light‐induced retinal responses until reaching 18 months of age. By this age, all photoreceptors had already disappeared, and no responses were found in the EGRs. Exogenous administration of melatonin improved the visual response of P23H rats. In fact, the maximum b‐wave recorded at 14 months of age was significantly higher in melatonin‐treated P23H rats than in the control animals. Furthermore, the maximum b‐wave recorded for P23H rats at the age of 14 months significantly correlated with RA, IS, and IV. This leads us to conclude that vision loss in P23H rats is correlated with a progressive fragmentation of their circadian patterns. Both effects are partially reversed by melatonin administration.
Conservation Laws, Hamiltonian Structure, Modulational Instability Properties and Solitary Wave Solutions for a Higher‐Order Model Describing Nonlinear Internal Waves

Recent theoretical advances in connecting the wave‐induced mean flow with the conserved pseudomomentum per unit mass has permitted the first rational derivation of a model that describes the weakly nonlinear propagation of internal gravity plane waves in a continuously stratified fluid. Depending on the particular parameter regime examined the new model corresponds to an extended bright or dark derivative nonlinear Schrödinger equation or an extended complex‐valued modified Korteweg‐de Vries or Sasa–Satsuma equation. Mass, momentum, and energy conservation laws are derived. A noncanonical infinite‐dimensional Hamiltonian formulation of the model is introduced. The modulational stability characteristics associated with the Stokes wave solution of the model are described. The bright and dark solitary wave solutions of the model are obtained.
Are mastectomy rates really increasing in the United States?

PURPOSE After the National Institutes of Health Consensus Statement in 1990, breast-conserving surgery (BCS) became more common while mastectomy rates decreased. However, several recently published single-institution studies have reported an increase in mastectomy rates in the past decade. We conducted a population-based study to evaluate national trends in the surgical treatment of breast cancer from 2000 through 2006. PATIENTS AND METHODS Using the Surveillance, Epidemiology, and End Results database, we conducted a retrospective cohort analysis of women undergoing surgical treatment for breast cancer. We evaluated variation in mastectomy rates by demographic and tumor factors and calculated differences in mastectomy rates across time. We utilized logistic regression to identify time trends and patient and tumor factors associated with mastectomy, testing for significance using two-sided methods. RESULTS We identified 233,754 patients diagnosed with ductal carcinoma in situ or stage I to III unilateral breast cancer from 2000 to 2006. The proportion of women treated with mastectomy decreased from 40.8% in 2000 to 37.0% in 2006 (P < .001). These patterns were maintained across patient and tumor factors. Although the unilateral mastectomy rate decreased during the study period, the contralateral prophylactic mastectomy rate increased. Women were less likely to receive mastectomy over time (odds ratio, 1.18 for 2000 v 2006; 95% CI, 1.14 to 1.23; P < .0001), after adjusting for patient and tumor factors. CONCLUSION In contrast to single-institution studies, our population-based analysis found a decrease in unilateral mastectomy rates from 2000 to 2006 in the United States. Variations in referral patterns and patient selection are potential explanations for these differences between single institutions and national trends.
No match for money: Even in intimate relationships and collectivistic cultures, reminders of money weaken sociomoral responses

Abstract The present research tested two competing hypotheses: (1) as money cues activate an exchange orientation to social relations, money cues harm prosocial responses in communal and collectivistic settings; (2) as money can be used to help close others, money cues increase helping in communal or collectivistic settings. In a culture, characterized by strong helping norms, money cues reduced the quality of help given (Experiment 1), and lowered perceived moral obligation to help (Experiment 2). In communal relationships, money reminders decreased willingness to help romantic partners (Experiment 3). This effect was attenuated among people high on communal strength, although money cues made them upset with help requests (Experiment 4). Thus, the harmful effects of money on prosocial responses appear robust.
Constellation Subset Selection: Theories and Algorithms

Constellation subset selection is a new topic emerging in the adaptive modulation communications. How to choose the subset of the original constellation phasers appears to be challenging and interesting to the researchers. There hardly exists any literature which studies the feasibility and the solution of constellation subset selection in details. Here we dedicate to this problem in both theoretical exploration and algorithm design. In this paper, we introduce the detailed theoretical analysis regarding the mathematical properties of the commonly-used constellations and then facilitate the constellation subset selection problem. Based on our problem formulation, we design two algorithms to solve this problem thereby. Our complexity analysis evinces the effectiveness of the proposed algorithms.
Translation dynamics of single mRNAs in live cells and neurons

The when, where, and how of translation High-resolution single-molecule imaging shows the spatial and temporal dynamics of molecular events (see the Perspective by Iwasaki and Ingolia). Wu et al. and Morisaki et al. developed an approach to study the translation of single messenger RNAs (mRNAs) in live cells. Nascent polypeptides containing multimerized epitopes were imaged with fluorescent antibody fragments, while simultaneously detecting the single mRNAs using a different fluorescent tag. The approach enabled a direct readout of initiation and elongation, as well as revealing the spatial distribution of translation and allowing the correlation of polysome motility with translation dynamics. Membrane-targeted mRNAs could be distinguished from cytoplasmic mRNAs, as could single polysomes from higher-order polysomal complexes. Furthermore, the work reveals the stochasticity of translation, which can occur constitutively or in bursts, much like transcription, and the spatial regulation of translation in neuronal dendrites. Science, this issue p. 1430, p. 1425; see also p. 1391 Single-molecule imaging of nascent proteins reveals translation dynamics in the endoplasmic reticulum and neuronal dendrites. Translation is the fundamental biological process converting mRNA information into proteins. Single-molecule imaging in live cells has illuminated the dynamics of RNA transcription; however, it is not yet applicable to translation. Here, we report single-molecule imaging of nascent peptides (SINAPS) to assess translation in live cells. The approach provides direct readout of initiation, elongation, and location of translation. We show that mRNAs coding for endoplasmic reticulum (ER) proteins are translated when they encounter the ER membrane. Single-molecule fluorescence recovery after photobleaching provides direct measurement of elongation speed (5 amino acids per second). In primary neurons, mRNAs are translated in proximal dendrites but repressed in distal dendrites and display “bursting” translation. This technology provides a tool with which to address the spatiotemporal translation mechanism of single mRNAs in living cells.
Image completion with dynamic patches

This paper presents an approach of structure-preserving image completion with dynamic patches. Existing image completion methods may generate unnatural abnormal structures or structure disorders due to limited patches and patterns availability. Our structure-preserving image completion utilizes objective function minimization considering the coherence not only within the image cavity but also with global constraints. A series of dynamic patch-based optimizations are applied to fulfill the cavity. Unlike traditional fixed-size patch-based methods, our image completion with competitive dynamic patch-matching mechanism provides more effective structure restoration. Parallel searching of different-sized patches is performed to retrieve optimal patches for completing the image cavity with nice structure preservation. The experiments show that the realistic completed images by our approach are visually pleasing with nice structural coherence.
Mitochondrial reactive oxygen species are required for hypoxia‐induced degradation of keratin intermediate filaments

Hypoxia can cause stress and structural changes to the epithelial cytoskeleton. The intermediate filament (IF) network is known to reorganize in response to stress. We examined whether rats exposed to hypoxia had altered keratin IF expression in their alveolar epithelial type II (ATII) cells. There was a significant decrease in keratin protein levels in hypoxic ATII cells compared with those in ATII cells isolated from normoxic rats. To define the mechanisms regulating this process we studied changes to the keratin IF network in A549 cells (an alveolar epithelial cell line) exposed to 1.5% oxygen. We observed a time‐dependent disassembly‐degradation of keratin 8 and 18 proteins, which was associated with an increase in reactive oxygen species (ROS). Hypoxia‐treated A549 cells deficient in mitochondrial DNA or A549 cells treated with a small interfering RNA against the Rieske iron‐sulfur protein of mitochondrial complex III did not have increased levels of ROS nor was the keratin IF network disassembled and degraded. The superoxide dismutase (SOD)/catalase mimetic (EUK‐134) prevented the hypoxia‐mediated keratin IF degradation as did the overexpression of SOD1 but not of SOD2. Accordingly, we provide evidence that hypoxia promotes the disassembly and degradation of the keratin IF network via mitochondrial complex III‐generated reactive oxygen species. —N. , Chandel, N. S. , Litvan, J., Ridge, K. M. Mitochondrial reactive oxygen species are required for hypoxia‐induced degradation of keratin intermediate filaments. FASEB J. 24, 799–809 (2010). www.fasebj. org
The Soil Moisture Active Passive Validation Experiment 2012 (SMAPVEX12): Prelaunch Calibration and Validation of the SMAP Soil Moisture Algorithms

The National Aeronautics and Space Administration (NASA) Soil Moisture Active Passive (SMAP) satellite is scheduled for launch in January 2015. In order to develop robust soil moisture retrieval algorithms that fully exploit the unique capabilities of SMAP, algorithm developers had identified a need for long-duration combined active and passive L-band microwave observations. In response to this need, a joint Canada-U.S. field experiment (SMAPVEX12) was conducted in Manitoba (Canada) over a six-week period in 2012. Several times per week, NASA flew two aircraft carrying instruments that could simulate the observations the SMAP satellite would provide. Ground crews collected soil moisture data, crop measurements, and biomass samples in support of this campaign. The objective of SMAPVEX12 was to support the development, enhancement, and testing of SMAP soil moisture retrieval algorithms. This paper details the airborne and field data collection as well as data calibration and analysis. Early results from the SMAP active radar retrieval methods are presented and demonstrate that relative and absolute soil moisture can be delivered by this approach. Passive active L-band sensor (PALS) antenna temperatures and reflectivity, as well as backscatter, closely follow dry down and wetting events observed during SMAPVEX12. The SMAPVEX12 experiment was highly successful in achieving its objectives and provides a unique and valuable data set that will advance algorithm development.
The Gesture Imitation in Alzheimer's Disease Dementia and Amnestic Mild Cognitive Impairment.

BACKGROUND Alzheimer's disease dementia (ADD) has become an important health problem in the world. Visuospatial deficits are considered to be an early symptom besides memory disorder. OBJECTIVES The gesture imitation test was devised to detect ADD and amnestic mild cognitive impairment (aMCI). METHODS A total of 117 patients with ADD, 118 with aMCI, and 95 normal controls were included in this study. All participants were administered our gesture imitation test, the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Clock Drawing Test (CDT), and the Clinical Dementia Rating Scale (CDR). RESULTS Patients with ADD performed worse than normal controls on global scores and had a lower success rate on every item (p < 0.001). The area under the curve (AUC) for the global scores when comparing the ADD and control groups was 0.869 (p < 0.001). Item 4 was a better discriminator with a sensitivity of 84.62% and a specificity of 67.37%. The AUC for the global scores decreased to 0.621 when applied to the aMCI and control groups (p = 0.002). After controlling for age and education, the gesture imitation test scores were positively correlated with the MMSE (r = 0.637, p < 0.001), the MoCA (r = 0.572, p < 0.001), and the CDT (r = 0.514, p < 0.001) and were negatively correlated with the CDR scores (r = -0.558, p < 0.001). CONCLUSIONS The gesture imitation test is an easy, rapid tool for detecting ADD, and is suitable for the patients suspected of mild ADD and aMCI in outpatient clinics.
A new diarylheptanoid and a new diarylheptanoid glycoside isolated from the roots of Juglans mandshurica and their anti-inflammatory activities

Abstract A new diarylheptanoid, (2S,3S,5S)-2,3,5-trihydroxy-1,7-bis(4-hydroxy- 3-methoxyphenyl)heptane (1), and a new diarylheptanoid glycoside, (2S,3S,5S)-2,3-dihydroxy-5-O-β-d-xylopyranosyl-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)heptane (2), together with three known compounds, rhoiptelol C (3), rhoiptelol B (4) and 3′,4″-epoxy-2-O-β-d-glucopyanosyl-1-(4-hydroxyphenyl)- 7-(3-methoxyphenyl)heptan-3-one (5) were isolated from the roots of Juglans mandshurica (Juglandaceae). The structures of compounds 1 and 2 were identified based on HR-ESI-MS, 1D and 2D NMR spectroscopic methods. Compounds 1–5 were assayed for their inhibitory effects on the production of NO, TNF-α and IL-6 in LPS-stimulated RAW264.7 cells.
Elastic Behavior of Cross-Linked and Bundled Actin Networks

Networks of cross-linked and bundled actin filaments are ubiquitous in the cellular cytoskeleton, but their elasticity remains poorly understood. We show that these networks exhibit exceptional elastic behavior that reflects the mechanical properties of individual filaments. There are two distinct regimes of elasticity, one reflectingbendingof single filaments and a second reflectingstretchingof entropic fluctuations of filament length. The mechanical stiffness can vary by several decades with small changes in cross-link concentration, and can increase markedly upon application of external stress. We parameterize the full range of behavior in a state diagram and elucidate its origin with a robust model.