Miracle-dz/UniFAR-FTUs huggingface dataset:
Modality-Specific Cognitive Function of Medial and Lateral Human Brodmann Area 6

Despite the fact that human Brodmann area 6 (BA6), a traditional “motor” area, is active during higher motor control involving various cognitive operations, the functional specialization within BA6 in the cognitive domain is essentially unknown. Furthermore, its functional relevance in cognition has been questioned because brain activity in BA6 during cognitive tasks has often been explained away as a concomitant, latent motor process. Therefore, we examined the structural-functional relationship of human BA6 in nonmotor cognitive functions and its functional relevance using both functional magnetic resonance imaging (fMRI) and repetitive transcranial magnetic stimulation (rTMS). Subjects performed mental-operation (MO) tasks in which they serially updated verbal and spatial mental representations (MO-v and MO-s). In the fMRI experiments, activity in the medial BA6 was more increased in MO-v, whereas the activity in the lateral BA6 in both hemispheres was more in MO-s. Low-frequency rTMS to the medial BA6 disrupted only the performance of MO-v, whereas rTMS to the lateral BA6 in both hemispheres disrupted only MO-s. Hence the converging results demonstrate a functional double dissociation in which medial BA6 has a critical role in updating verbal information and lateral BA6 has a role in updating spatial information. The present study provides direct physiological evidence of modality-specific cognitive function within human BA6.
Synthesis of Nucleo Aminooxy Acid Derivatives

Abstract Nucleobase-functionalized peptides have attracted increasing interest because of their well-ordered secondary structures and stability toward enzymatic degradations. We have designed and synthesized nucleo aminooxy acids as novel building blocks for nucleopeptides. Four nucleo aminooxy acid derivatives with cytosine or thymine in the side chain linked by an amide or a triazole moiety have been synthesized from l-serine.
Euclid near infrared spectrophotometer instrument concept and first test results at the end of phase B

The Euclid mission objective is to understand why the expansion of the Universe is accelerating by mapping the geometry of the dark Universe by investigating the distance-redshift relationship and tracing the evolution of cosmic structures. The Euclid project is part of ESA's Cosmic Vision program with its launch planned for 2020. The NISP (Near Infrared Spectro-Photometer) is one of the two Euclid instruments and is operating in the near-IR spectral region (0.9-2μm) as a photometer and spectrometer. The instrument is composed of: - a cold (135K) optomechanical subsystem consisting of a SiC structure, an optical assembly (corrector and camera lens), a filter wheel mechanism, a grism wheel mechanism, a calibration unit and a thermal control system - a detection subsystem based on a mosaic of 16 Teledyne HAWAII2RG cooled to 95K with their front-end readout electronic cooled to 140K, integrated on a mechanical focal plane structure made with Molybdenum and Aluminum. The detection subsystem is mounted on the optomechanical subsystem structure - a warm electronic subsystem (280K) composed of a data processing / detector control unit and of an instrument control unit that interfaces with the spacecraft via a 1553 bus for command and control and via Spacewire links for science data This presentation describes the architecture of the instrument at the end of the phase B (Preliminary Design Review), the expected performance, the technological key challenges and preliminary test results obtained on a detection system demonstration model.
ATM-Dependent Phosphorylation of MEF2D Promotes Neuronal Survival after DNA Damage

Mutations in the ataxia telangiectasia mutated (ATM) gene, which encodes a kinase critical for the normal DNA damage response, cause the neurodegenerative disorder ataxia-telangiectasia (AT). The substrates of ATM in the brain are poorly understood. Here we demonstrate that ATM phosphorylates and activates the transcription factor myocyte enhancer factor 2D (MEF2D), which plays a critical role in promoting survival of cerebellar granule cells. ATM associates with MEF2D after DNA damage and phosphorylates the transcription factor at four ATM consensus sites. Knockdown of endogenous MEF2D with a short-hairpin RNA (shRNA) increases sensitivity to etoposide-induced DNA damage and neuronal cell death. Interestingly, substitution of endogenous MEF2D with an shRNA-resistant phosphomimetic MEF2D mutant protects cerebellar granule cells from cell death after DNA damage, whereas an shRNA-resistant nonphosphorylatable MEF2D mutant does not. In vivo, cerebella in Mef2d knock-out mice manifest increased susceptibility to DNA damage. Together, our results show that MEF2D is a substrate for phosphorylation by ATM, thus promoting survival in response to DNA damage. Moreover, dysregulation of the ATM–MEF2D pathway may contribute to neurodegeneration in AT.
Sorafenib Enhances the Antitumor Effects of Chemoradiation Treatment by Downregulating ERCC-1 and XRCC-1 DNA Repair Proteins

Head and neck squamous cell carcinoma remains a challenging clinical problem because of the persisting high rate of local and distant failure due to the acquisition of chemo- and radioresistance. In this study, we examined if treatment with sorafenib, a potent inhibitor of Raf kinase and VEGF receptor, could reverse the resistant phenotype in tumor and tumor-associated endothelial cells, thereby enhancing the therapeutic efficacy of currently used chemoradiation treatment. We used both in vitro and in vivo models to test the efficacy of sorafenib either as a single agent or in combination with chemoradiation. Sorafenib, as a single agent, showed antitumor and angiogenesis properties, but the effects were more pronounced when used in combination with chemoradiation treatment. Sorafenib significantly enhanced the antiproliferative effects of chemoradiation treatment by downregulating DNA repair proteins (ERCC-1 and XRCC-1) in a dose-dependent manner. In addition, combination treatment significantly inhibited tumor cell colony formation, tumor cell migration, and tumor cell invasion. Combination treatment was also very effective in inhibiting VEGF-mediated angiogenesis in vitro. In a severe combined immunodeficient mouse xenograft model, combination treatment was very well tolerated and significantly inhibited tumor growth and tumor angiogenesis. Interestingly, following combination treatment, low-dose sorafenib treatment alone was highly effective as a maintenance regimen. Taken together, our results suggest a potentially novel strategy to use sorafenib to overcome chemo- and radioresistance in tumor and tumor-associated endothelial to enhance the effectiveness of the chemoradiation therapy. Mol Cancer Ther; 10(7); 1241–51. ©2011 AACR.
First human impacts and responses of aquatic systems: A review of palaeolimnological records from around the world

Lake sediments constitute natural archives of past environmental changes. Historically, research has focused mainly on generating regional climate records, but records of human impacts caused by land use and exploitation of freshwater resources are now attracting scientific and management interests. Long-term environmental records are useful to establish ecosystem reference conditions, enabling comparisons with current environments and potentially allowing future trajectories to be more tightly constrained. Here we review the timing and onset of human disturbance in and around inland water ecosystems as revealed through sedimentary archives from around the world. Palaeolimnology provides access to a wealth of information reflecting early human activities and their corresponding aquatic ecological shifts. First human impacts on aquatic systems and their watersheds are highly variable in time and space. Landscape disturbance often constitutes the first anthropogenic signal in palaeolimnological records. While the effects of humans at the landscape level are relatively easily demonstrated, the earliest signals of human-induced changes in the structure and functioning of aquatic ecosystems need very careful investigation using multiple proxies. Additional studies will improve our understanding of linkages between human settlements, their exploitation of land and water resources, and the downstream effects on continental waters.
Differential expression of cone opsin mRNA levels following experimental retinal detachment and reattachment.

PURPOSE To identify changes in S- and M-sensitive cone opsin gene expression following retinal detachment (RD) and reattachment. METHODS Cat retinas were detached for 1, 3, 7, or 28 days, or reattached after 1 h, 1 day, or 3 days of RD and fixed in 4% paraformaldehyde. Pieces of mid-peripheral retina were removed from the same region of each detached, normal (attached), and reattached retina and embedded in paraffin. Paraffin sections (8 mm) were processed for in situ hybridization using S- or M-cone opsins, rod opsin, or phosducin riboprobes in vitro transcribed from cat partial cDNAs. Labeled cells were counted to obtain the number of labeled cells/mm retina. RESULTS The number of cells labeled with the anti-sense cone opsin riboprobes, and the intensity of this label, decreased after RD. The number of cones labeled with the anti-sense S-opsin riboprobe decreased to 42% of normal at 3 days of RD. The number of M-opsin mRNA-positive cones decreased to 4% of normal at 3 days of RD. The number of cells positive for M-opsin or S-opsin mRNA recovered to near normal levels after reattachment. Phosducin and rod opsin mRNA labeling was near normal in surviving rod photoreceptors after RD. CONCLUSIONS Cones and rods behave differently after detachment. There are significant obstacles to overcome in order to study the responses of cones after RD because surviving cells no longer label with antibodies used as cone markers in normal retina. The results of this study show that: (1) After RD, surviving cones decrease their expression of opsin mRNA while rods do not; (2) Upon reattachment of the retina, the cones once again begin to express their opsins; (3) Most cones survive short-term detachments; and (4) Defects in cone-based vision after reattachment may not be based mainly on the loss of cones but due to other changes in these cells, for example, reduced phototransduction and/or changes in synaptic connectivity to second order neurons.
Parameter Optimization in Control Software Using Statistical Fault Localization Techniques

Embedded controllers for cyber-physical systems are often parameterized by look-up maps representing discretizations of continuous functions on metric spaces. For example, a non-linear control action may be represented as a table of pre-computed values, and the output action of the controller for a given input computed by using interpolation. For industrial-scale control systems, several man-hours of effort are spent in tuning the values within the look-up maps. %and sub-optimal performance is often associated with %inappropriate values in look-up maps. Suppose that during testing, the controller code is found to have sub-optimal performance. The parameter fault localization problem asks which parameter values in the code are potential causes of the sub-optimal behavior. We present a statistical parameter fault localization approach based on binary similarity coefficients and set spectra methods. Our approach extends previous work on (traditional) software fault localization to a quantitative setting where the parameters encode continuous functions over a metric space and the program is reactive. We have implemented our approach in a simulation workflow for control systems in Simulink. Given controller code with parameters (including look-up maps), our framework bootstraps the simulation workflow to return a ranked list of map entries which are deemed to have most impact on the performance. On a suite of industrial case studies with seeded errors, our tool was able to precisely identify the location of the errors.
Text-Enriched Representations for News Image Classification

Images have a prominent role in the communication of news on the Web. We propose a novel method for image classification with subject categories when limited annotated images are available for training the classifier. A neural network based encoder learns image representations from paired news images and their texts. Once trained, this encoder transforms any image to a text-enriched representation of the image, which is then used as input for the classifier that categorizes an image according to its subject category. We have trained classifiers with different amounts of annotated images and found that the image classifier that uses the text-enriched image representations outperforms a baseline model that only uses image features especially in cases with limited training examples.
Electron cryotomography reveals novel structures of a recently cultured termite gut spirochete

Electron cryotromography, a relatively new methodology in the field of microbiology, has been exploited by Murphy et al. (in this issue of Molecular Microbiology) in their analysis of the recently isolated termite gut spirochete Treponema primitia. Unique structures (bowls, arcades of hooks, cones at the cell ends, two layers of wall material) were evident from the analysis of its surface and internal constituents. These results, coupled to video microscopy analysis of swimming cells, allowed the authors to propose a model of cell motility. This highly significant paper highlights the importance of electron cryotomography to the field of microbiology. It also illustrates that newly cultured recalcitrant bacteria from complex environments are likely to possess novel structures not previously seen in other species.
Measurement of 3-D head kinematics in impact conditions employing six-accelerometers and three-angular rate sensors (6aω configuration)

The ability to measure 3-D head kinematics in motor vehicle crash conditions is important for assessing head-neck loads as well as brain injuries. A method for obtaining accurate 3-D head kinematics of post mortem human subjects (PMHS) in short duration impact conditions is proposed and validated in this study. The proposed methodology utilizes six accelerometers and three angular rate sensors (6aω configuration) such that an algebraic equation is used to determine angular acceleration with respect to the body-fixed coordinate system, and angular velocity is measured directly rather than numerically integrating the angular acceleration. Head impact tests to validate the method were conducted using the internal nine accelerometer head of the Hybrid III dummy and the proposed 6aω scheme in both low (2.3 m/s) and high (4.0 m/s) speed impact conditions. A rear impact sled test (10.5g and 24 km/h) using the Hybrid III dummy was also conducted to validate the 6aω scheme on a tetrahedron fixture which can be installed on the head of a PMHS. For both test conditions, the 6aω method was compared with a nine accelerometer array sensor package (NAP) as well as a configuration of three accelerometers and three angular rate sensors (3aω), both of which have been commonly used to measure 3-D kinematics of the head for assessment of brain and neck injuries. The ability of each of the three methods (6aω, 3aω, and NAP) to accurately measure 3-D head kinematics was quantified by calculating the normalized root mean squared deviation (NRMSD), which provides an average percent error over time. Results from the head impact tests indicate that angular acceleration obtained from the 6aω scheme was comparable to that determined from the NAP scheme, while angular acceleration derived from the 3aω scheme was not accurate in the high speed head impact condition. Results from the rear impact sled test indicate that all three schemes (NAP, 3aω and 6aω) provide accurate linear acceleration in the body-fixed coordinate system on the head as well as in the global coordinate system, while the 6aω and 3aω scheme produce more accurate results for the angular displacement (rotation) in the global coordinate system than the NAP scheme. Overall the proposed 6aω scheme provides more accurate kinematics in the global coordinate system and a more accurate transformation matrix at each time step, since the error due to numerical integration and numerical differentiation is minimized in the transformation of head kinematics to the global (inertial) coordinate system.
Sustained spatiotemporal release of TGF‐β1 confers enhanced very early chondrogenic differentiation during osteochondral repair in specific topographic patterns

The continuous presence of TGF‐β is critically important to induce effective chondrogenesis. To investigate chondrogenesis in a cartilage defect, we tested the hypothesis that the implantation of TGF‐β1‐releasing scaffolds improves very early cartilage repair in vivo. Spatiotemporal controlled release of TGF‐β1 was achieved from multiblock scaffolds that were implanted in osteochondral defects in the medial femoral condyles of adult minipigs. We observed a sustained presence of TGF‐β1 at 4 wk in vivo, which significantly promoted structural aspects of early overall cartilage repair, especially cellularity, cellular morphology, and safranin O staining intensity. Furthermore, early aggrecan and type II collagen production were both increased in specific topographic patterns in cartilaginous repair tissue. Sustained release of TGF‐β1 also increased cell numbers and proliferation, staining intensities for the stem cell surface marker, CD105, and number of stromal cell‐derived factor‐1 (SDF‐1) ‐positive cells within cartilaginous repair tissue. These data identify a mechanism by which TGF‐β1 modulates early chon‐ drogenesis by primarily increasing the number of progenitor cells arising from the subchondral bone marrow compartment via the SDF‐1/chemokine (CXC motif) receptor 4 pathway, their proliferation, differentiation, and extracellular matrix deposition in specific topographic patterns, highlighting the pivotal role played by TGF‐ β1 during this crucial phase. —Asen, A. ‐K. , Goebel, L. , Rey‐Rico, A. , Sohier, J., Zurakowski, D. , Cucchiarini, M. , Madry, H. Sustained spatiotemporal release of TGF‐β1 confers enhanced very early chondrogenic differentiation during osteochondral repair in specific topographic patterns. FASEB J. 32, 5298–5311 (2018). www.fasebj. org
L-Ascorbic Acid and α-Tocopherol Reduces Hepatotoxicity Associated with Arsenic Trioxide Chemotherapy by Modulating Nrf2 and Bcl2 Transcription Factors in Chang liver Cells

ABSTRACT Arsenic trioxide (As2O3) is a promising new regimen for the treatment of acute promyelocytic leukemia (APL). The induction of oxidative stress mediated by reactive oxygen species (ROS) and excessive intracellular calcium influx are the main reasons behind As2O3 toxicity. Since liver is the major organ for xenobiotic metabolism, it is always under stress. Antioxidant vitamins such as L-Ascorbic acid (L-AA) and α-Tocopherol (α-TOC) have been proposed to have beneficial effects against a variety of pathological conditions and are known by their free radical scavenging properties. The present study evaluates the curative efficacy of L-AA and α-TOC against As2O3 toxicity using immortalized human Chang liver cells. Our results suggest that L-AA (100 µM) and α-TOC (50 µM) recovered As2O3 (10 µM) cytotoxicity. Furthermore, As2O3 treatment showed an increase in lipid peroxidation and depletion in antioxidant status, mitochondrial trans membrane potential and values of total antioxidant capacity. Cotreatment of antioxidant vitamins with As2O3 resulted in a significant reversal of oxidative stress markers. Our findings substantiate the effect of antioxidant vitamins in protecting the hepatocytes from oxidative stress which may be attributed through Nrf2 (Nuclear factor erythroid 2-related factor 2) mediated upregulation of Bcl2 (B-cell lymphoma 2) expression.
Daily activity recognition based on DNN using environmental sound and acceleration signals

We propose a new method of recognizing daily human activities based on a Deep Neural Network (DNN), using multimodal signals such as environmental sound and subject acceleration. We conduct recognition experiments to compare the proposed method to other methods such as a Support Vector Machine (SVM), using real-world data recorded continuously over 72 hours. Our proposed method achieved a frame accuracy rate of 85.5% and a sample accuracy rate of 91.7% when identifying nine different types of daily activities. Furthermore, the proposed method outperformed the SVM-based method when an additional "Other" activity category was included. Therefore, we demonstrate that DNNs are a robust method of daily activity recognition.
On the Efficacy of Source Code Optimizations for Cache-Based Systems

Obtaining high performance without machine-specific tuning is an important goal of scientific application programmers. Since most scientific processing is done on commodity microprocessors with hierarchical memory systems, this goal of "portable performance" can be achieved if a common set of optimization principles is effective for all such systems. It is widely believed, or at least hoped, that portable performance can be realized. The rule of thumb for optimization on hierarchical memory systems is to maximize temporal and spatial locality of memory references by reusing data and minimizing memory access stride. We investigate the effects of a number of optimizations on the performance of three related kernels taken from a computational fluid dynamics application. Timing the kernels on a range of processors, we observe an inconsistent and often counterintuitive impact of the optimizations on performance. In particular, code variations that have a positive impact on one architecture can have a negative impact on another, and variations expected to be unimportant can produce large effects. Moreover, we find that cache miss rates - as reported by a cache simulation tool, and confirmed by hardware counters - only partially explain the results. By contrast, the compiler-generated assembly code provides more insight by revealing the importance of processor-specific instructions and of compiler maturity, both of which strongly, and sometimes unexpectedly, influence performance. We conclude that it is difficult to obtain performance portability on modern cache-based computers, and comment on the implications of this result.
Characterization of an epithelial cell line from bovine mammary gland

SummaryElucidation of the bovine mammary gland's unique characteristics depends on obtaining an authentic cell line that will reproduce its function in vitro. Representative clones from bovine mammary cell populations, differing in their attachment capabilities, were cultured. L-1 cells showed strong attachment to the plate, whereas H-7 cells detached easily. Cultures established from these clones were nontumorigenic upon transplantation to an immunodeficient host; they exhibited the epithelial cell characteristics of positive cytokeratin but not smooth muscle actin staining. Both cell lines depended on fetal calf serum for proliferation. They exhibited distinct levels of differentiation on Matrigel in serum-free, insulin-supplemented medium on the basis of their organization and β-lactoglobulin (BLG) secretion. H-7 cells organized into mammospheres, whereas L-1 cells arrested in a duct-like morphology. In both cell lines, prolactin activated phosphorylation of the signal transducer and activator of transcription, Stat5—a regulator of milk protein gene transcription, and of PHAS-I—an inhibitor of translation initiation in its nonphosphorylated form. De novo synthesis and secretion of BLG were detected in differentiated cultures: in L-1 cells, BLG was dependent on lactogenic hormones for maximal induction but was less stringently controlled than was β-casein in the mouse CID-9 cell line. L-1 cells also encompassed a near-diploid chromosomal karyotype and may serve as a tool for studying functional characteristics of the bovine mammary gland.