Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Cytomegalovirus IE2 Protein Disturbs Brain Development by the Dysregulation of Neural Stem Cell Maintenance and the Polarization of Migrating Neurons

ABSTRACT Despite the high incidence of severe defects in the central nervous system caused by human cytomegalovirus (HCMV) congenital infection, the mechanism of HCMV neuropathogenesis and the roles of individual viral genes have not yet been fully determined. In this study, we show that the immediate-early 2 (IE2) protein may play a key role in HCMV-caused neurodevelopmental disorders. IE2-transduced neural progenitor cells gave rise to neurospheres with a lower frequency and produced smaller neurospheres than control cells in vitro, indicating reduction of self-renewal and expansion of neural progenitors by IE2. At 2 days after in utero electroporation into the ventricle of the developing brain, a dramatically lower percentage of IE2-expressing cells was detected in the ventricular zone (VZ) and cortical plate (CP) compared to control cells, suggesting that IE2 concurrently dysregulates neural stem cell maintenance in the VZ and neuronal migration to the CP. In addition, most IE2+ cells in the lower intermediate zone either showed multipolar morphology with short neurites or possessed nonradially oriented processes, whereas control cells had long, radially oriented monopolar or bipolar neurites. IE2+ callosal axons also failed to cross the midline to form the corpus callosum. Furthermore, we provide molecular evidence that the cell cycle arrest and DNA binding activities of IE2 appear to be responsible for the increased neural stem cell exit from the VZ and cortical migrational defects, respectively. Collectively, our results demonstrate that IE2 disrupts the orderly process of brain development in a stepwise manner to further our understanding of neurodevelopmental HCMV pathogenesis. IMPORTANCE HCMV brain pathogenesis has been studied in limited experimental settings, such as in vitro HCMV infection of neural progenitor cells or in vivo murine CMV infection of the mouse brain. Here, we show that IE2 is a pivotal factor that contributes to HCMV-induced abnormalities in the context of the embryonic brain using an in utero gene transfer tool. Surprisingly, IE2, but not HCMV IE1 or murine CMV ie3, interferes pleiotropically with key neurodevelopmental processes, including neural stem cell regulation, proper positioning of migrating neurons, and the callosal axon projections important for communication between the hemispheres. Our data suggest that the wide spectrum of clinical outcomes, ranging from mental retardation to microcephaly, caused by congenital HCMV infection can be sufficiently explained in terms of IE2 action alone.
A wideband programmable-gain amplifier for 60GHz applications in 65nm CMOS

In this paper, a novel circuit topology of programmable-gain amplifier (PGA) is presented for 60GHz applications. To attain wideband characteristics, a modified Cherry-Hooper amplifier is employed as the gain cell while series binary-weighted resistor networks are adopted in both the feedback path and the source degeneration. As a result, a pseudo-exponential approximation is performed, leading to programmable linear-in-dB gain-tuning operations. By cascading four gain cells along with a dc offset cancellation circuit and an output buffer stage, a 3-bit digital-controlled wideband PGA is implemented. Fabricated in a 65nm CMOS process, the proposed PGA exhibits a 3dB bandwidth more than 1.92 GHz and a dB-linear gain range from -9.6 to 34.5 dB with a maximum gain error of ±0.54 LSB. The core circuit consumes a dc power of 4.9 mW from a 1-V supply voltage while the chip occupies a small active area of 0.03 mm2.
Efficient program tracing and monitoring through power consumption - with a little help from the compiler

Ensuring correctness and enforcing security are growing concerns given the complexity of modern connected devices and safety-critical systems. A promising approach is non-intrusive runtime monitoring through reconstruction of program execution traces from power consumption measurements. This can be used for verification, validation, debugging, and security purposes. In this paper, we propose a framework for increasing the effectiveness of power-based program tracing techniques. These systems determine the most likely block of source code that produced an observed power trace (CPU power consumption as a function of time). Our framework maximizes distinguishability between power traces for different code blocks. To this end, we provide a special compiler optimization stage that reorders intermediate representation (IR) and determines the reorderings that lead to power traces with highest distances between each other, thus reducing the probability of misclassification. Our work includes an experimental evaluation, using LLVM for an ARM architecture. Experimental results confirm the effectiveness of our technique.
Early Increases in Bile Acids Post Roux-en-Y Gastric Bypass Are Driven by Insulin-Sensitizing, Secondary Bile Acids.

CONTEXT Roux-en-Y gastric bypass (RYGB) is the most effective treatment for morbid obesity and resolution of diabetes. Over the last decade, it has become well accepted that this resolution of diabetes occurs before significant weight loss; however, the mechanisms behind this effect remain unknown and could represent novel therapeutic targets for obesity and diabetes. Bile acids have been identified as putative mediators of these weight loss-independent effects. OBJECTIVE To identify the longitudinal changes in bile acids after RYGB, which may provide mechanistic insight into the weight loss-independent effects of RYGB. DESIGN Observational study before/after intervention. SETTING Academic medical center. PATIENTS/PARTICIPANTS Samples were collected from morbidly obese patients (n = 21) before and after RYGB. INTERVENTION RYGB. MAIN OUTCOME MEASURES Seventeen individual bile acid species were measured preoperatively and at 1, 6, 12, and 24 months postoperatively. Anthropometric, hormonal, and hyperinsulinemic-euglycemic clamp data were also examined to identify physiological parameters associated with bile acid changes. RESULTS Fasting total plasma bile acids increased after RYGB; however, increases were bimodal and were observed only at 1 (P < .05) and 24 months (P < .01). One-month increases were secondary to surges in ursodeoxycholic acid and its glycine and taurine conjugates, bacterially derived bile acids with putative insulin-sensitizing effects. Increases at 24 months were due to gradual rises in primary unconjugated bile acids as well as deoxycholic acid and its glycine conjugate. Plasma bile acid changes were not significantly associated with any anthropometric or hormonal measures, although hepatic insulin sensitivity was significantly improved at 1 month. CONCLUSIONS Overall findings suggest that bacterially derived bile acids may mediate the early improvements at 1 month after RYGB. Future studies should examine the changes in specific bile acid chemical species after bariatric procedures and bile acid-specific signaling changes.
Polyunsaturated fatty acids influence inflammatory markers in a cellular model for canine osteoarthritis

Although it is well recognized that dietary supplementation with fish oil improves clinical symptoms in dogs suffering from osteoarthritis, the molecular basis for the dietary benefit is not yet completely resolved in dogs. This study was designed to further clarify how polyunsaturated fatty acids (PUFA) affect key factors of cartilage degeneration in a canine cell culture system mimicking osteoarthritis. Canine chondrocytes were incubated either without or with 10 μm of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA) or 3.6 μm ibuprofen (Ibu) as positive control for 6 days. After the supplementation, cells were stimulated with 10 ng/ml interleukin-1β (IL-1β) for another 48 hr to induce osteoarthritic changes, or left unstimulated. We analysed fatty acid uptake via gas-liquid chromatography, nitric oxide (NO) production via Griess assay, prostaglandin E (PGE) production via ELISA and relative gene expression of several cartilage matrix proteinases, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 via RT-qPCR. After supplementation, the chondrocytes rapidly incorporated the PUFA into their fatty acid pools. The stimulation with IL-1β caused a marked increase of most of the inflammatory markers measured. N-3 PUFA EPA reduced IL-induced gene expression of iNOS and corresponding production of NO. N-6 PUFA AA also decreased iNOS and NO, but furthermore lowered gene expression of matrix metalloproteinase-3. On the other hand, AA upregulated the aggrecanase ADAMTS-5 and augmented the release of PGE. The effect of n-3 PUFA DHA turned out to be negligible. Our results reveal molecular mechanisms by which PUFA affect degenerative joint disease in dogs. Of particular importance is that not only EPA but also AA decreased several inflammatory markers in our model. Thus, we conclude that an appropriate balance of both n-3 and n-6 fatty acids deserves more attention in dietary interventions.
Dynamics of genomic innovation in the unicellular ancestry of animals

Which genomic innovations underpinned the origin of multicellular animals is still an open debate. Here, we investigate this question by reconstructing the genome architecture and gene family diversity of ancestral premetazoans, aiming to date the emergence of animal-like traits. Our comparative analysis involves genomes from animals and their closest unicellular relatives (the Holozoa), including four new genomes: three Ichthyosporea and Corallochytrium limacisporum. Here, we show that the earliest animals were shaped by dynamic changes in genome architecture before the emergence of multicellularity: an early burst of gene diversity in the ancestor of Holozoa, enriched in transcription factors and cell adhesion machinery, was followed by multiple and differently-timed episodes of synteny disruption, intron gain and genome expansions. Thus, the foundations of animal genome architecture were laid before the origin of complex multicellularity – highlighting the necessity of a unicellular perspective to understand early animal evolution. DOI: http://dx.doi. org/10.7554/eLife.26036. 001
Tinnitus: Prospects for Pharmacological Interventions With a Seesaw Model

Chronic tinnitus, the perception of lifelong constant ringing in ear, is one capital cause of disability in modern society. It is often present with various comorbid factors that severely affect quality of life, including insomnia, deficits in attention, anxiety, and depression. Currently, there are limited therapeutic treatments for alleviation of tinnitus. Tinnitus can involve a shift in neuronal excitation/inhibition (E/I) balance, which is largely modulated by ion channels and receptors. Thus, ongoing research is geared toward pharmaceutical approaches that modulate the function of ion channels and receptors. Here, we propose a seesaw model that delineates how tinnitus-related ion channels and receptors are involved in homeostatic E/I balance of neurons. This review provides a thorough account of our current mechanistic understanding of tinnitus and insight into future direction of drug development.
Transmitted phase code/receive filter design for high reverberating environment: A cognitive approach

In this paper, we consider the problem of knowledge-aided transmit signal and receive filter design for a point-like target embedded in a high reverberating signal dependent environment. We focus on phase-only waveforms and devise a constrained optimization procedure which sequentially improves the Signal to Interference plus Noise Ratio (SINR), forcing a similarity constraint between the transmitted signal and a known radar waveform sharing a good ambiguity function. The computational complexity of the proposed algorithm is linear with the number of iterations and polynomial with the receive filter length. At the analysis stage, the performances of the technique are assessed in the presence of a homogeneous clutter scenario.
Influenza A Virus in Backyard Pigs and Poultry in Rural Cambodia

Surveillance of influenza virus in humans and livestock is critical, given the worldwide public health threats and livestock production losses. Livestock farming involving close proximity between humans, pigs and poultry is often practised by smallholders in low-income countries and is considered an important driver of influenza virus evolution. This study determined the prevalence and genetic characteristics of influenza A virus (IAV) in backyard pigs and poultry in Cambodia. A total of 751 animals were tested by matrix gene-based rRT-PCR, and influenza virus was detected in 1.5% of sampled pigs, 1.4% of chickens and 1.0% of ducks, but not in pigeons. Full-length genome sequencing confirmed triple reassortant H3N2 in all IAV-positive pigs and various low pathogenic avian influenza subtypes in poultry. Phylogenetic analysis of the swine influenza viruses revealed that these had haemagglutinin and neuraminidase genes originating from human H3N2 viruses previously isolated in South-East Asia. Phylogenetic analysis also revealed that several of the avian influenza subtypes detected were closely related to internal viral genes from highly pathogenic H5N1 and H9N2 formerly sequenced in the region. High sequence homology was likewise found with influenza A viruses circulating in pigs, poultry and wild birds in China and Vietnam, suggesting transboundary introduction and cocirculation of the various influenza subtypes. In conclusion, highly pathogenic subtypes of influenza virus seem rare in backyard poultry, but virus reassortment, involving potentially zoonotic and pandemic subtypes, appears to occur frequently in smallholder pigs and poultry. Increased targeted surveillance and monitoring of influenza circulation on smallholdings would further improve understanding of the transmission dynamics and evolution of influenza viruses in humans, pigs and poultry in the Mekong subregion and could contribute to limit the influenza burden.
Mixing, mass transfer and energy analysis across bioreactor types in microalgal cultivation and lipid production

ii Abstract Microalgae are recognised as a source of lipids for bioenergy, nutrients and pharmaceuticals. Photobioreactors, closed vessels for microalgal cultivation, are known to have high energy consumption due to mixing and aeration. Sparging is commonly used for mixing and gas-liquid mass transfer in photobioreactors, but is energy intensive. The aim of this work was to reduce these energy requirements by optimising conventional sparging and considering surface aeration coupled with mechanical agitation as an alternative. An airlift photobioreactor was used as a base for comparison with two novel, surface aerated reactors: oscillatory baffled and wave photobioreactors. The three bioreactors were compared in terms of power input, mixing, CO2 mass transfer, algal growth and lipid production. Prior to comparison, each photobioreactor was optimised based on these parameters. To calculate power input, isothermal gas expansion equations were used for sparged systems and calorimetry was used for mechanically agitation systems. Mixing was investigated using a salt tracer and phenolphthalein indicator and mass transfer was measured using the gassing-in method. Scenedesmus sp. , a high lipid-producer, was cultivated in low nitrate media across a range of mixing rates in each photobioreactor. In the airlift photobioreactor a critical minimum CO2 supply rate (of 2.7×10 -5 m s) was found, below which carbon was limiting and above which energy was spent on sparging without increased productivity (0.20 g L d biomass; 0.03 g L d lipid). In the oscillatory baffled reactor, insufficient mass transfer limited algal productivity (0.11 g L d biomass; 0.02 g L d lipid). The wave reactor had high CO2 mass transfer coefficients (10 – 140 h ) in comparison to the airlift (2.7 – 40 h) and oscillatory baffled reactors (6.3 – 37 h). Sufficient biomass productivity (0.18 g L-1 d) and higher lipid productivity (0.045 g L d) at lower power input in the wave reactor resulted in higher energy efficiency compared to the airlift reactor. Life cycle analysis of simulated algal biodiesel production showed that bioreactor energy contributed 99% of total energy consumption. Therefore, the global warming potential was reduced by 73% when the airlift reactor was operated at the critical minimum CO2 supply (with gas compression to 2 bar) and a further 19% when the wave reactor was used. This work offers an energy efficient alternative to sparging, through the generation of a well-mixed wave in a surface aerated bioreactor. It also offers methods for optimisation of energy usage with respect to mixing and aeration. Reducing bioreactor energy consumption is key to feasibility, and was demonstrated here to reduce energy-related environmental burdens.
Mutations in the Human ROBO1 Gene in Pituitary Stalk Interruption Syndrome

Context Pituitary stalk interruption syndrome (PSIS) is characterized by a thin or absent pituitary stalk usually in association with an ectopic posterior pituitary and hypoplasia/aplasia of the anterior pituitary. Associated phenotypes include varied ocular anomalies, hypoglycemia, micropenis/cryptorchidism, growth failure, or combined pituitary hormone deficiencies. Although genetic causes have been identified, they explain only around 5% of PSIS cases. Objective To identify genetic causes of PSIS by exome sequencing. Design Exon enrichment was performed using the Agilent SureSelect Human All Exon V4. Paired-end sequencing was performed on the Illumina HiSeq2000 platform with an average sequencing coverage of ×50. Patients Patients with unexplained PSIS were included in the study. Results In five cases of unexplained PSIS including two familial cases, we identified a novel heterozygous frameshift and nonsense and missense mutations in the ROBO1 gene (p.Ala977Glnfs*40, two affected sibs; p.Tyr1114Ter, sporadic case, and p.Cys240Ser, affected child and paternal aunt) that controls embryonic axon guidance, and branching in the nervous system. Interestingly, four of the five cases of PSIS also presented with ocular anomalies, including hypermetropia with strabismus as well as ptosis. Conclusions These data suggest that mutations in ROBO1 contribute to PSIS and associated ocular anomalies.
Botulinum Toxin in Aesthetic Medicine: Myths and Realities

BACKGROUND Several formulations of Botulinum toxin serotype A (BoNT-A) for aesthetic indications are available, with numbers likely to increase. Preparations are not interchangeable, based on dose unit comparisons. OBJECTIVE Numerous myths and misconceptions regarding the use of BoNT-A for aesthetic indications have arisen, which this review aims to lay to rest. MATERIALS AND METHODS This review assesses evidence for and against each of the most common myths regarding BoNT use in aesthetics. RESULTS BoNT-A neurotoxin/protein complexes are irrelevant to the toxin's therapeutic/aesthetic indications. BoNT-A neurotoxin/protein complexes do not influence movement from injection site or immunogenicity. Any relationship between neutralizing antibody formation and clinical response is complex and clinicians should consider other factors that may induce an apparent loss of clinical response. Diffusion appears predominately, perhaps exclusively, dose dependent. Careful placement and correct dosing optimizes likelihood of good outcomes. Manufacturers recommend reconstitution of products with sterile nonpreserved saline. However, compelling evidence suggests that reconstitution using preserved saline dramatically improves patient comfort without compromising efficacy. Several post-treatment instructions/restrictions are widely used despite the lack of evidence, but muscle activity after injection may be beneficial. Cooling the treatment area might hinder BoNT-A translocation and should probably be abandoned. CONCLUSION The existing evidence suggests that experienced users should achieve equivalent results regardless of BoNT-A formulation, but additional, well-designed, adequately powered, controlled randomized studies should be performed.
Bottom-Up Merging Segmentation for Color Images With Complex Areas

Most color images obtained from the real world usually contain complex areas, such as nature scene images, remote sensing images, and medical images. All these type of images are very difficult to be separated accurately and automatically for complex color and structures included. In this paper, we focus on detecting hybrid cues of color image to segment complex scene in a bottom-up framework. The main idea of the proposed segmentation method is based on a two-step procedure: 1) a reasonable superpixels computing method is conducted and 2) a Mumford–Shah (M–S) optimal merging model is proposed for presegment suerpixels. First, a set of seed pixels is positioned at the lowest texture energy map computed from structure tensor diffusion features. Next, we implement a growing procedure to extract superpixels from selected seed pixels with color and texture cues. After that, a color-texture histograms feature is defined to measure similarity between regions, and an M–S optimal merging process is executed by comparing the similarity of adjacent regions with standard deviation constraints to get final segmentation. Extensive experiments are conducted on the Berkeley segmentation database, some remote sensing images, and medical images. The results of experiments have verified that the segmentation effectiveness of the proposed method in segmenting complex scenes and indicated that it is more robust and accurate than conventional methods.
Identification of flexible structures for robust control

Documentation is provided of the authors' experience with modeling and identification of an experimental flexible structure for the purpose of control design, with the primary aim being to motivate some important research directions in this area. A multi-input/multi-output (MIMO) model of the structure is generated using the finite element method. This model is inadequate for control design, due to its large variation from the experimental data. Chebyshev polynomials are employed to fit the data with single-input/multi-output (SIMO) transfer function models. Combining these SIMO models leads to a MIMO model with more modes than the original finite element model. To find a physically motivated model, an ad hoc model reduction technique which uses a priori knowledge of the structure is developed. The ad hoc approach is compared with balanced realization model reduction to determine its benefits. Descriptions of the errors between the model and experimental data are formulated for robust control design. Plots of select transfer function models and experimental data are included. <<ETX>>