Miracle-dz/UniFAR-FTUs huggingface dataset:
Ultralow-Power (1.59 mW/Gbps), 56-Gbps PAM4 Operation of Si Photonic Transmitter Integrating Segmented PIN Mach–Zehnder Modulator and 28-nm CMOS Driver

A highly power-efficient silicon (Si) photonic PAM4 transmitter was developed by integrating a Si segmented Mach–Zehnder modulator and a CMOS driver chip. Si p-i-n-type phase shifters are directly driven with a CMOS inverter driver array to realize a low power operation. A passive <italic>RC</italic> equalizing technique was adopted to extend the modulation bandwidth up to 20 GHz while maintaining a low power consumption. By integrating a passive <italic>RC</italic> filter within the photonics chip, we achieved a very compact foot print for the transmitter (450 × 950 <italic>μ</italic>m). The fabricated modulator exhibited a low VπL of 0.19 V·cm and a moderate insertion loss of 23.7 dB/cm. The transmitter successfully demonstrated clear eye openings of PAM4 signal up to 56 Gbps together with a record-high-efficiency of 1.59 mW/Gbps. A low bit-error-rate below KP4 FEC limit ( <inline-formula><tex-math notation="LaTeX">$ <{\text{2.0}}\times {\text{10}}^{-4}$</tex-math></inline-formula>) was also confirmed at 50-Gbps PAM4 operation even with an unequalized receiver.
A Phase I Study of Abiraterone Acetate Combined with BEZ235, a Dual PI3K/mTOR Inhibitor, in Metastatic Castration Resistant Prostate Cancer

Abstract Lessons Learned. The combination of standard dose abiraterone acetate and BEZ235, a pan‐class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC. Although the clinical development of BEZ235 has been discontinued in prostate cancer, agents that more selectively target PI3K‐AKT‐mTOR signaling may have a more favorable therapeutic index and should continue to be explored. Background. Androgen receptor (AR) and phosphatidylinositol‐3 kinase (PI3K) signaling are two commonly perturbed pathways in prostate cancer. Preclinical data have shown that the two pathways compensate for each other when one is inhibited, and combined inhibition of AR and PI3K signaling may be a viable strategy to prevent or overcome castration resistance. Methods. This phase I study evaluated the safety and tolerability of abiraterone acetate and prednisone combined with BEZ235, a dual PI3K and mTORC1/2 inhibitor, in men with progressive metastatic castration resistant prostate cancer (mCRPC) who have not received prior chemotherapy. Results. Six patients (n = 6) were treated at the starting dose level of abiraterone acetate 1,000 mg with prednisone 5 mg twice daily and BEZ235 200 mg twice daily in a 3 + 3 dose escalation design. The study was terminated early because three of the six patients (50%) experienced dose‐limiting toxicities: grade 3 mucositis, grade 3 hypotension, and grade 4 dyspnea and pneumonitis. All six patients had previously progressed on abiraterone/prednisone. The median treatment duration was 27 days (range: 3–130 days). No prostate‐specific antigen (PSA) decline or objective response were observed. Conclusion. The combination of standard‐dose abiraterone/prednisone with BEZ235 200 mg twice daily was poorly tolerated in patients with mCRPC. The on‐target and off‐target effects of dual PI3K and mTORC inhibition likely contributed to the unacceptable toxicity profile. The Oncologist 2017;22:503–e43
Self-Test Procedures for Gas Sensors Embedded in Microreactor Systems

Metal oxide (MOX) gas sensors sensitively respond to a wide variety of combustible, explosive and poisonous gases. However, due to the lack of a built-in self-test capability, MOX gas sensors have not yet been able to penetrate safety-critical applications. In the present work we report on gas sensing experiments performed on MOX gas sensors embedded in ceramic micro-reaction chambers. With the help of an external micro-pump, such systems can be operated in a periodic manner alternating between flow and no-flow conditions, thus allowing repetitive measurements of the sensor resistances under clean air, R0, and under gas exposure, Rgas, to be obtained, even under field conditions. With these pairs of resistance values, eventual drifts in the sensor baseline resistance can be detected and drift-corrected values of the relative resistance response Resp=(R0−Rgas)/R0 can be determined. Residual poisoning-induced changes in the relative resistance response can be detected by reference to humidity measurements taken with room-temperature-operated capacitive humidity sensors which are insensitive to the poisoning processes operative on heated MOX gas sensors.
Performance analysis of Hoyt-lognormal composite fading channel

Hoyt distribution is used to model the wireless communication system with more severe channel fading conditions. The large-scale signal power variation is statistically modeled by the lognormal distribution. Due to mathematical complexity, performance parameters of Hoyt-lognormal composite fading channels are not present in closed-form. In this paper, we have analyzed the performance of Hoyt-lognormal channel by using the Gaussian-Hermite quadrature sum method. The performance analysis of probability density function (PDF) of the signal to noise ratio (SNR), outage probability (Pout), amount of fading (AF), average symbol error probability (ASEP) are analyzed and expressed in closed form. With high accuracy, the proposed closed form approximation of composite fading channel is compared with the exact results.
A theoretical insight into selectivity of inhibitors toward two domains of bromodomain‐containing protein 4 using molecular dynamics simulations

Bromodomains (BRDs) have been an attractive candidate for development of efficient inhibitors toward gene transcription. Molecular dynamics (MD) simulations followed by principal component (PC) analysis were performed to investigate binding selectivity of inhibitors RVX297, BSP, JQ1, SF2523, and CPD2 toward two domains (BD1 and BD2) of bromodomain‐containing protein 4 (BRD4). The results show that inhibitor bindings exert different effect on motions of the BC‐loops in BD1 and BD2. The rank of binding free energies calculated using molecular mechanics Poisson–Boltzmann surface area (MM‐PBSA) method agrees with the one determined by experiment. The results also suggest that the binding ability of RVX297, BSP, and JQ1 to BD2 is stronger than that of them to BD1, while the binding ability of SF2523 to BD2 is obviously weaker than that of SF2523 to BD1. Alanine mutation calculations and the calculated inhibitor–residue interaction spectrum prove that the current five inhibitors have obvious binding selectivity toward BD1 and BD2. This study is not only helpful for further understanding the differences in internal dynamics of BD1 and BD2 caused by inhibitor bindings, but also can theoretically contribute significant guidance to designs of effective and high selective anticancer drugs targeting BD1 and BD2 in BRD4.
Aquatic toxicity of one dimensional carbon nanomaterials

Silicon carbide nanowires (SiCNW) are insoluble in water. When released into an aquatic environment, SiCNW would likely accumulate in sediment. The objective of this study was to assess the toxicity of SiCNW to four freshwater sediment-dwelling organisms: amphipods (Hyalella azteca), midge (Chironomus dilutus), oligochaetes (Lumbriculus variegatus), and mussels (Lampsilis siliquoidea). Amphipods were exposed to either sonicated or non-sonicated SiCNW in water (1.0 g SiCNW /L) for 48 h. Midge, mussels, and oligochaetes were exposed only to sonicated SiCNW in water for 96 h. In addition, amphipods were exposed to sonicated SiCNW in whole-sediment for 10 d (44% SiCNW on dry weight basis of sediment). Mean 48-h survival of amphipods exposed to non-sonicated SiCNW (83% survival) in water was not significantly different from the control (90% survival), whereas mean survival of amphipods exposed to sonicated SiCNW in two 48-h exposures (0 or 15% survival) was significantly different than the control (90 or 98% survival). In contrast, no effect of sonicated SiCNW was observed on survival of midge, mussels, or oligochaetes. Survival of amphipods was not significantly reduced in 10-d exposures to sonicated SiCNW either mixed in the sediment or layered on the sediment surface.
Physical Activity and Sedentary Behaviors Among Lesbian, Bisexual, and Heterosexual Women: Findings from the Nurses' Health Study II.

INTRODUCTION Lesbian and bisexual (LB) women are at greater risk of obesity than heterosexuals. However, few studies have examined sexual orientation differences in physical activity (PA) and even fewer have examined differences in sedentary behaviors. This study assessed PA more comprehensively than previous research by including aerobic PA, strengthening PA, and sitting time, to explore sexual orientation differences among adult women. METHODS Nearly 100,000 women from Nurses' Health Study II were included in multivariable-adjusted repeated measures analyses. PA and sedentary behaviors were assessed in 1989, 1991, 1997, 2001, 2005, and 2009 (age range: 24-64 years). Aerobic PA was converted to metabolic equivalent task (MET)-hours/week, whereas strengthening PA and sedentary behaviors were measured in hours/week. About 1.3% of the sample identified as lesbian (n = 926) or bisexual (n = 415). RESULTS On average over repeated measures, LB women reported engaging in 2-3 MET-hours/week more of total aerobic PA (β [95% confidence interval, CI]: lesbian: 2.0 MET-hours/week [0.6-3.4]; bisexual: 2.8 MET-hours/week [0.7-4.7]) than heterosexual women. Bisexual women reported engaging in 0.2 hours/week more of strengthening PA (95% CI: 0.06-0.42) than heterosexuals; there were no differences between lesbians and heterosexuals in strengthening PA. LB women reported sitting an average of 4-5 hours/week more than heterosexuals (lesbian: 4.1 hours/week [3.1-5.2]; bisexual: 5.1 hours/week [3.6-6.7]). CONCLUSIONS Interventions promoting less sitting time among LB women may be warranted. Additionally, findings highlight need for more research into other modifiable factors besides PA, such as minority stress or disordered eating behaviors that may contribute to greater obesity among LB women.
Security analysis and enhancement of model compressed deep learning systems under adversarial attacks

Thanks to recent machine learning model innovation and computing hardware advancement, the state-of-the-art of Deep Neural Network (DNN) is presenting human-level performance for many complex intelligent tasks in real-world applications. However, it also introduces ever-increasing security concerns for those intelligent systems. For example, the emerging adversarial attacks indicate that even very small and often imperceptible adversarial input perturbations can easily mislead the cognitive function of deep learning systems (DLS). Existing DNN adversarial studies are narrowly performed on the ideal software-level DNN models with a focus on single uncertainty factor, i.e. input perturbations, however, the impact of DNN model reshaping on adversarial attacks, which is introduced by various hardware-favorable techniques such as hash-based weight compression during modern DNN hardware implementation, has never been discussed. In this work, we for the first time investigate the multi-factor adversarial attack problem in practical model optimized deep learning systems by jointly considering the DNN model-reshaping (e.g. HashNet based deep compression) and the input perturbations. We first augment adversarial example generating method dedicated to the compressed DNN models by incorporating the software-based approaches and mathematical modeled DNN reshaping. We then conduct a comprehensive robustness and vulnerability analysis of deep compressed DNN models under derived adversarial attacks. A defense technique named “gradient inhibition” is further developed to ease the generating of adversarial examples thus to effectively mitigate adversarial attacks towards both software and hardware-oriented DNNs. Simulation results show that “gradient inhibition” can decrease the average success rate of adversarial attacks from 87.99% to 4.77% (from 86.74% to 4.64%) on MNIST (CIFAR-10) benchmark with marginal accuracy degradation across various DNNs.
Control of Fast-Reaching Movements by Muscle Synergy Combinations

How the CNS selects the appropriate muscle patterns to achieve a behavioral goal is an open question. To gain insight into this process, we characterized the spatiotemporal organization of the muscle patterns for fast-reaching movements. We recorded electromyographic activity from up to 19 shoulder and arm muscles during point-to-point movements between a central location and 8 peripheral targets in each of 2 vertical planes. We used an optimization algorithm to identify a set of time-varying muscle synergies, i.e., the coordinated activations of groups of muscles with specific time-varying profiles. For each one of nine subjects, we extracted four or five synergies whose combinations, after scaling in amplitude and shifting in time each synergy independently for each movement condition, explained 73–82% of the data variation. We then tested whether these synergies could reconstruct the muscle patterns for point-to-point movements with different loads or forearm postures and for reversal and via-point movements. We found that reconstruction accuracy remained high, indicating generalization across these conditions. Finally, the synergy amplitude coefficients were directionally tuned according to a cosine function with a preferred direction that showed a smaller variability with changes of load, posture, and endpoint than the preferred direction of individual muscles. Thus the complex spatiotemporal characteristics of the muscles patterns for reaching were captured by the combinations of a small number of components, suggesting that the mechanisms involved in the generation of the muscle patterns exploit this low dimensionality to simplify control.
Differential Expression of MicroRNAs in Uterine Cervical Cancer and Its Implications in Carcinogenesis; An Integrative Approach

Objectives Cervical cancer is the second most common cancer in women in developing countries, including India. Recently, microRNAs (miRNAs) are gaining importance in cancer biology because of their involvement in various cellular processes. The present study aimed to profile miRNA expression pattern in cervical cancer, identify their target genes, and understand their role in carcinogenesis. Methods Human papillomavirus (HPV) infection statuses in samples were assessed by heminested polymerase chain reaction followed by direct DNA sequencing. Next-generation sequencing and miRNA microarray were used for miRNA profiling in cervical cancer cell lines and tissue samples, respectively. MicroRNA signature was validated by quantitative real-time PCR, and biological significance was elucidated using various in silico analyses. Results Cervical cancer tissues samples were mostly infected by HPV type 16 (93%). MicroRNA profiling showed that the pattern of miRNA expression differed with respect to HPV positivity in cervical cancer cell lines. However, target and pathway analyses indicated identical involvement of these significantly deregulated miRNAs in HPV-positive cervical cancer cell lines irrespective of type of HPV infected. Microarray profiling identified a set of miRNAs that are differentially deregulated in cervical cancer tissue samples which were validated using quantitative real-time PCR. In silico analyses revealed that the signature miRNAs are mainly involved in PI3K-Akt and mTOR pathways. Conclusions The study identified that high-risk HPV induces similar carcinogenic mechanism irrespective of HPV type. The miRNA signature of cervical cancer and their target genes were also elucidated, thereby providing a better insight into the molecular mechanism underlying cervical cancer development.
Galactosylation of the Secondary Cell Wall Polysaccharide of Bacillus anthracis and Its Contribution to Anthrax Pathogenesis

ABSTRACT Bacillus anthracis, the causative agent of anthrax disease, elaborates a secondary cell wall polysaccharide (SCWP) that is essential for bacterial growth and cell division. B. anthracis SCWP is comprised of trisaccharide repeats with the structure, [→4)-β-ManNAc-(1→4)-β-GlcNAc(O3-α-Gal)-(1→6)-α-GlcNAc(O3-α-Gal, O4-β-Gal)-(1→]6-12. The genes whose products promote the galactosylation of B. anthracis SCWP are not yet known. We show here that the expression of galE1, encoding a UDP-glucose 4-epimerase necessary for the synthesis of UDP-galactose, is required for B. anthracis SCWP galactosylation. The galE1 mutant assembles surface (S) layer and S layer-associated proteins that associate with ketal-pyruvylated SCWP via their S layer homology domains similarly to wild-type B. anthracis, but the mutant displays a defect in γ-phage murein hydrolase binding to SCWP. Furthermore, deletion of galE1 diminishes the capsulation of B. anthracis with poly-d-γ-glutamic acid (PDGA) and causes a reduction in bacterial virulence. These data suggest that SCWP galactosylation is required for the physiologic assembly of the B. anthracis cell wall envelope and for the pathogenesis of anthrax disease. IMPORTANCE Unlike virulent Bacillus anthracis isolates, B. anthracis strain CDC684 synthesizes secondary cell wall polysaccharide (SCWP) trisaccharide repeats without galactosyl modification, exhibits diminished growth in vitro in broth cultures, and is severely attenuated in an animal model of anthrax. To examine whether SCWP galactosylation is a requirement for anthrax disease, we generated variants of B. anthracis strains Sterne 34F2 and Ames lacking UDP-glucose 4-epimerase by mutating the genes galE1 and galE2. We identified galE1 as necessary for SCWP galactosylation. Deletion of galE1 decreased the poly-d-γ-glutamic acid (PDGA) capsulation of the vegetative form of B. anthracis and increased the bacterial inoculum required to produce lethal disease in mice, indicating that SCWP galactosylation is indeed a determinant of anthrax disease.
Double‐wave‐vector diffusion‐weighted imaging reveals microscopic diffusion anisotropy in the living human brain

Diffusion‐tensor imaging is widely used to characterize diffusion in biological tissue, however, the derived anisotropy information, e.g., the fractional anisotropy, is ambiguous. For instance, low values of the diffusion anisotropy in brain white matter voxels may reflect a reduced axon density, i.e., a loss of fibers, or a lower fiber coherence within the voxel, e.g., more crossing fibers. This ambiguity can be avoided with experiments involving two diffusion‐weighting periods applied successively in a single acquisition, so‐called double‐wave‐vector or double‐pulsed‐field‐gradient experiments. For a long mixing time between the two periods such experiments are sensitive to the cells' eccentricity, i.e., the diffusion anisotropy present on a microscopic scale. In this study, it is shown that this microscopic diffusion anisotropy can be detected in white matter in the living human brain, even in a macroscopically isotropic region‐of‐interest (fractional anisotropy = 0). The underlying signal difference between parallel and orthogonal wave vector orientations does not show up in standard diffusion‐weighting experiments but is specific to the double‐wave‐vector experiment. Furthermore, the modulation amplitude observed is very similar for regions‐of‐interest with different fractional anisotrpy values. Thus, double‐wave‐vector experiments may provide a direct and reliable access to white matter integrity independent of the actual fiber orientation distribution within the voxel. Magn Reson Med 69:1072–1082, 2013. © 2012 Wiley Periodicals, Inc.
Primary aldosteronism and thyroid disorders in atrial fibrillation: A Swedish nationwide case–control study

Background Atrial fibrillation is associated with hyperthyroidism. Patients with primary aldosteronism have an increased prevalence of atrial fibrillation. However, the prevalence of primary aldosteronism in the atrial fibrillation population is unknown. Aim This nationwide case–control study aimed to compare the prevalence of primary aldosteronism and thyroid disorders in patients with atrial fibrillation with that of age- and sex-matched controls. Methods We identified all atrial fibrillation cases in Sweden between 1987 and 2013 (n = 713,569) by using the Swedish National Patient Register. A control cohort without atrial fibrillation was randomly selected from the Swedish Total Population Register with a case to control ratio of 1:2. This control cohort was matched for age, sex and place of birth (n = 1,393,953). Results The prevalence of primary aldosteronism in December 2013 was 0.056% in the atrial fibrillation cohort and 0.024% in controls. At the same time, the prevalence of hypothyroidism was 5.9% in the atrial fibrillation cohort and 3.7% in controls. The prevalence of hyperthyroidism was 2.3% in the atrial fibrillation cohort and 0.8% in controls. Conclusion This study shows, for the first time, a doubled prevalence of primary aldosteronism in a large cohort of patients with atrial fibrillation compared with the general population. There is also an increased prevalence of hypo- and hyper-thyroidism in patients with atrial fibrillation compared with the general population.
Balancing CPU and Network in the Cell Distributed B-Tree Store

In traditional client-server designs, all requests are processed at the server storing the state, thereby maintaining strict locality between computation and state. The adoption of RDMA (Remote Direct Memory Access) makes it practical to relax locality by letting clients fetch server state and process requests themselves. Such client-side processing improves performance when the server CPU, instead of the network, is the bottleneck. We observe that combining server-side and client-side processing allows systems to balance and adapt to the available CPU and network resources with minimal configuration, and can free resources for other CPU-intensive work. We present Cell, a distributed B-tree store that combines client-side and server-side processing. Cell distributes a global B-tree of "fat" (64MB) nodes across machines for server-side searches. Within each fat node, Cell organizes keys as a local B-tree of RDMA-friendly small nodes for client-side searches. Cell clients dynamically select whether to use client-side or server-side processing in response to available resources and the current workload. Our evaluation on a large RDMA-capable cluster show that Cell scales well and that its dynamic selector effectively responds to resource availability and workload properties.
The Mixed Chinese Postman Problem Parameterized by Pathwidth and Treedepth

In the mixed Chinese postman problem (MCPP), given a weighted mixed graph $G$ (it may have both edges and arcs), our aim is to find a closed walk of minimum weight traversing each edge and arc at least once. The MCPP parameterized by the number of edges in $G$ or the number of arcs in $G$ is fixed-parameter tractable as proved by van Bevern et al. in 2014 and Gutin, Jones, and Sheng in 2014, respectively. Solving an open question of van Bevern et al., we show that somewhat unexpectedly the MCPP parameterized by the (undirected) treewidth of $G$ is W[1]-hard. In fact, we prove that even the unweighted MCPP parameterized by the pathwidth of $G$ is W[1]-hard. On the positive side, we show that MCPP parameterized by treedepth is fixed-parameter tractable (even with arbitrary integer weights). We are unaware of any widely studied graph parameters between pathwidth and treedepth and so our results provide a close characterization of the complexity of MCPP.