bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Bottleneck Structure of Congestion-Controlled Networks
Authors: Ros-Giralt Jordi , Bohara Atul , Yellamraju Sruthi , Langston M. Harper , Lethin Richard , Jiang Yuang , Tassiulas Leandros , Li Josie , Tan Yuanlong , Veeraraghavan Malathi
Published: December 2019

In this paper, we introduce theTheory of Bottleneck Ordering, a mathematical framework that reveals the bottleneck structure of data networks. This theoretical framework provides insights into the inherent topological properties of a network in at least three areas: (1) It identifies the regions of influence of each bottleneck; (2) it reveals the order in which bottlenecks (and flows traversing them) converge to their steady state transmission rates in distributed congestion control algorithms; and (3) it provides key insights into the design of optimized traffic engineering policies. We demonstrate the efficacy of the proposed theory in TCP congestion-controlled networks for two broad classes of algorithms: Congestion-based algorithms (TCP BBR) and loss-based additive-increase/multiplicative-decrease algorithms (TCP Cubic and Reno). Among other results, our network experiments show that: (1) Qualitatively, both classes of congestion control algorithms behave as predicted by the bottleneck structure of the network; (2) flows compete for bandwidth only with other flows operating at the same bottleneck level; (3) BBR flows achieve higher performance and fairness than Cubic and Reno flows due to their ability to operate at the right bottleneck level; (4) the bottleneck structure of a network is continuously changing and its levels can be folded due to variations in the flows' round trip times; and (5) against conventional wisdom, low-hitter flows can have a large impact to the overall performance of a network.
A Metric-Guided Method for Discovering Impactful Features and Architectural Insights for Skylake-Based Processors
Authors: Yasin Ahmad , Haj-Yahya Jawad , Ben-Asher Yosi , Mendelson Avi
Published: December 2019

The slowdown in technology scaling puts architectural features at the forefront of the innovation in modern processors. This article presents a Metric-Guided Method (MGM) that extends Top-Down analysis with carefully selected, dynamically adapted metrics in a structured approach. Using MGM, we conduct two evaluations at the microarchitecture and the Instruction Set Architecture (ISA) levels. Our results show that simple optimizations, such as improved representation of CISC instructions, broadly improve performance, while changes in the Floating-Point execution units had mixed impact. Overall, we report 10 architectural insights—at the microarchitecture, ISA, and compiler fronts—while quantifying their impact on the SPEC CPU benchmarks.
Exploring Complex Brain-Simulation Workloads on Multi-GPU Deployments
Authors: Vlag Michiel A. van der , Smaragdos Georgios , Al-Ars Zaid , Strydis Christos
Published: December 2019

In-silico brain simulations are the de-facto tools computational neuroscientists use to understand large-scale and complex brain-function dynamics. Current brain simulators do not scale efficiently enough to large-scale problem sizes (e.g., >100,000 neurons) when simulating biophysically complex neuron models. The goal of this work is to explore the use of true multi-GPU acceleration through NVIDIA’s GPUDirect technology on computationally challenging brain models and to assess their scalability. The brain model used is a state-of-the-art, extended Hodgkin-Huxley, biophysically meaningful, three-compartmental model of the inferior-olivary nucleus. The Hodgkin-Huxley model is the most widely adopted conductance-based neuron representation, and thus the results from simulating this representative workload are relevant for many other brain experiments. Not only the actual network-simulation times but also the network-setup times were taken into account when designing and benchmarking the multi-GPU version, an aspect often ignored in similar previous work. Network sizes varying from 65K to 2M cells, with 10 and 1,000 synapses per neuron were executed on 8, 16, 24, and 32 GPUs. Without loss of generality, simulations were run for 100 ms of biological time. Findings indicate that communication overheads do not dominate overall execution while scaling the network size up is computationally tractable. This scalable design proves that large-network simulations of complex neural models are possible using a multi-GPU design with GPUDirect.
Data-driven Mixed Precision Sparse Matrix Vector Multiplication for GPUs
Authors: Ahmad Khalid , Sundar Hari , Hall Mary
Published: December 2019

We optimize Sparse Matrix Vector multiplication (SpMV) using a mixed precision strategy (MpSpMV) for Nvidia V100 GPUs. The approach has three benefits: (1) It reduces computation time, (2) it reduces the size of the input matrix and therefore reduces data movement, and (3) it provides an opportunity for increased parallelism. MpSpMV’s decision to lower to single precision is
data driven
, based on individual nonzero values of the sparse matrix. On all real-valued matrices from the Sparse Matrix Collection, we obtain a maximum speedup of 2.61× and average speedup of 1.06× over double precision, while maintaining higher accuracy compared to single precision.
Heavy-traffic Delay Optimality in Pull-based Load Balancing Systems
Authors: Zhou Xingyu , Tan Jian , Shroff Ness
Published: December 2019

In this paper, we consider a load balancing system under a general pull-based policy. In particular, each arrival is randomly dispatched to any server whose queue length is below a threshold; if no such server exists, then the arrival is randomly assigned to any server. We are interested in the fundamental relationship between the threshold and the delay performance of the system in heavy traffic. To this end, we first establish the following necessary condition to guarantee heavy-traffic delay optimality: the threshold needs to grow to infinity as the exogenous arrival rate approaches the boundary of the capacity region (i.e., the load intensity approaches one) but the growth rate should be slower than a polynomial function of the mean number of tasks in the system. As a special case of this result, we directly show that the delay performance of the popular pull-based policy Join-Idle-Queue (JIQ) is not heavy traffic optimal, but performs strictly better than random routing. We further show that a sufficient condition for heavy-traffic delay optimality is that the threshold grows logarithmically with the mean number of tasks in the system. This result directly resolves a generalized version of the conjecture by Kelly and Laws.
Network Resilience Assessment via QoS Degradation Metrics
Authors: Nguyen Lan N. , Thai My T.
Published: December 2019

This paper focuses on network resilience to perturbation of edge weight. Other than connectivity, many network applications nowadays rely upon some measure of network distance between a pair of connected nodes. In these systems, a metric related to network functionality is associated to each edge. A pair of nodes only being functional if the weighted, shortest-path distance between the pair is below a given threshold T. Consequently, a natural question is on which degree the change of edge weights can damage the network functionality? With this motivation, we study a new problem, Quality of Service Degradation: given a set of pairs, find a minimum budget to increase the edge weights which ensures the distance between each pair exceeds T. We introduce four algorithms with theoretical performance guarantees for this problem. Each of them has its own strength in trade-off between effectiveness and running time, which are illustrated both in theory and comprehensive experimental evaluation.
A TTL-based Approach for Data Aggregation in Geo-distributed Streaming Analytics
Authors: Kumar Dhruv , Li Jian , Sitaraman Ramesh , Chandra Abhishek
Published: December 2019

Streaming data analytics has been an important topic of research in recent years. Large quantities of data are generated continuously over time across a variety of application domains such as web and social analytics, scientific computing and energy analytics. One of the key requirements in modern data analytics services is the real-time analysis of these data streams to extract useful and timely information for the analyst. Several distributed data analytics platforms have been developed in recent times to meet this growing requirement of real-time streaming analytics. Nowadays, a large amount of data is generated continuously by geographically distributed sources (e.g., agents, sensors, mobile devices, edge nodes, etc.) in many streaming applications. For instance, services like Facebook, Twitter and Netflix continuously gather data from the end users for a variety of analytical purposes such as finding the popular web content amongst their users or monitoring the QoS metrics. Large content delivery networks (CDNs) like Akamai that serve a significant fraction of content on the Internet continuously collect data from their edge servers and clients from around the globe to understand what, where and how content is accessed for the purpose of providing content analytics insights to businesses.
Architecture-Aware Approximate Computing
Authors: Karakoy Mustafa , Kislal Orhan , Tang Xulong , Kandemir Mahmut Taylan , Arunachalam Meenakshi
Published: December 2019

Observing that many application programs from different domains can live with less-than-perfect accuracy, existing techniques try to trade off program output accuracy with performance-energy savings. While these works provide point solutions, they leave three critical questions regarding approximate computing unanswered: (i) what is the maximum potential of skipping (i.e., not performing) data accesses under a given inaccuracy bound?; (ii) can we identify the data accesses to drop randomly, or is being architecture aware critical?; and (iii) do two executions that skip the same number of data accesses always result in the same output quality (error)? This paper first provides answers to these questions using ten multithreaded workloads, and then presents a program slicing-based approach that identifies the set of data accesses to drop. Results indicate 8.8% performance improvement and 13.7% energy saving are possible when we set the error bound to 2%, and the corresponding improvements jump to 15% and 25%, respectively, when the error bound is raised to 4%.
Competitive Online Optimization under Inventory Constraints
Authors: Lin Qiulin , Yi Hanling , Pang John , Chen Minghua , Wierman Adam , Honig Michael , Xiao Yuanzhang
Published: December 2019

This paper studies online optimization under inventory (budget) constraints. While online optimization is a well-studied topic, versions with inventory constraints have proven difficult. We consider a formulation of inventory-constrained optimization that is a generalization of the classic one-way trading problem and has a wide range of applications. We present a new algorithmic framework, CR-Pursuit, and prove that it achieves the optimal competitive ratio among all deterministic algorithms (up to a problem-dependent constant factor) for inventory-constrained online optimization. Our algorithm and its analysis not only simplify and unify the state-ofthe- art results for the standard one-way trading problem, but they also establish novel bounds for generalizations including concave revenue functions. For example, for one-way trading with price elasticity, CR-Pursuit achieves a competitive ratio within a small additive constant (i.e., 1/3) to the lower bound of ln θ + 1, where θ is the ratio between the maximum and minimum base prices.
Proactive Caching for Low Access-Delay Services under Uncertain Predictions
Authors: Liu Ran , Yeh Edmund , Eryilmaz Atilla
Published: December 2019

Network traffic for delay-sensitive services has become a dominant part in the network. Proactive caching with the aid of predictive information has been proposed as a promising method to enhance delay performance. In this paper, we analytically investigate the problem of how to efficiently utilize uncertain predictive information to design proactive caching strategies with provably good access-delay characteristics. We first derive an upper bound for the average amount of proactive service per request that the system can support. We then analyze the behavior of a family of threshold-based proactive strategies using an innovative Markov chain analysis, and show that the average amount of proactive service per request can be maximized by properly selecting the threshold. Finally, we propose the UNIFORM strategy, which is the threshold-based strategy with the optimal threshold. Surprisingly, we show that it outperforms the commonly used Earliest-Deadline- First (EDF) type proactive strategies in terms of delay. We perform extensive numerical experiments to demonstrate the influence of thresholds on delay performance, and explicitly compare performance of the EDF strategy and the UNIFORM strategy.
Demystifying ComplexWorkload-DRAM Interactions
Authors: Ghose Saugata , Li Tianshi , Hajinazar Nastaran , Senol Cali Damla , Mutlu Onur
Published: December 2019

It has become increasingly difficult to understand the complex interaction between modern applications and main memory, composed of Dynamic Random Access Memory (DRAM) chips. Manufacturers and researchers are developing many different types of DRAM, with each DRAM type catering to different needs (e.g., high throughput, low power, high memory density). At the same time, the memory access patterns of prevalent and emerging applications are rapidly diverging, as these applications manipulate larger data sets in very different ways. As a result, the combined DRAM-workload behavior is often difficult to intuitively determine today, which can hinder memory optimizations in both hardware and software.
An efficient reduction strategy for signature-based algorithms to compute Gröbner basis
Authors: Sakata Kosuke
Published: December 2019

This paper introduces a strategy for signature-based algorithms to compute Gröbner basis. In comparison with Buchberger algorithm, signature-based algorithms generate S-pairs instead of S-polynomials, and operate
s
-reductions instead of usual reductions which is used in Buchberger algorithm. There are two strategies for
s
-reductions: one is only-top reduction strategy which is the way that only leading monomials are
s
-reduced. The other is full reduction strategy which is the way that all monomials are
s
-reduced. New strategy for
s
-reduction of S-pairs, which we call selective-full strategy, is introduced in this paper. The idea of the strategy is that when we have computed a signature Gröbner basis, there are unnecessary elements for a minimal Gröbner basis, so candidates of elements included in a minimal Gröbner basis should be sufficiently reduced. According to the experimental result, proposed strategy is efficient for computing the reduced Gröbner basis. For computing a signature Gröbner basis, it's the most efficient or not the worst of the three strategies.
R-spondin3 promotes the tumor growth of choriocarcinoma JEG-3 cells
Authors: Chen Zhilong , Zhang Juzuo , Yuan Anwen , Han Jinyu , Tan Lunbo , Zhou Zhuoqun , Zhao Huashan , Su Rui , Huang Binbin , Wang Baobei , Sun Beini , Fan Xiujun , Yang Qing
Published: December 2019

R-spondin3 (RSPO3), an activator of Wnt/β-catenin signaling, plays a key role in tumorigenesis of various cancers, but its role in choriocarcinoma remains unknown. To investigate the effect of RSPO3 on the tumor growth of choriocarcinoma JEG-3 cells, the expression of RSPO3 in human term placenta was detected, and a stable RSPO3-overexpressing JEG-3 cell line was established via lentivirus-mediated transduction. The expression of biomarkers involved in tumorigenicity was detected in the RSPO3-overexpressing JEG-3 cells, and cell proliferation, invasion, migration, and apoptosis were investigated. Moreover, soft agar clonogenic assays and xenograft tumorigenicity assays were performed to assess the effect of RSPO3 on tumor growth in vitro and in vivo. The results showed that RSPO3 was widely expressed in human term placenta and overexpression of RSPO3 promoted the proliferation and inhibited the migration, invasion, and apoptosis of the JEG-3 cells. Meanwhile, RSPO3 overexpression promoted tumor growth both in vivo and in vitro. Further investigation showed that the phosphorylation levels of Akt, phosphatidylinositol 3-kinase (PI3K), and ERK as well the expression of β-catenin and proliferating cell nuclear antigen (PCNA) were increased in the RSPO3-overexpressing JEG-3 cells and tumor xenograft. Taken together, these data indicate that RSPO3 promotes the tumor growth of choriocarcinoma via Akt/PI3K/ERK signaling, which supports RSPO3 as an oncogenic driver promoting the progression of choriocarcinoma.
Airway smooth muscle tone increases actin filamentogenesis and contractile capacity
Authors: Gazzola Morgan , Henry Cyndi , Lortie Katherine , Khadangi Fatemeh , Park Chan Young , Fredberg Jeffrey J. , Bossé Ynuk
Published: December 2019

Force adaptation of airway smooth muscle (ASM) is a process whereby the presence of tone (i.e., a sustained contraction) increases the contractile capacity. For example, tone has been shown to increase airway responsiveness in both healthy mice and humans. The goal of the present study is to elucidate the underlying molecular mechanisms. The maximal force generated by mouse tracheas was measured in response to 10−4M of methacholine following a 30-min period with or without tone elicited by the EC30of methacholine. To confirm the occurrence of force adaptation at the cellular level, traction force generated by cultured human ASM cells was also measured following a similar protocol. Different pharmacological inhibitors were used to investigate the role of Rho-associated coiled-coil containing protein kinase (ROCK), protein kinase C (PKC), myosin light chain kinase (MLCK), and actin polymerization in force adaptation. The phosphorylation level of the regulatory light chain (RLC) of myosin, the amount of actin filaments, and the activation level of the actin-severing protein cofilin were also quantified. Although ROCK, PKC, MLCK, and RLC phosphorylation was not implicated, force adaptation was prevented by inhibiting actin polymerization. Interestingly, the presence of tone blocked the activation of cofilin in addition to increasing the amount of actin filaments to a maximal level. We conclude that actin filamentogenesis induced by tone, resulting from both actin polymerization and the prevention of cofilin-mediated actin cleavage, is the main molecular mechanism underlying force adaptation.
BMPR2 dysfunction impairs insulin signaling and glucose homeostasis in cardiomyocytes
Authors: Hemnes Anna R. , Fessel Joshua P. , Chen Xinping , Zhu Shijun , Fortune Niki L. , Jetter Christopher , Freeman Michael , Newman John H. , West James D. , Talati Megha H.
Published: December 2019

Insulin resistance and right ventricular (RV) dysfunction are associated with lipotoxicity in heritable forms of pulmonary arterial hypertension (PAH), commonly due to mutations in bone morphogenetic protein receptor type 2 (BMPR2). How BMPR2 dysfunction in cardiomyocytes alters glucose metabolism and the response of these cells to insulin are unknown. We hypothesized that BMPR2 mutation in cardiomyocytes alters glucose-supported mitochondrial respiration and impairs cellular responses to insulin, including glucose and lipid uptake. We performed metabolic assays, immunofluorescence and Western analysis, RNA profiling, and radioactive isotope uptake studies in H9c2 cardiomyocyte cell lines with and without patient-derived BMPR2 mutations (mutant cells), with and without insulin. Unlike control cells, BMPR2 mutant cardiomyocytes have reduced metabolic plasticity as indicated by reduced mitochondrial respiration with increased mitochondrial superoxide production. These mutant cells show enhanced baseline phosphorylation of insulin-signaling protein as indicated by increased Akt, AMPK, and acetyl-CoA carboxylase phosphorylation that may negatively influence fatty acid oxidation and enhance lipid uptake, and are insulin insensitive. Furthermore, mutant cells demonstrate an increase in milk fat globule-EGF factor-8 protein (MFGE8), which influences the insulin-signaling pathway by phosphorylating AktSer473 via phosphatidylinositol 3-kinase and mammalian target of rapamycin. In conclusion, BMPR2 mutant cardiomyocytes have reduced metabolic plasticity and fail to respond to glucose. These cells have enhanced baseline insulin-signaling pattern favoring insulin resistance with failure to augment this pattern in response to insulin. BMPR2 mutation possibly blunts glucose uptake and enhances lipid uptake in these cardiomyocytes. The MFGE8-driven signaling pathway may suggest a new mechanism underlying RV lipotoxicity in PAH.
Intact rather than total circulating insulin-like growth factor binding protein-1a is a negative indicator of growth in masu salmon
Authors: Kaneko Nobuto , Nilsen Tom Ole , Tanaka Hanae , Hara Akihiko , Shimizu Munetaka
Published: December 2019

Insulin-like growth factor binding protein (IGFBP)-1a is one of three major circulating forms in salmon and induced under catabolic conditions. However, there is currently no immunoassay available for this form because of a lack of standard and specific antibodies. We developed a time-resolved fluoroimmunoassay (TR-FIA) for salmon IGFBP-1a using recombinant protein for labeling, an assay standard, and production of antiserum. The TR-FIA had a low cross-reactivity (3.6%) with IGFBP-1b, another major form in the circulation. Fasting for 4 wk had no effect on serum immunoreactive (total) IGFBP-1a levels in yearling masu salmon, whereas 6-wk fasting significantly increased it. There was a significant, but weak, negative relationship between serum total IGFBP-1a level and individual growth rate ( r2 = 0.12, P = 0.01). We next developed a ligand immuno-functional assay (LIFA) using europium-labeled IGF-I to quantify intact IGFBP-1a. In contrast to total IGFBP-1a, serum intact IGFBP-1a levels increased after 4 wk of fasting, and refeeding for 2 wk restored it to levels similar to those of the fed control. Serum intact IGFBP-1a levels showed a significant negative correlation with individual growth rate ( r2 = 0.52, P < 0.001), which was as good as that of IGFBP-1b. Our findings using newly developed TR-FIA and LIFA suggest that regulation of intact IGFBP-1a levels has an important effect on growth in salmon and that intact IGFBP-1a is a negative index of salmon growth.
Rapid crossed responses in an intrinsic hand muscle during perturbed bimanual movements
Authors: Khong Katie Y. W. , Galán Ferran , Soteropoulos Demetris S.
Published: December 2019

Mechanical perturbations in one upper limb often elicit corrective responses in both the perturbed as well as its contralateral and unperturbed counterpart. These crossed corrective responses have been shown to be sensitive to the bimanual requirements of the perturbation, but crossed responses (CRs) in hand muscles are far less well studied. Here, we investigate corrective CRs in an intrinsic hand muscle, the first dorsal interosseous (1DI), to clockwise and anticlockwise mechanical perturbations to the contralateral index finger while participants performed a bimanual finger abduction task. We found that the CRs in the unperturbed 1DI were sensitive to the direction of the perturbation of the contralateral index finger. However, the size of the CRs was not sensitive to the amplitude of the contralateral perturbation nor its context within the bimanual task. The onset latency of the CRs was too fast to be purely transcortical (<70 ms) in 12/12 participants. This confirms that during isolated bimanual finger movements, sensory feedback from one hand can influence the other, but the pathways mediating the earliest components of this interaction are likely to involve subcortical systems such as the brainstem or spinal cord, which may afford less flexibility to the task demands.

NEW & NOTEWORTHY An intrinsic hand muscle shows a crossed response to a perturbation of the contralateral index finger. The crossed response is dependent on the direction of the contralateral perturbation but not on the amplitude or the bimanual requirements of the movement, suggesting a far less flexible control policy than those governing crossed responses in more proximal muscles. The crossed response is too fast to be purely mediated by transcortical pathways, suggesting subcortical contributions.
The small fiber neuropathy NaV1.7 I228M mutation: impaired neurite integrity via bioenergetic and mitotoxic mechanisms, and protection by dexpramipexole
Authors: Lee Seong-il , Hoeijmakers Janneke G. J. , Faber Catharina G. , Merkies Ingemar S. J. , Lauria Giuseppe , Waxman Stephen G.
Published: December 2019

Gain-of-function variants in voltage-gated sodium channel NaV1.7 that increase firing frequency and spontaneous firing of dorsal root ganglion (DRG) neurons have recently been identified in 5–10% of patients with idiopathic small fiber neuropathy (I-SFN). Our previous in vitro observations suggest that enhanced sodium channel activity can contribute to a decrease in length of peripheral sensory axons. We have hypothesized that sustained sodium influx due to the expression of SFN-associated sodium channel variants may trigger an energetic deficit in neurons that contributes to degeneration and loss of nerve fibers in SFN. Using an ATP FRET biosensor, we now demonstrate reduced steady-state levels of ATP and markedly faster ATP decay in response to membrane depolarization in cultured DRG neurons expressing an SFN-associated variant NaV1.7, I228M, compared with wild-type neurons. We also observed that I228M neurons show a significant reduction in mitochondrial density and size, indicating dysfunctional mitochondria and a reduced bioenergetic capacity. Finally, we report that exposure to dexpramipexole, a drug that improves mitochondrial energy metabolism, increases the neurite length of I228M-expressing neurons. Our data suggest that expression of gain-of-function variants of NaV1.7 can damage mitochondria and compromise cellular capacity for ATP production. The resulting bioenergetic crisis can consequently contribute to loss of axons in SFN. We suggest that, in addition to interventions that reduce ionic disturbance caused by mutant NaV1.7 channels, an alternative therapeutic strategy might target the bioenergetic burden and mitochondrial damage that occur in SFN associated with NaV1.7 gain-of-function mutations.

NEW & NOTEWORTHY Sodium channel NaV1.7 mutations that increase dorsal root ganglion (DRG) neuron excitability have been identified in small fiber neuropathy (SFN). We demonstrate reduced steady-state ATP levels, faster depolarization-evoked ATP decay, and reduced mitochondrial density and size in cultured DRG neurons expressing SFN-associated variant NaV1.7 I228M. Dexpramipexole, which improves mitochondrial energy metabolism, has a protective effect. Because gain-of-function NaV1.7 variants can compromise bioenergetics, therapeutic strategies that target bioenergetic burden and mitochondrial damage merit study in SFN.
Association of Immune Thrombocytopenia and T-Lymphoblastic Lymphoma in a Pediatric Patient
Authors: Denu Ryan A. , Matson Daniel R. , Davis Matthew J. , Tedford Natalie J. , Brichta Christine E. , Diamond Carol A. , Hoover-Regan Margo L.
Published: December 2019

Immune thrombocytopenia (ITP) is characterized by isolated thrombocytopenia of unclear etiology. We present a unique case of an 8-year-old girl with chronic ITP who was subsequently diagnosed with T-lymphoblastic lymphoma at age 11. The clinical course was complicated by the occurrence of nonepileptiform events with bizarre behavior changes following the administration of nelarabine and intrathecal and high-dose systemic methotrexate. This case highlights an unusual co-occurrence of hematologic malignancy and chronic ITP in an otherwise healthy child. We speculate that underlying genetic or immunologic lesions may predispose a subset of pediatric ITP patients to the development of hematologic malignancies.
A Massive Extradural Hematoma in Sickle Cell Disease and the Importance of Rapid Neuroimaging
Authors: Iversen Per Ole , Jacob Mboka , Makame Jamila , Abisay Mclean , Yonazi Mbonea , Schuh Anna , Makani Julie
Published: December 2019

Sickle cell disease (SCD) is an inherited hemoglobinopathy leading to several serious organ complications and early death. It is mostly found in equatorial countries like Tanzania. Extradural hematoma (EDH) is a rare, but serious complication to SCD and may have debilitating consequences. Hitherto, there is no report of EDH in SCD where neuroimaging has been available before, during, and after such an event. Here, we describe a young female SCD patient who developed EDH that required surgical evacuation. She had made full recovery after three months. Neuroimaging performed two years prior to this event was unremarkable except for multiple small cerebral infarcts. On admission, neuroimaging revealed a subgaleal hematoma, possibly indicating disruption of the skull cortex due to increased hematopoiesis. Three months after evacuation of the hematoma, neuroimaging showed evidence of brain atrophy and the previously reported cerebral infarcts and multifocal bone infarction, but no vasculopathy. Possibly, disruption of the skull cortex with subsequent bleeding caused the EDH. As the differential diagnoses of neurological complications in SCD are many and some complications are reversible, neuroimaging should be performed without delay.
Clinical Features, Treatment, and Surveillance of Hyperparathyroidism-Jaw Tumor Syndrome: An Up-to-Date and Review of the Literature
Authors: Torresan Francesca , Iacobone Maurizio
Published: December 2019

Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is an autosomal dominant disorder characterized by parathyroid tumors in association with fibro-osseous jaw tumors and uterine and renal lesions. HPT-JT syndrome is caused by germline mutations of the cell division cycle 73 (CDC73) gene that encodes the parafibromin, a 531-amino acid protein with antiproliferative activity. Primary hyperparathyroidism is the main finding of HPT-JT syndrome, usually caused by a single-gland parathyroid involvement (80% of cases), at variance with other variants of hereditary hyperparathyroidism, in which a multiglandular involvement is more frequent. Moreover, parathyroid carcinoma may occur in approximately 20% of cases. Surgery is the treatment of choice for primary hyperparathyroidism, but the extent of surgery remains controversial, varying between bilateral neck and focused exploration, with subtotal or limited parathyroidectomy. Recently, more limited approaches and parathyroid excisions have been suggested in order to decrease the risk of permanent hypoparathyroidism, the main surgical morbidity following more extensive surgical approaches. Ossifying fibromas of the mandible or maxilla may present only in a minority of cases and, even if benign, they should be surgically treated to avoid tumor growth and subsequent functional limitations. Benign and malignant uterine involvement (including leiomyomas, endometrial hyperplasia, adenomyosis, multiple adenomyomatous polyps, and adenosarcomas) is the second most common clinical feature of the syndrome, affecting more than 50% of CDC73-carrier women. Genetic testing should be performed in all family members of affected individuals, in young patients undergoing surgery for primary hyperparathyroidism, or in presence of other associated tumors, allowing early diagnosis and prompt treatment with more tailored surgery. Moreover, CDC73 mutation carriers should be also periodically screened for primary hyperparathyroidism and the other associated tumors. The present review was aimed to summarize the main clinical features of HPT-JT syndrome, focusing on genetic screening and surgical treatment, and to revise the available literature.
Hepatoprotective Activity of Some Medicinal Plants in Sudan
Authors: Ali Sumaia A. , Sharief Noha H. , Mohamed Yahya S.
Published: December 2019

Background. Liver disorders are common in Sudan and elsewhere. These are traditionally treated by medicinal plants especially in rural areas where they are widely available. Methods. This review was based on scientific research in hepatoprotective plants performed in Sudan for the period between 2001 and 2016 AD. Data collection was done through scientific evidence of local and international published data, theses, and publications from some libraries in Sudanese universities. Internet was also used to collect published data in different international scientific journals. Results. In this study, 21 plants from different families were reviewed for the hepatoprotective activity in Sudan. These plants are widely used in traditional medicine for their availability and cheap prices. All of these plants have been scientifically investigated through experimental animal models which confirmed their hepatoprotective activities. This was evaluated by measuring several parameters including liver markers (AST, ALT, ALP, total protein, albumin, and bilirubin) and histopathological investigation. Nineteen (90.5%) of the herbal plants were found to possess significant hepatoprotective activity in animal models. Two (9.5%) of the plants were devoid of this activity. The action of these plants is largely attributed to their phytoconstituents such as flavonoids, antioxidant, and anti-inflammatory effects. Conclusion. Sudanese herbs may offer novel alternatives to treat liver disorders. Yet determination of the active principle responsible for hepatoprotection needs to be investigated. Further studies on these plants are necessary to establish the efficacy, safety, and exact mechanism of action as a moral alternative in the treatment of liver disorders.
Ensuring the Confidentiality of Nuclear Information at Cloud Using Modular Encryption Standard
Authors: Shabbir Aysha , Shabbir Maryam , Rizwan Muhammad , Ahmad Fahad
Published: December 2019

Lifeblood of every organization is its confidential information. The accentuation on cybersecurity has expanded considerably in the course of the last few years because of the expanded number in attacks at the individual and organization and even at the state level. One specific zone of consideration is the assurance of the security of nuclear information. This may relate to both Instrumentation and Control (I&C) and Information Technology (IT). The present security measures are insufficient for nuclear information because of their lack of identification, classification, and securing measures (because of their multifaceted nature). With the increasing trends of data storage and management with the assistance of cloud, data confidentiality threats are immensely increasing. As there is no such safeguard that can make our systems a hundred percent secure, the best approach is to provide security at distinct layers. The basic purpose of layered security is to have the benefit that if one layer fails or compromised, the other layer compensates or maintains that confidentiality with the access control in the owner’s hand. In this paper, we have proposed a multilevel approach with protection-based computing by using Modular Encryption Standard (MES). We proposed a cloud framework as well to further enhance its security by utilizing a multicloud and modular approach. By performing simulations, the obtained results depicted that our proposed scheme works efficiently than other commonly used schemes.
Autophagy Deficiency Leads to Impaired Antioxidant Defense via p62-FOXO1/3 Axis
Authors: Zhao Lin , Li Hao , Wang Yan , Zheng Adi , Cao Liu , Liu Jiankang
Published: December 2019

Autophagy, an intracellular degradation mechanism eliminating unused or damaged cytoplasmic components for recycling, is often activated in response to diverse types of stress, profoundly influencing cellular physiology or pathophysiology. Upon encountering oxidative stress, autophagy acts rapidly and effectively to remove oxidized proteins or organelles, including damaged mitochondria that generate more ROS, thereby indirectly contributing to the maintenance of redox homeostasis. Emerging studies are shedding light on the crosstalks among autophagy, mitochondria, and oxidative stress; however, whether and how autophagy could directly modulate antioxidant defense and redox homeostasis remains unaddressed. Here, we showed mitochondrial dysfunction, elevated ROS level, impaired antioxidant enzymes, and loss of FOXO1/3 in autophagy deficiency cellular models established by either chemical inhibitors or knocking down/out key molecules implementing autophagy, and overexpression of FOXO1/3 restored antioxidant enzymes hence suppressed elevated ROS; knockdown of p62 increased protein level of FOXO1/3 and recovered FOXO1 in Atg5-knockdown cells. Our data demonstrates that the loss of FOXO1/3 is responsible for the impairment of antioxidant enzymes and the consequent elevation of ROS, and accumulation of p62 under condition of autophagy deficiency might be mediating the loss of FOXO1/3. Furthermore, we found in an animal model that the p62-FOXO1/3 axis could be dominant in aging liver but not in type 2 diabetic liver. Together, these evidences uncover the p62-FOXO1/3 axis as the molecular cue that underlies the impairment of antioxidant defense in autophagy deficiency and suggest its potential involvement in aging, substantiating the impact of inadequate autophagy on mitochondria and redox homeostasis.
Study on Seismic Behavior of Steel Frame‐Steel Shear Wall with Assembled Two‐Side Connections
Authors: Zhang Yuben , Zhan Xun
Published: December 2019

Low‐cycle reciprocating loading tests were carried out on a steel frame with prefabricated beam‐only connected steel plate shear wall (specimen A) and a steel frame with welded beam‐only connected steel plate shear wall (specimen B). The seismic performance of the two different types of steel frame‐steel plate shear wall specimens was studied and the failure modes, hysteresis curve, skeleton curve, and seismic performance index, etc of two groups of specimens were obtained, together with the studies of failure characteristics, ductility, energy dissipation, and stiffness degradation of the two specimens. The results showed that the assembled steel frame‐steel plate shear wall with connection joints of steel shear wall with discontinuous cover plate connected on both sides (DCPC) have good seismic performance. On the basis of no loss of seismic performance, DCPC joints can provide better energy dissipation capacity than traditional welded steel plate shear wall structures and ensure the good postearthquake repair function.
Movement Assessment Battery for Children-Second Edition (MABC2): Cross-Cultural Validity, Content Validity, and Interrater Reliability in Thai Children
Authors: Jaikaew Rujira , Satiansukpong Nuntanee
Published: December 2019

Introduction. The Movement Assessment Battery for Children-Second Edition (MABC2) is a standardized test for detecting children with movement difficulty. It was established and is used widely in Western countries. Studying cross-cultural validity and reliability was necessary before using the MABC2 with Thai children. Purposes. To study cross-cultural validity, content validity, and interrater reliability of the MABC2. Method. The MABC2-Age Band 2 (AB2: children aged 7-10 years) was translated into Thai from the source version of the MABC2 by using the following steps: forward translation, backward translation, panel discussion, and testing of the prefinal version of the Thai-MABC2-AB2. Five occupational therapists checked the content validity of the test. Twenty-nine children, aged 7-10 years, were examined by two testers in order to establish interrater reliability. Results. This cross-cultural study demonstrated validity in the Thai context. Content validity was good with an item-objective congruence (IOC) range from 0.73 to 0.95. The intraclass correlation coefficient (ICC) of interrater reliability ranged from 0.71 to 1.00. Conclusion. The Thai-MABC2-AB2 is a good fit for use in a clinical and Thai cultural setting. Interrater reliability was moderate to good, which meant results between testers were consistent.
Analysis of Spiders’ Joint Kinematics and Driving Modes under Different Ground Conditions
Authors: Hao Xin , Ma Wenxing , Liu Chunbao , Li Yilei , Qian Zhihui , Ren Luquan , Ren Lei
Published: December 2019

Although the hydraulic transmission system in spider legs is well known, the spider’s mechanism of locomotion during different terrain conditions still need to be explored further. In this study, spider locomotion was observed in detail on three pavement test platforms: horizontal hard pavement, horizontal soft pavement, and sloped soft pavement. The movement characteristics and joint kinematics ofGrammostola rosealegs were captured by high-speed cameras and Simi Motion 3D tracking software. These observations showed that the gait pattern was basically consistent with an alternating tetrapod gait; however, the pattern observed on the sloped soft pavement was slightly different from that of the two horizontal pavements. In particular, the duty factor of the spiders was 0.683 when walking on the horizontal hard pavement, 0.668 on the horizontal soft pavement, and 0.630 on the sloped soft pavement. The duty factor was greater than 60% in all three pavement environments, which was minimal when walking on the sloped soft pavement. This pattern showed that spiders might have superior stability when walking, but their stability decreased in the sloped soft pavement environment. The ranges of joint angles through the spiders’ gait cycles in every pavement environment were also analysed and compared. The findings showed that the hydraulically driven femur-patella and tibia-metatarsal joint angles varied widely, which confirmed that hydraulically driven joints had major functions and obvious effects on the walking process. The kinematic patterns identified in this study provide improved understanding of the hydraulic transmission mechanisms, the factors that affect motion stability, and the design of biomimetic systems.
Central Nervous System Double Relapse of Acute Promyelocytic Leukemia and Acute Myelomonocytic Leukemia
Authors: Stanko Laura M. , Reddy Vishnu , Mikhail Fady M. , Papadantonakis Nikolaos
Published: December 2019

Relapse of acute promyelocytic leukemia (APL) and non-M3-acute myeloid leukemia in the central nervous system (CNS) are rare events. Here, we describe a case of simultaneous relapses of APL and acute myelomonocytic leukemia on the CNS of a patient after allogeneic bone marrow transplant. This extremely unusual case highlights the difficulties that CNS leukemia relapses pose in the post-transplant setting.
Superior Approach of Recurrent Laryngeal Nerve: Review of the Literature
Authors: Fatogoma Issa Koné , Sidiki Dao , Naouma Cissé , Kassim Diarra , N’Faly Konaté , Djibril Samaké , Neuilly Tafo , Abdoul Wahab Haidara , Boubacary Guindo , Siaka Soumaoro , Kadidiatou Singaré , Samba Karim Timbo , Mohamed Amadou Kéita
Published: December 2019

The identification and dissection of the recurrent laryngeal nerve is essential to guarantee its anatomical and functional integrity. The superior approach of the recurrent nerve is a reliable surgical alternative. Various indications are recognized with a reliable landmark. This is the entry point into the larynx under the inferior horn of the thyroid cartilage. The limits of this technique, namely, the extralaryngeal divisions and the hemorrhages encountered at the point of entry of the larynx are a source of morbidity of the recurrent laryngeal nerve. A careful dissection, respect for the surgical steps, and the surgeon's experience are guarantees of a good result. We wanted through a review of the literature and our experience in the superior approach to discuss surgical indications, to identify landmarks at the point of entry of the larynx, to determine the limits of this approach, and to take precautions to mitigate the risk of recurrent laryngeal nerve injury.
Patient Preferences for Nonvitamin K Antagonist Oral Anticoagulants in Stroke Prevention: A Multicountry Discrete Choice Experiment
Authors: Wilke Thomas , Meinecke Anna-Katharina , Schaefer Bernhard , Buchwald Sandra , Eriksson Daniel , Müller Sabrina
Published: December 2019

Purpose. The patient’s perspective is becoming increasingly important in clinical and policy decisions. This study examined atrial fibrillation (AF) patient preferences for different characteristics of nonvitamin K antagonist oral anticoagulants (NOACs). Methods. A discrete choice experiment (DCE) addressing AF patients treated with NOACs in France, Germany, and the United Kingdom was conducted. The DCE included the following attributes: frequency of administration (once/twice daily), size of tablet/capsule (6–9 mm/20 mm), meal-related intake (intake with food required/independent), and distance to treating physician (1 km/10 km). Preferences were analyzed based on a conditional logit regression model. Results. In total, 758 patients (males: 57.3%; mean age: 71.4 years) with an average disease duration of 5.5 years were included (apixaban/dabigatran/edoxaban/rivaroxaban: 34.0%/14.5%/6.6%/44.9%, respectively). Patients preferred NOAC treatment options characterized by once-daily dosing regimens (42.8%; p<0.001), shorter distance to treating physicians (25.0%; p<0.001), a small-sized tablet (21.5%; p<0.001), and intake independent of food (10.6%; p<0.001). Conclusions. Patients primarily prefer a once-daily NOAC regimen. Individual preferences should be considered for the treatment of AF patients as this may result in improved treatment adherence and consequently better effectiveness and safety in routine clinical practice.
Clinical Characteristics and Risk Factors of Lung Cancer-Associated Acute Ischemic Stroke
Authors: Lin Jiacai , Wu Siting , Xu Rui , Shi Qiang , Tian Chenglin , Cui Fang , Shao Xue , Liu Hui
Published: December 2019

Objective. To research the clinical characteristics and risk factors of lung cancer-associated acute ischemic stroke (LCA-AIS). Methods. Patients diagnosed with LCA-AIS, simple lung cancer, and simple AIS were enrolled. The primary information, laboratory results, tumor histopathology, neurological deficits, and survival time of the patients were collected and analyzed. Results. (1) In the LCA-AIS group, the pathology of 69.56% patients were adenocarcinoma, and the proportion of poorly differentiated patients was significantly more than that in moderately differentiated or highly differentiated. The number of stage IV lung cancer patients in the LCA-AIS group was significantly more common than in other stages. (2) 56.52% of patients with lung cancer were diagnosed before AIS, and the peak of AIS attack was 1–6 months after the diagnosis of lung cancer. (3) The independent risk factors of LCA-AIS were CYFRA-211 (OR 1.070; 95% confidence interval 1.005, 1.139; p=0.035), TT (OR 1.275; 95% confidence interval 1.089, 1.493; p=0.003), and Hct (OR 0.878; 95% confidence interval 0.779, 0.990; p=0.034), making ROC curve, suggesting the area under the curve is 0.871. (4) The neurological deficit of patients in the LCA-AIS group was similar to the simple AIS group and could not be identified by the severity of neurological deficits. (5) The median survival time of LCA-AIS group patients was five months (95% confidence interval 3.796, 6.204). There were statistical differences in survival time between LCA-AIS group and simple AIS group patients (p<0.001).Conclusions. The interaction between lung cancer and AIS may shorten patients’ life expectancy and worsen their quality of life.