Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal Structure of the N-Acetylmannosamine Kinase Domain of GNE

Background UDP-GlcNAc 2-epimerase/ManNAc 6-kinase, GNE, is a bi-functional enzyme that plays a key role in sialic acid biosynthesis. Mutations of the GNE protein cause sialurea or autosomal recessive inclusion body myopathy/Nonaka myopathy. GNE is the only human protein that contains a kinase domain belonging to the ROK (repressor, ORF, kinase) family. Principal Findings We solved the structure of the GNE kinase domain in the ligand-free state. The protein exists predominantly as a dimer in solution, with small populations of monomer and higher-order oligomer in equilibrium with the dimer. Crystal packing analysis reveals the existence of a crystallographic hexamer, and that the kinase domain dimerizes through the C-lobe subdomain. Mapping of disease-related missense mutations onto the kinase domain structure revealed that the mutation sites could be classified into four different groups based on the location – dimer interface, interlobar helices, protein surface, or within other secondary structural elements. Conclusions The crystal structure of the kinase domain of GNE provides a structural basis for understanding disease-causing mutations and a model of hexameric wild type full length enzyme. Enhanced Version This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.
Frontal cortical mitochondrial dysfunction and mitochondria-related β-amyloid accumulation by chronic sleep restriction in mice

Mitochondrial dysfunction induced by mitochondria-related &bgr;-amyloid (A&bgr;) accumulation is increasingly being considered a novel risk factor for sporadic Alzheimer’s disease pathophysiology. The close relationship between chronic sleep restriction (CSR) and cortical A&bgr; elevation was confirmed recently. By assessing frontal cortical mitochondrial function (electron microscopy manifestation, cytochrome C oxidase concentration, ATP level, and mitochondrial membrane potential) and the levels of mitochondria-related A&bgr; in 9-month-old adult male C57BL/6J mice subjected to CSR and as an environmental control (CO) group, we aimed to evaluate the association of CSR with mitochondrial dysfunction and mitochondria-related A&bgr; accumulation. In this study, frontal cortical mitochondrial dysfunction was significantly more severe in CSR mice compared with CO animals. Furthermore, CSR mice showed higher mitochondria-associated A&bgr;, total A&bgr;, and mitochondria-related &bgr;-amyloid protein precursor (A&bgr;PP) levels compared with CO mice. In the CSR model, mouse frontal cortical mitochondrial dysfunction was correlated with mitochondria-associated A&bgr; and mitochondria-related A&bgr;PP levels. However, frontal cortical mitochondria-associated A&bgr; levels showed no significant association with cortical total A&bgr; and mitochondrial A&bgr;PP concentrations. These findings indicated that CSR-induced frontal cortical mitochondrial dysfunction and mitochondria-related A&bgr; accumulation, which was closely related to mitochondrial dysfunction under CSR.
Membrane composition-mediated protein-protein interactions

The authors investigate membrane composition-mediated interactions between proteins adsorbed onto a two-component lipid bilayer close to critical demixing using coarse-grained molecular dynamics simulations and a phenomenological Ginzburg-Landau theory. The simulations consist of three-bead lipids and platelike proteins, which adsorb onto the membrane by binding preferentially to one of the two lipid species. The composition profile around one protein and the pair correlation function between two proteins are measured and compared to the analytical predictions. The theoretical framework is applicable to any scalar field embedded in the membrane, and although in this work the authors treat flat membranes, the methodology extends readily to curved geometries. Neglecting fluctuations, both lipid composition profile and induced protein pair potential are predicted to follow a zeroth order modified Bessel function of the second kind with the same characteristic decay length. These predictions are consistent with our molecular dynamics simulations, except that the interaction range is found to be larger than the single profile correlation length.
Pseudononlinear ultrasound simulation approach for reverberation clutter

Abstract. Multipath scattering, or reverberation, takes a substantial toll on image quality in many clinical exams. We have suggested a model-based solution to this problem, which we refer to as aperture domain model image reconstruction (ADMIRE). For ADMIRE to work well, it must be trained with precisely characterized data. To solve this specific problem and the general problem of efficiently simulating reverberation, we propose an approach to simulate reverberation with linear simulation tools. Our simulation method defines total propagation time, first scattering site, and a final scattering site. We use a linear simulation package, such as Field II, to simulate scattering from the final site and then shift the simulated wavefront later in time based on the total propagation time and the geometry of the first scattering site. We validate our simulations using theoretical descriptions of clutter in the literature and data acquired from ex vivo tissue. We found that ex vivo tissue clutter had a mean speckle SNR of 1.40±0.23, which we could simulate with about 2 scatterers per resolution cell. Axial clutter distributions drawn from an exponential distribution with a mean of 5 mm and at least 0.5 scatters per resolution cell resulted in clutter that was statistically indistinguishable from the van Cittert–Zernike behavior predicted by literature.
Comparison of glomerular filtration rate estimating equations derived from creatinine and cystatin C: validation in the Age, Gene/Environment Susceptibility-Reykjavik elderly cohort

Background Validation studies comparing glomerular filtration rate (GFR) equations based on standardized creatinine and cystatin C assays in the elderly are needed. The Icelandic Age, Gene/Environment Susceptibility-Kidney cohort was used to compare two pairs of recently developed GFR equations, the revised Lund-Malmö creatinine equation (LMRCr) and the arithmetic mean of the LMRCr and Caucasian, Asian, Paediatric and Adult cystatin C equations (MEANLMR+CAPA), as well as the Full Age Spectrum creatinine equation (FASCr) and its combination with cystatin C (FASCr+Cys), with the corresponding pair of Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPICr and CKD-EPICr+Cys). Methods A total of 805 individuals, 74-93 years of age, underwent measurement of GFR (mGFR) using plasma clearance of iohexol. Four metrics were used to compare the performance of the GFR equations: bias, precision, accuracy [including the percentage of participants with estimated GFR (eGFR) within 30% of mGFR (P30)] and the ability to detect mGFR <60 mL/min/1.73 m2. Results All equations had a P30 >90%. LMRCr and FASCr yielded significantly higher precision and P30 than CKD-EPICr, while bias was significantly worse. LMRCr, FASCr and CKD-EPICr showed similar ability to detect mGFR <60 mL/min/1.73 m2 based on the area under the receiver operating characteristic curves. MEANLMR+CAPA, FASCr+Cys and CKD-EPICr+Cys all exhibited consistent improvements compared with the corresponding creatinine-based equations. Conclusion None of the creatinine-based equations was clearly superior overall in this community-dwelling elderly cohort. The addition of cystatin C improved all of the creatinine-based equations.
Cervical Lateral Glide Neural Mobilization Is Effective in Treating Cervicobrachial Pain: A Randomized Waiting List Controlled Clinical Trial

Background Cervicobrachial pain (CP) is a high-incidence and prevalent condition. Cervical lateral glide (CLG) is a firstline treatment of CP. There is a current lack of enough high-quality randomized controlled double-blind clinical trials that measure the effectiveness of neural tissue mobilization techniques such as the CLG and its specific effect over CP. Objectives The aim of the present study was to assess the effect of CLG neural mobilization in treating subjects who suffer from CP, compared with the complete absence of treatment. Study Design This investigation was a single-center, blinded, parallel randomized controlled clinical trial (RCT). Setting One hundred forty-seven individuals were screened in a medical center from July to November 2015. Fifty-eight participants were diagnosed with CP. Methods Participants were recruited and randomly assigned into two groups of 29 subjects. The intervention group received CLG treatment, and the control group (CG) was assigned to a six-week waiting list to receive treatment. Randomization was carried out by concealed computer software randomized printed cards. The primary outcome was pain intensity, reported through the Numeric Rating Scale for Pain (NRSP). Secondary outcomes were physical function involving the affected upper limb using the Quick DASH scale and ipsilateral cervical rotation (ICR) using a CROM device. Assessments were made at baseline and one hour after treatment. Results The CLG group NRSP mean value was significantly (P < 0.0001) superior to those obtained by the CG. Subjects treated with CLG reported an average NRSP decrease of 2.16 points (35%). CROM device and Quick DASH outcome values also reported significant (P < 0.0001) improvements only in the CLG group. Cohen's d showed a very large effect of the CLG intervention at subject discharge. Limitations Due to the lack of dipper subgroup analysis and additional reproductions of the applied protocol, the authors considered the generalization of the study results to be impossible. Conclusions CLG is superior to the absence of treatment in reducing pain and increasing the affected upper limb function of subjects who suffer from CP. CLG may be considered an effective treatment in specific cases of CP.
Age Estimation in Living Egyptians Using Signal Joint T‐cell Receptor Excision Circle Rearrangement

Age estimation is one of the challenges in forensic sciences. There are many techniques to estimate the age. Molecular biology approach is one of these techniques. Signal joint T‐cell receptor excision circles gene (sjTRECs), is one of this approach. We aimed to use sjTRECs as a suitable marker for age estimation among Egyptian population. TaqMan qPCR approach was used to quantify sjTREC levels in blood samples obtained from 153 healthy Egyptian individuals ranging from a few weeks to 70 years. Our results showed a significant negative correlation between sjTREC levels and age with p ≤ 0.05. Moreover, the individual's age can be determined through this formula Age = −30.671+ (−5.998Y) (Y is dCtTBP − sjTREC) with standard error ±7.35 years. Within the forensic context, sjTREC' levels can be used to estimate the Egyptian individual's age accurately.
Toll-like receptor 3 as an immunotherapeutic target for KRAS mutated colorectal cancer

New therapeutic interventions are essential for improved management of patients with metastatic colorectal cancer (mCRC). This is especially critical for those patients whose tumors harbor a mutation in the KRAS oncogene (40-45% of all patients). This patient cohort is excluded from receiving anti-EGFR monoclonal antibodies that have added a significant therapeutic benefit for KRAS wild type CRC patients. Reovirus, a double stranded (ds) RNA virus is in clinical development for patients with chemotherapy refractory KRAS mutated tumors. Toll Like Receptor (TLR) 3, a member of the toll like receptor family of the host innate immune system is the pattern recognition motif for dsRNA pathogens. Using TLR3 expressing commercial HEK-Blue™-hTLR3 cells we confirm that TLR3 is the host pattern recognition motif responsible for the detection of reovirus. Further, our investigation with KRAS mutated HCT116 cell line showed that effective expression of host TLR3 dampens the infection potential of reovirus by mounting a robust innate immune response. Down regulation of TLR3 expression with siRNA improves the anticancer activity of reovirus. In vivo experiments using human CRC cells derived xenografts in athymic mice further demonstrate the beneficial effects of TLR3 knock down by improving tumor response rates to reovirus. Strategies to mitigate the TLR3 response pathway can be utilized as a tool towards improved reovirus efficacy to specifically target the dissemination of KRAS mutated CRC.
Adjuvant Chemotherapy vs Postoperative Observation Following Preoperative Chemoradiotherapy and Resection in Gastroesophageal Cancer: A Propensity Score–Matched Analysis

Importance Distant recurrence following preoperative chemoradiotherapy and resection in patients with gastroesophageal adenocarcinoma is common. Adjuvant chemotherapy may improve survival. Objective To compare adjuvant chemotherapy with postoperative observation following preoperative chemoradiotherapy and resection in patients with gastroesophageal adenocarcinoma. Design, Setting, and Participants Propensity score–matched analysis using the National Cancer Database. We included adult patients who received a diagnosis between 2006 and 2013 of clinical stage T1N1-3M0 or T2-4N0-3M0 adenocarcinoma of the distal esophagus or gastric cardia who were treated with preoperative chemoradiotherapy and curative-intent resection. Patients receiving adjuvant chemotherapy were matched by propensity score to patients undergoing postoperative observation. Exposures Adjuvant chemotherapy and postoperative observation. Main Outcomes and Measures Overall survival. Results We identified 10 086 patients (8840 [88%] male; mean [SD] age, 61 [9.5] years), 9272 in the postoperative observation group and 814 in the adjuvant chemotherapy group. Patients receiving adjuvant chemotherapy were younger (18-54 years: 252 [31%] vs 1989 [21%]; P < .001) and were more likely to have advanced disease (ypT3/4: 458 [62%] vs 3531 [46%]; P < .001; ypN+: 572 [72%] vs 3428 [39%]; P < .001), as well as shorter postoperative inpatient stays (>2 weeks: 94 [13%] vs 1589 [20%]; P < .001). A total of 732 patients in the adjuvant chemotherapy group were matched by propensity score to 3660 patients in the postoperative observation group. Adjuvant chemotherapy was associated with improved overall survival compared with postoperative observation (median survival: 40 months; 95% CI, 36-46 months vs 34 months; 95% CI, 32-35 months; stratified log-rank P < .001; hazard ratio, 0.79; 95% CI, 0.72-0.88). Overall survival at 1, 3, and 5 years was 88%, 47%, and 34% in the observation group, and 94%, 54%, and 38% in the adjuvant chemotherapy group, respectively. Adjuvant chemotherapy was associated with a survival benefit compared with postoperative observation in most patient subgroups. Conclusions and Relevance For patients with locally advanced gastroesophageal adenocarcinoma treated with preoperative chemoradiotherapy and resection, adjuvant chemotherapy was associated with improved overall survival. Our findings have important implications for the postoperative treatment of this patient group for which few data are available.
AMC: an adaptive multi‐level cache algorithm in hybrid storage systems

Hybrid storage systems that consist of flash‐based solid state drives (SSDs) and traditional disks are now widely used. In hybrid storage systems, there exists a two‐level cache hierarchy that regard dynamic random access memory (DRAM) as the first level cache and SSD as the second level cache for disk storage. However, this two‐level cache hierarchy typically uses independent cache replacement policies for each level, which makes cache resource management inefficient and reduces system performance. In this paper, we propose a novel adaptive multi‐level cache (AMC) replacement algorithm in hybrid storage systems. The AMC algorithm adaptively adjusts cache blocks between DRAM and SSD cache levels using an integrated solution. AMC uses combined selective promote and demote operations to dynamically determine the level in which the blocks are to be cached. In this manner, the AMC algorithm achieves multi‐level cache exclusiveness and makes cache resource management more efficient. By using real‐life storage traces, our evaluation shows the proposed algorithm improves hybrid multi‐level cache performance and also increases the SSD lifetime compared with traditional multi‐level cache replacement algorithms. Copyright © 2015 John Wiley & Sons, Ltd.
The grand challenges of Science Robotics

These 10 grand challenges may have major breakthroughs, research, and/or socioeconomic impacts in the next 5 to 10 years. One of the ambitions of Science Robotics is to deeply root robotics research in science while developing novel robotic platforms that will enable new scientific discoveries. Of our 10 grand challenges, the first 7 represent underpinning technologies that have a wider impact on all application areas of robotics. For the next two challenges, we have included social robotics and medical robotics as application-specific areas of development to highlight the substantial societal and health impacts that they will bring. Finally, the last challenge is related to responsible innovation and how ethics and security should be carefully considered as we develop the technology further.
Plasmonic Sensing in D-Shaped POFs With Fluorescent Optical Fibers as Light Sources

We present a new experimental investigation about the possibility to use fluorescent optical fibers as light sources, instead of halogen lamps, for plasmonic sensing. The novel configuration has been first introduced, and then the components’ properties and the experimental results have been illustrated. Two sensor systems have been realized and characterized by exploiting red and blue fluorescent optical fibers to illuminate different plasmonic sensors and observe the transmitted spectra by a spectrometer. In particular, the plasmonic sensors have been realized with two different metals, gold and silver, sputtered on D-shaped plastic optical fibers (POFs) with an optical buffer layer between the metal film and the POF core. We have matched the metal’s plasmonic resonance wavelength with the emission of a specific fluorescent optical fiber. The good quality of the experimental results, the low-power consumption, the low cost, the remote sensing capability, the small size, and the simple scheme of the configuration make this strategy a potentially suitable diagnostic tool for biosensing applications.
The biasing of baryons on the cluster mass function and cosmological parameter estimation

We study the effect of baryonic processes on the halo mass function in the galaxy cluster mass range using a catalogue of 153 high resolution cosmological hydrodynamical simulations performed with the AMR code ramses. We use the results of our simulations within a simple analytical model to gauge the effects of baryon physics on the halo mass function. Neglect of AGN feedback leads to a significant boost in the cluster mass function similar to that reported by other authors. However, including AGN feedback not only gives rise to systems that are similar to observed galaxy clusters, but they also reverse the global baryonic effects on the clusters. The resulting mass function is closer to the unmodified dark matter halo mass function but still contains a mass dependent bias at the 5-10% level. These effects bias measurements of the cosmological parameters, such as $\sigma_8$ and $\Omega_m$. For current cluster surveys baryonic effects are within the noise for current survey volumes, but forthcoming and planned large SZ, X-ray and multi-wavelength surveys will be biased at the percent level by these processes. The predictions for the halo mass function including baryonic effects need to be carefully studied with larger and improved simulations. However, simulations of full cosmological boxes with the resolution we achieve and including AGN feedback are still computationally challenging.
Using the Berlin Questionnaire to Predict Obstructive Sleep Apnea in the General Population.

STUDY OBJECTIVES The Berlin questionnaire is a self-administered questionnaire that was developed to identify subjects with obstructive sleep apnea (OSA) in primary care settings. This study evaluated the performance of the questionnaire to predict OSA in the general population. METHODS A sample of 242 subjects in a population-based cohort completed a home-based sleep study with an Embletta device (type 3 monitor). Subjects completed the Berlin questionnaire on the evening just prior to the sleep study. The sleep studies were manually scored according to the 2012 American Academy of Sleep Medicine (AASM) criteria. RESULTS The prevalence of moderate-to-severe and severe OSA defined as apnea-hypopnea index (AHI) of ≥ 15 and ≥ 30 was 28.1% and 10.7%, respectively. Seventy-nine subjects (32.6%) were classified as high risk according to the Berlin questionnaire. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the questionnaire to predict an AHI ≥ 15 was 58.8%, 77.6%, 82.9%, and 50.6%, respectively. The area under the receiving operator characteristic (ROC) curve for moderate-to-severe OSA was 0.682. When used to predict an AHI ≥ 30, the sensitivity of the questionnaire increased to 76.9% with a small drop in specificity to 72.7%. The corresponding NPV, PPV, and area under the ROC curve of the questionnaire to predict severe OSA were 96.3%, 25.3%, and 0.748, respectively. CONCLUSIONS The Berlin questionnaire may have utility in the general population setting as a screening tool for OSA in view of its good sensitivity and high NPV in ruling out severe OSA.