cssi/SciSciGPT-SciSciNet huggingface dataset:
Prostate cancer diagnosis using epigenetic biomarkers, 3D high-content imaging and probabilistic cell-by-cell classifiers.

// Darko Stefanovski 1 , George Tang 2 , Kolja Wawrowsky 3 , Raymond C. Boston 1 , Nils Lambrecht 4, 5 and Jian Tajbakhsh 2, 6 1 Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA 2 Translational Cytomics Group, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA 3 Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA 4 Pathology and Laboratory Medicine Service, Veterans Affairs Medical Center, Long Beach, CA, USA 5 Department of Pathology and Laboratory Medicine, University of California Irvine, Orange, CA, USA 6 Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA Correspondence to: Jian Tajbakhsh, email: tajbakhshj@cshs.org Keywords: prostate cancer, epigenetics, 3D high-content imaging, tissue diagnostics, cell heterogeneity Received: September 07, 2016 Accepted: June 02, 2017 Published: July 05, 2017 ABSTRACT Background: Prostate cancer (PCa) management can benefit from novel concepts/biomarkers for reducing the current 20-30% chance of false-negative diagnosis with standard histopathology of biopsied tissue. Method: We explored the potential of selected epigenetic markers in combination with validated histopathological markers, 3D high-content imaging, cell-by-cell analysis, and probabilistic classification in generating novel detailed maps of biomarker heterogeneity in patient tissues, and PCa diagnosis. We used consecutive biopsies/radical prostatectomies from five patients for building a database of ~140,000 analyzed cells across all tissue compartments and for model development; and from five patients and the two well-characterized HPrEpiC primary and LNCaP cancer cell types for model validation. Results: Principal component analysis presented highest covariability for the four biomarkers 4’,6-diamidino-2-phenylindole, 5-methylcytosine, 5-hydroxymethylcytosine, and alpha-methylacyl-CoA racemase in the epithelial tissue compartment. The panel also showed best performance in discriminating between normal and cancer-like cells in prostate tissues with a sensitivity and specificity of 85%, correctly classified 87% of HPrEpiC as healthy and 99% of LNCaP cells as cancer-like, identified a majority of aberrant cells within histopathologically benign tissues at baseline diagnosis of patients that were later diagnosed with adenocarcinoma. Using k-nearest neighbor classifier with cells from an initial patient biopsy, the biomarkers were able to predict cancer stage and grade of prostatic tissue that occurred at later prostatectomy with 79% accuracy. Conclusion: Our approach showed favorable diagnostic values to identify the portion and pathological category of aberrant cells in a small subset of sampled tissue cells, correlating with the degree of malignancy beyond baseline.
Direct Loading of iTEP-Delivered CTL Epitope onto MHC Class I Complexes on the Dendritic Cell Surface.

Cytotoxic T lymphocyte (CTL)-mediated immune responses are the primary defense mechanism against cancer and infection. CTL epitope peptides have been used as vaccines to boost CTL responses; however, the efficacy of these peptides is suboptimal. Under current vaccine formulation and delivery strategies, these vaccines are delivered into and processed inside antigen-presenting cells such as dendritic cells (DCs). However, the intracellular process is not efficient, which at least partially contributes to the suboptimal efficacy of the vaccines. Thus, we hypothesized that directly loading epitopes onto MHC class I complexes (MHC-Is) on the DC surface would significantly improve the efficacy of the epitopes because the direct loading bypasses inefficient intra-DC vaccine processing. To test the hypothesis, we designed an immune-tolerant elastin-like polypeptide (iTEP)-delivered CTL vaccine containing a metalloproteinase-9 (MMP-9)-sensitive peptide and an CTL epitope peptide. We found that the epitope was rel...
The Academic Library’s Contribution to Student Success: Library Instruction and GPA

This study examines the relationship between library instruction and graduating students’ four-year cumulative grade point averages for the classes of 2012-2015. After normalizing the GPAs by departments to account for differences in departmental grading, a two-tailed t-test indicated a statistically significant increase in GPA among graduating students who were enrolled in classes in which at least one library instruction session was held (n=1,265) over students who were enrolled in no classes with library instruction (n=115). Librarians are using the results to demonstrate the relationship between the library and student success, and to promote library instruction on campus.
Mandating Staffing Ratios in Hemodialysis Facilities: California SB 349 and Unintended Consequences.

Maintenance hemodialysis is a life-sustaining treatment that imposes significant clinical challenges and expenses to the health care system, particularly Medicare. The Centers for Medicare and Medicaid Services, which oversees the payment and quality of care for patients receiving dialysis, does not
Correcting deregulated Fxyd1 expression rescues deficits in neuronal arborization and potassium homeostasis in MeCP2 deficient male mice

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the MECP2 gene. In the absence of MeCP2, expression of FXYD domain-containing transport regulator 1 (FXYD1) is deregulated in the frontal cortex (FC) of mice and humans. Because Fxyd1 is a membrane protein that controls cell excitability by modulating Na+, K+-ATPase activity (NKA), an excess of Fxyd1 may reduce NKA activity and contribute to the neuronal phenotype of Mecp2 deficient (KO) mice. To determine if Fxyd1 can rescue these RTT deficits, we studied the male progeny of Fxyd1 null males bred to heterozygous Mecp2 female mice. Maximal NKA enzymatic activity was not altered by the loss of MeCP2, but it increased in mice lacking one Fxyd1 allele, suggesting that NKA activity is under Fxyd1 inhibitory control. Deletion of one Fxyd1 allele also prevented the increased extracellular potassium (K+) accumulation observed in cerebro-cortical neurons from Mecp2 KO animals in response to the NKA inhibitor ouabain, and rescued the loss of dendritic arborization observed in FC neurons of Mecp2 KO mice. These effects were gene-dose dependent, because the absence of Fxyd1 failed to rescue the MeCP2-dependent deficits, and mimicked the effect of MeCP2 deficiency in wild-type animals. These results indicate that excess of Fxyd1 in the absence of MeCP2 results in deregulation of endogenous K+ conductances functionally associated with NKA and leads to stunted neuronal growth.
Automatic Video Activity Recognition

With the demands on public security and the availability of large storage systems, an increasing number of video surveillance systems are being deployed all over the world to help people detect interesting target events. However, most of these systems require intensive human monitoring, or require human operators to review video footage corresponding to extended periods of time, only to find a few short clips that are of interest. The problem fosters a demand of an automatic computer surveillance system, which can assist the human operators in identifying possible interesting events. This challenge has attracted researchers from different domains, leading to a variety of proposed approaches, particularly in the field of human activity recognition. These approaches vary in the choice of representation and methodologies as well. This chapter gives a survey and reviews the state of the art approaches to automatic human activity recognition in videos.
Codes from Modular Curves

One of the most interesting class of curves, from the perspective of arithmetical algebraic geometry, are the so-called modular curves. Some of the most remarkable applications of algebraic geometry to coding theory arise from these modular curves. It turns out these algebraic-geometric codes (“AG codes”) constructed from modular curves can have parameters which beat the Gilbert–Varshamov lower bound if the ground field is sufficiently large.
The Conciliatory Style

Conciliation is a third ideal type of social control. The parties involved in conciliatory control work together or with the aid of third parties to negotiate a mutually agreeable outcome. Solutions are obtained through mutual bargaining between the parties involved, not coerced through imposed sanctions.
COX-1 mediates IL-33-induced extracellular signal-regulated kinase activation in mast cells: Implications for aspirin sensitivity.

Background Classical FceRI-induced mast cell (MC) activation causes synthesis of arachidonic acid (AA)–derived eicosanoids (leukotriene [LT] C4, prostaglandin [PG] D2, and thromboxane A2), which mediate vascular leak, bronchoconstriction, and effector cell chemotaxis. Little is known about the significance and regulation of eicosanoid generation in response to nonclassical MC activation mechanisms. Objectives We sought to determine the regulation and significance of MC-derived eicosanoids synthesized in response to IL-33, a cytokine critical to innate type 2 immunity. Methods We used an ex vivo model of mouse bone marrow–derived mast cells and an IL-33–dependent in vivo model of aspirin-exacerbated respiratory disease (AERD). Results IL-33 potently liberates AA and elicits LTC4, PGD2, and thromboxane A2 production by bone marrow–derived mast cells. Unexpectedly, the constitutive function of COX-1 is required for IL-33 to activate group IVa cytosolic phospholipase A2 with consequent AA release for synthesis of all eicosanoids, including CysLTs. In contrast, COX-1 was dispensable for FceRI-driven CysLT production. Inhibition of COX-1 prevented IL-33–induced phosphorylation of extracellular signal-related kinase, an upstream effector of cytosolic phospholipase A2, which was restored by exogenous PGH2, implying that the effects of COX-1 required its catalytic function. Administration of a COX-1–selective antagonist to mice completely prevented the generation of both PGD2 and LTC4 in a model of AERD in which MC activation is IL-33 driven. Conclusions MC-intrinsic COX-1 amplifies IL-33–induced activation in the setting of innate type 2 immunity and might help explain the phenomenon of therapeutic desensitization to aspirin by nonselective COX inhibitors in patients with AERD.
Salvaging the Unavoidable: A Review of Complications in Pediatric Tissue Expansion.

Background Tissue expansion, while a mainstay of reconstruction for pediatric cutaneous lesions, has significant complication rates. The authors review the complications in a single-surgeon series of tissue expansion to identify risk factors for complications and guide subsequent therapy so that reconstructive goals in patients can be met irrespective of intervening complications. Methods A retrospective chart review was conducted of all pediatric patients who underwent tissue expansion performed by the senior author (A.K.G.) over a 12-year period. In total, 282 expanders were placed in 94 patients. Results A total of 65 complications occurred in 39 of 94 patients (41.5 percent), involving 65 of the 282 expanders (23.0 percent) placed. Major complications that required expander removal included exposure (n = 11), rupture (n = 15), and migration (n = 11). The most frequent minor complications, which did not require immediate expander removal, included migration (n = 13) and port malfunction (n = 9). The majority of expanders were placed in the scalp (n = 114), followed by the torso (n = 100), face and neck (n = 52), and the extremities (n = 16). Serial expansion beyond the second round resulted in a marked increase in complications. Despite complications, tissue expansion in the majority of patients could be salvaged, and a satisfactory outcome was achieved. Conclusions Families must be made aware that approximately one-third of patients may have a complication requiring additional surgery or modification of the initial reconstructive plan. However, these complications need not preclude attainment of reconstructive goals. Clinical question/level of evidence Therapeutic, IV.
PEGylation of model drug carriers enhances phagocytosis by primary human neutrophils.

Abstract Targeted drug carriers are attractive for the delivery of therapeutics directly to the site of a disease, reducing systemic side effects and enhancing the efficacy of therapeutic molecules. However, the use of particulate carriers for drug delivery comes with its own set of challenges and barriers. Among these, a great deal of research effort has focused on protecting carriers from clearance by phagocytes via altering carrier surface chemistry, mostly with the use of polyethylene glycol (PEG) chain coatings. However, few papers have explored the effects of PEGylation on uptake by freshly-obtained primary human phagocytes in physiological conditions. In this work, we investigate the effect of PEGylation on particle uptake by primary human neutrophils in vitro and compare these effects to several cell lines and other model phagocytic cells systems. We find that human neutrophils in whole blood preferentially phagocytose PEGylated particles (e.g., ∼40% particle positive neutrophils for PEGylated versus ∼20% for carboxylated polystyrene microspheres) and that this effect is linked to factors present in human plasma. Model phagocytes internalized PEGylated particles less efficiently or equivalently to carboxylated particles in culture medium but preferentially phagocytosed PEGylated particles in the human plasma (e.g., ∼86% versus ∼63% PEGylated versus carboxylated particle positive cells, respectively). These findings have significant implications for the efficacy of PEGylation in designing long-circulating drug carriers, as well as the need for thorough characterization of drug carrier platforms in a wide array of in vitro and in vivo assays. Statement of Significance The work in this manuscript is highly significant to the field of drug delivery, as it explores in-depth the effects of polyethylene glycol (PEG) coatings, which are frequently used to prevent phagocytic clearance of particulate drug carriers, on the phagocytosis of such carriers by neutrophils, the most abundant leukocyte in blood circulation. Surprisingly, we find that PEGylation enhances uptake by primary human neutrophils, specifically in the presence of human plasma. This result suggests that PEGylation may not confer the benefits in humans once thought, and may help to explain why PEG has not become the “magic bullet” it was once thought to be in the field of particulate drug delivery.
How Genomics Is Personalizing the Management of Dyslipidemia and Cardiovascular Disease Prevention

To summarize advances in genomic medicine and anticipated future directions to improve cardiovascular risk reduction. Mendelian randomization and genome-wide association studies have given significant insights into the role of genetics in dyslipidemia and cardiovascular disease (CVD), with over 160 gene loci found to be associated with coronary artery disease to date. This has enabled the creation of genetic risk scores that have demonstrated improved risk prediction when added to clinical markers of CVD risk. Incorporation of genomic data into clinical patient care is on the horizon. Genomic medicine is expected to offer improved risk assessment, determination of targeted treatment strategies, and improved detection of lipid disorders causal to CVD development.
Beyond the “Sinew of War”: The Political Economy of Security as a Subfield

Since at least Cicero, we have known that “money is the sinew of war.” Is it possible for a political economy of security (PES) subfield to contribute knowledge beyond Cicero's claim? This article ...
Proceedings of the 1st ACM workshop on Hot topics in wireless

It is our great pleasure to welcome you to the 4th ACM Workshop on Hot Topics in Wireless, focused on disruptive wireless technologies and systems that can enable orders of magnitude improvements in performance and novel wireless applications. Our goal is to provide a launching pad for bold and visionary ideas, and bring together experts in hardware, physical layer, networks, and systems to address core technical challenges in these emerging wireless technologies. HotWireless will provide a venue for debating future research agendas, technology trends, and application domains of wireless technology, and for presenting innovative and/or risky ideas that have potential for significant impact. The call for papers attracted submissions from Asia, Europe, and the United States. The program committee reviewed 16 submissions and accepted 10 technical papers to appear in the program. We also encourage attendees to attend the keynote and invited talk presentations. These valuable and insightful talks can and will guide us to a better understanding of the future: Is Wireless Research Still Hot: A Perspective from the National Science Foundation, Thyaga Nandagopal (NSF) Device-Free Decade: the Past and Future of RF Sensing Systems, Neal Patwari (University of Utah)
The Politics of Women's History: Collecting for the Centennial of Women's Suffrage in New York State:

The 2017 New York State suffrage centennial provided momentum for institutions to review and reimagine their women's history collections. Five of the many museum exhibitions timed to this anniversa...
Radical S -adenosylmethionine maquette chemistry: Cx 3 Cx 2 C peptide coordinated redox active [4Fe–4S] clusters

The synthesis and characterization of short peptide-based maquettes of metalloprotein active sites facilitate an inquiry into their structure/function relationships and evolution. The [4Fe-4S]-maquettes of bacterial ferredoxin metalloproteins (Fd) have been used in the past to engineer redox active centers into artificial metalloenzymes. The novelty of our study is the application of maquettes to the superfamily of [4Fe-4S] cluster and S-adenosylmethionine-dependent radical metalloenzymes (radical SAM). The radical SAM superfamily enzymes contain site-differentiated, redox active [4Fe-4S] clusters coordinated to Cx3Cx2C or related motifs, which is in contrast to the Cx2Cx2C motif found in bacterial ferredoxins (Fd). Under an optimized set of experimental conditions, a high degree of reconstitution (80-100%) was achieved for both radical SAM- and Fd-maquettes. Negligible chemical speciation was observed for all sequences, with predominantly [4Fe-4S]2+ for the 'as-reconstituted' state. However, the reduction of [4Fe-4S]2+-maquettes provides low conversion (7-17%) to the paramagnetic [4Fe-4S]+ state, independent of either the spacing of the cysteine residues (Cx3Cx2C vs. Cx2Cx2C), the nature of intervening amino acids, or the length of the cluster binding motif. In the absence of the stabilizing protein environment, the reduction process is proposed to proceed via [4Fe-4S]2+ cluster disassembly and reassembly in a more reduced state. UV-Vis and EPR spectroscopic techniques are employed as analytical tools to quantitate the as-reconstituted (or oxidized) and one-electron reduced states of the [4Fe-4S] clusters, respectively. We demonstrate that short Fd and radical SAM derived 7- to 9-mer peptides containing appropriate cysteine motifs function equally well in coordinating redox active [4Fe-4S] clusters.
Optimization of the Single Emulsion Method for Encapsulation of a Cancer Drug in Nanoparticles

The goal of this study is to apply and optimize the single emulsion technique for encapsulation of an anti-tumor drug, Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), in nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA), as a step towards targeted delivery of this drug. We previously showed that the nanoprecipitation technique can effectively produce PLGA NPs carrying this drug. Here, we aim to examine the single emulsion technique as an alternative for the preparation of these NPs and to compare the resultant NPs to those from nanoprecipitation. We fabricated NPs with variations in (i) injection rate, (ii) the amount of surfactant poly (vinyl alcohol) (PVA) in aqueous phase, and (iii) concentration of PLGA in the organic phase. These NPs were characterized for size, surface potential, and encapsulation efficiency. The results revealed that increasing the injection rate (from manual addition to 90 mL/hr via syringe pump) greatly reduced the size of NPs (by 48%) and decreasing the PVA concentration in the aqueous phase (from 5 to 1% w/v) further reduced the NP size (by 32%) to 329 nm. All tested NP formulations had negative surface potential, suggesting good colloidal stability for these NPs. Focusing on the optimal injection rate and PVA percentage, we found that reducing the concentration of PLGA, from 100 to 1 mg/mL, significantly reduced the NP size to 136 nm, which is close to the optimal range for cancer therapeutic delivery. NPs produced by this method had a high encapsulation efficiency of 77% for Dp44mT and reducing the PLGA concentration slightly lowered this value to 74%. Overall, these NPs were comparable to those produced by nanoprecipitation and can thus, serve as an effective alternative for delivery of Dp44mT to cancer cells.
All-Optical Processing with Dynamic Frequency Transformations

We propose an all-optical frequency processor (AFP) for transparent optical networking, based on optical pulse shaping and electro-optic phase modulation. We numerically examine the AFP for frequency channel hopping and broadcasting operations, and show the required number of components scales favorably with the network size.
Diurnal Variation in Systemic Acute Inflammation and Clinical Outcomes Following Severe Blunt Trauma.

Circadian oscillations of immunity and inflammation have been characterized, and animal studies suggest that the time of day is a determinant of the immunological response to both injury and infection. We hypothesized that due to this diurnal variation, time of injury can affect the systemic inflammatory response and outcomes post-trauma and tested this hypothesis by examining the dynamics of circulating inflammatory mediators in blunt trauma patients injured during daytime vs. nighttime. From a cohort of 472 blunt trauma survivors, two stringently matched sub-cohorts of moderately/severely injured patients [injury severity score (ISS) >20] were identified. Fifteen propensity-matched, daytime-inured (“mDay”) patients (age 43.6 ± 5.2, M/F 11/4, ISS 22.9 ± 0.7) presented during the shortest local annual period (8:00 am-5:00 pm), and 15 propensity-matched “mNight” patients (age 43 ± 4.3, M/F 11/4, ISS 24.5 ± 2.5) presented during the shortest night period (10:00 pm-5:00 am). Serial blood samples were obtained (3 samples within the first 24 h and daily from days 1-7) from all patients. Thirty-two plasma inflammatory mediators were assayed. Two-way Analysis of Variance (ANOVA) was used to compare groups. Dynamic Network Analysis (DyNA) and Dynamic Bayesian Network (DyBN) inference were utilized to infer dynamic interrelationships among inflammatory mediators. Both total hospital and intensive care unit length of stay were significantly prolonged in the mNight group, despite a greater need for surgical interventions in mDay group. Circulating IL-17A was elevated significantly in the mNight group from 24 h – 7 days post-injury. Circulating MIP-1alpha, IL-7, IL-15, GM-CSF, and sST2 were elevated in the mDay group. DyNA demonstrated elevated network complexity in the mNight vs. the mDay group. DyBN suggested that cortisol and sST2 were central nodes upstream of TGF-beta1, chemokines, and Th17/protective mediators in both groups, with IL-6 being an additional downstream node in the mNight group only. Our results suggest that time of injury affects the clinical outcomes in severely injured patients in a manner associated with an altered systemic inflammation program, possibly implying a role for circadian variation in the response to traumatic injury.
Copper-Catalyzed Oxidative Acetalization of Boronic Esters – An Umpolung Strategy for Cyclic Acetal Synthesis

A protocol for the acetalization of boronic esters is described. The reaction is catalyzed by copper, and the conditions proved to be mild and were amenable to a variety of functional groups. We expanded the Chan-Lam coupling to include C(sp3) nucleophiles and converted them into corresponding acetals. This method allows for the orthogonal acetalization of substrates with reactive, acid-sensitive functional groups.
Identification of DNA methylation associated enrichment pathways in adults with non-specific chronic low back pain

Chronic low back pain (cLBP) that cannot be attributable to a specific pathoanatomical change is associated with high personal and societal costs. Still, the underlying mechanism that causes and su...
Trends in Poor Health Indicators Among Black and Hispanic Middle-aged and Older Adults in the United States, 1999-2018.

Importance Adults who belong to racial/ethnic minority groups are more likely than White adults to receive a diagnosis of chronic disease in the United States. Objective To evaluate which health indicators have improved or become worse among Black and Hispanic middle-aged and older adults since the Minority Health and Health Disparities Research and Education Act of 2000. Design, Setting, and Participants In this repeated cross-sectional study, a total of 4 856 326 records were extracted from the Behavioral Risk Factor Surveillance System from January 1999 through December 2018 of persons who self-identified as Black (non-Hispanic), Hispanic (non-White), or White and who were 45 years or older. Exposure The 1999 legislation to reduce racial/ethnic health disparities. Main Outcomes and Measures Poor health indicators and disparities including major chronic diseases, physical inactivity, uninsured status, and overall poor health. Results Among the 4 856 326 participants (2 958 041 [60.9%] women; mean [SD] age, 60.4 [11.8] years), Black adults showed an overall decrease indicating improvement in uninsured status (β = −0.40%;P Conclusions and Relevance This study suggests that Black-White disparities increased in diabetes, hypertension, and asthma, while Hispanic-White disparities remained in diabetes, hypertension, and uninsured status.
Classification of broiler behaviours using triaxial accelerometer and machine learning.

Abstract Understanding broiler behaviours provides important implications for animal well-being and farm management. The objectives of this study were to classify specific broiler behaviours by analysing data from wearable accelerometers using two machine learning models, K-Nearest Neighbour (KNN) and Support Vector Machine (SVM). Lightweight triaxial accelerometers were used to record accelerations of nine 7-week-old broilers at a sampling frequency of 40 Hz. A total of 261.6-min data were labelled for four behaviours – walking, resting, feeding and drinking. Instantaneous motion features including magnitude area, vector magnitude, movement variation, energy, and entropy were extracted and stored in a dataset which was then segmented by one of the six window lengths (1, 3, 5, 7, 10 and 20 s) with 50% overlap between consecutive windows. The mean, variation, SD, minimum and maximum of each instantaneous motion feature and two-way correlations of acceleration data were calculated within each window, yielding a total of 43 statistic features for training and testing of machine learning models. Performance of the models was evaluated using pure behaviour datasets (single behaviour type per dataset) and continuous behaviour datasets (continuous recording that involved multiple behaviour types per dataset). For pure behaviour datasets, both KNN and SVM models showed high sensitivities in classifying broiler resting (87% and 85%, respectively) and walking (99% and 99%, respectively). The accuracies of SVM were higher than KNN in differentiating feeding (88% and 75%, respectively) and drinking (83% and 62%, respectively) behaviours. Sliding window with 1-s length yielded the best performance for classifying continuous behaviour datasets. The performance of classification model generally improved as more birds were included for training. In conclusion, classification of specific broiler behaviours can be achieved by recording bird triaxial accelerations and analysing acceleration data through machine learning. Performances of different machine learning models differ in classifying specific broiler behaviours.
Time Domain Reflectometry Accuracy Control for Via Characterizations in High Speed Links

The time domain reflectometry (TDR) is a very popular tool for high speed link characterizations. However, its modeling and simulations for vias constantly face accuracy challenges due to vias’ small dimensions. While many existing papers discussed discontinuity analysis of transmission lines, in this paper, we focus on the accuracy control methods in TDR modeling and analysis for vias in PCBs for high speed signal integrity (SI). There are many practical factors affecting the via impedance result in TDR, such as frequency domain simulation setups, TDR window selections, discontinuities before and after via structures, etc. Based on the principle analysis, we proposed a practical verification approach that jointly use different window functions, different bandwidth extractions to justify the correct locations and impedance values of the via structures. The proposed method can also be used for other small.
Evaluation of the accuracy of buccal bone thickness measurement from cone beam computed tomography compared with histologic analysis.

Abstract Statement of problem Three-dimensional radiographic assessment of buccal bone thickness and its integrity from cone beam computed tomography (CBCT) plays an essential role in immediate implant placement. However, the accuracy of CBCT measurements for the assessment of buccal bone thickness adjacent to maxillary anterior teeth is not well understood. Purpose The purpose of this observational study was to evaluate the accuracy of measuring the buccal bone thickness of maxillary anterior teeth from CBCT compared with direct measurement from histologic sections. A secondary objective was to analyze whether a minimal level of buccal bone thickness of maxillary anterior teeth can be detected from the CBCT scan. Material and methods Five embalmed human cadavers with a complete anterior dentition were included in this study, providing 30 teeth for evaluation. After preparing reference notches at the gingival margin of each tooth, the anterior segments were scanned. The buccal bone thickness at 3, 5, and 7 mm from the notches was measured on the cross-sections obtained from the CBCT and histomorphometric images for a total of 90 sites. The CBCT measurements were compared with the histomorphometric measurements, and their agreement was assessed by using the Bland-Altman plots and intraclass correlation coefficients. The sensitivity and specificity of buccal bone detection were calculated from the CBCT scan. Results Histologic examination showed absence of the buccal bone in 29 sites (32%). The mean ±standard deviation thickness of the buccal bone was 0.52 ±0.05 mm (range: 0 to 1.97 mm) from the CBCT analysis and 0.40 ±0.05 mm (range: 0 to 1.67 mm) from histology. Measurements obtained from the CBCT sections significantly overestimated the buccal bone thickness when compared with the histologic evaluation (P=.001). The intraclass correlation coefficient of buccal bone thickness between the CBCT and histology was ≤0.53, an agreement considered as poor. The sensitivity of the CBCT as a diagnostic tool to detect the presence or absence of the buccal bone was 75.4%, and the specificity was 65.5%. Conclusions The buccal bone thickness of maxillary anterior teeth was less than 2 mm at all sites as measured with both CBCT and histology evaluations. CBCT measurements had relatively low accuracy and reliability for the measurement of buccal bone thickness. These findings should be considered when using CBCT as a measuring tool for thin bone structures.
Turning Saccharomyces cerevisiae into a Frataxin-Independent Organism

Frataxin (Yfh1 in yeast) is a conserved protein and deficiency leads to the neurodegenerative disease Friedreich’s ataxia. Frataxin is a critical protein for Fe-S cluster assembly in mitochondria, interacting with other components of the Fe-S cluster machinery, including cysteine desulfurase Nfs1, Isd11 and the Isu1 scaffold protein. Yeast Isu1 with the methionine to isoleucine substitution (M141I), in which the E. coli amino acid is inserted at this position, corrected most of the phenotypes that result from lack of Yfh1 in yeast. This suppressor Isu1 behaved as a genetic dominant. Furthermore frataxin-bypass activity required a completely functional Nfs1 and correlated with the presence of efficient scaffold function. A screen of random Isu1 mutations for frataxin-bypass activity identified only M141 substitutions, including Ile, Cys, Leu, or Val. In each case, mitochondrial Nfs1 persulfide formation was enhanced, and mitochondrial Fe-S cluster assembly was improved in the absence of frataxin. Direct targeting of the entire E. coli IscU to ∆yfh1 mitochondria also ameliorated the mutant phenotypes. In contrast, expression of IscU with the reverse substitution i.e. IscU with Ile to Met change led to worsening of the ∆yfh1 phenotypes, including severely compromised growth, increased sensitivity to oxygen, deficiency in Fe-S clusters and heme, and impaired iron homeostasis. A bioinformatic survey of eukaryotic Isu1/prokaryotic IscU database entries sorted on the amino acid utilized at the M141 position identified unique groupings, with virtually all of the eukaryotic scaffolds using Met, and the preponderance of prokaryotic scaffolds using other amino acids. The frataxin-bypassing amino acids Cys, Ile, Leu, or Val, were found predominantly in prokaryotes. This amino acid position 141 is unique in Isu1, and the frataxin-bypass effect likely mimics a conserved and ancient feature of the prokaryotic Fe-S cluster assembly machinery.
A Study of the Stationary Volumetric Elastic Modulus during Dehydration and Rehydration of Stems of Pea Seedlings.

The relationship between cortical-cell turgor pressure (P) and tissue water mass (W) was determined for stem segments of pea (Pisum sativum L.) seedlings subjected to hydration and dehydration. This allowed a test for elastic hysteresis in the cortical cells. The P-W curves for dehydration and hydration were not coincident. In some experiments, the P-W curves exhibited a “roll-off” at high P, similar to the “plateau effect” sometimes observed in pressure-chamber studies. When hydration was followed by a 4-h dehydration, the tissue water mass (W0) at minimum turgor was reduced. This might reflect a reduction in apoplastic water mass and/or a contraction of the symplast during dehydration. Neglecting the decrease in W0 leads to underestimates of the stationary volumetric elastic modulus ([epsilon]stat). The result of an analysis that assumes W0 was constant during hydration suggests that there was no significant difference in [epsilon]stat between dehydration and hydration and, hence, no significant elastic hysteresis. However, a 16-h dehydration increased [epsilon]stat; this might be a response to water stress.
Tissue-based microarray expression of genes predictive of metastasis in uveal melanoma and differentially expressed in metastatic uveal melanoma.

Purpose: To screen the microarray expression of CDH1, ECM1, EIF1B, FXR1, HTR2B, ID2, LMCD1, LTA4H, MTUS1, RAB31, ROBO1, and SATB1 genes which are predictive of primary uveal melanoma metastasis, and NFKB2, PTPN18, MTSS1, GADD45B, SNCG, HHIP, IL12B, CDK4, RPLP0, RPS17, RPS12 genes that are differentially expressed in metastatic uveal melanoma in normal whole human blood and tissues prone to metastatic involvement by uveal melanoma. Methods: We screened the GeneNote and GNF BioGPS databases for microarray analysis of genes predictive of primary uveal melanoma metastasis and those differentially expressed in metastatic uveal melanoma in normal whole blood, liver, lung and skin. Results: Microarray analysis showed expression of all 22 genes in normal whole blood, liver, lung and skin, which are the most common sites of metastases. In the GNF BioGPS database, data for expression of the HHIP gene in normal whole blood and skin was not complete. Conclusions: Microarray analysis of genes predicting systemic metastasis of uveal melanoma and genes differentially expressed in metastatic uveal melanoma may not be used as a biomarker for metastasis in whole blood, liver, lung, and skin. Their expression in tissues prone to metastasis may suggest that they play a role in tropism of uveal melanoma metastasis to these tissues.
Effect of rapamycin on the fate of P23H opsin associated with retinitis pigmentosa (an American Ophthalmological Society thesis).

Purpose To determine the effect of rapamycin on the fate of misfolded opsin associated with retinitis pigmentosa. Methods Stable cell lines separately expressing WT and P23H opsins and WT and DeltaF508 CFTR were used. Cells were incubated with complete media or amino acid-depleted medium or in the presence of rapamycin. At various time points thereafter, quantitative opsin and CFTR immunoblotting was performed. Immunofluorescence and electron microscopy were also performed to observe the expression and colocalization of autophagy specific marker proteins with opsin or CFTR. Results Upon incubation with rapamycin, the levels of P23H opsin and DeltaF508 CFTR were reduced more rapidly than in untreated controls while no observable changes in the amounts of WT opsin was seen. The autophagy specific marker proteins, Atg7, Atg8 (LC3), and LAMP-1, which associate with autophagic vacuoles, colocalized with P23H opsin. A dramatic increase in the immunofluorescence signals of Atg7, LC3, and LAMP-1 was observed. All three of these proteins were found to decorate P23H opsin, suggesting that autophagy may be directly responsible for the clearance of this protein. Also, it was determined that neither the unfolded protein response nor the heat shock response was induced upon rapamycin-associated degradation of P23H opsin. Conclusions These data suggest that rapamycin induces the loss of P23H opsin and DeltaF508 CFTR from the cell under the experimental conditions described. Concomitantly, there is increased expression and colocalization of autophagy marker proteins with P23H opsin. Immunogold electron microscopic studies demonstrate autophagic vacuoles clustered in physical proximity to the aggregates of P23H opsin, suggesting that some of the loss of P23H is related to the induction of autophagy. Thus, rapamycin may be useful to clear misfolded proteins associated with retinal degeneration.
Conséquences de l’adoption des IFRS sur l’information et les marchés financiers - Dix ans de littérature (2005-2014)

On the basis of a review of the papers published on the last decade (2005-2014), the article deals with the effects of IFRS adoption on the financial information and financial markets. After a descriptive analysis of 207 articles identifying various domains of researches, the article focuses on the impacts of the IFRS according to the information disclosure (value relevance, earnings management, quality and comparability) and the financial markets actors’ perception (analysts’ earnings forecasts, investment, stock and credit markets, cost of capital).
Determining the state-of-health of maintenance-free aircraft batteries

This paper presents an overview of methods to determine the state-of-health of maintenance-free aircraft batteries. The various failure modes of aircraft batteries are discussed, along with methods of detecting failed batteries. Specific examples of detection methods are presented for the F-16, F-18, AV-8B, B-1B, and B-52 aircraft batteries. >
Is the distal hyperplastic polyp a marker for proximal neoplasia

CONTEXT: The current literature is unclear about the association between distal hyperplastic polyps and synchronous neoplasia (adenomatous polyps and cancer) in the proximal colon.
Virtual rapport 2.0

Rapport, the feeling of being "in sync" with your conversational partners, is argued to underlie many desirable social effects. By generating proper verbal and nonverbal behaviors, virtual humans have been seen to create rapport during interactions with human users. In this paper, we introduce our approach to creating rapport following Tickle-Degnen and Rosenberg's threefactor (positivity, mutual attention and coordination) theory of rapport. By comparing with a previously published virtual agent, the Rapport Agent, we show that our virtual human predicts the timing of backchannel feedback and end-of-turn more precisely, performs more natural behaviors and, thereby creates much stronger feelings of rapport between users and virtual agents.
Simultaneous Bilateral Total Knee Arthroplasty: What Is the Value?

Total knee arthroplasty has long been shown to be both safe and efficacious for the treatment of degenerative conditions of the knee—relieving pain, restoring function, correcting deformity, and providing measurable improvements in quality of life. Total knee arthroplasty also has been demonstrated to be very cost-effective from a societal perspective, with estimates between ten and twenty thousand dollars per quality-adjusted life year (QALY)1. Frequently, patients present with bilateral symptomatic disease and deformity, prompting patients and surgeons to consider simultaneous bilateral total knee arthroplasty. The number of total knee arthroplasties performed and rate of utilization in the United States has grown exponentially over the last several decades. In fact, more than 700,000 were performed in 2010, with projections of more than three million total knee arthroplasties expected to be performed annually by 20302. The surgical demand creates major financial strains on the American health-care system and, in part, is responsible for the pay-for-performance measures enacted by the Centers for Medicare & Medicaid Services (CMS) and the recent public reporting of outcomes for total hip and total knee arthroplasty surgery. Simultaneous bilateral total knee arthroplasty has represented a consistent 4% to 6% of total knee arthroplasties performed annually in the United States1,3,4. Despite a lengthy history of surgeons performing simultaneous bilateral total knee arthroplasty, there continues to be debate about the indications for the procedure and concern regarding its overall safety. Those surgeons who support the use of simultaneous bilateral total knee arthroplasty cite decreased cost, improved recovery time, the utilization of a single anesthetic, and equal functional outcomes when compared with staged bilateral total knee arthroplasty. Those surgeons who favor staged bilateral total knee arthroplasty cite increased mortality, both in-hospital and within thirty days …
Reproductive Experience Alters Prolactin Receptor Expression in Mammary and Hepatic Tissues in Female Rats

Recent studies have reported that reproductive experience in female rats alters prolactin (PRL) receptor gene expression in the brain as well as neural sensitivity to PRL. Given PRL's actions in nonneural tissues, that is, mammary tissue and liver, it was asked whether reproductive experience may also alter prolactin receptor (Prlr) gene expression in these tissues. Groups of age-matched female rats were generated with varying reproductive histories. Separate groups of primiparous (first lactation) and multiparous (second lactation) had mammary tissue and liver samples collected on Day 3 or 10 of lactation. A fifth group raised one litter to weaning and then resumed estrous cyclicity. This group and a final group of age-matched, virgin controls were killed on diestrus. Tissue was processed by quantitative PCR for expression rates of the long and short forms of Prlr mRNA as well as casein beta mRNA (mammary tissue only). Western blots were performed to quantify receptor protein content. Multiple lactations as well as lactation itself resulted in alterations in Prlr expression. Prlr gene expression in mammary tissue was increased in primiparous mothers compared with that in multiparous dams, whereas in the liver, Prlr expression was reduced during an initial lactation. In contrast, PRLR protein levels declined during lactation in mammary, but not hepatic, tissues. Overall, the results demonstrate that the prolactin receptor system is altered in nonneural tissues as a result of the female's reproductive history. The findings are discussed in the context of milk and bile production and PRL's possible role in breast cancer.
Treatment of corticosteroid-resistant polymyositis with methotrexate

Summary Seven patients with corticosteroid-resistant polymyositis were treated with intermittent, intravenous methotrexate. Five of the seven improved significantly as demonstrated by (1) improvement in muscle strength and in skin lesions; (2) return of at least three out of four serum-enzyme levels to normal or near-normal levels; and (3) ability to taper prednisone without causing deterioration in (1) and (2). Toxicity attibutable to methotrexate was not important. These studies indicate that methotrexate represents effective, relatively non-toxic treatment for polymyositis, especially when the disease has become refractory to corticosteroids.
Patterns of body temperatures: Is lizard thermoregulation chaotic?

We surveyed body temperature (Tb) fluctuations of 23 species of thermoregulating lizards (9 families, 305 individuals) for pattern similarities. Here we report that the Tb time-series patterns of all species and almost all individuals met both qualitative criteria and quantitative criteria (positive Lyapunov exponent and capacity and/or correlation dimensions less than 5, and Hurst exponent not equal to 0.5) for deterministic chaos. Chaotic thermoregulation appears controlled, but at unpredictable times becomes disturbed and exhibits nonlinear behaviors before returning to control. This chaotic pattern of regulation is common to sufficiently diverse species to suggest that it is likely a primitive lacertilian, and perhaps reptilian, physiological characteristic.
Effect of Hydrogen on the Superplastic Behavior of Ti-6Al-4V Alloy

The superplastic behaviour of Ti-6Al-4V alloy containing various amounts of hydrogen (0.07∼0.33wt%) has been investigated by tensile tests at temperatures of 800∼950°C. Results show that the solution of hydrogen in the alloy helps to reduce the flow stress with strain rate in the range of 1.67×10−4∼1.67×10−2s−1 and makes the temperature of superplastlc deformation become lower (810∼870°C). Nevertheless, it also causes a decrease of the strain rate sensitivity exponent and tensile elongation. However, by a suitable alloying with hydrogen (∼0.1wt%), the alloy can be made to undergo superplastlc deformation at a rather tow temperature (840°C) with an acceptable loss of superptastic ductility.
Efficient parallel volume rendering of large-scale adaptive mesh refinement data

Adaptive Mesh Refinement is a popular approach for allocating scarce computing resources to the most important portions of the simulation domain. This approach implies spatial compression and the large simulation sizes which necessitate it. We present a novel, cluster- and GPU-parallel rendering scheme for AMR data, which is built on previous work in the GPU ray casting of AMR data. Our approach utilizes the existing AMR structure to subdivide the problem into convexly-bounded chunks and perform static load-balancing. We take advantage of data locality within chunks to interpolate directly between blocks without the need to store ghost cells on the interior boundaries. We also present a novel block decomposition method, and analyze its performance against two alternative methods. Finally, we examine the interactivity of our renderer for multiple datasets, and consider its scalability across a large number of GPUs.