Rats given continuous access to etonitazene hydrochloride in their drinking water (5 micrograms per milliliter) more than doubled their drug intake while deprived of food. Another group of rats with implanted jugular catheters self-administered etonitazene (10 micrograms per kilogram) intravenously on a continuous reinforcement schedule, and the number of infusions increased significantly on days when they were deprived of food. These results suggest that feeding condition may be a powerful determinant of drug-reinforced behavior.


ABSTRACT: A grid based daily hydrologic model for a watershed with paddy fields was developed to predict the stream discharge. ASCII formatted elevation, soil, and land use data supported by the GRASS Geographic Information System are used to generate distributed results such as surface runoff and subsurface flow, soil water content, and evapotranspiration. The model uses a single flow path algorithm and simulates a water balance at each grid element. A linear reservoir assumption was used to predict subsurface runoff components. The model was applied to a 75.6 km2 watershed located in the middle of South Korea, and observed stream flow hydrographs from 1995 and 1996 were compared to model predictions. The stream flow predictions of 1995 and 1996 generally agreed with the observed flow, resulting in a Nash‐Sutcliffe efficiency R2 of 0.60 and 0.62, respectively. The hydraulic conductivity for percolating water through the saturated layer affected baseflow generation. The levee height of the paddy influenced the time and magnitude of the surface runoff, depending on irrigation management. The model will be used for making low flow management decisions by evaluating the role of each land use to stream flow, especially in case of paddy decrease by gradual urbanization of a watershed.


IMPORTANCE
The autosomal dominant spinocerebellar ataxias (SCAs) are a complex group of neurodegenerative disorders with significant genetic heterogeneity. Despite the identification of 20 SCA genes, the cause of the disorder in a significant proportion of families with SCA remains unexplained. In 1972, a French-Canadian family segregating a combination of SCA and erythrokeratodermia variabilis (EKV) in an autosomal dominant fashion was described.

OBJECTIVE
To map and identify the causative gene in this large family with SCA and EKV using a combination of linkage analysis and whole-exome sequencing.

DESIGN, SETTING, AND PARTICIPANTS
A total of 32 individuals from the family have undergone complete neurologic and dermatologic examinations.

MAIN OUTCOMES AND MEASURES
Mutations in ELOVL4 have been reported in families with macular degeneration. Recently, homozygous mutations were found in patients with ichthyosis, spastic paraplegia, and severe neurodevelopmental defects. In the present study, we report on a heterozygote mutation in ELOVL4 in affected individuals from the family with SCA and EKV. The mutation segregates with a milder phenotype consisting of early-onset patches of erythema and hyperkeratosis, as well as SCA manifesting in the fourth or fifth decade of life.

RESULTS
We describe the mapping and the identification of a c.504G>C transversion in ELOVL4 resulting in the p.L168F substitution. We also provide clinical characterization of the phenotypes in 19 mutation carriers.

CONCLUSIONS AND RELEVANCE
We report, to our knowledge, the first mutation in ELOVL4 that is associated with SCA and EKV. This gene encodes a member of the elongase family, which is responsible for the elongation of very long-chain fatty acids (at least 26 carbons). These fatty acids participate in a wide variety of physiological functions, including skin barrier formation and peroxisome β-oxidation. Overall, these results provide additional insight into the pathogenesis of these complex neurodegenerative disorders.


Purpose of review To provide a clinically relevant synopsis of recent research findings as well as updated recommendations from the American Academy of Pediatrics (AAP) and Advisory Committee on Immunization Practices (ACIP) regarding adolescent immunizations. Recent findings Coverage rates for the adolescent vaccinations continue to lag behind those of the childhood vaccinations, despite their importance. Recent research has focused on the reasons for suboptimal adolescent vaccination rates as well as strategies for improvement. By more fully understanding the barriers to immunization, efforts can be implemented to address these concerns and to ensure that all eligible adolescents receive their vaccinations. In addition, much work has focused on the duration of protection induced by childhood and adolescent vaccinations and the need for booster doses in older adolescents. Because immunity has been found to wane after vaccination, these booster doses can serve to more fully protect adolescents. This article reviews selected recent publications on human papillomavirus, meningococcal conjugate, and tetanus and diphtheria toxoids and acellular pertussis vaccines. Summary Adolescent vaccinations will continue to be studied and this research will serve to shape future recommendations. Through this work, we can learn the best methods to optimize the protection of all adolescents against these very serious diseases.


Space-time ratios in electronic beam are examined. Expression for distances between electrons in the accelerated beam is received. The criterion of existence of particle waves is received.


The effect of residual stress on energy storage property was investigated for a series of PbZrO3 thin films on SrTiO3 and Si substrates. Compressive or tensile residual stress influences the critical electric field EA for the ferroelectric-to-antiferroelectric phase transition, thus for films with (110)/(101) orientation, energy density W of films on SrTiO3 is 38% larger than films on Si; in contrast, (001)-oriented PbZrO3 films on SrTiO3 show slightly smaller W compared to films on Si. We conclude that the different responses of W to stress are related to the different constrain states in films with different orientations.


N-Acetyl-L-cysteine (NAC) is an antioxidant and anti-inflammatory agent with significant potential in clinical applications including stroke and neuroinflammation. The drug shows high plasma binding upon IV administration, requiring high doses and associated side effects. Through the use of an appropriate delivery vehicle, the stability and efficacy of NAC can be significantly improved. Dendrimers are an emerging class of nanoscale drug delivery vehicles, which enable high drug payloads and intracellular delivery. Poly(amidoamine) (PAMAM) dendrimer-NAC conjugates having cleavable disulfide linkages are designed for intracellular delivery based on glutathione levels. We have successfully synthesized two conjugates with a cationic G4-NH(2) and an anionic G3.5-COOH PAMAM dendrimer with NAC payloads of 16 and 18 per dendrimer, respectively, as confirmed by (1)H NMR and MALDI-TOF analysis. NAC release from the conjugates at intracellular and extracellular glutathione (GSH) concentrations were evaluated by reverse phase HPLC (RP-HPLC) analysis, and approximately 70% of NAC payload was released within one hour at intracellular GSH concentrations (approximately 10 mM), whereas negligible NAC release was observed at extracellular GSH levels (2 microM). FITC-labeled conjugates showed that they enter cells rapidly and localize in the cytoplasm of lipopolysaccharide (LPS)-activated microglial cells (the target cells in vivo). The significantly improved efficacies of dendrimer-NAC conjugates in activated microglial cells was confirmed by measuring the nitrite inhibition in the cell culture medium, which is an indication of the antioxidative property of the drug. Both G4-NH(2) and G3.5-COOH conjugates showed significantly better nitrite inhibition both at 24 and 72 h compared to free NAC, by as much as a factor of 16. The results indicate that PAMAM dendrimer conjugates produce higher local NAC concentration inside the cells, with GSH-sensitive disulfide linker enabling efficient and rapid cellular release of the drug.


The use of disinfection and cleaning chemicals in several municipal facilities, such as swimming pools and drinking water treatment plants, causes the degradation of various types of wood, which leads to failures in equipment and the corresponding need for maintenance. This degradation creates added costs for municipalities, as well as the closure of certain facilities due to curative or preventive maintenance and, in many cases, public health issues, due to the water being contaminated with deteriorating products. Through a thorough study of the degradation effect on the products, more resistant materials can be found which are able to withstand these adversities and increase the lifespan of wood in regular contact with chemical agents. This is achievable by the determination of the cost-effectiveness of the substitute material to replace these components with alternative ones, with properties that better resist the deterioration effects promoted by aggressive environments. No studies have been found so far strictly focused on this matter. The objective of this study is to evaluate the degradation presented by two types of wood, beech and oak, which are exposed to the action of chlorine in municipal facilities. This degradation varies according to the chlorine content and the materials' time of contact with the chemical agent, allowing the selection of new materials which will provide an extended lifetime of the components, reducing maintenance drastically, as well as costs for the facilities and the risk to public health. The performed experimental tests have shown that the oak wood has the best results regarding chlorine degradation resistance.


Three different anesthetics were tried on wild marmots to immobilize them sufficiently for intra-oral physiologic measurements and dental examination. Essentially the same procedure was performed or attempted on 15 animals. The droperidol (20 mg/ml) and fentanyl (0.4 mg/ml) combination gave better results than sodium pentobarbital or ketamine hydrochloride and was therefore used in most instances. We concluded that the dose rate should be adjusted to the nutritional state of the animal as well as to the absolute weight.


A 75-year-old man was hospitalised for bronchoscopy with biopsy due to a suspicious pulmonary mass at chest tomography. He had significant dyspnoea, constipation, nausea, vomiting, anorexia and a 33% loss of weight in the past 3 months. Biopsy revealed a pulmonary squamous cell carcinoma, which was inoperable. Tramadol used at home for 3 months was replaced by morphine on admission. The patient remained constipated despite prokinetics and laxatives, leading to the diagnostic hypothesis of paraneoplastic motility disorder and opioid-induced constipation. Abdominal tomography ruled out the possibility of mechanical obstruction. As complications, the patient presented superior vena cava syndrome and opioid (morphine) intoxication. The patient died a few days later. The management of this case highlights the importance of multidisciplinary care and the challenges of palliative oncology care. Paraneoplastic motility disorder must always be considered among the mechanisms of intestinal dysfunction in patients with advanced oncological disease.


Objective The aim of this article was to conduct a survey on the quality of care standards in nursing/midwifery training hospital of Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia. Methods A multiple methods design was used for the study. For the quantitative phase, 35 nurses, 35 patients, and 52 patient charts were selected by simple random sampling from eight randomly selected wards of the hospital. For the qualitative phase, purposive sampling was employed to select participants for focus group discussion and in-depth interview. Twelve instructors and 11 head nurses were recruited. The Quality Audit tool developed by Ethiopian Federal Ministry of Health was applied. Results It was found that the nursing and midwifery service quality standards were low and did not meet Ministry of Health standards. The chart review showed that 83% of nursing and midwifery assessments were not completed within eight hours of patient arrival, and in over half the charts (58%), there was no written evidence of compilation of data based on Gordon's functional model. Only two wards met Standard 1 with adequate medical equipment for nursing diagnosis or intervention. Seventy-five percent of the wards had a scarcity of materials and supplies needed to provide a quality nursing service. Half the nursing stations had adequate patient visibility, and half had an organized chart filing system based on the patient's bed number. Conclusion A high proportion of wards were not meeting Ministry of Health standards for nursing midwifery services. Improvement in care standards is vital to enable the hospital to function as a clinical setting for the education of health-care students. This might be achieved through ongoing attention to quality improvement and a program of in-service training regarding national care quality standards for managers, nurses, and midwives.


Objective: The aim of this study was to determine the role of biochemical markers in identifying the delayed onset muscle soreness among recreational athletes.Methods: This study was conducted in Saveetha University, college of physiotherapy, outpatient department. Eighty recreational athletes participated in this study. For all we measured the biochemical markers, Creatine kinase (CK), and Lactate dehydrogenase (LDH) enzymatic activity at the baseline and Delayed Onset Muscle Soreness (DOMS) were induced to elbow flexors by eccentric loading protocol and again the biochemical parameters measurement were repeated at 24 hours and 48 hours.
Results: Paired t test analysis revealed significant differences (p<0.05) between 0 hr and 48 hours, as well as between 0 hr and 24 hours. Conclusion: Serum creatine kinase level and lactate dehydrogenase level remains elevated until 48 hours after inducing delayed onset muscle soreness and these biochemical markers can be used to identify the level of muscle soreness.


Raman and FTIR spectroscopies are used to investigate the sorption mechanisms of benzene, toluene, and 2- and 4-picoline onto silica as models for volatile aromatic pollutant interactions with a soil constituent. Benzene and toluene vapor adsorption on silica occurs via weak π-system−hydrogen bonding with silanols on the silica surface. This weak interaction would likely result in low vadose zone retention, especially in wet conditions where water adsorption would successfully compete for surface sites. The vapor adsorption of 2- and 4-picoline (2- and 4-methylpyridine) is studied to model aza-arene environmental contaminants. These species adsorb to surface silanols by a more specific and stronger hydrogen-bonding mechanism involving the lone pair electrons on the N atom. The strength of these interactions is probably sufficient to result in their retention by dry or damp vadose zone soil, slowing their transport. This work illustrates the utility of these vibrational spectroscopic techniques in elucidat...


Abstract The article presents a process model of the least formalized phase of enterprise change, in which management and all other interested parties identify a need for change, assess what change methodology is adequate to handle that change and make preparations for enacting that change process. This process is intended to be embedded in a complete enterprise engineering/ enterprise integration methodology. The aim has been to give a more detailed account of the first phase of enterprise integration, called the 'identification' phase of the enterprise life-cycle. A top level of the methodology's process is presented as a series of IDEF0 diagrams and their companion explanations, although future versions may be developed in more elaborate languages (e.g. CIMOSA modelling constructs). The original aim to develop this part of the methodology was for the method to be especially suitable for the service industry; it has been found that there was no need to be service industry specific on this level and that...


Fullerene derivatives have often been used as effective scavengers for reactive oxygen species (ROS). This study was designed to test whether polyhydroxylated fullerene derivatives [C(60)(OH)(7+/-2)] protect against oxidative stress in cultured RAW 264.7 cells and ischemia-reperfused (IR) lungs. In RAW 264.7 cells, sodium nitroprusside (SNP, 1 mM) and H(2)O(2) (400 microM) caused a marked (90%) decrease in cell viability, and this decrease was dose dependently reversed by pretreatment with C(60)(OH)(7+/-2) (10-50 microM). The increase in ROS production induced by SNP and H(2)O(2) was significantly suppressed by C(60)(OH)(7+/-2). Also, the decrease in mitochondrial membrane potential induced by SNP and H(2)O(2) was significantly reversed by C(60)(OH)(7+/-2). However, high concentration of C(60)(OH)(7+/-2) (1 and 1.5 mM) lead to cell death (apoptosis or necrosis). In the isolated rat lung, the increases in pulmonary artery pressure and capillary filtration pressure induced by SNP during IR were reversed significantly by C(60)(OH)(7+/-2) (10 mg/kg). These results indicate that polyhydroxylated fullerene derivatives C(60)(OH)(7+/-2) at low concentrations protect against oxidative stress in RAW 264.7 cells and IR lungs.


Supercritical flow experiments were conducted at University of Manitoba using supercritical flow facility-vertical (SFF-V), which is a two vertical parallel channel assembly. The working fluid was CO2 at supercritical pressure and was driven by natural convective forces rather than a pump. Different system pressures (7.4 MPa–9.1 MPa), inlet temperatures (7 °C–30.1 °C) and various outlet-channel k-factors were used. A total of eleven parallel channel out-of-phase instability boundary points were obtained and the details of those cases are reported herein. These results can be used for code validation, to enrich the limited database of supercritical parallel-channel instability and to lend further insight into supercritical flow instability in heated parallel channels.


The appearance of Clostridium botulinum type E organisms and of toxin in experimentally inoculated packages of turkey roll was followed to study the time relationship between the presence of vegetative cells and the demonstration of toxin. The presence of vegetative cells was determined by immunofluorescence, and animal tests were used to assay toxin production. Growth initiated from detoxified spores of C. botulinum type E resulted in toxin formation within 24 hr. Presence of fluorescing vegetative cells and of toxin coincided from 1 to 14 days of incubation. Beginning with the next testing date, day 21, differences were observed. Toxin could be detected for a longer time than vegetative cells. Neither toxin nor organisms could be found after 56 days of incubation. The mouse lethal dose tests (MLD per gram of turkey roll) showed fluctuations in the amount of toxin present throughout the period of testing. Maximal amounts of toxin were present during the period when fluorescing organisms were also more numerous. The applications of immunofluorescence in the study and in the diagnosis of botulism is discussed.


ABSTRACT Blockchain technology can benefit inter-organizational activities by improving data integrity, increasing transaction transparency, and decreasing transaction costs. In this paper, we discuss the strategic and economic value of this technology by applying it to the value-added tax (VAT) reporting system, focusing on blockchain's characteristic traceability. By effectively increasing financial transparency, the application of blockchain to the VAT system can prevent VAT-related fraud (e.g., underreported VAT) that can arise due to the information asymmetry that exists at different stages of the supply chain. We develop a game theoretical model that involves a retailer and two vendors in order to study the players' strategic decisions regarding blockchain adoption and to examine the effects on social welfare. We also show how the decision to adopt blockchain depends on considerations such as adoption costs, the vendors' VAT reporting behavior, the retailer's profit margins, and inter-vendor competition. Furthermore, we find that under certain conditions, policymakers can increase social welfare by providing subsidies to encourage blockchain adoption.88


Cryo-electron tomography provides 3D images of macromolecules in their cellular context. To detect macromolecules in tomograms, template matching (TM) is often used, which uses 3D models that are often reliable for substantial parts of the macromolecules. However, the extent of rotational searches in particle detection has not been investigated due to computational limitations. Here, we provide a GPU implementation of TM as part of the PyTOM software package, which drastically speeds up the orientational search and allows for sampling beyond the Crowther criterion within a feasible timeframe. We quantify the improvements in sensitivity and false-discovery rate for the examples of ribosome identification and detection. Sampling at the Crowther criterion, which was effectively impossible with CPU implementations due to the extensive computation times, allows for automated extraction with high sensitivity. Consequently, we also show that an extensive angular sample renders 3D TM sensitive to the local alignment of tilt series and damage induced by focused ion beam milling. With this new release of PyTOM, we focused on integration with other software packages that support more refined subtomogram-averaging workflows. The automated classification of ribosomes by TM with appropriate angular sampling on locally corrected tomograms has a sufficiently low false-discovery rate, allowing for it to be directly used for high-resolution averaging and adequate sensitivity to reveal polysome organization.


As a key technology in 4G-LTE, heterogeneous networks can effectively extend the coverage and capacity of wireless networks by deploying multiple micro-nodes on top of the conventional macro base stations (BS). The deployed micro-nodes differ in transmission power and processing capabilities, leading to new challenges in interference management, mobile association, and radio resource management (RRM). In this paper, we consider RRM for heterogeneous networks with relays (RN) where the RNs have full RRM capabilities and can be viewed as micro BSs. A radio resource allocation framework is proposed with the objective to ensure proportional fairness among the UEs. An asymptotically optimal solution is derived by applying the gradient-based scheduling scheme and the Karush-Kuhn-Tucker (KKT) conditions for optimality. To implement RRM in networks with RNs, the resource consumption in the backhaul links, which depends on the demand of the UEs associated with the RN, should be counted at both the BS and the RN. The derived resource allocation scheme gives insight on the optimal radio resource allocation for heterogeneous networks with RNs.


Objective. Intracortical recordings have now been combined with functional electrical stimulation (FES) of arm/hand muscles to demonstrate restoration of upper-limb function after spinal cord injury. However, for each desired limb position decoded from the brain, there are multiple combinations of muscle stimulation levels that can produce that position. The objective of this simulation study is to explore how modulating the amount of coactivation of antagonist muscles during FES can impact reaching performance and energy usage. Stiffening the limb by cocontracting antagonist muscles makes the limb more resistant to perturbation. Minimizing cocontraction saves energy and reduces fatigue. Approach. Prior demonstrations of reaching via FES used a fixed empirically-derived lookup table for each joint that defined the muscle stimulation levels that would position the limb at the desired joint angle decoded from the brain at each timestep. This study expands on that previous work by using simulations to: (a) test the feasibility of controlling arm reaching using a suite of lookup tables with varying levels of cocontraction instead of a single fixed lookup table for each joint, (b) optimize a simple function for automatically switching between these different cocontraction tables using only the desired kinematic information already being decoded from the brain, and (c) compare energy savings and movement performance when using the optimized function to automatically modulate cocontraction during reaching versus using the best fixed level of cocontraction. Main results. Our data suggests energy usage and/or movement performance can be significantly improved by dynamically modulating limb stiffness using our multi-table method and a simple function that determines cocontraction level based on decoded endpoint speed and its derivative. Significance. By demonstrating how modulating cocontraction can reduce energy usage while maintaining or even improving movement performance, this study makes brain-controlled FES a more viable option for restoration of reaching after paralysis.


This study examined effect of working capital management on profitability containing twenty manufacturing firms listed in Nairobi securities exchange. Kenya's manufacturing sector has been hit by poor working capital management leading to unstable profits. Despite various scholars conducting studies concerning Kenyan manufacturing firms' working capital, lack of consistence revenues require further examination on what causes these deviations. Current study was piloted by following specific objectives; Influence of inventories, receivable, payable, and cash managements on profitability of manufacturing firms. Theories that guided this study were: agency, transaction cost, and cash conversion cycle. Descriptive statistics was used on analysis especially, minimum, maximum, mean and standard deviation. Mathematical data evaluation involved inferential statistics. In addition, study model quantitative data was presented in tables. The study accepted census sampling method for collecting secondary data from population of 20 companies listed for five years from 2016 to 2020. Secondary details were found in financial statements of manufacturing firms and Nairobi Securities Exchange. Data was collected using checklist. The study recommended that manufacturing companies should estimate desirable quantity of working capital and concluded that increased working capital should match increased expenses, sales and revenue.


Abstract The subgenus Tinotus Sharp, 1833, stat. n., of the genus Aleochara Gravenhorst, 1802 (Aleocharini: Aleocharina) from Japan, Taiwan, and the Russian Far East is revised. Tinotus is a new record from the latter two regions. Three species are recognized: Aleochara (Tinotus) morion Gravenhorst, 1802, comb. n. [Japan (new record), the Russian Far East (new record)], Aleochara (Tinotus) eoa nom. n. [replacement name for Tinotus japonicus Cameron, 1933; Japan, Taiwan (new record)], and Aleochara (Tinotus) takashii sp. n. (central Honshû, Japan). The systematic position of Tinotus is discussed. All species are (re-)described, keyed, and figured. A world checklist of Tinotus species, comprising 40 valid species, is provided in an appendix. Additional taxonomic changes are proposed, including a new synonymy, a revalidation, 13 new replacement names, and 27 new combinations.


Abstract Eculizumab has been developed as a breakthrough treatment for paroxysmal nocturnal hemoglobinuria (PNH). Not only for breakthroughs, eculizumab therapy is also known to increase the risk of invasive meningococcal infection. It has also been recently reported that, although rarely, administration of eculizumab may result in disseminated gonococcal infection (DGI). We report here a case in which a young patient who had used eculizumab for PNH developed DGI. A 22-year-old Japanese male with PNH who had been treated with eculizumab complained of high fever, mild nausea, headache and right knee joint pain. The patient was admitted and suspected to have sepsis due to meningococcal infection and began to receive ceftriaxone (CTRX). Gonococci were detected in a venous blood culture a few days later, and this case was diagnosed as DGI. CTRX was effective, and the patient was discharged. However, four weeks later, he complained of the same subjective symptoms as at the beginning and was hospitalized again. The presence of gonococcus was proven by venous blood culture, CTRX was re-administered and the patient responded. After discharge, he was counseled on safer sexual activity, including accurate and consistent use of condoms, by urologists. He has not relapsed with DGI for more than one year. When serious signs of infection occur in patients receiving eculizumab, it is recommended to consider DGI as well as invasive meningococcal infection, and CTRX should be given.


The physico-chemical properties of binary blends of palm oil products with deodorised cocoa butter (DCB, IV 32.7) at levels ranging from 10% to 90% (w/w) were evaluated. Cocoa butter equivalent (CBE, IV 32.4) showed full compatibility with DCB at all concentrations and crystallised to form a strong b in a mixture of b + bʹ polymorphic forms. Results of solid fat content (SFC) show that the addition of 10% to 20% palm-mid fraction (PMF, IV 41) and cocoa butter substitute (CBS, IV 0.3) with DCB gave rise to eutectic effects and that the mixture crystallised to form a strong bʹ in a mixture of b + bʹ polymorphic forms. The differential scanning calorimetry (DSC) melting thermograms of the CBE and DCB blends showed a single melting peak at ± 19.5°C. There were two prominent melting peaks observed in the blends containing more than 10% to


In this paper, an index of the depth of experience with state-level institutions, or state antiquity, is derived for a large set of countries. We show that state antiquity is significantly correlated with measures of political stability and institutional quality, with income per capita, and with the rate of economic growth between 1960 and 1995. State antiquity contributes significantly to the explanation of differences in growth rates, explaining half of the differences in growth rates between countries like China and Mauritania, which are located at the two ends of the spectrum. It is also a good instrument for "social infrastructure," which explains cross-country differences in worker productivity.


The paper presents our considerations related to the creation of a digital corpus of Bulgarian dialects. The dialectological archive of Bulgarian language consists of more than 250 audio tapes. All tapes were recorded between 1955 and 1965 in the course of regular dialectological expeditions throughout the country. The records typically contain interviews with inhabitants of small villages in Bulgaria. The topics covered are usually related to such issues as birth, everyday life, marriage, family relationship, death, etc. Only a few tapes contain folk songs from different regions of the country. Taking into account the progressive deterioration of the magnetic media and the realistic prospects of data loss, the Institute for Bulgarian Language at the Academy of Sciences launched in 1997 a project aiming at restoration and digital preservation of the dialectological archive. Within the framework of this project more than the half of the records was digitized, de-noised and stored on digital recording media. Since then restoration and digitization activities are done in the Institute on a regular basis. As a result a large collection of sound files has been gathered. Our further efforts are aimed at the creation of a digital corpus of Bulgarian dialects, which will be made available for phonological and linguistic research. Such corpora typically include besides the sound files two basic elements: a transcription, aligned with the sound file, and a set of standardized metadata that defines the corpus. In our work we will present considerations on how these tasks could be realized in the case of the corpus of Bulgarian dialects. Our suggestions will be based on a comparative analysis of existing methods and techniques to build such corpora, and by selecting the ones that fit closer to the particular needs. Our experience can be used in similar institutions storing folklore archives, history related spoken records etc.


With the growing adoption of AI, trust and explainability have become critical which has attracted a lot of research attention over the past decade and has led to the development of many popular AI explainability libraries such as AIX360, Alibi, OmniXAI, etc. Despite that, applying explainability techniques in practice often poses challenges such as lack of consistency between explainers, semantically incorrect explanations, or scalability. Furthermore, one of the key modalities that has been less explored, both from the algorithmic and practice point of view, is time-series. Several application domains involve time-series including Industry 4.0, asset monitoring, supply chain or finance to name a few. The AIX360 library (https://github.com/Trusted-AI/AIX360) has been incubated by the Linux Foundation AI & Data open-source projects and it has gained significant popularity: its public GitHub repository has over 1.3K stars and has been broadly adopted in the academic and applied settings. Motivated by industrial applications, large scale client projects and deployments in software products in the areas of IoT, asset management or supply chain, the AIX360 library has been recently expanded significantly to address the above challenges. AIX360 now includes new techniques including support for time-series modality introducing time series based explainers such as TS-LIME, TS Saliency explainer, TS-ICE and TS-SHAP. It also introduces improvements in generating model agnostic, consistent, diverse, and scalable explanations, and new algorithms for tabular data. In this hands-on tutorial, we provide an overview of the library with the focus on the latest additions, time series explainers and use cases such as forecasting, time series anomaly detection or classification, and hands-on demonstrations based on industrial use-cases selected to demonstrate practical challenges and how they are addressed. The audience will be able to evaluate different types of explanations with a focus on practical aspects motivated by real deployments.


Membrane fusion in all eukaryotic cells is regulated by the formation of specific SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complexes. The molecular mechanisms that control this process are conserved through evolution and require several protein families, including Sec1p/Munc18 (SM) proteins. Here, we demonstrate that the mammalian SNARE protein syntaxin 16 (Sx16, also known as Syn16) is a functional homologue of the yeast SNARE Tlg2p, in that its expression fully complements the mutant phenotypes of tlg2Δ mutant yeast. We have used this functional homology to demonstrate that, as observed for Tlg2p, the function of Sx16 is regulated by the SM protein Vps45p. Furthermore, in vitro SNARE-complex assembly studies demonstrate that the N-terminal domain of Tlg2p is inhibitory to the formation of SNARE complexes, and that this inhibition can be lifted by the addition of purified Vps45p. By combining these cell-biological and biochemical analyses, we propose an evolutionarily conserved regulatory mechanism for Vps45p function. Our data support a model in which the SM protein is required to facilitate a switch of Tlg2p and Sx16 from a closed to an open conformation, thus allowing SNARE-complex assembly and membrane fusion to proceed.


This paper presents an Ant Colony Optimization (ACO) based design methodology for improving the efficiency besides reducing the material cost of Induction Motor (IM). ACO is inspired from the foraging behaviour of ants, and in particular, how ants can find shortest paths between food sources and their nest. It does not require initial values for the decision variables and uses a stochastic random search that is based on the chemical pheromone trail so that the derivative information is unnecessary. Among the number of design variables of the IM, seven variables are branded as primary design variables and the ACO based design strategy is built to optimize the chosen primary variables with a view to obtain the global best design. The developed methodology is applied in solving two IM design problems and the results are presented with a view of exhibiting the superiority of the developed algorithm.


Introduction HLA class I is associated with the outcome of hepatitis C virus (HCV) infection. Tapasin is a member of the peptide loading complex that loads self and viral peptides onto HLA class I. Presentation of viral peptides by HLA class I is critical in generating an effective cytotoxic T lymphocyte (CTL) response, and hence in clearing HCV infection. However, not all HLA alleles require tapasin for efficient peptide loading. Thus polymorphisms in the tapasin gene could affect clearance of HCV in combination with specific "tapasin-dependent" HLA class I alleles. The SNP rs2071888 is a non-synonymous polymorphism in exon 4 of the Tapasin gene causing an arginine to threonine change that could affect tapasin function. We have investigated the effect of this SNP in resolving hepatitis C virus (HCV) infection in a cohort of 336 patients from the UK. Aim We have investigated the effect of the SNP rs2071888 in resolving hepatitis C virus (HCV) infection in a cohort of 336 patients from the UK. Method Genomic DNA from 216 chronically infected individuals and 120 spontaneous resolvers of HCV was genotyped with an allele specific PCR designed to identify the G/C SNP in exon 4 of the Tapasin gene. Individuals were also typed for HLA-A, -B and -C. Results were analysed for association with hepatitis C outcome. Results Overall the G allele of tapasin was associated with protection against chronic HCV infection (p=0.018, OR=1.99, 95% CI 1.14 to 3.46). Interestingly, in combination with heterozygosity at the HLA-B locus, heterozygosity at the tapasin locus was also protective (Abstract OP04 figure 1, p trend =0.005). Furthermore, we identified specific HLA-B alleles associated with protection in the context of the Tapasin G, but not Tapasin C allele. Specifically the G allele was most protective in the context of B*0702 (p=0.029, OR=4.56, 95% CI 1.2 to 17.27), and B*5701 (p=0.029, OR=12, 95% CI 1.2 to 120). Tapasin has been shown to bind specifically to amino acids 114 and 116 of HLA class I. Consistent with this functional interaction we found that aspartate at position 114 and serine at 116 were most beneficial in the context of both the G allele (D114/TapG, p<0.0001, OR=3.3, 95% CI 1.83 to 5.98; S116/TapG, p<0.0001, OR=2.73, 95% CI 1.57 to 4.76).Abstract 0P04 Figure 1 Association Of tapasin and HLA-B Heterozygosity with resoution of hepatitis c infection (p=0.005(trend test)).protection was not significantly associated with heterozygosityat HLA-A or HLA-c and tapsain. Conclusion The G allele of tapasin was associated with protection from chronic HCV infection, both alone and in combination with specific HLA class I alleles. Individuals who are heterozygous for both tapasin and HLA-B are relatively protected from chronic HCV infection. This heterozygosity may allow them to present a broader range of peptides to CTL and thus mount a more effective anti-HCV immune response.


A protein kinase phosphorylating sea urchin spermatogenous histones, H1 and H2B, was found in sea urchin egg homogenate and purified. The kinase is activated by cAMP and is composed of two different types of subunits with molecular masses 41 and 46 kDa. The kinase phosphorylates a peptide, Ser-Pro-Arg-Lys-Ser-Pro-Arg-Lys, which is a double repeat of the DNA-binding SPKK motif [Suzuki M., (1989) EMBO J. 8, 797-804]. We name this kinase SPkinase because it exclusively phosphorylates H1 and H2B, the only histones containing SPKK motifs. Phosphorylation of H1 by SPkinase decreases the DNA-binding ability of H1. This paper is the first to report purification of a kinase which affects the DNA-binding ability of a gene regulatory protein.


Acknowledgments, Prologue: "Borderline" Women Among the Mentally Ill, From Witchcraft to Hysteria to BPD: A Brief History of Female Insanity, Women and Madness: A Historical View, A "Chattering, Canting Age," Two Women's Histories: Charlotte Perkins Gilman and Alice James, Taxonomy as Destiny? The Birth of Labels, "Mad" Women and "Bad" Men, Mental Illness and Labeling Theory: Are We Blaming the Victim?, Gender Roles, Mental Illness, and the Price of Deviance, Psychiatry's Family Bible: DSM, The Clinical Realities of Naming and Diagnosis, The Personality Disorders: Prevalence and Politics, Gender Bias in Diagnosis, The Rise and Fall of the Borderline Concept, Object Relations, Developmental Arrest, and the Borderline Syndrome, Critiques of Theoretical Formulations, Toward an Etiology of Borderline Symptomatology, Biology as Destiny? Abuse Traumata and Psychological Distress, The BPD/PTSD Controversy: Who's on First?, Development of the Self, Developmental Psychopathology and the Borderline Disorder, Through the Looking Glass: Female Socialization and Personality Disorder, In the Looking Glass, A Case of Privileged Meaning: The Reification of Autonomy, Continuities and Discontinuities in Women's Coming of Age, Anger, Dependency, and Fear: Women at the Border, Member of the Wedding, Autonomy Revisited: Personality Disorder and Ideas About Autonomy, Anger, Dependency, and Personality Disorder, "Borderline" Self-Destructiveness and Therapeutic Breakdown, Self-Injury and BPD, Borderline Women and the Dialogue of Suicide, Treatment at the Border, Notes, References, About the Book and Author, Index


Connection between optical active/passive elements and libers is very important in practical device packaging. Multichannel connection is very hard if we use liber array direct coupling to multichannel elements such as laser diode arrays, matrix switches, and grating filters. Minford et al. reported a Ti:LiNbO3 seven-channel waveguide concentrator between a single-mode fiber array and a grating filter with a GRIN lens.1 However, Ti:LINbO3 has a relatively low ΔN and needs a large bending radius and connection length to expand the interchannel distance with low insertion loss. To realize compact connecting circuits, a large ΔN waveguide is needed.


Carbon(C) nanomaterials (e.g. grapheme(G), carbon nanotubes(CNTs), crystalline diamond, diamond-like carbon nanoparticles(CNPs), nanofibers) are continuously more sophisticated in their range of physicochemical tunable properties (e.g. 2D surfaces, 3D structures, stiffness, porosity, permeability, biodegradability, and biocompatibility), and their range of applications for biomedical and biochemical sensing (e.g. microbiology, environmental chemistry, oncology, regenerative medicine, tissue engineering, stem cell culture, and maintenance) continues to grow, potentially enhancing bioefficacy and biosafety.


Issues of international cooperation in the field offorensic expert activity are always relevant both for judicial power in general and for itself. The importance of such cooperation has increased in connection with the reform of political, economic, social and law enforcement systems in Ukraine. The main reasons for the need of international forensic- expert cooperation are the integration and globalization of international scientific relations and the implementation of its results in its own legislative and other bases. The issues of international forensic-expert cooperation have found their reflection in the international treaties in the field of expert activity with European countries, countries of the near and far east. These agreements define the procedure for calling experts abroad, give guarantees for the protection of experts, provide the right of the expert to reimburse travel and stay costs, as well as the right to payfor the work done. An urgent issue of international cooperation of Ukrainian expert institutions in the field of forensic expert activity is the entrance to the European Network of Forensic Science Institutes (ENFSI). Since 2002, the State Research Expert-criminalistic Center of the Ministry of Internal Affairs of Ukraine is a full member of ENFSI. To date, two expert institutions of the Ministry of Justice of Ukraine are members of the ENFSI - it's the Hon. Prof. M. S. Bokarius Kharkiv Research Institute of Forensic Examinations and Kiyiv Research Institute of Forensic Examinations. International cooperation in the field of forensic-expert activity in Ukraine is a dynamically developing system that meets the interests of not only forensic experts, but also all the subjects ofpublic and political life. Integration of international standards into the nationalforensic- expert activity is conditioned by the development of innovative expert methods and techniques, which, in their turn, enhance the prestige and professionalism of Ukrainian expert institutions.


INTRODUCTION
In some cases, surgical treatment is necessary to manage intussusception despite advances in enema reduction. The purpose of this study was to analyse treatment in two tertiary referral university centres for paediatric surgery to identify time-related factors influencing treatment of intussusception.

METHODS
This was a retrospective two-centre chart review, performed for all patients under the age of 16 years who underwent treatment for intussusception during the period from 2005 to 2015. Demographic data and data on different time intervals from symptom debut to end of treatment and compliacations were retrieved from the medical record.

RESULTS
A total of 158 children were included. Non-surgical reduction was used as the primary treatment modality in 48% and intussusception was successfully reduced in 32% of these cases. The non-surgical success rate was found to be significantly higher when the diagnosis was confirmed within four hours of hospitalisation (p = 0.003). A lower rate of bowel resection was observed when the diagnosis was confirmed within four hours of hospitalisation (p = 0.026) and treatment was initiated within six hours of hospitalisation (p = 0.033).

CONCLUSIONS
This study found a relatively low utilisation rate for enema reduction and an overall low enema success rate. The success rate of enema was significantly higher and the intestinal resection rate lower when the diagnosis was confirmed within four hours of hospitalisation, which underpins the importance of a quick and timely diagnosis.

FUNDING
none.

TRIAL REGISTRATION
not relevant.


The source process of the 1995 Kobe earthquake is determined using teleseismic body waves. The source parameters obtained for the total source are: focal mechanism [strike, dip, rake] equal to [233°, 86°, 167°], nearly pure strike-slip with an EW compression axis; the seismic moment, M_o= 2.5×10^(19) Nm (M_w= 6.9); and source duration T=11s. The rupture process consists mainly of three subevents with source durations of 5-6 s: two are nearly pure strike-slip with slightly different fault strikes, and the other is dip-slip. Combining the source location with the aftershock distribution, we infer that the first subevent is a bilateral rupture and the later subevents are unilateral propagating NE and reaching the Kobe area. The total fault length is 40 km, the averaged dislocation is 2.1 m, and the averaged stress drop is 8 MPa. These source parameters indicate that the Kobe earthquake was a typical shallow inland earthquake which occurred on a previously mapped Quaternary fault zone. The directivity toward Kobe determined from teleseismic data was probably one of the main factors responsible for the heavy damage. The combined use of regional networks and teleseismic networks as demonstrated in this study will continue to be important for rapidly assessing the overall social impact of an earthquake in the very early stage of sequence.


Telmatobius macrostomus and Telmatobius brachydactylus are two high Andean aquatic frogs categorized as "Endangered" by the Red List of the International Union for Conservation of Nature and by the Peruvian Legislation. With the aim of evaluating the water quality of their habitats, four bimonthly samplings in the field were carried out at 12 study sites located in the Junin and Pasco regions of Peru. Physicochemical, hydrological and microbiological variables were measured. Samples of aquatic macroinvertebrates were taken and the following water quality indices were applied: Andean Biotic Index (ABI) and Family Biotic Index (FBI). The results show that the environmental variables total dissolved solids (TDS) and total coliforms exceed the Environmental Quality Standards (ECA) for water according to Peruvian regulations. The aquatic macroinvertebrate community showed differences in its community structure between sampling stations and indicated moderate to good water quality according to the applied indices, except in the stations that would be being impacted by cattle farming and chuño production (ancestral activity whereby freeze-dried potatoes are fermented in cold, running stream water), both activities impact the water quality of the studied habitats and could influence the presence of frogs, because both species generally inhabit clean aquatic ecosystems.


Background: The WNT/ β-catenin signaling pathway has been shown to play a key role in both normal development and tumorigenesis (Polakis, 2007; MacDonald et al., 2009). We have developed a monoclonal antibody, vantictumab, that blocks canonical WNT/β-catenin signaling through binding of five FZD receptors (1, 2, 5, 7, 8). This antibody inhibits the growth of several tumor types, including pancreas, breast, colon and lung. Furthermore, our studies showed that vantictumab reduces tumor-initiating cell frequency and exhibits synergistic activity with standard-of-care (SOC) chemotherapeutic agents (Gurney et al., 2012). Material and methods: We set out to identify a predictive biomarker for the response to vantictumab in pancreatic cancer patients by analyzing mRNA-seq gene expression data from 14 patient-derived xenograft (PDX) models. These 14 minimally passaged pancreatic xenograft tumors were tested in vivo and their responses to vantictumab, in combination with the current SOC gemcitabine and nab-paclitaxel were established. Samples from these experiments were collected for Pharmacodynamic (PD) biomarker analysis. We utilized a two-sample Welch9s t-test to identify genes that can distinguish between responders and non-responders and the K-nearest neighbor (KNN, Altman 1992) algorithm for classification. A leave-one-out cross-validation was used to measure area under the ROC curve (Fawcett et al., 2006, AUC), accuracy (ACC), positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity of the model. Results: PD biomarker analysis confirmed inhibition of genes in Wnt and stem cell pathways by vantictumab in combination with gemcitabine as well as gemcitabine plus nab-paclitaxel. The selected 3-gene signature comprising TGFB3, IGF2 and SMO achieved the best performance (AUC = 0.875, ACC = 0.93, PPV = 0.91, NPV = 1, sensitivity = 1, specificity = 0.75) in the 14 PDX pancreatic tumor models. In addition, a strong correlation between the gene signature biomarker and the ratio of tumor inhibition (RTI) in the pancreatic xenograft experiments was observed. The identified 3-gene biomarker was used to predict the response to vantictumab in combination with gemcitabine and nab-paclitaxel in three additional pancreatic PDX tumor models. The efficacy in the three models was successfully predicted by the biomarker. Conclusions: The 3-gene biomarker is being evaluated in a Phase 1b study of vantictumab in combination with gemcitabine and nab-paclitaxel in previously untreated stage IV pancreatic cancer (NCT02005315). Citation Format: CHUN ZHANG, Fiore Cattaruzza, Pete Yeung, Wan-Ching Yen, Marcus Fischer, Claire Guo, Alayne Brunner, Min Wang, Belinda Cancilla, Austin Gurney, Rainer Brachmann, John Lewicki, Tim Hoey, Ann M. Kapoun. Predictive biomarker identification for response to vantictumab (OMP-18R5; anti-Frizzled) using primary patient-derived human pancreatic tumor xenografts. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3129.


This article presents the rationale for using multilevel analysis to address the broad environmental contexts in patient satisfaction research. This study utilized patient satisfaction data and the American Hospital Association Hospital Guide Book (2004). This study found significant contributions of individual patient attribute reactions (nursing care, physician care, etc.), and also clearly demonstrated hospital-level effects and cross-level interactions on patient satisfaction. Thus, it is clear that patient satisfaction is not solely explained by patients' attribute reactions and their demographic variables, but is also explained by patients' hospital levels. This approach would offer additional understanding in patient satisfaction research.


INTRODUCTION
Little is known of the changes in patients' health condition while in hospital in low-resource settings. The aim of this exploratory study is to examine dependency of patients on hospital admission and discharge in a low-resource sub-Saharan hospital.

METHODS
We carried out a retrospective observational study of changes in the health condition, as reflected by their mental status, mobility and vital signs, of 5,888 consecutive patients between hospital admission and discharge.

RESULTS
Mental status, mobility and vital signs were normal in 25% of patients on hospital admission and 30% of patients at discharge. Although very few patients with normal mental status, mobility and vital signs on admission died in hospital, the condition of 40% of them deteriorated.

CONCLUSION
No comparative data on changes in health condition between hospital admission and discharge have been published. Our proposed health condition categories identify changes that may matter most to patients and should be considered as a standard metric of hospital care.


Clustering the process of grouping homogeneous objects is an important data mining process. Few algorithms exist to cluster categorical data. K-Modes is the scalable and efficient algorithm to cluster the categorical data. In this paper we propose a new distance measure for K-Modes based on the cardinality of domain of attribute. The proposed method is experimented with data sets obtained from UCI data repository. Results prove that the proposed measure generates better clusters than the K-Modes algorithm.


This paper introduces hybrid structures with unit cells that are a combination of lattice and ladder topologies. These unit cells dramatically increase the quality factor, miniaturization, and maximum frequency of synthetic transmission lines. Also, it is shown that lattice topologies in general are less vulnerable to the effect of parasitics, such as self resonance of loading capacitors or mutual inductance between different cells. The underlying theory is studied, and simple formulas are given for predicting the behavior of these lines. A few examples are presented that, based on full-wave simulations, show the large gain in minia- turization, quality factor, or bandwidth compared to the simple ladder or lattice structures. Measured results for a fabricated synthetic line are presented that show a miniaturization factor of for and a very small dispersive behavior from dc to 2.5 GHz.


In this study, we examine how technological regime affects the performance of technology development projects (i.e., project quality, sales, and profit). Technological regime is defined as the set of attributes of a technological environment where the innovative activities of firms take place. Technological opportunity, appropriability of innovations, cumulativeness of knowledge and capabilities, and closeness of knowledge base to basic sciences (versus applied sciences) are attributes of technological regime. Using data from 381 firms across five industries, we show that high levels of technological opportunity, appropriability, and closeness of knowledge base to basic sciences are associated with higher project performance. Cumulativeness is associated with higher project quality, but not higher sales and profit. We also show that the effect of technological opportunity on project performance is moderated by two other determinants of technological regime: cumulativeness and nature of knowledge base. We find that cumulativeness has a negative moderating effect on the positive relationship between technological opportunity and project performance, while closeness of knowledge base to basic sciences positively moderates the effect of technological opportunity on project performance. We discuss the implications of our findings for new product development research and practice.


Mouse oocytes arrested in metaphase II exhibit zona hardening and a reduced fertilization rate after exposure to the cryoprotectant dimethylsulfoxide (Johnson J, In Vitro Fertil Embryo Transfer 6:168–175, 1989) but do not undergo parthenogenetic activation (Johnson and Pickering, Development 100:313–324, 1987). This paper shows that dimethylsulfoxide cause proteolytic modification of the zona pellucida glycoprotein ZP2 and inhibition of sperm binding. These effects of dimethylsulfoxide are caused by premature exocytosis of the cortical granules, a process that is initiated usually on fertilization. A model for the mechanism of action of dimethylsulfoxide is proposed based on the combined effects of cytoskeletal modification and osmotic shock. The presence of serum before and during the exposure to dimethylsulfoxide was found to reduce significantly these deleterious effects on the mouse zona pellucida without inhibiting the cortical granule release. These results highlight the suitability of dimethylsulfoxide as a tool to study the mechanisms leading to cortical granule release. Use of dimethylsulfoxide allows the separation of oocyte parthenogenetic activation from cortical granule release, and addition of serum allows separation of cortical granule release from the action of the cortical granule contents. Their use allows a dissection of the mechanisms underlying each of these three related events.


Monoclonal antibodies (mAbs) have emerged as indispensable assets in medicine, and are currently at the forefront of biopharmaceutical product development. However, the growing market demand and the substantial doses required for mAb clinical treatments necessitate significant progress in its large-scale production. Most of the processes for industrial mAb production rely on batch operations, which result in significant downtime. The shift towards a fully continuous and integrated manufacturing process holds the potential to boost product yield and quality, while eliminating the extra expenses associated with storing intermediate products. The integrated continuous mAb production process can be divided into the upstream and downstream processes. One crucial aspect that ensures the continuity of the integrated process is the switching of the capture columns, which are typically chromatography columns operated in a fed-batch manner downstream. Due to the discrete nature of the switching operation, advanced process control algorithms such as economic MPC (EMPC) are computationally difficult to implement. This is because an integer nonlinear program (INLP) needs to be solved online at each sampling time. This paper introduces two computationally-efficient approaches for EMPC implementation, namely, a sigmoid function approximation approach and a rectified linear unit (ReLU) approximation approach. It also explores the application of deep reinforcement learning (DRL). These three methods are compared to the traditional switching approach which is based on a 1% product breakthrough rule and which involves no optimization.


The paper surveys the characteristics of multimedia systems. Multimedia applications today are dominated by compression and decompression, but multimedia devices must also implement many other functions, such as security and file management. We introduce some basic concepts of multimedia algorithms and the larger set of functions that multimedia systems-on-chips must implement.


The mitochondria play an important role in both apoptosis and heme synthesis. In patients with Myelodysplastic syndrome (MDS) the marrow is characterized by defective hematopoiesis, increased apoptosis and the presence of iron laden mitochondria. The molecular mechanisms responsible for increased apoptosis remain incompletely understood. Frederic's ataxia (FRDA), the most common inherited ataxia, is a severe autosomal-recessive disease characterized by neurodegeneration, cardiomyopathy and diabetes, resulting from reduced synthesis of the mitochondrial protein frataxin which is involved in mitochondrial energy production and other cellular functions by providing iron for heme synthesis and iron–sulfur cluster (ISC) assembly and repair, serving as a Fe (II) donor for ferrochelatase. The underlying mutation consists of an unstable expansion of GAA repeats in the first intron of the frataxin gene. Long expansions of a GAA tri-nucleotide in FRDA patients range from 66 to more than 1,700 repeats, whereas the normal range of repeats varies from 7 to 36. Abnormal expansion results in reduced frataxin mRNA levels, leading to reduced function of the respiratory chain. The aim of the present study was to determine if frataxin gene mutations occurred in MDS patients. We analyzed DNA from peripheral blood (PB) of 29 MDS patients and from 22 healthy marrow (BM) donors using repeat-Primed PCR. We also sampled genomic DNA products from buccal smears of the MDS patients. In MDS patients PCR of PB in 9 out of 24 patients (37%) showed short length (2–8 repeats), whereas PB of the remaining 15 patients (62.5%) showed longer PCR products (10–43 repeats, still in the "normal" range for FRDA). The PCR products of the buccal smears from all 14 patient samples were short (2–7 repeats), including those from 9 patients who had longer repeats in PB. In healthy BM donors, PCR of PB detected short length repeats (4–5 repeats) in17 of 20 individuals (85%), whereas 3 samples (15%) had longer PCR products (11–26 repeats). This was statistically significantly different from patients with MDS (P= 0.0014). The results indicate that MDS patients exhibit longer frataxin gene products than healthy individuals in PB, but not in buccal DNA. These data suggest a somatic mutation in the frataxin gene in hematopoetic cells of patients with MDS. Further studies will explore the impact of this mutation on mitochondrial function and on the pathophysiology of MDS.


The Weberian apparatus of otophysan fishes confers acute hearing that is hypothesized to allow these fishes to assess the environment and to find food resources. The otophysan family Serrasalmidae (piranhas and pacus) includes species known to feed on falling fruits and seeds (frugivore/granivores) that splash in rivers, herbivorous species associated with torrents and rapids (rheophiles), and carnivores that feed aggressively within shoals. Relevant sound stimuli may vary among these ecological groups and hearing may be tuned to different cues among species. In this context, we examined size variation of the Weberian ossicles, swim bladder chambers, and otoliths of 20 serrasalmid species from three broad feeding ecologies: frugivore/granivores, rheophiles, and carnivores. We performed 3D‐reconstructions of high resolution tomographic data (μCT) from 54 museum specimens to estimate the size of these elements. We then tested for an ecology effect on covariation of auditory structure size and body size and accounted for phylogeny with phylogenetic generalized least squares analyses. Among ecological groups, we observed differences in relative sizes of otoliths associated with sound pressure and particle motion detection, and variation in Weberian ossicle size that may impact sound transmission. Rheophiles, which live in noisy environments, possess the strongest modifications of these structures.


Purpose

This paper aims to review the potential application of surface plasmon resonance (SPR) in diagnosis of dengue virus (DENV-2) E-protein and the development of SPR to become an alternative DENV sensor.

Design/methodology/approach

In this review, the existing standard laboratory techniques to diagnosis of DENV are discussed, together with their drawbacks. To overcome these drawbacks, SPR has been aimed to be a valuable optical biosensor for identification of antibodies to the DENV antigen. The review also includes the future studies on three-dimensional poly(amidoamine) (PAMAM) dendrimer-surface-assembled monolayer (SAM)-Au multilayer thin films, which are envisaged to have high potential sensitive and selective detection ability toward target E-proteins.

Findings

Application of SPR in diagnosis of DENV emerged over recent years. A wide range of immobilized biorecognition molecules have been developed to combine with SPR as an effective sensor. The detection limit, sensitivity and selectivity of SPR sensing in DENV have been enhanced from time to time, until the present.

Originality/value

The main purpose of this review is to provide authors with up-to-date and useful information on sensing DENV using SPR and to introduce a novel three-dimensional PAMAM-SAM-Au multilayer thin films for future research on SPR sensing applications.


The c-ERBB-2 gene is frequently amplified in various cancers. During the course of studies on the structural characterization of the amplification units, we isolated four cDNA clones, A39, GRB7, C51 and CAB1 with corresponding genes localized on the c-ERBB-2 locus. A tentative gene, C51, was located at about 12 kb upstream of the c-ERBB-2 gene. By molecular cloning of a full-length cDNA clone of C51 and the reverse transcription PCR (RT-PCR) method, we identified a novel transcript of c-ERBB-2 containing new 5' sequences including the C51 sequence, demonstrating that the c-ERBB-2 gene has a novel promoter and new exons. The structural organization of the novel promoter and exons of c-ERBB-2 was revealed by complete sequence analysis of a total size of about 20 kb of genomic DNA clones containing the 5'-flanking region of the previously described c-ERBB-2 gene. Transient expression of the newly identified promoter-reporter gene constructs in breast cancer cell line MCF-7 showed that the elements responsible for promoter activity were contained in a 697 bp region upstream of the transcriptional start site. The new transcript may encode a protein different in the portion of the extracellular domain. Although the presence of the predicted protein product was not examined, this report is important in that it provides a new aspect of the c-ERBB-2 protooncogene products.


The global changes in gene expression in injured murine skin were characterized following a second-degree scald burn. Dorsal skin was harvested from uninjured and from burned mice at 2 h and at 3 and 14 days following immersion in 65 degrees C water for 45 s. Gene expression was surveyed using an Affymetrix U74Av2 GeneChip, and patterns of gene expression were analyzed using hierarchical clustering and supervised analysis. Burn injury produced significant alterations in the expression of a number of genes, with the greatest changes seen 3 and 14 days after the scald burn. Using a supervised analysis with a false discovery rate of 1% or 5%, differences in the expression of 192 or 1,116 genes, respectively, discriminated among the unburned skin and the three time points after the burn injury. Gene expression was primarily a transient and time-dependent upregulation. The expression of only 24 of the 192 discriminating genes was downregulated after the burn injury. No gene exhibited a sustained increase in expression over the entire 14 days following the burn injury. Gene ontologies revealed an integrated upregulation of inflammatory and protease genes at acute time intervals, and a diminution of cytoskeletal and muscle contractile genes at 3 or 14 days after the injury. Following a second-degree scald burn, global patterns of gene expression in the burn wound change dramatically over several weeks in a time-dependent manner, and these changes can be categorized based on the biological relevance of the genes.


This paper presents an analysis of environmental policy in imperfectly competitive markets. We investigate how environmental taxes should be optimally levied in a precommitment policy game and their e§ects on social welfare. The paper also examines the potential impacts of the regulatoris environmental conscience on policy setting. We start the analysis with a benchmark model where all players are environmentally dirty in the marketplace. We then extend the model to the case in which the market is composed of a mix of dirty and clean strategic players. We show that, in both cases, the regulator must necessarily trade o§ between regulation of environmental quality and the industry production ine¢ ciency problems. Furthermore, the results show how higher levels of concern for environmental issues outweigh the under taxation problem that arises in order to avoid further reductions in welfare. Finally, we show that the existence of clean players produces positive social externalities. Under an ex ante environmental policy game, higher social welfare outcomes are possible.


Children with immune thrombocytopenia (ITP) rarely suffer from life-threatening bleeds (eg, intracranial hemorrhage). In such settings, the combination of IV methylprednisolone (IVMP) with IV immune globulin (IVIG) is used to rapidly increase platelet counts (PCs). However, there are no controlled data to support using combination therapy over IVIG alone. We conducted a randomized, double-blind, placebo-controlled study to evaluate the rapidity of the PC increment and associated adverse events (AEs) between 2 regimens: A (IV placebo) and B (IVMP 30 mg/kg), both given over 1 hour, followed in both cases by IVIG (Gamunex 10%) 1 g/kg over 2-3 hours in children 1-17 years old with primary ITP and PCs <20 × 109/L in whom physicians had decided to treat with IVIG. Thirty-two children (ages: median, 8 years; range, 1.2-17.5 years) with a mean baseline PC of 9.2 × 109/L participated. Eighteen were randomized to regimen A and 14 to regimen B. By 8 hours after initiating therapy, 55% of all children had a PC ≥20 × 109/L (no group difference). By 24 hours, mean PCs were 76.9 × 109/L (B) vs 55 × 109/L (A) (P = .06; P = .035 when adjusted for intergroup differences in patient ages). No patient experienced severe bleeding/unexpected severe AEs. There were statistically fewer IVIG-related headaches in the group receiving combination therapy (P = .046). Our findings show a rapid response to IVIG with/without steroids and provide evidence to support the use of IVMP+IVIG in life-threatening situations. This trial was registered at www.clinicaltrials.gov as #NCT00376077.


A brief historical overview shows the main Christian claims aboutmorality and proper conduct, looking at questions about both prescriptions ('normative ethics') and foundations ('metaethics'). Jesus did not leave a fully articulated ethical system, and hence it fell to his followers to tease out such a system from hism sayings and actions. Particularly important for Catholic thinking has been the natural law theory of St. Thomas Aquinas. Particularly important for Protestant thinking have been the directives of the Gospel stories, although different branches of Protestantism emphasize different parts of Christ's teachings. Foundationally important for all Christians is God's will or desire, and it is necessary to show that this does not commit the believer to potentially capricious divine directives.


The authors investigated the autonomic nervous activity during sleep stages by means of power spectrum density of heart rate variability signal. Spectral estimation was performed by autoregressive modelling of RR series. The data obtained suggest an augmented sympathetic activity during REM sleep and a progressive decrease of it when passing from awake state to stages 1,2,3-4.


The present paper aims at concentrating on Judith Butler's theory of gender as performance and how Virginia Woolf challenges the assumptions of heterosexuality in Virginia Woolf's Orlando (1992). Woolf rebels against the traditional view of gender as two separate categories by presenting Orlando as an androgynous and bisexual character. Orlando's transformation from male to female and exhibition of the characteristics of both feminist and masculinity expose how gender norms are socially instituted. Woolf portrays Orlando's attraction to both men and women. He/she loves Sasha regardless of what changes her body undergoes, but he/she marries Shelmerdine because he/she is bisexual. Woolf also shows clothing as signifiers of the social construction of gender and how characters flout this convention by using cross dressing.


The first type of active RC networks referred to in the title use operational amplifiers, and the second use negative-impedance converters (NICs). Five networks using operational amplifiers, of which two are new, are found to be special cases of the same general network. They all realize a transfer function using single inversion. They are compared (1) Experimentally (all realizing a fourth order function). (2) Theoretically (second order function) with respect to (a) sensitivity to all passive components varying simultaneously (an appropriate sensitivity measure is introduced), (b) sensitivity to an arrangement they employ to produce -1 voltage gain, (c) the error introduced by the finite gain of the operational amplifier. One of the networks using two operational amplifiers, which is particularly suitable for the realization of any fourth order function, is found to be superior to all the others. An equivalent circuit of an uncompensated (non-ideal) NIC is introduced. Two well known synthesis procedures, those of Linvill and Yanagisawa, are extended, subject to a definite restriction, to use non-ideal NICs; the procedures are verified experimentally by realizing high-Q second order functions and the fourth order Bessel delay function. The sensitivity of four high-Q networks suitable for use with non-ideal NIC is studied and some useful properties of these networks discussed.


Immunocytochemical labeling using a specific antibody against vasopressin V1a receptor allowed the localization of this receptor within a subset of cells from male rat anterior pituitary. The presence of transcripts of the corresponding gene in the anterior pituitary was confirmed by RT-PCR. Multiple immunocytochemical labeling combined with confocal microscopy allowed the identification of the V1a-labeled cells as gonadotropes. At the subcellular level, the vasopressin V1a receptor was mainly associated with cytoplasmic vesicles dispersed throughout the cell, which were not the secretory granules storing LH or FSH. In addition to effects exerted by vasopressin via central targets involved in the reproductive pathways, the presence of vasopressin V1a receptors on gonadotropes supports the controversial hypothesis of a local direct action of the neuropeptide on this cell type.


The challenges facing the Department of Homeland Security (DHS) require not only multi-dimensional, but also multi-scale data analysis. In particular, the ability to seamlessly move from summary information, such as trends, into detailed analysis of individual entities, while critical for law enforcement, typically requires manually transferring information among multiple tools. Such time-consuming and error prone processes significantly hamper the analysts' ability to quickly explore data and identify threats. As part of a DHS Science and Technology effort, we have been developing and deploying for Immigration and Customs Enforcement the CubeLink system integrating information between relational data cubes and link analytical semantic graphs. In this paper we describe CubeLink in terms of the underlying components, their integration, and the formal mapping from multidimensional data analysis into link analysis. In so doing, we provide a formal basis for one particular form of automatic schema-ontology mapping from OLAP data cubes to semantic graphs databases, and point the way towards future "intelligent" OLAP data cubes equipped with meta-data about their dimensional typing.


This paper presents the findings of a study on adsorption of poly chlorinated biphenyl (PCBs) nano-alumina. PCBs are of significant concern due their high toxicity and long environmental half-lives. Experiments were conducted using batch adsorption procedures at different PCBs concentrations, from 10 to 60 mg/L. The amounts of nano-alumina used were 0.25%, 0.50%, 0.75%, 1%, 2% and 10%. The adsorption of PCBs solution onto the nano-alumina was characterized by an initial rapid adsorption which eventually became constant within 17 hours. Results of this study indicated that nano-alumina was a good adsorbent material for PCB in this study. While at 10% of nano-alumina 54% PCB were removed by nano-alumina. The effect of pH and temperature were also investigated. The Freundlich isotherm adsorption and Langmuir isotherm adsorption were used to analysis the result of the study.


A high plasma total homocysteine concentration is associated with increased risk of cardiovascular disease. Consumption of unfiltered or filtered coffee raises total homocysteine concentrations in healthy volunteers. Caffeine might be a factor that elevates the total homocysteine concentration, because it may inhibit the conversion of homocysteine to cysteine by acting as a vitamin B6 antagonist. Hence, the present study was designed to investigate the effect of filter coffee and instant coffee consumption on the fasting plasma homocysteine levels of healthy female volunteers, who are non-coffee drinkers.Nine healthy female volunteers between 18-22yrs, who are non-coffee drinkers were selected. Filter coffee and instant coffee powder, which are 100% coffee as per label were selected, prepared and standardized. Supplementation period lasted for five weeks. The volunteers were provided with 400ml(400mg caffeine) of filter coffee per day per volunteer for the first period of two weeks and to the same group, after a week of washout period, 500ml(402mg caffeine) of instant coffee per day per volunteer for the next two weeks. The plasma fasting homocysteine concentration was estimated on the blood collected before and after the supplementation of coffee groups.There was a significant increase in the fasting plasma homocysteine levels of both the groups after two weeks of coffee consumption. This increase was statistically significant at 5%level. But when the increase in the fasting plasma homocysteine levels between two groups was compared, there was no significant difference at 5%level.It could be concluded from the study that consumption of filter coffee and instant coffee for a period of two weeks had an effect on the fasting plasma homocysteine levels of healthy female volunteers. No difference between the two groups could be due to equal amount of caffeine intake. Elevated plasma homocysteine levels are reported to be a positive risk factor in CHD.


In nine critically ill newborns, five of them with intractable diarrhea and four surgical patients, we administered a 5% crystalline aminoacids solution (AA) and glucose in sufficient amount to provide 120 cal times kg. in 24 hours. Six of them recovered after receiving parenteral alimentation for 3 to 15 days, gained weight during or after treatment and were discharged from the hospital in good conditions. Three died, one of them presented septicemia and two pneumonia and pulmonary infarcts. The solution used generated few metabolic alterations, the acid-base status remained within normal range and there were not important changes in the sodium and potassium serum concentrations. On the contrary, children with hyponatremia and hypokalemia at the beginning of the treatment, normalized these constants within the first hours, as diarrhea ceased. The most frequent complications were infiltrations and reaction of the surrounding tissue of the catheterized vein and local skin infection. Only one patient died of septicemia, possibly caused by this proceeding. In summary, parenteral alimentation though not free from risk, seems to be a useful proceeding when oral feeding is impossible or inadvisable. The utmost danger is septicemia. Metabolic changes are minimal and they do not mean a risk for child's life; nevertheless, there is a need for long term studies to bring up definite conclusions. The solutions in actual use are probably not the most physiological for the newborn. It is necessary to adequate them according to the new advances made on child nourishment during his first days of life.


This paper presents a model predictive control (MPC) strategy for efficient energy production in BioGrate boiler. In addition to compensating for the main disturbances caused by variations in fuel quality such as fuel moisture content, and variations in fuel feed, this strategy models water evaporation, and models and controls the fuel bed height of the grate. Usually, combustion power in a furnace have been estimated by utilizing oxygen consumption. There is however a need for more accurate prediction and control of combustion power, which is greatly affected by the fuel bed height and fuel moisture content. It is shown that water evaporation and thermal decomposition of dry fuel can be estimated by utilizing fuel moisture soft-sensor and oxygen consumption calculations respectively. As a result, the primary air can be adjusted to produce the necessary combustion power, and the power output of the boiler can be accurately predicted. This enables efficient stabilization of plant operations. To verify the model, experiments were performed at a BioPower 5 CHP plant, which utilizes BioGrate combustion technology to enable the use of wet biomass fuels with a moisture content as high as 65%. Then the MPC strategy was compared with the currently used control strategy. Finally, the results are presented, analyzed, and discussed.


During digital image deblurring, a priori knowledge of blurred image is incorporated into regularization to adoptively adjust the global regularization parameter for better preserving the edge in the image and suppressing ringing effects. So the weighting matrix in the spatial domain is constructed by calculating the gradient amplitude of each pixel based on Abdou operator with the consideration of human visual system. It equals that all pixels in the image are processed with different regularization parameter when the weighting matrix is applied to the solution. The final step is to solve the problem by the method of Conjugate Gradient. Compared with the method proposed by Lagendijk which is based on local variance, algorithm based on Abdou operator is feasible and quite simple with good deblurring results.


Apart from the energy gap law, control parameters over nonradiative transitions are so far only scarcely regarded. In this work, the impact of both covalence of the lanthanoid–ligand bond and varying bond distance on the magnitude of the intrinsic nonradiative decay rate between the excited 6P5/2 and 6P7/2 spin–orbit levels of Gd3+ is investigated in the chemically related compounds Y2[B2(SO4)6] and LaBO3. Analysis of the temperature‐dependent luminescence spectra reveals that the intrinsic nonradiative transition rates between the excited 6PJ (  J = 5/2, 7/2) levels are of the order of only 10 ms−1 (Y2[B2(SO4)6]:Gd3+: 8.9 ms−1; LaBO3:Gd3+: 10.5 ms−1) and differ due to the different degree of covalence of the GdO bonds in the two compounds. Comparison to the established luminescent Boltzmann thermometer Er3+ reveals, however, that the nonradiative transition rates between the excited levels of Gd3+ are over three orders of magnitude slower despite a similar energy gap and the presence of a single resonant phonon mode. This hints to a fundamental magnetic dipolar character of the nonradiative coupling in Gd3+. These findings can pave a way to control nonradiative transition rates and how to tune the dynamic range of luminescent Boltzmann thermometers.


The result of treatment of children with ITP, who received either 0.5, 1 or 2 mg/kg per day of prednisolone showed that 1 mg/kg per day gave the best response, the least failure rate and the duration of treatment was not different compared to 2 mg/kg per day. It was concluded that the proper dosage of the prednisolone given to these children should be 1 mg/kg per day. However the number of the patients in the study were rather small further clinical studies and treatment with 1 mg/kg and 2 mg/kg per day of prednisolone in childhood ITP are warranted.


BACKGROUND
Squamous cell carcinoma (SCC) of the head and neck region is rare in young patients and even less frequent in children 15 years or younger children. The patients reported in the literature are isolated cases and their management is always difficult because there is no large experience or a convincing theory to support treatment decisions for every child.

PROCEDURES AND RESULTS
Four patients aged 15 years or younger were treated for SCC of head and neck between 1977 and 1995 at the Head and Neck Service of Heliópolis Hospital, São Paulo, Brazil, and with this paper we are reporting our experience with their treatment, including a genetic investigation in two cases (immunohistochemical analysis using monoclonal antibodies against p53 and c-erbB-2 oncogenes). These patients had no history of tobacco or ethanol abuse and no history of cancer in their families. Many authors attribute an unusual aggressiveness to SCC in childhood, with propensity to locoregional recurrence and high death rates and therefore, propose aggressive multidisciplinary therapy. Our cases, with the exception of one, had an early diagnosis and were treated using the same method we use for adults; the results were very good.

CONCLUSIONS
We recommend for these cases the same protocol as for older patients. In these cases, however, the primary lesion is resected with a safety margin which is usually 2 to 3 mm larger than usual safety margins and selective neck dissection is routinely indicated. This management is adopted in an attempt to avoid postoperative irradiation which may prove to be dangerous in the future for young patients. On the other hand, we recognize that due to a small number de patients, definitive treatment recommendations cannot be made at this time.


Prior research on suicidal ideation and its correlates among South Asian American individuals has been limited. Given that South Asian American individuals are a burgeoning ethnic subgroup in the United States population, research regarding these factors is necessary to inform culturally competent suicide screening, prevention, and intervention among this increasingly prominent group. We examined depressive symptoms, hopelessness, and suicidal ideation among a sample of 204 undergraduate South Asian American (96 Bangladeshi American, 67 Asian Indian, and 41 Pakistani American) emerging adult students (66% female), ages 18 to 24 (M = 18.52, SD = 0.93). Participants completed measures of hopelessness, depressive symptoms, and suicidal ideation. Bangladeshi American ethnicity was associated with significantly lower levels of suicidal ideation than Asian Indian ethnicity. There was a non-significant trend for Pakistani American ethnicity to be associated with lower levels of suicidal ideation than Asian Indian ethnicity. Additionally, Bangladeshi American ethnicity and Pakistani American ethnicity each interacted with hopelessness, such that hopelessness was associated with lower levels of suicidal ideation among these groups than among their Asian Indian peers. Being of Asian Indian ethnicity may deleteriously influence vulnerability to suicidal ideation, while being of other South Asian American ethnicities may buffer against suicidal ideation, both independently and in interaction with hopelessness. Such contingencies should be considered during suicide screening, prevention, and intervention.


Identification of writers of handwritten historical documents is an important and challenging task. In this paper we present several feature extraction and classification approaches for the identification of writers in historical Arabic manuscripts. The approaches are able to successfully identify writers of multipage documents. The feature extraction methods rely on different principles, such as contour-, textural- and key point-based and the classification schemes are based on averaging and voting. For all experiments a dedicated data set based on a publicly available database is used. The experiments show promising results and the best performance was achieved using a novel feature extraction based on key point descriptors.


Background Electronic health record (EHR)–based disease registries have aided health care professionals and researchers in increasing their understanding of chronic illnesses, including identifying patients with (or at risk of developing) conditions and tracking treatment progress and recovery. Despite excessive alcohol use being a major contributor to the global burden of disease and disability, no registries of alcohol problems exist. EHR-based data in Kaiser Permanente Northern California (KPNC), an integrated health system that conducts systematic alcohol screening, which provides specialty addiction medicine treatment internally and has a membership of over 4 million members that are highly representative of the US population with access to care, provide a unique opportunity to develop such a registry. Objective Our objectives were to describe the development and implementation of a protocol for assembling the KPNC Adult Alcohol Registry, which may be useful to other researchers and health systems, and to characterize the registry cohort descriptively, including underlying health conditions. Methods Inclusion criteria were adult members with unhealthy alcohol use (using National Institute on Alcohol Abuse and Alcoholism guidelines), an alcohol use disorder (AUD) diagnosis, or an alcohol-related health problem between June 1, 2013, and May 31, 2019. We extracted patients' longitudinal, multidimensional EHR data from 1 year before their date of eligibility through May 31, 2019, and conducted descriptive analyses. Results We identified 723,604 adult patients who met the registry inclusion criteria at any time during the study period: 631,780 with unhealthy alcohol use, 143,690 with an AUD diagnosis, and 18,985 with an alcohol-related health problem. We identified 65,064 patients who met two or more criteria. Of the 4,973,195 adult patients with at least one encounter with the health system during the study period, the prevalence of unhealthy alcohol use was 13% (631,780/4,973,195), the prevalence of AUD diagnoses was 3% (143,690/4,973,195), and the prevalence of alcohol-related health problems was 0.4% (18,985/4,973,195). The registry cohort was 60% male (n=432,847) and 41% non-White (n=295,998) and had a median age of 41 years (IQR=27). About 48% (n=346,408) had a chronic medical condition, 18% (n=130,031) had a mental health condition, and 4% (n=30,429) had a drug use disorder diagnosis. Conclusions We demonstrated that EHR-based data collected during clinical care within an integrated health system could be leveraged to develop a registry of patients with alcohol problems that is flexible and can be easily updated. The registry's comprehensive patient-level data over multiyear periods provides a strong foundation for robust research addressing critical public health questions related to the full course and spectrum of alcohol problems, including recovery, which would complement other methods used in alcohol research (eg, population-based surveys, clinical trials).


The first case presenting infestation caused by Dermatobia hominis (human botfly) was reported in Ayacucho, Peru in August 2011. A six-year old girl having a tumor and induration in the external region of the left arm with 8 months of natural history and receiving previous treatment without knowing the cause of the ailment was reported. At her arrival the signs worsened and the clinical along with epidemiological diagnoses were conducted complemented by the entomological analysis. Surgical treatment was performed, removing two larvae that presented entomological characteristics of the parasite. Surgical wound was sutured and followed up without complications. A brief medical literature review about myiasis was also carried out.


Background Among women with an elevated risk of hereditary breast and ovarian cancer who previously tested negative for pathogenic mutations in BRCA1 and BRCA2, a subset remain at increased risk of having hereditary breast, ovarian or other cancers, and should be offered multi-gene panel testing. We tested three groups of women who were enrolled in the UCSF Cancer Genetics and Prevention Program: (i) 97 women with a personal history of bilateral breast cancer, (ii) 104 women with a personal history of breast cancer and a first-degree or second-degree relative with ovarian cancer, and (iii) 99 women with a personal history of ovarian, fallopian tube, or primary peritoneal cancer. All women previously tested negative for pathogenic BRCA1 and BRCA2 mutations by either limited or comprehensive testing. Methods We performed comprehensive next-generation sequencing using a panel of 19 genes developed by Color Genomics (a CLIA-certified laboratory) covering ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53. Results Across the groups tested, 9% had pathogenic mutations in one or more of the genes analyzed (8% in genes other than BRCA1 and BRCA2). Among these women, Ashkenazi Jewish and Hispanic women had elevated mutation rates compared to those of other ethnicities. In addition, we identified two women with pathogenic mutations in two cancer susceptibility genes, which has significant implications for family testing. These results demonstrate the importance of genetic testing of genes other than BRCA1 and BRCA2. Conclusions Among women with an elevated risk of hereditary breast and ovarian cancer who have previously tested negative for BRCA1 and BRCA2 mutations, we propose that women with characteristics of any of the three groups above be considered for subsequent multi-gene panel testing. Additionally, ethnicity and the possibility of multiple mutations may be indications for additional testing in these women and in family members of carriers. Citation Format: Crawford BB, Adams SB, Sittler T, Van den Akker J, Chan SB, Leitner O, Ryan LN, Gil E, Van 9t Veer LJ. Multi-gene panel testing for hereditary cancer predisposition in unsolved high risk breast and ovarian cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-08-02.


There are some problems when the discriminative features are used in the traditional kinship verification methods, such as focusing on the local region information, containing a lot of noisy in non-face regions and redundant information in overlapping regions, manual parameters setting and high dimension. To solve the above problems, a novel kinship verification method based on deep transfer learning and feature nonlinear mapping is proposed in this paper. Firstly, a new deep learning model trained on the face recognition dataset is transferred to the kinship datasets to extract high-level feature. Secondly, siamese multi-layer perceptrons and triangular similarity metric learning are combined to reduce the dimensionality of feature vector by nonlinear mapping. Meanwhile it would guarantee a smaller distance between kin pairs while a larger distance between non-kin pairs. Lastly, the cosine similarity of feature vector pairs is computed, and traditional classifier, such as SVM, is used. Experiments on the TSKinFace, KinFace W-I and KinFace W-II datasets indicate the proposed method could achieve better performance than the traditional methods.


Broca's area is preferentially activated by reversible sentences with complex syntax, but various linguistic factors may be responsible for this finding, including syntactic movement, working-memory demands, and post hoc reanalysis. To distinguish between these, we tested the interaction of syntactic complexity and semantic reversibility in a functional magnetic resonance imaging study of sentence–picture matching. During auditory comprehension, semantic reversibility induced selective activation throughout the left perisylvian language network. In contrast, syntactic complexity (object-embedded vs. subject-embedded relative clauses) within reversible sentences engaged only the left inferior frontal gyrus (LIFG) and left precentral gyrus. Within irreversible sentences, only the LIFG was sensitive to syntactic complexity, confirming a unique role for this region in syntactic processing. Nonetheless, larger effects of reversibility itself occurred in the same regions, suggesting that full syntactic parsing may be a nonautomatic process applied as needed. Complex reversible sentences also induced enhanced signals in LIFG and left precentral regions on subsequent picture selection, but with additional recruitment of the right hemisphere homolog area (right inferior frontal gyrus) as well, suggesting that post hoc reanalysis of sentence structure, compared with initial comprehension, engages an overlapping but larger network of brain regions. These dissociable effects may offer a basis for studying the reorganization of receptive language function after brain damage.