Retained foreign bodies are a common and frequently complicated presentation in both the emergency department as well as outpatient medical offices. While retained foreign bodies are usually superficial, they can be missed even when a well-trained clinician performs a thorough history and physical. Therefore, retained foreign bodies are one of the leading causes of malpractice lawsuits in the emergency department. If not found, they can lead to inflammation, delayed healing, and damage to surrounding tissues. Organic objects, such as thorns, splinters, or spines, can cause severe inflammation, hypersensitivity reactions, and even infections. These infections are very resistant to antibiotic treatment and require surgical removal of the foreign body for definitive treatment.[1][2][3] Most foreign bodies are locatable during an extensive wound-probing, physical exam. Imaging studies are necessary in cases of suspected but not identified, foreign bodies. Imaging is especially necessary following the removal of multiple foreign body pieces or when wound exploration is not possible. Imaging modalities available for detecting foreign bodies include plain film radiographs, computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound. Each modality has its strengths and weaknesses that vary depending on the composition material of the foreign body, as well as the object's location.[4][5]


The coronavirus disease 2019 (COVID-19) is a deadly viral infection causing death due to impaired immunity. Therefore, an investigation of factors affecting the immune system should be considered. It is well documented that regular sessions of moderate-intensity exercise training with up to 1-hour duration boost the immune functions through anti-inflammatory and antioxidant effects. Besides, a diet containing functional and nutritious foods is also needed to aid the immune system. Herein, we have summarized available data on how exercise and nutritional factors help promote immunity against various infections. More importantly, this review provides practical and valuable guidance for sedentary adult people and nonprofessional athletes on how to do aerobic and resistance training and stretching exercises at home with no special types of equipment required during the outbreaks of delta variant-COVID-19. Some significant exercise-related nutritional considerations regarding carbohydrates, fibers, vitamins, zinc, and omega-3 fatty acids were also supplied that help to create better adaptations and improve immune responses.


Objective: To investigate the role of transcription factor specificity protein 1 (SP1) in proliferation, migration and invasion in head and neck squamous cell carcinoma (HNSCC), and the role of SP1 in transcription regulation of microRNA (miRNA)-92b. Methods: Predicted the possible target miRNA of transcription factor SP1 by bioinformatic analysis. Furthermore, confirmed the binding sites of transcription factor SP1 and miRNA-92b promoter regions by chromatin immunoprecipitation. After transfecting SP1 siRNA and negative control siRNA, also performed quantitative real-time PCR (qPCR), cell proliferation assay and Transwell assay. Results: The bioinformatic analysis shows SP1 is a possible transcription factor of miRNA-92b. Chromatin immunoprecipitation suggests there are three binding sites in miRNA-92b promoter regions that can be combined with SP1. qPCR suggests in PCI-4A and PCI-37A cells the expression of SP1 in experimental group (respectively was 0.064±0.020 and 0.639±0.008) were significantly lower than negative control group (both were 1)(P<0.05). In PCI-4A and PCI-37A cells the expression of miRNA-92b in experimental group (respectively was 0.215±0.033 and 0.497±0.104) were significantly lower than negative control group (both were 1)(P<0.05). In experimental group proliferation of SP1 in PCI-4A and PCI-37A cells value A were significantly lower than negative control group (P<0.05). In experimental group migration of SP1 in PCI-4A and PCI-37A cells (respectively was 37.0±4.6 and 40.7±2.1) were significantly lower than negative control group (101.0±5.3 and 82.7±5.7) (P<0.05). In experimental group invasion of SP1 in PCI-4A and PCI-37A cells (respectively was 31.3±10.8 and 37.0±4.6) were significantly lower than negative control group (92.3±3.1 and 70.3±3.1)(P<0.05). Conclusions: SP1 promotes proliferation, migration and invasion abilities of HNSCC cells. SP1 is a transcription factor of miRNA-92b and can directly be involved in transcription regulation of miRNA-92b.


To identify effects of glass bead (GB) content on the dynamic mechanical properties of filled low-density-polyethylene (LDPE) composites, the storage modulus, loss modulus, glass transition temperature, and mechanical damping of these composites were measured using a Du Pont dynamical mechanical analysis instrument in temperature range from −150 to 100°C. It was found that the storage modulus increased nonlinearly with an increase of the GB volume fraction. On the basis of Eshelby's method and Mori's work, an equation describing the relationship between the relative storage modulus (E′R) and filler volume fraction for polymeric composites was proposed, and the E′R of LDPE/GB composites were estimated by means of this equation at temperatures of −25, 0, and 25°C, and the calculations were compared with the experimental data, good agreement was showed between the predictions and the measured data. Furthermore, this equation was verified by the experimental from Al(OH)3 filled EPDM composites at glassy state reported in a reference. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009


This article analyzes the myths of the Khori`s migration and archeological sites which are related to the origin of the ancient Korean people. There are places where the myths on the Khori`s migration are passed down: the eastern area of Baikal lake of Federal Relations in Russia, surrounding area of Buir Lake in Khalkha-gol sum of Dornod aimag, Dariganga sum and Naran sum of Sukhebaatar aimag in Mongolia. Among them, the myths on the migration of the Khori and archeological sites of agriculture are remained on the area around Buir Lake, especially where is lain from Mongolia to city of Kolen-Buir in Inner Mongolia of the People`s Republic of China. The myths on the Khori`s migration are structurally similar with them on migration of Khorilartai-Mergen as recorded on the Secret History of the Mongols. The author contemplated the relevance of the ancient Korean people with Barkhujin tokum and Burkhan-Khaldun as occupying prominent place in the myths of origin of the Mongols and Khori Buriad. As the result, it is found that Burkhan-Khaldun mountain in Barkhujin and the mountain with the same name in Khenti are the similar mountains in their structures of mythical image or of natural geographical element. Periodically, Burkhan-Khaldun mountain in Barkhujin is found as older than the mountain in Khenti. It is particularly noted that the former in Barkhujin is geographically matched with Black mountain(黑山) of Ukhan or Kitay, not with Burkhan-Khaldun of Jusen recorded on Sanhaijing (山海經). Finally, it is thought that 'Bata(Bada)' shown in Erdeni-yin Tobchi could be the name or a byname of the Khori.


Abstract The effectiveness of a tongue‐retaining device (TRD) was examined at the baseline without any TRD [TRD(–)] and then with a TRD [TRD(+)] in eight patients with obstructive sleep apnea (OSA). In terms of the 3+ % oxygen desaturation index (ODI3), lowest percutaneous oxygen saturation (SpO2), and time spent SpO2 < 90%, there were significant differences (P < 0.01–0.05) between the findings for TRD(–) and TRD(+). The ODI3 dropped below the baseline by more than 50% in five patients (63%) and dropped to fewer than 10 events/ h in six patients (75%). The results indicate that oral appliances help patients with mild to moderate OSA; however, patients with more severe OSA may also be treated effectively with a TRD.


Localised specific power loss was determined for surface treated Metglas® 2605SC amorphous ribbons. The energy saving was maximum if the inhomogenity was reduced by polishing both surfaces. However, a further saving was noticed on the scratched samples. The optimum scratching interval for maximum energy saving was found to be 3 mm. The anomaly factor was also found to alter due to the domain wall spacing and loss measurement. The experimental findings showed that existing theory can reliably explain the power loss in amorphous ribbon.


This is a review of Hossenfelder's book, 'Lost in Math: How Beauty Leads Physics Astray'. The book gives a breezy exposition of the present situation in fundamental physics, and raises important questions: both about the content of the physics, and the way physics research is organized. I first state my main disagreements. Then, I mostly praise the book: I concentrate on Hossenfelder's discussion of supersymmetry, naturalness and the multiverse.


Objective: To evaluate the effect of induction chemotherapy on swallowing and swallowing-related quality of life of patients with oropharyngeal, laryngeal and hypopharyngeal cancer. Study design: Prospective study of 33 patients with locally advanced tumors who were eligible for treatment with neoadjuvant chemotherapy followed by radiotherapy and concurrent chemotherapy. A multidimensional assessment of swallowing was performed using the following tools: (1) Clinical analysis, numerical scale for general pain and painful swallowing, American Speech and Hearing Association (ASHA) Functional Communication Measures (FCM) swallowing assessment scales, (2) assessment of Swallowing-Related Quality of Life (The MD Anderson Dysphagia Inventory - MDADI), and (3) swallowing videofluoroscopy. Results: There was a reduction in general pain scale (p=0.021), and quality of life (emotional, functional and physical) improved from average limitation (score of 61-80) to minimal limitation (81-100) after induction chemotherapy. According to the swallowing videofluoroscopy results, 26 (78.7%) of the patients had some degree of dysphagia pre-treatment, which decreased to 21 (63.6%) after induction. Conclusion: Our results suggest that induction chemotherapy improves numerous aspects of swallowing and has a positive impact on the quality of life of pre-chemoradiotherapy patients.


ABSTRACT Clinicians at the bedside and researchers at the bench make the discoveries that shape the future of medicine. With this issue (p 1562), JAMA inaugurates a column of clinically oriented, basic science research in review. The column will permit physicians to glimpse the future of medicine and to gain a better understanding of the scientific basis of their practice. This new department, entitled BENCH AND BEDSIDE, reflects the relevance of basic science research to medical practice. It acknowledges the vital contributions that clinical and basic science research make to medicine.The following editorial principles will apply to all articles published in BENCH AND BEDSIDE:Columns will be focused reviews of important basic science work. The articles will emphasize highlights and major trends in medical research. They will not assume exhaustive archival functions that would make them unwieldy or impenetrable for the physician-reader. They will not attempt to cover vast expanses


In this review male-pattern baldness [androgenetic alopoecia (AA)] is discussed. AA is characterized as a physiological process. Some of the reactions that take place in its pathogenesis and many of the substrates involved in androgen metabolism are now known, but the question as to the androgen stimulus leads to retrograde transformation of the hair follicles only in skin of the parieto-occipital scalp can still not be answered. Specific antiandrogens for the treatment of AA are not available for either topical application or systemic administration. Minoxidil seems to have a positive effect in the treatment of AA but in most cases the cosmetic result is not satisfactory.


In order to clarify which of the two, insulin resistance or hyperinsulinemia, are more contributable to non obese and non diabetic hypertension, insulin sensitivity test was performed. By multiple regression analysis, mean, systolic, and diastolic blood pressure were inversely correlated with glucose clearance. During insulin sensitivity test, plasma catecholamines levels and FENa were not changed by insulin infusion. In the present study, it is demonstrated that insulin has no hypertensive effect under the mild hyperinsulinemia (45-55 microU/ml). We conclude that insulin resistance rather than hyperinsulinemia may be more closely associated with non obese and non diabetic hypertension.


MANY YEARS AGO, an executive called Addis was wrongfully dismissed by the Gramophone Company. He sued, claiming damages. He maintained that he was entitled not only to the remuneration which he would have received, had he been given his proper notice, but also money to compensate him because as a result of the wrongful dismissal he had lost status and was in fact permanently out of work.


The paper briefly analyses the problems currently faced by the plantation companies and explains why the price of crude palm oil (CPO) has fallen month by month through 2000, with sharper falls since January 2001 and why the price has not recovered. Some fundamental strategies to help the palm oil industry sustain through these difficult times and to strengthen and transform it overtime are suggested, covering stock reduction and management, marketing and sales, shipping, port improvements, improving storage capacities in mills and refineries, replanting and revamping the organization structure of estate


BACKGROUND
Reducing the leg wound morbidity is crucial for the patients undergoing coronary artery bypass grafting (CABG) with great saphenous vein (SV) grafts harvested by no-touch (NT) technique. This study was to summarize the experience of skin bridging technique for reducing wound morbidity and the influence of it on one-year bypass graft patency.

METHODS
According to skin bridging or not, harvesting times, graft length, number of bleeding branches, postoperative subjective perception assessment scale (ASEPSIS) scores and one-year patency rate were analyzed.

RESULTS
From June 2018 to February 2019, 60 patients underwent CABG with SV grafts either with open-incision NT or skin bridging NT (30 in each group). There were no significant differences in age (71.4 ± 5.1 years vs. 68.9 ± 5.5 years) or graft length (23.3 ± 1.1 cm vs. 23.9 ± 1.3 cm) between the two groups. The bridging/NT group had a significantly longer harvest time (38.5 ± 4.9 min vs. 18.5 ± 2.6 min; P < 0.001) and a significantly greater number of bleeding branches (1.9 ± 1.2 vs. 0.8 ± 0.8; P < 0.001) than the open NT group. The open NT group had a significantly higher ASEPSIS score (23.8 ± 2.0 vs. 15.7 ± 2.6; P < 0.001). There was no significant difference in patency rate at one-year follow-up.

CONCLUSION
Obtaining the SV by the combined NT/discontinuous skin bridging technique is a satisfactory method for patients who underwent CABG. This method has important clinical significance in reducing wound morbidity in the harvest of NT grafts.


Endometrial cancer (EC) is a hormone-dependent cancer that currently represents the most frequent malignancy of the female reproductive tract. The involvement of steroid hormones in EC etiology and progression has been reported. More recently, gonadotropins, and, in particular LH/hCG, are emerging as novel regulators of tumor progression. In the present review, we discuss the role of the LH/hCG axis (i.e. LH/hCG and its receptors, LH/hCG-R) in both gonadal and nongonadal tissues, in physiological and neoplastic conditions. In cancer cells, LH/hCG mainly controls cell proliferation and apoptosis. In particular, in EC LH/hCG improves cell invasiveness, through a mechanism which involves the LH/hCG-R, which in turn activate protein kinase A and modulate integrin adhesion receptors. Indeed, the LH/hCG-R mRNA is expressed in primary ECs and this expression correlates with LH/hCG-induced cell invasiveness in vitro. These results lead to hypothesize that recurrent and metastatic ECs, which express LH/hCG-R, could benefit from therapies aimed at decreasing LH levels, through Gn-RH analogues. Hence, the LH/hCG axis could represent a prognostic factor and a new therapeutic target in EC.


Nickel/detonated nanodiamond composites were prepared using the powder metallurgy technique. Detonated nanosized diamond particles were reinforced in the nickel matrix. The investigated powder was used to prepare homogenous diamond/nickel composite mixtures with different detonated nanodiamond content of weight percentage (0.2, 0.4, 0.6, and 0.8 wt.%). The produced mixtures were cold pressed into a cylindrical die shape under compaction pressure of 400 MPa followed by sintered at 1,000°C for 120 min under a controlled atmosphere of 1:3 hydrogen/nitrogen gas mixture. Phase identification and microstructure of the produced sintered samples were investigated using X-ray diffraction and scanning electron microscope, respectively. The results of the microstructure show a good distribution of the detonated nanodiamond in the nickel matrix, especially in the 0.8 wt% diamond/nickel sintered sample. The densities of the obtained sintered samples were measured by applying the Archimedes principal. As the detonated nanodiamond content was increased in the nickel matrix, the density of the sintered samples was decreased. The thermal expansion, electrical conductivity, and hardness of the produced diamond/nickel composites were measured. The coefficient of thermal expansion and electrical conductivity were decreased, but the hardness was increased by increasing the detonated nanodiamond weight percentage.


The scattering of a plane acoustic wave by an infinite penetrable or impenetrable circular cylinder, parallel with another one, also penetrable or impenetrable, of acoustically small radius, is considered. The method of separation of variables, in conjunction with translational addition theorems for cylindrical wave functions, is used. Analytical expressions are obtained for the scattered pressure field and the various scattering cross sections, for normal incidence. Numerical results are given for penetrable and impenetrable cylinders.


Background: Auto-approval (also known as autoverification) is the task of automatically evaluating the consistency of a test result throughout the laboratory information system rather than its manual evaluation by the biochemists. Most of the existing auto-approval systems rely on a rule-based solution obtained from expert knowledge. However, it is a challenging issue to produce a complete and general rule-base for every single test type. To that end, the studies have relied only on a small subset of laboratory tests. Methods: The rule-based auto-approval process was re-investigated in this study, and the rules predetermined by human experts were utilized as a pre-filtering step for grouping the laboratory test result via some common criteria. Subsequently, a machine learning-based approval method, smart-approval, was proposed to approve the tests more precisely. At this point, the expert knowledge in the rule-based pre-filtering was extended by the tendency to imitate the experts' behavior in the smart-approval step. Two novel datasets (entitled with plot and real-time datasets) containing human experts' responses to previously studied tests have been used to train the machine learning models. Results: Experiments have been handled on several machine learning models on plot dataset to obtain the trained models based on cross-validation. Here, the random forest classifier provided the best approval performance while also outperforming the approval success of existing studies in the literature. To observe the real-time performance of these trained models, they were also evaluated on real-time unseen data for 4 months. Here, random forest reaffirmed that it was the best approval model. Conclusions: The proposed auto-approval system relying on random forest can provide convincing classification performance on both of the obtained datasets. With the correct approval rate of 98.51%, it surpasses many powerful approval methods in the literature.


A systematic study of spherical indentations on various glasses has shown that for small indenters (<or approximately=1 mm) plastic flow as well as Hertzian cone cracking occurs. What is of more interest however, is that on unloading, a series of radial cracks forms about the area of contact. With continued unloading, these cracks grow and just before complete unloading, an entirely independent system of lateral cracks, which are responsible for material removal processes, occurs. The indentation process was followed using an inverted microscope and indentation stress-strain curves were produced. These curves were compared with recent indentation correlation expressions and found to fit reasonably well. The radial cracking about the contact site was analysed in terms of a stress field which was a composite of the normal Hertzian loading situation coupled with the expansion of a cavity adjacent to a free surface. This model agrees reasonably well with experiment and provides a qualitative treatment of lateral cracking phenomena.


Coronavirus disease 2019 (COVID-19) has become a global pandemic to date. Some studies reported gastrointestinal tract (GIT) bleeding occurs in several patients hospitalized with COVID-19. Medications known to be associated with an increased risk of GIT bleeding were not associated with GIT bleeding in COVID-19 patients. Objectives: To examined the risk of gastrointestinal tract (GIT) bleeding in COVID-19 patients based on antiviral drugs at Dr. M. Djamil General Hospital Padang. Methods: A nested cohort study was conducted in Dr. M. Djamil General Hospital Padang from May until October 2021. All COVID-19 patients who received antiviral drugs with GIT bleeding with onset days 0 - 7 were included. COVID-19 was confirmed by RT-PCR swab. Data entry and analysis were conducted by computerized. Results: 30 patients were involved in this study. 43,3% COVID-19 Moderate stage and 56,7% Severe stage. 63,3% were treated with remdesivir and 36,7% were treated with favipiravir. Onset on GIT tract bleeding at day 4 (23,3%), day 5 (26.7%), day 6 (30%), and day 7 (20%). The Chi-square test to determine the factors associated with GIT bleeding in COVID-19 patients including COVID-19 severity, type of antiviral drugs, anticoagulant, and corticosteroid revealed that none of all potential factors above related to GI bleeding. Conclusion: The type of antiviral drugs was not related to GIT bleeding in COVID-19 patients.Keywords: antiviral drugs,  COVID-19, gastrointestinal tract bleeding


Hepatitis delta virus (HDV) is a naturally occurring satellite of hepatitis B virus (HBV). There are few studies of the effects of the combination of HBV and HDV proteins (HDV antigens [HDAgs]) on intracellular signaling pathways. To understand the influence of HBV and HDV coinfection on hepatocytes, we investigated the effect of HBV proteins and HDAgs on the serum response element (SRE)-dependent pathway. Reporter assays revealed that only HBV X protein (HBx), alone or with the large isoform of HDAg (LHDAg), synergistically activated the SRE-dependent pathway. The effect of HBx and LHDAg on Elk1 or serum response factor (SRF) was examined, because both proteins bind to the SRE. HBx activated the transcriptional ability of Elk1, whereas LHDAg activated the transcriptional ability of SRF. Thus, HBx and LHDAg synergistically activated the SRE-dependent pathway. These results may help us understand clinical phenomena in patients coinfected with HBV and HDV.


We present a new LIDAR modelling for automotive applications. Many simulators already exist for this problem, but most of these simulators represent only a punctual modelling of the LASER impacts or cannot simulate the real-time LIDAR operation. The model considers the LASER beam propagation as well as the attenuation of LASER energy not only in clear weather, but also under harsh weather conditions such as fog and rain. The main objective from a LIDAR sensor point of view is to detect all the targets within the observation zone and simultaneously estimate the distance and relative reflectivity of the target in real time. The use of this sensor simulation can easily and effectively replace real LIDAR test campaigns to measure their performance. By comparing real sensors with our model, we demonstrate that this virtual sensor accurately reproduces real LIDAR sensors' behaviour.


A listing of some eating options within comfortable walking distance of the MSU Main Library. Hours are for summer 2016


Magnetotactic bacteria (MTB) are a group of Gram-negative bacteria characterized by synthesizing magnetosomes and swimming along geomagnetic field lines. Phylogenetically, they belong to different taxonomic lineages including Proteobacteria, Nitrospirae, Omnitrophica, Latescibacteria and Planctomycetes phyla on the phylogenetic tree. To date, six Nitrospirae MTB phylotypes have been identified from freshwater or low-salinity environments and described in the literature. Here, we report the identification of two Nitrospirae MTB phylotypes collected, for the first time, from the marine environment. Both have a spherical morphology with a cell size of ~ 5 μM and similar motility but are different colours (black-brown and ivory-white) under the optic microscope. They synthesized bullet-shaped iron-oxide magnetosomes that were arranged in multiple bundles of chains. Moreover, the cytoplasm of the black-brown Nitrospirae MTB contained sulphur inclusions that conferred on cells a rough, granular appearance. Phylogenetic analysis based on their 16S rRNA gene sequences revealed that they are two novel species and cluster with the previously reported MTB affiliated with the phylum Nitrospirae, thus extending the distribution of Nitrospirae MTB from freshwater to the marine environment.


Cyclothiazide (CTZ) is a potent blocker of AMPA receptor desensitization. We have recently demonstrated that CTZ also inhibits GABAA receptors. Here we report that CTZ induces robust epileptiform activity in hippocampal neurons both in vitro and in vivo. We first found that chronic treatment of hippocampal cultures with CTZ (5 μm, 48 h) results in epileptiform activity in the majority of neurons (80%). The epileptiform activity lasts more than 48 h after washing off CTZ, suggesting a permanent change of the neural network properties after CTZ treatment. We then demonstrated in in vivo recordings that injection of CTZ (5 μmol in 5 μl) into the lateral ventricles of anaesthetized rats also induces spontaneous epileptiform activity in the hippocampal CA1 region. The epileptogenic effect of CTZ is probably due to its enhancing glutamatergic neurotransmission as shown by increasing the frequency and decay time of mEPSCs, and simultaneously inhibiting GABAergic neurotransmission by reducing the frequency of mIPSCs. Comparing to a well‐known epileptogenic agent kainic acid (KA), CTZ affects neuronal activity mainly through modulating synaptic transmission without significant change of the intrinsic membrane excitability. Unlike KA, which induces significant cell death in hippocampal cultures, CTZ treatment does not result in any apparent neuronal death. Therefore, the CTZ‐induced epilepsy model may provide a novel research tool to elucidate the molecular and cellular mechanisms of epileptogenesis without any complication from drug‐induced cell death. The long‐lasting epileptiform activity after CTZ washout may also make it a very useful model in screening antiepileptic drugs.


A `colossal' oxygen isotope shift of the charge-ordering temperature was discovered in . Upon replacing with , the charge-ordering temperature increases by 21 K under zero magnetic field. With an increase of the magnetic field, the oxygen isotope shift increases rapidly and reaches a magnitude of about 43 K under a magnetic field of 5.4 T. The very strong magnetic field dependence of the oxygen isotope effect is difficult to explain within the existing theories of the charge-ordering transition in manganites.


In this article, we critically study whether social networks can explain the emergence of cooperative behavior. We carry out an extensive simulation program in which we study the most representative social dilemmas. For the Prisoner's Dilemma, it turns out that the emergence of cooperation is dependent on the microdynamics. On the other hand, network clustering mostly facilitates global cooperation in the Stag Hunt game, whereas degree heterogeneity promotes cooperation in Snowdrift dilemmas. Thus, social networks do not promote cooperation in general, because the macro-outcome is not robust under change of dynamics. Therefore, having specific applications of interest in mind is crucial to include the appropriate microdetails in a good model.


Protein-energy malnutrition, occurring in 44% of chronic uremic patients at the initiation of dialysis, is strongly associated with high morbidity and mortality rates. Many factors can engender the malnutrition, such as protein and amino acid losses in dialysate and inadequate protein intake. A total of 15 chronic peritoneal dialysis patients, with a serum albumin level of 3.5 g/dl and normalized protein equivalent of nitrogen appearance (nPNA) 0.9 gm/kg/day of ideal body weight, were enrolled into this study. And a daily infusion of 2-L 1.1 % amino acid dialysate (Nutrineal(superscript ®)) was administered over six months. There were 12 patients (3 male and 9 female) completed this study. Assessments of serum albumin, anthropometry, and body compositions by dual energy X-ray absorptiometry (DEXA) were performed before and after six months of Nutrineal(superscript ®) treatment. No significant change was found in serum albumin level and subjective global assessment. There were a small, but insignificant, increment of triceps skin fold, and a decrease, but of no significance, in mid-arm muscle circumference or muscle area. Also, there were a trend to decline in lean body mass and a tendency increase in body fat mass before and after six months of Nutrineal(superscript ®) treatment. In addition, bone mineral content did not change during this period. These findings indicated that daily administration of 2-L 1.1% amino acid dialysate for six months in malnourished patients on chronic peritoneal dialysis did not improve the anthropometry and change the body composition.


Introduction The need to prevent falls and related injuries among seniors is a significant public health issue in Canada, and all nations where an aging demographic puts higher numbers at risk. To address this costly and complex problem, a sustained collaboration has occurred over the past 20 years among falls prevention leaders within government, the health system, academia and local communities. Methods This review summarizes key elements of a coordinated, public health approach to the prevention of falls and related injuries among those aged 65 years, with an epidemiological analysis of fall-related hospital and mortality data for persons aged 65 years and older. Review methods included a synthesis of historical records, a scan of existing programs and findings from in-depth interviews with key informants. Results Outcomes of this sustained approach include a significant reduction in fall-related hospitalization and death rates in some Canadian provinces, which is paralleled by a growth in evidence-based falls prevention programs and services for those at risk. Conclusion This presentation concludes with a summary of the key developments in the evolution of fall and related injury prevention activities over the past two decades. In particular, how the sustained, collaborative efforts have resulted in Canada emerging as an example of success in the formation of comprehensive networks for the integration of evidence-based falls prevention into health service delivery for seniors.


We examine the spectroscopic signatures of tunneling through a Kitaev quantum spin liquid (QSL) barrier in a number of experimentally relevant geometries. We combine contributions from elastic and inelastic tunneling processes and find that spin-flip scattering at the itinerant spinon modes gives rise to a gapped contribution to the tunneling conductance spectrum. We address the spectral modifications that arise in a magnetic field, which is applied to drive the candidate material α-RuCl_{3} into a QSL phase, and we propose a lateral 1D tunnel junction as a viable setup in this regime. The characteristic spin gap is an unambiguous signature of the fractionalized QSL excitations, distinguishing it from magnons or phonons. We discuss the generalization of our results to a wide variety of QSLs with gapped and gapless spin correlators.


Over the last 20 years, visualization courses have been developed and offered at universities around the world. Many of these courses use established visualization libraries and tools (e.g. VTK, ParaView, AVS, VisIt) as a way to provide students a hands‐on experience, allowing them to prototype and explore different visualization techniques. In this paper, we describe our experiences using VisTrails as a platform to teach scientific visualization. VisTrails is an open‐source system that was designed to support exploratory computational tasks such as visualization and data analysis. Unlike previous scientific workflow and visualization systems, VisTrails provides a comprehensive provenance management infrastructure. We discuss how different features of the system, and in particular, the provenance information have changed the dynamics of the Scientific Visualization course we offer at the University of Utah. We also describe our initial attempts at using the provenance information to better assess our teaching techniques and student performance.


As a quantitative analysis tool in the research field of Social Science. Social Network Analyses has been more and more applied to the field of education these years. The thesis takes e-portfolio website as learning and assessing platform. Summed up the data of the learning and Process Assessment, and analyzed it by the angel of InDegree, OutDegree and Betweenness, etc. Finally, compared the student's score which have the extreme value of Betweenness and analyzed the relationship between student's score and the value of Betweenness.


AIM
The purpose of the study was to determine if there had been any changes in the clinical practice and attitudes to the care of children by general dental practitioners over a ten year period from 1986 to 1996, following the introduction of a system of capitation payments in the United Kingdom.

METHODS
A questionnaire was mailed to 1,290 general dental practitioners practicing in Yorkshire (UK) in an identical way to a previous survey ten years before. Practitioners were asked questions concerning their practice of dental caries prevention, behaviour management, restoration of primary teeth and pulp therapy. Responses were compared with the results of the 1986 survey.

RESULTS
Of the total of 687 replies (53.2% response) 61% practiced, or said they practiced, diet evaluation and gave dietary advice. Oral hygiene instruction was reported by 87% and 57% used fissure sealants. The routine use of amalgam, previously 80%, had declined to 35% in favour of glass ionomer cements (57%). There had been a significant improvement in the use of pulp therapy for primary teeth at 35% compared with previous 3%. The use of rubber dam also increased, but only from 0% before to 9% in the present study. The usage of stainless steel crowns had changed from 2% over ten years to 8% and strip crowns from 1% to 5%.

CONCLUSION
The use of paediatric dental techniques by general dental practitioners had generally increased, particularly in preventive measures and pulp treatment. Restorative techniques had marginally changed, but a dramatic shift away from amalgam had occurred. There was still a very low usage of stainless steel crowns and rubber dam was also not used to the extent that it should be.


In eddy-current non-destructive evaluation, an electromagnetic field is induced in a metal by means of an eddy–current probe and the presence of a flaw is indicated by a change in probe impedance. In order to predict the impedance change, it is necessary to calculate the electromagnetic field in the region of the flaw. We present a new method, based on the geometrical theory of diffraction, by which approximate analytical solutions for the electromagnetic field near to a crack can be calculated for intermediate and high frequencies. Two-dimensional field solutions are found for (i) a buried crack and (ii) a surface-breaking crack in a conducting half-space. The fields are constructed using solutions which satisfy the field equations exactly but approximate the boundary conditions. The degree to which the predicted fields match the required boundary values on the plane of the crack and the air––conductor interface plane is assessed and very good agreement is obtained for cracks whose edges lie half a skin–depth or more below the conductor surface. The impedance change due to the crack is calculated in closed form.


The development of Escherichia coli biofilm requires the differential expression of various genes implicated in cell signalling, stress responses, motility and the synthesis of structures responsible for cell attachment. The ibpAB operon is among the stress-response genes most induced during growth of the E. coli biofilm. In this study we demonstrated, to our knowledge for the first time, that the lack of IbpAB proteins in E. coli cells inhibited the formation of biofilm at the air-liquid interface, although it allowed normal planktonic growth. We showed that ibpAB mutant cells experienced endogenous oxidative stress, which might result from a decreased catalase activity. The endogenous oxidative stress in ibpAB cells led to increased expression of tryptophanase, an enzyme which catalyses the synthesis of indole. We demonstrated that the formation of biofilm by the ibpAB mutant was delayed due to the increase in the extracellular concentration of indole, which is known to play the role of a signal molecule, inhibiting biofilm growth.


A cancer diagnosis is life altering and frequently associated with both acute and long-lasting psychosocial and behavioral distress for patients. The impact of a diffuse glioma diagnosis on mental health is an important aspect of the patient experience with their disease. This needs to be understood by neurosurgeons so these concerns can be appropriately addressed in a timely fashion and integrated into the multidisciplinary care of neuro-oncology patients. The relatively grave prognosis associated with diffuse gliomas, the morbidity associated with treatment, and the constant threat of developing a new neurological deficit all can negatively affect a patient's mental ability to cope and ultimately manifest in mental health disorders such as anxiety and depression. The objective of this systematic review was to describe the variety of behavioral health disorders patients may experience following a glioma diagnosis and discuss possible treatment options. The PubMed, Web of Science, Embase, and PsycINFO databases were searched through July 1, 2022, using broad search terms, which resulted in 5028 studies that were uploaded to Covidence systematic review software. Duplicates, non-English-language studies, and studies with irrelevant outcomes or incorrect design were removed (n = 3167). A total of 92 articles reporting behavioral health outcomes in brain tumor patients were categorized and extracted for associations with overall mental health, anxiety, depression, distress, stress, pharmacology, interventions, and mental health in caregivers. The authors identified numerous studies reporting the prevalence of mental health disorders and their negative influence in this population. However, there is a paucity of literature on therapeutic options for patients. Given the strong correlation between patient quality of life and mental well-being, there is a considerable need for early recognition and treatment of these behavioral health disorders to optimize everyday functioning for patients.


Background Chronic use of psychoactive drugs can lead to many clinical adverse events (AE), especially in elderly populations due to the associated polypharmacy and their pathophysiological conditions. Purpose To optimise psychoactive medications of polymedicated elderly psychiatric patients in an elderly healthcare centre, to achieve better efficiency and safety profiles. Material and methods In an elderly psychiatric inpatient care unit from a 103 bed long term healthcare facility, a multidisciplinary adequacy programme of pharmacotherapy was implemented; the team was composed by pharmacists, geriatricians and a psychiatrist. The selection criteria (SC) included in the programme were based according to the psychoactive medication prescribed to the patients: SC-1: patients with ≥3 neuroleptic prescribed; SC-2: patients with ≥3 neuroleptic prescribed plus ≥1 hypnotic; SC-3: patients with ≥2 hypnotics prescribed; SC-4: patients with typical antipsychotics prescribed (not indicated in elderly patients). The patient's pharmacotherapy was checked and discussed weekly following STOPP-START-2014 criteria over a period of 2 months, reducing the use of potentially inappropriate drugs and/or decreasing their dose. After patient inclusion, drug prescription changes and clinical evolution were registered. Results Of 36 patients admitted to the psychiatric ward, 13 met the inclusion criteria (2 patients with SC-1, 6 patients with SC-2, 1 patient with SC-3 and 8 patients with SC-4; 4 patients met 2 SC). Following STOPP-START-2014 criteria, we implemented 40 changes in pharmacotherapy (>3 changes per patient): 24 drugs were stopped and 16 doses were modified (8 dose reductions, 5 'as needed' prescription modifications and 3 exchanges to a suitable option). Only 4 interventions due to the changes implemented were needed: 1 increase in neuroleptic night dose and 3 cases of 'as needed' prescription (2 benzodiazepines for insomnia and 1 neuroleptic for agitation). Conclusion A multidisciplinary adequacy programme was successfully implemented to optimise psychoactive pharmacotherapy prescriptions in elderly psychiatric patients. This implementation allowed deprescription and/or dose reduction of psychoactive drugs and, in consequence, decreased the risk of AE due to those medications. References and/or acknowledgements Acknowledgement to the nursing team for implementing the changes from the programme and monitoring patients' clinical evolutions. No conflict of interest


Radiology reports are detailed text descriptions of the content of medical scans. Each report describes the presence/absence and location of relevant clinical findings, commonly including comparison with prior exams of the same patient to describe how they evolved. Radiology reporting is a time-consuming process, and scan results are often subject to delays. One strategy to speed up reporting is to integrate automated reporting systems, however clinical deployment requires high accuracy and interpretability. Previous approaches to automated radiology reporting generally do not provide the prior study as input, precluding comparison which is required for clinical accuracy in some types of scans, and offer only unreliable methods of interpretability. Therefore, leveraging an existing visual input format of anatomical tokens, we introduce two novel aspects: (1) longitudinal representation learning -- we input the prior scan as an additional input, proposing a method to align, concatenate and fuse the current and prior visual information into a joint longitudinal representation which can be provided to the multimodal report generation model; (2) sentence-anatomy dropout -- a training strategy for controllability in which the report generator model is trained to predict only sentences from the original report which correspond to the subset of anatomical regions given as input. We show through in-depth experiments on the MIMIC-CXR dataset how the proposed approach achieves state-of-the-art results while enabling anatomy-wise controllable report generation.


Background
For subjects with out-of-hospital cardiac arrest (OHCA), bag-valve mask (BVM), endotracheal intubation (ETI), and laryngeal mask airway (LMA) are the most common methods of ventilatory support; however, the best choice remains controversial.

Methods
A comprehensive search of online databases was performed. A traditional meta-analysis was performed to determine the risk ratio of BVM vs. LMA and ETI vs. LMA. Indirect treatment comparisons (ITCs) were conducted to compare BVM and ETI.

Results
A total of 13 full-text articles reporting the efficacy of BVM, ETI, and LMA were considered in this analysis. BVM and LMA had the same effect regarding return of spontaneous circulation (ROSC) (23% vs. 24%; RR =0.84), survival rate at admission (19% vs. 21%; RR =0.82) or discharge (6% vs. 4%; RR =0.61). ETI was superior to LMA in terms of ROSC (48% vs. 23%; RR =0.72) and survival rate at both admission (27% vs. 19%; RR =0.85) and discharge (12% vs. 4%; RR =0.90). BVM was inferior to ETI in terms of ROSC (24% vs. 48%; RR =0.86), survival to admission rate (21% vs. 27%; RR =1.037), and survival to discharge rate (6% vs. 12%; RR =1.476).

Conclusions
ETI should be considered for airway management as early as possible, which can improve the subject's success rate of recovery and survival to admission rate. In future, large-scale, multi-center, randomized controlled studies should be conducted to evaluate the exact efficacy of BVM, ETI, and LMA for the first aid of subjects with OHCA.


It will be shown that the Reeh-Schlieder property holds for states of quantum fields for ultrahyperfunctional Wightman theory. As by product, it is shown that the Reeh-Schlieder property also holds for states of quantum fields on a non-commutative Minkowski space in the setting ultrahyperfunctional.


The predictability of the opinions provided in expert reports produced in Australian takeovers has led repeatedly to public criticism. This study assesses the validity of this criticism by comparing expert valuations with the recommendations of target firm directors. The results indicate that expert valuations typically agree with directors' recommendations, with the rate of agreement being 95% for reject recommendations. Consistent with expert valuations provided in rejected takeovers being inflated, these bids are associated with similar premiums to accepted bids. Additionally, rejected offers that succeed do so at well below the experts valuation, and prices in unsuccessful rejected offers do not increase towards the experts valuation.


Menhaden fish oil (FO) containing n-3 fatty acids dramatically extends the life span and delays the onset and progression of autoimmune disease in (NZBxNZW)F1 (B/W) female mice as compared to those fed corn oil (CO) rich in n-6 lipids. As an inefficient antioxidant defense system has been linked to autoimmune diseases, the present study was undertaken to determine whether the protective action of n-3 lipids is mediated through their antioxidant defense system. Weanling B/W mice were fed a nutritionally adequate, semipurified diet containing CO or krill oil (KO) or FO at 10% level (w/w) ad libitum until the mice were 6.5 months old. All diets contained the same level of vitamin E (21.5 mg/100 g diet). We compared the effects of feeding n-6 and n-3 lipids on survival, kidney disease, hepatic microsomal lipid composition, peroxidation, and on the activity and mRNA expression of the antioxidant enzymes catalase, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in 6.5-month-old B/W mice. The results showed that when compared to livers from CO-fed mice, livers from KO- and FO-fed mice showed: (i) significantly higher (P < 0.001) activities and expression of CAT, GSH-Px and SOD; (ii) significantly lower (P < 0.001) arachidonic acid (20:4n-6) and linoleic acid (18:2n-6) and higher (P < 0.001) eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) levels in hepatic microsomes; and (iii) significantly lower (P < 0.001) estimated peroxidation indices and thiobarbituric acid reactive substances generation.(ABSTRACT TRUNCATED AT 250 WORDS)


The number and distribution of Leu-7 + cells, a subset of Natural Killer cells clustered as CD 57 + cells, were studied with an immunoperoxidase technique on reactive lymph nodes (n = 13), malignant lymphomas (n = 60) and Hodgkin's disease (n = 22). Results of paraffin-section immunocytochemistry were compared with those obtained of frozen sections of the same tissues. CD 57 + cells are small lymphocytes mainly located in the germinal centers of reactive lymph nodes and in their malignant counterpart, i.e. the follicular lymphomas. The paragranuloma of Hodgkin's disease, type I nodular, contained high numbers of CD 57+ cells. Nine cases of CD 57+ lymphomas are reported, which were of high grade of malignancy. Their histological subtypes were anaplastic (3 cases) immunoblastic (2 cases), pleomorphic medium and large cell (3 cases), unclassifiable (1 case). Their diverse T-cell (4 cases) or B-cell (2 cases) origin and the various expression of epithelial membrane antigen (EMA) or Kil/Ber-H2 (CD 30) suggest an aberrant CD 57+ phenotype of a subset of large cell lymphomas.


The healthcare construction boom requires evidence for effective design of nurse stations, including evidence supporting workflow processes, computerization, integration of technology, communication of caregivers, and optimal patient outcomes. This article describes the examination of a traditional centralized nursing station using a total patient care delivery model and minimal computerization and a highly computerized, decentralized nursing station using a team nursing model. Results specific to communication activities, time with patients, number of patient visits per registered nurse, and patient satisfaction with response time are reported.


Abstract The degree of rangeland degradation in the United States is unknown due to the failure of traditional field-based monitoring to capture the range of variability of ecological indicators and disturbances, including climatic effects and land use practices, at regional to national spatial scales, and temporal scales of decades. Here, a protocol is presented for retrospective monitoring and assessment of rangeland degradation using historical time series of remote sensing data and catastrophe theory as an ecological framework to account for both gradual and rapid changes of state. This protocol 1) justifies the use of time-series satellite imagery in terms of the spatial and temporal scale of data collection; 2) briefly explains how to acquire, process, and transform the data into ecological indicators; 3) discusses the use of time-series analysis as the appropriate procedure for detecting significant change; and 4) explains what reference conditions are appropriate. Landsat data have been collected and archived since 1972, and include complete coverage of US rangelands. Characteristics of land degradation can be retrospectively measured for a nearly 33-year trend using surrogate remote sensing–based indicators that correlate with changes in life-form composition (time series of thematic maps), declines in vegetation productivity (vegetation indices), accelerated soil erosion (soil indices), declines in soil quality (piospheric analysis), and changes in landscape configuration (time series of thematic maps). Aspects of 2 retrospective studies are presented as examples of application of the protocol to considerations of the land use impacts from military training and testing and ranching activities on rangelands.


In the new era of technology, internet turns to be one of the main sources of information, since it is considered cheaper and easier to use. Hence in tourism, two main pull factors influencing potential tourist to visit a destination are recognized as nature and culture which a destination offers. The acceptance of culture as one of the important factors in tourists' motivation, heritage sites become popular in many countries especially those which are nominated as world heritage sites. This paper is to analyze the condition of available online information about George Town world heritage spots (Penang, Malaysia). As far as heritage is one of the products of tourism and tourism, on the other hand, is a big help for sustainability of heritage sites, providing sufficient information about tourism heritage sites as a promotional key is very important. Top ten tourism websites were chosen and content analysis was performed to find the current situation of those websites. By recognizing heritage as tangible and intangible, the result shows that although the intangible heritages need more concern in sustainability matter, but the information about them are not as complete as the tangible ones. Lack of proper information was seen in most websites and the focus of information was more on tangible heritage and among intangible heritage, the main focus was on food. To support the result of analysis, in-dept interviews were conducted by couple of heritage offices in the city. The main reason behind the lack of sufficient information about intangible heritage seems to be the lack of complete list of them and moreover, promoting this division of heritage needs negotiation with the local residence involving in those activities. The paper suggests providing a complete list of George Town world heritage as far as some of them are disappearing lately, and keeping this valuable world heritage sustainable for next generation needs detailed study and completing the list as soon as possible. In this regard those intangible heritages which are in hazard of disappearing can be maintained by the effort of key holders of the field. Moreover, providing the mentioned list helps the information providers, especially related websites to focus equally on tangible and intangible George Town world heritage.


The aim was to assess the blood levels of heavy metals (Copper – Zinc and lead)  in autistic patients where have these metals could be correlated with this disease.
This study was conducted on 498 autistic  patients aged between  1-16  years  of both sexes , at the autism center in Thi-qar health department official center during 2016 .
Blood samples were collected from patients analyzed for Pb , Cu , Zn .
The results showed  increase in the levels of  (Cu- Zn and Pb) :  Pb> Cu>Zn  .
The result   also, showed that  there is a relationship between the disease and the age, where the age group (4-6 years) recorded the highest percentage, as well as the relationship of a positive correlation with (A blood group) as follows A > B>  AB > O , the sex percentage was recorded that  (9 :1)  males :females .
The conclusion of  this  high  percentage of male to female might be  due to sex–affected or from environmental impacts which are have more influence on males .


1074 Resveratrol inhibits tumor initiation, promotion and progression which has mainly been explained by its properties in cell cycle control and apoptosis induction. So far, ambiguous observations have been published regarding its influence on genomic stability. To study resveratrol´s effects on DNA double-strand break (DSB) repair we applied the established EGFP and I-Sce I based assay system on resveratrol-treated lymphoblastoid cell lines (LCLs). DSB repair measurements performed in parallel to cell cycle and apoptosis analyses, showed that resveratrol inhibits both, homologous recombination (HR) and non homologous end-joining (NHEJ) independently of its known growth and death regulatory functions. Using (i) the isogenic cell lines TK6 and WTK1, which differ in their p53 status, (ii) LCLs from patients with ataxia telangiectasia (AT-cells), (iii) shRNA mediated p53 knockdown, and (iv) chemical inhibition of ATM/ATR by caffeine, we established an ATM-p53-dependent pathway of homologous recombination inhibition by resveratrol. Additional use of LCLs from Nijmegen breakage syndrome (NBS) patients furthermore provided evidence for an ATM/ATR-Nbs1-dependent inhibition of microhomology-mediated NHEJ (MM-NHEJ) after resveratrol-treatment. We propose that activation of ATM and /or ATR is a central effect of resveratrol. Repression of error-prone recombination subpathways could at least partially explain the chemopreventive effects of this natural plant constituent in animal cancer models.


This volume claims to be the 'first systematic attempt to establish Sheridan as a major figure in the history of English comedy'. The claim is quite misleading. The book consists of essays written by a variety of individuals examining different facets of Sheridan's career there is nothing systematic about the choice or content of the essays, and the quality fluctuates widely. In structural terms the book offers an impressionistic view of Sheridan the man and of his work as writer and politician. Most of the contributors have either written books on or edited works by Sheridan. With some notable exceptions their essays for this volume read like a collection of afterthoughts. The exceptions include Jack Durant's finely crafted piece 'Sheridan and Language', Christopher Reid's penetrating analysis of 'Argument and Identity in Sheridan's Speeches', and Marc Baer's detailed and convincingly illustrated account of "The Rise and Fall of Sheridan as Political Reformer'. Closing the volume is an interview with the director Peter Wood who, with elegiac nostalgia, recalls his production of The Rivals 'before the dark time of deconstructive thinking . . . militant feminism, and political correctness engulfed our culture'. He goes on to comment perceptively on the warmth of characterization in The Rivals in contrast to the chilling nature of The School for Scandal.


Chiamydia culture service We read with interest the paper by J R Willcox et all advocating a routine chlamydial isolation service. They found that almost 40% of Chlamydia trachomatis-positive female patients had no history of contact with a patient with urethritis and therefore would not have received antichlamydial therapy. Kinghorn and Waugh2 have recently published similar data. The results of previous series,3 4 however, have suggested that chlamydia are rarely found in the absence of a history of contact with either nongonococcal urethritis (NGU) or gonorrhoea. We are conducting a study of unselected female patients attending two venereal disease clinics. So far, C trachomatis has been isolated from 50 (21 %) of 241 patients, a figure compatible with those of other studies. 1-4 Of these 50 patients, 40 had a definite history of contact with a man suffering from NGU, gonorrhoea, or an unspecified urethritis, and another two women had an infection with Neisseria gonorrhoeae and can therefore be presumed to have had a contact in the above categories. Only eight (16%) chlamydia-positive patients therefore had


The invention (a) epoxy resin, (b) a hardener and (c) in accordance with and, if necessary, contains an epoxy resin and the incompatible polymer compounds (d) filler and / or (e) an adhesive composition containing a curing accelerator; (A) an epoxy resin and (b) a curing agent and a method of manufacturing an adhesive composition comprising mixing (c) the epoxy resin and the incompatible polymer compound, a mixture thereof by mixing a filler (d); Adhesive film obtained by forming the adhesive composition into a film; The chip mounting surface of the circuit board substrate for semiconductor mounting having the adhesive film; And It discloses a semiconductor device using the adhesive film or a semiconductor mounting board. Adhesive composition, adhesive film, the substrate and the semiconductor device for mounting a semiconductor


The automatic recognition of the modulation format of a detected signal, the intermediate step between signal detection and demodulation, is a major task of an intelligent receiver, with various civilian and military applications. Obviously, with no knowledge of the transmitted data and many unknown parameters at the receiver, such as the signal power, carrier frequency and phase offsets, timing information, etc., blind identification of the modulation is a difficult task. This becomes even more challenging in real-world. In this paper modulation classification for QAM is performed by Genetic Algorithm followed by Template matching, considering the constellation of the received signal. In addition this classification finds the decision boundary of the signal which is critical information for bit detection. I have proposed and implemented a technique that casts modulation recognition into shape recognition. Constellation diagram is a traditional and powerful tool for design and evaluation of digital modulations. The simulation results show the capability of this method for modulation classification with high accuracy and appropriate convergence in the presence of noise.


A correlation between three molecular connectivity indexes and the muscarinic receptor affinity of 104 acetylcholine antagonists was found. Analysis of structure from these indexes reveals not only the importance of the onium and the bulky portions of the molecule but also their virtual independence of each other on the affinity. Analysis of the onium group portion of the molecules indicates that its contribution to the experimental affinity is virtually constant through a variety of structural variations. The influence of the bulky side chains, in contrast, is quite structure dependent. The equation relating connectivity indexes to muscarinic affinity of antagonists is capable of predicting the affinity of other antagonists as well as a number of agonist molecules.


Separation theorems, distribution of zeros of solutions, and disconjugacy criteria for linear third-order differential equations are discussed. For instance, it is proved that the equation y'" +py"+qy' +ry = 0, where p&C", gSC, and r£C on an interval I, is disconjuga te on I if p does not change sign and if ggO, rèO, 2-2/)'áO, and r-g'+£"â0on 7. We shall consider the third-order equation of the form (1) /" + py" + qy' + ry = 0, where p, q, and r are real-valued, continuous functions defined on an interval I. The oscillatory behavior of solutions of (1) has been extensively studied by Hanan [4], Azbelev and Caljuk [l], Lazer [ó], and Barrett [2]. An up-to-date review of the oscillation theory of the linear third-order differential equation may be found in a recent article by Barrett [3]. In this paper we shall discuss separation theorems, distribution of zeros of solutions, and disconjugacy criteria for equation (1). (1) is said to be disconjugate on the interval 7 if no nontrivial solution of (1) has more than two zeros (counting multiplicities) on I. A nontrivial solution of (1) is said to be oscillatory on I if it has an infinite number of zeros on I. If (1) has an oscillatory solution, it is said to be oscillatory. Theorem 1. Assume that p, q, rEC[a, b] and that £ = 0, g = 0, r^Oon [a,b]. Let u and v be two solutions of (1), and put Dij = {(¡) "<i) 0úi<jú2, i, j = 0,1,2. If Doi(a), D02(a), and Di2(a) are nonnegative, but not all zero, then (i) neither u nor v have a double zero on (a, b], (ii) um and vm cannot have a common zero on (a, b], k = 0, 1; and (iii) between any two zeros of u on (a, b], there is a zero of v. Received by the editors February 13, 1970. A MS 1969 subject classifications. Primary 3442, 3436.


High-intensity focused ultrasound (HIFU) is a minimally-invasive and non-ionizing promising technology and has been assessed for its role in the treatment of not only primary tumors but also metastatic lesions under the guidance of ultrasound or magnetic resonance imaging. Its performance is notably effective in neurological, genitourinary, hepato-pancreato-biliary, musculoskeletal, oncological and other miscellaneous applications. In this article, we executed a review of the emerging technology of HIFU and its clinical applications.


In an 11-y period (2000–2010) 126 tornadoes affected central Oklahoma within a 111-km (60-nm) radius of the Twin Lakes, Oklahoma (KTLX) WSR-88D. The tornadoes resulted in 265 injuries and 3 deaths. This study used archived WSR-88D data to obtain information about storm characteristics such as mode, width, height, and measures of the mesocyclone, at the time of initial tornado formation. The radar data provided information about the supercell spectrum and highlighted differences between tornado-producing supercells and tornado-producing quasi-linear convective systems (QLCSs), especially with respect to midlevel rotational velocity. Warning lead-time information also was obtained and compared with the radar characteristics. No specific radar attribute was strongly correlated with lead time, likely due to the multitude of variables involved in the tornado warning process. A strong correlation did exist between lead time and storm mode. Applying these findings in an operational environment similar to that found in central Oklahoma may enhance tornado warning performance.


We describe a 3D+T active surface model for segmentation and tracking of the left ventricular endocardium within 3D MRI sequences of the cardiac cycle. In order to perform segmentation and tracking simultaneously, the surface structure is divided through both time and space, and is therefore handled as an array of planar active contours, interconnected between adjacent slices and frames, providing spatial and temporal consistency. In a given frame, the stacking of slice contours constitute a 3D triangular mesh with a cylindrical topology. Extraction of ventricle border is performed by means of energy minimization, using a combination of boundary-based term and a new region-based term, computed with respect to the narrow band principle.


Machine learning models trained on confidential datasets are increasingly being deployed for profit. Machine Learning as a Service (MLaaS) has made such models easily accessible to end-users. Prior work has developed model extraction attacks, in which an adversary extracts an approximation of MLaaS models by making black-box queries to it. However, none of these works is able to satisfy all the three essential criteria for practical model extraction: (1) the ability to work on deep learning models, (2) the non-requirement of domain knowledge and (3) the ability to work with a limited query budget. We design a model extraction framework that makes use of active learning and large public datasets to satisfy them. We demonstrate that it is possible to use this framework to steal deep classifiers trained on a variety of datasets from image and text domains. By querying a model via black-box access for its top prediction, our framework improves performance on an average over a uniform noise baseline by 4.70x for image tasks and 2.11x for text tasks respectively, while using only 30% (30,000 samples) of the public dataset at its disposal.


Dogs are hosts of parasites with different pathogenicities and zoonotic risks. The aim of our study was to assess factors that could affect the occurrence of endoparasitic infections in dogs using questionnaires for owners and examining canine faeces. Based on the responses of dog owners, we evaluated ways of the preventive and therapeutic use of antiparasitic drugs. One faecal sample was obtained from each dog (391 samples total), and then examined by flotation, larvoscopic, and polymerase chain reaction (PCR) methods. We focused on zoonotic tapeworms Echinococcus multilocularis and Taenia crassiceps. The answers in the dog owners' questionnaires showed that owners most often dewormed their dogs irregularly (96.4%), namely, twice a year (24.3%). In coprological examinations the following parasites were detected: Giardia spp., Cystoisospora ohioensis complex, Neospora caninum/Hammondia heydorni, Toxocara canis, Toxascaris leonina, Capillaria spp., Trichuris spp., Angiostrongylus vasorum, Crenosoma vulpis, Ancylostoma spp. and Taenia spp. A total of 4 out of 391 PCR investigated samples of faeces were positive for DNA of Taenia species. Sequences were obtained for 3 of them, confirming 100% identity with T. crassiceps. The zoonotic helminths Toxocara canis were the more prevalent species (9.3%, 4.3%, 1.9% group A, B, C). We consider the presence of T. crassiceps in 3 dog faecal samples to be serious due to its zoonotic potential. Data collected within this study showed that the prevention against endoparasites carried out at the breeders' discretion is insufficient to ensure the health of their dogs or to cover the risk of zoonotic transmission.


Bayesian predictive functions for future observations from a generalized Pareto distribution based on generalized order statistics are obtained. Two cases are considered unknown one parameter and unknown two parameters. We also consider two cases fixed sample size and random sample size. The Bayesian predictive functions are specialized to ordinary order statistics, progressive type II censoring and upper record values. Examples are calculated for the lower and the upper bounds for the future observation based on ordinary order statistics, progressive type II censoring and upper record samples.


Many fascinating astrophysical phenomena can be simulated insufficiently by standard numerical schemes for the compressible hydrodynamics equations. In the present work, a high performant 2D hydrodynamical code has been developed. The model is designed for the planetary formation that consists of momentum, continuity and energy equations. Since the two-phase model seems to be hardly executed, we will show in a simplified form, the implementation of this model in one-phase. It is applied to the Solar System that such stars can form planets. The finite volume method (FVM) is used in this model. We aim to develop a first-order well-balanced scheme for the Euler equations in the the radial direction, combined with second-order centered ux following the radial direction. This conception is devoted to balance the uxes, and guarantee hydrostatic equilibrium preserving. Then the model is used on simplified examples in order to show its ca- pability to maintain steady-state solutions with a good precision. Additionally, we demonstrate the performance of the numerical code through simulations. In particularly, the time evolution of gas orbited around the star, and some proper- ties of the Rossby wave instability are analyzed. The resulting scheme shows consequently that this model is robust and simple enough to be easily implemented.


At the moment the housing demand needs estimated at the level of provinces and big cities. But at the level of small cities and smaller administrative unit like Goon, it is not, for lack of appropriate estimating method. Therefore it is very much required to develope appropriate estimating method at such levels. This study is an attempt to apply to some local areas the estimating method developed by Professor Miyqke of Japan as is suggested in his article. "How to Estimate the Housing Demand in Relation with the Different of Poulation Structure." The result shows that the applied local areas showed repective characteristics distinguished from one another in the pattern of housing demand, to prove the approprateness of the method when applied to the areas at the level of small cities and Goons.


The fine temporal and spatial resolution of Doppler lidar observations has been highly effective in the study of wind and turbulence dynamic in the nocturnal boundary layer during Lamar Low-Level Project in 2003. The High-Resolution Doppler Lidar (HRDL), designed and developed at the National Oceanic and Atmospheric Administration (NOAA) Earth System Research Laboratory (ESRL), measures range-resolved profiles of line-of sight (LOS) Doppler velocity and aerosol backscatter with a pulse repetition frequency of 200 Hz, velocity precision about 10 cm s-1, and a very narrow beam width. The majority of the lidar-measured wind speed and variance profiles were derived using a vertical-scan mode and the application of a vertical binning technique. The profile data were used to calculate quantities important for wind energy applications, including turbulence intensity, wind and directional shear through the layer of the turbine rotor. Profiles of all quantities show a strong variation with height. The mean wind fields, the turbulence, and turbulence intensities show a good agreement with sonic anemometer sodar high confidence (high SNR) measurements. The ability of HRDL to provide continuous information about wind and turbulence conditions at the turbine height and above the range of the tower measurements made HRDL as a powerful instrument for studies of the nighttime boundary layer features. Such information is needed as turbine rotors continue to rise higher into the boundary layer.


In this paper we present the concurrent constraint functional programming language CCFL and an abstract machine for the evaluation of CCFL programs in a multicore environment. The source language CCFL is a simple lazy functional language with a polymorphic type system augmented by ask-/tell-constraints and conjunctions to express concurrent coordination patterns. As execution model for CCFL we propose the abstract machine ATAF. ATAF implements a G-machine to evaluate functional expressions and provides facilities to run multiple cooperating processes on a fixed set of CPUs. Processes communicate via a shared constraint store realizing residuation semantics and committed choice. We show a few scaling results for parallel programs obtained with a prototypical implementation of ATAF on a quadcore machine.


The length of a promotional cycle for a film generally begins with the emergence of a poster or a film trailer that attempts to both "announce wares" and "win patrons" (Staiger 1990, 3). Traditionally, film trailers and posters have been used to draw audiences to the cinematic space to consume a feature film. But as film promotion has increasingly shifted from the spaces of the cinema and television, and from being tied to the event of film going, objects of film promotion can be consumed and enjoyed for their own sake at any point in a film's promotional life. The presence of trailers on DVDs and on the Internet mean that Consumers can watch a trailer well after a film has been released and for purposes other than choosing which upcoming feature to watch. Recut trailers, which are typically uploaded to the video-sharing site YouTube, involve the recutting or splicing together of footage from one or more sources to create a trailer for a film that does not and will not exist. In some instances, footage is shot specifically for the trailer. Recut trailers alter the typical path of film promotion, which seeks to announce a film, build an audience, and draw viewers to the space of the cinema. Famous examples of recut trailers include The Shining (1980, Stanley Kubrick) recut as a family comedy or footage from Back to the Future (1985, Robert Zemeckis) recut to mimic the narrative of Brokeback Mountain (2006, Ang Lee). Although they take the form of an advertisement, recuts seek to advertise something that cannot be obtained, since a hybrid film such a Brokeback to the Future (Chocolate Cake City 2006) will not eventuate. Recut trailers reflect and embody audience desire to see an existing feature be extended into a sequel, create a cycle of films, or generate multiplicities through a series of links between disparate films. This chapter outlines the numerous ways that recut trailers play with the temporality of a feature film's promotion, as well as how they may shift our understanding of what may constitute filmic multiplicities. Recut trailers allow users and audiences to revisit, rework, and augment their memory of a feature film, identifying latent story lines, shifting the genre of a film, or allowing a character from a film to exist in a newly imagined film. They consequently disrupt the typical longevity of a film, leaving tangible objects of audience desire that can be revisited to keep a film almost timeless, allowing an older feature film to be reinvigorated through any of the aforementioned strategies. I discuss the creation of multiplicities through three case studies in this chapter. First, through an analysis of recuts and originally shot trailers created in the wake of Snakes on a Plane 's release (2006, David R. Ellis), I position the recut trailer as a form through which audiences can mock and subvert attempts by Hollywood studios to create film cycles and multiplicities. Second, I use Inception (2010, Christopher Nolan) to demonstrate how sound can be used to create multiplicities of a singular film, drawing connections where none were thought to exist. Finally, I discuss fake sequels created for the blockbuster historical action film Titanic (1997, James Cameron) to establish how recurs can act as material traces of audience desire to extend a singular film into a series, in particular by combining intertextual references to locate the narrative of Titanic as one part of the larger narrative of the characters Jack (Leonardo DiCaprio) and Rose (Kate Winslet).


The formation of adventitious branch roots in the secondary tissues of parental root axes is a widespread and frequent occurrence under field conditions. Anatomical features diagnostic for the recognition of adventitious roots were utilized to confirm the occurrence of adventitious roots on roots of 22 species from 12 families in nine orders of dicotyledonous plants. Adventitious roots may play an important role in generating the population of fine roots as part of root turnover in the soil.


The instantaneous unit hydrograph is conceived as a random function of climate and geomorphology varying with the characteristics of the rainfall excess. The probability density functions of the peak and time to peak of the IUH are analytically derived as functions of the rainfall characteristics and the basin geomorphological parameters. The main characteristics of these pdf's are studied, and a new approach to hydrologic similarity is initiated under the concept of the geomorphoclimatic IUH. For a given set of geomorphologic characteristics and a particular intensity and duration of rainfall, the peak and time to peak of the IUH corresponding to those values can be easily estimated.


A rare case of a single temporal pterygium is reported. The etiology of pterygium and its predilection for the nasal side is discussed. A hypothesis is presented to explain why a pterygium never extends beyond the center of the cornea. Whenever a single temporal pterygium is noted it should be excised to determine the true nature of the lesion.


We present a systematic approach for the separation of variables for the two-dimensional (2D) Dirac equation in polar coordinates. The three vector potential, which couple to the Dirac spinor via minimal coupling, along with the scalar potential are chosen to have angular dependence which emanate the Dirac equation to complete separation of variables. Exact solutions are obtained for a class of solvable potentials along with their relativistic spinor wavefunctions. Particular attention is paid to the situation where the potentials are confined to a quantum dot region and are of scalar, vector and pseudo-scalar type. The study of a single charged impurity embedded in a 2D Dirac equation in the presence of a uniform magnetic field was treated as a particular case of our general study.


Training deep networks is expensive and time-consuming with the training period increasing with data size and growth in model parameters. In this paper, we provide a framework for distributed training of deep networks over a cluster of CPUs in Apache Spark. The framework implements both Data Parallelism and Model Parallelism making it suitable to use for deep networks which require huge training data and model parameters which are too big to fit into the memory of a single machine. It can be scaled easily over a cluster of cheap commodity hardware to attain significant speedup and obtain better results making it quite economical as compared to farm of GPUs and supercomputers. We have proposed a new algorithm for training of deep networks for the case when the network is partitioned across the machines (Model Parallelism) along with detailed cost analysis and proof of convergence of the same. We have developed implementations for Fully-Connected Feedforward Networks, Convolutional Neural Networks, Recurrent Neural Networks and Long Short-Term Memory architectures. We present the results of extensive simulations demonstrating the speedup and accuracy obtained by our framework for different sizes of the data and model parameters with variation in the number of worker cores/partitions; thereby showing that our proposed framework can achieve significant speedup (upto 11X for CNN) and is also quite scalable.


We present a method of improving automatic speech recognition performance under noisy conditions by using a source separation approach to extract the underlying clean speech signal. The feature enhancement processing is complemented with heuristic estimates of the uncertainty of the source separation, that are used to further assist the recognition. The uncertainty heuristics are converted to estimates of variance for the extracted clean speech using a Gaussian Mixture Model based mapping, and applied in the decoding stage under the observation uncertainty framework. We propose six heuristics, and evaluate them using both artificial and real-world noisy data, and with acoustic models trained on clean speech, a multi-condition noisy data set, and the multi-condition set processed with the source separation front-end. Taking the uncertainty of the enhanced features into account is shown to improve recognition performance when the acoustic models are trained on unenhanced data, while training on enhanced noisy data yields the lowest error rates.


Orientational defects in hexagonal ice were investigated using molecular dynamics simulations. Energy relaxation during L- and D-defect migration was shown to be associated with improved alignment of water molecules along the local electric fields. Two new forms of defects, an "L+D complex," and a "5+7 defect," were characterized. These forms appear in ice trajectories close to the melting point, and in the course of L- and D-pair recombination process. Defect pair recombination was shown to be a complex process, involving collective H-bond changes in groups of molecules.


During the Run 2 period of the LHC, the ATLAS and CMS experiments have accumulated proton-proton collision data corresponding to an integrated luminosity of around 3 fb$^{-1}$ in 2015 and 36 fb$^{-1}$ in 2016 at a center of mass energy of 13 TeV. In the journey of finding new physics, it is of importance to understand the standard model which seems to be complete after the Higgs discovery. Precision tests must be performed in every corner of the phase space since new physics can appear in any different places. In this proceedings, measurements of the differential cross sections of global event variables from the top quark pair productions at the both experiments using the data collected during the Run 2 period by the time of the year 2016 are presented.


Relatively frequent, adrenal masses include a multitude of different tumor types: uni- or bilateral hyperplasias, adenomas, and the rare entity of adrenocortical carcinomas. With significant progress in our appreciation of their underlying molecular pathomechanisms and from analysis of affected individuals and their families, a number of inherited diseases and tumor syndromes have been linked to adrenocortical tumorigenesis. These syndromes and diseases include the Carney complex, the McCune-Albright syndrome, multiple endocrine neoplasia type 1, familial adenomatosis coli, congenital adrenal hyperplasia, familial forms of primary aldosteronism, the Beckwith-Wiedemann syndrome, and the Li-Fraumeni syndrome. The key to successful management of these syndromes is identification of patients harboring adrenal tumors within the context of hereditary diseases, since diagnostic procedures, therapy and follow-up may significantly differ from the management of sporadic, isolated adrenal tumors. This review explores the underlying genetic defects, diagnosis and therapy of the major heritable tumor syndromes associated with adrenocortical tumorigenesis.


To the Editor: We read with interest the recent article by Camus et al1 mainly comparing 3 risk scores to predict outcome of severe lower gastrointestinal bleeding (LGIB). They did provide some information in need for real practice, however, results from the current study could be interpreted with the following considerations. As the authors revealed, no risk scores have been adopted for outcome prediction in patients of LGIB. Although the American Society of Anesthesiologists classification has proved to be an excellent predictive score for assessing the availability of patients for surgery and Charlson comorbidity index has also proved to be one of the risk factors for 30-day mortality in patients hospitalized with LGIB,2,3 yet, no prospective researches consisted of large sample sizes have made a validation of these predictive scores for evaluating the outcome predicting for LGIB. Hence, the authors are welcomed to make a validation of these risk scores first through the 235 patients before comparison of their predictive ability by receiver operator characteristic analysis. Furthermore, as the characteristics of patients at admission were presented (Table 2), these information would be of little value if the authors neglected to take the possible factors affecting prognosis into account, while evaluating the accuracy of these scores in outcome prediction. As we know, other factors, including a history of LGIB, adequacy of hemostasis therapy, the risk of a thromboembolic event, different medications or treatments and so on could be candidate factors for the risk of adverse outcomes in these patients.4,5 Several binary logistic regression models in regards to rebleeding, surgery, mortality or low risk within 30 days are recommended to be carried out to make an adjustment of the influence of these potential confounders on different outcomes. Altogether, the comparison of these risk scores in patients of LGIB may be arbitrary, from a statistical point of perspective. Further welldesigned investigations are needed to confirm the effect of these predictive scores for outcome predicting.


A method of making a coated abrasive article having a patterned surface, comprising the deposition of abrasive grain on a substrate by an electrostatic centrifugal technique that uses a field that is produced by opposed electrodes carry different charges, whereby the field through which the is controlled grain is thrown, so that the grain is preferably deposited on the substrate in a desired pattern.


Objectives This study demonstrates the feasibility of using a modified mixture of experts (ME) model with repeated measured tumoural Ktrans value to perform an automatic diagnosis of responder based on perfusion magnetic resonance imaging (MRI) of rectal cancer. Methods The data used in this study was obtained from 39 patients with primary rectal carcinoma who were scheduled for preoperative chemoradiotherapy. The modified ME model is a joint modeling of the ME model via the linear mixed effect model. First, we considered two local experts and a gating network, and the modified expert network as a liner mixed effect model. Afterward, the finding estimates were obtained via the expectation-maximization algorithm. All computation was performed by R-2.15.2. Results We found that two experts have different patterns. The feature of expert 1 (n = 10) had a higher baseline value and a lower slope than expert 2 (n = 29). A comparison of the estimated experts and responder/non-responder groups according to T-downstaging criteria showed that expert 1 had a more effect treatment responder than expert 2. Conclusions A novel feature of this study is that it is an extension of classical ME models in case of repeatedly measured data. The proposed model has the advantages of flexibility and adaptability for identifying distinct subgroups with various time patterns, and it can be applied to biomedical data which is measured repeatedly, such as time-course microarray data or cohort data. This method can assist physicians as important diagnostic decision making mechanism.


Hyaluronan oligo- and polysaccharides are abundant in the human body. Depending on the chain length, hyaluronan is an important structural component or is involved in influencing cell responses during embryonic development, healing processes, inflammation and cancer. Due to these diverse roles of hyaluronan, there are multiple applications already in use or in development, such as supplementation of fluid in eyes and joints, cosmetic tissue augmentation, enhancing wound healing, tissue engineering, cancer treatment, controlled drug release and targeted drug delivery. State-of-the-art hyaluronan production techniques include bacterial fermentation to produce long hyaluronan polymers with a small chain length distribution and in vitro enzymatic systems to produce hyaluronan oligosaccharides of one chain length. Both production strategies make use of hyaluronan synthase (HAS), an enzyme that elongates UDP-glucuronic acid (UDP-GlcUA) and UDP-N-acetylglucosamine (UDP-GlcNAc) into hyaluronan. The main question in hyaluronan production today is how the chain length of the products can be controlled. Since most production processes use hyaluronan synthases, the aim of this thesis was to elucidate the polymerization mechanism of Pasteurella multocida hyaluronan synthase (PmHAS) from a biochemical point of view. In addition, the acquired knowledge is used for improving the control on hyaluronan chain length in polymerization reactions using PmHAS. Valuable information important for production processes on the intrinsic properties of the enzyme, such as substrate affinity, can be obtained by kinetic studies using single-step elongations. Kinetic studies also provide insights on how polymerization is achieved and, combined with structural studies, the identification of amino acid residues that are important for polymerization. This knowledge can be used for improving the hyaluronan synthesis performance of the enzyme. Kinetic studies require purified substrates in quantities of mg-scale. Hyaluronan (HA) oligosaccharides were obtained through stepwise hyaluronan cleavage using hyaluronidase and consecutive separation of the reaction mixture by flash-chromatography (Chapter 2). The enzymatic hydrolysis was optimized by experimental design studies with pH, enzyme concentration and reaction time as parameters. Empirical models were developed for the yield of each individual target HA oligosaccharide using the results from a central composite design. Selective production of short HA oligomers (HA ≤ 10) or longer oligosaccharides (HA > 10) was made possible through implementation of the reaction conditions indicated by the empirical models. Separated HA oligomers were characterized by a combination of anion exchange chromatography and matrix-assisted laser desorption/ionization mass spectrometry with time-off-flight analysis. Using these techniques, the desired quantities of purified target HA oligosaccharides (n = 4, 6, 8 and 10) were obtained and used in further studies. Besides the single-step elongations assessed in kinetic studies, full polymerization studies with both UDP-sugars available were used to investigate the influence of substrate concentrations on the chain length distribution of the hyaluronan products. In order to quantify all oligosaccharides formed during PmHAS polymerization in μl-scale reactions, HA templates consisting of a fluorophore-labeled HA tetrasaccharide (HA4) were generated (Chapter 3). A fast, simple and sensitive assay was developed based on fluorophore-assisted carbohydrate electrophoresis (FACE) that was used for quantification and characterization of PmHAS polymerization products. The individual β1,3-glucuronyl-transferase (UA-transferase) and β1,4-N-acetylglucosamine-transferase (NAc-transferase) activities of PmHAS were investigated separately using kinetic studies, where the reaction of an HA oligosaccharide was followed with, respectively, UDP-GlcUA or UDP-GlcNAc in single-step elongations. In Chapter 4, the influence of HA oligosaccharide length (n = 4, 5, 6, 7, 8 and 9) on the polymerization reaction was investigated by one-substrate kinetics, varying only the HA oligosaccharide concentration at saturating UDP-sugar concentration. These reactions followed Michaelis Menten kinetics, although HA oligosaccharides may become inhibiting at elevated concentrations above 6 mM. The observed kcat values increased with increasing HA oligosaccharide length to a constant value at HA6 and HA7. The specificity constant kcat/Km values for HA oligosaccharides in the UA-transferase domain increased at increasing oligosaccharide length, whereas in the NAc-transferase domain kcat/Km values were constant at a low value. This indicates that there are two separate oligosaccharide binding sites of different lengths, one in each transferase domain of PmHAS. In Chapter 4, it was demonstrated that the chain-lenght distribution in PmHAS polymerization reactions can be decreased, and thus improved, by using saturating concentrations of both HA oligosaccharides and UDP-sugars. Chapter 5 describes two-substrate kinetic studies, where in single-step elongations both HA oligosaccharide and one of the UDP-sugars were varied, to investigate the polymerization mechanism of each individual transferase domain in PmHAS. Dead-end inhibition studies and goodness-of-fit parameters were used to distinguish between two-substrate models. From this analysis follows that both transferase domains elongate the UDP-sugar through a sequential mechanism, which is most likely an ordered one. In this proposed mechanism, the UDP-sugar is first bound followed by binding of the HA oligosaccharide, after which first the elongated HA oligosaccharide and then UDP is released. Large differences between Km values for UDP-GlcNAc and UDP-GlcUA, also found in Class I HAS enzymes, suggest that UDP-GlcNAc concentration is involved in the regulation of HAS activity and thus the chain length of hyaluronan products. Structural studies were used to evaluate the results obtained with kinetic studies. In Chapter 4, a structural homology model of PmHAS was built based on crystal structure K4CP chondroitin polymerase in E. coli, which has a high sequence identity of 62% and high sequence homology of 78% with PmHAS. The active sites of PmHAS are structurally related to other glycosyltransferases and this provided information on where the oligosaccharide binding sites could be located. These putative oligosaccharide binding sites differ in size, as was predicted by kinetic studies (Chapter 4). Furthermore, structural similarities between PmHAS, α1,3-galactosyltransferase (α3GT) and β1,4-galactosyltransferase (β4Gal-T1) demonstrated that PmHAS contains in each transferase domain one flexible loop that forms a bridge over the active site. In crystal structures of α3GT and β4Gal-T1, these flexible loops have been shown to change conformation upon binding the UDP-sugar. Based on similarities in kinetic mechanisms and structures between PmHAS, α3GT and β4Gal-T1, it is likely that the flexible loops in PmHAS follow a similar conformational change, which makes the proposed ordered mechanism the only possible mechanism (Chapter 5). In Chapter 6, the knowledge on the PmHAS polymerization mechanism gained in earlier chapters is reviewed and used to create new insights in the polymerization mechanism of Class I HAS enzymes. Both Class I HASs and PmHAS are used in hyaluronan production, and, therefore, the differences and similarities are discussed in Chapter 6. During hyaluronan production, there are many different aspects, such as intrinsic properties of the enzyme, cell metabolism and fermentation reaction conditions, that influence hyaluronan chain length and yield (Chapter 6). Moreover, hyaluronan production systems that are able to produce hyaluronan of desired length are discussed in Chapter 6 and a personal view of how these systems can be improved is presented.


Abstract Guilherme, JPLF, Semenova, EA, Borisov, OV, Kostryukova, ES, Vepkhvadze, TF, Lysenko, EA, Andryushchenko, ON, Andryushchenko, LB, Lednev, EM, Larin, AK, Bondareva, EA, Generozov, EV, and Ahmetov, II. The BDNF-increasing allele is associated with increased proportion of fast-twitch muscle fibers, handgrip strength, and power athlete status. J Strength Cond Res 36(7): 1884–1889, 2022—The brain-derived neurotrophic factor (BDNF) is involved in neurogenesis and formation of regenerated myofibers following injury or damage. A recent study suggested that the BDNF overexpression increases the proportion of fast-twitch muscle fibers, while the BDNF deletion promotes a fast-to-slow transition. The purpose of this study was to evaluate the association between the BDNF gene rs10501089 polymorphism (associated with blood BDNF levels), muscle fiber composition, and power athlete status. Muscle fiber composition was determined in 164 physically active individuals (113 men, 51 women). BDNF genotype and allele frequencies were compared between 508 Russian power athletes, 178 endurance athletes, and 190 controls. We found that carriers of the minor A-allele (the BDNF-increasing allele) had significantly higher percentage of fast-twitch muscle fibers than individuals homozygous for the G-allele (males: 64.3 [7.8] vs. 50.3 [15.8]%, p = 0.0015; all subjects: 64.1 ± 7.9 vs. 49.6 ± 14.7%, p = 0.0002). Furthermore, the A-allele was associated (p = 0.036) with greater handgrip strength in a sub-group of physically active subjects (n = 83) and over-represented in power athletes compared with controls (7.7 vs. 2.4%, p = 0.0001). The presence of the A-allele (i.e., AA+AG genotypes) rather than GG genotype increased the odds ratio of being a power athlete compared with controls (odds ratio [OR]: 3.43, p = 0.00071) or endurance athletes (OR: 2.36, p = 0.0081). In conclusion, the rs10501089 A-allele is associated with increased proportion of fast-twitch muscle fibers and greater handgrip strength, and these may explain, in part, the association between the AA/AG genotypes and power athlete status.