Acquired drug resistance is an increasing challenge in treating cancer with chemotherapy. One mechanism behind this resistance is the increased inflammation that supports the progression and development of cancer that arises because of the drug's presence.
Integrative oncology is the field that focuses on including natural products alongside traditional therapy to create a treatment that focuses on holistic patient well-being. In this in vitro study, we hypothesized that the use of an herbal formulation, consisting of turmeric and green tea, alongside a traditional chemotherapeutic drug, 5-fluorouracil (5-FU), can reduce the expression of two pro-cancer cytokines in breast cancer cells.
Breast cancer cells were cultured and then treated with both 5-FU and the herbal formulation. We conducted enzyme-linked immunosorbent assays (ELISAs) to measure VEGF and TGFβ in the cell culture supernatant. The results clearly demonstrate that the use of the herbal formulation alongside the chemo drug significantly decreases the level of cytokines produced when compared to the levels produced when exposed solely to the chemo drug.
Hence, we conclude that this combination of treatment, based on the principle of integrative oncology, shows potential for reducing the resistance against treatment conferred through increased inflammation. Consequently, this suggests a prospective way forward in improving the efficacy of cancer treatment.


Cell-free protein production is an attractive alternative to cell-based expression. Rapid results, small-volume reactions, irrelevance of protein toxicity, flexibility, and openness of the system are strong points in favor of the cell-free system. However, the in vitro situation lacks the cellular quality control machinery comprising e.g., the translocon for inserting membrane proteins into lipid bilayers, and chaperon-assisted protein degradation pathways. Here, we compare yield and protein quality of the lactate transporter, PfFNT, from malaria parasites when produced in Pichia pastoris yeast, or in an Escherichia coli S30-extract-based cell-free system. Besides solubilization and correct folding, PfFNT requires oligomerization into homopentamers. We assessed PfFNT folding/oligomerization and function by transmission electron microscopy imaging, transport assays, and binding of small-molecule inhibitors. For the latter, we used chromatography of the PfFNT-inhibitor complex with dual-wavelength detection, and biolayer interferometry. Our data show, that PfFNT possesses an intrinsic capability for assuming the correct fold, oligomerization pattern, and functionality during in vitro translation. This competence depended on the detergent present in the cell-free reaction. The choice of detergent further affected purification and inhibitor binding. In conclusion, in the presence of a suitable detergent, cell-free systems are very well capable of producing high quality membrane proteins.


We present the first results on the search for very bright (M AB –21) galaxies at redshift z ~ 8 from the Brightest of Reionizing Galaxies (BoRG) survey. BoRG is a Hubble Space Telescope Wide Field Camera 3 (WFC3) pure-parallel survey that is obtaining images on random lines of sight at high Galactic latitudes in four filters (F606W, F098M, F125W, and F160W), with integration times optimized to identify galaxies at z 7.5 as F098M dropouts. We discuss here results from a search area of approximately 130 arcmin2 over 23 BoRG fields, complemented by six other pure-parallel WFC3 fields with similar filters. This new search area is more than two times wider than previous WFC3 observations at z ~ 8. We identify four F098M-dropout candidates with high statistical confidence (detected at greater than 8σ confidence in F125W). These sources are among the brightest candidates currently known at z ~ 8 and approximately 10 times brighter than the z = 8.56 galaxy UDFy-38135539. They thus represent ideal targets for spectroscopic follow-up observations and could potentially lead to a redshift record, as our color selection includes objects up to z ~ 9. However, the expected contamination rate of our sample is about 30% higher than typical searches for dropout galaxies in legacy fields, such as the GOODS and HUDF, where deeper data and additional optical filters are available to reject contaminants.


The ability of hydroperoxidase activity of soybean lipoxygenase to co-oxidize xenobiotics was examined in the presence of linoleic acid. The guaiacol oxidation rate was proportional to the linoleic acid dioxygenation rate of the enzyme preparation. The tetraguaiacol formation was dependent upon the concentration of guaiacol, linoleic acid and the amount of enzyme. Boiled enzyme was devoid of activity suggesting enzymatic nature of the co-oxidation reaction. Besides guaiacol, benzidine, tetramethyl-p-phenylenediamine, dimethoxybenzidine, 2,2'-azinobis(3-ethyl-benzothiazoline-6-sulfonic acid), p-phenylenediamine and tetramethylbenzidine were oxidized suggesting that the hydroperoxidase activity of lipoxygenase may be a potential pathway of xenobiotic oxidation.


Deep neural networks (DNNs) are emerging as important drivers for GPU (Graphical Processing Unit) usage. Routinely, now, cloud offerings include GPU-capable VMs, and GPUs are used for training and testing DNNs. A popular way to run inference (or testing) tasks with DNNs is to use middleware called a serving system. Tensorflow-Serving (TF-Serving) is an example of a DNN serving system. In this paper, we consider the problem of carefully scheduling multiple concurrent DNNs in a serving system on a single GPU to achieve fairness or service differentiation objectives, a capability crucial to cloud-based TF-Serving offerings. In scheduling DNNs, we face two challenges: how to schedule, and switch between, different DNN jobs at low overhead; and, how to account for their usage. Our system, Olympian, extends TF-Serving to enable fair sharing of a GPU across multiple concurrent large DNNs at low overhead, a capability TF-Serving by itself is not able to achieve. Specifically, Olympian can run concurrent instances of several large DNN models such as Inception, ResNet, GoogLeNet, AlexNet and VGG, provide each with an equal share of the GPU, while interleaving them at timescales of 1-2 ms, and incurring an overhead of less than 2%. It achieves this by leveraging the predictability of GPU computations to profile GPU resource usage models offline, then using these to achieve low overhead switching between DNNs.


To continuously improve jet-engines, it is necessary to precisely predict gas turbine flow fields using computational fluid dynamics (CFD). The results of the simulations are validated with pressure probe measurements. The pressure probe is intended to determine the flow field between the blade rows but as the probe is positioned in the flow passage, it disturbs the flow field. This study investigates the influence of a multi-hole pressure probe on the flow field in a multistage axial air-turbine. To this end, probe measurements are conducted, and the experimental results are compared to the results of CFD simulations. These simulations are done with and without the probe in the flow passage to investigate the effect the probe has on the flow field numerically. The simulations with and without probe are in good agreement for flow areas with low gradients. In areas with high velocity gradients, the probe shifts the vane wake circumferentially and reduces the wake magnitude. The numerical probe measurements agree well with the experimental probe measurements especially in the wake region. Based upon these results, the differences between probe measurements and numerical results are mainly caused by the potential effect of the probe. This effect must be considered in the analysis of experimental data of multi-hole pressure probes.


Background: Intestinotrophic therapies, such as glucagon-like peptide-2 (GLP-2) analogs, may enhance intestinal adaptation and reduce dependence on parenteral nutrition (PN) in patients with intestinal failure associated with short bowel syndrome (SBS-IF). However, because GLP-2 enhances cellular growth, there is concern that GLP-2 analogs may also encourage growth of malignant cells. Aims: To histologically examine the effects of teduglutide, a recombinant human GLP-2 analog, on the mucosa of the small and large intestine for indications of dysplastic transformation. Methods: In a multicenter, prospective, randomized, placebo-controlled study, 83 PN-dependent patients with SBS-IF were monitored for several weeks to ensure optimal and stable PN. Patients were then randomized to receive 24 weeks of placebo (n=16), teduglutide (0.5 mg/kg/d; n=35), or teduglutide (0.10 mg/kg/d; n=32). Results: Biopsies were obtained from 77 patients to yield 390 individual histologic interpretations. After 6 months of treatment, no features of dysplasia were found in any biopsy from the large or small intestine of patients receiving placebo or either dose of teduglutide. New secondary diagnoses, such as eosinophilic colitis or Crohn's disease, were found at a low frequency overall: teduglutide (0.05 mg/kg/d; range, 3.1% to 6.3%); teduglutide (0.10 mg/kg/d, 3.3%); placebo (range, 6.7% to 13.3%). Conclusions: Although this histologic substudy of biopsy samples was not powered to detect differences in occurrence of dysplasia between teduglutide-treated patients and those randomized to placebo, it demonstrated that no dysplasia or other pathologic processes were evident within the intestinal mucosa in the placebo group or the 2 teduglutide groups after 6 months of treatment.


A technique suitable for mapping pi+/- stopping density distributions in patients or phantoms is described. As a position sensitive detector a multiwire proportional chamber with a slit or a hole collimator in front was applied. Results using a water and a Rando phantom are presented for various momenta and momentum band widths of the pi+/- beam. To our knowledge the two-dimensional visualization of a pi- stopping density distribution was realized for the first time.


All forms of tobacco lead to an increased risk of cardiovascular disorders. During the past few decades, the number of people who consume tobacco has increased worldwide because of an overall increase in the global population. It is estimated that close to 80% of the >1.3 billion people who smoke tobacco in the world are in low- and middle-income countries. Smokeless forms of tobacco are also widely consumed in low- and middle-income countries, including chewable and snuffed forms. Lack of targeted and effective strategies to control tobacco consumption contributes to a large burden of cardiovascular disorders in low- and middle-income countries, where cardiovascular disorders have become the leading cause of morbidity and mortality. In this review, we evaluate the epidemiology of tobacco use in low- and middle-income countries and assess the public health policies needed to control tobacco use in such regions for the prevention of cardiovascular disorders and other tobacco-related morbidities and mortality.


BACKGROUND
There has been increasing concern and scrutiny in the use of mesh for certain pelvic organ prolapse procedures. However, mesh erosion was often associated with sites of suture fixation of the mesh to the rectum or vagina. Thus, in response to this finding, we replaced our suture material with absorbable monofilament suture.

OBJECTIVE
The purpose of this study was to compare the rates of mesh-related complications after laparoscopic ventral mesh rectopexy, according to the type of suture used in fixation of mesh.

DESIGN
This was retrospective cohort study.

SETTINGS
This study was performed at a high-volume, tertiary care center. It was conducted using a prospective database including patients who underwent laparoscopic ventral mesh rectopexy over a 7-year period.

PATIENTS
A total of 495 cases were included; 296 (60%) laparoscopic ventral mesh rectopexies were performed using a nonabsorbable suture compared with 199 (40%) with an absorbable suture in a case-matched analysis. In addition, 151 cases of laparoscopic ventral mesh rectopexy with nonabsorbable were matched based on age, sex, and time of follow-up, with an equal number of patients using absorbable monofilament suture.

MAIN OUTCOMES MEASURES
Primary outcome was symptomatic mesh erosion after rectopexy. Secondary outcomes included other mesh-related complications and/or reoperations.

RESULTS
The erosion rate was 2% (6/495) in the nonabsorbable suture group, including 4 erosions into the rectum and 2 into the vagina. There was no erosion in the group with absorbable suture. This difference was maintained after matching: after a median follow-up of 6 (12) months, there was no erosion in the absorbable suture group versus 3.3% erosion (n = 5) in the nonabsorbable suture group (p = 0.03).

LIMITATIONS
This study was limited by its retrospective design.

CONCLUSIONS
Mesh-related complications are reduced using absorbable sutures compared with nonabsorbable sutures when performing laparoscopic ventral mesh rectopexy with synthetic mesh without an increase in rectopexy failures. See Video Abstract at http://links.lww.com/DCR/B49.


OBJECTIVE
To elucidate the clinical features of patients at early stage of severe acute respiratory syndrome (SARS).

METHODS
Fifty-three cases of early SARS were studied retrospectively. The data reviewed included those of epidemiology, clinical manifestations, laboratory investigation and roentgenology.

RESULTS
The patients consisted of 24 men and 29 women, aged 10.85 years (mean 38+/-16.7 years), including 9 infected health-care professionals (17.0%). The mean incubation period was 7.3+/-7.0 days (3.14 days). The onset symptoms were characterized by fever (100%), cough (49.1%), maylgia (24.5%), shortness of breath (20.8%), malaise (17.0%),and diarrhea (5.7%). Routine blood test during the first to the fifth day of the disease revealed WBCs less than 4.0x10(9) /L in 33 patients (62.3%), 4.0-10.0x10(9)/L in 18 patients (34.0%), lymphopenia in 36 patients (67.9%), and PLT less than 100.0x10(9) in 7 patients (13.2%). The main abnormal X-ray finding was single (75.4%) or bilateral (15.1%) localized patchy clouding opacity. The decrease of arterial partial pressure of oxygen occurred in 26 patients (49.1%). The damage of several organs was common, including the elevated ALT or AST in 20 patients (37.7%), elevated BUN or SCR in 6 patients (11.3%) and elevated LDH or CK or HBDH in 23 patients (43.4%).

CONCLUSION
The clinical manifestations of SARS at the early stage were complex. The close monitoring of the blood cell counts, the blood gas analysis and chest radiography might be crucial to the early diagnosis.


ABSTRACT Objective: Describe the lived experience of a grassroots, non-governmental disaster medical team (DMT) through a research lens and share practical lessons learned, based on the DMT's experience to support and inform future response teams. Methods: Forty-five days after Hurricane Maria, a non-governmental DMT provided primary medical care via community based pop-up clinics and home visitations in 5 different areas of Puerto Rico. Observational data, photo images, and debriefing notes were collected and documented in the response team's daily activity log. Field notes were coded using a descriptive coding method and then categorized into 2 domains specific to public health and medical diagnosis. Results: Medical aid was provided to nearly 300 (N = 296) residents. Field note observations identified exhaustion related to living conditions and the exacerbation of underlying conditions such as reactive airway diseases, diabetes, hypertension, and depression due to the compounding effects of multiple post-disaster triggers. During home visitations, feelings of sadness and helplessness were identified secondary to natural disaster trauma and current living conditions. Conclusion: Our non-governmental DMT displayed similar characteristics demonstrated by federal DMTs post natural disaster. A number of strategic lessons learned emerged from the public health intervention important to future non-governmental DMTs.


Atmospheric turbulence studies indicate the presence of self-similar scaling structures over a range of scales from the inertial outer scale to the dissipative inner scale. A measure of this self-similar structure has been obtained by computing the fractal dimension of images visualizing the turbulence using the widely used box-counting method. If applied blindly, the box-counting method can lead to misleading results in which the edges of the scaling range, corresponding to the upper and lower length scales referred to above are incorporated in an incorrect way. Furthermore, certain structures arising in turbulent flows that are not self-similar can deliver spurious contributions to the box-counting dimension. An appropriately trained Convolutional Neural Network can take account of both the above features in an appropriate way, using as inputs more detailed information than just the number of boxes covering the putative fractal set. To give a particular example, how the shape of clusters of covering boxes covering the object changes with box size could be analyzed. We will create a data set of decaying isotropic turbulence scenarios for atmospheric turbulence using Large-Eddy Simulations (LES) and analyze characteristic structures arising from these. These could include contours of velocity magnitude, as well as of levels of a passive scalar introduced into the simulated flows. We will then identify features of the structures that can be used to train the networks to obtain the most appropriate fractal dimension describing the scaling range, even when this range is of limited extent, down to a minimum of one order of magnitude.


By using affinity-chromatography and isoelectric-focusing techniques, several forms of glutathione transferase (GSTs) were resolved from human prostate cytosol. All the three major classes of GST, i.e. Alpha, Mu and Pi, are present in human prostate. However, large inter-individual variation in the qualitative and quantitative expression of different isoenzymes resulted in the samples investigated. The most abundant group of prostate isoenzymes showed acid (pI 4.3-4.7) behaviour and were classified as Pi class GSTs on the basis of their immunological and structural properties. Immunohistochemical staining of Pi class GSTs was prevalently distributed in the epithelial cells surrounding the alveolar lumen. Class Mu GSTs are also expressed, although in small amounts and in a limited number of samples, by human prostate. The major cationic isoenzyme purified from prostate, GST-9.6; (pI 9.6; apparent subunit molecular mass of 28 kDa), appears to be different from the cationic GST alpha-epsilon forms isolated from human liver and kidney as evidenced by its structural, kinetical and immunological properties. This enzyme, which accounts for about 20-30% (on protein basis) of total amount of GSTs, is expressed by only 40% of samples. GST-9.6 has the ability to cross-react in immunoblotting analysis with antisera raised against rat liver GST 2-2, rather than with antisera raised against members of human Alpha, Mu and Pi class GSTs. Although prostate GST-9.6 shows close relationship with the human skin GST pI 9.9, it does not correspond to any other known human GST.


In this study, which aims to examine the effects of non-controllable factors as well as input parameters on the efficiency performances of Turkish Coal Mine Enterprises, eight enterprises within Turkish Coal Enterprises (TCE) were examined. In order to keep the study as up-to-date as possible, data from the latest year (2005) was examined. For each enterprise, the outputs consisted of the amount of the production sold and the total income gained in the corresponding year; the controllable inputs consisted of investment expenditure, overburden stripping and number of staff; and non-controllable inputs consisted of total reserve and low heat values. In order to measure the effects of non-controllable inputs on enterprise efficiency, three-stage modified data envelopment analysis (DEA) model was employed. In the first stage, information concerning the efficiency of the enterprises was gained by using only the controllable inputs and outputs. In the second stage, the effects of non-controllable inputs on controllable inputs in inefficient enterprises were examined. Lastly in the third stage, the new efficiency values were calculated by means of DEA where controllable inputs and outputs modified according to non-controllable inputs were used. Considering the non-controllable inputs as a result of the analyses conducted with three-stage DEA model, it was determined that the average efficiency value of Turkish Coal Enterprises increased from 87.5% to 92.3%.


Today's cloud computing platforms have seen much success in running compute-bound applications with time-varying or one-time needs. In this position paper, we will argue that the cloud paradigm is also well suited for handling data-intensive applications, characterized by the processing and storage of data produced by high-bandwidth sensors or streaming applications. The data rates and the processing demands vary over time for many such applications, making the on-demand cloud paradigm a good match for their needs. However, today's cloud platforms need to evolve to meet the storage, communication, and processing demands of data-intensive applications. We present an ongoing GENI project to connect high-bandwidth radar sensor networks with computational and storage resources in the cloud and use this example to highlight the opportunities and challenges in designing end-to-end data-intensive cloud systems.


SUMMARY : Many investigators have shown that stress suppresses food intake and reduces body weight in rats. The effect of vitamin E on body weight and food intake in rats exposed to stress were studied. Male Sprague Dawley rats (n = 80) were fed with either normal chow, vitamin E deficient diet or vitamin E with or without oral supplementation of either tocopherol, tocotrienol or Tocomin at 60mg/kg body weight. The rats were treated with these different diet regimes for 28 days prior to exposure to stress. Repetitive stress was applied, whereby the rats were restrained 2 hours daily for 4 consecutive days. The body weight and food intake was measured, weekly and after exposure to stress. The findings showed that vitamin E deficiency induced by feeding rats with vitamin E deficient diet for 28 days resulted in significantly lower body weight and food intake compared to the control animals given (normal chow). Supplementation with vitamin E in different forms, tocopherol, tocotrienol or Tocomin to the deficient diet was unable to increase the body weight or food intake, where both parameters were comparable with rats fed with deficient diet alone. It is possible that the dose of the vitamin E given was inadequate to maintain the food consumption and prevent the drop in body weight. Exposure to stress caused a further reduction in both the food intake and body weight in all groups and this suggests that the normal level of vitamin E in normal chow nor the supplementation with tocopherol and tocotrienol at the dose 60mg/kg was able to protect against changes in the body weight and food intake due to stress. We therefore conclude that vitamin E deficiency and stress can reduce food intake and cause a reduction in body weight. Stress can worsen the status of the two parameters and in vitamin E supplementation at 60 mg/kg body weight is not sufficient to prevent the changes in the body weight or food intake due to vitamin E deficiency or stress.


PBRM1 is a novel tumor suppressor gene that can inhibit cancer cell proliferation and predict the outcome of renal cell carcinoma (RCC), but its biological role needs further elucidation. We examined expression of the PBRM1 gene in RCC cell lines and the effect of PBRM1 on cell proliferation and cell cycle in RCC ACHN cells. Microarray processing and analysis was used to explore novel pathways involved in tumorigenesis related to PBRM1 knockdown. PBRM1 was expressed at high levels in RCC ACHN cells and lentivirus-mediated PBRM1 knockdown in these cells caused an increase in the proportion of cells in S phase of the cell cycle and promoted in vitro proliferation and migration. In vivo experiments showed that downregulation of PBRM1 promoted tumorigenesis in nude mice. In pathway gene chip analysis, the chemokine/chemokine receptor interaction pathway showed the greatest difference in gene expression upon PBRM1 knockdown. Protein levels of IL6ST and CCL2 were increased, whereas levels of interleukin (IL)-8, IL-6, and CXCL2 were decreased, in knockdown cells. Re-expression of IL-8 in PBRM1 knockdown ACHN cells could significantly decrease cell proliferation/migration and induced cell arrest in the G2/M phase. These findings indicate that PBRM1 alters cell cycle progression and inhibits proliferation and migration of ACHN cells through the chemokine/chemokine receptor pathway.


Ensemble learning is a methodology that integrates multiple DNN learners for improving prediction performance of individual learners. Diversity is greater when the errors of the ensemble prediction is more uniformly distributed. Greater diversity is highly correlated with the increase in ensemble accuracy. Another attractive property of diversity optimized ensemble learning is its robustness against deception: an adversarial perturbation attack can mislead one DNN model to misclassify but may not fool other ensemble DNN members consistently. In this paper we first give an overview of the concept of ensemble diversity and examine the three types of ensemble diversity in the context of DNN classifiers. We then describe a set of ensemble diversity measures, a suite of algorithms for creating diversity ensembles and for performing ensemble consensus (voted or learned) for generating high accuracy ensemble output by strategically combining outputs of individual members. This paper concludes with a discussion on a set of open issues in quantifying ensemble diversity for robust deep learning.


In dogs, pituitrin increases, and isadrin reduces, the tonicity of coronary arteries. Successive administration of the two agents to rabbits causes functional and metabolic unbalance of the heart, with resultant myocardial necrotic foci in the presence of blood hypercoagulation and heart muscle contractility disordered. The disorder of cardiomyocyte stereo architectonics is an essential element of the pathophysiologic mechanism of small-focal myocardial infarction.


Lucerne (Medicago sativa) has many qualities associated with sustainable agriculture such as nitrogen fixation and high biomass yield. Therefore, there is interest in whether lucerne is a suitable biomass substrate for bioethanol production, and if hydrothermal pretreatment (HTT) of lucerne improves enzymatic convertibility, providing sufficient enzymatic conversion of carbohydrate to simple sugars for ethanol production. The HTT process was optimised for lucerne hay, and the pretreated biomass was assessed by carbohydrate analysis, inhibitor characterisation of liquid phases, and by simultaneous saccharification and fermentation (SSF) of the whole slurry with Cellubrix enzymes and Saccharomyces cerevisiae yeast. The optimal HTT conditions were 205°C for 5 minutes, resulting in pentose recovery of 81%, and an enzymatic convertibility of glucan to monomeric glucose of 74%, facilitating a conversion of 6.2% w/w of untreated material into bioethanol in SSF, which is equivalent to 1,100 litre ethanol per hectare per year.


Abstract I investigated the potential role of intra- and interspecific competition for food in Midland Watersnakes (Nerodia sipedon pleuralis) and Diamond-Backed Watersnakes (Nerodia rhombifer rhombifer) during the summers of 1999 and 2000. Snakes offered prey (juvenile spotted bass, Micropterus punctulatus) at low densities (five fish/enclosure/week) had significantly lower proportional changes in mass than snakes offered prey at high densities (10 fish/enclosure/week). However, differences in mass changes of N. sipedon were not significant at constant relative densities of prey to snakes. Nerodia sipedon and N. rhombifer that were offered 10 fish per week and tested individually had significantly higher mass changes than snakes tested in intraspecific pairs. For snakes maintained in interspecific pairs and offered 10 fish per week, N. sipedon had higher mass changes than N. rhombifer, although the difference was not significant. I lab-tested the potential for exploitation as a mechanism of competition between N. sipedon and N. rhombifer by comparing rates of gastric breakdown after feeding snakes a goldfish (Carassius auratus), forcing regurgitation at six, 12, and 18 h after ingestion, and comparing ash-free dry masses (AFDMs) of the digested fish. Relatively higher AFDMs of digested fish were obtained from N. sipedon than from N. rhombifer at six and 12 hours after ingestion. Thus, the former species exhibited a faster rate of gastric breakdown than the latter. These differences in competitive abilities may potentially contribute to the higher abundance of N. sipedon than N. rhombifer in the upper Pascagoula River system of southeastern Mississippi.


Developing new products and services, which create value for customers in dynamic business environments, is highly challenging. A deep understanding of potential customers and their problems is required before deciding which features or capabilities to develop. In order to gain a better understanding of the problems it is helpful to engage with potential customers, ask them about their pains and listen closely to what they say. Lean and agile product management approaches provide techniques for exploring problems, revealing the underlying problem-related assumptions, and validating problems. Until now, these methods have been mainly used in Business-to-Consumer (B2C) domains. There is a lack of reported experience and knowledge about challenges when applying problem exploration and validation techniques in the Business-toBusiness (B2B) domain. This article presents a case study about a product development effort in a large IT company offering software-intensive products and services in the B2B domain. The objective of the study is to identify the B2B-specific challenges with respect to problem exploration and validation. Results from the case study show that the huge number of various problems and their variations in B2B contexts, partially caused by different company environments, makes it difficult to identify the most relevant problems and to align them with a suitable customer segment. By utilizing an approach that iterates problem exploration and problem validation, it is possible to create a ranked problem list that can support customer segmentation and guide the product development.


Endocrine or pancreatic neuroendocrine tumors (PNET) were first cited in the 1950s; they may be sporadic or associated with hereditary syndromes, benign or malignant, functioning or non-functioning. Nowadays, NF-PNETs are the most frequent and their prevalence ranges from 50% to 91%. In our current series (including 70 cases, 33% malignant, 52 operated) the frequency was 72% as compared to 37% in the historical series.


Context: It has been proved from many epidemiological studies that the inhalation of the radioactive, inert gas radon (222Rn) is the main cause of lungs cancer after smoking. Objective: The survey was conducted to estimate the indoor radon concentration, the annual effective dose rate and the annual dose equivalent rate to the lung. Material and Methods: Altogether 50 dwellings were chosen randomly at 5 different districts of Nepal. The dosimetric measurements were carried out over a period of 3 months using time-integrated passive radon detectors, CR-39 based on type II Solid State Nuclear Track Detector (SSNTD) technique. The type of houses was concrete with plastered walls and mud house. Results: The minimum concentration of radon in the study areas was found to be <20Bq.m-3 and the maximum concentration was 110±20Bq.m-3. Also the corresponding values of annual effective dose and annual equivalent dose to the lung respectively varied from <0.60 to 3.30mSv.y-1 and 0.16—10-7 to 0.88A—10-7 Sv.y-1. The uncertainty was measured at 95% confidence level. Conclusion: The indoor radon concentration varies considerably with the ventilation condition, lifestyle of the people, construction of the dwellings and climate of the areas. The measurements show that the radon concentrations were found to be well below the reference levels of ICRP.
KEYWORDS: Indoor Radon; Annual Effective Dose; CR-39; Ventilation Condition; Dwelling.


An Internet survey was conducted among 511 respondents in Victoria, Australia, to ascertain their support for possible government fruit and vegetable promotion policies. The findings suggest that there is a strong and widespread support for policies which encourage country of origin labelling, local and increased production, subsidies, bans and taxes, and communication campaigns. The respondents' Universalism values (e.g. valuing nature, harmony and beauty) were more pervasive predictors of their opinions than their demographic characteristics. The findings suggest that many Australians hold different views to the prevailing neoliberal views of the political establishment.


Microcystis aentginosa (MA), which is one kind of cyanobacteria, is the primary algal species in Taihu Lake. The MA bloom has a significantly negative effect on the human health and water environment ecosystem. The monitoring and prediction of MA bloom become more and more critical for the security of drinking water source and environment in the Taihu Lake area. In this paper, the percentage of MA was estimated from remote-sensing reflectance via a novel spectral shape genetic optimization algorithm. This algorithm focuses on the shape of remote-sensing reflectance, and it can remove the influence of the amplitude of remote-sensing reflectance from the retrieval result. The accuracy of this optimization algorithm is acceptable according to both simulated and in situ data. The percentage of mean square root (RMSP) of the percentage of the phytoplankton absorption coefficient to the total absorption coefficient at 440 nm [ar (440 nm)] between the retrieved and the simulated is 18.39%. The RMSP of the total absorption coefficient at 440 nm [a (440 nm)] between the retrieved and the simulated is 3.65%. The RMSP of the percentage of MA [Sf] between the retrieved and the simulated is 13.60%. The RMSP of the colored dissolved organic matter (CDOM) absorption coefficient slope [S] between the retrieved and the simulated is 5.89%. The RMSP of the particle backscatter coefficient slope [Y] between the retrieved and the simulated is 30.46%. In Taihu Lake, the RMSPs of ar (440 nm), a (440 nm), Sf , and S between the retrieved and the measured are 36.59%, 35.70%, 19.25%, and 16.80%, respectively. The retrieved percentage of MA (Sf) and Scenedesmus obliquus (1 - Sf) by this model from August 2006, October 2006, to November 2008 indicates the variation trend of algal species in different seasons. This trend accords with the results from previous studies and observations. This paper extends and advances the previous retrieval methods and confirms that the genetic optimization algorithm can be used to retrieve the information of water constituents in the high turbid and eutrophic inland water mass.


Purpose: Intimal hyperplasia is known to promote in-stent restenosis after vascular stent implantation. Although previous studies have presented a variety of evidence that suggests the mechanisms of intimal lesion formation, it is still controversial which factor(s) predominantly contribute to the development of in-stent restenosis. In this study, we hypothesized that heterogenous mechanisms coexist in the same lesion and then assessed the validity with resected whole arteries with in-stent lesions. Methods: Whole arterial specimens with in-stent lesions were surgically resected from five patients who had undergone implantation of a Palmaz-Schatz stent 7 to 19 months previously and were histologically analyzed. For assessment of the pathogenetic heterogeneity of in-stent lesions, we divided each cross section into three parts: the inner intima within 250 μm from the luminal surface (zone A), the area surrounding the stent struts within 250 μm from the strut hole (zone B), and the remaining part of the intimal layer (zone C). We then evaluated cell density, cell replication, and cellular composition in each zone. Cell replication and cellular composition were analyzed with immunohistologic staining with antibodies against proliferating cell nuclear antigen and cell-specific antibodies. Each section was also stained with Alcian blue or Elastica van Gieson method for detection of matrix components. Results: In all samples, the cell density of zone A was significantly higher than that of zone B (P <.05). Proliferating cell nuclear antigen staining results showed significantly higher cell replication in zone A as compared with that in other zones (P <.05). To the contrary, cell-specific immunostaining results revealed marked accumulation of leukocytes, macrophages, and T lymphocytes in zone B (P <.05). Regarding matrix components, proteoglycan was predominantly stained around stent struts and in the inner intima. Conclusion: The data of this study showed that two different pathogenetic processes in different zones possibly contributed to in-stent lesion formation at the same time. One process was an increase of cell number in the inner intima, which was the result of a prolonged increase of cell replication. The other process was accumulation of matrix around stent struts, which was suggested to be linked to infiltration of inflammatory cells in the same zone.


A serious challenge in current Western societies is the increasing number of patients with chronic diseases due to unhealthy lifestyle and the growing number of older people. Currently, more than 52% of the Dutch people have a chronic disease of which at least 33% have multiple diseases. Unfortunately, the number of people with a chronic disease is expected just to increase leading to a higher pressure on the quality of healthcare and rising healthcare costs. Personalised coaching to support patients' self-efficacy on self-management could be a key solution to address these problems. In the last decade, innovative technologies have been developed that focus on self-management of patients. However, this support cannot be fully tailored to the patient as these apps usually do not take into account patients' behaviour. Therefore, the development of e-supporter has been started in September 2018. E-supporter is an element of the Centre for Care Technology Research (CCTR) e-manager project that aims to improve the quality of life and perceived quality of care in patients with chronic conditions. The concept of e-supporter has been based on literature research, expert meetings and pilot studies. E-supporter will integrate various e-coaching apps that help patients with COPD, asthma and diabetes mellitus type 2 (DM2) to self-manage their disease. These apps have been developed by Maastricht University Medical Centre (MUMC+), TNO, University of Twente and commercial parties. E-supporter will promote pursuing a personalised treatment plan in daily life by using an intelligent interface that uses information from the ABCC tool, the various integrated e-coaching apps and daily health behaviour, thoughts and moods of the patient. The ABCC tool assesses the disease state, disease burden, and personalized goals that the patient has set together with the healthcare professional during consultation. Tailored coaching content will be developed based on the I-Change model and prediction models that inform the patient of expected consequences and benefits of their behaviour. In addition, e-supporter also helps healthcare professionals to be better informed about patients to enhance personalised care. This all will lead to healthcare that is more efficient, cost-effective, sustainable and of high quality.


Single mode silicon-on-insulator rib waveguides offer a weak lateral confinement, which makes it difficult to design high-performance multimode interference couplers (MMIs) based on these waveguides. Here, a complete design procedure for single etch step MMIs with tapered rib access waveguides is presented, which yields low excess loss (0.1 dB) and good imbalance (0.02 dB). Furthermore, polarization dependence is low, and high fabrication tolerances are achieved, especially with respect to etch depth.


Periodic arrays of resonant shunted piezoelectric patches are employed to control the wave propagation in a two-dimensional (2D) acoustic metamaterial. The performance is characterized by the finite element method. More importantly, we propose an approach to solving the conventional issue of the nonlinear eigenvalue problem, and give a convenient solution to the dispersion properties of 2D metamaterials with periodic arrays of resonant shunts in this article. Based on this modeling method, the dispersion relations of a 2D metamaterial with periodic arrays of resonant shunted piezos are calculated. The results show that the internal resonances of the shunting system split the dispersion curves, thereby forming a locally resonant band gap. However, unlike the conventional locally resonant gap, the vibrations in this locally resonant gap are unable to be completely localized in oscillators consisting of shunting inductors and piezo-patches.


MUSLIM Institute UK Chapter organised a Round Table Discussion "Challenges to Implementation of Climate Change Policies" on Thursday Jan 23, 2020; at the Record Hall London. Dr. Yves Plancherel Lecturer Grantham, InstituteClimate Change & the Environment and Dr. Iqbal Hussain President MUSLIM Institute UK Chapter shared their views on the occasion. Mr. Rao Ali Khan, Research Associate MUSLIM Institute gave the opening remarks. Mr. Ali Iftikhar Programme Manager, The MUSLIM Debate, moderated the proceedings of the discussion.


In Reply .—There are a number of points in DeSanto's letter that require comment. We are unsure of DeSanto's intent in commenting on the selection of patients described in our article.1 Our article concerned early supraglottic carcinoma that we defined as stage T1 and T2 NO MO, and we naturally sought to compare patients so staged on clinical examination with those similarly staged and categorized in other reports. At no point did we state that "patients who in the beginning do not do well with irradiation are excluded and placed in a separate category," and in fact we did not do this. 2. The confusion about the number of patients in the Mayo Clinic series with positive neck nodes arose from our misinterpretation of the statement by Coates et al2 "that the 71 patients with NO cervical nodes clinically who were treated by initial neck dissection included two who at operation


Mixed linkage (1→3),(1→4)-β-d-glucan (BG) is a soluble fibre available from oat and barley grains that has been gaining interest due to its health-promoting role in cardiovascular diseases and its ability to modulate the glycaemic index which is beneficial for people with diabetes. This study investigates the effect of three purified barley BGs, with different molecular weight and block structure, on faecal bile acid excretion in hypercholesterolaemic rats. Wistar rats (48 male) were divided in four groups: Control group fed with the cellulose-rich diet (CON); Glucagel group fed with the commercial BG (GLU, 100 kDa), and rats fed with low molecular weight BG (LBG, 150 kDa) and medium molecular weight BG (MBG, 530 kDa). The bile acid profiles of rat faecal samples were measured using gas chromatography-mass spectrometry (GC-MS). A metabolite profiling approach led to the identification of 7 bile acids and 45 other compounds such as sterols, fatty acids and fatty alcohols. Subsequent application of ANOVA-simultaneous component analysis and Principal Component Analysis revealed that all three BG diets increased bile acid faecal excretion compared to the control group. The bile acid excretion was found to be different in all three BG diets and the MBG group showed a significantly higher level of faecal secondary bile acids, including deoxycholic acid, hyodeoxycholic acid, and lithocholic acid. We hypothesise that the hydrophobic surface of the secondary bile acids, which are known to cause colon cancer, has high affinity to the hydrophobic surfaces of cellulosic blocks of the BG. This in vivo study demonstrates that the molecular weight and/or block structures of BG modulate the excretion of secondary bile acids. This finding suggests that developing diets with designed BGs with an optimal molecular structure to trap carcinogenic bile acids can have a significant impact on counteracting cancer and other lifestyle associated diseases.


Prognostics performance evaluation has gained significant attention in the past few years. As prognostics technology matures and more sophisticated methods for prognostic uncertainty management are developed, a standardized methodology for performance evaluation becomes extremely important to guide improvement efforts in a constructive manner. This paper is in continuation of previous efforts where several new evaluation metrics tailored for prognostics were introduced and were shown to effectively evaluate various algorithms as compared to other conventional metrics. Specifically, this paper presents a detailed discussion on how these metrics should be interpreted and used. Several shortcomings identified, while applying these metrics to a variety of real applications, are also summarized along with discussions that attempt to alleviate these problems. Further, these metrics have been enhanced to include the capability of incorporating probability distribution information from prognostic algorithms as opposed to evaluation based on point estimates only. Several methods have been suggested and guidelines have been provided to help choose one method over another based on probability distribution characteristics. These approaches also offer a convenient and intuitive visualization of algorithm performance with respect to some of these new metrics like prognostic horizon and alpha-lambda performance, and also quantify the corresponding performance while incorporating the uncertainty information.


Abstract Recent findings are reviewed from observations in the field on the generation of the δ13C signal in shells of live (Rose Bengal stained) benthic foraminifera, and end up with implications for the interpretation of fossil signatures. The δ13C values of calcite tests of preferentially epifaunal foraminifera principally reflect the δ13C of dissolved inorganic carbon (DIC) of ambient seawater, whereas infaunal species record a porewater signal, both with an offset from equilibrium calcite. Species occupying the deepest average living depth in the sediment usually exhibit lowest δ13C test values, but δ13C values of conspecific specimens at a single site do not decrease with increasing subbottom depth and decreasing porewater δ13CDIC. Organic carbon fluxes to the sediment surface are generally reflected by infaunal species such that lowered δ13C values coincide with high fluxes, but even strictly epifaunal species may reflect seasonally pulsed phytodetritus supply by depleted test δ13C. In high-productivity environments, however, where dissolved oxygen and sedimentary carbonate contents are low, benthic foraminiferal tests show 13C enrichment probably due to carbonate-ion undersaturation. Ontogenetic increase in δ13C values of certain infaunal species suggests a slow-down of metabolic rates during test growth and decreasing fractionation with age. At sites of active methane discharge δ13C values of infaunal species reflect low pore water δ13CDIC values, documenting active methane release in the sediment, whereas lowered δ13C values of strictly epifaunal species are most probably the result of incorporation of 13C depleted methanotrophic biomass.


Abstract. High mountains divide Costa Rica, Central America, into two main climate regions, the Pacific and Caribbean slopes, which are lee and windward, respectively, according to the North Atlantic trade winds – the dominant wind regime. The rain over the Pacific slope has a bimodal annual cycle, having two maxima, one in May–June and the other in August-September-October (ASO), separated by the mid-summer drought in July. A first maximum of deep convection activity, and hence a first maximum of precipitation, is reached when sea surface temperature (SST) exceeds 29 °C (around May). Then, the SST decreases to around 1 °C due to diminished downwelling solar radiation and stronger easterly winds (during July and August), resulting in a decrease in deep convection activity. Such a reduction in deep convection activity allows an increase in down welling solar radiation and a slight increase in SST (about 28.5 °C) by the end of August and early September, resulting once again in an enhanced deep convection activity, and, consequently, in a second maximum of precipitation. Most of the extreme events are found during ASO. Central American National Meteorological and Hydrological Services (NMHS) have periodic Regional Climate Outlook Fora (RCOF) to elaborate seasonal predictions. Recently, meetings after RCOF with different socioeconomic stakeholders took place to translate the probable climate impacts from predictions. From the feedback processes of these meetings has emerged that extreme event and rainy days seasonal predictions are necessary for different sectors. As is shown in this work, these predictions can be tailored using Canonical Correlation Analysis for rain during ASO, showing that extreme events and rainy days in Central America are influenced by interannual variability related to El Nino-Southern Oscillation and decadal variability associated mainly with Atlantic Multidecadal Oscillation. Analyzing the geographical distribution of the ASO-2010 disaster reports, we noticed that they did not necessarily agree with the geographical extreme precipitation event distribution, meaning that social variables, like population vulnerability, should be included in the extreme events impact analysis.


Shiga toxin-producing Escherichia coli (STEC) O157:H7 is a public health threat and outbreaks occur worldwide. Here, we investigate genomic differences between related STEC O157:H7 that caused two outbreaks, eight weeks apart, at the same restaurant. Short-read genome sequencing divided the outbreak strains into two sub-clusters separated by only three single-nucleotide polymorphisms in the core genome while traditional typing identified them as separate phage types, PT8 and PT54. Isolates did not cluster with local strains but with those associated with foreign travel to the Middle East/North Africa. Combined long-read sequencing approaches and optical mapping revealed that the two outbreak strains had undergone significant microevolution in the accessory genome with prophage gain, loss and recombination. In addition, the PT54 sub-type had acquired a 240 kbp multi-drug resistance (MDR) IncHI2 plasmid responsible for the phage type switch. A PT54 isolate had a general fitness advantage over a PT8 isolate in rich medium, including an increased capacity to use specific amino acids and dipeptides as a nitrogen source. The second outbreak was considerably larger and there were multiple secondary cases indicative of effective human-to-human transmission. We speculate that MDR plasmid acquisition and prophage changes have adapted the PT54 strain for human infection and transmission. Our study shows the added insights provided by combining whole-genome sequencing approaches for outbreak investigations.


This paper presents field tests of challenging flight applications obtained with a new family of lightweight low-power INS/GNSS (inertial navigation system/global satellite navigation system) solutions based on MEMS (micro-electro-mechanical- sensor) machined sensors, being used for UAV (unmanned aerial vehicle) navigation and control as well as for aircraft motion dynamics analysis and trajectory surveying. One key is a 42+ state extended Kalman-filter-based powerful data fusion, which also allows the estimation and correction of parameters that are typically affected by sensor aging, especially when applying MEMS-based inertial sensors, and which is not yet deeply considered in the literature. The paper presents the general system architecture, which allows iMAR Navigation the integration of all classes of inertial sensors and GNSS (global navigation satellite system) receivers from very-low-cost MEMS and high performance MEMS over FOG (fiber optical gyro) and RLG (ring laser gyro) up to HRG (hemispherical resonator gyro) technology, and presents detailed flight test results obtained under extreme flight conditions. As a real-world example, the aerobatic maneuvers of the World Champion 2016 (Red Bull Air Race) are presented. Short consideration is also given to surveying applications, where the ultimate performance of the same data fusion, but applied on gravimetric surveying, is discussed.


Retiring land from crop production under the Conservation Reserve Program is expensive and often unnecessary. Instead, more emphasis should be placed on providing incentives for farmers to reduce erosion by adopting better cropping practices. This would cost less than current programs and allow more land to be enrolled, thereby conserving as much or more soil.


Non-small cell lung cancers (NSCLC) harboring molecular oncogenic activations (e.g., EGFR, MET, BRAF mutations, ALK, ROS1 fusions) represent a peculiar subgroup of disease. Indeed, the availability of targeted agents deeply impacts on the prognosis of patients suffering from these tumors. Moreover, the sequential administration of specific inhibitors allows more and more prolonged survival (1-5). Besides EGFR-driven lung cancers, depending on the detection of T790M mutation to switch to osimertinib when resistance to first-line targeted therapy occurs, ALK-positive disease is an emblematic example of the clinical success of sequential inhibitors (6).


While obesity is a major risk factor for preeclampsia (PE), the mechanisms whereby obesity increases the risk for developing pregnancy-induced hypertension are unclear. Since blood pressure regulation during gestation relies greatly on the nitric oxide (NO) system, we aimed to determine the effects of a HFD on blood pressure and fetal outcomes in pregnant rats treated with NG-nitro-L-arginine methyl ester (L-NAME), a non-specific inhibitor of NO synthases. Twelve-week-old Sprague-Dawley female rats were fed a normal diet (ND, 13% fat kcal) or a HFD (40% fat kcal) ad libitum. Body weight (BW) and total fat mass (FM, measured by EchoMRI) were recorded weekly. After 9 weeks of diet treatment, rats were allowed to breed. On gestation day (GD) 14, L-NAME at the concentration 100 mg/L was added to the drinking water of a sub-group of animals (ND + water, n=5; ND + L-NAME, n=6; HFD + water, n=18; HFD + L-NAME, n=16). On GD 19, mean arterial pressure (MAP) was assessed consciously via carotid catheters. Animals were then euthanized and tissues were harvested. Initial BW and FM were similar in ND + water, ND + L-NAME, HFD + water, and HFD + L-NAME (BW: 239.5±4.1 vs. 241.2±4.8 vs. 238.2±2.5 vs. 241.4±2.5 g and FM: 20.4±2.9 vs. 17.9±2.2 vs. 18.2±1.8 vs. 17.4±2.0 g, respectively). By the end of the study, HFD had no effects on BW and FM in pregnant rats (BW: 472.3±5.2 vs. 468.0±10.1 vs. 461.6±12.2 vs. 462.4±8.9 g and FM: 97.5±2.4 vs. 87.3±9.3 vs. 103.3±7.3 vs. 97.5±6.0 g, respectively). Although MAP was elevated in L-NAME treated pregnant rats, HFD did not alter MAP or exacerbate the effect of L-NAME on MAP (106.6±5.0 vs. 131.3±4.9 vs. 116.0±2.7 vs. 130.2±2.8 mmHg, respectively; P<0.05). Neither HFD nor L-NAME affected litter size (13.0±0.8 vs. 13.2±1.2 vs. 12.0±1.0 vs. 12.1±0.8 number of fetuses per rat, respectively). However, HFD reduced fetal weight equally in water and L-NAME treated pregnant rats (2.2±0.0 vs. 2.2±0.1 vs. 2.1±0.0 vs. 2.0±0.0 g, respectively; P<0.05). In summary, while HFD had a detrimental effect on fetal weight, it had no effect on blood pressure regulation during pregnancy.


Tbx6 was shown to be a T-box transcription factor expressed in the primitive streak and presomitic mesoderm of the developing mouse embryo; null mutations in Tbx6 resulted in ectopic neural tube formation in place of posterior somites and embryonic lethality. However nothing was known about expression, transcriptional activity, or downstream targets of Tbx6 protein. Using antibodies generated against Tbx6, Tbx6 was confirmed to be a 58 kDa protein in vivo, and Tbx6 protein and mRNA have similar spatial and temporal expression patterns. T-box proteins were defined by the presence of the T-domain, the DNA binding region. Given the conservation of the T-domain, it was not surprising that many of the characterized T-box binding sites were also somewhat conserved. Therefore, I first demonstrated that Tbx6 recognized the T palindromic consensus sequence and half-site sequence in vitro and then determined that the Tbx6 consensus binding site was 5'- AGGTGTBRNNN -3' using a PCR-based binding site selection assay. Using luciferase reporter assays in cell culture, Tbx6 was determined to be a weak transcriptional activator. Lastly, initial studies with T and Tbx6 suggested that these T-box proteins do not synergistically activate a luciferase reporter.In other work, the spontaneous mutation rib-vertebrae was determined to be a Tbx6 hypomorphic mutation due to an insertion of 185 bp into a Tbx6 enhancer. Finally, I also sought to understand how the Notch signaling pathway and Tbx6 interacted. The Notch transcription factor, RBP-J?, was demonstrated to control the maintenance of Tbx6 in the PSM. Furthermore, Tbx6 bound to several putative binding sites in vitro within a previously known mesodermal Dll1 enhancer. These results suggested that Notch signaling functions upstream and downstream of Tbx6. The work described in this thesis used a variety of in vivo and in vitro approaches, molecular and biochemical, to gain further understanding into how Tbx6, a member of a large family of transcription factors, functions in the context of a developing embryo in the presence of other family members to regulate the expression of target genes.


We study mechanisms contributing to proton precipitation from the ring current during the May 14–16, 1997, geomagnetic storm. This storm was caused partly by Bz< 0 fields in the sheath region behind an interplanetary shock and partly by the magnetic cloud driving the shock. The storm was characterized by a maximum Kp=7− and a minimum Dst=−115 nT and had a distinctive two-phase decay related to the passage of the ejection at the Earth. We model the ring current development caused by adiabatic drifts and losses due to charge exchange, Coulomb collisions, wave-particle interactions, and atmospheric collisions at low altitudes. The nightside magnetospheric inflow is simulated using geosynchronous Los Alamos National Laboratory data, whereas the dayside free outflow corresponds to losses through the dayside magnetopause. We calculate the equatorial growth rate of electromagnetic ion cyclotron waves with frequencies between the oxygen and helium gyrofrequencies and their integrated wave gain as the storm progresses. The regions of maximum wave amplification compare reasonably well to satellite observations. A time-dependent global wave model is constructed, and the spatial and temporal evolution of precipitating proton fluxes during different storm phases is determined. We find that the global patterns of proton precipitation are very dynamic: located at larger L shells during prestorm conditions, moving to lower L shells as geomagnetic activity increases during storm main phase, and receding back toward larger L shells with storm recovery. However, the most intense fluxes are observed along the duskside plasmapause during the main and early recovery phase of the storm and are caused by plasma wave scattering. This study is relevant to the analysis of the anticipated new data sets from the Imager for Magnetopause-to-Aurora Global Exploration (IMAGE) and Thermosphere Ionosphere Mesosphere Energetics Dynamics (TIMED) missions.


The post-translational modification of proteins with ubiquitin is a dynamic multifaceted process affecting all aspects of eukaryotic cellular biology. The complexity of ubiquitin modifications arises from their ability to form architecturally distinct polyubiquitin chains1-3. Despite our understanding of the importance of these signals, we currently lack tools and methods to study them. Here we describe an approach, termed Ub-clipping, which provides unprecedented insight into ubiquitin chain architecture. This protocol is related to our recent Nature paper titled, "Insights into ubiquitin chain architecture using Ub-clipping". This technology takes advantage of an engineered viral protease, Lbpro*, which 'clips' ubiquitin such that the information on the site of modification is retained and the remaining ubiquitin and substrate polypeptides are kept intact. The goal of this protocol is to allow researchers to efficiently adapt our new technology to their proteomic workflows. We anticipate this method will continue to shed light on the architecture of ubiquitin signals, and therefore further our understanding of the ubiquitin code across a broad spectrum of biological systems.


Impact damage of prestressed concrete bridge girders was studied through field inspections and laboratory tests of a damaged girder. Nondestructive techniques for evaluating the extent of damage and the quality of repairs were examined. Various materials and procedures for repairing damage to the concrete and the strands were considered. A prestressed concrete bridge girder, damaged by impact from an overheight vehicle, was removed from a bridge in Austin, Texas. The damaged girder was transported to the laboratory for evaluation and repair. Several nondestructive methods were studied to evaluate the effectiveness of each in assessing the extent of concrete damage resulting from overheight vehicle impact. The surface hardness of the damaged girder was measured using a rebound hammer. Impact echo and spectral analysis of surface waves techniques were used to assess the extent of damage. All three methods were also used to evaluate the effectiveness of the concrete repairs that were undertaken. Several classes of premanufactured patch materials were used to repair the damaged concrete girder. Materials consisted of cast-in-place concrete and hand-applied mortars. Cast-in-place materials were either magnesium-phosphate based or portland-cement based. The mortars were either latex-modified or fiber-reinforced, silica fume modified. Preload was applied to the girder, the damaged concrete was replaced and allowed to cure, and the preload was removed. Static loads were applied to investigate the flexural characteristics of the repaired girder. Internal prestressing strand splice techniques were used to repair intentionally damaged strands of the same prestressed girder. Four different types of splice hardware were installed and evaluated. Each splice was tested to failure separately in a test machine to evaluate the strength and critical components of each assembly. Finally, the results were used to suggest a procedure for rapid initial assessment of damage. The procedure should allow field personnel to distinguish between various types and locations of impact damage and to determine the course of action to be taken regarding the evaluation, repair, or replacement of an impact-damaged girder.


Citric acid (CA), as the most important platform compound, has attracted much attention because of its broad applications in many areas. Here, we constructed a segmentation fermentation process which effectively separated cell growth and CA production. Through a pellet-dispersion strategy, the CA yield decline caused by the mycelium structure of Aspergillus niger was solved. In particular, CA production was significantly increased from 70.3 g L−1 to 97.0 g L−1. Furthermore, the segmentation fermentation conditions were optimized to improve the CA production. Evidence showed that the process was stable during ten batches of recycling fermentation in 5 L five-conjoined-fermenters, from which the CA yield even increased by 1.4 g L−1 (by 1.26%) compared with the control. All of these results confirm that the strategy could enhance productivity and avoid the traditional long process (about 30 days) of seed culturing (including spore preparation). It could be also applied in other fermentation industries involving filamentous fungi.


Tamoxifen (TAM) is widely used in the treatment of hormone receptor-positive breast cancer. TAM is metabolized into the active secondary metabolite endoxifen (ENDO), primarily by CYP2D6. We aimed to investigate the effects of an African-specific CYP2D6 variant allele, CYP2D6*17, on the pharmacokinetics (PK) of TAM and its active metabolites in 42 healthy black Zimbabweans. Subjects were grouped based on CYP2D6 genotypes as CYP2D6*1/*1 or *1/*2 or *2/*2 (CYP2D6*1 or *2), CYP2D6*1/*17 or 2*/*17, and CYP2D6*17/*17. PK parameters for TAM and three metabolites were determined. The pharmacokinetics of ENDO showed statistically significant differences among the three groups. The mean ENDO AUC0-∞ in CYP2D6*17/*17 subjects was 452.01 (196.94) h·*ng/mL, and the AUC0-∞ in CYP2D6*1/*17 subjects was 889.74 h·ng/mL, which was 5-fold and 2.8-fold lower than in CYP2D6*1 or *2 subjects, respectively. Individuals who were heterozygous or homozygous for CYP2D6*17 alleles showed a 2- and 5-fold decrease in Cmax, respectively, compared to the CYP2D6*1 or *2 genotype. CYP2D6*17 gene carriers have significantly lower ENDO exposure levels than CYP2D6*1 or *2 gene carriers. Pharmacokinetic parameters of TAM and the two primary metabolites, N-desmethyl tamoxifen (NDT) and 4-hydroxy tamoxifen (4OHT), did not show any significant difference in the three genotype groups. The African-specific CYP2D6*17 variant had effects on ENDO exposure levels that could potentially have clinical implications for patients homozygous for this variant.


Fields of generalised power series (or Hahn fields), with coefficients in a field and exponents in a divisible ordered abelian group, are a fundamental tool in the study of valued and ordered fields and asymptotic expansions. The subring of the series with non-positive exponents appear naturally when discussing exponentiation, as done in transseries, or integer parts. A notable example is the ring of omnific integers inside the field of Conway's surreal numbers.
In general, the elements of such subrings do not have factorisations into irreducibles. In the context of omnific integers, Conway conjectured in 1976 that certain series are irreducible (proved by Berarducci in 2000), and that any two factorisations of a given series share a common refinement.
Here we prove a factorisation theorem for the ring of series with non-positive real exponents: every series is shown to be a product of irreducible series with infinite support and a factor with finite support which is unique up to constants. From this, we shall deduce a general factorisation theorem for series with exponents in an arbitrary divisible ordered abelian group, including omnific integers as a special case. We also obtain new irreducibility and primality criteria.
To obtain the result, we prove that a new ordinal-valued function, which we call degree, is a valuation on the ring of generalised power series with real exponents, and we formulate some structure results on the associated RV monoid.


We derive the recent star formation histories (SFHs) of 23 active dwarf galaxies using Hubble Space Telescope observations from the Legacy Extragalactic UV Survey. We apply a color–magnitude diagram (CMD) fitting technique using two independent sets of stellar models, PARSEC-COLIBRI and MIST. Despite the nonnegligible recent activity, none of the 23 star-forming dwarfs show enhancements in the last 100 Myr larger than three times the 100 Myr average. The unweighted mean of the individual SFHs in the last 100 Myr is also consistent with a rather constant activity, irrespective of the atomic gas fraction. We confirm previous results that for dwarf galaxies, the CMD-based average star formation rates (SFRs) are generally higher than the FUV-based SFRs. For half of the sample, the 60 Myr average CMD-based SFR is more than two times the FUV SFR. In contrast, we find remarkable agreement between the 10 Myr average CMD-based SFR and the Hα-based SFR. Finally, using core helium-burning stars of intermediate mass, we study the pattern of star formation spatial progression over the past 60 Myr and speculate on the possible triggers and connections of the star formation activity with the environment in which these galaxies live. Approximately half of our galaxies show spatial progression of star formation in the last 60 Myr and/or very recent diffuse and off-center activity compared to RGB stars.


Objective: Ovarian adenosarcoma is a very rare tumour for which treatment options vary. We will consider the option of optimal cytoreductive surgery followed by adjuvant chemotherapy consisting of ifosamide (mesna) and adriamycin to prevent systemic metastasis, and will observe the role of serial CA-125 levels as a follow-up marker. Case report: We report a case of ovarian adenosarcoma in a 38-year-old woman presenting with abdominal pain, distention due to massive ascites. She had undergone total abdominal hysterectomy 8 months previously for abnormal uterine bleeding. She underwent paracentesis followed by optimal cytoreductive surgery. A post-operative histopathologic diagnosis of primary adenosarcoma was confirmed. She was assigned a stage III C cancer. She received five cycles of ifosamise (mesna) and adriamycin and is on follow-up with serial CA-125 levels. There is no evidence of recurrence clinically, biochemically, or radiologically for more than 12 months. Conclusion: Multimodality treatment comprising optimal cytoreductive surgery followed by ifosamide (mesna) and adriamycin-based chemotherapy may be an option for treatment of these aggressive tumours. Follow-up with serial CA-125 values in advanced stage adenosarcoma of the ovary is a novel observation which needs to be researched.


All transfer applicants must meet the following requirements to be considered for admission: • Complete a minimum of 60 CSU-transferable semester units. • Complete General Education (GE) requirements in written communication, oral communication, critical thinking, and mathematics with a "C" or higher in each course. • Earn a minimum 2.0 cumulative CSU-transferable GPA. Applicants must meet this GPA at the time of application and must maintain the GPA prior to transfer. • Be in good standing at the last college or university attended. Applicants who meet the requirements listed above will be ranked based on the completion of lower division General Education and preparation for the major coursework. Out-of-service area applicants will be selected based on a GPA ranking that may be higher than the major GPA. Visit www.sdsu.edu/admissions for details.


In infrastructure and industrial plants the rapid growth creating environmental issues like pollution (Air, Water, Noise), climate change, malfunctioning and has greatly consequence for the requirement of an, operationally adaptable, efficient, cheap and smart monitoring systems. In this context where combination of many challenges of computer science, wireless communication and electronics; the Smart Sensor Networks are an emerging field of research. In this paper a solution to monitor the air and noise pollution levels in industrial environment or by using wireless embedded computing system a particular area of interest is proposed. The technology like Internet of Things (IoT) is included in the form of solution which is outcome of merged field of computer science and electronics. For monitoring the fluctuation of parameters like noise and air pollution levels from their normal levels in this case the sensing devices are connected to the embedded computing system. For the requirement of continuous monitoring, controlling and behavior analysis this model is adaptable and distributive for any infrastructural environment. The working appearance of the proposed model is evaluated using prototype implementation, consisting of AVR UNO board, sensor devices and MATLAB with AVR hardware support package. For two or three parameters like noise, CO and radiation levels the implementation is tested with respect to the normal behavior levels or given specifications which provide a monitoring over the pollution control to make the environment smart and ecofriendly. The basic mission of the Air Quality Planning and Standards is to preserve quality of air .The level of pollution in air can be measured by measuring the pollutants such as humidity level, temperature level, dust level, CO level, smoke level etc present in the air of that area. Here we propose an air quality pollution monitoring system that allows us to monitor and check live air quality in a particular areas through IoT. With the fast growing technology, it would be great to get to know about our surrounding weather parameters in this widely connected environment of internet when one can easily access the rarest and the farthest information at one's own fingertips. This project is based on IoT (Internet of Things), which is an emerging field in which all the devices are connected to a channel made by self (private channel). The channel is used to view the weather parameters with unique API key of channel of a particular user. Every channel has both Read and Write API keys to get the access. Wi-Fi module, temperature, humidity, gas, and dust sensors are interfaced with the Xmega 2560. The user is prompted to provide the API key of channel. ESP8266-01 reads the key and sends it to the Xmega 2560. If the key is matched, then the data transmission can be carried out between the channel and the microcontroller. The module is connected to the Wi-Fi through some AT Commands.


OBJECTIVE
To investigate the role of phospholipid transfer protein (PLTP) in cigarette smoke extract (CSE)-induced apoptosis of rat alveolar type II cells (RLE-6TN) in vitro.

METHODS
Rat alveolar epithelial cell line RLE-6TN were transfected with a small interfering RNA (siRNA) targeting PLTP prior to exposure to different concentrations of CSE for 24 or 48 h. The morphological changes of the apoptotic cells were observed by fluorescence microscopy with Hochest staining, and the cell apoptosis rate was measured with flow cytometry. The expression level of PLTP and caspase-3 activity in the cells were examined with Western blotting.

RESULTS
Exposure to CSE significantly increased the cell apoptosis rate from (1.68∓0.098)% to (18.663∓0.964)% (P<0.001). Hoechst staining revealed distinct apoptotic changes in CSE-treated cells, which showed increased PLTP expression and caspase-3 activity. PLTP knockdown with the specific siRNA partly suppressed the SCE-induced enhancement of caspase-3 activity in the cells.

CONCLUSION
PLTP may play a role in CSE-induced apoptosis of rat alveolar cells in vitro.


This paper examines the nexus of disaggregated energy consumption and industrial output in Pakistan. The annual time series data over the period 1990-2019 has been taken for current research. ARDL technique has been employed for empirical analysis. The results show that oil consumption, electricity consumption and gas consumption are positively and significantly connected with the industrial output in long run. Similarly, trade openness, labour and capital also have the same association with the industrial output and have significant outcomes in the long run. The results of Granger causality show that there exists a unidirectional causality from electricity consumption to industrial output. The study concludes that oil, gas and electricity are contributing a large share in industrial growth so that it would be made an effort to install the plants relevant with these energy sources to meet the affordable demand in the industry sector.


In this communication, we report a new method for the isolation of betulin, a triterpenoid with interesting pharmacological activities, from birch outer bark. Remarkably high purity betulin raw extracts were obtained, ca. 95 wt%, through microwave assisted extraction with limonene. This saves time and energy when compared to the conventional methods.


Purpose: To develop two new types of clinical feedback for final year medical students using OSCE mark sheets and to evaluate their effectiveness, cost-effectiveness and student satisfaction in a randomized trial. Methods: A randomized trial was conducted with two groups (Cohort A and B) of students (n = 350) at the University of Birmingham (UK) participating in a two stage Objective Structured Clinical Examination (OSCE) (November 2011 and April 2012). Students were randomly assigned to receive one of three feedback interventions (skills-based, station-based, or both) after the November OSCE. Multivariate regression analysis was used to test if feedback intervention was a significant predictor of April OSCE score, while controlling for November OSCE score. Secondary outcomes were cost-effectiveness and student satisfaction. Results: Feedback group was not a significant predictor of April scores for Cohort B. In Cohort A, the station-based group did better than the group who received both types of feedback (2.8%, 95% CI 0.4% to 5.2%, p = 0.022). There was no difference between the skills-based and station-based groups. The cost of providing the station-based feedback was double of that for the skills-based. Questionnaires were received from 245 students (70%). Students who received both types of feedback were the most satisfied, followed by those in the station-based group. Conclusion: There was no consistent difference in effectiveness across the three trial groups. Students tended to prefer station-based feedback over skills-based feedback, but students found elements of the standard feedback more helpful than the feedback evaluated in this trial.


This thesis examines the long--run behaviour of both differential and difference, deterministic and stochastic linear Volterra equations.
Firstly we consider a stationary autoregressive conditional heteroskedastic (ARCH) process of order infinity. This type of process is used in time series analysis due to its non-constant conditional variance. In describing the extent of the dependence of the current values of the process upon past values we are led to the study of the autocovariance function. Necessary and sufficient conditions are established for the autocovariance function to lie in a particular class of slowly decaying (subexponential) sequences.

We develop sharp conditions for solutions of linear Volterra summation equations to lie in a class of sequences which is characterised by having a subexponential rate of decay coupled with a periodic fluctuation. This theory illustrates and clarifies the effect of the kernel upon the solution of Volterra-type summation equations. In particular this theory is applied to the autocovariance function of ARCH infinity processes.

A stochastic admissibility theory of stochastic Volterra operators is developed. In particular necessary and sufficient conditions for mean square convergence and sufficient conditions for almost sure convergence are established for stochastic integrals. This theory is then applied to stochastic linear functional equations of Volterra and finite delay type.

Lastly, we introduce a particular stochastic differential equation with an average functional which may be viewed as modelling the demand of traders in an inefficient financial market. The asymptotic behaviour of this process is determined for almost all values of the parameters of the model. A discretisation of this stochastic differential equation is also studied. The asymptotic behaviour of the discretisation is shown to mirror that of the continuous-time equation.


This study presents a preliminary exploration of music therapists' first-hand experiences of engaging in verbal dialogue with clients in their clinical practice. To the authors' knowledge no previous studies have examined the role of verbal dialogue from the first-hand perspectives of experienced professionals working in the field. Three individual interviews were conducted with three accredited Irish music therapists. Four central themes emerged as a result of thematic content analysis: content and function of verbal dialogue, the use of verbal dialogue may contribute to professional ambiguity, returning to the music, and the dyadic relationship between musical and verbal exchange. The findings revealed verbal dialogue to be a topic of interest for the participants in this study, one which stimulated meaningful reflections about clinical practice. The implications for professional identity and clinical practice which arose distinguished verbal dialogue as a potential area for further research and professional discourse within the wider music therapy community. Suggestions were made for additional areas of learning that may assist in preparing trainee and newly-qualified music therapists for potentially challenging verbal encounters with


The main focus of this work concerned with the development of integrated electronic and optoelectronic circuits and devices for pulsed time-of-flight laser rangefinding is on the construction of the receiver channel, system level integration aimed at realisation of the laser radar module and in integration of all the receiver functions of laser radar on one chip. Since the timing discriminator is a very important part of a pulsed time-of-flight laser rangefinder, two timing discrimination methods are presented and verified by means of circuit implementations, a leading edge discriminator and a high-pass timing discriminator. The walk error of the high-pass timing discriminator is ±4 mm in a dynamic range of 1:620 and the uncompensatable walk error of the leading edge discriminator is ±30 mm in a dynamic range of 1:4000. Additionally a new way of combining the timing discriminator with time interval measurement is presented which achieves a walk error of ±0.5 mm in a dynamic range of 1:21. The usability of the receiver channel chip is verified by constructing three prototypes of pulsed TOF laser radar module. The laser radar achieves mm-level accuracy in a measurement range from 4 m to 34 m with non-cooperative targets. This performance is similar to that of earlier realisations using discrete components or even better and has markedly reduced power consumption and size. The integration level has been increased further by implementing a photodetector on the same chip as the rest of the receiver electronics. The responsivity of the photodetector is about 0.3 A/W at 850 nm wavelength and the noise of the receiver is reduced by a factor of about two relative to realisations using an external photodetector, because of the absence of parasitic capacitances and inductances caused by packages, PCB wiring, bond wires and ESD and I/O cell structures. The functionality of a multi-channel pulsed TOF laser radar chip is demonstrated using the photodiode structure investigated here. The chip includes four photodetectors with receiver channels and a three-channel time-to-digital converter. The chip together with external optics and a laser pulse transmitter enables distances to be measured in three directions with a single optical pulse, thus showing the feasibility of implementing all the receiver functions of a pulsed time-of-flight imager on a single chip using a current semiconductor process.


Energy is essential for human existence and our future depends on plentiful and accessible sources of energy. The world population is fast growing and the average energy used per capita increases. One of the greatest challenges for human beings is that of meeting the growing demand for energy in a responsible, equitable and sustainable way. The possibility to obtain energy by "fusing" light atoms addresses these needs. Nuclear fusion reactions are clean, safe and the amount of fuel present on Earth (hydrogen isotopes) is practically inexhaustible and well distributed. Nuclear fusion is a natural process that occurs in all active stars like our Sun. Since the first demonstration of a deuterium fusion reaction (Rutherford 1933), researchers worldwide have tried to replicate this process on Earth by building a thermonuclear fusion reactor. Nevertheless, the challenge posed by the construction of a nuclear fusion reactor is greater than the one presented earlier by the development of a fission reactor. During the IAEA Conference in Geneva in the early 1958, L.A.Artsimovich declared: "Plasma physics is very difficult. Worldwide collaboration is needed for progress" and E.Teller, at the same conference: "Fusion technology is very complex. It is almost impossible to build a fusion reactor in this century". They were right. The extremely high temperature and density necessary to fuse hydrogen isotopes makes it difficult indeed to create a successful fusion reactor. Even though the physics of the fusion reaction appears clear, we are still facing problems on the road towards bulding the "box" that can efficiently confine the hot gas in the state of plasma. The best results so far have been obtained confining a plasma with strong magnetic fields in a toroidal configuration ("tokamak"). The Centre de Recherches en Physique des Plasmas in Switzerland actively studies this promising configuration towards the development of a nuclear fusion reactor. The experimental activity of the Tokamak a Configuration Variable (TCV) mainly focuses on the research of optimized plasma shapes capable of improving the global performance and solve the technological challenges of a tokamak reactor. Several theoretical and experimental results show the importance of the plasma shape in tokamaks. The maximum value of β (an indicator of the confinement efficiency) is for example related to the ratio between the height and the width of the plasma. The plasma shape can also affect the power necessary to access improved confinement regimes, as well as the plasma stability. This thesis reports on a contribution towards the optimization of the tokamak plasma shape. In particular, it describes the theoretical and experimental studies carried out in the TCV tokamak on two innovative plasma shapes: the doublet shaped plasma and the snowflake divertor. Doublet shaped plasmas have been studied in the past by the General Atomics group. Since then, the development of new plasma diagnostics and the discovery of new confinement regimes have given new reasons for interest in this unusual configuration. TCV is the only tokamak worldwide theoretically able to establish and control this configuration. This thesis illustrates new motivations for creating doublet plasmas. The vertical stability of the configuration is studied using a rigid model and the results are compared with those obtained with the KINX MHD stability code. The best strategy for controlling a doublet on TCV is also investigated, and a possible setup of the TCV control system is suggested for the doublet configuration. Analyzing the possible scenarios for doublet creation, the most promising scenario consists of the creation of two independent plasmas, which are subsequently merged to establish a doublet. For this reason, particular attention needs to be devoted to the problem of the plasma start-up. In this thesis, a general analysis of the TCV ohmic and assisted with ECH plasma start-up is presented, and recent attempts to create a doublet plasma are reported. Since the magnetic field reconstruction at the breakdown time is important to better diagnose these plasmas, the entire magnetic system of TCV has been calibrated with an original technique, also described in the manuscript. The last part of this thesis is devoted to the snowflake divertor configuration. This innovative plasma shape has been proposed and theoretically studied by Dr. D.D.Ryutov from the Lawrence Livermore National Laboratory. In Ryutov's articles, this configuration was proposed to alleviate the problems of the plasma-wall interaction and possibly affect the plasma edge stability. The TCV tokamak was the first to report the creation and control of a snowflake configuration, and the candidate was the principal investigator of this work. These results are accordingly discussed in this thesis. Details are provided in particular on the strategy used to establish the configuration. An edge-localized mode (ELM) H-mode regime, supported by electron cyclotron heating, has been successfully established in a snowflake. This regime exhibits 2 to 3 times lower ELM frequency but only a 20%-30% increase in normalized ELM energy (ΔWELM/WP ) compared to an identically-shaped, conventional, single-null, diverted H-mode. Enhanced stability of mid- to high-toroidal-mode-number ideal modes is consistent with the different snowflake ELM phenomenology. Finally, the capability of the snowflake to redistribute the edge power on the additional strike points has been confirmed experimentally and is also reported in this thesis.


Botrytis cinerea is a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops. A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. Deletion of bcdh or double deletion of both bcdh and bcer has no apparent effect on fungal development or pathogenicity. Interestingly, deletion of the bcer gene alone adversely affects fungal development, giving rise to altered hyphal growth and morphology, as well as reduced sporulation, sclerotia production and virulence. Treatments with wall stressors suggest the alteration of cell wall integrity. Analysis of nucleotide sugars reveals the accumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain. UDP-KDG could not be detected in hyphae of the wild-type strain, indicating fast conversion to UDP-rhamnose by the BcEr enzyme. The correlation between high UDP-KDG and modified cell wall and developmental defects raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition, and hence on virulence. This is the first report demonstrating that the accumulation of a minor nucleotide sugar intermediate has such a profound and adverse effect on a fungus. The ability to identify molecules that inhibit Er (also known as NRS/ER) enzymes or mimic UDP-KDG may lead to the development of new antifungal drugs.


The quality of psychomotor activity has often been described as a correlate of psychological well-being or illness. In this paper a theoretical position is described regarding the planned use of psychomotor activity as a therapeutic vehicle. Specifically, psychomotility is viewed as a tool to help bring about increased organization of thought processes in severely disorganized patients. A clinical illustration supporting the theory is presented in detail. Implications of this therapeutic approach are also discussed.


Abstract Humans process faces by using a network of face-selective regions distributed across the brain. Neuropsychological patient studies demonstrate that focal damage to nodes in this network can impair face recognition, but such patients are rare. We approximated the effects of damage to the face network in neurologically normal human participants by using theta burst transcranial magnetic stimulation (TBS). Multi-echo functional magnetic resonance imaging (fMRI) resting-state data were collected pre- and post-TBS delivery over the face-selective right superior temporal sulcus (rpSTS), or a control site in the right motor cortex. Results showed that TBS delivered over the rpSTS reduced resting-state connectivity across the extended face processing network. This connectivity reduction was observed not only between the rpSTS and other face-selective areas, but also between nonstimulated face-selective areas across the ventral, medial, and lateral brain surfaces (e.g., between the right amygdala and bilateral fusiform face areas and occipital face areas). TBS delivered over the motor cortex did not produce significant changes in resting-state connectivity across the face processing network. These results demonstrate that, even without task-induced fMRI signal changes, disrupting a single node in a brain network can decrease the functional connectivity between nodes in that network that have not been directly stimulated.


Introduction Stress among medical students induced by academic pressures is on the rise among the student population in Pakistan and other parts of the world. Our study examined the relationship between two different systems employed to assess academic performance and the levels of stress among students at two different medical schools in Karachi, Pakistan. Methods A sample consisting of 387 medical students enrolled in pre-clinical years was taken from two universities, one employing the semester examination system with grade point average (GPA) scores (a tiered system) and the other employing an annual examination system with only pass/fail grading. A pre-designed, self-administered questionnaire was distributed. Test anxiety levels were assessed by The Westside Test Anxiety Scale (WTAS). Overall stress was evaluated using the Perceived Stress Scale (PSS). Results There were 82 males and 301 females while four did not respond to the gender question. The mean age of the entire cohort was 19.7±1.0 years. A total of 98 participants were from the pass/fail assessment system while 289 were from the GPA system. There was a higher proportion of females in the GPA system (85% vs. 59%; p<0.01). Students in the pass/fail assessment system had a lower score on the WTAS (2.4±0.8 vs. 2.8±0.7; p=0.01) and the PSS (17.0±6.7 vs. 20.3±6.8; p<0.01), indicating lower levels of test anxiety and overall stress than in students enrolled in the GPA assessment system. More students in the pass/fail system were satisfied with their performance than those in the GPA system. Conclusion Based on the present study, we suggest governing bodies to revise and employ a uniform assessment system for all the medical colleges to improve student academic performance and at the same time reduce stress levels. Our results indicate that the pass/fail assessment system accomplishes these objectives.


Background: Although nurses worldwide are experienced violence in their workplace, how nurses experiences violence in India remains unclear. Objectives: The objectives of this study were to (1) determine the occurrence of violence towards nurses. (2) compare the physical and verbal violence towards nurses. (3)find the association between the violence and selected variables.
Methods: A descriptive survey design Setting: Mental health hospital (A), Bangalore, Karnataka, India. Participants: Purposive sampling technique was used which includes the nurses (1) working in Hospital A, (2) having minimum 6 (Six) months of experience. (3) who were available during data collection. (4) who were willing to participate in the study. majority i.e. 165 (92.2%) of the subjects are females and 14 (7.8%) are males, data further show that 147 (82.1%) subjects are staff nurses. A validated and reliable self administered questionnaire developed by the investigator was administered from 24th April 2006 to 25th May 2006.
Results: Majority i.e. 156 (87.2%) of subjects experience violence, out of that 1O2 (57%) subjects experienced mild violence, whereas 23 subjects i.e. 12.8% never experienced violence, and fifty four (30.2%) experience moderate violence. The mean verbal violence score (5.40) is apparently higher than the mean physical violence score (1.55).
Conclusion: These results suggest that nurses need to be trained in therapeutic communication and nonviolence self-defence techniques.


Learning pragmatics involves learning linguistic forms and their communicative functions as well as the context where the form-function relationships are realized. Given its socially grounded, context-sensitive nature, pragmatics may be best learned in a technology-enhanced environment that provides direct access to contextualized communicative practice. Technology can help produce rich multimodal input, opportunities for interaction with consequences, and experience-based learning, which are all important elements of pragmatics learning. This lecture highlights these benefits of technology-enhanced pragmatics learning using a digital game as a sample platform. We created a digital game to teach request-making in English by having participants experience interpersonal consequences of their request as feedback (observing their interlocutor's reactions to their choice of request-making forms). Using the digital game with Chinese learners of English, a series of studies were conducted to investigate a variety of topics, such as the effects of different feedback conditions on learning outcomes, role of metapragmatic knowledge in learning, and transfer of request-making knowledge to a novel speech act. This lecture presents findings from these studies and concludes with future research directions on technology-enhanced pragmatics learning.