Objectives The aim of this study was to conduct a cost-effectiveness analysis (CEA) of a high-intensity and a low-intensity smoking cessation treatment programme (HIT and LIT) using long-term follow-up effectiveness data and to validate the cost-effectiveness results based on short-term follow-up. Design and outcome measures Intervention effectiveness was estimated in a randomised controlled trial as numbers of abstinent participants after 1 and 5–8 years of follow-up. The economic evaluation was performed from a societal perspective using a Markov model by estimating future disease-related costs (in Euro (€) 2018) and health effects (in quality-adjusted life-years (QALYs)). Programmes were explicitly compared in an incremental analysis, and the results were presented as an incremental cost-effectiveness ratio. Setting The study was conducted in dental clinics in Sweden. Participants 294 smokers aged 19–71 years were included in the study. Interventions Behaviour therapy, coaching and pharmacological advice (HIT) was compared with one counselling session introducing a conventional self-help programme (LIT). Results The more costly HIT led to higher number of 6-month continuous abstinent participants after 1 year and higher number of sustained abstinent participants after 5–8 years, which translates into larger societal costs avoided and health gains than LIT. The incremental cost/QALY of HIT compared with LIT amounted to €918 and €3786 using short-term and long-term effectiveness, respectively, which is considered very cost-effective in Sweden. Conclusion CEA favours the more costly HIT if decision makers are willing to spend at least €4000/QALY for tobacco cessation treatment.


The likelihood ratio (LR) is the "logically and legally correct" (Rose and Morrison 2009:143) framework for the estimation of strength-of-evidence under two competing hypotheses. In forensic voice comparison these considerations are reduced to the similarity and typicality of features across a pair of suspect and offender samples. However, typicality can only be judged against patterns in the relevant population (Aitken and Taroni 2004:206). In calculating numerical LRs typicality is assessed relative to a sub-section of that population. This study considers issues of variability relating to the delimitation of reference data with regard to the number of speakers and number of tokens per speaker. Using polynomial estimations of F1 and F2 trajectories from spontaneous GOOSE (Wells 1982), LR comparisons were performed against a reference set of up to 120 speakers and up to 13 tokens per speaker. Results suggest that mean same-speaker LRs are robust to such variation until the reference data is limited to small numbers of speakers and tokens. However, variance and severity of error may be continually reduced with the inclusion of more data. The definition of the relevant population with regard to regional variety is also assessed. Results for LRs are presented across four sets of test data where only one set matches the reference population for accent. In the absence of differences in levels of within-speaker variation, the magnitude of same-speaker LRs and severity of error are shown to be considerably higher for the 'mismatch' test sets. However, results indicate that the removal of regionally-defining acoustic information may reduce the effect of accent divergence between the evidential and reference data. This has positive implications for the application of the numerical LR approach.


Turmeric powder (Curcuma longa) is a yellow powder obtained by grinding dried matured rhizomes. Curcuma longa is utilized in culinary and cosmetic preparations, as well as medicinal formulations. It's available in Kajuru LGA, Kaduna state, Nigeria's Maro ward. The purpose of this study was to carry out a health risk assessment of Na, Mg, K, Ca, and Fe metals in turmeric cultivated within Maro, Chibiya, Karamai, and Angwan Gamu farm lands. Using the Perkin Elmer pin AAcle 900H, four Curcuma longa samples were obtained from diverse fields and subjected to AAS analysis following wet digestion to assess metal contents. The data was examined statistically using analysis of variance (ANOVA).  Ca>Mg>Na>K>Fe were found to be the most abundant metals in Curcuma longa. The maximum level advised by the World Health Organization for all elements was not exceeded (WHO). At P>0.05, there were substantial differences in metal content in Tumeric across all farmlands. Consumers of Curcuma longa cultivated in Maro will not be exposed to any potential health problems because the Target Hazard Quotient (THQ) value of all metals was less than one and the Hazard Index (HI) value for Fe metal was less than one. It was suggested that more research be done on the health risks of other metal content in Curcuma longa rhizome.


Carotid body expresses neutral endopeptidase (NEP)-like enzyme activity and phosphoramidon, an inhibitor of NEP augments sensory response of the carotid body to hypoxia (Kumar et al., 1990). NEP hydrolyzes substance P (SP) and methionine enkephalin (Met-ENK) in the nervous system. In the present study, we determined whether NEP hydrolyzes Met-ENK and SP in the carotid body and whether these peptides contribute to the phosphoramidon-induced potentiation of the sensory response to hypoxia. Experiments were performed on carotid bodies excised from anaesthetized adult cats. HPLC analysis showed that both SP and Met-ENK were hydrolyzed by the carotid body. Phosphoramidon (400 microM) markedly inhibited SP (approximately 90%) but had only marginal effect on Met-ENK hydrolysis (approximately 15%). Sensory responses of the carotid body in vitro to hypoxia (pO2, 68 +/- 6 mmHg) and SP (10 nmoles) were potentiated by phosphoramidon by approximately 80% and approximately 275% respectively (p < 0.01). SP-receptor antagonist abolished phosphoramidon-induced potentiation of the sensory response to hypoxia as well as to SP. These results demonstrate that SP is a preferred substrate for NEP in the carotid body and SP plays a major role in the potentiation of the hypoxic response of the carotid body by phosphoramidon.


A network, which can learn temporal patterns incrementally, is proposed. The network uses: a) Gaussian functions to represent various output values and b) chunking to group similar patterns so that a compact network can be realized. The learning capacity limits of the network are evaluated for the worst case sequences. Learning of sequences can be performed using a simple one step algorithm.


INTRODUCTION
Use of smokeless tobacco (ST) is a significant public health problem for young adults, many of whom want to quit. We describe the outcome of a Randomized Controlled Trial (RCT) examining the efficacy of two web-based ST cessation interventions targeting young chewers.

METHODS
One thousand seven hundred and sixteen ST users wanting to quit were recruited online to the MyLastDip program and randomly assigned to one of two fully automated web-based ST cessation interventions: (a) an Enhanced Condition (N = 857) with tailored treatment recommendations and interactive features, or (b) a Basic Condition (N = 859) that provided an online ST cessation guide in static text.

RESULTS
Assessment completion rates at 3 months, 6 months, and for both 3 and 6 months were 73%, 71%, and 65%, respectively. No significant differences were found between conditions. Using complete case analysis for repeated point prevalence (3- and 6-month assessments), all tobacco abstinence was 28.9% for participants in the Enhanced Condition and 25.6% in the Basic Condition. Using intent-to-treat analysis, abstinence rates were 35.2% versus 32.3%. Similar results were obtained for ST abstinence. Participants reported being satisfied with their programs and the Enhanced Condition participants were relatively more engaged. Differences in program engagement were not related to tobacco abstinence at 6 months.

CONCLUSIONS
Both web-based ST cessation programs encouraged robust levels of absolute tobacco and ST abstinence at follow-up. The absence of between-group differences was discussed in terms of composition of the control condition and implications for next steps in treatment development and testing.


A problem cited by critics of preparation programs in sport management has been the lack of specialty tracks. Therefore, responses regarding the perceived importance of job responsibilities, demographic information, and educational recommendations were solicited from athletic directors (ADs) (n = 58) of NCAA Division I-A football programs and from general managers (GMs) (n = 62) within professional sport to characterize the two areas. Multivariate contrasts upon groups of items in all areas of job responsibility yielded significant differences. The GMs rated the areas of labor relations and personnel evaluations as more important, while the ADs assigned higher ratings to all other categories (i.e., marketing, financial management, administration, public relations). A discriminant function analysis upon the individual job items corroborated these differences. These findings were discussed in terms of recommendations for the education of sport administrators.


We report some recent results obtained for large N gauge theo ries which support the idea of volume reduction. Results for the string tension of the Twis ted Eguchi-Kawai model match with those obtained from extrapolation from finite N. Determinat ion of other observables is currently under way. Application of the twisted reduction idea to the c ase of 1 or 2 flavours of quarks in the adjoint representation of the group offers promising re sults. Preliminary results for the string tension point towards a very different behaviour for 1 and 2 fl avours. While the string tension remains finite for 1 flavour at the critical massless quark lim it, it seems to vanish with a large anomalous dimension for the Nf = 2 case. This is consistent with the predicted Infrared fixed point expected in the latter case.


Bone marrow is a tissue with a high mitotic activity, and consequently exquisitely radiosensitive. The clinical effects of bone marrow irradiation and its ability of regeneration are related to the volume irradiated. Management of hematopoietic side effects of radiation include surveillance, antibiotics, blood products transfusion, and more scarcely hematopoietic growth factors, bone marrow transplantation and peripheral blood stem cells reinfusion.


Research from the 20th century showed that ethnic minorities under-performed White British on measures of cognitive ability in the United Kingdom. However, academic qualification results from the first two decades of the 21st century suggest minimal to reverse ethnic differences. To better understand the pattern of contemporary cognitive differences among adolescents in the 21st century, we analyzed academic achievements at age 16 in the GCSE and cognitive ability in four cognitive tests: the National Reference Test, NRT; the Programme for International Student Assessment, PISA; Cognitive Ability Test 3 (CAT3); and Center for Evaluation and Monitoring (CEM) 11-plus. Results from the PISA, CAT3 and CEM 11-plus tests correlate strongly across ethnic groups. These results show that Bangladeshi, Pakistani and Black students score approximately one half of a standard deviation below Indian and White students, while Chinese students perform significantly above the latter groups. In contrast, but consistent with academic qualifications, results based on the NRT suggest smaller ethnic gaps.


This article elaborates upon the paper by O. Tretyak and D. Klimanov published in the Russian Management Journal vol. 14, issue 1. It demonstrates a practical application of the approach to business model (BM) analysis and change management, developed by the authors and based on organizational networks theory. The study is devoted to the example of Russian pharmaceutical market and the international manufacturing company that specializes in ophthalmology, medical aesthetics and neurosciences. The results obtained are based on a number of expert interviews with the representatives of company management. In line with three suggested levels of BM analysis, the authors conducted a sequence of procedures that allowed not only to highlight the specifics of the approach and clarify it, but also to offer concrete directions for BM change in order to increase the value that is jointly created by BM actors for the final consumer.


The vitamin D3 metabolite, 20S,23S-dihydroxyvitamin D3, was chemically synthesized for the first time and identified to be the same as the enzymatically produced metabolite. The C23 absolute configurations of both 20S,23S/R-dihydroxyvitamin D3 epimers were unambiguously assigned by NMR and Mosher ester analysis. Their kinetics of CYP27B1 metabolism were investigated during the production of their 1α-hydroxylated derivatives. Bioactivities of these products were compared in terms of vitamin D3 receptor activation, anti-inflammatory, and antiproliferative activities.


Three studies were conducted to test the hypothesis that judgments of average females' attractiveness or dating desirability will be adversely affected by exposing judges to extremely attractive prior stimuli (i.e., judgments will show a "contrast effect"). Study 1 was a field study in which male dormitory residents watching a popular TV show, whose main characters are three strikingly attractive females, were asked to rate a photo of an average female (described as a potential blind date for another dorm resident). These subjects rated the target female as significantly less attractive than did a comparable control group. Two other studies demonstrated analogous effects in a more controlled laboratory setting. In addition, the third study indicated a direct effect of informational social influence on physical attractiveness judgments. Implications are discussed, with particular attention to mass media impact.


In recent decades we have observed a progressive aging of the society. A growing number of elderly people is associated with an increase in the percentage of people whose cognitive functions are decreasing. It is important to counteract this process and develop lifestyle recommendations that will allow to delay the process of cognitive decline. Regular physical activity has a beneficial effect on health and cognitive performance, especially on executive functions. Data shows the positive impact of physical exercise, both aerobic and resistance training, and their combination, on cognitive performance. Potential biological mechanisms that may underlie the effectiveness of physical exercise include increased blood flow through the brain, changes in the release of neurotransmitters, and the process of neurogenesis. The aim of the article is to analyze the recent research taking into account the relationship between physical activity and cognitive skills. The research published in 2015-2020 was analyzed. The review concerns the effect of physical activity, not a combination of cognitive training and physical exercise, on cognitive skills in a group of healthy adults and the elderly. Studies that defined physical activity as sports, as well as increasing daily activity to reduce a sedentary lifestyle, were analyzed. The analysis of the available data indicates that researchers report positive effects of increasing physical activity on cognitive performance, mainly executive functions (e.g., working memory), but also attention and memory. Only a few studies have not reported any significant differences. However, the analysis of the research shows the lack of uniform methods of measuring the intensity of physical activity, as well as efficiency of cognitive functions. More research is needed to examine the long-term effects. Another study should be conducted to present the most effective intervention techniques and prepare recommendations for maintaining preserved cognitive functions. Further research should be conducted to control variables that affect the acquisition of cognitive skills and cognitive effectiveness during the intervention. Med Pr. 2021;72(4).

http://medpr.imp.lodz.pl/pdf-136230-69090?filename=The impact of physical.pdf


Breast cancer ranks first in terms of mortality and incidence rates worldwide among women. The HER2+ molecular subtype is one of the most aggressive subtypes; its treatment includes neoadjuvant chemotherapy and the use of a HER2 antibody. Some patients develop resistance despite positive results obtained using this therapeutic strategy. Objective. To identify prognostic markers for treatment and survival in HER2+ patients. Methods. Patients treated with neoadjuvant chemotherapy were assigned to sensitive and resistant groups based on their treatment response. Differentially expressed genes (DEGs) were identified using RNA-seq analysis. KEGG pathway, gene ontology, and interactome analyses were performed for all DEGs. An enrichment analysis Gene set enrichment analysis was performed. All DEGs were analyzed for overall (OS) and disease-free survival (DFS). Results. A total of 94 DEGs were related to treatment resistance. Survival analysis showed that 12 genes (ATF6B, DHRS13, DIRAS1, ERAL1, GRIN2B, L1CAM, IRX3, PRTFDC1, PBX2, S100B, SLC9A3R2, and TNXB) were good predictors of disease-free survival, and eight genes (GNG4, IL22RA2, MICA, S100B, SERPINF2, HLA-A, DIRAS1, and TNXB) were good predictors of overall survival (OS). Conclusion: We highlighted a molecular expression signature that can differentiate the treatment response, overall survival, and DFS of patients with HER2+ breast cancer.


As contrasted with vertical component of turbulence intensity, lateral component increases with an average time. For a period of one hour, it is up to 19% and anisotropy of the turbulence is significant. In order to reproduce such turbulence in the wind tunnel, an oscillating blade cascade was developed by author. When angular motion of the blade cascade was random, the distribution of mean velocity, turbulence intensities, turbulence scales and spectral structures were similar to those of the atmospheric boundary layer. However, since all blades were driven by only one servo motor, blade motions were the same. Turbulence coherence in a lateral direction is thus much greater than that of the natural wind. To improve the disagreement of coherence, all blades were made to be driven independently. 15 random angular time series of blades were made from an objective spectrum, coherence and phase functions by the multidimensional auto regression method of Akaike. The coherence and spectra of generated turbulence were found to be similar to those of the natural wind.


Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA

INTRODUCTION: Hyaluronic acid (HA), a glycosaminoglycan, is associated with prostate cancer (PCa) progression and metastasis. 4-methylumbelliferone (4-MU) is dietary supplement that inhibits HA-synthesis. In this study we evaluated chemopreventive and therapeutic efficacy of 4-MU to prevent PCa growth and metastasis in three PCa models.

METHODS: Efficacy of daily oral gavage of 4-MU was evaluated in 3 PCa models: Model 1: TRAMP mice (n = 8-20/group) were treated with vehicle or 4-MU (450 mg/kg) by starting stage-specific treatment at 8 (PIN stage), 12 (adenocarcinoma) and 22 (invasive carcinoma) wks of age. Model 2: Mice were treated with 4-MU (200 mg/kg or 450 mg/kg) following intracardiac injection of Luciferase expressing PC3-ML cells. 3. Palpable DU145 xenografts were treated with 4-MU (200 and 450 mg/kg). Effect of 4-MU on EMT markers, HA receptors was evaluated by Q-PCR, immunoblotting and/or immunohistochemistry in PCa cells and xenograft tissues. HA add back and overexpression studies were conducted to evaluate the mechanism of action of 4-MU.

RESULTS: In the TRAMP model, at 28 wks, 100% of vehicle treated mice developed PCa, but tumor growth and progression was inhibited in all 4-MU treated groups; P+SV weight (g): vehicle: 3.2±2.9; 8 wk: 0.43±0.14; 12 wk: 0.35±0.04; 22 wk: 1.0±0.35 g. The P+SV weight in TRAMP mice at 22 wks of age was 0.9±0.04, showing that late stage administration of 4-MU halted further tumor progression. Animals in 8, 12 and 22 wk groups remained tumor free until 52, 44 and 34 wks respectively, even after stopping treatment at 28 wks. While 55% of vehicle treated animals developed metastasis, none of the treated groups had metastasis. In the PC3-ML intracardiac model, 100% of the mice in the vehicle group but none in the treatment group developed skeletal metastasis. In the DU145 model, 4-MU inhibited tumor growth. No serum/organ toxicity or weight loss was observed in any treatment groups. In all models, 4-MU treatment downregulated HA, HA receptors (CD44, RHAMM) and EMT markers (β-catenin, Zeb2) by >2-fold) but up-regulated E-cadherin. HA addition and overexpression of myristoylated AKt inhibited 4-MU effects.

CONCLUSION: 4-MU is a potent non-toxic, oral chemopreventive agent, which inhibits PCa growth and metastasis by abrogating HA-signaling and reversing EMT.

Support: R01 CA 123063-04 (VBL); R01 CA 72821-11 (VBL)

Note: This abstract was not presented at the meeting.

Citation Format: Travis Yates, David Alonzo, Soum Lokeshwar, Kelly Hoye, Luis E. Lopez, Marie Hupe, Vinata Lokeshwar. 4-methylumbelliferone: Dietary supplement turned chemo-preventive and anti-metastatic agent for prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2681. doi:10.1158/1538-7445.AM2014-2681


We present a flexible optimization framework to design spectral-selective radiofrequency pulses using numerical optimization on Bloch equation simulation. The RF pulse performance is assessed using a composite loss function for both fat suppression and power requirement. The framework was used to design three binomial (1-1, 1-2-1 and 1-3-3-1) and one cubic B-splines interpolated RF pulses. These pulses were then tested in vitro as well as in vivo in the knee and in the heart, where they demonstrated robust fat suppression comparable to a state-of-the-art water-selective pulse.


We analyse new results of Chandra and Suzaku Observatories which found a flux of hard X-ray emission from the compact region around Sgr A � (r � 100 pc). We suppose that this emission is generated by accretion processes onto the central supermassive blackhole when an unbound part of captured stars obtains an additional momentum. As a result a flux of subrelativistic protons is generated near the galactic center which heats the background plasma up to temperatures about 6–10 keV and produces by inverse bremsstrahlung a flux of non-thermal X-ray emission in the energy range above 10 keV.


Hydroponics has been used during years for research in the field of plant mineral nutrition and related topics. Today the soilless culture method is the most intensive horticulture production and is being applied with success in developed countries for commercial purposes. The growing and future of hydroponics in Latin America will much depend of the developing and adaptation of less sophisticated commercial systems. These have to be cost competitive with respect to the high sophisticated technology generated and used in developed countries, using natural and local substrates, developing native or endemic crops of the Region with economical potential for its high feed or medicinal value, among others. Meanwhile, as there is a considerable decreasing of agricultural soils in the world, soilless culture would be an important production alternative in urban and peri-urban areas, mainly in undeveloped countries. Inside the context of urban agriculture, hydroponics could be applied in the cities with more simple and low cost of technologies, mainly in extreme poverty areas, as a way to spread vegetables for self-consumption and to support the family or community income. Also to create micro-companies that will generate employments. There are no official statistics on the evolution of the state of the hydroponic cultures in Latin America. The main hydroponic systems used are the drip irrigation and NFT system. According with their profits, the main hydroponic crops are lettuce, tomato, pepper and strawberry. In Andean countries like Peru, Bolivia, Colombia and Ecuador, aeroponics is being developing to obtain basic potato tuber seed, free of virus. In relation to the media used in soilless culture, there is no ideal or optimum substrate, because a great diversity in media could be used, as pure or as mix form. Among the inorganic substrates it is possible to use quarry, river and quartz sand, gravel, pumice and tezontle. Husk rice, coco fiber, peat moss and sawdust are used as organic media. The use of rock wool is not generalized in the Region, but in countries like Mexico and Chile it is mainly used in tomato crop with drip irrigation system. Brazil and Mexico are the more representative hydroponic countries in Latin America. The area of soilless culture is increasing in the Region and every day there is much interest to learn and to dominate this technique of plants production without using soil. A great number of international courses, seminaries, congresses and symposia organized in countries like Peru, Mexico, Brazil, Costa Rica and Chile demonstrate this affirmation. Finally, it is necessary to obtain a hydroponic certification, as well as the organic products, to support the hydroponic growers in our countries.


Background:Menarche is the first menstrual flow of the female. It occurs at a mean age of 12.16 years in black American girls, and 12.88 years in white American girls according to the American Congress of Obstetricians and Gynecologist (ACOG). In Cameroon, in 1999, it was reported that menarche occurs at a mean age of 13.18 ±1.08 years in girls in urban areas; 13.98 ± 1.55 years in girls in suburban areas; and 14.72 ±1.18 years in girls in rural areas. Studies show that urbanization has greatly influenced the age at menarche and a number of factors have been found to collectively or individually influence it.
The objective was to determine the age at menarche in rural (Bamougoum) and urban (Yaounde) settings, while identifying factors influencing age at onset of menarche among girls aged 9 to 16years.
Methods: We conducted from 1st October to 30th March a cross sectional survey targeting female students aged 9 to 16 years in Yaounde town and Bamougoum village. Participants were included by a randomized cluster sampling and data collected using an auto-administrable questionnaire. Data was analyzed using the statistical software Epi-Info version 3.5.4. With a statistically significant threshold set at p-value≤0.05, the odds ratio was used as the measure of association between age at menarche and selected covariates.
Results: 1157 participants were included in the study, 49.3% were from an urban setting and 50.7% from a rural setting. The ages of the participants ranged from 10 to 16years with a median age of 15.0 years. Majority of parents of participants of the urban setting had attained higher education (52.98%), whereas in the rural setting, majority of parents ended at primary school (33.73%). Regarding the knowledge of our participants, 67.20% of rural participants had good knowledge as concerns puberty, menarche and menstrual cycle whereas only 46.00% had good knowledge of it in the urban setting. The mean age at menarche in our study population was 12.76±1.33years, with a mean age of menarche in the urban setting (Yaounde) of 12.48±1.12years and in the rural setting (Bamougoum) of 13.03±1.46years. Urban/rural resident, the number of parents alive, occupation of the parents, quality of nutrition, overweight/obesity and first sexual contact before/after menarche was found to have statistically significant associations with age at menarche.
Conclusion: The age of the onset of menarche in girls aged 9 to 16 years in Yaounde is significantly lower compared to the age at menarche in their Bamougoum counterparts (p-value<0.001). Participants from Bamougoum however have a comparatively better knowledge compared to their Yaounde counterparts. The age of the onset of menarche is significantly influenced by Urban/rural resident, the number of parents alive, occupation of the parents, quality of nutrition, overweight/obesity and first sexual contact before/after menarche.
Key words: Age, Menarche, puberty , Cameroon


To meet a specific objective, it is frequently the case that several criteria will need to be evaluated. Such a procedure is called multi-criteria evaluation (MCE). A study using GIS aided multi-criteria evaluation approach in flood hazard zonation was described in this paper. Bogra district of Bangladesh was selected for this study. The main objective of this study was to develop a flood hazard zone map of the study area with selected eight criterions viz. water level rise flood zone, flood return period, probability of flood occurrence, flood depth, observed flood frequency, population density, runoff potential and rainfall along with MCE technique. To generate necessary layers (Factors and Constraints) for the MCE approach, remote sensing and GIS integrated techniques and models were applied. To standardize the factors and establishing the factors weight for the MCE, analytical hierarchy process (AHP) method was used in this study. Finally to perform the multi-criteria evaluation (MCE) for flood hazard zonation, MCE module of IDRISI software was used. The results depicted that about 17.14% and 20.08% of the total area is classified under very high and high flood hazard zone respectively and 35.36% of the total area is found to be the least vulnerable (low to very low hazard zone) to flood hazard. On the other hand, Dhunat, Adamdighi and Gabtali thanas are the most vulnerable in respect to flood hazard in the study area. So, this study reveals that MCE technique can be utilized advantageously and effectively for flood hazard zonation in a flood prone area.


In this paper, synthesis of polysubstituted maleimides was described via cascade reaction of isocyanides and α-diazoketones. This strategy features readily available substrates, high atom-economy and metal-free conditions. A variety of valuable polysubstituted maleimides are assembled in good yields.


Metallosis and metal-induced synovitis are well-recognized complications of metal-backed polyethylene joint prostheses and have been frequently described in the orthopedic surgery literature; however, relatively fewer articles discussing the radiologic aspects of this complication have been published. To illustrate the importance of radiologic findings in the diagnosis and management of these patients, we present a case of metallosis and metal-induced synovitis complicating two revisions of a total knee arthroplasty, caused by polyethylene liner wear and dissociation of the polyethylene liner from the metal-backed patellar prosthesis. Specific attention is given to reviewing signs that aid in diagnosis, such as the "bubble sign," "cloud sign," and "metal-line signs."


This design aims to 1) figure out the macro and micro concepts in designing an Integrated Cattle Processing Industry in Gorontalo Regency, 2) find the design and application in terms of structure and arrangement using Green Architecture, and 3) realize an Integrated Cattle Processing Industry building that has adequate and proper facilities. The data collection methods used in this design are observation covering observations of internal and external conditions and through secondary data collection, namely by conducting literature studies and documents as support in design. The result of this design is located in a strategic area that follows the Spatial and Regional Plans of Gorontalo Regency, Gorontalo Province.
Keyword: cattle farm, integrated cattle processing, green architectur


In the 'thermo-acoustic sensing technique' (TAST), a burst of sound, called the 'thermometer' beam is passed through tissue and its transit time is measured. A focused sound field, called the heating field, then warms a small volume in the path of the therometer beam, in proportion to the absorption. Finally, the therometer beam burst is repeated and its transit time subtracted from that of the initial thermometer burst. This difference measures the velocity perturbation in the tissue produced by the heating field. The transit time difference is td = K integral of infinity-infinity IP dchi where K is the instrument constant, I the heating field intensity, and P a perturbation factor which characterizes the tissues. The integration is carried out along the path of the thermometer beam. The perturbation factor is P = (formula: see text) where C is the specific heat, rho the denisty, V the velocity of sound, (formula: see text) the temperature coefficient of velocity and alpha the heating field absorption coefficient which is apparently sensitive to tissue structure and condition. Experiments on a fixed human brain showed an ability to distinguish between various tissue types combined with a spatial resolution of better than 3 mm. Should predictions based on the data and theory prove correct, TAST may become a non-invasive alternative to biopsy.


This work is a threefold optical study of two perovskites: the very well known but still surprisingly intriguing SrTiO3 and its almost unexplored magnetic relative EuTiO3. A major extension to previous work is the very broad energy scale from the microwave to the ultra-violet region on which phenomena have been studied. Central in the thesis is the novel technique of time-domain spectroscopy in the THz range, a relatively unexplored range which clarifies and illustrates textbook phenomena of low energy physics. The thesis built up as follows. Chapter 1 introduces the theory of the interaction of light with matter and existing optical concepts needed in the following chapters. One part needs to be highlighted, it is a magnetic sum rule specially derived for the use in chapter 4, which relates the spectral weight of magnetic dipole transitions to the total magnetization of the system. Chapter 2 describes how SrTiO3 is tuned towards the formation of electron-phonon coupling by using chemical substitution of niobium as a control parameter. In chapter 3 it is shown that pristine SrTiO3 tuned by an external static electric field approaches a quantum ferroelectric state and shows an intriguing universal behavior below 20 K. Chapter 4 is devoted to influence of a magnetic field on the low energy optical properties of EuTiO3, which leads to a strong absorption due to the resonance of the electron spins, a so-called ferromagnetic spin resonance.


Australian attempts to value the environment began at least 40 years ago. Since then, environmental protection and natural resource management have become major national issues. But have the methods of valuation kept pace with the importance of the issues that they are meant to resolve? Can environmental and resource values actually be measured? This paper chronicles, reviews, and assesses the valuations of 40 years and more than 100 Australian authors.


Image retrieval methods mainly depend on image tags. Nonetheless, images are uploaded to WEB with noisy image tags or not a single tag at all. On the other hand, generating tags for every image on the WEB is a time consuming job. In this paper, we present a novel method to improve image retrieval problem using additional text corpora which resides in WEB. Proposed method works in two modes, each of which tries to solve following problems separately; 1) cleaning irrelevant image tags from a noisy image tag list, 2) generating a tag list for an untagged image. In this manner, we designed two models which operates on bag of visual words namely Statistical Matching Model and Variance Model. Test results show that proposed methods are very successful in terms of both image tag cleaning and tag generation.


A flexible supercapacitor (SC) is an attractive energy storage device for powering low-power sensors, since it can be built using only nontoxic and sustainable materials. In this study, the advantages of using biodegradable polylactic acid (PLA) substrate for printed SC are investigated by studying the SC's cyclic bending reliability, failure mechanism, and the impact of the bending radius. The results confirm that the SCs with laminated PLA with polymer barrier substrate exhibited the highest bending reliability, stability, and capability in preventing liquid electrolyte evaporation among the investigated substrates. Besides, the reliability decreased with the decreasing bending radius only when the strongly impacted areas lie on the electrode, the flaking and cracking of which was found to be the failure mechanisms of the tested SCs, except for the SCs with PLA/Al substrate, which failed due to the Al cracking. This research suggests that using PLA/barrier substrate, developing more robust activated carbon electrodes, developing cellulose paper with more dense fiber structure and smaller porous areas, and controlling the bending radius are crucial to improving the SC's reliability.


Introduction: The aim of this study was to evaluate the relationship between metacognitive components and dysfunctional attitudes in outpatients with bipolar mood disorder II. Methods: Thirty-six young adult outpatients with current diagnoses of BMD II(20 females and 16 males) were recruited from Esfahan Counseling Center. Diagnoses were based on the Structured Clinical Interview for DSM-IV Axis I Disorder-Clinical Version(SCID-CV). A battery of questionnaires including Metacognition Questionnaire and Dysfunctional Attitude Scale(DAS) were self-assessed by patients before medical therapy. Results: Pearson's correlation analysis showed that the components of metacognition and its relationship with dysfunctional attitudes is positive and significant(r= 28/0, p<0/05). Multiple regression analysis showed that two of the metacognitive components emerged as potentially useful in prediction of dysfunctional attitudes(negative beliefs about uncontrollability, danger and thoughts control). Also, results indicated that those two components have a significant positive relationship with vulnerability, perfectionism and effectiveness(R2= 0/29, 0/35; p<0/05). Components of positive beliefs about worry and beliefs about cognitive self-consciousness related to cognitive confidence in predicting the criterion variable and its components showed no significant contribution. Conclusion: Study findings suggest that DSM-IV BMD II outpatients with metacognitive distortions have shown higher levels of dysfunctional attitudes.


Recent studies have shown that oestrogen can induce desensitization to its own gonadotrophin-inhibiting effect in female rats by an action on the medial preoptic area (MPOA). Probably as a consequence of this action, sensitivity to the negative oestrogen feedback declines markedly between metoestrus and dioestrus of the 4-day ovarian cycle. To study this desensitization process in 5-day cyclic rats, females exhibiting regular 5-day vaginal cyclicity were ovariectomized on consecutive days of the cycle, injected with oestradiol benzoate (OB) or oil on the day of ovariectomy and autopsied 24 h after the injection. Estimation of the serum concentration of LH revealed that desensitization to negative oestrogen feedback occurred only between day 2 of dioestrus and pro-oestrus, i.e. 2 days later than in females with a 4-day cycle. In the latter animals, an injection of progesterone in metoestrus or early dioestrus, which induced lengthening of the ovarian cycle for 1 day, delayed the onset of desensitization to a degree similar to that found in spontaneously 5-day cyclic rats. In acutely ovariectomized females, progesterone implants placed in the MPOA, but not those located in the mediobasal hypothalamus, increased the LH-inhibiting effect of low doses of OB. The results suggest that the prolonged secretion of progesterone recorded in 5-day cyclic rats retards follicle maturation and delays the forthcoming ovulation by acting, at least partly, on the MPOA and antagonizing the desensitizing effect of oestrogen. In this way, inhibition of gonadotrophin secretion by oestrogen is enhanced and the increase in tonic LH secretion necessary for the completion of follicle maturation is retarded.


Radiation characteristics of a probe-fed open circular loop antenna are presented when the antenna is printed on a layered dielectric sphere. A smaller parasitic circular loop has been incorporated in the configuration to enhance the circular polarization (CP) bandwidth. The structure has been analyzed rigorously using the method of moments (MoM), where the sphere has been represented using the spherical dyadic Green's function (DGF). The computation efficiency has been enhanced using asymptotic extraction as well as closed form integrations to compute the MoM impedance matrix elements. The computed results are in close agreement with those obtained from measurements.


The evolution of drug therapy in solid tumors primarily leads to the increase in cancer specific survival, but inevitably raises financial burden. So far, none of the countries can venture total reimbursement with all necessary contemporary drugs for all patients. Doubling of expenses for cancer drug therapy in Russia in 2019 allowed oncologists using the most expensive treatments in more than 70 % of patients. Purpose : To evaluate efficacy of various treatment types of non‑small cell lung cancer in real clinical setting. Material and methods . We included patients with histologically verified metastatic non‑small cell lung cancer without activating mutations treated with first or second line therapy in 2018 – 2019. In total 287 patients were included: 230 — for the first line efficacy analysis, 100 — for the second. Time to disease progression, overall survival and objective response rate were evaluated. Results . The use of checkpoint inhibitors in accordance with all actual recommendations (first line pembrolizumab monotherapy in PD-L1 > 50 %, chemoimmunotherapy in first line or monotherapy in the second line irrespectively to PD-L1 status) decreased one‑year mortality from 61 % in 2018 to 33 % in 2019, but significantly increased financial cost (p < 0.000). Moreover, checkpoint inhibitors in combination with chemotherapy irrespectively of PD-L1 expression increased response rate (from 10 % and 21 % for monotherapy and platinum doublet, respectively, to 33,2 % for chemoimmunotherapy). PD‑1 inhibitors as monotherapy increased median time to disease progression (4,1 and 6,2 months for monotherapy with chemotherapy and platinum doublet, respectively, to 6,5 months and not achieved for chemoimmunotherapy and monotherapy with checkpoint inhibitors). Conclusion . More than doubling of financial costs spent for non‑small cell lung cancer treatment allowed access to contemporary treatment for all patients. Such unprecedented measures significantly improved efficacy, including double decrease of one‑year mortality. Nevertheless, rational design of regional clinical guidelines interpretation is of great importance in accurate and effective use of the healthcare budget.


The US Food and Drug Administration (FDA) has approved several new drugs in the past 2 years. This article provides an overview of some of the newer drugs that are likely to find wider use in the future. The drugs reviewed in this article can be used to treat cardiovascular system problems, diabetes mellitus, multiple sclerosis, hepatitis B infection, hyponatremia, Parkinson's disease, rheumatoid arthritis, pain, constipation, and insomnia. Another drug discussed can be used to help a patient stop smoking. The article also discusses Gardasil, the recombinant vaccine against human papilloma virus (types 6, 11, 16, and 18).


Fundamental expressions for analyzing potential modulated fluorescence (PMF) responses were derived within the framework of a phenomenological model for adsorption and transfer of ionic species across polarized liquid|liquid interfaces. For small periodic perturbations of the Galvani potential difference, PMF signals can be linearized and the contribution of each process can be uncoupled in the frequency domain. The PMF response for kinetically controlled adsorption is expressed as a semicircle in the complex plane in which the characteristic frequency of maximum imaginary component is proportional to the adsorption and desorption rate constants. Considering that the potential dependence of adsorption exhibits opposite sign whether the process take place from the aqueous or organic phase, the corresponding PMF responses appear in different quadrants of the complex plane. The present model delivers useful diagnostic criteria for analyzing the nature of the various processes contributing to the periodic flu...


Lake Biwa is an ancient freshwater lake that was formed approximately 4 Mya and harbours many coastal plants that commonly inhabit the seashore. We used chloroplast DNA haplotype analysis using two spacer sequences and simple sequence repeat (SSR) analysis using eight nuclear microsatellite markers to detect genomic signatures indicating long-term isolation of inland populations of Calystegia soldanella in Lake Biwa from coastal populations. We used 348 samples from 63 populations for haplotype analysis and 478 samples from 27 populations for SSR analysis covering the inland and coastal distribution of the species. We detected seven haplotypes, and the distribution pattern of these haplotypes was geographically highly structured between Lake Biwa and the coast. Nuclear SSR analysis also supported genetic differentiation between Lake Biwa and coastal populations (analyses of molecular variance, 43%), and the grouping of Lake Biwa and coastal populations by a Neighbour-joining tree. In addition, genetic diversity of the inland populations (mean HE = 0.153) was significantly lower than that of coastal populations (mean HE = 0.328). These results suggested that inland populations at Lake Biwa have been isolated from coastal populations for a very long time. The inland populations most likely experienced a bottleneck effect, resulting in sufficient in situ genetic divergence to clearly distinguish them from coastal populations. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 102, 51–66.


Word knowledge acquisition is an incremental process that relies on exposure. As a result, word knowledge can broadly range from recognizing the word's lexical status, to knowing its meaning in context, and to knowing its meaning independent of context. The present study aimed to model incremental word knowledge in 1454 upper primary school children from grades 3 to 5 by investigating their abilities on three word knowledge tasks originating from the same set of 300 words: lexical decision, context decision, and definitional decision. A mixed-effects model showed significant differences in performance between tasks and between grades, and a significant interaction indicating that task differences were different for children in grade 5 compared to children in grades 3 and 4. In order to examine further the different task relation patterns at the word level, a cluster analysis was performed using the observed item means, which were corrected for the guessing chance. The analysis showed that for most words, recognition of its lexical status was easier than knowing its meaning in context, which in turn was easier than knowing its meaning independent of context. It is concluded that task relation patterns differ based on mean log frequency as a proxy of word exposure.


Charge pump circuit is widely used in many systems due to its low power consumption, high performance, small area and low current drivability. This paper presents a low-voltage, high performance charge pump circuit suitable for low-voltage applications such as EEPROM of Radio Frequency Identification (RFID) tag. Designed in 0.18-μm CMOS process, the proposed charge pump circuit is able to pump an input voltage of 1.8V to a measured output of 5.95V through 20MHz clock signal with each pumping capacitor of 0.1pF and smoothing capacitor of 0.1pF at the output. Simulation result shows that the proposed charged pump circuit offers higher pumping gain compared with the existing charge pump circuit. Besides the RFID tag, the charge pump circuit can also be used in other memory circuits.


Flow diverter stents have been used widely for treatment of cerebral aneurysms in the US and EU. Although flow diverter stents are very promising, there are a few clinical concerns such as delayed rupture or incomplete occlusion. Engineers have been addressing these issues using computational fluid dynamics simulations (CFD). Because flow diverter stents have "flow diverting" effects, as the name indicates, we consider that the effects could be predicted by CFD. In this review, I will describe CFD research on clinical aspects of flow diverter stents.


In addition to government‐sponsored health insurance schemes (GSHIS), many microfinance institutions (MFIs) and community‐based organizations (CBOs) in India have started microinsurance health insurance schemes. These include health mutuals for the benefit of their members. This article explores these as an alternative health‐financing model in India. A literature search produced 926 relevant publications. After applying advanced search options and removing duplicates, abstracts of 324 papers were read and then 47 papers reviewed, and finally 29 were included in this review. Five key themes emerged: (1) "Health for all" arguments and opportunities in favour of micro health insurance schemes; (2) micro health insurance products; (3) impact of micro health insurance schemes; (4) systematic irregularities and regulatory framework; and (5) innovation. We also look at the emerging market patterns that will define micro health insurance products. Health mutuals can effectively provide mass health protection to the poor and not so poor through efficient business models, bespoke benefit packages and multiple payment plans. They can reduce financial vulnerability and improve health outcomes. While GSHIS can cover a substantial tranche of expected health‐related costs, the balance can be supplemented through innovative financial products that reduce financial risk.


Computer-assisted interpreting (CAI) tools have the potential to benefit the interpreting profession and to improve its ecosystem considerably. Academic interest in this field has intensified in recent years. However, there have been no thorough analyses of the definitions and classifications of CAI tools or of the empirical studies on the subject. This study overviews CAI tools holistically. It describes advances as well as gaps that remain to be filled. It also provides an in-depth examination of the status quo and suggests potential avenues for improvement. The article begins by distinguishing between CAI tools in the broad sense and CAI tools in the narrow sense. By bridging the conceptual gaps between the two, we propose a unified description and a categorisation that reflects the main features of CAI tools. This comprehensive review analyses 27 empirical studies and examines the manner in which CAI tools affect interpreters' performance. Since the influencing factors that have been identified in previous experiments vary between interpreters-related (e.g. interpreters' profiles) and settings-related (e.g. reference information display modes), the contribution of CAI tools to overall interpreter performance can be different. Product-driven, practice-driven, and process-driven studies are identified as future trends in studies of CAI tools.


We study the intrinsic transformation of feature maps across convolutional network layers with explicit top-down control. To this end, we develop top-down feature transformer (TFT), under controllable parameters, that are able to account for the hidden layer transformation while maintaining the overall consistency across layers. The learned generators capture the underlying feature transformation processes that are independent of particular training images. Our proposed TFT framework brings insights to and helps the understanding of, an important problem of studying the CNN internal feature representation and transformation under the top-down processes. In the case of spatial transformations, we demonstrate the significant advantage of TFT over existing data-driven approaches in building data-independent transformations. We also show that it can be adopted in other applications such as data augmentation and image style transfer.


Testing of wireless sensor network protocols can be tedious for large networks when mobility is added. Mainly because these networks involve a large number of nodes scattered in an ad-hoc configuration. Although there are several publicly available static sensor network testbeds, testbeds where mobility is facilitated are very rare. One of the main objectives of this work is to provide a general hardware platform, which supports to implement different protocols for mobile sensor networks. The testbed is implemented with one base station node, one mule and five sensor nodes, where data mules move in a random manner through a community of fixed sensor nodes. As the mule comes within range of each sensor node, it collects the available data. After collecting data from all the sensor nodes, the mule returns to a central node, where it uploads all the data collected. The motes are connected to the central node through a Local Area Network (LAN), which provides a monitoring backbone network to the testbed. Testbed provides the facility of analyzing protocols with various user friendly features at the central node. Motes behavior when communicating with the mule can be monitored in real time. Communication protocols for data transfer between a mobile node and a fixed node were developed and tested on the testbed platform The designed test bed is a useful tool for educational and research purposes in the area of wireless sensor networks.


Conducting interviews with "high-stake" offenders, especially those accused of murder and sexual offences, represents a complex and emotive area of work for police officers. Using an English sample of 59 actual police interviews, the effects of empathy and question type on the amount of investigation-relevant information obtained from interviews with suspects of child murder, child sex offences and adult murder were analysed and compared. No direct effects of empathy on the amount of information elicited were found. However, in interviews classified as empathic, interviewers asked significantly more appropriate questions than they did in interviews classified as non-empathic, and significantly more items of information were elicited from appropriate questions. There was a significant effect of offence type on the number of inappropriate, questions asked, with significantly more inappropriate questions being asked in interviews with suspects of child sex offences than in interviews with suspects of child or adult murder.


Precambrian Ashe Formation. No correlation between mineral assemblages and metamorphic zones. Modal analyses and quantitative chemical analyses for Mg, Al, Ca, Fe, Ni, Mn, Cu, Co, K, and Zn lead to the recognition of two distinct types of metamorphosed ultramafic bodies based on the degree of metasomatic alteration. A retrograde hydration of the ultramafic protolith produced the tremolite-chlorite-talc anthophyllite assemblage with relict olivine. In a second stage, serpentine replaced some of the tremolite and olivine. A later partial dehydration led to the more strongly foliated tremolite-chlorite-talc schist or phyllonite.--Modified journal abstract.


ABSTRACT: Global adoption of International Financial Reporting Standards (IFRS) is thought to increase financial statement reliability and comparability. Although IFRS is required or allowed in over 130 nations, some countries modify IFRS as issued by the International Accounting Standards Board (IASB). This study is designed to closely examine each country that modifies IFRS in an effort to determine whether these modifications impair financial statement comparability. First is that countries lack the resources to implement the newest version of IFRS or ensure proper translation of the standards. Second is that countries make specific changes to allow IFRS to better meet the needs of their financial reporting environment. I categorize the first set of countries as default countries and the second set as design countries. The study results in several interesting and useful contributions. First, I develop a new typology for future IFRS research that includes not only the locally adopted category, but also ...


Map matching, the ability to match a local map built by a mobile robot to previously built maps, is crucial in many robotic mapping, self-localization, and simultaneous localization and mapping (SLAM) applications. In this paper, we propose a solution to the "map-to-text (M2T)" problem, which involves the generation of text descriptions of local map content based on scene understanding to facilitate fast succinct text-based map matching. Unlike previous local feature approaches that trade discriminativity for viewpoint invariance, we develop a holistic view descriptor that is view-dependent and highly discriminative. Our approach is inspired by two independent observations: (1) The behavior of mobile robots given a local map can often be characterized by a unique viewpoint trajectory, and (2) a holistic view descriptor can be highly discriminative if the viewpoint is unique given the local map. Our method consists of three distinct steps: (1) First, an informative local map of the robot's local surroundings is built. (2) Next, a unique viewpoint trajectory is planned in accordance with the given local map. (3) Finally, a synthetic view is described at the designated viewpoint. Because the success of our holistic view descriptor depends on the assumption that the viewpoint is unique given a local map, we also address the issue of viewpoint planning and present a solution that provides similar views for similar local maps. Consequently, we also propose a practical map-matching framework that combines the advantages of the fast succinct bag-of-words technique and the highly discriminative M2T holistic view descriptor. The results of experiments conducted using the publicly available radish dataset verify the efficacy of our proposed approach. Further, although this paper focuses on the standard 2D pointset map, we believe that our approach is sufficiently general to be applicable to a broad range of map formats, such as the 3D and general view-based maps.


Objective: To identify articles related to nursing care of critically ill patients during the immediate postoperative period in the postanesthesia care unit. Method: Integrative literature review included the following steps: develop guiding question; establish inclusion and exclusion criteria; define the information to be extracted from the study; assess the studies included in the research; interpret the results; and present the review. The following databases and/or portals were used: BVS, PubMed, Scopus, COCHRANE, Web of Science, and CINAHL. Results: Seven articles were found. The nursing care evidenced in this study was composed of performing invasive and noninvasive hemodynamic monitoring, pulmonary physical examination, urinary output control, fluid, electrolytes and acid-base balance, laboratory tests of samples and their interpretation, and recommendations for interventions during respiratory distress. Conclusion: It became clear that there is a need for a critical eye associated with the nurses' clinical knowledge to provide patients with intensive care during their stay in the postanesthesia care unit. Keywords: Postanesthesia nursing. Perioperative nursing. Intensive care


I read the article by Bar-Or et al.1 with interest. I am curious why the authors chose to give Pneumovax 23 (PPSV23) first and then, for the OCR1 group, gave Prevnar (PCV13) 4 weeks after? This is not consistent with CDC recommendations. These recommendations state that for patients with iatrogenic immunosuppression—e.g., on ocrelizumab—PCV13 should be given first and then PPSV23 no sooner that 8 weeks later. However, in cases in which PPSV23 was given first, PCV13 should not be given sooner than 1 year later. The trial design in VELOCE to give PCV13 4 weeks after PPSV23 is not consistent with CDC recommendations and can be misinterpreted by readers as the correct order and timeframe in which to give these immunizations. See immunize.org/catg.d/p3075.pdf for further information.


Loss of Kv11.1 potassium channel function is the underlying cause of pathology in long-QT syndrome type 2, one of the commonest causes of sudden cardiac death in the young. Previous studies have identified the cytosolic PAS (Per/Arnt/Sim) domain as a hotspot for mutations that cause Kv11.1 trafficking defects. To investigate the underlying basis of this observation, we have quantified the effect of mutants on domain folding as well as interactions between the PAS domain and the remainder of the channel. Apart from R56Q, all mutants impaired the thermostability of the isolated PAS domain. Six mutants, located in the vicinity of a hydrophobic patch on the PAS domain surface, also affected binding of the isolated PAS domain to an N-terminal truncated hERG (human ether-a-go-go-related gene) channel. Conversely, four other surface mutants (C64Y, T65P, A78P and I96T) and one buried mutant (L86R) did not prevent the isolated PAS domain binding to the truncated channels. Our results highlight a critical role for interactions between the PAS domain and the remainder of the channel in the hERG assembly and that mutants that affect PAS domain interactions with the remainder of the channel have a more severe trafficking defect than that caused by domain unfolding alone.


OBJECTIVE
To explore (i) the potential of polyethylenimine (PEI) nanoparticles as a vector for delivering genes into equine corneal fibroblasts (ECFs) using green fluorescent protein (GFP) marker gene, (ii) whether PEI nanoparticle-mediated decorin (DCN) gene therapy could be used to inhibit fibrosis in the equine cornea using an in vitro model.

PROCEDURE
Polyethylenimine-DNA nanoparticles were prepared at nitrogen-to-phosphate (N-P) ratio of 15 by mixing 22 kDa linear PEI and a plasmid encoding either GFP or DCN. ECFs were generated from donor corneas as previously described. Initially, GFP was introduced into ECFs using PEI nanoparticles to confirm gene delivery, then DCN was introduced to evaluate for antifibrotic effects. GFP gene delivery was confirmed with real-time qPCR and ELISA. Changes in fibrosis after DCN therapy were quantified by measuring α-smooth muscle actin (αSMA) mRNA and protein levels with qPCR, immunostaining, and immunoblotting. Cytotoxicity was determined by evaluating cell morphology, cellular viability, and TUNEL assay.

RESULTS
Polyethylenimine-green fluorescent protein-treated cultures showed 2.2 × 10(4) GFP plasmid copies/μg of cellular DNA and 2.1 pg of GFP/100 μL of lysate. PEI-DCN delivery significantly attenuated TGFβ-induced transdifferentiation of fibroblasts to myofibroblasts (2-fold decrease of αSMA mRNA; P = 0.05) and significant inhibition of αSMA (49 ± 14.2%; P < 0.001) in immunocytochemical staining and immunoblotting were found. Furthermore, PEI-DNA nanoparticle delivery did not alter cellular phenotype at 24 h and cellular viability was maintained.

CONCLUSIONS
Twenty-two kilo dalton Polyethylenimine nanoparticles are safe and effective for equine corneal gene therapy in vitro. PEI-mediated DCN gene delivery is effective at inhibiting TGFβ-mediated fibrosis in this model.


Objectives: Better dressings are needed for both receiver and donor sites in clinical management of burn wounds. Current study aims to check the efficacy and safety of BloodSTOP iX Wound Heal Nanocellulose Matrix (BSM) in managing burn wound.

Materials and methods: Characterization of BloodSTOP iX Nanocellulose Matrix was assayed with scanning electron microscope (SEM) and Fourier Transform Infrared Spectroscopy (FT-IR). For the preclinical study, two burn injury animal models were established: a contusion model and partial-thickness burn model. A total of 12 rabbits (male/female; 2.0-2.5 kg) were used in this initial experiment. Assessments were made at two time points: 1 week and 2 weeks post-injury. Six rabbits underwent skin contusion and six partial-thickness skin burn. At 1 week and two weeks post-injury, gross pathologic and histologic observations of changes and scarring were conducted. For clinical trial, during September 2015 to September 2016, a total 46 patients from two medical centers were enrolled in this study, including control group 16 cases and BSM 30 case. Each group has been sub-grouped into skin donor site and transplanted site. At 7, 14 and 20 days post treatment, clinical outcome were assayed.

Results: The microstructure of Nanocellulose and nano-structure of BloodSTOP iX Wound Heal Nanocellulose Matrix was confirmed. Preclinical results demonstrated that BSM promoted the burn wound healing in both animal models. In the clinical experiment, BSM decreased recurrence of bleeding post application and burning/pain feeling, while an anti-infection effect was also noted. More strikingly, BSM promoted skin epithelialization and improved scar tissue. Those effects were observed in both donor and receiver sites.

Conclusion: BloodSTOP iX Wound Heal Nanocellulose Matrix (BSM) is safe and effective in burn wound care for skin grafting on both donor site and transplanted site.


Irregular exercise or insufficient physical activity may disrupt the biological clock and secretion of the melatonin hormone, which is important in sleep regulation. Regular exercise with a certain intensity and duration can help the body to increase melatonin production which can reduce sleep disorders. A search of full-text articles relevant to exercise and sleep quality was conducted in this literature review. We used four international databases: PubMed, PMC, Wiley Library, and ProQuest. We searched for articles published from 2017 to 2021. After screening the collected articles, only 12 articles were included. The articles were assessed using the JBI appraisal tools and the data were analyzed using descriptive methods. It was found that regular exercise at a certain intensity and duration affects the production of the melatonin hormone in humans. 6 out of the 12 articles revealed that melatonin levels changed in the study participants after doing exercise. Furthermore, 6 other articles mentioned that exercise had an impact on improving sleep quality.
Keywords: physical activity, exercise, sleep quality, melatonin hormone


Obstructive sleep apnoea is highly prevalent in acute coronary syndrome patients eligible for enrolment in cardiac rehabilitation programmes. This condition is an independent predictor of increased morbidity and comorbid conditions in the general population and can lead to an increase in major adverse cardiac events such as revascularization, heart failure and hospital readmission in cardiac patients. There is convincing evidence that treatments such as continuous positive airway pressure or mandibular advancement devices can successfully treat obstructive sleep apnoea and these conditions can be improved or negated resulting in improved cardiac rehabilitation outcomes and improved health related quality of life. Given the potential benefits of obstructive sleep apnoea treatment it would make sense to screen for this condition upon entry to out-patient cardiac rehabilitation programmes. A two-stage approach to screening is recommended, where patients are initially evaluated for the probability of having obstructive sleep apnoea using a brief questionnaire (The STOP-Bang) and then followed up with objective evaluation (portable home monitor or polysomnography) where necessary. Potential barriers to further referral and treatment could be partly mitigated by the training of cardiac rehabilitation staff in sleep disorders and screening.


Microgravity coupled with increased radiation exposure aboard the ISS provides a unique environment to simulate and study response to injury, inflammatory signaling, aging, and (pre-)malignant transformation of normal human hematopoietic stem cells (HSCs) in an accelerated timeframe. The NASA Twins study suggests that genomic, epigenomic, epitranscriptomic, and proteomic changes may detrimentally impact hematopoietic stem and immune cell fitness and induce stem cell exhaustion (Garrett-Bakelman et al., Science, 2019). Moreover, changes indicative of pre-cancer stem cell generation such as increased chromosome translocations and inversions occurred and persisted post-flight. Additionally, a recent publication entitled Multisystem Toxicity in Cancer: Lessons from NASA's Countermeasures Program found significant similarities between the multisystem physiological toxicities in cancer patients and during spaceflight (Scott et al, Cell 2019). These reports highlight the benefits of studying injury response, changes in mutational profiles and cancer evolution in microgravity at the stem cell level.
 For this study, we designed a novel bioreactor system to support the culture of donor-derived human HSCs in low Earth orbit (LEO). A sponge matrix and stromal cells model the microenvironment HSCs reside in within the bone marrow niche. Testing on Earth confirmed our system's ability to maintain stem cell fitness over several weeks. To assess stem cell physiology in LEO over time, we lentivirally transduce a reporter into the HSCs pre-flight (Pineda et al., Scientific Reports 2016), which allows for cell cycle tracking via fluorescence imaging. This will provide data for assessment of stem cell health, maintenance and functionality. Furthermore, we will be analyzing mutational status post-flight, with a focus on signatures we have previously connected to (pre-)malignant transformation via RNA sequencing analysis (Jiang, Cancer Cell 2019). Our bioreactors are scheduled to launch as part of the SpaceX CRS-24 mission on Dec 21, 2021. This investigation may provide valuable insights into the maintenance of hematopoietic stem cell health and functionality, response to injury through accumulation of mutations and, eventually, the mechanisms fueling long-term (pre-)malignant transformation into leukemia stem cells.
 Citation Format: Luisa Ladel, Jessica Pham, Isabelle Oliver, Larisa Balaian, Catriona HM Jamieson. Assessing hematopoietic stem cell fitness within a nanobioreactor in microgravity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3154.


INTRODUCTION The mechanical environment due to different implant designs and fixation methods has received relatively little attention despite the fact that femoral component loosening is a major contributor to the need for revision surgery. This study considers the stresses in the distal femur due to two different implant geometry variations: a pegged or cruciate retaining (CR) implant and a box section or posterior stabilizing (PS) implant. Three dimensional finite element (FE) models of the intact femur and femur with the above implants were constructed and computationally subjected to loading representing a walking cycle to evaluate changes in the stress field.


Ideology is a system of belief. It is one variant form of those comprehensive patterns of cognitive and moral beliefs about man, society, and the universe in relation to man and society, which flourish in human societies. Ideologies are characterized by a high degree of explicitness of formulation over a very wide range of the objects with which they deal; for their adherents there is an authoritative and explicit promulgation. As compared with other patterns of beliefs, ideologies are relatively highly systematized or integrated around one or a few pre-eminent values, such as salvation, equality, or ethnic purity.


Because it is a slice of one's life as well as a method for gathering data and insights, and because it entails socio-cultural immersion and interpersonal trust, field research confronts political scientists with a special set of normative issues not encountered in libraries, laboratories, or home countries. This essay weighs four plausible yet fallible positions on the ethics of fieldwork overseas, with particular reference to American political science research in the Arabic-speaking world in the 21st century. I am raising questions I cannot really answer: specifically, amidst American military engagement and a good deal of spying by governments all around, can we, or ought we, practice scholarly detachment, reciprocity, activism, or, perhaps, espionage?


Sources localization is an important theme of antenna and signal processing researches since decades. It has a lot of applications for source characterization, which leads to object detection, used in submarine field as well as seismic and remote sensing studies. The particularity of array processing is that we are looking at spatio-temporal vector signals which are generated by both radiating sources or reflected by buried objects and ambient medium. These signals are generally corrupted by an additive noise. When the number of sources is greater than the number of the sensors of the smart antenna system, classical methods become unusable. Recently, a new subspace method called incoherent sensor by sensor processing (ISSP) for estimation of directions of arrival (DOAs) is proposed. It is based on a study sensor by sensor to estimate firstly times of arrival(TOAs), then the DOAs of the sources are estimated. The main drawback of this method is the computational load needed to estimate accurately the DOAs. In this paper, we propose new faster methods thanks to the numerical complexity reduction of the existing algorithms. This last point is important nowadays to make embedded systems faster.


Lung adenocarcinomas (LUAD) represent the most common lung cancer subtype and frequently harbor somatic mutations in the KRAS oncogene (KM-LUADs). While enhanced screening has improved early diagnosis of KM-LUAD, patient prognosis remains moderate to poor. Decoding the earliest events driving KM-LUADs can inform of ideal targets for its interception. Previous work showed that tobacco carcinogen (NNK) exposure leads to a pervasive field of injury comprised of molecular (e.g., KRAS mutations) and inflammatory changes that are shared between LUADs and their adjacent normal-appearing ecosystem. We and others have also shown that early immune and inflammatory alterations are implicated in the progression of normal lung (NL) epithelia and premalignant lesions (PMLs) to KM-LUAD. Yet, we still do not know the identities of specific epithelial subsets or how they promote a field of injury and inspire KM-LUAD pathogenesis. Here, we performed single-cell RNA-sequencing (scRNA-seq) of lungs from a human-relevant mouse model that develops PMLs and somatic KM-LUADs following NNK exposure. Analysis of 203,991 cells including 19,513 epithelial subsets after NNK cessation and at the onset of KM-LUADs revealed a unique population of alveolar cells that closely associated with tumor inception. These cells were highly evident in NNK- but not in control saline-exposed animals. Trajectory analysis showed that tumor clones developed through these transitionary cells, henceforth referred to as alveolar intermediate cells (AICs). Notably, AICs persisted for months after NNK cessation and acquired the same driver Kras mutations found in the resultant LUADs, thus supporting a role for AICs as KM-LUAD progenitors. Intriguingly, AICs harbored elevated expression of key components of p53 signaling (Trp53, Cdkn2a) and pro-inflammatory responses (IL-1β receptor Il1r1, NF-κB), and augmented cell-cell communication with Il1b+ macrophages which were enriched in LUAD-bearing lungs. Indeed, targeting IL-1β attenuated KM-LUAD development and increased anti-tumor immunity. In parallel, murine AIC expression profiles were significantly enriched in transcriptomes of human PMLs and LUADs. We thus probed our in-house and expanding scRNA-seq cohort of enriched (by sorting) epithelial subsets from human LUADs and NL, including 191,491 alveolar cells. AICs were not only evident in human lung tissues, but their fractions were also significantly increased in LUADs relative to NL. In conclusion, we identified a unique alveolar cell state that typified KM-LUAD progenitors, associated with inflammatory cues, and progressed along the pathologic continuum of damaged epithelium to KM-LUADs. Ongoing studies are evaluating whether AICs, in concert with tumor-initiating inflammation, trigger a field of injury that may underlie early phenotypic initiation and development of KM-LUAD.
 Citation Format: Ansam Sinjab, Guangchun Han, Warapen Treekitkarnmongkol, Dapeng Hao, Enyu Dai, Luisa M. Solis, Seyed Javad Moghaddam, Junya Fujimoto, Jichao Chen, Matthew Edwards, Christopher S. Stevenson, Avrum E. Spira, Linghua Wang, Humam Kadara. An emerging role for inflammation-associated alveolar intermediate cells in early phenotypic development of KRAS-mutant lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1586.


In Mobile World Interoperability for Microwave Access (also known as IEEE802.16e), a standard power-saving mechanism (PSM) that alternates between sleep and wake modes is adopted to extend the lifetime of mobile stations (MSs), but it simultaneously induces a medium access control (MAC) service data unit (SDU) response delay. The standard PSM defines three power-saving classes (PSCs), among which Type I is based on a binary-exponential increase in the sleep window, and Type II is based on a constant sleep window. Over the years, most studies have mainly focused on PSC Type I, while only a few have considered Type II. This study derives several analytical models of PSC Type II and evaluates the power consumption and MAC SDU response delay performance. Based on the derived models, an optimised power under delay-bound mechanism (OPDBM) is proposed to find the optimal initial sleep window parameter that minimises the power consumption of an MS while satisfying a given MAC SDU response delay constraint. Both numerical analysis and simulation experiments show that the OPDBM effectively minimises the power consumption of an MS while guaranteeing any imposed/required MAC SDU response delay constraint in a wide variety of environments.


The representations and memory of living space are essential to developing mental maps and cartographic documents. In this regard this investigation as a primary objective to understand how mind maps can contribute pedagogically classes in Geography and History as well, breaking the dichotomy space / time. From the point of view of theoretical and methodological the research relied on the analysis of the school project "Our Neighborhood, Our Place" developed at the Municipal School "Vereador Hamilton Teodoro" in Governador Valadares (MG), along with a group of 7th grades from elementary school and the articulation of authors who discuss the concepts of representation, memory, space and place.


Abstract The increasing demand of the chiral compounds in drug and food industries has stimulated the considerable attention towards the chiral recognition and separation methods. For this, a number of chiral selectors have been employed for the recognition of enantiomers. In this context, chiral ionic liquids (CILs) have appeared as cheap and lucrative chiral selectors. The present report enlightens the role of CILs in chiral recognition of the enantiomers using various analytical techniques such as NMR and fluorescence spectroscopy, liquid and gas chromatography and capillary electrophoresis. Due to plethora of reports published in this direction, we have tried to limit our discussion about the literature published in the last decade only.


The goals of the Iris database management system are to enhance database programmer productivity and to provide generalized database support for the integration of future applications. Iris is based on an object and function model. Iris objects are typed but unlike other object systems, they contain no state. Attribute values, relationships and behavior of objects are modeled by functions. The Iris architecture efficiently supports the evaluation of functional expressions. The goal of the architecture is to provide a database system that is powerful enough to support the definition of functions and procedures that implement the semantics of the data model. An overview of the data model is provided, the architecture is described in detail, and implementation experience and usage of the system are discussed. >


The non-homogeneous electromagnetic plane waves are characterized by a wave four-vector depending on space-time. We give here their covariant form.


Both community development and community participation are dealt with as two faces to one coin. However, Community participation in Jordan is seen as a secondary element to be affiliated with the community development. This understanding is clearly apparent throughout the absence of meaningful role for local people in the planning, implementation and the evaluation of the social centres' programmes. Local administration committees and women committees, which are formed in each centre to help in administering the centres are not effective enough to achieve their stated goals. The reasons may be referred to the unrealization of the importance of their participation, besides the centres' managements intention to marginalize their role. The aforesaid are resulted in the absence of their role in participating in planning, implementation and evaluation of the centres' programmes. Therefore, there is a clear absence for effective planning, implementation and evaluation of any programme provided by the social services centres, while planning, implementation and evaluation if they do exist are always carried out in unsystematic manner. Overall, community participation in the programmes of the social centres in Jordan is unplanned and suffers of many obstacles. Some of these obstacles are related to the sponsor agency (i.e. QAF). Whereas others related to the beneficiaries themselves and largely represented in the weakness of their motivation to have voice in planning, implementation and evaluation of any programme.


OBJECTIVE
Consistent continuous glucose monitoring (CGM) use is a challenge in youth with type 1 diabetes. This study aimed to investigate patient and family behavioral and clinical characteristics associated with interest in implementing CGM.

RESEARCH DESIGN AND METHODS
In a cross-sectional study, we compared 120 youth interested in starting CGM (the CGM group) with a general sample of 238 youth with type 1 diabetes (the Standard group). Youth and their parents completed validated surveys assessing adherence to diabetes management, diabetes-specific family conflict, parent involvement in diabetes management, and youth quality of life. Demographic and clinical data were obtained from chart review and interview.

RESULTS
Youth participants had a mean age of 13.0±2.8 years, diabetes duration of 6.3±3.4 years, and hemoglobin A1c (HbA1c) level of 8.2±1.0% (66±11 mmol/mol). Youth in the CGM group performed more frequent blood glucose monitoring, had lower HbA1c levels, and were more likely to be treated by continuous subcutaneous insulin infusion (CSII) and to be living in two-parent homes than youth in the Standard group. Compared with the Standard group, youth interested in wearing a CGM device and their parents reported greater adherence to diabetes management, less diabetes-specific family conflict, and higher youth quality of life. No differences were found between groups with respect to parent involvement in diabetes management by both youth and parent reports.

CONCLUSIONS
In efforts to enhance CGM uptake, it is important to address factors such as blood glucose monitoring frequency, CSII use, adherence, and diabetes-specific family conflict when considering youth with type 1 diabetes for CGM implementation.


Maharanga bicolor, Boraginaceae, is used in the Nepalese ethnomedicine for the treatment of several diseases. In the course of screening investigations the dichloromethane extract of the roots of Maharanga bicolor was found to inhibit the growth of gram positive bacteria. Bio-assay directed fractionation led to the isolation of five active naphthazarins, deoxyalkannin (1), alkannin (2), acetylalkannin (3), alkannin beta-hydroxyisovalerate (4) and alkannin beta-acetoxyisovalerate (5). Compounds 2-5 showed antibacterial activity against multi resistant human pathogenic Staphylococcus and Enterococcus species and 1, 4 and 5 showed antiviral activity against herpes simplex virus type-1.


Well baby clinic records on 1, 186 infants born in 1975 to 1976 on the island of Tutuila, American Samoa, form the basis for this study of the growth in weight and length from birth to 12 months. Semi‐longitudinal curves of weight and length indicate that these infants have median weights near the NCHS 75th percentile (boys) and 90th percentile (girls) up to 6 months, falling to just below the 75th percentile by 12 months. Median lengths are between the NCHS 50th and 25th percentile. Weight gain from birth to six months was found to be higher than for any other reported population (4.92 kg, sexes combined). The infant feeding pattern was found to exert a significant influence on rate of weight gain for boys between birth and 1–4 months, with the breast‐fed boys gaining more rapidly than artificial‐fed infants.


ABSTRACT Introduction: Semaglutide once-weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) injection has been approved as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus (T2DM). Areas Covered: The safety and efficacy of the semaglutide once-weekly injection are reviewed using results from preliminary pharmacology studies and later-phase randomized control trials (RCTs) and meta-analyses. Semaglutide once-weekly is compared to placebo and active comparators for T2DM in the SUSTAIN clinical trial series, with outcomes of: glycemic control, weight loss, major adverse cardiovascular events, and adverse effects. Risk for diabetic retinopathy complications (DRCs) is reviewed in detail, due to significantly higher risk for DRCs seen in SUSTAIN 6. SUSTAIN 6 is the first instance of a GLP-1 RA demonstrating significantly increased risk for DRCs. Semaglutide's current regulatory approvals, practice considerations, and cost-effectiveness compared to similar therapies are also considered. Expert Commentary: Semaglutide demonstrates high glycemic efficacy and favorable safety profile, and reduces the risk for cardiovascular events. Mild to moderate gastrointestinal events and retinopathy complications were more common with semaglutide compared to placebo, though serious adverse events were similar to controls and infrequent. Improved clinical efficacy should be carefully weighed against the risk for GI and retinopathy complications.


In natural waterways and estuaries, an understanding of turbulent mixing is critical to the knowledge of sediment transport, storm-water runoff during flood events, and release of nutrient-rich wastewater into ecosystems. The predictions of contaminant dispersion in estuaries can rarely be predicted analytically without exhaustive field data for calibration and validation. Why? In natural estuaries, the flow Reynolds number is typically within the range of 10 to 10 and more. The flow is turbulent, and there is an absence of fundamental understanding of the turbulence structure. Any turbulent flow is characterised by an unpredictable behaviour, a broad spectrum of length and time scales, and its strong mixing properties. In his classical experiment, Osborne REYNOLDS (1842-1912) illustrated this key feature with the rapid mixing of dye of a turbulent flow (REYNOLDS 1883). This is seen in Figure 1 showing the original Reynolds experiment and a modified Reynolds experiment. In turbulent flows, the fluid particles move in very in'egular paths, causing an exchange of momentum from one portion of the fluid to another, as shown in Figure 1 where dye is rapidly dispersed in the turbulent flow regime (Re = 2.3 10\ In natural estuaries, strong momentum exchanges occur and the mixing processes are driven by turbulence. Interestingly Osborne REYNOLDS himself was involved in the modelling of estuaries (REYNOLDS 1887). Relatively little systematic research was conducted on the turbulence characteristics in natural estuarine systems, in particular in relatively shallow-water systems. Long-duration


Prostate cancer (PCa) remains the second leading cause of death in men, despite the multimodal options offered in the clinics. Long latency and indolent nature of PCa provides window of opportunity for preventive interventions using natural and synthetic agents. Quercetin, a bioflavonoid abundant in fruits and vegetables, has been reported to inhibit growth in cancer and reduce inflammation in conditions like prostatitis. Considering this, we investigated the chemo-preventive effects of Quercetin on PCa. The effects of Quercetin on apoptosis and associated proteins on both RNA and protein levels were determined using apoptosis assay, real-time qPCR and western blot, respectively. Furthermore, an antibody microarray was performed to observe changes induced by Quercetin on signaling molecules and possible mechanism of cell survival/apoptosis in PCa. PCa cells treated with Quercetin showed decreased cell proliferation in a time and dose dependent manner, while no significant effect was seen on normal prostate cells. Quercetin treatment also significantly induced apoptosis in PCa cells, as compared with untreated controls. Different phosphorylation status of key molecules (Bcl-2, Akt-1 and NF-k B) was observed following Quercetin treatment in PCa cell lines, as compared with untreated controls, which are known to be involved in supporting PCa progression. These results suggest that Quercetin could be a potential chemo-preventative agent capable of slowing down the progression of PCa, by increasing apoptosis and decreasing cell proliferation. Note: This abstract was not presented at the meeting. Citation Format: Ashely B. Ward, Hina Mir, Neeraj Kapur, Shailesh Singh. Quercetin inhibits prostate cancer by modulating molecules involved in apoptosis and cell proliferation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4642. doi:10.1158/1538-7445.AM2015-4642


Human embryonic stem (hES) cell lines are of great potential in cell transplantation therapy. However, recipients of such allogeneic transplants probably need treatment with immunosuppressants. Recently, Taylor et al. [Lancet 2005;366:2019–2025] proposed banking of hES cell lines and estimated the required number of hES cell lines for beneficial human leukocyte antigen (HLA) matching in the U.K. population. Here, we carried out such an estimation in the Japanese population. We calculated the proportion of patients who can find at least one HLA‐matched donor at three loci of HLA‐A, ‐B, and ‐DR. With a bank of hES cell lines from 170 randomly selected donated embryos, 80% of patients were expected to find at least one hES cell line with a single mismatch at one HLA locus or a better match. Furthermore, 80% of patients are expected to find at least one donor with complete matching at the three HLA loci if parthenogenetic homozygous hES cell lines are established from 55 randomly selected donated oocytes. The relatively low ethnic diversity of the Japanese population may have resulted in a high success rate in beneficial matching. Moreover, parthenogenetic hES cell lines can greatly reduce the number required for a higher degree of HLA matching.


Abstract. Organosulfates make significant contributions to atmospheric secondary organic aerosol (SOA), but little is known about the thermodynamic properties of atmospherically relevant organosulfates. We have used the COSMOtherm program to calculate both the gas- and condensed-phase properties of previously identified atmospherically relevant monoterpene- and isoprene-derived organosulfates. Properties include solubilities, activities and saturation vapor pressures, which are critical to the aerosol-phase stability and atmospheric impact of organosulfate SOA. Based on the estimated saturation vapor pressures, the organosulfates of this study can all be categorized as semi-volatile or low-volatile, with saturation vapor pressures 4 to 8 orders of magnitude lower than that of sulfuric acid. The estimated p Ka values of all the organosulfates indicate a high degree of dissociation in water, leading in turn to high dissociation-corrected solubilities. In aqueous mixtures with inorganic sulfate, COSMOtherm predicts a salting-out of both the organosulfates and their sodium salts from inorganic co-solutes. The salting-out effect of ammonium sulfate (less acidic) is stronger than of ammonium bisulfate (more acidic). Finally, COSMOtherm predicts liquid–liquid-phase separation in systems containing water and monoterpene-derived organosulfates. The COSMOtherm-estimated properties support the observed stability of organosulfates as SOA constituents and their long-range transport in the atmosphere but also show significant variation between specific compounds and ambient conditions.


Abstract In addition to model validation techniques and intermodel comparison projects, the authors propose the use of software engineering metrics as an additional tool for the enhancement of "quality" in climate models. By discriminating between internal, directly measurable characteristics of structural complexity, and external characteristics, such as maintainability and comprehensibility, a way to benefit climate modeling by the use of easily derivable metrics is explored. As a small illustration, the results of a pilot project are presented. This is a subproject of the Project for Intercomparison of Landsurface Parameterization Schemes in which the authors use some typical structural complexity metrics, namely, for control flow, size, and coupling. Finally, and purely indicatively, the authors compare the results obtained from these metrics with scientists' subjective views of the psychological complexity of the programs.


The conventional methods of treating cancer with chemo- and radiotherapy present plenty of serious problems, such as low therapeutic index and high systemic toxicity. The advanced cancer treatment strategies utilize nanoformulations of drugs that can enter a tumor due to the enhanced permeability and retention (EPR) effect. However, EPR fails in the treatment of several human diseases. Mainstream biomedical studies are focused on creating the drugs that would enter the tumor with higher effectiveness and require smaller doses for administration. A two-stage drug delivery system is an encouraging alternative solution. At first, the primary, non-toxic targeting module is delivered to the tumor cells, followed by injection of the second complementary targeting module at a considerably lower dose, thus decreasing systemic toxicity. To meet the challenge, we have developed a two-stage drug delivery system (DDS), mediated by the high-affinity binding of the Barnase*Barstar protein pair. Barnase and Barstar act as lego bricks linking the first and the second modules on the surface of the cancer cell. Barnase (12 kDa) is a natural ribonuclease from Bacillus amyloliquefaciens, while Barstar (10 kDa) is its natural inhibitor. The Barnase*Barstar is one of the strongest known protein*protein complexes with Kaff = 1014 M−1 exhibiting extraordinarily stability in severe conditions. Artificial scaffold polypeptide DARPin9_29 genetically fused with Barstar served is a first module of the developed two-step DDS. DARPin9_29 (14 kDa) specifically recognizes the tumor marker HER2 overexpressed on human breast cancer cells. As a second module, a therapeutic nano-cargo was developed based on fluorescent polymer PLGA nanoparticles loaded with diagnostic Nile Blue dye and the chemotherapeutic drug doxorubicin. This nano-PLGA structure was covalently coupled to Barnase. We showed two-stage efficient labeling of HER2-overexpressing cancer cells using the first non-toxic module DARPin9_29-Barstar and the second toxic nano-module PLGA-Barnase. We demonstrated the doxorubicin-induced cytotoxicity of this two-step DDS based on polymer nanoparticles and proteinaceous Barnase-Barstar interface and showed more than 10-fold therapeutic dose reduction versus free doxorubicin. We believe that the developed two-step DDS based on PLGA nano-cargo and protein interface will promote the creation of new-generation cancer treatment strategies.


Dane-particle cores labelled with [3H]TTP were subjected to ultracentrifugation in a metrizamide density gradient. Two populations of core particles with different densities were obtained, and radioactivity was found only in the cores that sedimented at the lower density (1.19-1.23 g/cm3). All the cores in this group, when spread in a monolayer, were found to expel a closed circular double-stranded DNA molecule. In contrast, the core particles that sedimented at the higher density (1.23-1.27 g/cm3) were not associated with radioactivity, nor was any DNA strand extruded from them. These results show that metrizamide density gradients allow the separation of complete hepatitis B virions for the study of viral DNA.