Direct volume rendering is a key technology for visualizing large 3D data sets from scientific or medical applications. Transfer functions are particularly important to the quality of direct volume-rendered images. A transfer function assigns optical properties, such as color and opacity, to original values of the data set being visualized. Unfortunately, finding good transfer functions proves difficult. It is one of the major problems in volume visualization. The article examines four of the currently most promising approaches to transfer function design. The four approaches are: trial and error, with minimum computer aid; data-centric, with no underlying assumed model; data-centric, using an underlying data model; and image-centric, using organized sampling.


Large-scale uniform α-Co(OH)₂ nanowire arrays (NWAs) with an average length of ∼20 μm grown on pyrolytic graphite (PG) were successfully synthesized by a hydrothermal method at 120 °C. Ultrasonication test was carried out toward the as-made nanoarray products and the result demonstrated their robust adhesion to graphitic substrate. After 300 s of sonication testing, α-Co(OH)₂ NWAs could still possess both integrated one-dimensional (1D) nanoarray architecture and good electronic connections with current collector. When investigated as electrochemical pseudocapacitor electrodes, α-Co(OH)₂ NWAs exhibited good energy-storage performance in terms of high specific capacitance of 642.5 F/g, good rate capability, and excellent capacity retention. Our work not only presents a cost-effective and scale-up synthetic method for α-Co(OH)₂ NWAs but also holds promise in general synthesis of long arrays of other metal hydroxides/oxide (TiO₂, Fe₂O₃, SnO₂, etc.) nanostructures on PG substrate by using α-Co(OH)₂ NWAs as sacrificial templates.


This research aims to see the flagship sector or the base sector in Merauke Regency. The type of data in this research is the data that is made from the central body statistic the District of Merauke with a time period 2016-2018.
The method used in this study is the Location Quotient (LQ) which is often used to see the development of the base sector in an area with the criteria LQ > 1 = base sector, LQ < 1 = Not a superior sector and if LQ = 1 Then the sector is only able to Meet the needs of its own region.
                The results of this study were obtained, almost all the business sector in Merauke District is a base sector. Where there are 3 sectors that are with the average value of LQ for the last three years, government administration, defence and social Security mandatory 0.04, Real Estate 0.97, as well as mining and excavation with LQ of 0.04 that is not a base sector. While 17 of the total sectors of 14 of them are the basis sectors where the results of the LQ showed that the agriculture, forestry, and fisheries sectors are still very superior to the average LQ 2.10 It is undeniable that the district Merauke is one of the largest rice suppliers for the surrounding area, such as Asmat District, Mappi and some other areas even the intereste state of Papua New Guinea.p
Keywords: Featured sector, Location Quotient


Objective To identify the determinants of children's iodine nutrition and their goitrous and nodular prevalence in iodine excessive areas before withdrawing iodized salt.Methods Three townships were selected by simple random sampling among the townships with median water iodine being 200~300 μg/L in Hengshui prefecture of Hebei Province.Results A total of 326 spot urinary samples of children aged 8~10 years were collected and measured.The median iodine of these samples ranged from 478.4~571.3 μg/L,and the proportions of urinary samples with iodine content over 300 μg/L varied from 77.9% to 86.6%.Children's urinary median iodine in each of 12 villages showed correlated positively with the median water iodine of the corresponding village(Spearsman,R=0.79,P=0.002),but not with median salt iodine(Spearsman,R=-0.17,P=0.6).Children's urinary median iodine had a linear correlation with median water iodine(R=0.83,F=22.0,P=0.001),and the linear regression equation was as follows:urinary iodine=318.1+0.829*water iodine.A total of 452 children aged 8~10 years were measured by ultrasound in these 3 townships,identifying 37 cases of goiter with goiter rate being 8.2%.There was no significant difference in goiter rates across gender and age groups.In 2 out of the 3 townships,15 cases of nodules were detected with average detection rate being 5.6%.The detection rates across gender and age groups were not significantly different.Conclusions Children's iodine over-nutrition could be mainly attributed to excessive water iodine,while being aggravated by iodized salt.Goiter was prevailing in these areas,and a high detection rate of thyroid nodules was also identified.The cause and prevalence of thyroid nodule need to be further studied.


The growth in Islamic Finance in many regions of the world during the last decade has been both significant and rapid, and has provided both individuals and businesses with the possibility of raising capital on a risk-shared basis rather than the more conventional debt finance. The chaotic and aggressive credit growth that partially led to the global economic crisis of 2008 has turned the attention of academicians and regulators to alternative lending methods, including Islamic Finance. According to The Banker, about USD 144BN was issued globally under Islamic finance instruments in 2012, with an annual growth rate of 20-25% and expected another USD 100BN in 2013, which totals to USD 400BN in Islamic bonds outstanding. Kazakhstan, along with other Central Asian countries has also experienced significant growth in Islamic Finance, both at personal and business level, and the stage is set for Islamic Finance to grow and to diversify into a major form of development finance. Some experts predict that the potential market size for Islamic financial instruments can easily reach USD 10BN within several years, but this requires much effort and aggressive promotion of products. This paper summaries the recent growth in Islamic Finance in the Republic of Kazakhstan and assesses the prospects for future growth of this form of finance in both Kazakhstan and the Central Asian Region.


of assessments used to give grades or to satisfy the accountability demands of an external authority, but rather the kind of assessment that can be used as a part of instruction to support and enhance learning. On this topic, I am especially interested in engaging the very large number of educational researchers who participate, in one way or another, in teacher education. The transformation of assessment practices cannot be accomplished in separate tests and measurement courses, but rather should be a central concern in teaching methods courses. The article is organized in three parts. I present, first, an historical framework highlighting the key tenets of social efficiency curricula, behaviorist learning theories, and "scientific measurement." Next, I offer a contrasting socialconstructivist conceptual framework that blends key ideas from cognitive, constructivist, and sociocultural theories. In the third part, I elaborate on the ways that assessment practices should change to be consistent with and support socialconstructivist pedagogy. The impetus for my development of an historical framework was the observation by Beth Graue (1993) that "assessment and instruction are often conceived as curiously separate in both time and purpose" (p. 291, emphasis added). As Graue notes, the measurement approach to classroom assessment, "exemplified by standardized tests and teacher-made emulations of those tests," presents a barrier to the implementation of more constructivist approaches to instruction. To understand the origins of Graue's picture of separation and to help explain its continuing power over presentday practice, I drew the chronology in Figure 1. A longerterm span of history helps us see that those measurement perspectives, now felt to be incompatible with instruction, came from an earlier, highly consistent theoretical framework (on the left) in which conceptions of "scientific measurement" were closely aligned with traditional curricula and beliefs about learning. To the right is an emergent, constructivist paradigm in which teachers' close assessment of students' understandings, feedback from peers, and student self-assessments would be a central part of the social processes that mediate the development of intellectual abilities, construction of knowledge, and formation of students' identities. The best way to understand dissonant current practices, shown in the middle of the figure, is to realize that instruction (at least in its ideal form) is drawn from the emergent paradigm, while testing is held over from the past. Historical Perspectives: Curriculum, Psychology, and Measurement


Efficient homologous recombination permits the directed introduction of specific mutations into the yeast genome. Here we describe a cloning-free, PCR-based allele replacement method that simplifies allele transfer between yeast strains. The desired allele from one strain is amplified by PCR, along with a selectable/counterselectable marker. After transformation, the resident allele in the target strain is replaced by creating a duplication of the new allele. Selection for direct repeat recombinants results in a single copy of the new allele in the target strain. Specifically, the desired allele is amplified by PCR with a pair of adaptamers, which are chimeric oligonucleotides that are used to amplify the allele and differentially tag its 5' and 3' ends. These tags allow the directed fusion to two different, but overlapping, regions of an appropriately tagged selectable/counterselectable marker after a second round of PCR amplification. Following cotransformation of the two fusion fragments into yeast, homologous recombination efficiently generates a duplication of the amplified allele flanking the intact selectable marker in the genome. After counterselection, only the desired allele is retained as a result of direct repeat recombination. A simple modification of this method allows the creation of de novo mutations in the genome.


LC50s and LT50s of boric acid and polybor formulated in water and 10% sucrose were determined for 3- to 5-d-old adult house flies, Musca domestica (L.), of mixed sex. Differences between boric acid and polybor toxicities were significant in 10% sucrose, but not in water. However, borates formulated in water had significantly lower LC50s than those formulated in 10% sucrose. Rate of kill for formulations in water was fairly uniform over time, whereas mortality from sucrose formulations was not observed until 17 h after treatment. Reasons for differences in the manifestation of mortality and possibilities for practical application are discussed.


Determinants of the probability of homeownership are analysed using a 20 per cent random sample of Danish homes with data covering characteristics of both the homes and their inhabitants. The sample data are from the beginning of the year 2004 and the analysis is based on a logistic regression. The paper adds to earlier papers by the same authors where determinants of the homeownership rate were found using (average) data for 270 Danish municipalities. By using data directly related to individual households whose inhabitants have chosen to be or not to be homeowners, the analysis reveals characteristics and restrictions that influence the choice between renting and ownership. Among the determinants investigated is civil and social status of the breadwinner and various household characteristics including income. The empirical results generally suggest that the impact of the determinants corresponds to theory. JEL Classification: R21.


Banana is an important source of food and income for millions of people in sub-Saharan Africa and Uganda in particular. This makes it one of the most important food crops in the country. However, production is limited by both biotic and abiotic constraints. Among the biotic constraints, is the decline in soil fertility. In addressing some of these biotic and abiotic constraints, banana breeding programmes are developing and releasing new banana varieties with limited information of their efficiency to capture soil nutrients. This study was to establish the physiological nutrient use efficiency of three new banana varieties namely FHIA17, M9 and M2 at harvesting time. The study was carried out in 8 (eight) districts of Uganda. Soil and tissue samples were collected from already established banana plantations for analysis of N, P, K, Ca and Mg. Tissue samples were collected by destructive sampling. Means of nutrients within district were separated using the Least Significant Difference (LSD) test at 5% level of significance (SAS, 2008). The nutritional status of bananas and the concentrations in various organs were, with respect to N, P, K, Ca and Mg, levels subjected to ANOVA. The relationship between plant content of the five nutrients and their concentration in the soil was determined by coefficient of correlation (r). The results showed no major significant nutrient use efficiencies between cultivars with FHIA 17 having the highest nutrient use efficiency. There were a few positive correlations between soil and plant nutrients.

 Key words: Nutrient concentrations, Banana cultivars, destructive sampling, nutrient interactions.


Dentinogenic ghost cell tumor (DGCT) is a rare neoplasm, representing 1.9% to 2.1% of all odontogenic tumors. Peripheral DGCT is a rare tumor with only 25 cases previously described in the English literature. The majority of cases have been reported to occur in the anterior part of the jaws. A rare case of peripheral DGCT is reported, located in the lingual side of the anterior mandible of a 68-year-old man. The patient presented a pedunculated painless growth of 1.5cm in diameter. Radiographically, no bone involvement was found. The lesion was excised and histologically characterized by islands of epithelial cells showing ameloblastoma-like features within fibrous background tissue. Dysplasic dentin and ghost cells with calcifications were frequently observed. Areas showing a connection between tumor cells and the overlying mucosa were also identified.


A new relationship type of social networks - online dating - are gaining popularity. With a large member base, users of a dating network are overloaded with choices about their ideal partners. Recommendation methods can be utilized to overcome this problem. However, traditional recommendation methods do not work effectively for online dating networks where the dataset is sparse and large, and a two-way matching is required. This paper applies social networking concepts to solve the problem of developing a recommendation method for online dating networks. We propose a method by using clustering, SimRank and adapted SimRank algorithms to recommend matching candidates. Empirical results show that the proposed method can achieve nearly double the performance of the traditional collaborative filtering and common neighbor methods of recommendation.


Introduction:
 A deep learning ECG algorithm, rECHOmmend, can accurately identify patients with any of seven structural heart diseases: five valvular diseases, low ejection fraction and interventricular septal (IVS) thickening. Components of the rECHOmmend composite label (IVS>15mm, mitral regurgitation) are also associated with hypertrophic cardiomyopathy (HCM). We hypothesized that despite being trained without HCM-specific labels, rECHOmmend can reliably identify HCM patients and achieve comparable performance to an HCM-specific classifier.

 Methods:
 Algorithms were developed from 2,898,979 ECGs acquired from 661,366 patients between 1984-2021. rECHOmmend was trained on a composite label derived from echocardiography and electronic health record (EHR) data. This ensemble model consists of 7 disease specific models with an aggregate model to predict a composite structural heart disease endpoint with shared clinical actionability. Separately, an HCM-specific model was trained on a binary label derived from EHR. To enable comparison, both classifiers were tested on a shared ECG holdout set (ECG prevalence 1.24%, patient prevalence 0.52%).

 Results:
 Despite being trained without HCM specific labels, the rECHOmmend ensemble showed comparable performance to a HCM-specific classifier (C-statistic: 0.92 [0.90-0.93] vs 0.90 [0.89-0.91]). At an operating point optimized for the F1-score, the sensitivity to HCM was higher for rECHOmmend at 0.42 [0.33-0.50] compared to 0.18 [0.15-0.21] for the HCM-specific classifier. rECHOmmend sustained performance across a range of IVS thicknesses, suggesting it was not solely reliant on IVS thickening for HCM identification and other ensemble components contributed to performance.

 Conclusions:
 A composite deep learning algorithm trained to identify structural heart diseases can identify clinically ascertained HCM with good performance, despite being trained without HCM-specific labels.


This paper investigates the dissipativity and performance characteristics of the semiactive control of the base isolated benchmark structure with magnetorheological (MR) fluid dampers. Previously, the authors introduced the concepts of dissipativity and dissipativity indices in the semiactive control of structures with smart dampers and studied the dissipativity characteristics of simple structures with idealized dampers. To investigate the effects of semiactive controller dissipativity characteristics on the overall performance of the base isolated benchmark building, a clipped optimal control strategy with a linear quadratic Gaussian (LQG) controller and a 20 ton MR fluid damper model is used. A cumulative index is proposed for quantifying the overall dissipativity of a control system with multiple control devices. Two control designs with different dissipativity and performance characteristics are considered as the primary controller in clipped optimal control. Numerical simulations reveal that the dissipativity indices can be classified into two groups that exhibit distinct patterns. It is shown that the dissipativity indices identify primary controllers that are more suitable for application with MR dampers and provide useful information in the semiactive design process that complements other performance indices. The computational efficiency of the proposed dissipativity indices is verified by comparing computation times.


Abstract : The RAND National Defense Research Institute assessed the potential impact that fielding the five Army vehicle modernization programs would have on the operational energy requirements of combat, combat support, and combat service support forces. The modernization programs planned at the start of the research were the Ground Combat Vehicle (since cancelled), the Armored Multi-Purpose Vehicle, the Joint Light Tactical Vehicle, the Paladin Integrated Management program vehicle, and the Modular Fuel System. The authors developed and applied a methodology that leveraged detailed combat effectiveness models to account for the operational energy needs associated with supporting combat missions. RAND s methodology enables a system-level examination of the battlefield. Using this framework, one can examine both the interplay between the Blue combat force and the Red threat, and the interactions among all the elements on the battlefield, including the support force and the protection force. The team assessed the modernization programs by simulating an MCO scenario with three phases: a combat phase, a combat support phase, and a combat service support phase, examining both the operational energy needs within these phases along with the combat effectiveness of the force. The methodology developed by RAND is suitable for a range of analyses that aim to address the systemwide impact of force modernization initiatives to specifically include both logistics and combat effectiveness.


The fused in sarcoma (FUS) protein is a 526 amino acid and its expression is ubiquitous. Recently, mutations in a gene coding FUS have been identified in familial amyotrophic lateral sclerosis (ALS). Also, FUS has been found in neuronal cytoplasmic inclusions in sporadic forms of ALS, suggesting that FUS has an important role in the neurodegeneration occurring in sporadic disease. However, there has been no study of FUS in ALS skin.


How can you get paid to blog? Learn the secret from the creator of ConcreteLoop.com.Self-taught Angel Laws, the founder of ConcreteLoop.com, created a successful and profitable blog, one that receives more than 500,000 unique hits a day. Offering readers simple, step-by-step advice on how to turn a blog into a careeror at the very least a money makerLaws will help anyone with an interest in this field. Using this guide to the art of blogging about celebrities, fashion, music, and entertainment, you will learn how to: Pick the right name for your blog Brand your blog, bringing your readers, money, and fame Use social networks to your advantage Generate ad revenue and know what to look out for Manage your blog, from content to comments And so much more! Peppered with insider stories about the movers and shakers of the entertainment worldthe kind of stuff only someone behind the scenes knowsConcreteLoop.com Presents: Angels Laws of Blogging is the book to read if you want your blog to succeed. 30 color illustrations


Background: Specialist palliative care services have various configurations of staff, processes and interventions, which determine how care is delivered. Currently, there is no consistent way to define and distinguish these different models of care. Aim: To identify the core components that characterise and differentiate existing models of specialist palliative care in the United Kingdom. Design: Mixed-methods study: (1) semi-structured interviews to identify criteria, (2) two-round Delphi study to rank/refine criteria, and (3) structured interviews to test/refine criteria. Setting/participants: Specialist palliative care stakeholders from hospice inpatient, hospital advisory, and community settings. Results: (1) Semi-structured interviews with 14 clinical leads, from eight UK organisations (five hospice inpatient units, two hospital advisory teams, five community teams), provided 34 preliminary criteria. (2) Delphi study: Round 1 (54 participants): thirty-four criteria presented, seven removed and seven added. Round 2 (30 participants): these 34 criteria were ranked with the 15 highest ranked criteria, including setting, type of care, size of service, diagnoses, disciplines, mode of care, types of interventions, 'out-of-hours' components (referrals, times, disciplines, mode of care, type of care), external education, use of measures, bereavement follow-up and complex grief provision. (3) Structured interviews with 21 UK service leads (six hospice inpatients, four hospital advisory and nine community teams) refined the criteria from (1) and (2), and provided four further contextual criteria (team purpose, funding, self-referral acceptance and discharge). Conclusion: In this innovative study, we derive 20 criteria to characterise and differentiate models of specialist palliative care – a major paradigm shift to enable accurate reporting and comparison in practice and research.


The 8 main tidal constituents were computed using a finite element, hydrodynamic ocean tide model over the South Indian Ocean region. The discretization of the domain is of the order of 100 km over the deep ocean and a few hundred meters near the coast. Such refinement in the grid resolution enables wave propagation and damping on the continental shelves to be solved correctly. The model used the GEBCO 1‐minute global bathymetric grid which was improved with updated topographic data. The model solutions show good agreement with in‐situ observations and Topex‐Poseidon altimeter measurements and are significantly better than previously published solutions. We obtain a combined standard deviation of 1.4 cm for differences of our new regional model against independent observations compared to about 2.5 cm for the other tide models. The greatest improvements are found around the Kerguelen Islands, around Antarctica and beneath the Amery Ice Shelf and can be explained by the high grid resolution used and the particular attention given to the accuracy of the bathymetry in those regions.


The utility of firefly luciferase as a reporter was tested in Streptococcus mutans. Under control of an endogenous promoter, the luciferase coding sequence was strongly expressed, while a promoterless version was indistinguishable from the background. Luciferase activity was easily extracted and the assay rapid and reproducible. In addition, the half-life of luciferase activity was found to be comparable to those of other frequently used reporters. Thus, firefly luciferase can readily be used as a reporter in S. mutans, a useful alternative to methods requiring radioactive isotopes.


We propose and experimentally demonstrate a microfiber-graphene device. Owing to the interaction between the graphene film and the evanescent field leaked from the microfiber, the hybrid photoconductive device exhibits a high photoresponse. A maximum photocurrent responsivity of ~2.81 mA/W is achieved in the telecommunication band. A nearly flat photoresponse spectrum within broad operational band ranging from 1500 nm to 1600 nm is also obtained as a consequence of the dispersionless and flat absorption of graphene. These results show that the proposed photocurrent generation device could provide an effective solution for broadband photodetection.


A major threat to public health worldwide is that the antimicrobial activity of the established drugs is constantly reduced due to the resistance that bacteria develop throughout the years. Some transition metal complexes show higher antibacterial activity against several bacteria compared to those of clinically used antibiotics. Novel classes of molecules provide new challenges and seem promising to solve the crisis that the overuse of antibiotics has led over the last years. This review discusses the challenges of chromium-based metallodrugs as antimicrobial agents. In particular, the synthetic routes, the structural characteristics, as well as the antimicrobial activity of 32 chromium (III) complexes have been presented.


Activated microglia promote central nervous system (CNS) inflammation through antigen presentation and secretion of pro-inflammatory cytokines and chemokines. Although this activation is necessary to protect the brain during infection, aberrant release of pro-inflammatory and/or cytotoxic factors such as tumor necrosis factor-α, interleukin-1β, nitric oxide and reactive oxygen substances may lead to neuronal damage and degeneration.  Targeting microglia during neuroinflammation to regulate the expression of cytokines without affecting other cell types in the CNS is challenging since no specific microglial markers have yet been established that distinguish microglia from infiltrating, peripheral myeloid cells. Therefore, we propose that a viral-based gene delivery system might be a better strategy to regulate gene expression in microglia. Using the recombinant Adeno-associated virus (AAV) vector pseudotype 2/5, which preferentially infects microglia (, we constructed a plasmid backbone which contains GFP under the control of the F4/80 promoter, a macrophage-specific marker. In order to demonstrate the specificity of this promoter for macrophages, we transfected human kidney cells HEK 293 cells, mouse leukemic macrophages RAW 264.7 cells, human hepatocytes cell line (HepG2) and human ovarian carcinoma cell line (1A9) with the AAV-F4/80-eGFP construct or the control plasmid AAV-CAG-eGFP. Our results indicate that the rAAV-F4/80-GFP construct is selective for macrophages.  To begin to assess the usefulness of this system to alter microglia function, we have cloned the Membrane Associated Ring-CH protein (MARCHI) into the rAAV-F4/80-eGFP vector that has been shown earlier to regulate antigen presentation by inducing the intracellular sequestration of MHC class II. We were able to confirm this finding by transfecting interferon gamma stimulated macrophages cell line RAW 264.7 cells via our constructed AAV-F4/80-MARCHI-eGFP vector and demonstrate the ability of our recombinant AAV vector that is driven by specific promoter to deliver and express MARCHI to induce MHC class II sequestration. Together this work will lead to the development of tools that will allow us to dissect the pathways by which microglia promote neuroinflammation.


Background: The ubiquitin-proteasomal pathway has been found to be involved in the etiology of Parkinson's disease (PD). Numerous single-nucleotide polymorphisms (SNPs) in both USP24 and USP40 genes have been linked to increased risks of late-onset PD, but the association has not been confirmed in the residents of mainland China, especially the Han population. Methods: We included 378 unrelated Han Chinese PD patients from south west China and 274 unrelated Han Chinese healthy controls from the same region. Multiple SNPs, including rs13312, rs1165226, rs487230, and rs287235 of USP24 and rs1048603 of USP40, were genotyped using Sequenom iPLEX Assay technology. Results: No significant differences in the genotype frequencies and minor allele frequency of all SNPs were observed between the PD and control groups, between the early-onset PD and control groups, between the late-onset PD and control groups, and between the early-onset PD and late-onset PD groups. Conclusion: The present study is the first to report a lack of association between SNPs of USP24 and USP40 and PD in Han Chinese patients. Other association studies with larger numbers of participants are necessary to confirm the present findings.


This is a digital image of the original printed map held by the Maryland Room, University of Maryland Libraries. Call no. BC 009, Map 0063. Our thanks to generous support of the Maryland Room staff for helping us make this map available.


This guides supports the Native Voices: Native Peoples' Concepts of Health and Illness grant. The Native Voices traveling exhibition will be at Tarrant County College-Southeast Campus from August 21 to September 27, 2017.


KEY FINDINGS
Data from the National Health Interview Survey, 2013-2014. Single parents, especially women, were more likely than adults in other types of families to have short sleep duration, frequently have trouble falling asleep and staying asleep, and frequently wake up feeling not well-rested. Within family types, women were more likely than men to frequently have trouble falling asleep and staying asleep, and to frequently wake up feeling not well-rested. Overall, adults in two-parent families were less likely than adults in other types of families to have taken sleep medication four times or more in the past week.


The evaluation of some microbial species for the decolourization and degradation of textile dye has been investigated. Six microbial strains were isolated from soil contaminated with textile waste effluents using the spread plate technique and the isolates were identified as bacterial isolates (Pseudomonas fluorescence, Pseudomonas nigificans, and Pseudomonas gellucidium) and fungal isolates ( Aspergillus niger, Proteus morganii and Fusarium compacticum} based on gram staining, morphological and biochemical tests. They were evaluated for their capability to remove colour and degrade dye, reduce chemical oxygen demand (COD) and biological oxygen demand (BOD) levels of textile waste effluents. The results revealed that all the bacterial and fungal isolates have a good potential to remove colour and degrade dye, reduce the COD and BOD levels of the textile waste effluents with percent colour removal, COD and BOD reductions between 39 and 48%, 74 and 97% and 77 and 95%, respectively. Binary mixed culture of Pseudomonas fluorescence and Aspergillus niger was efficiently utilized for the removal of different initial concentration (10, 15, 20, 25 and 30 mg/l) of dye from textile waste effluents. It had a higher percent decolourization than individual isolates. The stirred tank bioreactor was found to be very effective for efficient biotreatment of textile waste effluents.


Background The most important part of the state social and economic policy is optimization of the healthcare system, where the loss of public health leads to economic damage. Against this background, forecasting the work of medical institutions is the basis for the successful development of healthcare, despite the fact that the healthcare system, indicators and standards of medical and social welfare are still not stable, and a clear development strategy for the shortand long-term period has not been worked out. Aim of study Determining the most optimal method for predicting the work of a medical institution, based on identification of the main trends in the time series when constructing a model of the dependence of parameters or determining the behavior of data as a stochastic series (i.e. modeling random processes and random events with some random error). Material and methods To predict the main statistical indicators of N.V. Sklifosovsky Research Institute for Emergency Medicine based on a retrospective analysis, data were used that were submitted to the City Bureau of Medical Statistics and entered into official reporting forms (form № 30, approved by Goskomstat of the Russian Federation dated September 10, 2002, № 175): the number of hospitalized patients and mortality rates in inpatient and intensive care units. To select the optimal methodology for the experimental forecast model, data were used for the period from 1991 to 2016. Indicators for 2017 were taken as control values. Results As a result of the comparison of several methods (moving averages, least squares approach, Brown model, Holt–Winters method, autocorrelation model, Box–Jenkins method) as applied to the work of N.V. Sklifosovsky Research Institute for Emergency Medicine, the Holt–Winters model was chosen as the most appropriate one for the data characteristics. Findings 1. When using methods of moving averages, least squares, Box-Jenkins, as well as Brown model and autocorrelation, the forecast result is not always influenced by strictly straight-line indicators of the time series, due to the heterogeneity of the time series and the presence of outliers (often found in a medical institution providing emergency care), which lead to a significant decrease in the reliability of forecasting. 2. The application of the Holt–Winters model, which takes into account the exponential trend (the trend of time series indicators) and additive season (periodic fluctuations observed in the time series), is most suitable for processing statistical data and forecasting for long-term, medium-term and short-term periods taking the specifics of a hospital providing emergency care into account. 3. The choice of the optimal method for predicting the work of a medical institution, based on the identification of the main trends in the time series, taking most of the features in the modeling of random processes and events into account, allowed to reduce the relative forecast error.


Exposure to environmental or occupational substances may affect penile erectile function, and it would add to a growing list of pathogenic risk factors associated with erectile dysfunction. Several lines of evidence gained by clinical epidemiologic and biomedical investigations lend support to this viewpoint. Some environmental toxicants, including smoke, lead, organic solvents, and pesticides, are potential hazards, whose effects on the nervous and hormonal systems have been proposed as the leading mechanisms by which environmental toxicants adversely impact erectile function. A synthesis of current data suggests a possible association between environmental exposure and erectile dysfunction, but evidence is not yet sufficient to support a direct causal link for the time being. More studies are needed to identify specific environmental agents that may harm erectile function and to define their exact action mechanisms in this regard.


The next-generation networks improve people's quality of life with new services and applications. The evolution of Internet technologies also promoted the development of electronic commerce and the evolution of mobile payments. Near field communication NFC was proposed as a new short-range wireless technology and can play an important role in such issues. Money transactions among mobile devices could play an important role in a near future in order to simplify and perform such operations safely. Furthermore, it is important that tasks are easy to perform. Then, this paper presents a mobile solution based on a peer-to-peer communication system for money transfer, based on NFC and Bluetooth communications. A hybrid communication protocol combining the security characteristics of NFC and better Bluetooth data transfer rates is proposed. The proposal was deployed in real environments, and it was evaluated, demonstrated, and validated with different NFC tags and the Bluetooth traffic was also analyzed. It was shown that system presents good response times. The solution offers a friendly user's interface and very easy to use, guaranteeing the security of money transfer, and it is ready for use. Copyright © 2013 John Wiley & Sons, Ltd.


The breeding behaviour of female Brown-headed cowbirds, Molothrus ater, is remarkably distinct from that of females of most other passerine species. Cowbirds are brood parasites that do not build nests, incubate eggs or feed young. Instead, they have an extended egg-laying stage, and deposit eggs in the nests of hosts within large breeding territories that are defended from other female cowbirds. In this communication, we report the changes in plasma levels of circulating hormones and in morphological characteristics that occur in free-living female Brown-headed cowbirds over a breeding season.

Plasma LH in female cowbirds increases at the onset of breeding and remains elevated for approximately eight weeks, at which time levels decline to basal values. This pattern is similar to that of follicle development, and is consistent with the prolific reproductive output by individuals of this species. Circulating E, levels are quite variable and do not demonstrate any discernible pattern, while plasma B is elevated during the egg-laying period and declines subsequently.

Testosterone titre (T) is highest early in the breeding season, when territorial interactions are generally most frequent. T levels decline slowly thereafter, reaching their lowest values at the season's end. Plasma DHT levels are slightly higher than those for T; DHT exhibits little change until late in the breeding season, when it declines. Fat scores are highest prior to egg laying, and fat reserves diminish as the breeding season progresses. In contrast, body weight increases during the reproductive season, probably as a result of developing eggs in the ovary. These results are consistent with the hypothesis that temporal patterns of hormone secretion are correlated with the expression of social systems.


This paper discusses the semilossless text compression. The data compression method is classified into lossless and lossy methods. Lossless methods include usually those applied on text files or other data for which no loss of information can be tolerated, lossy techniques are generally applied to image files as well as to video and audio data, for which the overall knowledge a user might extract does not seem significantly reduced even if a part of the data is omitted.


This article presents a new semanticbased transfer approach developed and applied within the Verbmobil Machine Translation project. We give an overview of the declarative transfer formalism together with its procedural realization. Our approach is discussed and compared with several other approaches from the MT literature. The results presented in this article have been implemented and integrated into the Verbmobil system.


The single excitor motoneuron to the limb opener muscle in the crayfish Procambarus clarkii provides multiterminal innervation to individual muscle fibers. At low impulse frequencies, these neuromuscular synapses generate a threefold larger junctional potential in fibers of the proximal region of the muscle compared to those in the central region. Focal extracellular recording from synapse‐bearing "boutons" showed more quantal release at low frequencies in the proximal region. Structural correlates for the physiological differences were sought. Fluorescence microscopy of surface innervation stained with a vital fluorescent dye, 4‐Di‐2‐Asp, showed that density of innervation was not greater in the proximal region and thus could not account for the overall differences in synaptic strength. Freeze fracture studies showed that the intramembrane organization of excitatory synapses and their active zones was qualitatively similar in proximal and central sites. Serial section electron microscopy of several innervation sites in proximal and central regions showed homogeneity in number and size of synapses. However, presynaptic dense bars (at release sites, or active zones) were longer and occurred at a higher density in proximal than in central synapses. The differences in number and length of presynaptic dense bars correlate positively with the differences in synaptic strength represented by junctional potential amplitudes and quantal contents of individual surface recording sites. Since many individual proximal synapses have multiple dense bars, co‐operativity among these may serve to enhance transmitter output. It is concluded that occurrence of dense bars is a significant pre synaptic correlate of synaptic strength in this neuron. © 1994 Wiley‐Liss, Inc.


Abstract
In order to study the dynamic evolution law of ground fissures in shallow coal seam mining under ditch,taking the 14210 working face of a mine in northern Shaanxi as an example, this paper analyzes the dynamic development law of ground fissures in the process of mining under ditch through similar material simulation combined with the VIC-3D monitoring system. The results show that there are 20 ground fissures in the 14210 working face. The development width of ground fissures increases first, then decreases rapidly, and finally closes at the bottom of the ditch. The ground uplifts with a height of 1.5 m. The development width of ground fissures increases first, then decreases slightly, and finally tends to stabilize on the left and the right slopes, resulting in staggered steps with a height of 1.6 m and 0.7 m respectively. This change process is consistent with that of the strain of the underlying overburden obtained by VIC-3D strain analysis. According to their development positions and strain changes, the ground fissures are divided into three categories: tensile ground fissures on the left slope T1-T8, squeeze ground fissures at the bottom of the ditch T9-T13, and tensile ground fissures on the right slope T14-T20. Finally the safety analysis of mining under ditch in the 14210 working face is carried out.


The aim of this study was to assess the influence of season, farm management (organic, biodynamic, integrated, and conventional), and soil chemical, physical, and biological properties on gross nitrogen (N) fluxes and bacterial community structure in the semi-arid region of Western Australia. Moisture availability was the dominant factor mediating microbial activity and carbon (C) and N cycling under this climate. In general, microbial biomass N, dissolved organic N, and potentially mineralisable N were greater in organic and biodynamic than integrated and conventional soil. Our results indicate that greater silt and clay content in organic and biodynamic soil may also partly explain these differences in soil N pools, rather than management alone. Although plant-available N (NH4+ + NO3–) was greater in conventional soil, this was largely the result of higher NO3– production. Multiple linear modelling indicated that soil temperature, moisture, soil textural classes, pH, electrical conductivity (EC), and C and N pools were important in predicting gross N fluxes. Redundancy analysis revealed that bacterial community structure, assessed by denaturing gradient gel electrophoresis of 16S rDNA, was correlated with C and N pools and fluxes, confirming links between bacterial structure and function. Bacterial community structure was also correlated with soil textural classes and soil temperature but not soil moisture. These results indicate that across this semi-arid landscape, soil bacterial communities are relatively resistant to water stress.


One- and two-dimensional photonic crystals are obtained by electron beam lithography and reactive ion etching on silicon-on-insulator waveguides. Variable-angle reflectance is measured and calculated in the 0.2-2-eV energy range, giving evidence of the quasi-guided modes of the photonic structure. Photonic bands in the one-dimensional case are determined and compare very well to those calculated with an expansion on the basis of the waveguide modes.


Negative frequent itemsets (NFIS), which refer to frequent itemsets with non-occurring and occurring item(s) like (a1a2¬a3a4), have become increasingly important in real applications, such as bioinformatics and healthcare management. Very few methods have been proposed to mine NFIS and most of them only satisfy the user-specified single minimum support, which implicitly assumes that all items in the database are of the same nature or of similar frequencies in the database. This is often not the case in real-life applications. Although several methods have been proposed to mine frequent itemsets with multiple minimum supports (MMS), these methods only mine positive frequent itemsets (PFIS) and do not handle NFIS. So in this paper, we propose an efficient method, called e-msNFIS, to efficiently identify NSP with MMS by only using the identified PFIS without re-scanning database. We also solve the problem of how to set up minimum support to an itemset with negative item(s). To the best of our knowledge, e-msNFIS is the first method to mine NFIS with MMS. Experimental results on real datasets show that the e-msNFIS is highly effective and efficient.


Continuous glucose monitoring (CGM) is a method of glucose testing in which a sensor is inserted into the skin and continuously monitors interstitial glucose concentrations. Real-time continuous glucose monitoring (rtCGM) systems automatically measure glucose and display a recent glucose value.
Evidence suggests that rtCGM may improve hemoglobin A1C and time in range in adults and pediatric patients with type 1 diabetes, but this is uncertain.
Limited evidence suggests that in people with type 1 diabetes, there is little to no difference between rtCGM and self-monitoring of blood glucose (SMBG) on quality of life, diabetic ketoacidosis, and severe adverse events.
Safety evidence suggests that rtCGM may decrease severe hypoglycemia in adults and pediatric patients with type 1 diabetes, but this is uncertain.
rtCGM may be more cost-effective in the long term than SMBG in adults with type 1 diabetes.


Introduction: Clindamycin is most commonly used drug in treatment of erythromycin resistant Staphylococcus aureus causing skin and soft tissue infection. In vitro routine tests for clindamycin susceptibility may fail to detect inducible clindamycin resistance due to erm genes leading to treatment failure. Thus it is necessary to detect such resistance by simple D test on regular basis.
Aim: To study the induction of clindamycin resistance and characterize the Staphylococcus aureus phenotypes based on their susceptibility pattern and induction testing.
Material & Methods: Total 400 Staphylococcus aureus strains were isolated from different clinical samples. All isolates were tested for MRSA using Cefoxitin (30µg) by Kirby Bauer disc diffusion method. All 400 S. aureus strains were tested to see different induction phenotypes by D test as per CLSI guidelines.
Result: Out of 400 isolates of S. aureus, 75 (18.7%) isolates showed inducible clindamycin resistance, 117 (29.3%) isolates showed constitutive resistance, 79(19.7%) isolates showed MS phenotype of resistance and 129 (32.3%) isolates were sensitive to both erythromycin and clindamycin drugs. Inducible resistance was more in MRSA strain (32.3%) as compared to the MSSA strain (9.9%).
Conclusion: This study showed that D test should be done as routine disc diffusion test to detect inducible clindamycin resistance in Staphylococcus aureus strains so clindamycin therapeutic failure can be reduced.

Keywords: Inducible clindamycin resistance, Constitutive resistance, MS phenotype, MRSA


The recently proposed crystal graph convolutional neural network (CGCNN) offers a highly versatile and accurate machine learning (ML) framework by learning material properties directly from graph-like representations of crystal structures ("crystal graphs"). Here, we develop an improved variant of the CGCNN model (iCGCNN) that outperforms the original by incorporating information of the Voronoi tessellated crystal structure, explicit 3-body correlations of neighboring constituent atoms, and an optimized chemical representation of interatomic bonds in the crystal graphs. We demonstrate the accuracy of the improved framework in two distinct illustrations: First, when trained/validated on 180,000/20,000 density functional theory (DFT) calculated thermodynamic stability entries taken from the Open Quantum Materials Database (OQMD) and evaluated on a separate test set of 230,000 entries, iCGCNN achieves a predictive accuracy that is significantly improved, i.e., 20% higher than that of the original CGCNN. Second, when used to assist high-throughput search for materials in the ThCr2Si2 structure-type, iCGCNN exhibited a success rate of 31% which is 310 times higher than an undirected high-throughput search and 2.4 times higher than that of the original CGCNN. Using both CGCNN and iCGCNN, we screened 132,600 compounds with elemental decorations of the ThCr2Si2 prototype crystal structure and identified a total of 97 new unique stable compounds by performing 757 DFT calculations, accelerating the computational time of the high-throughput search by a factor of 130. Our results suggest that the iCGCNN can be used to accelerate high-throughput discoveries of new materials by quickly and accurately identifying crystalline compounds with properties of interest.


This paper describes a dual rate 8kb/s / I6kb/s low delq CELP speech coder with a 5ms frame length. Our studies have focused on the design of a classified structure based on both a long term (voiced / unvoiced) and a short term segmentation of the speech signal. This classifcation enables to combine a backward and forward LPC structure in a same codec. The bit allocation can then be better optimized according to the characteristics of rhe input signal and the desired bit rate. Results of formal tests are presented and show that the quality is equivalent to the G729 ITV-T codec at 8kb/s (preliminary version of October 94) and outperforms significantly G728 at 16kb/s.


Similarity search, or query by content, is an important operation for time series databases. While the research community has been quite active in this area, we are yet to see full support for these operations and data from commercial Database Management Systems (DBMS). In this work we explore how efficiently can similarity search algorithms be implemented inside a DBMS with User Defined Functions (UDFs). We concentrate our work on querying Electrocardiograms (ECG), a biosignal and a particular type of time series data. Given the lack of support for time series as an standard data type, we identify two alternatives for managing a database of ECG signals using a DBMS, namely using either references to flat files on the operating system, or using Binary Large Object (BLOB) attributes. Our experiments show a significant overhead in the total elapsed time while doing similarity search on signals stored as BLOB. On the other hand, querying signals stored as files using UDFs is as competitive as using an ad-hoc implementation of the query by content algorithm running as a stand-alone application on the operating system.


Immunological detection of proteins is an essential method to demonstrate to undergraduate biology students, however, is often difficult in resource and time poor student laboratory sessions. This method describes a failsafe method to rapidly and economically demonstrate this technique using biotinylated proteins or biotin itself as targets for detection. This negates the need for a specific primary antibody, saving cost and time. In addition, the easily available and safe reagents allow the methods to be readily adopted without specialist technical expertise. As a result, staff can confidently transfer ownership of the task to the student so as to also develop scientific inquiry skills which promotes student motivation and engagement.


Calcium hypochlorite commercially known as bleaching powder is used as a bleaching agent in shrimp processing industries in many countries and known to effect biochemical alteration in shrimp muscle. Studies were, therefore, undertaken to determine their effect in different concentrations viz., 10, 20, 30, 40 and 50 ppm with different time intervals on the quality of head-on, headless shell-on and peeled giant freshwater prawn (Macrobrachium rosenbergii) by determining biochemical and organoleptic aspects. Myofibrillar protein solubility of fresh head-on, headless shell-on and peeled samples were 90.5%, 90% and 88%, respectively indicating a gradual decrease in protein solubility with increasing concentration of bleaching powder. Decrease in protein solubility was also higher in samples kept at longer duration in different concentration of bleaching powder. At a given concentration of 50 ppm for 30 min treatment, the loss of myofibrillar protein was higher (26.14%) in peeled samples than those of head-on and headless shell-on samples (20.44% and 21.11%). Shelf life of bleaching powder treated prawn samples was found to be reduced to 4 - 5 days in iced condition compared to 6 - 7 days for control samples. Peeled samples were also found to be more susceptible to bleaching powder than that of head-on and headless shell-on samples.


Abstract:Insulin and amino acids are key factors in regulating protein synthesis. The mechanisms of their action have been widely studied for several years. The insulin signal is mediated by the activation of intracellular kinases such as phosphatidylinositol–3'kinase and the mammalian target of rapamycin (mTOR), affecting the phosphorylation of some major effectors involved in the regulation of translation initiation, i.e. p70 S6 kinase (p70S6K) and the translational repressor eukaryotic initiation factor 4E binding protein (4E-BP1). The amino acid–induced signalling cascade also originates from mTOR and promotes p70S6K and 4E–BP1 activation. However, the mechanisms of regulation are complex and little understood, especially in vivo. Elucidating these mechanisms is important for both fundamental physiology and nutritional applications, i.e. better control of the use of nutrients and optimisation of dietary amino acid supplies in various physiological and physiopathological situations. In comparative physiology, the chicken is an interesting model to gain better understanding of the nutritional regulation of mRNA translation because of the very high rates of muscle growth and protein synthesis, and the unusual features compared with mammals. In the present review we provide an overview of the roles of insulin and amino acids as regulators of protein synthesis in both mammals and avian species.


A novel fluorescent (p-phenylene ethynylene)-calix(4)arene-based polymer (CALIX-PPE) has been successfully synthesized by cross-coupling polymerization of bis-calix(4)arene 1 with 1,4-diethynylbenzene. The polycondensation was carried out in toluene/NEt3 at 35 8C for 24 h, using PdCl2(PPh3)2/CuI as the catalytic system, furnishing CALIX-PPE in excellent isolated yields (higher than 95%, several runs). The yellow polymer is freely soluble in several nonprotic organic solvents. The GPC trace of the isolated polymer showed a monomodal distribution and a number-aver- age molecular weight of 23,300 g mol � 1 (Mw/Mn ¼ 2.05). No evidence was found in the structural analysis (FTIR and 1 H/ 13 C NMR) regarding the formation of alkyne homocoupled segments along the polymer chain. For comparative purposes, the syn- thesis of an analogous poly(p-phenylene ethynylene) containing p-t-butyl-phenoxy- methyl side chains (TBP-PPE) was also undertaken. A great similarity was found between the photophysical properties of CALIX-PPE and TBP-PPE in solution (UV-vis and laser induced luminescence), clearly demonstrating their unique de- pendence on the structure and conformation of the conjugated PPE backbone. The fluorescence spectra of polymers are of nearly identical shape, displaying their maxi- mum emission around 420 nm. The calculated solution photoluminescence quantum yields of CALIX-PPE and TBP-PPE are of similar magnitude (/F(CALIX-PPE) ¼ 0.43; /F(TBP-PPE) ¼ 0.51). V C 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6477-6488, 2008


Q values for Lg and its coda exhibit significant lateral variations across the United States, some of which correlate with known variations in the thickness of shallow sedimentary layers. The possibility that all variations in Lg attenuation are caused by changes in the thickness of shallow sediments is investigated by computing multi-mode synthetic seismograms for crustal models with various thicknesses of low- Q sediments. Using crustal velocity and Q models obtained in previous studies, and reasonable values for the thicknesses and intrinsic Q values of sediments in several regions, we find that the variation of Lg Q values between the Appalachian and Rocky Mountains can easily be produced by varying accumulations of sandstone and shale of Mesozoic age and younger. By contrast, throughout most of the Western United States, neither the low Lg Q values which have been observed nor the regional variation of those values can be explained by accumulations of low- Q sediments. Instead, their explanation appears to require low and laterally varying values of Q in the crystalline crust.


The recent trend in the U.S. hospital closures can have important impacts on the healthcare sector by changing the operational efficiency and quality of care of the remaining hospitals. We investigate the impact of hospital closures on the surrounding hospitals' efficiency and quality and shed light on mechanisms through which they can be affected. Using and combining various data sources, we find that when a hospital closes, its nearby hospitals improve their operational efficiency without expanding their resources. However, they do so via a speed-up behavior (i.e., by reducing their service durations) instead of an effort to lower their average bed idle time. Importantly, we find that this speed-up response to the increased demand by nearby hospitals negatively affects some (but not all) aspect of the care, including the 30-day patient mortality. Furthermore, hospital closures induce changes in directions that widen social disparity, as their adverse consequences fall disproportionately among hospitals or patients with limited resources. Our results have implications for both hospital administrators and policymakers who strive to improve the efficiency and quality of the healthcare system.


The presented paper aims to reveal internationalization barriers and motives of Lithuanian small and medium size enterprises (SMEs). The perceptions of internationalized and non-internationalized firms were assessed. The present study applied a survey method of data collection. Profit goals and networks are seen as the main drivers of internationalization. However, intense competition abroad was seen as the most significant factor, hindering expansion of firms. The assessment of strengths revealed the difference between internationalized and non-internationalized firms. The availability of advantageous products and services in domestic markets was seen as important factor for internationalization. The findings of the survey led us to elaborate implications and policy measures.


Affirmative action policies have polarized the American public for over a quarter of a century. With regard to undergraduate university admissions, the Department of Education has not issued a definitive policy stance and has chosen to rely upon the results of previous and forthcoming research. Most scholars have not seized the opportunity to explore the effectiveness of affirmative action on a university's minority admission or enrollment rates. Additionally, scholars have not established the role that other confounding factors, such as financial aid and academic preparation, play in determining admission or enrollment rates. This research explores the role of affirmative action policies and percentage plans in determining the admission and enrollment rate of African Americans and Hispanics at the University of California and the State University System of Florida. Results indicated that affirmative action increased the admission rates of the three underrepresented minority groups while it decreases the enrollment rates of same groups in California. The amount of financial aid was also tatistically significant when used to determine a minority group's admission or enrollment rate. In the Florida case, affirmative action was a factor in determining undergraduate admissions and enrollment rates. However, the models did not have the explanatory power of the California models. These findings have substantial implications for current public policy as the U.S. Supreme Court will consider two lawsuits against the University of Michigan and its various admissions policies. This article is available in Res Publica Journal of Undergraduate Research: https://digitalcommons.iwu.edu/ respublica/vol8/iss1/7 Contentious Policies: The Experiment with Affirmative Action in Undergraduate Admissions to Public Universities


We investigate techniques for similarity analysis of spatio-temporal trajectories for mobile objects. Such data may contain a large number of outliers, which degrade the performance of Euclidean and time warping distance. Therefore, we propose the use of non-metric distance functions based on the longest common subsequence (LCSS), in conjunction with a sigmoidal matching function. Finally, we compare these new methods to various L/sub p/ norms and also to time warping distance (for real and synthetic data) and present experimental results that validate the accuracy and efficiency of our approach, especially in the presence of noise.


The hypoxia-inducible factor (HIF)-1α and HIF-2α are closely related, key transcriptional regulators of the hypoxic response, countering a low oxygen situation with the up-regulation of target genes associated with numerous processes, including vascularization and glycolysis. This involves a dual mechanism of control through both stabilization and transactivation, regulated via prolyl and asparaginyl hydroxylation. Despite high similarity with respect to protein sequence and activation pathway, a growing number of physiological and mechanistic differences between HIF-1α and HIF-2α are being reported. To further characterize this nonredundancy, the stabilization of endogenous proteins and regulation of the transactivation domains were compared in a graded oxygen environment across a series of cell lines. Although generally similar results were found, interesting and specific differences between the HIF-α proteins were observed within certain cell lines, such as rat adrenal PC12s, emphasizing the cell-specific nature of HIF-α regulation. We characterize a conserved amino acid substitution between HIF-1α and HIF-2α that contributes to the intrinsically higher FIH-1-mediated asparaginyl hydroxylation of HIF-1α and, hence, lower HIF-1α activity. In addition, our data demonstrate that the different cell lines can be classified into two distinct groups: those in which stabilization and transactivation proceed in conjunction (HeLa, 293T, and COS-1) and those cells in which HIF-α is stabilized prior to transactivation (PC12, HepG2, and CACO2). Interestingly, the initial stabilization of HIF-α prior to transactivation up-regulation predicted from in vitro derived hydroxylation data is only true for a subset of cells.


Background: The increasing prevalence of extensively drug-resistant Klebsiella pneumoniae (XDR-KP) poses a serious threat to clinical anti-infective treatment. This retrospective study assessed the molecular epidemiology of and risk factors for infections with XDR-KP to investigate the mechanism of drug resistance and the epidemiological characteristics. Methods: A retrospective 1:2 case-control study was conducted at Chongqing Renji Affiliated Hospital of the Chinese Academy of Sciences University from January 2015 to December 2017. A total of 69 non-repetitive XDR-KP strains were collected. Patients infected with XDR-KP comprised the case group, and 138 matched patients with non-XDR-KP infection at the same site comprised the control group. The chi-square test and logistic regression were performed to evaluate the related risk factors. Molecular typing was performed by multilocus sequence typing (MLST). Potential resistance genes were detected by polymerase chain reaction (PCR) and sequencing. Predictors of 28-day mortality in patients with XDR-KP infection were also identified in our study. Results: Only tigecycline and polymyxin B showed favorable in vitro drug sensitivity tests. These XDR-KP strains had a high prevalence rate (n = 66, 95.7%) of carbapenemase-related drug resistance genes. Among them, KPC-2 was the most frequently detected gene (n = 52, 75.4%). Particularly, all of the isolates harbored multiple drug resistance genes. Epidemiological analysis showed that fifty-eight XDR-KP isolates were resistant strains with the ST-11 genotype. Multivariate logistic regression analysis showed that ICU admission (OR: 3.28, 95% CI: 1.66–6.49, P < 0.001), tracheal cannula (OR: 3.16, 95% CI: 1.48–6.76, P = 0.003), and carbapenem exposure (OR: 3.16, 95% CI: 1.25–7.98, P = 0.015) were independent risk factors for XDR-KP infection. Solid tumors (OR: 7.22, 95% CI: 1.84–28.34, P = 0.005) and septic shock (OR: 9.46, 95% CI: 2.00–44.72, P = 0.005) were independent risk factors for 28-day mortality from XDR-KP infection. Conclusion: This study showed that XDR-KP isolates were highly resistant and exhibited clonal transmission. ST11 was the predominant epidemic type of XDR-KP producing KPC-2 in Southwestern China. Physicians should be aware of these high-risk patients with notable predictive factors for XDR-KP infection. These findings may provide some recommendation for the diagnosis and treatment of patients infected with XDR-KP strains in Southwestern China.


Strategic alliances between academic and corporate partners can provide exceptional benefits and reveal new opportunities for shared value. Benefits and opportunities include alternative sources of funding to support academic programs, more effective and efficient matching of students with prospective employers, applied research for faculty, innovative and mutual learning environments, and improved business practices. The focus of this paper will describe how three corporate‐alliance relationships with Northern Illinois University's College of Business were initiated and developed. Other schools and companies looking to develop similar relationships may hopefully benefit from the College of Business's experience. Moreover, corporate and academic alliances provide a potentially rich area of research.


In this work we provide a general overview about the natural and synthetic antioxidants and studies carried out to improve their potential. These compounds are able to scavenge free radicals that cause deterioration of food and pharmaceutical products during processing and storage. Today there are several known natural compounds with antioxidant properties that are extracted from plants, which are mainly phenols and polyphenols. The limit for the use of these compounds in the food and pharmaceutical industry as antioxidants concerns their poor solubility in hydrophobic environment. This limitation was overcame in the past years by the introduction of synthetic antioxidants, such as BHA (butylated hidroxy anisole), BHT (butylated hydroxyl toluene), TBHQ (tert butyl hydroquinone) and PG (propyl gallate). Unfortunately several authors showed that BHA, BHT, TBHQ and PG may present adverse effects on the health of living organisms. In recent years novel antioxidants have been synthesized from natural polyphenols in order to modify the hydrophilicity/lipophilicity balance and increase their biological functionalities arising from insertion of new functional groups or molecule moieties in pre-existing natural polyphenols. The aim of these modifications was to avoid the major adverse effects associated with the use of BHT, BHA, TBHQ and PG.


The present study focused on priming effects on pointing with everyday objects. In a set of four experiments, a visuomotor priming paradigm was used to investigate the nature of visuomotor processing (automatic versus task relevant). By manipulating congruency of orientation and location we found that location congruency facilitates the initiation time of pointing whereas orientation congruency does not. We provide evidence to show that motor planning is influenced by the goal of the action, and that how visual information is processed and held in memory depends on the task relevance. These data are consistent with the proposed interaction between visuomotor and higher processes during the planning and execution of actions such as pointing.


Prolapse of loop colostomy or ileostomy is a common complication and markedly reduces patient quality of life. Many techniques have been reported for surgical or nonsurgical management of prolapse. We here report a simple laparoscopic technique for loop stoma prolapse. The prolapsed intestine (usually distal limb) was fixed to the abdominal wall by laparoscopic suturing. This technique should represent a good option for management of loop colostomy prolapse and can be applied to loop ileostomy or single stoma prolapse.


Two experiments are presented which used a form of the Stroop colour-word task to study the processing of target and distractor information under changing conditions of temporal and spatial proximity. Experiment 1 focused on the marked empirical discrepancies in previous research reported in the recent literature. A coloured target and a distractor (neutral, facilitative or interfering) that were separated by variable onset asynchronies were presented foveally to observers. The findings of this study indicate strong distractor effects on response latency at the intermediate stimulus onset asynchronies (SOAs) (around 0 ms) and a clear monotonic decrease in reaction time for colour naming at extreme positive and negative SOAs. Experiment 2 used this same task but presented targets parafoveally and distractors foveally. This manipulation resulted in the same general pattern of processing as found in Expt 1. In addition, a laterality effect was found when the target and distractor were incongruent; the left visual field/right hemisphere showed significantly greater interference as indicated by longer reaction times. These results are discussed in terms of current models of information processing of compound stimuli.


Blockchain commoditizes confidence in a step to grid flexibility and allows decentralized smart contracts to enforce auditable multiparty payments based on established standards among distributed power suppliers and customers. Smart contracts reduce the need to communicate with foreign entities, making it feasible for distributed energy trades and exchanges, including energy flows and financial activity, to be implemented and monetized. It might help decrease the cost of transactive energy and increase protection. This work provides how a renewable energy business is secure and how privacy and anonymity are given for such a system through blockchain implementation.


N-Methyl-d-aspartate (NMDA) receptors play a variety of physiologic roles and their proper signaling is essential for cellular homeostasis. Any disruption in this pathway, leading to either enhanced or decreased activity, may result in the manifestation of neuropsychiatric pathologies such as schizophrenia, mood disorders, substance induced psychosis, Huntington's disease, Alzheimer's disease, and neuropsychiatric systemic lupus erythematosus. Here, we explore the notion that the overlap in activity of at least one biochemical pathway, the NMDA receptor pathway, may be the link to understanding the overlap in psychotic symptoms between diseases. This review intends to present a broad overview of those neuropsychiatric disorders for which alternations in NMDA receptor activity is prominent thus suggesting that continued direction of pharmaceutical intervention to this pathway may present a viable option for managing symptoms.


Estimates of the distribution of wealth in the rural areas of developing countries are virtually unknown. In some countries there are of course data on the distribution of land, but even where such data exist, they are woefully inadequate. First, land is measured in physical units. Adjustments seldom are made to take differences in the quality of land into account, although rough corrections occasionally are made to distinguish between irrigated and unirrigated land. Almost never is land measured in value terms and hence all factors apart from irrigation which affect the economic value of land are ignored. Second, where data exist, they often refer to the distribution of operational holdings rather than to units of ownership. In countries where large farms are broken up into small tenant holdings, data on the distribution of operational holdings tend to understate the degree of inequality in land ownership. This problem is compounded in countries where large landowners own more than one farm, often in different localities. Third, the data on the distribution of land usually focus on the distribution among tenant cultivators or, alternatively, among landowners. In both cases landless agricultural wage workers are excluded from consideration. What is needed however are data which refer to the distribution of land (correctly valued) among the entire rural population, including those who possess no land at all as well as small and large landowners.


Macrophages must engulf dead cells, debris, and pathogens, while selecting against healthy cells to prevent autoimmunity. Healthy cells express CD47 on their surface, which activates the SIRPA receptor on macrophages to suppress engulfment. Cancer cells overexpress CD47 to evade clearance by the innate immune system, making the CD47-SIRPA signaling axis an appealing therapeutic target. However, the mechanism by which CD47-SIRPA inhibits engulfment remains poorly understood. Here, we dissect SIRPA signaling using a reconstituted target with varying concentrations of activating and inhibitor ligands. We find that SIRPA is excluded from the phagocytic synapse between the macrophage and its target unless CD47 is present. Artificially directing SIRPA to the kinase-rich synapse in the absence of CD47 activates SIRPA and suppresses engulfment, indicating that the localization of the receptor is critical for inhibitory signaling. CD47-SIRPA inhibits integrin activation in the macrophage, reducing macrophage-target contact and suppressing phagocytosis. Chemical activation of integrins can override this effect and drive engulfment of CD47-positive targets, including cancer cells. These results suggest new strategies for overcoming CD47-SIRPA inhibition of phagocytosis with potential applications in cancer immunotherapy.


Background Both serum drug level testing (1) and ultrasound joint evaluation (2) might be usefull to increase the accuracy of correct evaluation of the response to treatment in patients with rheumatoid arthritis treated with biologics. Objectives To evaluate the possibile correlations between serum drug level of anti TNF drugs and ultrasound evaluation in rheumatoid arthritis patients treated with etanercept (ETA), adalimumab (ADL) and infliximab (IFX). Methods 52 consecutive rheumatoid arthritis patients on stable anti TNF treatment for more than 6 months were evaluated. Clinical and US evaluation was performed by two independent assessors, the same day as all laboratory tests. US of boths hands (dorsal wrist, 2nd to 5th volar metacarpophalangeal and 2nd to 4th volar proximal interphalangeal) was performed with an ESAOTE MY LAB70 machine using a linear probe of 15 MHz. Synovial hypertrophy and power Doppler (PD) signal were scored (grades 0–3). Synovial hypertrophy >2 plus power Doppler signal was classified as active synovitis. Serum drug level was measured just before the next iv infusion or sq injection by ELISA Kit Promonitor®, Progenika SA for ETA, ADL, IFX. All patients were divided in two groups according to the detectable or undetectable serum drug level. Statistical analysis was performed using IBM SPSS v20.0. Results All of the patients included had the biologic associated to DMARD, 80.8% were females, mean age 60.44 (11.39), mean disease duration 13.08 (7.05). 53.8% (28) patients were treated with ETN, 34.6% (18) with ADL and 11.5% (9) with IFX. All ETN patients, 61.11% ADL and 57.14% IFX patients had dosable drug level. No statistical significant difference between dosable and undosable drug level was found regarding age, disease duration, rheumatoid factor or ACPA positivity. The presence of dosable drug level negativelly correlated with markers of inflammation, ESR (p=0.030, r-0.357) C reactive protein (p=0.016, r-0.394), physician global assessement (PGA p=0.034, r-0.349). Regarding US parameters (see table) the only significant correlation was found between the number of PD joints and undetectable drug level. There were no statistically significant differences between anti TNF antagonists used. Undosable drug level Dosable drug level p Grey Scale Joint No 6.00 (3.83) 6.02 (2.44) 0.980 Power Doppler Joint No 2.02 (1.53) 0.7 (0.82) 0.012 Total Grey Scale score 10.30 (8.87) 9.10 (3.75) 0.683 Total Power Doppler score 2.5 (2.03) 1.60 (2.22) 0.223 Conclusions Drug serum levels of TNF antagonists correlates with markers of inflammation, number of power Doppler joints but not with total power Doppler score or total Grey scale score. References Krieckaert, C et al. Personalised treatment using serum drug levels of adalimumab in patients wih rheumatoid arthritis:an evaluation of costs and effects. Ann Rheum Dis Nov 21,2013; Ramirez J et al, Patients with rheumatoid arthritis in clinical remission and ultrasound-defined active synovitis exhibit higher disease activity and increased serum levels of angiogenic biomarkers, Arthritis Research & Therapy 2014, 16:R5 Acknowledgements This paper is partially supported by the Sectoral Operational Programme Human Resources Development (SOP HRD), financed from the European Social Fund POSDRU/159/1.5/S/137390. Disclosure of Interest None declared


There has occured a significant economical decline spread all over the sphere of state economy of the country in connection with ransformation of the former Soviet republics from planned economy to market system of the management and under influence of the civil war in Tajik republic. This decline has felt also housekeeper's rural local households. The result of research has shown that households striving to raise the level of the family income, to enlarge a number of profit gaining sourses they occupy simultaneously severaljobs in other sectors of the rural economy. The significant share in household budget is received from migration. To keep neede able-bodied people villagers have to choose the alternative sources of incomet, which provides increasing of living standard of rural population and region as a whole.


Abstract Background: Acute rheumatic fever (RF) is a common, preventable health problem in developing countries. Sporadic outbreaks and the prevalence in some indigenous populations have renewed interest in RF in developed countries also. Aims: To describe the clinical, laboratory and echocardiographic features, outcome and value of echocardiography in detecting valvular disease in RF. Methods: A prospective, cross-sectional study was conducted over 2 years. Patients under 14 years admitted to the cardiology unit of Kanti Children's Hospital, Kathmandu with RF using the Jones criteria were recruited consecutively. Results: The median age (range) of the 51 patients was 11 (5–14) years, the male:female ratio was 1.6:1 and 39% had a history of a sore throat. Clinical and laboratory features detected were as follows: carditis 92%, arthritis 33%, chorea 8%, subcutaneous nodules 4%, fever 51%, arthralgia 37%, elevated antistreptolysin O titre 94%, elevated CRP 78%, prolonged PR interval 45%, pericardial effusion 22% and cardiac failure 28%. In total, 36 patients (71%) complained of joint pains. A murmur on auscultation was significantly associated with underlying diseased valves confirmed by echocardiography (p=0.001). A murmur was audible in 78.4% and diseased valves were confirmed by echocardiography in 88.2%. The mitral valve was the most commonly involved valve (82%) and mitral regurgitation the commonest lesion (24%). A thickened mitral valve predicted carditis (p=0.007). Five (10%) patients died. Conclusion: Inclusion of echocardiographic evidence of carditis and possibly arthralgia as major criteria would improve case detection.


DNA unwinding is an important cellular process involved in DNA replication, transcription and repair. In cells, molecular crowding caused by the presence of organelles, proteins, and other molecules affects numerous internal cellular structures. Here, we visualize plasmid DNA unwinding and binding dynamics to an oligonucleotide probe as functions of ionic strength, crowding agent concentration, and crowding agent species using single-molecule CLiC microscopy. We demonstrate increased probe-plasmid interaction over time with increasing concentration of 8 kDa polyethylene glycol (PEG), a crowding agent. We show decreased probe-plasmid interactions as ionic strength is increased without crowding. However, when crowding is introduced via 10% 8 kDa PEG, interactions between plasmids and oligos are enhanced. This is beyond what is expected for normal in vitro conditions, and may be a critically important, but as of yet unknown, factor in DNA's proper biological function in vivo. Our results show that crowding has a strong effect on the initial concentration of unwound plasmids. In the dilute conditions used in these experiments, crowding does not impact probe-plasmid interactions once the site is unwound.


1. The short-circuit current and absolute fluxes of Na(+) and Cl(-) across the gastric mucosa of the 28-day rabbit foetus have been measured in vitro.2. Substitution of Na(+) in the solution bathing the mucosal surface by choline ion or K(+) resulted in a 70% decrease in short-circuit current which was reversed when Na(+) was restored to the mucosal solution. The portion of the short-circuit current dependent on the presence of Na(+) in the mucosal solution was found to be equivalent to the net flux of Na(+) from mucosa to serosa.3. The net flux of Cl(-) from serosa to mucosa was compared with the short-circuit current persisting when Na(+) had been replaced in the mucosal solution. Averaged results from sixteen experiments indicated that the net flux of Cl(-) was equivalent to 166% of the Na(+) independent short-circuit current.4. The results indicated that the component of short-circuit current associated with acid secretion was independent of the presence of Na(+) in the mucosal solution.5. The small scale of the experiments and the secretion of mucus by the preparation did not permit successful simultaneous measurement of H(+) secretion and short-circuit current.6. Replacement of Cl(-) by SO(4) (2-) or glucuronate in the solutions on both sides did not result in a reversal or decrease in magnitude of the Na(+) independent short-circuit current, even after allowing time for the tissue to become depleted of Cl(-). It is suggested that a non-specific active anion transport was occurring.


Accurate surgical staging is critical to the management of early ovarian cancers. A patient with squamous cell carcinoma arising from a mature cystic teratoma was found to have paraaortic nodal metastasis as her only evidence of extraovarian disease. Extended field radiation therapy to the pelvis and paraaortic nodes with concomitant cisplatin and adjuvant chemotherapy failed to control her disease. Inadequate surgical staging may explain the recurrences in apparent stage I disease.


The rapid dominance of evidence-based medicine has sparked a philosophical debate concerning the concept of evidence. We urge that evidence-based medicine, if it is to be practised in accordance with its own mandate, should also acknowledge the importance of understanding causal mechanisms.1–7 The undersigned include 42 clinicians and philosophers from interdisciplinary research networks working specifically on questions related to causation in medicine worldwide.

Our research has developed out of a conviction that philosophical analysis ought to have a direct impact on the practice of medicine. In particular, if we are to understand what is meant by 'evidence', what is the 'best available evidence' and how to apply it in the context of medicine, we need to tackle the problem of causation head on.1 8–12 In practice, this means understanding the context in which evidence is obtained, as well as how the evidence might be interpreted and applied when making practical clinical decisions.7 13 It also means being explicit about what kind of causal knowledge can be gained through various research methods. The possibility that mechanistic and other types of evidence can be used to add value or initiate a causal claim should not be ignored.3–7 14 15 This appeal for a broader approach to evidence is also important to patients, who need clear information on the benefits and harms of medicines.16

We have arrived at several overlapping conclusions with implications for policy and practice in research and clinical care, which we summarise briefly:

1. 'Evidence' is typically evidence of causation. Common terms used in EBM , such as 'intervention', 'outcome' or 'increased risk', are relevant to evidence-based decision-making only insofar as they point to causal matters: causal interventions and their effects. Although there is growing …


The use of pulse width-modulated amplifiers for dc servo systems, in order to reduce the power dissipation in the output stage is proposed. The amplifier transistors can be switched in different sequences, and the amplifier will operate accordingly in three possible modes, namely the bipolar, the unipolar, and the limited unipolar modes. The principle of operation and the mathematical model for each case are described along with the special features of this amplifier which include the power dissipation in the motor and the selection of the switching frequency.


The introduction of post-transplant cyclophosphamide (PTCy) has circumvented the need for T-cell depletion following haploidentical stem cell transplantation (SCT). By expanding the donor pool for patients from certain ethnic minorities, this has addressed to some degree an important health care disparity issue in SCT. However, a recent registry study showed increased incidence GvHD and inferior outcomes in patients receiving haploidentical SCT with PTCy, tacrolimus and mycophenolate mofetil for GvHD prevention as opposed to matched unrelated donor SCT with PTCy-based GvHD prevention. Seeking to improve the results of GvHD prevention in the setting of haploidentical SCT, we examined a combination of PTCy, abatacept and a short course of tacrolimus (CAST). Abatacept is a recombinant soluble fusion protein composed of the extracellular domain of cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) fused to the Fc region of IgG1. Abatacept blocks CD28-CD80I86 axis and prevents T-cell co-stimulation. In early studies, abatacept has shown promising results when added to methotrexate and tacrolimus in matched and mismatched donor SCT. We initiated a phase Ib-II clinical trial for patients with hematological malignancies undergoing haploidentical SCT. Patients received G-CSF mobilized peripheral blood grafts from related haploidentical donors. GvHD prevention consisted of PTCy 50mg/kg IV on day +3 and +4 with forced hydration, abatacept 10mg/kg IV on day +5, +14 and +28 and tacrolimus. Tacrolimus was started on day +5 at 0.02mg/kg/day by continuous IV and adjusted thereafter to maintain a trough level of 5-12ng/mL. Tacrolimus taper was planned to begin on day +60 and complete by day +90 in the absence of GvHD. All patients received standard supportive care including levofloxacin until neutrophil engraftment, posaconazole until day +75, acyclovir for 1 year and, if CMV positive by serology, letermovir until day +100. Pneumocystis Jiroveci prophylaxis was started after neutrophil engraftment and continued until 6 months post-transplant. G-CSF was administered routinely until neutrophil engraftment.
 Since September 2020, 19 patients were enrolled. Three patients are too early in their post-transplant course and were excluded from this analysis. Patients' characteristics are summarized in the table. All but 2 patients received cryopreserved products. Median times to ANC and platelet engraftment were 18.5 days (14-30) and 28.5 (16-61). All 16 patients achieved full whole blood donor chimerism by day +30. There was no secondary graft failure. With a median follow-up was 149.5 days (41-308) with 10 patients having >120 days and 8 >180 days of follow-up, 4 patients developed skin acute GvHD (all grade I). No patient developed grade II-IV acute GvHD. Two patients developed skin chronic GvHD (limited, both moderate). Both cases were diagnosed following COVID-19 vaccination. Fifteen patients completed tacrolimus taper by day +90. Two patients received systemic steroids, one for treatment of cGvHD. The remaining patients required no further immunosuppressive therapy beyond day +90. CMV activation rate was 25%. One patient had EBV reactivation and required preemptive therapy with 2 weekly rituximab doses. There were no cases of adenovirus, HHV-6 virus or BK virus reactivation. Four patients developed renal insufficiency (3 in the setting of acute sepsis and 1 with thrombotic microangiopathy, which resolved after tapering off tacrolimus. One patient with adult T-cell leukemia/lymphoma relapsed and died. All other patients are alive and well.
 In summary, our preliminary results suggest that CAST with shortened course of tacrolimus is feasible and seems to offer very promising outcomes with low rates of acute GvHD. The study is accruing actively and the results of a larger cohort with longer follow-up will be presented at the meeting. If confirmed, by improving the outcomes of haploidentical SCT, this regimen may further address a health care disparity issue, offering almost every patient in need of allogeneic SCT an alternative donor option with equal outcomes.
 Figure 1 Figure 1.

 Al-Homsi: Daichii Sanyko: Consultancy; Celyad: Other: Advisory Board. Abdul-Hay: Abbvie: Consultancy; Servier: Other: Advisory Board, Speakers Bureau; Jazz: Other: Advisory Board, Speakers Bureau; Takeda: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees.

 Abatacept - off label use as GvHD prevention Cyclophosphamide - off label use as GvHD prevention


This paper describes a design and fabrication of Si micro transportation systems (MTS) to drive microcars based on ratchet mechanism and electrostatic comb-drive actuators. This MTS consists of linear and rotational comb actuators, microcars, and micro ratchet mechanism. The microcars can be moved with different velocities by comb-drive actuators through ratchet teeth. In this study, the MTS was fabricated by using SOI wafer with device layer of 30µm, buried SiO2 layer of 4µm, and with only one mask. In our experiments, the movement of the microcar has been tested with driving frequency ranges from 5Hz to 40Hz. The velocity of the microcar was proportional to the driving frequency, and it matched well with theoretical calculation.


Background:
 Discontinuation of tyrosine kinase inhibitors (TKIs) is feasible in a subset of CML patients who have maintained a deep molecular response for at least two years. Numerous discontinuation trials have been performed and consistently show approximately 50% of patients relapse after stopping TKIs. A recent study examining rates of treatment free remission (TFR) after a second attempt at stopping TKIs found, with a median follow up time of 38.3 months, 64.3% of patients had a molecular relapse (defined as a loss of major molecular response (MMR)). At 12, 24 and 36 months, TFR rates were 48%, 42% and 35%, respectively. These data suggest some patients with a history of molecular relapse upon TKI cessation could successfully stop treatment on a subsequent attempt, yet the majority will relapse a second time. 'Complete eradication' of CML remains elusive in most patients likely as a result of minimal residual disease (MRD), which is the result of BCR-ABL independent drug resistance. More specifically, CML cells that reside in sanctuary sites such as the bone marrow adhere to fibronectin and demonstrate cell adhesion mediated drug resistance (CAM-DR). The bone marrow microenvironment contains many cytokines and growth factors capable of inducing STAT3-Y705 phosphorylation via the JAK-STAT pathway leading to protection against TKI-induced cell death. Inhibiting JAK2 and TYK2 leads to complete inhibition of pSTAT3-Y705, thereby implicating the role of activation of JAK2 and TYK2 in STAT3-Y705 phosphorylation and resistance towards BCR-ABL TKI-induced cell death. A phase I clinical trial combined ruxolitinib, which inhibits JAK2 and TYK2, plus nilotinib in chronic phase (CP) CML patients and found that ruxolitinib 15mg PO BID was safe and well tolerated with 4/10 patients achieving undetectable BCR-ABL1 transcripts by PCR.
 Study Design and Methods:
 This single arm phase II study (NCT03610971) will enroll 41 subjects from the H Jean Khoury Cure CML Consortium. Eligible subjects must have a confirmed diagnosis of CP-CML and have previously attempted to discontinue TKI therapy per NCCN guidelines and had molecular recurrence, defined as loss of MMR, and were restarted on TKI.
 This trial combines ruxolitinib 15mg BID plus BCR-ABL TKI (imatinib, dasatinib, nilotinib or bosutinib) for 12 28-day cycles in the combination treatment phase (CTP). RQ-PCR to measure BCR-ABL transcripts will be checked at screening and every three months during the CTP. In the event that a subject experiences intolerance to a TKI, has confirmed loss of MMR, or loss of MR4.5 (>0.0032% IS) on two central PCR results, or discontinues ruxolitinib, the subject will be removed from CTP and enter into long term follow-up (LTFU).
 CTP phase will be followed by further RQ-PCR screening for the concurrent TFR phase. At this time ruxolitinib will be discontinued and any subject who has met the criteria for the TFR phase will be enrolled. During the TFR phase, subjects will discontinue their TKI and be monitored off treatment with RQ-PCR checked monthly for the first year, every six weeks for year two, and every 12 weeks during year three. Upon molecular recurrence, defined as loss of MMR, TKIs will be restarted.
 The primary endpoint is the 12-month TFR rate subsequent to completion of 12 cycles of combination therapy; however, subjects will remain in the TFR phase for three years. Therefore, the total duration of the trial will be approximately five years (one year on CTP + three years in the TFR phase + one-year LTFU). Study statistical design was calculated to yield a one-sided type I error rate of 0.025 and power of 65% when the true one-year relapse rate is 35%.
 This study will additionally assess patient-reported outcomes in conjunction with RQ-PCR testing. PROMIS and other measures will be self-administered through REDCap. Correlative studies will include comparing changes in pSTAT3 in K562 and KU812 cell lines using plasma from CML patients being treated with TKIs plus ruxolitinib, using the plasma inhibitory assay technique. Changes in pSTAT3 and pSTAT5 will be correlated with clinical response and rate of TFR. Additional correlatives include multiparameter flow-based assessment of the T-cell compartment (activity/polarization) as well as natural killer cell fractions in CML patients at various time points (TKIs alone, TKIs plus ruxolitinib and during TFR).
 Thus far, 14 patients have been enrolled.

 Sweet: Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Bristol Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Atallah: Amgen: Consultancy; BMS: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Abbvie: Consultancy, Speakers Bureau. Radich: Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Thompson: Novartis/ Bristol-Myers Squibb: Research Funding. Mauro: Pfizer: Consultancy; Takeda: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Sun Pharma / SPARC: Research Funding. Pinilla Ibarz: AbbVie, Janssen, AstraZeneca, Novartis, TG Therapeutics, Takeda: Consultancy, Other: Advisory; Sellas: Other: ), patents/royalties/other intellectual property; MEI, Sunesis: Research Funding; AbbVie, Janssen, AstraZeneca, Takeda: Speakers Bureau.

 Ruxolitinib is being used off-label in chronic myeloid leukemia