Introduction: Poly (ADP-ribose) polymerase inhibitors (PARPi's) represent a newer class of antineoplastic agents targeting cancers with defective DNA-damage repair. PARPi's indications include subtypes of ovarian, fallopian tube and primary peritoneal cancer as well as subsets of patients with breast pancreatic and prostate cancers. There are currently 4 PARPi approved by the Food and Drug Administration (FDA): olaparib (approved 12/19/2014), rucaparib (approved 12/19/2016), niraparib (approved 3/27/2017), and talazoparib (approved 10/16/2018). The incidence of AML/MDS is known to be increased following chemotherapy, with a standardized incidence ratio (observed number of cases of AML/MDS among those treated with chemotherapy/expected number of cases in the general population) of 5.8 among patients with ovarian cancer, and 3.8 among patients with breast cancer (Morton et al, JAMA Onc 2018). All 4 PARPi also carry the potential risk of AML/MDS as an adverse event (AE), but a causal relationship has not been established. Notably, almost all patients treated with a PARPi would have exposure to cytotoxic chemotherapy prior to or during PARPi therapy. For patients treated with PARPi's in clinical trials, the duration of therapy prior to cases of AML/MDS emerging ranged from <1 month to 28 months. The incidence of AML/MDS observed in clinical trials with olaparib was <1.5%, rucaparib 1.1%, niraparib 0.8%, and talazoparib 0.3%. Real-world data regarding this rare but life-threatening AE in PARPi-treated patients is needed. We evaluated reports of AML/MDS associated with PARPi's in the post-approval setting.
 Methods: The FDA Adverse Events Reporting System (FAERS) database was queried for AEs associated with any of the 4 approved PARPi's, from the date of the initial FDA approval for each agent (irrespective of the indication) through March 31, 2020. The FAERS database contains de-identified reports of product-related AEs, coded using the Medical Dictionary for Regulatory Activities (MedDRA) and classified as serious or non-serious. Cases reported outside the United States were excluded. The proportion of AML/MDS reports was analyzed overall and by PARPi. To account for the variation in length of time on the market due to the different approval dates, reports of AML/MDS for each PARPi were analyzed in the first 17 months after approval (the post-marketing period for the most recently approved agent). The indication for which the PARPi was used, the sex and age of the patient experiencing the AE, and the seriousness and outcome of the AE were assessed. Comparisons of the proportion of AML/MDS cases by agent were made using the Chi-square test; statistical significance was determined at a two-sided α=0.05.
 Results: A total of 12823 post-marketing AE reports were associated with PARPi's, with 88 (0.7%) reporting cases of AML/MDS (Table). The largest proportion of AML/MDS cases were associated with olaparib (54 of a total of 2121 AE reports; 2.5%, p<0.00001 vs. all other PARPi), followed by niraparib (23 of a total of 5879 AE reports; 0.4%) and rucaparib (11 of a total of 4707 AE reports; 0.2%). No AML/MDS cases were associated with talazoparib (0 of a total 116 AE reports). During the first 17 months following each agent's approval, 14 cases of AML/MDS were reported in association with olaparib, 10 with rucaparib, 9 with niraparib, and 0 with talazoparib. The majority of cases of AML/MDS occurred in women (73%), and the most common indication for treatment was ovarian cancer (52%). The median age of the patients in the AML/MDS reports was 66 years. Nearly all cases were classified as serious (98%), and the outcome of the AE was death for 28% of cases, hospitalization for 17% of cases.
 Conclusions: Our retrospective analysis found that AML/MDS associated with PARPi's was reported rarely in the post-marketing setting, and that 60% involved olaparib. This study is limited by its retrospective design, and the possibility of under-reporting of cases to the FAERS database. Additionally, the time elapsed since approval differed by agent, and lower observed incidence of AML/MDS for some agents may reflect the limited duration of surveillance. No data is available in the case reports regarding length of exposure to chemotherapy. This real-world analysis complements existing clinical trial data and provides insight into AML/MDS associated with 4 different PARPi's in clinical practice.

 Gajra: Cardinal Health: Current Employment. Zettler:Cardinal Health: Current Employment. Klink:Cardinal Health: Current Employment. Feinberg:Cardinal Health: Current Employment.


There is growing evidence that tolerogenic dendritic cells (DCs) play an important role in maintaining peripheral tolerance through the induction of anergic or regulatory T cells. However, in humans, little is known about the ability of tolerogenic DCs to induce tolerance to autoantigens in autoimmune patients. Idiopathic thrombocytopenic purpura (ITP) is an immune-mediated disease in which platelets are destroyed by antiplatelet autoantibodies. Here, we explored in vitro the ability of four subsets of tolerogenic DCs (i.e., immature DCs (imDCs), IL-10-modulated DCs (IL-10-DCs), vasoactive intestinal peptide-modulated DCs (VIP-DCs) or plasmacytoid DCs (pDCs)) derived from patients with ITP, to induce an anergic state or regulatory T cells in autologous platelet glycoprotein (GP)-specific T cells. GPIIb/IIIa-reactive T cells were preincubated with GPIIb/IIIa-loaded imDCs, IL- 10-DCs, pDCs or VIP-DCs, and then rechallenged with autologous mature DCs (mDCs) in the presence of GPIIb/IIIa. Only when T cells were cultured with GPIIb/IIIa-loaded VIP-DCs in primary incubation, inhibited proliferation of GPIIb/IIIa-reactive T cells could be observed at rechallenge with GPIIb/IIIa-loaded mDCs. The anergic state of VIPDC- primed GPIIb/IIIa-reactive T cells could be reversed when rechallenged with GPIIb/ IIIa-loaded mDCs in the presence of a high concentration of exogenous IL-2. Meanwhile, GPIIb/IIIa-reactive T cells were also cultured with VIP-DCs loaded with tetanus toxoid (TT). In contrast to T cells pretreated with GPIIb/IIIa-loaded VIP-DCs, GPIIb/IIIareactive T cells pretreated with TT-loaded VIP-DCs proliferated when rechallenged with GPIIb/IIIa-loaded mDCs, which demonstrated that the induced anergy of autoreactive T cells is antigen specific. Additionally, functional analysis showed that VIP-DC-modulated T cells could not suppress the proliferation of newly induced GPIIb/IIIa-reactive T cells when cocultured with GPIIb/IIIa-loaded mDCs. These results indicated that VIP-DCs could induce autoreactive T cells anergic but not functionally suppressive. Moreover, we found that coculture of VIP-DCs with autologous PBMCs resulted in reduced production of anti-GPIIb/IIIa antibodies, suggesting that GPIIb/IIIa-reactive T cells lost their helper function for inducing autoantibody production by B cells. In contrast, reduced antibody production could not be found when autologous PBMCs were cocultured with imDCs, IL-10-DCs or pDCs. In conclusion, our studies revealed the therapeutic potential of VIPDCs, compared with imDCs, IL-10-DCs or pDCs, to induce autoreactive T-cell anergy to GP antigens, which would in turn facilitate the reestablishment of autoantigen-specific tolerance in patients with ITP.


Probiotics may offer protection against Salmonella enteritidis serovar Typhimurium infection via different mechanisms. The aim of this study is to investigate, using mouse models, the effect of the administration of fermented milk containing the probiotic bacteria L. casei DN-114 001 in the protection against Salmonella enteritidis serovar Typhimurium when this product is administered continuously before and after infection or only post-infection. The adjuvant effect of this probiotic fermented milk (PFM) against S. Typhimurium was also evaluated in newborn mice, whose mothers received the PFM during the suckling period or their offspring after weaning. The results obtained showed that PFM administration after salmonella infection was useful to decrease the severity of the infection. The best effect was obtained with continuous PFM administration. In the newborn mice model, PFM administration to the newborn mice after weaning showed the best effect against the pathogen. PFM administration to the mother during the suckling period was beneficial against this enterophatogen when their offspring did not receive probiotics after weaning. Continuous PFM administration to adult mice (before and after infection) was important to maintain the intestinal barrier and the immune surveillance in optimal conditions to diminish the pathway of entrance of salmonella and the spread of this pathogen to deeper tissues. In the newborn mice model, it was observed that PFM administration to the offspring after weaning or their mother during the suckling period had a protective effect against salmonella infection, however, in the mice from mothers that received PFM during nursing which were fed with PFM after weaning, we found a down regulated immune maturity that was not protective against this infection.


Spontaneous spinal epidural haematomas are quite rare. We report here the case of a 27-year-old woman, without previous history of relevant medical disorder, who presented with acute paraplegia at 36 weeks of gestation. MRI performed in emergency revealed a T8 epidural haematoma. The management consisted in an emergency Caesarean section under general anaesthesia, followed immediately by a T8 laminectomy allowing the spinal cord decompression 14 hours after the first symptoms. Neurologic recovery was rapid and complete, except for bladder dysfunction persisting one month later. Spontaneous spinal epidural haematomas require a prompt diagnosis because neurologic prognosis essentially depends on the interval of time between onset of symptoms and surgical decompression. Obstetrical management especially depends on the term of pregnancy. For the anaesthesiologist, the difficulty is the management of both pregnant condition (full stomach general anaesthesia) and spinal cord compression (maintenance of spinal cord perfusion pression and limitation of ischaemia and oedema).


Feline panleukopenia (FPL) was diagnosed in 185 of 7043 feline admissions (2.63%) at a university veterinary hospital over an eight-year period. FLP has a distinct seasonal pattern, occurring during July, August and September. Seasonal peaks were noted in all the years studied. Cats less than one year of age accounted for 70% of the total morbidity. The birth of felines in the United States also assumes a distinctly seasonal pattern. Analysis of 47,786 purebred litters born during 1970-1972 revealed a peak during April, May and June with a national median of May 29. A unifying hypothesis is presented to account for the seasonal occurrence of FPL. An influx of susceptible cats occurs annually following the birth of large numbers of kittens each spring, and disappearance of maternal immunity during the next two to three months. The addition of a large number of susceptible kittens leads to the development of summertime epidemics and serves to exemplify the principles of "herd immunity."


This study determined the relationship between childrearing practices and demographic variables of parents as well as academic performances of pupils. A total of 204 parent-pupil tandem was purposively selected from two research locales, public and private elementary schools. The population was further categorized into academically high performing and academically low performing pupils with each group comprised of 102 members. The parent-respondents were asked to answer a survey questionnaire which determined their demographic profile and identified the method of childrearing they practice. Distribution of parent-respondents of respective high performing and low performing groups in terms of demographic profile are as follows: occupation – 50% and 47% employed; educational attainment – 46% and 29% college graduate; average monthly family income (highest frequency) – 33% (Php7,501-15,000) and 46% (Php2,501-7,500); and number of children (highest frequency, both 3-5 children) – 55% and 57%. Extent of identified childrearing practices of parent-respondents of academically high performing groups revealed very highly extensive practices in care giving (4.72) and forming values (4.62); highly extensive practices among observing rules (4.04), imposing discipline (4.38), rewarding-punishing (4.30); and moderately extensive practice in nutrition (3.44). On the part of the academically low performing group, except for the moderately extensive practice of childrearing related to nutrition (3.29), all the identified childrearing practices are being done in a highly extensive manner with mean average ranging from 3.63 to 4.46. Correlational statistics revealed a significant relationship between childrearing practices and demographic profile of parent-respondents along educational attainment (r = 0.521), income (r = 0.408) and number of children (r = -0.252); likewise significant relationship between childrearing practices and academic performance of pupils belonging to academically low performing groups was observed (r = 0.527). No significant relationship was established between childrearing practice high performing groups. In conclusion, variation in childrearing practices is due to differences in educational attainment of parents, monthly family income and number of children in the family. Further, due to established self-efficacy values of academically high performing groups, only the academic performances of low performing groups are affected by the type of childrearing practices. Forwarded recommendations focused on creation of programs both on the school and government levels, for responsible parenting intensification.


Now a days data is increasing exponentially daily in terms of velocity, variety and volume which is also known as Big data. When the dataset has small number of dimensions, limited number of clusters and less number of data points the existing traditional clustering al- gorithms will give the expected results. As we know this is the Big Data age, with large volume of data sets through the traditional clus- tering algorithms we will not be able to get expected results. So there is a need to develop a new approach which gives better accuracy and computational time for large volume of data processing. The Proposed new System Architecture is a combination of canopy, Kmeans and RK sorting algorithm through Map Reduce Hadoop frame work platform. The analysis shows that the large volume of data processing will take less computational time and higher accuracy, and the RK sorting does not require swapping of elements and stack spaces.


The crystal structure of merimepodib has been solved and refined using synchrotron X-ray powder diffraction data and optimized using density functional theory techniques. Merimepodib crystallizes in space group P212121 (#19) with a = 4.60827(3), b = 12.30400(14), c = 37.9583(4) Å, V = 2152.241(20) Å3, and Z = 4. The crystal structure is dominated by two chains of N–H⋯O hydrogen bonds along the a-axis. The solid-state conformation has a similar general shape to the minimum-energy conformation, but different orientations of several of the rings. The differences indicate that intermolecular interactions are important in determining the solid-state conformation. The powder pattern has been submitted to ICDD for inclusion in the Powder Diffraction File™ (PDF®).


The invention relates to performance improved dish washing machine detergents. Said detergents provide improved washing performance even when a smaller dosage is used at a lower temperature and for a shorter period of washing time. Like traditional dishwashing machine detergents ("cleaners") the inventive detergents can be produced in both powder or granular form or in a tablet or pourable form as well as in the form of a combined product ( a "2 in 1" product which washes and rinses, or as a "3 in 1" product, which washes, rinses, and replaces salt), containing 0.1 - 50 wt. % of one or more non-ionic surfactants which have a diffusion co-efficient of at least 9 * 10 m s for a concentration of 0.01 g/l in distilled water.


Background: Migraine affects about 16% of the worldwide population. The pathogenesis of the disease consists of a combination of genetic and environmental factors. Given that, according to different polymorphism studies, ethnicity has a role in the gene diversity of migraine, this study was designed to determine the role of MTHFR C677T gene polymorphism in people from Tehran, Iran, who suffer from migraine headaches.
Materials and methods: In this case control study, we determined the prevalence of common MTHFR C677T polymorphism in 132 migraine patients in line with IHS criteria (37 migraine patients with aura and 95 migraine patients without aura) and compared it to that in 142 matched healthy controls. The correlation between migraine and genotype was investigated using the chi-square test. The Bonferroni adjusted P-value was also used for pairwise comparison.
Results: Our findings demonstrated that there was no significant difference in the frequencies of the TT genotype or T allele distributions between the migraine patients with aura and the control subjects. On the other hand, the frequency of the TT genotype among migraine patients without aura was significantly lower than those in the control group or the patients with aura group.
Conclusion: MTHFR C677T polymorphism, which is responsible for reducing MTHFR activity in the folate metabolism, is not a major genetic susceptibility factor for migraine in the investigated population.


This paper studies the robustness of estimated policy effects to changes in the distribution of covariates. Robustness to covariate shifts is important, for example, when evaluating the external validity of quasi-experimental results, which are often used as a benchmark for evidence-based policy-making. I propose a novel scalar robustness metric. This metric measures the magnitude of the smallest covariate shift needed to invalidate a claim on the policy effect (for example, ATE ≥ 0) supported by the quasi-experimental evidence. My metric links the heterogeneity of policy effects and robustness in a flexible, nonparametric way and does not require functional form assumptions. I cast the estimation of the robustness metric as a de-biased GMM problem. This approach guarantees a parametric convergence rate for the robustness metric while allowing for machine learning-based estimators of policy effect heterogeneity (for example, lasso, random forest, boosting, neural nets). I apply my procedure to the Oregon Health Insurance experiment. I study the robustness of policy effects estimates of health-care utilization and financial strain outcomes, relative to a shift in the distribution of context-specific covariates. Such covariates are likely to differ across US states, making quantification of robustness an important exercise for adoption of the insurance policy in states other than Oregon. I find that the effect on outpatient visits is the most robust among the metrics of health-care utilization considered.


Ebstein's anomaly--is a complex disease of the heart, the main components of which are dysplasia and tricuspid valve malposition, causing hemodynamical disorders. Principal method of correction of this anomaly is surgical one. There are many surgical methods of correction of the anomaly proposed: tricuspid valve prosthesis, plastic operation, palliative methods. Indications for surgical treatment of Ebstein's anomaly is cyanosis, the blood flow insufficiency, severe disorders of the heart rate.


The discovery that smoke is an important stimulus of seed germination was made during a comprehensive study by Hannes de Lange on a threatened species in the Bruniaceae, Audouinia capitata. The role of fire in regeneration was one of the subjects investigated. Official approval was given for a controlled burn in the Cape of Good Hope Nature Reserve in an area containing one of the A. capitata populations. At 20 stations in this area of 4000 m3, heat-sensitive labels were buried at a depth of 10 mm prior to the burn. These labels were also buried at the same depth at four different spots 10 m outside the perimeter of the area to be burned.


Cave bears, an extinct subgenus (Spelearctos) of Ursus, were versatile enough to inhabit large areas of the northern hemisphere during the middle and late Pleistocene, yet they had evolved a specialized dentition that emphasized grinding functions, implying a heavy dietary reliance on tough, fibrous foods (i.e., plants). Isotope studies have yielded conflicting results on cave bear diet, however, often without consideration of the provenance of the samples or the possible contradictions that taphonomic and morphologic evidence might pose to dietary interpretations. It is likely that cave bear habits varied somewhat in response to environmental circumstance, and the limits on their abilities to do so remain unknown. If the larger goal of paleontological inquiry is to reconstruct the adaptations of cave bear species, then variation and commonalities among populations must be tracked closely, and the disparate lines of evidence currently available examined together on a case by case basis. Clearly, no single analytical technique can achieve this. By way of example we present the results of a cross-disciplinary collaboration that combines osteometric, isotopic, and taphonomic approaches to studying the paleoecology of a bear assemblage from Yarimburgaz Cave in northwest Turkey. Reference information on the linkages between diet, hibernation, and population structure in modern bears provides test implications for the investigation. Osteometric techniques demonstrate the presence of two coextant middle Pleistocene bear species in the sample–Ursus (Spelearctos) deningeri, a form of cave bear, and U. arctos or brown bear–the former abundant in the sample, the latter rare. An attritional mortality pattern for the bears and the condition of their bones show that most or all of the animals died in the cave from nonviolent causes in the context of hibernation. The study also elucidates several characteristics of the cave bear population in this region. Osteometric techniques show that the adult sex ratio of the cave bears is only slightly skewed toward females. This pattern lies near one extreme of the full range of possible outcomes in modern bear species and can only reflect a strong dietary dependence on seasonally available plants and invertebrates, showing that hibernation was a crucial overwintering strategy for both sexes; the results specifically contradict the possibility of regular, heavy emphasis on large game (hunted or scavenged) as a winter food source. The nature of wear and breakage to the adult cave bear teeth indicates that food frequently was obtained from cryptic sources, requiring digging and prying, and that extensive mastication was necessary, leading to complete obliteration of some cheek tooth crowns in old individuals. The patterns of tooth damage during life corroborate the dietary implications of the adult sex ratio and also argue for a diet rich in tough, abrasive materials such as nuts, tubers, and associated grit. The carbon and oxygen isotopic compositions of cave and brown bear tooth enamel from the site are virtually identical, and there is no evidence of a strong marine signal in either species, despite the cave's proximity to a modern estuary of the Sea of Marmara; nitrogen isotope ratios could not be examined because of poor protein preservation. The isotope results suggest that both bear species were highly omnivorous in the region during the middle Pleistocene and obtained nearly all of their food from terrestrial and fresh-water habitats. Bone pathologies, usually originating from trauma, occur in some of the adult bears, testifying to long lifespans of some individuals in this fossil population. The Yarimburgaz cave bears also exhibit great size dimorphism between the sexes, based on weight-bearing carpal bone dimensions, with adult males attaining roughly twice the body mass of adult females.


Pulmonary precapillary hypertension present only during exercise is the first stage of corpulmonale. Examination of the reaction of central haemodynamics to exercise is the only way to detect it. In a model situation like unilateral pulmonary artery occlusion (UPAO) in healthy subjects, an increase in pulmonary artery pressure (Ppa) during exercise is a linear function of restriction of the pulmonary vascular bed and blood flow increase. Central haemodynamics during exercise in younger subjects after pneumonectomy (PNE) resemble the situation with UPAO provided the remaining lung is intact. In older patients after PNE the same rise of blood flow is associated with a considerably greater rise of Ppa. PNE patients compared to healthy individuals increase their cardiac output during exercise more by increasing stroke volume. Patients with pulmonary fibrosis show a disproportionate rise in Ppa in relation to flow. This is due to reduced distensibility of the pulmonary system. Hypoxia also seems to be involved in pulmonary hypertension during exercise. Pulmonary wedge pressure rises at work but remains within the normal range, even in patients having marked hypoxaemia at rest and during exercise. In idiopathic intersitial pulmonary fibrosis (IIPF), pulmonary hypertension during exercise is greater than in other forms of pulmonary fibrosis. Inhalation of oxygen during exercise in patients IIPF leads to a reversal of hypoxaemia but the decrease of Ppa is small and due to a passive decrease of cardiac output. Finally right ventricular function in restrictive pneumopathies is discussed.


Lee Yeo-seong(1901~?), both an ideologue and critical adviser of the social democracy of Yeo Un-hyeong, the leader of the center-left, served to establish the new nation through Movement to unite the Left and the Right and National United Front just after its liberation. The purpose of this thesis is to search for the theoretical foundation of the center-left, post liberation, through the perspective of Lee's thoughts in the 1920s. Lee, convicted of being a strong nationalist and active participant in the March 1st Movement - an independence movement against Japanese imperialism - served time in prison, after which he went to Tokyo, Japan and become a socialist. His theory on national independence movement was Line of a Legitimate Proletariat Political Party and Line of the National United Front, which were compound of nationalism, socialism and democracy. It was that the proletariat should strive to form a legitimate political party, become a majority in the parliament to secure bourgeois democracy and, at the same time, affiliate itself with nationalism to defeat Japanese Imperialism. The political system of the new independent country that he devised matches the parliament-centered bourgeois democratic system, which is the goal of Line of the Left Lawful Political Movement. If achieved, the new country would inevitably be expected to be a proletariat democracy. Lee's national liberation movement theory evidently implies the sole purpose of social democracy: 1) every individual's right to vote and democratic participation in politics 2) realization of legitimate political parties involvement 3) pursuing not an under-ground party but an official political party, 4) cooperation and coexistence of nationalism and socialism 5) national independence. His social democracy was not the type directly imported from the West, but the spontaneously reconstructed socialism and nationalism under the name of democracy, faced with the immediate issue of national liberation. Therefore, it can be argued that communism in Korea was divided into Bolshevism and social democracy since the 1920's import of the idea through Lee's work and theory, and that the national liberation movement theory was Line of the National United Front and Line of a Legitimate Proletariat Political Party, which imply social democracy. However, such social democracy was spontaneous and was limited due to the fact that social democracy and Bolshevism were not yet clearly distinguished. Although Lee's national socialism and social democracy theory became a ideological base of Yeo's center-left movement after independence, its limit also became a significant obstacle which caused center-the left not to be able to secure its position in post-liberated Korean society.


PRECIS
A pathogenic autosomal dominant MYOC mutation N480K detected in six generations of an Indian family is primarily responsible for JOAG and adult-onset POAG, emphasizing the importance of screening this mutation at a younger age.

PURPOSE
To screen myocilin mutations in a large South Indian family with early-onset Juvenile (JOAG) and adult-onset primary open-angle glaucoma (POAG).

METHODS
In a large South Indian family with 20 members, eight members diagnosed as JOAG, seven members as POAG, four members as JOAG suspect, and one member as POAG suspect were screened for myocilin (MYOC) mutations using Sanger sequencing. Whole exome sequencing was performed on clinically suspected JOAG/ POAG individuals.

RESULTS
Myocilin gene mutation N480K (c.1440C>G) was detected in 20 family members including proband, of whom 8 were JOAG and 7 were POAG patients, three JOAG suspects and two were unaffected. Among the unaffected carriers, one was less than five years old, and another was 25 years old. The earliest to develop the disease was a ten-year-old child. The penetrance of the mutation was 95% over ten years of age. This family had JOAG/POAG suspects with no N480K MYOC mutation and they were further screened for other mutations using whole-exome sequencing. Polymorphisms CYP1B1 L432V and MYOC R76K were detected in three JOAG/POAG suspects, and among these three, one had another CYP1B1 polymorphic variant R368H. The presence of the CYP1B1 polymorphism along with a MYOC polymorphic variant among the JOAG/POAG suspects needs additional studies to explore their combined role in the onset of glaucoma.

CONCLUSIONS
This study reveals that MYOC mutation is primarily responsible for JOAG and adult-onset POAG in the Kadaladi family, emphasizing the importance of screening for this mutation at a younger age for early treatment.


Micro arrays are used to assess the transcriptome of many biological systems that has generated an enormous amount of data. Cluster analysis is a technique used to group and analyze micro array data. Identification of groups of genes that manifest similar expression patterns is a key step in the analysis of gene expression data. Hierarchical clustering is the one of the clustering techniques used for this purpose. In this paper, we design an enhanced hierarchical clustering algorithm which scans the dataset and calculates distance matrix only once unlike other papers, (up to authors' knowledge). Our main contribution is to reduce time, even when a large database is analyzed. Also, the results of hierarchical clustering are represented as a binary tree which gives clarity in grouping and further helps to find clustered objects easily. Our algorithm is able to retrieve number of clusters with the help of cut distance and measures the quality with validation index in order to obtain the best one; does not require initial parameter like number of clusters.


ABSTRACT Objectives: Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR). A bronchial provocation test (BPT) is used to test for AHR. However forced expiratory volume in one second (FEV1), used as outcome parameter is effort-related, in contrast to specific airway resistance (sRaw). This research was conducted to provide insight in the usefulness of sRaw as an outcome parameter in BPT. Methods: A total of 85 patients performing a BPT were included in the study. Bronchial reactivity was defined as the provocative dosage or provocative concentration causing a 20% decrease in FEV1 (PC-20) or a 100% increase in sRaw (PC+100). Results: No significant response in either FEV1 or sRaw was found in 20 patients (24%). Twenty-nine patients (34%) only had a positive response for sRaw; 24 out of these 29 patients recognized their symptoms. 36 patients (42%) showed a positive response for both PC-20 and PC + 100. Conclusions: Twenty-nine patients (34%) showed a significant increase in sRaw without a fall in FEV1. As performing sRaw is not a routine investigation, these patients are at risk of being excluded from a diagnosis of asthma. We suggest performing sRaw for patients without a fall in FEV1 during BPT when they report recognizable symptoms.


Recently, the tradeoff between energy consumption and fault-tolerance in real-time systems has been highlighted. These works have focused on dynamic voltage scaling (DVS) to reduce dynamic energy dissipation and on-time redundancy to achieve transient-fault tolerance. While the time redundancy technique exploits the available slack-time to increase the fault-tolerance by performing recovery executions, DVS exploits slack-time to save energy. Therefore, we believe there is a resource conflict between the time-redundancy technique and DVS. The first aim of this paper is to propose the use of information redundancy to solve this problem. We demonstrate through analytical and experimental studies that it is possible to achieve both higher transient fault-tolerance [tolerance to single event upsets (SEUs)] and less energy using a combination of information and time redundancy when compared with using time redundancy alone. The second aim of this paper is to analyze the interplay of transient-fault tolerance (SEU-tolerance) and adaptive body biasing (ABB) used to reduce static leakage energy, which has not been addressed in previous studies. We show that the same technique (i.e., the combination of time and information redundancy) is applicable to ABB-enabled systems and provides more advantages than time redundancy alone.


Titanium alloys with various porous structures can be fabricated by advanced additive manufacturing techniques, which are attractive for use as scaffolds for bone defect repair. However, modification of the scaffold surfaces, particularly inner surfaces, is critical to improve the osteointegration of these scaffolds. In this study, a biomimetic approach was employed to construct polydopamine-assisted hydroxyapatite coating (HA/pDA) onto porous Ti6Al4V scaffolds fabricated by the electron beam melting method. The surface modification was characterized with the field emission scanning electron microscopy, energy dispersive spectroscopy, water contact angle measurement, and confocal laser scanning microscopy. Attachment and proliferation of MC3T3-E1 cells on the scaffold surface were significantly enhanced by the HA/pDA coating compared to the unmodified surfaces. Additionally, MC3T3-E1 cells grown on the HA/pDA-coated Ti6Al4V scaffolds displayed significantly higher expression of runt-related transcription factor-2, alkaline phosphatase, osteocalcin, osteopontin, and collagen type-1 compared with bare Ti6Al4V scaffolds after culture for 14 days. Moreover, microcomputed tomography analysis and Van-Gieson staining of histological sections showed that HA/pDA coating on surfaces of porous Ti6Al4V scaffolds enhanced osteointegration and significantly promoted bone regeneration after implantation in rabbit femoral condylar defects for 4 and 12 weeks. Therefore, this study provides an alternative to biofunctionalized porous Ti6Al4V scaffolds with improved osteointegration and osteogenesis functions for orthopedic applications.


Radar ranging data taken along the +21.5° parallel of Mars have shown conclusively that elevation differences of up to 11 km occur on the planet. The highest areas observed are desert regions; the maria lie in low areas or on slopes. The canals identified in the radar data all occur in broad and frequently deep valleys which are related to a planet-wide lineament system. It was found that the topographic contours based on the radar data readily fit the visual surface features even in the areas where the features are very complex.


Stereotactic body radiation therapy (SBRT) is a newly developed technique currently in clinical use. SBRT originated from stereotactic radiosurgery for intracranial tumors. SBRT has been widely used clinically for lung cancer. The practice of SBRT demands different kinds of patient fixation, breathing control, target determination, treatment planning, and verifications. The history and current standard technique are reviewed. Clinical studies of lung cancer showed high local control rates with acceptable toxicities. Past and on-going clinical trials are reviewed.


Workplace sociopaths — about 1 individual in 25 — do not have a conscience. That's according to Martha Stout in The Sociopath Next Door. Workplace sociopaths have no feelings of guilt or remorse. When the opportunity exists, a workplace sociopath will manipulate reality; hide evidence; stab others in the back; fabricate compelling lies; attempt to ruin the reputations of others; steamroll the weak; and bring down people who are smarter, more accomplished, classier or more admirable, all in the name of fun, adrenaline rush and vengeance.


In the field of traffic-information acquisition, one pervasive solution is to use wireless sensor networks (WSNs) to realize vehicle classification and counting. By adopting heterogeneous sensors in a WSN, we can explore the potential of using complementary physical information to perform more complicated sensing computation. However, the collaboration among heterogeneous sensors, such as the collaborative sensing mechanism (CSM), is not well studied in current state-of-the-art research. In this paper, we design and implement EasiSee, a real-time vehicle classification and counting system based on WSNs. Our contributions are as follows. First, we propose a CSM, which coordinates the power-hungry camera sensor and the power-efficient magnetic sensors, reducing the overall system energy consumption and maximizing system lifetime. Second, we propose a robust vehicle image-processing algorithm, i.e., a low-cost image processing algorithm (LIPA). LIPA reduces environment noise and interference with low computation complexity. In the verification section, the vehicle detection accuracy turned out to be 95.31%, which pave the way for CSM. The time of image processing is around 200 ms, which indicates that our LIPA is computationally economical. With the overall energy consumption reduced, EasiSee achieves classification accuracy of 93%. Based on these experiments and analysis, we conclude that EasiSee is a practical and low-cost affordable solution for traffic-information acquisition.


Sir, The paper by Johnson et al. regarding routine amniotomy in labour (Vol 104, March 1997)' invites a response from Dublin where 'a woman in labour can expect her membranes to be ruptured artificially'. There are several reasons why the results of this study should not be compared with the results of active management of labour as practised at the National Maternity Hospital, Dublin. So-called 'early' amniotomy in this study did not occur until a median of 5 cm cervical dilatation (mean 5.2). Indeed, 23% of women in the treatment group were 8 cm dilated at the time of amniotomy. This is a very late amniotomy by our standards where 80% of nulliparous women receive an amniotomy at a cervical dilatation of 2 cm or less. By performing the amniotomy at such a late stage the authors leave little chance of detecting a big difference between their study groups as the median cervical dilatation of the control group at amniotomy was very similar to that of the study group (median 7 cm, mean 6.1 cm). Not surprisingly, some women progressed 'too rapidly' in labour for them to have their 'early' amniotomy performed. The duration of the first stage of labour is inversely proportional to cervical dilatation on admission. According to nomograms produced by Studd for a British population, once a nulliparous woman has reached 5 cm cervical dilatation, she can expect to reach full dilatation within 3 hours, even without an amniotomy*. If routine amniotomy is to significantly accelerate normal labour, it seems prudent to perform it in nulliparous women admitted in labour at 2 cm or less i.e. the women whom we know to be at risk of longer labours. An essential part of the active management of labour is the early and definitive diagnosis of labourl. This diagnosis is made at our institution within one hour of admission to the delivery suite i.e. by the presence of painful uterine contractions in association with dilatation and effacement of the cervix. The diagnosis is made at the admission vaginal examination or, if deemed not in labour at the time of admission, at a subsequent examination one hour later. In the study by Johnson et aL', the diagnosis of labour was 'subjective' and indeed incorrect in 10% of women. We suggest that more attention be paid to this critical aspect of labour. This trial ran for three and a half years, yet includes only 600 nulliparous women: active management of labour is confined to nulliparous women. It would also be important to know how representative the study groups are of the entire eligible hospital population. The findings of this study are not disputed i.e. that 'late' amniotomy confers limited benefit. It is not however valid to extrapolate the results to obstetric practice in Dublin where true 'early' amniotomy is performed, as one component of a very comprehensive 'package' of active management of labour.


The decision about marketing channels selection is critical as it ultimately affects the other supply chain activities of any business. The purpose of this study was to examine the redistribution role of distributors in the brewing industry. The study employed a survey using a single case study from the perspective of retail outlets. The study revealed that availability and visibility of brands increased brand penetration coupled with effective coverage and management of sales territories by the distributor. The outlets indicated that getting all the empties for their purchase of products was a challenge. The study suggests that distributors must be accountable and ensures flawless sales force coverage and effectiveness to avoid out-of-stocks situations. Manufacturers must intensify their trade and consumer promotions concurrently to really connect the push and pull aspect of distribution.


In the article ''Inflammatory Response After Laparoscopic Versus Open Resection of Colorectal Liver Metastases Data From the Oslo-CoMet Trial'', which appeared in Volume 94, Issue 42 of Medicine, the University of Oslo was not credited as the affiliation for several authors. The article has since been corrected online.


The purpose of this document is to identify the best position of an acoustic emission sensor in a gearbox for fault detection. The acoustic emission sensor was located in the four side walls of the gearbox, where three signals were acquired in each position to be analyzed in the time domain by condition indicators and finally the best signals were analyzed in the frequency do-main by means of the gear step frequency. As a result, it was obtained that the sensor must be positioned in the shorter length lateral parts of the gearbox


This paper highlights on the increasing fears that chemicals in agriculture have found their way into drinking water causing health complications. In fact many chemical s have not had these effects but waiting to do so b y moving into groundwater sinking slowly and finally going into t aps. Nitrate fertilizer is largely blamed for these fears. Use of fertilizers obviously would increase manifold to me et the food needs arising out of population explosi on and it would further aggravate the situation. Therefore th e use of chemicals in agriculture presents global a larm particularly for Andhra Pradesh where environmental degradation is rampant and unfortunately least gro undwater contamination resulting from application of agricul tural chemicals especially the fertilizer.


A number of places that feature in Strabo's description of the Asian peninsula were situated on the ancient road that ran between the Euphrates river and the city of Ephesus. It is likely that Strabo journeyed along the entire thousand-kilometre length of the road, even though he makes explicit reference to his presence in only a few locations. He most probably made the journey as a youth on his way to Roman Asia, in the south west of the peninsula, from Pontus in the north. Decades pass before Strabo, as an old man, writes the Geography and includes in it the memories of places he had visited. The outdated tone of some of his descriptions reflects this passage of time.


While the concept of "God in the courtroom" evokes a few grand images, there are numerous, often subtle, ways in which religion and law intersect. For example, religious beliefs might influence the decisions of legal decision makers, such as judges and jurors. Attorneys might rely on religion, both in the way they approach their professional practice generally and in specific trial tactics (e.g., using a scriptural rationale in arguing for a particular trial outcome). This book reviews legal developments and behavioral science research concerning the effects of religion on legal practice, decision-making processes of various legal actors, and trial outcomes. Chapters address jury selection and bias, attorneys' use of religion in legal movements, judges' religious beliefs and its role in their appointment, and the treatment of religious figures or institutions as litigants in court. By drawing from various research sources, the authors effectively explore the range of ways in which religion affects the actions of all of the major participants at trial: jurors, judges, attorneys, and litigants.


Abstract
This chapter reports on a qualitative study that investigated the functioning of school governing bodies as a tool for promoting democracy in two schools. Data was gathered through interviews, observations and document reviews. Findings revealed that democracy was in existence and practiced at both schools and that it was characterized by shared decision-making and acknowledged rights of individuals, representation, participation and equality. Two structures for promoting democracy were found to be in existence in both schools, and these are school governing bodies and representative councils for learners. Such structures were found to be functioning effectively and contributing to the democracy in schools. However, although the learner voice was represented at both schools, learner participation in crucial issues in both the schools was limited. The study recommends that all teachers, learners and parent representatives on the SGBs be trained in skills such as deliberation, debate, dialogue and managing differences. Furthermore, training or capacity building related to advocacy skills and leadership development should be provided for all members of the SGB including teachers. The more learners, parents and staff are involved in school policy and decision-making, the more there is a genuine community involvement in schools, and the more effective a school becomes. Also, schools need to move towards learner-initiated decision-making where learners initiate the process and invite adults to join them in decision-making. Also, there is need for teachers to be trained in democratic ways of operating in the school and classroom, which will possibly help them learn ways of working democratically in both the whole school and the classroom.


User-focused design processes are justly celebrated in the design community. But like any other design strategy, they can be used inaccurately, and they can be ineffective. Victor Seidel (University of Oxford) and John Pinto (Pinto Research) suggest some specific insights from the social sciences that can be applied most usefully. They also suggest that these same strategies may be applied to improving design management itself. This article offers six methods for examining both the user and the design team, with an eye to improving innovation, as well as design management.


The study examined exercise motivation and behavior of two cultural groups, American and Taiwanese. Gender and group differences on associated variables were studied. Also, relationships between psychological and personal variables were tested. Self-Motivation Inventory, Personal Incentives for Exercise Questionnaire, and Sport Orientation Questionnaire served as exercise motivation measures. Personal and program variables, and open-ended questions, were also included to assess relevant factors. English questionnaires were translated into Chinese for Taiwanese. A total of 391 American and Taiwanese exercisers participated in this study. The results indicated cultural, gender, and group differences on psychological, personal, and program variables. Relationships between psychological and personal variables were significant. Specifically, American exercisers were found more self-motivated and competitive, with higher incentives for exercise than Taiwanese. Older exercisers appeared to have different incentives than younger adults. Further, Four program factors—social support, exercise leadership, organized classes, and group activity—were important in both cultures. Finally, practical implications and recommendations for future research are discussed.


A field experiment was accomplished to establish appropriate plant spacing for summer season cabbage production in the rain fed condition of the high hills of eastern Nepal. The experiment was conducted during the summer of 1997, 1998 and 1999. Five different plant spacings (45- 60-cm, 45- 50-cm, 45- 40-cm, 45- 30-cm and 45- 20-cm) and two varieties, Green Stone and Green Coronet were tested. The interactive effect between variety and spacing was nonsignificant. However, among the tested spacings, head yields were statistically higher at 45- 30- cm and 45- 20-cm plant spacings. There was a positive linear correlation between closer plant spacing and cabbage head yield. The number of unmarketable heads and the lowest head compactness was recorded in 45- 20-cm spacing. Spacing of 45- 30-cm was found more economical. Plant population can be maintained as high as 74,074 number ha -1 by decreasing the spacing from 75- 60-cm to 45- 30-cm for the rainy season cabbage cultivation in high hills. By using this spacing, as high as 35 t ha -1 Key words: Cabbage; Hybrid; Plant spacing; Rainy season DOI: http://dx.doi.org/10.3126/narj.v4i0.4869 Nepal Agriculture Research Journal Vol. 4&5, 2001/2002 Page: 48-55 Uploaded date : 9 June, 2011


The effects of cooling rate, Ti content, and casting temperature on titanium compounds for high titanium steel were investigated. In-situ observation of high titanium steel during remelting and solidification was carried out by using a High Temperature Confocal Scanning Laser Microscope (HTCSLM), and the observed results were in good agreement with the thermodynamic and kinetic calculations. The observation and calculation results both show that the inclusions in high titanium steel first precipitate in the form of TiN, followed by TiC precipitates as temperature decreases, eventually forming TiCxN1-x type inclusions at room temperature. The initial precipitation temperature of the inclusions increases with the increase of Ti content in molten steel, whereas casting temperature has little effect on the initial precipitation temperature of inclusions. In addition, the size of TiN inclusions increases with the increase of Ti content in steel but decreases with the increase in cooling rate.


Background: Health-related quality of life (QOL) is considered as an important component in the diabetes care and management; unfortunately, assessments of diabetes interventions focus mainly on glycemic control with limited consideration of QOL.

Objective: Assessment of QOL among diabetic patients registered in primary health centers of Udupi taluk, Karnataka.

Materials and Methods: A cross-sectional study was done using, Short-Form (SF) 36 version2 to measure QOL among diabetic patients. Total numbers of participants included 138 subjects with diabetes. Participants were selected from the primary health centers located in the Udupi taluk. Data were analyzed using SPSS, version 15.00.

Results: The mean age of the study participants was 57.40 ± 11.10 years and the mean duration of diabetes was 9.29 ± 6.32 years. Physical activity (>30 minutes) per day was followed by 33.3% study participants. The overall SF-36 score was 43.12 ± 7.0; the domains of the SF-36 score were the following: physical functioning with 40.57 ± 6.34, role physical 44.20 ± 9.27, body pain 43.09 ± 7.91, general health 42.48 ± 7.33, vitality 45.13 ± 5.59, social functioning 42.91 ± 6.56, role emotional 38.50 ± 12.08, and mental health 44.68 ± 5.75. The two most affected domains were "physical functioning" and "role emotional" among the study participants. Overall, men had better QOL scores; this was found to be statistically significant (P = 0.002). QOL were better among the educated group of participants than illiterate group of participants.

Conclusion: In diabetes management, QOL needs to be emphasized in health program for more effective approach.


By means of an acoustic technique, we follow the time and space dependence of the concentration of a settling suspension composed of spherical glass beads in water. The concentration profile consists of two shock fronts, one at the top, one at the bottom of the sedimentation column. The velocity determination of these two fronts allows a precise analysis of how the settling velocity for suspension concentrations close to the packing vanishes.


The objective of this study was to evaluate the oral hygiene practices and dietary habits among a sample of children with Down's syndrome in Riyadh, Saudi Arabia, and to determine whether the mother's educational level and occupational status are related to these practices and habits. Two hundred and fifty families of children with Down's syndrome were selected for this study. These children attended three institutions in Riyadh, Saudi Arabia. The data for the study was obtained through a self-administered questionnaire distributed by the institutions principal. Two hundred and twentyfive questionnaires were returned giving a response rate of 90%. The results showed that nearly 75% of the children brushed their teeth once or more daily and that about 90% used the toothbrush. Of the surveyed sample, 60% received parental help with tooth brushing, and 12% were helped by the nanny. Children of mothers with university education were found to brush their own teeth or depend on the nanny's help (P=0.008, P=0.001 respectively). Also children of working mothers were found to brush their own teeth or rely on the nanny's help (P=0.034, P<0.0001 respectively). Only 7.3% of the mothers gave their children sweets or sweet snacks three times a day or more and 7% gave them sweet drinks as frequent. Over half of the mothers gave their children sweets and sweet snacks occasionally, and 42.8% gave them sweet drinks occasionally. No statistically significant differences, in these practices, were found in relation to the mother's educational levels or occupational status. The practice of giving sweets as a reward was low among the surveyed sample and the highest percentage (55.7%) of the respondents gave their children in-between meal snacks once/day. Statistically significant differences were found only in the frequency of consumption of sweets and sweet snacks between the children of working and non-working mothers as non-working mothers gave their children sweets and sweet snacks more frequently (P= 0.027).This study demonstrated that the overall level of oral hygiene practices and dietary habits among Down's syndrome children was satisfactory and that assisting the children with tooth brushing would improve their oral hygiene. With regards to the relationship between the Child's oral hygiene practices and dietary habits with the mother's educational level and occupational status, statistically significant associations were found only with the person responsible for brushing the teeth and the frequency of consumption of sweet snacks.


Sb2S3 thin films, deposited by the chemical bath deposition method, were treated with N2 plasma at 3.0 Torr during several minutes. The as-prepared Sb2S3 thin films and films treated with N2 plasma have been characterized using several techniques. X-ray diffraction studies have shown that plasma treatment induced recrystallization on the as-prepared Sb2S3thin films. The band gap values decreased from 2.37 to 1.82 eV after plasma treatment, and the electrical conductivity increased from 109 to 107 (Ωcm)-1 due to the annealing effect.


In this paper, we introduce a novel Markov Chain (MC) representation aided Minimum Bit Error Rate (MBER) detection method that is applicable to an M-QAM modulated SDM/SDMA uplink system. Compared to the conventional MBER scheme, the proposed MC-MBER scheme is capable of reducing the complexity imposed with the aid of its efficient detection candidate set generation assisted by the Markov chain process. Our performance results demonstrate that the MC-MBER Multi-User Detection (MUD) is capable of reducing the computational complexity by a factor of eight in comparison to the conventional MBER MUD in a rank-deficient system transmitting four 4-QAM uplink substreams with the aid of two receive antennas at the Base Station (BS), while achieving a BER performance comparable to that of the MBER MUD.


Classical systems stirred by random forces of given statistics may be described via a path integral formulation in which their degrees of freedom are stochastic variables themselves, undergoing a multiple-history probabilistic evolution. This framework seems to be easily applicable to resistive Magneto-Hydro-Dynamics (MHD). Indeed, MHD equations form a dynamic system of classical variables in which the terms representing the density, the pressure and the conductivity of the plasma are irregular functions of space and time when turbulence occurs. By treating those irregular terms as random stirring forces, it is possible to introduce a Stochastic Field Theory which should represent correctly the impulsive phenomena caused by the spece- and time-irregularity of plasma turbulence. This work is motivated by the recent observational evidences of the crucial role played by stochastic fluctuations in space plasmas.


The Supplemental Nutrition Assistance Program (SNAP) is the largest nutritional safety net in the United States. Prior research has found that participants have higher consumption shortly after receiving their benefits, followed by lower consumption towards the end of the benefit month. Known as the "SNAP benefit cycle," this consumption pattern has been found to have negative effects on beneficiaries. We hypothesize two behavioral responses of SNAP participants may work in tandem to drive much of the cycle: (1) short-run impatience—a higher preference to consume today, and (2) fungibility of income—the degree of substitutability between a SNAP dollar and a cash dollar. Using data from the National Food Acquisition and Purchase Survey (FoodAPS), a newly developed nationally representative survey of daily food acquisitions by SNAP households, we find evidence of both behavioral responses. However, the degree of short-run impatience and fungibility of income is found to differ significantly across poverty levels and use of grocery lists to plan food purchases. SNAP households could gain from food purchase planning education.


The objective of the present work was to study the impact of Focused Ion Beam (FIB) machining parameters on the thickness of the damaged layer within a thin film PZT. Therefore, different Ga+- ion doses and ion energies were applied to a standard PZT film (80/20 lead zirconium titanate) under two beam incidence angles (90° and 1°). The thicknesses of the corresponding Ga+-implanted layers were then determined by cross-sectional TEM in combination with energy dispersive spectroscopic (EDS) line-scans and correlated with polarisation hysteresis loops. The results show a decrease of Ga+-implanted layer thickness with decreasing inclination angle, whereas ion energy and ion dose could be correlated with gallium concentration in the implanted layers.. Under the most unfavorable conditions the depth of the affected zone was 26 nm, it was only 2 nm for the most favorable conditions. (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)


In female mammals reproduction is highly sensitive to the food supply. During lean times, females suspend reproductive attempts in favor of maintaining processes necessary for survival; fertility is restored once the food supply is again abundant. Nearly all aspects of reproduction are affected, including puberty, adult ovulatory cycles, and reproductive behaviors. Work with experimental animals reveals that caloric restriction inhibits release of luteinizing hormone (LH) and female sexual behavior via similar, although separate, processes. The primary metabolic event affecting LH release as well as female sexual behavior is the short-term (minute-to-minute, hour-to-hour) availability of oxidizable metabolic fuels, rather than any aspect of body size or composition (e.g., body fat content). Metabolic fuel availability is detected in the hindbrain and perhaps in peripheral tissues. Metabolic information is then transmitted synaptically from the visceral hindbrain to the forebrain effector circuits. In the forebrain, signaling via corticotropin-releasing hormone receptors appears to be crucial for inhibition of both LH secretion and female sexual behavior.


Culture procedures for isolation of thermophilic campylobacters from food matrices are complex, labor intensive, and time-consuming. Most available methods include the use of antibiotics as selective agents to prevent the growth of competing microflora. A simple procedure for isolation of thermophilic campylobacters after enrichment in Rosef's enrichment broth was developed using a hydrophobic grid membrane filter (HGMF) on semisolid medium (SSM). SSM contains no antibiotics, and the HGMF physically separates Campylobacter from the enrichment broth, allowing isolation based on differential motility. The HGMF-SSM method was compared to the Agriculture and Agri-Food Canada Food Safety Procedures Manual (FSPM-10) method (Isolation of Thermophilic Campylobacters from Fresh Pork, Beef Veal, Poultry and Ready-to-Eat Meat Products), which includes the use of selective antibiotics. During the initial study, after enrichment the HGMF-SSM method yielded pure cultures of campylobacters after 16 to 18 h (overnight) compared with 48 h for the FSPM-10 method. Ninety-four turkey samples collected at local retail stores and 38 frozen pig fecal samples were processed by both methods. Thirty-five samples (26.5%) were positive by the HGMF-SSM method; 24 (18.2%) of these positive samples contained Campylobacter jejuni and 11 (8.3%) contained Campylobacter coli. With the FSPM-10 method, 25 samples (18.9%) were positive: 21 (15.9%) with C. jejuni and 4 (3%) with C. coli. For a subsequent field study, only the HGMF-SSM method was used to isolate Campylobacter from 1,200 chicken samples and 454 turkey samples sold at retail. Analysis of five subisolates from various samples indicated that only one type of Campylobacter was recovered by the HGMF-SSM method, as ascertained by MICs for 10 antimicrobials, sequencing of the short variable region of the flaA gene, and fingerprinting based on amplified fragment length polymorphism. The absence of antibiotics in the SSM may explain the higher recovery of thermophilic campylobacters. The HGMF-SSM method resulted in improved isolation of campylobacters and is simpler, faster, cheaper, and less labor intensive than the FSPM-10 method. The recovery of one type of Campylobacter from the chicken samples may have important implications, particularly in epidemiological studies.


Gives an overview of how the openness of the future Internet affects digital rights management (DRM). There will be open and semi-open parts in the future Internet. DRM systems enable many important features of information product distribution on the Internet. At the same time, these systems have significant costs: how should content distributors maintain user friendliness and solve revenue-earning difficulties? While DRM systems enable efficient charging possibilities, it is a challenge to implement DRM in the open Internet in a way that attracts customers and really adds value to their experience. Plausibly, there will be many competing DRM solutions. They should, however, be standardized and interoperable enough to enable customers to use information products on different platforms. DRM systems must be appropriately applicable to both open and semi-open networks. It may be technically easier to implement a DRM system in a semi-open environment, but that is not a sufficient solution for a longer-term view. DRM system providers should at least have roadmaps of how to develop their products to work in an open network and on multiple platforms.


We previously reported that perinatal exposure to low levels of lead (Pb) results in a pronounced reduction of choline acetyltransferase (ChAT) activity in the septohippocampal pathway of the rat. In the present study we employed a ChAT specific 43-base oligonucleotide hybridization probe to compare the developmental expression of ChAT mRNA and ChAT activity in the septum of normal and Pb-exposed rats. Rats were exposed to Pb via maternal administration of 0.2% solution of Pb acetate in drinking water from one week before birth through postnatal day 21 (PN21). In normal animals, the developmental changes in the ChAT mRNA and activity levels were temporally correlated and approached adult levels by PN21. In the Pb-exposed pups, ChAT mRNA and activity levels were reduced respectively by 69% and 50% at PN7, 47% and 33% at PN14, and 47% and 22% at PN21. In contrast, Pb exposure had no significant effect on either ChAT mRNA or ChAT activity in the dams. These results indicate that cholinotoxicity of Pb in the septohippocampal pathway of the rat involves developmental stage-dependent disruption of ChAT gene expression.


Scholars of western classical music have predominantly studied it as a text and positioned it a site of 'absolute value' through which musicians and listeners 'transcend […] the bodily' (Johnson 2002). This thesis uses ethnography in order to critique this approach, exploring the experience of young people who participate in classical music ensembles in the south of England. It interrogates the relationship between classical music and the middle classes, asking what classed and gendered dispositions are being (re)produced through this musical practice. The thesis argues that rehearsal processes shape the embodied dispositions of young musicians to cultivate a mode of restraint and gendered control, which is congruent with a particular classed identity. This occurs within a powerful affective group setting, which interpellates participants as subjects of value through the intimate, embodied, non-linguistic call of this music.

This argument is built through four key claims. First, the boundary-drawing which legitimises the protected status of classical music draws on the classed, gendered history of its institutions in the Victorian period. This camouflages the ways in which musical standards of 'excellence' are formed socially, in and between certain bodies. Second, this musical practice simultaneously disciplines but also effaces the body. A major theoretical contribution of this thesis is to argue that the dispositions this produces are audible in the aesthetic of the music. Third, an ethic of correction is central to classical music education. Those in less privileged positions capitalise on this as a route towards classed self-improvement, gaining access to a musical world where they find an expressive voice, a strong sense of identity, and a supportive and intimate social scene. Fourth, mediated through sound, the sensuous body acts back against its disciplining to share powerful affective states with others, creating a powerful allegiance to bourgeois social norms and values.


This study was conducted to understand the effect of the livestock liquid fertilizer treatment at field-scale up to catchment-scale on the water quality properties. Cultivated paddy rice and upland plots located in Gyeonggi province, Korea were treated with two different liquid fertilizers, SP (Liquid fertilizer with storage process) and SCB (Liquid fertilizer with slurry composting and bio-filtration process). Plots with no fertilizer (control A) and chemical fertilizer (control B) were also prepared for comparison. Water quantity and quality were monitored at the catchment outlet for assessing the effect on water quality of stream water. As a result, the losses of N and P and the values of EC (Electronic Conductivity) in the surface drainage water from paddy rice plots treated with SP and SCB were higher than those from the control plots (A and B). In addition, the losses of N and P by the runoff water from upland plots with SP and SCB treatment were higher than those from control plots (A and B). The nutrient outflow from paddy rice fields and uplands with application of liquid pig manure was higher than those from the control plots (A and B). Particularly, the outflow from uplands may directly affect the water quality in neighboring streams. This caused the major eutrophication problem in stream water. In conclusion, it is necessary to establish the proper management practices to prevent the nutrient losses from agricultural fields and the pollutants against water environments.


Dimension reduction has two methods namely feature selection and feature extraction. Dimension reduction using the feature selection method has a better influence than the feature extraction method on the cluster results. However, there is still a need for feature extraction methods to reduce dimensions. For this reason, an alternative algorithm is needed from the feature extraction method. Self Organizing Map (SOM) is one of the artificial neural network models that has a special nature that is effectively able to create spatial internal representations of input data, or in general to create smaller data dimensions. This research was examining the capability of SOM compared to Singular Value Decomposition (SVD) in reducing data dimension of text documents before there were clustered by k-Means. Results show that SVD still better than SOM in cluster quality index but SOM faster than SVD in computation times.


Today, emerging technologies are reaching astronomical proportions. For example, the Internet of Things has numerous applications and consists of countless different devices using different technologies with different capabilities. But the one invariant is their connectivity. Consequently, secure communications, and cryptographic hardware as a means of providing them, are faced with new challenges. Cryptographic algorithms intended for hardware implementations must be designed with a good trade-off between implementation efficiency and sufficient cryptographic strength. Finite fields are widely used in cryptography. Examples of algorithm design choices related to finite field arithmetic are the field size, which arithmetic operations to use, how to represent the field elements, etc. As there are many parameters to be considered and analyzed, an automation framework is needed. This thesis proposes a framework for automated design, implementation and verification of finite field arithmetic hardware. The underlying motif throughout this work is "math meets hardware". The automation framework is designed to bring the awareness of underlying mathematical structures to the hardware design flow. It is implemented in GAP, an open source computer algebra system that can work with finite fields and has symbolic computation capabilities. The framework is roughly divided into two phases, the architectural decisions and the automated design generation. The architectural decisions phase supports parameter search and produces a list of candidates. The automated design generation phase is invoked for each candidate, and the generated VHDL files are passed on to conventional synthesis tools. The candidates and their implementation results form the design space, and the framework allows rapid design space exploration in a systematic way. In this thesis, design space exploration is focused on finite field arithmetic. Three distinctive features of the proposed framework are the structure of finite fields, tower field support, and on the fly submodule generation. Each finite field used in the design is represented as both a field and its corresponding vector space. It is easy for a designer to switch between fields and vector spaces, but strict distinction of the two is necessary for hierarchical designs. When an expression is defined over an extension field, the top-level module contains element signals and submodules for arithmetic operations on those signals. The submodules are generated with corresponding vector signals and the arithmetic operations are now performed on the coordinates. For tower fields, the submodules are generated for the subfield operations, and the design is generated in a top-down fashion. The binding of expressions to the appropriate finite fields or vector spaces and a set of customized methods allow the on the fly generation of expressions for implementation of arithmetic operations, and hence submodule generation. In the light of NIST Lightweight Cryptography Project (LWC), this work focuses mainly on small finite fields. The thesis illustrates the impact of hardware implementation results during the design process of WAGE, a Round 2 candidate in the NIST LWC standardization competition. WAGE is a hardware oriented authenticated encryption scheme. The parameter selection for WAGE was aimed at balancing the security and hardware implementation area, using hardware implementation results for many design decisions, for example field size, representation of field elements, etc. In the proposed framework, the components of WAGE are used as an example to illustrate different automation flows and demonstrate the design space exploration on a real-world algorithm.


Online detection of product defects using fast spectroscopic measurements is beneficial for producers in the dairy industry since it allows readjustment of product characteristics or redirection of product streams during production. Raman spectroscopy has great potential for such application due to the fast and simple measurement. Its suitability as online sensor for process control was investigated at typical control points in consumer milk production being raw milk storage, standardization, and heat treatment. Additionally, the appropriateness of Raman spectroscopy to act as indicator for product application parameters was investigated using the example of barista foam. To assess the suitability of a pure online system, the merit of Raman spectra was evaluated by a principal component analysis (PCA). Thereby, proteolytic spoilage due to the presence of extracellular enzymes of Pseudomonas sp. was detected and samples based on the applied heat treatment (extended shelf life (ESL) and ultra-high temperature (UHT)) could be separated. A correlation of the content of free fatty acids and foam stability with spectra of the respective milk samples was found, allowing a prediction of the technofunctional quality criterion "Barista" suitability of a UHT milk. The results underlined the suitability of Raman spectroscopy for the detection of deviations from a defined product standard of consumer milk.


Smartness in contemporary society implies the use of massive data to improve the experience of people with connected services and products. The use of big data to collect information about people's behaviours opens a new concept of "user-centred design" where users are remotely monitored, observed and profiled. In this paradigm, users are considered as sources of information and their participation in the design process is limited to a role of data generators. There is a need to identify methodologies that actively involve people and communities at the core of ecosystems of interconnected products and services. Our contribution to designing for social innovation in ecosystems relies on developing new methods and approaches to transform data-driven design using a participatory and co-creative data-enabled design approach. To this end, we present one of the methods we have developed to design "smart" systems called Experiential Design Landscapes (EDL), and two sample projects, Social Stairs and [Y]our Perspective. Social Stairs faces the topic of behaviour change mediated by sensing technologies. [Y]our Perspective is a social platform to sustain processes of deliberative democracy. Both projects exemplify our approach to data-enabled design as a social proactive participatory design approach.


Cluster ab initio quantum chemistry approach is developed to simulate the charge-transfer-to-solvent (CTTS) absorption band and satellite ligand field bands of hexaammineruthenium(II) ion in aqueous solution. Several cluster models, including 16, 21, and 38 water molecules, are explored for this purpose. TDDFT method with long-range corrected BLYP (LC-BLYP) functional is used to obtain the vertical transition characteristics, and DFT B3LYP is used for calculation of the ground state geometry and vibrational frequencies of the solvated complex. A simple harmonic bath model is employed to estimate the absorption bandwidths and coherence decay times with the parameters taken from the quantum chemistry calculations. The present approach provides rather reasonable estimates for the CTTS band position and shape, also giving an additional insight for the mechanism of the CTTS band broadening.


Face Recognition, a very challenging research area, is being studied for almost more than a decade to solve variety of problems associated with it e.g. PIE (pose, expression and illumination), occlusion, gesture, aging etc. Most of the time, these problems are considered in situations when images are captured from same sensors / cameras / modalities. The methods in this domain are termed as homogeneous face recognition. In reality face images are being captured from alternate modalities also e.g. near infrared (NIR), thermal, sketch, digital (high resolution), web-cam (low resolution) which further alleviates face recognition problem. So, matching faces from different modalities are categorized as heterogeneous face recognition (HFR). This dissertation has major contributions in heterogeneous
face recognition as well as its homogeneous counterpart.

The first contribution is related to multi-scale LBP, Sequential forward search and KCRC-RLS method. Multi scale approaches results in high dimensional feature vectors that increases computational cost of the proposed approach and overtraining problem. Sequential forward approach is adopted to analyze the effect of multi-scale.
This study brings an interesting facts about the merging of features of individual scale that it results in significant reduction of the variance of recognition rates among individual scales.

In second contribution, I extend the efficacy of PLDA to heterogeneous face recognition. Due to its probabilistic nature, information from different modalities can easily be combined and priors can be applied over the possible matching. To the best of author's knowledge, this is first study that aims to apply PLDA for intermodality face recognition.

The third contribution is about solving small sample size problem in HFR scenarios by using intensity based features. Bagging based TFA method is proposed to exhaustively test face databases in cross validation environment with leave one out strategy to report fair and comparable results.

The fourth contribution is about the module which can identify the modality types is missing in face recognition pipeline. The identification of the modalities in heterogeneous face recognition is required to assist automation in HFR methods.

The fifth contribution is an extension of PLDA used in my second contribution. Bagging based probabilistic linear discriminant analysis is proposed to tackle problem of biased results as it uses overlapping train and test sets. Histogram of gradient descriptors (HOG) are applied and recognition rates using this method outperform all the state-of-the-art methods with only HOG features.


The study analyzed the main determinants and the relationship between capital base, profit-generating capacity and operational efficiency of Nigerian commercial banks. This was with a view to providing empirical information on the relationship between capital base requirements and profit-generating capacity and efficiency in the Nigerian commercial banking sector.Secondary data covering 16years on key performance indicator of the banks such as total income, interest rates, total credits, and branch networks were sourced from the "fact books" published by the Nigerian Stock Exchange (NSE) and official publications of the selected banks. The data were subjected to the two-stage least square(TSLS) technique for the purpose of estimating the model. The results showed that capital base requirement was ineffective in reducing distress in the banking industry. The results further showed that the main determinants of bank capital base were lagged capital (t = -2.60, p<0.05), risk (t =2.30, p<0.05), size(t= -3.27, p<0.05), profit before tax (t =6.23, p<0.05), regulatory pressure (t=3.97, p<0.05) and profit generating capacity (t =2.54, p<0.05). It was also found that bank capital base significantly influenced bank efficiency (t= 2.14, p<0.05) and that changes in the bank capital determined the degree of efficiency of the banks (t =2.14, p<0.05). Furthermore, the capital base of the banks significantly influenced their profit generating capacity (t=10.2, p<0.05). This revealed that the Central Bank of Nigeria could use the regulatory power of raising the capital base of banks to stimulate greater profitability and efficiency in the banking sector. Keywords: Financial Deepening, Commercial Banks, Capital Base, Efficiency, Profit Generation, Nigeria.


Lymphocytic interstitial pneumonia of HIV-infected individuals and SIV pneumonia of macaques are both characterized by diffuse infiltration of the lungs with lymphocytes, plasma cells, and macrophages. This study was undertaken to determine whether there are specific, macrophage-tropic genotypes that selectively replicate in the lung of macaques with SIV pneumonia, as in SIV encephalitis. Using a rapid, reproducible SIV/macaque model of AIDS, 11 pig-tailed macaques were intravenously inoculated with an immunosuppressive viral strain, SIV/DeltaB670, and a macrophage-tropic molecule clone, SIV/17E-Fr, and euthanized at 3 months postinoculation. All 11 macaques had severe (6 macaques) or moderate (5 macaques) pneumonia. To identify the viral genotypes that were replicating in the lung parenchyma, bronchoalveolar lavage (BAL) cells, and peripheral blood mononuclear cells (PBMC) of each macaque, RNA was isolated and the SIV env V1 region was amplified, cloned, and sequenced. Lung homogenates and BAL cells contained a more limited repertoire of viral genotypes than PBMC. SIV/17E-Fr was the major genotype in the lungs of 5 macaques and in BAL cells of 6 macaques. The remainder of the macaques had SIV/17E-Fr and the macrophage-tropic strains of SIV/DeltaB670 clones 2 and 12. In contrast, SIV/17E-Fr was the predominant strain in the PBMC of only 3 of 11 macaques. The viral strain that predominated in PBMC was rarely the strain that predominated in the lungs (only 3 of 11 macaques). The severity of pulmonary lesions did not correlate with the levels of viral RNA in lung homogenates or in plasma. However, when only SIV/17E-Fr was expressed in the lung, the viral load in the lung was significantly higher (P = 0.016) than when SIV/DeltaB670 was present alone or in combination with SIV/17E-Fr. These data suggest that SIV pneumonia is associated with selective replication of specific macrophage-tropic genotypes in the lung and that SIV/17E-Fr has a selective advantage for replication in the lung.


Nowadays, Blockchain Technologies (BCT) could be characterized as one of the most promising trends. We are currently witnessing a plethora of implementations basically in the economic sector with the creation of cryptocurrencies. The majority of researchers and practitioners argues that many benefits could be derived from the use of this innovative technology with the most significant one being the improved sense of trust to BCT applications. At the same time governments pursue amplified trust from their citizens and BCT is gaining momentum since it addresses this of utmost importance problem based on its unique characteristics. More and more governments realize the advances of this technology and participate in pilot applications in different vertical governmental sectors. Even though there are several implementations in the Government sector, there is no comprehensive study towards the analysis of the major characteristics of these developments. This paper moves towards the fulfilment of this gap conducting a thorough analysis of e-Government pilot applications of BCT in a European level. Furthermore, this study discusses the key benefits and main barriers coming from the application of this technology in different domains with BCT experts.


The internal oscillation-mixing in TlBaCaCuO thin-film microbridge junctions has been studied at liquid nitrogen temperature. The TlBaCaCuO thin-film microbridge junctions were fabricated by the wet-etching technique. As TlBaCaCuO superconducting material is very sensitive to magnetic fields. It is crucial to use a magnetic shielding system in the experiments. In the presence of a magnetic shielding system, the authors obtained a -37 dB mW sensitivity for a TlBaCaCuO Josephson internal oscillator-mixer which is close to that of a YBaCuO Josephson internal oscillator-mixer.


Background: The risk of developing dementia by elderly patients with only subjective memory complaints (SMC) is unclear. Our objective was to assess the prognosis of such patients regarding subsequent development of dementia. Methods: From 1992 to 1996, 211 consecutive patients (age 67.4±9.4 years, mean±SD) were diagnosed as having SMC. These patients were followed for 3 years or to the time they were diagnosed with dementia, whichever came first. A survival analysis was performed for occurrence of dementia within 3 years. Results: The duration of memory decline was shorter among patients who developed dementia than among those who did not (32.6 vs. 49.9 months, F=3.3, p=0.07). Patients who developed dementia tended to be older at the reported onset of memory decline (71 vs. 66.2 years, F=3.2, p=0.07). Lower risk of dementia was associated with higher cognitive performance at entry [odds ratio (OR)=0.74 (0.59–0.92)] and longer time from onset of memory decline to referral [OR=0.91 (0.85–0.98)]. Conclusion: Subjects with SMC have an increased risk of developing dementia, particularly those with lower cognitive status at entry and with older age at onset of memory complaints, and shorter duration of their memory complaints.


Background: since October 2020, a second SARS-CoV-2 epidemic wave has hit Italy. We investigate the frequency of positive nasopharyngeal swabs among HCWs during the two waves and the association with occupation and demographic characteristics. Methods: this is a retrospective, observational study conducted in a large university hospital in Milan, Northern Italy. We defined two epidemic waves: 1st (February 2020–July 2020) and 2nd (August 2020–January 2021). Occupational and demographic characteristics of HCWs who underwent nasopharyngeal swabs for SARS-CoV-2 were collected. Results: in the 1st wave, 242 positive subjects (7.2%) were found among 3378 HCWs, whereas in the 2nd wave, the positive subjects were 545 out of 4465 (12.2%). In both epidemic waves positive NPSs were more frequent among HCWs with health-related tasks and lower among students (p < 0.001). However, in the 2nd wave, workers engaged in non-health-related tasks had a peak of 20.7% positivity. Among 160 positive HCWs in the 1st wave who were tested again in the 2nd wave, the rate of reinfection based on SARS-CoV2 RNA cycle quantification value was 0.6%. Conclusions: during the 2nd epidemic wave, we confirmed a significant impact of COVID-19 among HCWs. The rise of infection rate among HCWs seems to reflect the increasing spread of SARS-CoV-2 among the overall population.


In his 1993 essay 'The temporality of the landscape', Tim Ingold argued that landscape develops through processes of temporality, that is time as it emerges in the unfolding of life through action. This association between temporality and landscape was expressed by the term 'taskscape'. In our introduction to this section, we return to the concept of taskscape to assess its usefulness in light of a number of developments in the understanding of human–environment relations. These include the changing conceptualisation of 'landscape' and the emergence of new approaches for understanding relations across species. We explain the ways that the three authors in this section use taskscape to think through political tensions and to explore how landscapes are achieved through inter‐relating actions of humans and other beings. We conclude by emphasising the heuristic value of taskscape as a means of thinking through the implications of the Anthropocene. Both taskscape and Anthropocene are concepts that draw together human history and the shaping of the world and, as such, the taskscape offers a novel means to explore and understand the dynamics of Anthropocene environmental relations.


This study estimates the effects of the immigration stock, as well as those of immigrants' characteristics, such as having the same language as that of the host country and the level of qualification or entrepreneurship, on Portuguese intra-industry trade (IIT) by types, controlling for the effects of other socio-economic factors, like economic dimensions, price indexes and distance. In addition to the member-countries of the EU-27, the group of countries studied includes five African countries with Portuguese as their official language, known as the PALOPs, and the BRIC countries. Since indexes are fractional variables, the pseudo-likelihood Logit estimator was used on the panel data to obtain the empirical results. The study found that an increase of the immigrant stock will produce an increment in the trade indexes considered and this effect is enhanced if immigrants originate from a country where Portuguese is the official language, or if they are highly qualified, whereas immigrant entrepreneurs have no significant effect.


Infections caused by Candida albicans are of increasing concern, especially considering immunodepressed patients. The toxicity of most antifungal agents, the great number of cases with recidives, as well as the emergence of resistant samples has provoked the evaluation of new forms of therapy. In this context, the photodynamic therapy (PDT) presents auspicious antimicrobial properties, stimulating the development of trials employing several kinds of photosensitizers. In the present work, the application of different kind of Azure dyes as photosensitizer in PDT against C. albicans was evaluated through instrumental measurements of electronic spectroscopy. In fact, the values of optical density were a precise indicator of the growth inhibition of the microorganisms. Indeed, Azures are phenothiazinium derivatives that constitute a very relevant class of compounds with several biomedical applications, such as photoantimicrobial therapy against local bacterial infection, tuberculosis, trypanosomi- asis, malaria, Rickettsia, yeasts, viral infection n and cancer. Azure A, Azure B, Azure A thiocyanate, Azure B BF4 ,A zure A eosinate are the dyes tested against C. albicans. The results denoted completely distinct behaviors to the different types of Azure compound evaluated in this work. In fact, Azure A and Azure A eosinate presented significant results when irradiated with 56 J/cm 2 , since the growth inhibition of C. albicans reached approximately 60%. This Azure compounds have significant potential to be employed as photosensitizer (PS) in PDT, especially in cases of mucocutaneous candidosis. The spectroscopic evaluation was very effective to the detection of slight alterations in the growth of the microorganisms, denoting that this kind of analysis is an excellent alternative to determine growth inhibition of Candida albicans. The experimental data are discussed in details in agreement with recent results from literature.


Regarding CO2/O2-based mixture as an arc quenching gas in high-voltage circuit breakers, the predominant component species present in high numbers at temperatures of 300–20 000 K are determined in consideration of addition of CF3CFCH2 (hereinafter written as C3H2F4) gas to the CO2/O2-based mixture. In the determination, not only are 87 gaseous species but also condensed-phase carbon (hereinafter written as C(c)) taken into account as component species. The evaluation results reveal that CO2, O2, CF4 and HF in gaseous phase behave as the predominant component species at 300–1000 K for lower content additive-gas, whereas the species C(c) is also generated as the predominant component at the same temperature for higher content additive-gas. Subsequently, reactions of chemical elements C, O, F and H to form the above-described chemical species are successfully expressed using CO2, O2 and C3H2F4 contents as stoichiometric coefficients. Expressing the reactions furthermore enables us to formulate the prevent condition of the C(c) generation as a function of O2 content and C3H2F4 content . Similar formulations are successfully performed for CO2/O2/C4-FN and CO2/O2/C5-FK mixtures.


We used quantitative real-time polymerase chain reaction (qPCR) and high resolution melting (HRM) analyses for the detection of the common α-thalassemia (α-thal) genotypes in 40 northern Thai Hb H (β4) patients. The α0-thal [– –SEA (Southeast Asian) deletion] was detected by a multiplex gap real-time PCR. To determine the α+-thal, three primer pairs were designed. The A-primer pair was used to amplify the 3' terminal DNA sequences of the HBA2 gene, and the B-primer pair amplified the 5' flanking region of the HBA1 gene. The C-primer pair amplified the 3' terminal DNA sequences of the HBA1 gene and was used as an internal control. The –α4.2 (leftward) and –α3.7 (rightward) deletions were determined by monitoring the absence of PCR product(s). The Hb H patients who had a negative PCR result for the A-primer pair but positive for the B- and C-primer pairs carried the –α4.2 deletion, while the –α3.7 deletion carriers were negative for the A- and B-primer pairs. In the case of Hb H with Hb Constant Spring (Hb CS, α142, Term→Gln; HBA2: c.427T>C), all primer pairs were positive, HRM analysis of the PCR product of the A-primer pair was introduced to analyze the Hb CS gene. It can distinguish clearly between normal and Hb CS genotypes. The applied methods for the determination of the α0- and α+-thal genotypes revealed the results to be as accurate as conventional gap-PCR and the direct DNA sequencing methods but resulted in a much simpler and faster procedure.


Summary Translationally Controlled Tumour Protein (TCTP) is a pro-survival factor in tumor cells. TCTP inhibits the mitochondrial apoptosis pathway by potentiating the anti-apoptotic Bcl-2 family members Mcl-1 and Bcl-xL. Specifically, TCTP binds Bcl-xL and inhibits the Bax-dependent Bcl-xL-induced cytochrome c release and TCTP reduces Mcl-1 turnover by inhibiting its ubiquitinylation, thus resulting in decreased Mcl-1 mediated apoptosis. TCTP owns a BH3-like motif forming a β-strand buried in the globular domain of the protein. The crystal structure of TCTP BH3-like peptide in complex with Bcl-xL highlighted the α-helical conformation of TCTP BH3-like motif, suggesting major changes in TCTP structure upon complex formation. However, the structural impact of the interaction on the full-length TCTP and the structural description of TCTP/Mcl-1 interaction are still lacking. Here using biophysical/biochemical methods (NMR, SAXS, circular dichroism, limited proteolysis), we provide an in-depth description of the TCTP/Mcl-1 complex. We demonstrate that full length TCTP binds to the BH3 binding groove of Mcl-1 via its BH3-like motif which interconverts between different binding modes at the micro- to milli-second timescale. As a consequence of the engagement of the BH3-like motif in the interface, the TCTP globular domain is destabilized into a molten-globule state. We also establish that the residue D16 in TCTP BH3-like motif is crucial for the stability and dynamics of the intermolecular interface. As a conclusion, we reveal here in details the structural plasticity of TCTP and discuss its implications for TCTP biology and for future anticancer drug design strategies aiming at targeting TCTP complexes. Contact Ewen Lescop, email@example.com. Supplementary Information Supplementary figures, tables and files.


Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colon with sharply rising global prevalence. Dysfunctional epithelial compartment (EC) dynamics are implicated in UC pathogenesis although EC-specific studies are sparse. Applying orthogonal high-dimensional EC profiling to a Primary Cohort (PC; n=222), we detail major epithelial and immune cell perturbations in active UC. Prominently, reduced frequencies of mature BEST4+OTOP2+ absorptive and BEST2+WFDC2+ secretory epithelial enterocytes were associated with the replacement of homeostatic, resident TRDC+KLRD1+HOPX+ γδ+ T cells with RORA+CCL20+S100A4+ TH17 cells and the influx of inflammatory myeloid cells. The EC transcriptome (exemplified by S100A8, HIF1A, TREM1, CXCR1) correlated with clinical, endoscopic, and histological severity of UC in an independent validation cohort (n=649). Furthermore, therapeutic relevance of the observed cellular and transcriptomic changes was investigated in 3 additional published UC cohorts (n=23, 48 and 204 respectively) to reveal that non-response to anti-Tumor Necrosis Factor (anti-TNF) therapy was associated with EC related myeloid cell perturbations. Altogether, these data provide high resolution mapping of the EC to facilitate therapeutic decision-making and personalization of therapy in patients with UC.