This research was undertaken to determine the seroprevalence of HCV among patients attending antiretroviral therapy (ART) clinics in some parts of Abuja and Nasarawa States, Nigeria. A total of 522 sera samples were collected between March and August 2019, from HIV patients, recruited in the ART clinics of selected hospitals. Samples were screened using immunochromatographic assay, followed by a third-generation Enzyme-Linked Immunosorbent Assay (ELISA). 154 (29.5%) of these samples were from male patients, and 368 (70.5%), females with a ratio of 1:2.4. The mean age ( ± SD) of the patients was 38.0 ( ± 9.56). The presence of hepatitis C virus coinfection was observed in 82 (15.7%) patients. The male population had a higher co-infection rate (17.5%) than the female population (14.9%). Patients aged 31-40 had a higher hepatitis co-infection (6.7%) rate than the other age groups. Blood transfusion, sharing of sharp objects, and the number of sex partners were significantly associated with HCV co-infection. This study revealed high endemicity of hepatitis C virus co-infection with HIV in the study region. Preventive measures are thus advocated to curb the spread of the viral infection.


BACKGROUND
The functions of long noncoding RNAs (lncRNAs) have been identified in several cancers, but the roles of lncRNAs in colorectal cancer (CRC) are less well understood. The transcription factor MYC is known to regulate lncRNAs and has been implicated in cancer cell proliferation and tumorigenesis.

METHODS
CRC cells and tissues were profiled to identify lncRNAs differentially expressed in CRC, from which we further selected MYC-regulated lncRNAs. We used luciferase promoter assay, ChIP, RNA pull-down assay, deletion mapping assay, LC-MS/MS and RNA immunoprecipitation to determine the mechanisms of MYC regulation of lncRNAs. Moreover, soft agar assay and in vivo xenograft experiments (four athymic nude mice per group) provided evidence of MYC-regulated lncRNAs in cancer cell transformation and tumorigenesis. The Kaplan-Meier method was used for survival analyses. All statistical tests were two-sided.

RESULTS
We identified lncRNAs differentially expressed in CRC (P < .05, greater than two-fold) and verified four lncRNAs upregulated and two downregulated in CRC cells and tissues. We further identified MYC-regulated lncRNAs, named MYCLos. The MYC-regulated MYCLos may function in cell proliferation and cell cycle by regulating MYC target genes such as CDKN1A (p21) and CDKN2B (p15), suggesting new regulatory mechanisms of MYC-repressed target genes through lncRNAs. RNA binding proteins including HuR and hnRNPK are involved in the function of MYCLos by interacting with MYCLo-1 and MYCLo-2, respectively. Knockdown experiments also showed that MYCLo-2, differentially expressed not only in CRC but also in prostate cancer, has a role in cancer transformation and tumorigenesis.

CONCLUSIONS
Our results provide novel regulatory mechanisms in MYC function through lncRNAs and new potential lncRNA targets of CRC.


Although polar bears (Ursus maritimus) and brown bears (U. arctos) have been exhibited in zoological gardens for centuries, little is known about their nutritional needs. Multiple recent studies on both wild and captive polar bears and brown bears have found that they voluntarily select dietary macronutrient proportions resulting in much lower dietary protein and higher fat or digestible carbohydrate concentrations than are currently fed in most zoos. These lower protein concentrations selected by both species maximized growth rates and efficiencies of energy utilization in brown bears and may play a role in reducing kidney, liver, and cardiovascular diseases in both species. Therefore, we propose the need for the development of new dietary regimens for both species in managed care that better reflect their macronutrient needs. We developed a new kibble that is higher in fat and lower in protein than typical diets that have been fed in managed care, has a fatty acid profile more consistent with wild bear diets, and has been readily consumed by both brown bears and polar bears. The kibble can be fed as the sole diet or as part of more complex diets with additional fruits, meats, or vegetables. Because many nutritional deficiencies and related diseases can take months or years to appear, we urge caution and continued long-term monitoring of bears and their diets to ensure their optimal health.


Endoscopic pelvic lymph node dissection was performed in 30 patients as part of the staging of prostate (19) or bladder (11) cancers. The technique, using a procedure of detachment of the retroperitoneal space with CO2 insufflation, is described. Complete bilateral dissection of the ilio-obturator lymph nodes was performed in 24 patients (80%) using conventional laparoscopic surgical equipment. Only a unilateral dissection could be performed in 6 other patients because of technical difficulties. The mean operating time was 72 minutes. The intraoperative and postoperative complications consisted of 2 venous injuries and one infection. A prospective study of systemic diffusion of CO2 demonstrated that the blood Co2 level increased significantly during the procedure, but could be controlled by adaptation of the ventilation. Postoperative monitoring of blood CO2 levels using a capnograph is recommended. 4 out of 30 patients (13%), 2 with prostate cancer and 2 with bladder cancer, had lymph node metastases. Amongst the other 26 patients, 12 were treated by radiotherapy (bladder cancer), 12 patients underwent perineal prostatectomy and 12 others underwent retropubic prostatectomy (5) or prostatocystectomy (7]). No intraoperative and postoperative morbidity related to endoscopic lymph node dissection was observed in the patients subsequently undergoing a radical operation. Endoscopic retroperitoneal lymph node dissection with CO2 insufflation is a rapid, safe and effective technique for staging of malignant pelvic tumours and constitutes an alternative to open surgery and to endoscopic transperitoneal surgery.


A program that maintains key safety properties even when interacting with arbitrary untrusted code is said to enjoy robust safety. Proving that a program written in a mainstream language is robustly safe is typically challenging because it requires static verification tools that work precisely even in the presence of language features like dynamic dispatch and shared mutability. The emerging Move programming language was designed to support strong encapsulation and static verification in the service of secure smart contract programming. However, the language design has not been analysed using a theoretical framework like robust safety. In this paper, we define robust safety for the Move language and introduce a generic framework for static tools that wish to enforce it. Our framework consists of two abstract components: a program verifier that can prove an invariant holds in a closed-world setting (e.g., the Move Prover [16], [47]), and a novel encapsulator that checks if the verifier's result generalizes to an open-world setting. We formalise an escape analysis as an instantiation of the encapsulator and prove that it attains the required security properties. Finally, we implement our encapsulator as an extension to the Move Prover and use the combination to analyse a large representative benchmark set of real-world Move programs. This toolchain certifies >99% of the Move modules we analyse, validating that automatic enforcement of strong security properties like robust safety is practical for Move. Additionally, our results tell that security-centric language design can be effective in attaining strong security properties such as robust safety.


ABSTRACT Tillmann, T. and Wunderlich, J., 2013. Barrier rollover and spit accretion due to the combined action of storm surge induced washover events and progradation: Insights from ground-penetrating radar surveys and sedimentological data. Barrier islands and spits are geological young, highly dynamic and represent a complex coastal system that includes a number of different but closely related sedimentary depositional environments. In this study ground-penetrating radar data of different antenna frequencies and sedimentological data were combined to reveal the sedimentary structure and architecture of the southern barrier island spit of Sylt and to set up a barrier island stratigraphy. Based on these data, two sedimentological models have been generated for Southern Sylt which describes the inter-action between extreme events, coastal processes and sedimentary development and contains the major episodes of barrier island evolution. The first model is concerned with the spit add-on zone where the barrier spit is attached to the central island moraine core and shows a landward migration through barrier rollover affected by an interplay of barrier retreat and washover flooding associated with accumulation of sediment in a backbarrier environment as a result of several storm surges. The spit add-on zone reveals a transgressive coarsening upward sequence starting with sandy mud flat deposits at the bottom which turn into coarser sandy tidal flat deposits toward the top. Sandy tidal flat deposits are overlain by washover sheet and washover fan deposits. The second model demonstrates a barrier spit accretion through southerly directed progradation. Eroded sediment was transported along the west coast of Sylt by longshore drift and was added to the southern spit-end. Progradation and barrier spit accretion were interrupted by severe storm surges. Storm surge generated erosion unconformities in a foreshore to shoreface environment redraw old spit-end positions that represent stages of barrier spit progradation.


Huntington's disease (HD) is a hereditary neurodegenerative disease caused by the expansion of a polyglutamine stretch in the huntingtin (HTT) protein and characterized by dysregulated calcium homeostasis. We investigated whether these disturbances are correlated with changes in the mRNA level of the genes that encode proteins involved in calcium homeostasis and signaling (i.e., the calciosome). Using custom-made TaqMan low-density arrays containing probes for 96 genes, we quantified mRNA in the striatum in YAC128 mice, a model of HD, and wildtype mice. HTT mutation caused the increased expression of some components of the calcium signalosome, including calretinin, presenilin 2, and calmyrin 1, and the increased expression of genes indirectly involved in calcium homeostasis, such as huntingtin-associated protein 1 and calcyclin-binding protein. To verify these findings in a different model, we used PC12 cells with an inducible expression of mutated full-length HTT. Using single-cell imaging with Fura-2AM, we found that store-operated Ca2+ entry but not endoplasmic reticulum (ER) store content was changed as a result of the expression of mutant HTT. Statistically significant downregulation of the Orai calcium channel subunit 2, calmodulin, and septin 4 was detected in cells that expressed mutated HTT. Our data indicate that the dysregulation of calcium homeostasis correlates with changes in the gene expression of members of the calciosome. These changes, however, differed in the two models of HD used in this study. Our results indicate that each HD model exhibits distinct features that may only partially resemble the human disease.


Using editorials published in the Rhode Island Medical Journal's inaugural year, this article examines what it meant to practice medicine in Rhode Island in 1917. One hundred years ago, the state's medical community was undergoing rapid transformation epitomized by a turn toward the germ theory of disease, ongoing education and hospital reform, and a growing sense of the profession's political and social role. In many ways, the social and professional concerns of Rhode Island physicians in 1917 continue to resonate today. Physicians writing in the Journal were excited by but concerned about technological advancement in medicine, debating how new institutions and sites of care would shape their interactions with patients. They were also influenced by broader social changes affecting the medical profession, expressing ambivalence toward regulation, debating the implications of social insurance and compulsory health insurance, and reflecting on their financial livelihood and the social prestige of their profession. [Full article available at http://rimed.org/rimedicaljournal-2017-12.asp].


BackgroundMutations in the gene that encode cardiac troponin T (cTnT) account for ≈15% of cases of familial hypertrophic cardiomyopathy (HCM). These mutations are associated with a particularly severe form of HCM characterized by a high incidence of sudden death and a poor overall prognosis, despite subclinical or mild left ventricular hypertrophy. Methods and ResultsWe evaluated a family with HCM and multiple occurrences of sudden death in children. DNA samples were isolated from peripheral blood or paraffin-embedded tissue, and all protein-encoding exons of the cTnT gene were sequenced. A mutation was identified in exon 11 and is predicted to substitute a phenylalanine-for-serine mutation at residue 179 (Ser179Phe) in cTnT. Both parents and 3 of 4 surviving and clinically unaffected children were heterozygous for this mutation; another clinically unaffected child did not carry the mutation. Genetic analysis of DNA from a child who died suddenly at age 17 years demonstrated he was homozygous for this mutation. A review of his echocardiogram revealed profound left and right ventricular hypertrophy. ConclusionsAn homozygous Ser179Phe mutation in cTnT causes a severe form of HCM characterized by striking morphological abnormalities and juvenile lethality. In contrast, the natural history of the heterozygous mutation is benign. These studies emphasize the relevance of genetic diagnosis in hypertrophic cardiomyopathy and provide a new perspective on the clinical consequences of troponin T mutations.


In this paper a nonlinear filtering algorithm for count time series is developed that takes the non-negativity of the data into account and preserves positive definiteness of the covariance matrices of the model. For this purpose, a recently proposed variant of Kalman Filtering based on Singular Value Decomposition is incorporated into Iterative Extended Kalman Filtering, in order to estimate the states of a nonlinear state space model. The resulting algorithm is applied to the evaluation and design of therapies for patients suffering from Myoclonic Astatic Epilepsy, employing time series of daily seizure rate. The analysis provides a decision whether for a specific patient a particular anti-epileptic drug is increasing or reducing the seizure rate. Through a simulation study the proposed algorithm is validated. Additionally, for clinical data results obtained by the proposed algorithm are compared with the results from a Cox-Stuart trend test as well as with the visual assessment of experienced pediatric epileptologists.


The article analyzes the issues of value orientations of young people under the influence of advertising and advertising images.  The definition of "advertising", "value orientations" is revealed.  Research on this problem is analyzed, which can be divided into three areas: the study of the genesis of advertising, the study of advertising theory, as well as consumer behavior and the influence of psychological factors on product choice and perception of advertising.  Features of an age category (youth) which are subject to influence of advertising, owing to the psychological features, emotional instability are revealed.  The role of advertising, both positive and negative, in the choice of values, formation of motives, lifestyle, model of youth behavior is revealed.
The research was conducted on the basis of the Faculty of Social and Psychological Education of the Uman State Pedagogical University named after Pavlo Tychyna.  The sample was 50 students aged 18 to 22 years.  The gender aspect did not take into account.
The survey (survey) of student youth made it possible to determine the opinion of respondents who believe that advertising dictates a particular lifestyle, at the same time it helps to learn about products and navigate when buying, and a large percentage of respondents believe that advertising is depressing.  A significant number of respondents admitted that they made purchases under the influence of advertising.
Young people also point out that family, health and love are important values, although they do not put these values first.  Problems such as aimless leisure time on the Internet and in front of the TV, increased value of money and career in the life priorities of young people were revealed.
  The author concludes that the impact of advertising on the formation of value orientations has been confirmed, but is not critical, and there is a need to develop measures to reduce the impact of commercial advertising to correct the negative effect and create a basis for traditional values and behaviors.
Keywords: advertising, influence, youth, value orientations, advertising image, stand-marking.


This paper provides an example of developing a coding strategy to build theory of the roles of methods in IS development. The research seeks to identify and understand how system development methods are used in an IS department within a large Australian bank. The paper details a theoretical framework, particulars of data collection, and documents an early phase of analysis – data reduction and the generation of an initial coding scheme. Guided by a framework to study the use of methods, the analysis demonstrates the framework's plausibility in order to develop theoretical relationships with which to develop a grounded theory.


Nitrogen saturation is occurring throughout highelevation catchments of the Colorado Front Range. Annual inorganic N loading in wet deposition to the Front Range of ∼4 kg ha-1 yr-1 is about twice that of the Pacific States and similar to many sites in the northeastern United States. In the last ten years at Niwot Ridge/Green Lakes Valley and Glacier Lakes, annual minimum concentrations of NO3 in surface waters during the growing season have increased from below detection limits to∼10 μequiv L-1, indicating that these two catchments are at the threshold of N saturation. The Loch Vale watershed is N saturated, with annual minimum concentrations of NO3 in surface waters generally above 10 μequiv L-1; annual volume-weighted mean (VWM) concentrations of 16 μequiv L-1 in surface waters are greater than that of ∼11 μequiv L-1 NO3 in wet deposition. At these high-elevation catchments, there has been a shift in ecosystem dynamics from an N-limited system to an N-saturated system as a result of anthropogenically fixed N in wetfall and dryfall. Results from the Western Lakes Survey component of the National Surface Water Survey show that N saturation is a regional problem in the Colorado Front Range, with many lakes having (NO3) concentrations greater than 10 μequiv L-1. Foliar N:P ratios in bristlecone pine increase with elevation in the Colorado Front Range, indicating that at higher elevations P is translocated from foliar tissue more efficiently than N and that increasing atmospheric deposition of N with elevation is causing a change from N limitation to P limitation in the highest-elevation bristlecone pines. Current concepts of critical loads need to be reconsidered since only modest atmospheric loadings of N are sufficient to induce N leaching to surface waters in high-elevation catchments of the western United States.


Elevated blood pressure (BP) is an important risk factor not only for cardiovascular morbidity and mortality, but also for cognitive decline and loss of autonomy in later life. Randomized clinical trials (RCTs) in populations of older patients living at home with low comorbidity and preserved autonomy showed benefits of decreasing the elevated BP in patients older than 80 years. Older patients with frailty, loss of autonomy and other geriatric problems were systematically excluded from the RCTs. Observational studies in these groups of patients showed an increase in morbidity and mortality at a lower level of BP during antihypertensive therapy. Obviously, in very elderly patients a universal strategy for the BP lowering cannot be applied due to the significant heterogeneity of their functional status. In this review geriatric approach based on assessment of the functional status of the elderly patient, the presence of frailty and degree of loss of autonomy as a basis for decision-making process regarding the antihypertensive therapy is discussed.


Anecdotal and scientific evidence suggest that the sex hormone estrogen provides signifi - cant health benefits in women. Women have higher estrogen levels than men. Circulating estrogen reaches its highest level during the reproductive period and steadily declines with the onset of menopause. The role of estrogen and estrogen receptors in both cellular physiology and pathophysiology has been controversial. Estrogen has anti-inflammatory and anti-oxidant effects, which preserve cell viability during cardiovascular incidents, but it enhances disease progression in the context of breast cancer. Estrogen mediates these responses via activation of estrogen receptor subtypes located in the cell mem -brane, nucleus, and mitochondrion. Further, transcription of nuclear and mitochondrial genes by estrogen yields products that play an important role in regulating mitochon drial function. Mitochondria are part of a highly dynamic network and undergo fission and fusion, produce cellular energy, adenosine 5′ triphosphate (ATP), and regulate cell death. Herein, we review the cell and receptor specific effects of estrogen on mitochon - drial structure, function, and cell death under normal physiological conditions and in the context of cardiovascular disease, inflammation, neurodegeneration, and cancer. Further research is needed to elucidate the specific role of estrogenic control of mitochondria in health and disease.


This study reconsiders the question of Jesus' messianic self-consciousness in light of his proclamation of God's coming kingdom and its backdrop within Jewish texts that likely influenced or paralleled his own apocalyptic worldview (Second Isaiah, Daniel, the Dead Sea Scrolls, and the Similitudes of Enoch). Evidence mined from Gospel sources suggests that the historical Jesus' mission was both broadly 'messianic'—that is, as one closely associated with God's coming reign—and corporate in thrust—that is, involving others as active participants in that reign. Further, the communal dimension of Jesus' messianic role coheres with the Jewish writings explored here, which consistently situate individual messianic figures in dynamic relationship with the faithful, serving to bridge the chasm between the divine and human realms.


Here, we provide the first evidence for functional expression of a human olfactory receptor protein (OR17–40) and show that recombinant olfactory receptors can be functionally expressed in heterologous systems. A mixture of 100 different odorants (Henkel 100) elicited a transient increase in intracellular [Ca2+] in human embryonic kidney 293 (HEK293) cells stably or transiently transfected with the plasmid pOR17–40. By subdividing the odorant mixture into progressively smaller groups, we identified a single component that represented the only effective substance: helional. Only the structurally closely related molecule heliotroplyacetone also activated the receptor. Other compounds, including piperonal, safrole, and vanillin, were completely ineffective. Mock-transfected cells and cells transfected with other receptors showed no change in intracellular [Ca2+] in response to odor stimulation. We were also able to functionally express OR17–40 inXenopus laevis oocytes. Coexpression of a "reporter" channel allowed measurement of the response of oocytes injected with the cRNA of the human receptor to the odor mixture Henkel 100. The effective substances were the same (helional, heliotropylacetone) as those identified by functionally expressing the receptor in HEK293 cells and were active at the same, lower micromolar concentration. These findings open the possibility of now characterizing the sensitivity and specificity of many, if not all, of the hundreds of different human olfactory receptors.


Objective: The effects of 810 nm light-emitting diode (LED) photobiomodulation (PBM) on cerebral metabolism and cerebral hemodynamic were investigated by using a broadband near-infrared spectroscopy (bb-NIRS) under anesthesia conditions with isoflurane. Background data: PBM was supposed to increase cerebral hemodynamic and cerebral metabolism. There has been no study about the effect of 810 nm LED stimulation on cerebral hemodynamic and cerebral metabolism in vivo by using bb-NIRS measurement. Methods: PBM was applied to seven Sprague-Dawley rats at 50 mW/cm2 power density. The changes in hemoglobin concentration (ΔHbO2 and ΔHHb) and oxidized cytochrome c oxidase (CCO) concentration (ΔoxCCO) were measured using a bb-NIRS. The total hemoglobin and the difference in hemoglobin concentration changes were calculated by summation and difference of ΔHbO2 and ΔHHb, respectively. Results: PBM evoked the gradual increases of ΔHbO2 (+7.7 μM vs. baseline, p = 0.008), ΔHbT (+9.5 μM vs. baseline, p = 0.0044), and ΔHbD (+5.9 μM vs. baseline, p > 0.05) during light stimulation. Meanwhile, ΔoxCCO (-3.5 μM vs. baseline, p = 0.0019) was significantly decreased right after the onset of stimulation. Conclusions: PBM with 810 nm LED (50 mW/cm2) increased cerebral oxygenation and blood volume as expected. However, oxidized CCO concentration was decreased, which was contrary to most previous studies. The two pathways of PBM effects on mitochondria and the inhibition of complex I by isoflurane were suggested to explain the decreased ΔoxCCO during PBM, but further study is required for the verification.


Restricted and repetitive behaviours and interests (RRBIs) are a broad and heterogeneous class of behaviours that are present in a number of neuro-developmental conditions, such as, autism spectrum disorder (ASD) and Prader-Willi syndrome (PWS), but also feature in early typical development. The management of maladaptive RRBIs may present a considerable challenge to parents and the behaviours themselves may hamper the acquisition of new skills in affected individuals. Despite early research being fraught with lack of consensus in terminology and item overlap on standardised measures, the past decade has seen a resurgence of research in the area. Most systematic research, however, has been conducted in children with ASD and there are few studies that attempt to make links across disorders. Furthermore, debate over the structure of RRBIs and the use of domain scores in research has led to inconsistencies in studies attempting to identify their neuro-cognitive correlates. The collection of studies in this thesis attempt to move away from domain scores of repetitive behaviour by using factor analysis to parse the RRBI domain into homogeneous behavioural factors. These factors form the basis of studies in later chapters examining the relationship between RRBIs and executive functions (EF) in ASD, PWS and typical development. Results show that there is a differential pattern of association between different types of EF and specific RRBIs and findings across groups indicate possible common executive correlates of behaviour.


This paper explores the prospects of complementary rather than competitive dispute resolution and justice systems in Liberia. It specifically considers women's access to justice in relation to sexual and gender-based violence (SGBV), which remains prevalent in the post-conflict period, and in the context of a highly hybridised justice system. While the formal system has made great progress in reforming laws and institutions but is vastly under-resourced. Informal and traditional systems are widely considered more accessible and affordable. They are, however, also susceptible to corruption and co-option, and the state's oversight and curtailing of specific conflict resolution and punishment practices is considered to have rendered these systems less effective. Significantly, some cultural and traditional practices are themselves considered to facilitate and promote SGBV. These factors make complementary systems an imperative while working to address the deficiencies of both systems.


Article type Review article Cardiovascular is the major cause of death in chronic kidney disease and end-stage renal disease. The cardiovascular mortality rate of patients with renal impairment is evaluated to be higher than general population. Coronary artery disease seems to be an important type of cardiovascular complication among patients with chronic kidney disease and end-stage renal disease before the renal replacement therapy. Due to the strong association between chronic kidney disease and the incidence of coronary artery disease, accurate screening, diagnosis, and management of cardiovascular complications would be essential in patients at different stages of renal dysfunction. Despite the need for the comprehensive knowledge about different aspects of coronary artery disease in patients with renal failure, there is not sufficient evidence regarding the pathophysiology, ideal diagnosis, and treatment strategies for coronary heart disease in population with chronic kidney disease. In this study, we briefly reviewed the existing literatures about the possible screening, diagnosis, and the treatment approaches of risk of coronary heart disease in patients with kidney dysfunction.


Low anterior resection with total mesorectal excision and reconstruction with coloanal anastomosis is the optimal treatment of nondisseminated rectal cancer in selected patients and has seen a decrease in permanent stomas. However, up to 60% of patients can suffer from bothersome functional bowel complaints associated with the surgery and neo-adjuvant and adjuvant therapies, which are known as low anterior resection syndrome (LARS). LARS symptoms include faecal urgency, incontinence, frequency, constipation and incomplete emptying, in which patients may suffer from one or multiple symptoms. Patients should be informed about the possibility of permanent changes to their bowel function and what impact it could have on their quality of life. Nursing involvement is key to optimising symptoms and patient quality of life for patients suffering with LARS. Nursing management includes performing a physical assessment and determining the severity of LARS symptoms and effect on quality of life. Treatments available for LARS are based around the symptoms the patient is suffering and can include dietary modifications; biofeedback and pelvic floor physiotherapy; dietary fibre supplements / bulking agents; medications; transanal irrigation; surgical options and education.


Aim: The present study was aimed to study the use of cell counts as an early indicator of mammary health. Materials and Methods: Milk and blood cell counts were estimated from 8 healthy, 8 subclinical (SCM), and 8 clinically mastitis (CM) groups of Karan Fries (KF) cows. Results: Total leucocyte counts and neutrophil percent in blood and milk somatic cells and milk neutrophil percent of healthy cows increased significantly (p<0.05) in SCM cows and CM cows. Viability of blood and milk neutrophils was more in healthy cows, but decreased significantly (p<0.05) in SCM and CM cows. Significant (p<0.05) decrease were also observed in both the blood and milk lymphocytes and monocytes of SCM and CM cows. Phagocytic activity (PA) of blood neutrophils also decreased significantly (p<0.05) in SCM cows. There was no difference between the PA of SCM and CM cows. Milk neutrophil percent was more in the SCM and clinically infected milk than in the blood of these cows. About 96-97% of the neutrophils had segmented nucleus in both healthy and subclinical milk, whereas, 2-3% were having band shaped or immature nuclei. There was a significant decrease in the segmented neutrophils, whereas, band neutrophils increase significantly to about 5% in the infected milk of mastitic cows. Viability of the milk neutrophils decreased more in case of subclinical and clinical milk as compared to that of blood. PA was found to be highest in the milk of healthy group of cows, but decreased significantly (p<0.05) in subclinically infected cows. However, there was no difference between the PA of milk neutrophils of SCM and CM cows. PA of milk was also found to be significantly lower in the milk of healthy cows when compared to that of blood neutrophils. Conclusion: This study indicated that percent neutrophils and their type in conjunction with milk somatic cell counts can be used as a more reliable indicator of mammary health in cows.


This article describes how a system of interprofessional learning was established and developed. It gives practical tips on implementation and some short case studies demonstrating how students have benefited from this approach.


The study of the characteristics of various kinds of energy in the universe has become the main source of human success, in achieving faith in Allah. One of them is scientific proof of the truth of the Koran against science that has been tested theoretically and empirically. This study aims to find a meeting point between the Koran and modern science regarding the interpretation of the cosmic verses regarding the origin and extinction of the universe. The information provided by the Al-Qur'an will remain secret, until the human mind can properly digest the information provided. Along with the passage of time and the development of science, Allah has gradually proven the truth of the Qur'anic information about the universe. The results of this study indicate that the Al-Quran has far preached the theory of the universe before modern science revealed it in a study.


While this article mainly applies to practitioners who have responsibilities for leading teams or supervising practitioners, many of the skills and tools described here may also apply to students or junior practitioners. The purpose of this article is to highlight some of the main points about organisation, some of the organisational skills and tools that are available, and some examples of how these skills and tools can be used to make practitioners more effective at organising their workload. It is important to realise that organising work and doing work are two completely different things and shouldn't be mixed up. For example, it would be very difficult to start organising work in the middle of a busy operating list: the organisation of the work must come before the work starts and therefore preparation is often an important first step in organising work. As such, some of the tools and skills described in this article may need to be used hours or even days prior to the actual work taking place.


Is there a relationship between urban neighborhood safety and helpful or supportive user networks on Twitter? An interdisciplinary, community-partnered team analyzed one year (2013-2014) of geo-tagged tweets from a 16-county region to generate a network of users who expressed gratefulness to one another. Call counts to 911 (2013-2015) around locations in the urban center indicate safety-oriented activity in residential areas. We compared frequencies of 911-related police activity across geographic pockets (200m radius or 200×200 meter2 areas) where mutually helpful or thanked users lived or frequently tweeted, to pockets randomly selected in proximity. The 13 naturally helpful users with predicted home locations in this city lived where fewer 911 calls for police service were initiated over time, on average. Our results show that close neighborhood locations where 79 naturally helpful users had strong local geographic ties in this urban area, as evidenced by Twitter use patterns, functioned as safe zones needing fewer policing services on average than surrounding areas. We discuss the implications of predicting real-world needs for police services based on supportive qualities of one's social media neighborhoods.


Given the predominantly secular approach towards religion by anthropologists and sociologists, we contend that a discussion of the researcher's positionality with regard to faith and belief, as well as the autoethnographic approach in pilgrimage studies, is methodologically important. Drawing on years of volunteering at two pilgrimage sites, we explore what kind of methodological impact our role as volunteers and our private lives have had on both research at and interpretations of the pilgrimage sites. For one of us working as a volunteer was a personal choice motivated by faith, while for the other it was based on the pragmatics of doing research. In both cases gaining access involved the generation of social capital through the gifting of time and free labor within a hierarchical structure of power exchange. Our role as volunteers gave us an opportunity to explore the faith-based positionality and self-interest which informs pilgrimage volunteering and involves power exchange. Our article seeks to show how we address our own religious beliefs but, at the same time, stay grounded in ethnographic observations and analysis.


Large-scale graphs with node attributes are fundamental in real-world scenarios, such as social and financial networks. The generation of synthetic graphs that emulate real-world ones is pivotal in graph machine learning, aiding network evolution understanding and data utility preservation when original data cannot be shared. Traditional models for graph generation suffer from limited model capacity. Recent developments in diffusion models have shown promise in merely graph structure generation or the generation of small molecular graphs with attributes. However, their applicability to large attributed graphs remains unaddressed due to challenges in capturing intricate patterns and scalability. This paper introduces GraphMaker, a novel diffusion model tailored for generating large attributed graphs. We study the diffusion models that either couple or decouple graph structure and node attribute generation to address their complex correlation. We also employ node-level conditioning and adopt a minibatch strategy for scalability. We further propose a new evaluation pipeline using models trained on generated synthetic graphs and tested on original graphs to evaluate the quality of synthetic data. Empirical evaluations on real-world datasets showcase GraphMaker's superiority in generating realistic and diverse large-attributed graphs beneficial for downstream tasks.


This project broadly explores the discordant application of creativity requirements in national design regimes. It includes three separate empirical studies, each building on the next. The first examines a well-known but untested phenomenon in design regimes called Creativity Scaling. Broadly stated, the orthodox account of design regime typologies could be described as follows: patent approaches grant the strongest rights conditioned on the most creativity through their high obviousness-based standards; copyright approaches grant the weakest rights conditioned on the least creativity through their low originality-based standards; and sui generis regimes fit somewhere between these dominant regime archetypes. While the balance between requirement and reward are equally important to avoiding market failure, this project focuses on the elusive role of creativity. Through a series of internet-based surveys, it tests whether design regimes are indeed scaled. Moreover, it explores the role of viewpoint on the application of these legal determinations. The second study utilizes the lens of product semantics or design-based semiotics, to help explain why these standards are commonly portrayed as subjective. Specifically, it examines the relationship between the legal outcomes from the first set of surveys, and a second set aimed at unraveling how distinctions in semantic and symbolic product meanings can affect their outcomes. Lastly, the third and final study examines the relationship between creativity requirements and consumer preference. Simply put, people obtain the most hedonic value from objects with a moderate degree of novelty. Indeed, Raymond Loewy's famous design heuristic nicely encapsulates this relationship between novelty and consumer preference more broadly: Most Advanced, yet Acceptable (MAYA). Building on the results from the first study, this project closes by investigating how creativity requirements, which theoretically mandate disparate degrees of novelty, affect consumer preference for those designs.


The effects of temperature, Mg2+, ATP, and actin on the conformation of the neck region of the myosin head were studied by limited proteolysis of heavy meromyosin (HMM) and subfragment 1 (S1) preparations obtained by papain digestion of myosin in the presence of Mg2+ (Mg-S1) or EDTA (EDTA-S1). The preparations were fluorescently labelled at the SH1 thiol group to enable identification of the COOH-terminal fragments of the head portion of the heavy chain where this group is located. The results indicate that the head-rod junctional region of the myosin heavy chain contains at least three different sites readily susceptible to trypsin at 25 degrees C if the light chain LC2 or its LC2' fragment are absent. The susceptibility of one of these sites dramatically decreases when the temperature is lowered to 0 degree C, indicating a temperature-dependent conformational transition in the head-rod junction. With the method used, this transition is detectable only in LC2/LC'2-deficient preparations since all three sites are protected, although to different extents, by LC2 and its LC'2 derivative. It is, however, most probable that the effect of the light chain is confined to steric hindrance of trypsin access and that the temperature-dependent structural transition in the head-rod junction can occur in the presence of intact LC2 as well and may contribute to the temperature sensitivity of force generation in muscle.


Generalized ridge waveguides are analyzed using the mode-matching method. The characteristic impedance, attenua- tion, and power-handling capability of several types of ridge rect- angular waveguides and ridge circular waveguides are presented. Numerical results are obtained, which are useful in the design of many microwave components and subsystems.


Study Design A biomechanical study using human cadaveric lumbar spines. Objectives To determine the strength and stiffness of 3 carbon fiber cage designs in axial compression. To assess the effects of bone mineral density (BMD) on vertebral endplate failure with respect to the different cage patterns. Summary of Background Data Unilateral transforaminal approaches are gaining popularity compared with posterolateral lumbar interbody fusion. With differences in the inherent strengths of each quadrant of the endplate, the effect of different cage designs and their location on the endplate may affect subsidence and fusion success. Methods BMD measurements were obtained from 30 human spinal segments from L3 to L5. Discectomies were performed and cages were placed on the cephalad endplate of each vertebra in 3 configurations: 2 small posterolateral rectangular cages; 1 small anterior banana cage; and 1 small central rectangular cage. Each segment was tested under compression until endplate failure was recorded. Two-way analysis of variance was used to test for the effects of cage design on cage subsidence and endplate failure. Analysis of covariance was conducted to test for the effects of age, BMD, and vertebral levels on the failure load and stiffness for each cage design. Results Cage design was not significant in affecting failure force across the endplate. There were insignificant differences comparing stiffness in compression for the 3 different cage placements patterns. Low BMD adversely affected failure force and construct stiffness across all 3 cage patterns. Conclusions Cage design and position do not significantly affect failure of the construct or stiffness in compression across the endplate. BMD significantly affects both failure forces and stiffness but is not dependent on the positioning or design of the cage.


The developments of sustainable elastomers from natural biomass to compete fossil fuel-derived elastomers are gaining increasing attention during recent years. In this work, elastomer derived from soybean oil and lignin was developed via a metal-free thermal azide–alkyne cycloaddition reaction (TAAC). Azide-containing polymers derived from soybean oil and alkyne-functionalized lignin were first prepared and confirmed via FT-IR, NMR, and GPC. A mixture of azide-containing polymers/lignin-alkyne was then thermal cured via TAAC, which afforded thermoset elastomers. The mechanical properties as well as elasticity were calculated via tensile tests. Moreover, mechanical properties of these elastomers could be facilely tuned via controlling the azide content in the soy-based polymers and the ratio of lignin-alkyne cross-linkers.


In the past the European otter Lutra lutra was distributed throughout most of Europe but since the 1980s its distributional range has been reduced. Currently, the otter population is increasing. Conservation efforts have been implemented, however due to the natural elusiveness of the species it is difficult to monitor. Non-invasive sampling has proven to be the most effective method to derive population parameters such as presence/absence, genetic variability and population structure in European otters. The method to collect non-invasive samples is robust and provides reliable data. This study investigates the validity of the present state-of-the-art method of identifying otter feces, and suggests modifications and improvements of the method. Results from the comparison of field collected data and data derived from a blind test show that the method is applicable in areas abundant with otters, however the method loses its power in the periphery of the distributional range. In these areas, it would be relevant to supplement traditional sampling with DNA analysis to verify the identification of the sample.


Recently, audio-visual speech recognition (AVSR) has been studied to cope with noise problems in speech recognition. In this paper we propose a novel method of deciding weighting factors for audio-visual information fusion. We adopt the particle swarm optimization (PSO) to weighting factor determination. The AVSR experiments show that PSO-based normalized confidence measures (NCM) improve the rejection performance of mis-recognized words by 33%.


SUMMARY – The purpose of this study was to evaluate postoperative deturgescence of lamellar donor graft after conventional Descemet's stripping automated endothelial keratoplasty (DSAEK). It was a prospective study that included 55 eyes of patients (mean age 70.9±9.4 years; female 61.8%, male 38.2%). Preoperative thickness of lamella was compared with postoperative thickness six months after surgery. Central lamellar graft thickness decreased from 142±27 µm preoperatively to 124±20 µm 6 months postoperatively (p<0.01). After performing conventional DSAEK corneal transplantation, surgeons should expect deturgescence of corneal graft and reduction in thickness of lamellae by about 12% of initial thickness according to our results. We found this information important for better planning of surgical procedures and knowing what to expect after surgery, as well as for better cooperation with eye banks when ordering pre-cut corneal tissue.


Abstract Background ALIS (590 mg amikacin base) is liposome-encapsulated amikacin for inhalation, which delivers amikacin directly to the lung and limits systemic exposure. In the CONVERT phase 3 trial, significantly more adults with treatment-refractory MAC lung disease receiving ALIS plus guideline-based therapy (GBT) vs. GBT alone achieved sputum culture conversion by month 6 (29.0% vs. 8.9%, P < 0.0001). Amikacin treatment failure has previously been reported in patients with amikacin minimum inhibitory concentrations (MIC) >64 µg/mL. We analyzed the impact of amikacin MIC on culture conversion during treatment with add-on ALIS. Methods In CONVERT, patients were randomly assigned (2:1) to receive once daily ALIS+GBT (n = 224) or GBT alone (n = 112). Patients with amikacin-resistant MAC isolates (MICs >64 μg/mL by broth microdilution) were excluded prior to randomization. The primary endpoint was culture conversion, defined as 3 consecutive monthly MAC-negative sputum cultures by month 6. Amikacin MICs were correlated with culture conversion rates. Results Amikacin MIC distributions at baseline (day 1) were similar in both groups (Figure 1). Conversion rates in the ALIS+GBT arm were 28.6–34.5% for MAC with amikacin MICs of 8–64 µg/mL (Figure 2). Overall, 28 patients developed post-screening amikacin MIC >64 µg/mL, 4/112 in the GBT alone arm (post-baseline), and 24/224 in the ALIS+GBT arm (1 at baseline and 23 post-baseline after adding ALIS). Most of these (18/24) had MAC isolates with persistent amikacin MIC >64 µg/mL. Only 1/24 patients in the ALIS+GBT arm with amikacin MIC >64 µg/mL achieved culture conversion. No patient with both macrolide resistance and persistent amikacin MIC >64 µg/mL (8/24) converted. Conclusion In the ALIS+GBT arm of CONVERT, culture conversion rates were similar for amikacin MICs ranging from 8–64 µg/mL at baseline. Amikacin MIC >64 µg/mL emerged in 10.3% of patients after initiation of add-on ALIS treatment, and 3.6% in the GBT alone arm. Emergent amikacin MIC >64 µg/mL was associated with failure to convert, particularly with concurrent macrolide resistance. Determining amikacin susceptibility at both treatment initiation and during treatment may have utility for guiding treatment decisions. Disclosures B. A. Brown-Elliott, Insmed: Investigator, Research support. G. Eagle, Insmed Incorporated: Employee, Salary. R. J. Wallace, Insmed: Investigator, Research support. J. Van Ingen, Insmed: Investigator, Research support. L. J. Pennings, Insmed: Investigator, Research support. B. Berry, Insmed: Investigator, Research support. S. Pandey, Insmed: Investigator, Research support. C. Coulter, Insmed: Investigator, Research support. M. Syrmis, Insmed: Investigator, Research support. K. L. Winthrop, Insmed Incorporated: Consultant and Scientific Advisor, Consulting fee and Research grant. D. E. Griffith, Aradigm Corporation: Advisor/consultant and Speaker's Bureau, Consulting fee and Speaker honorarium. Bayer Healthcare Pharmaceuticals: Advisor/consultant, Consulting fee. Grifols: Advisor/consultant and Speaker's Bureau, Consulting fee and Speaker honorarium. Insmed Incorporated: Advisor/consultant, Grant Investigator and Speaker's Bureau, Consulting fee, Grant recipient and Speaker honorarium.


This thesis focuses on the development of the wireless applications for Ambient Assisted Living (AAL) system, the energy harvesting technique for powering the passive sensors in the building environment, and the flexible screen printed coils for Wireless Power Transfer (WPT) system to provide the power for a body-area sensor network in an AAL system. The AAL provides safe environments around assisted peoples and help them maintain independent living. The applications in AAL include the fixed monitor sensor in building environment and the wearable sensor on users body area. For supplying power for the applications of AAL wireless power supply provides the power without cables while offers a more environmentally friendly solution. Compared with energy harvesting technology, WPT is capable of supplying more power without increasing the size of the device. In this work, a solar powered PIR sensor demonstrates that the energy harvesting technique for a passive sensor application for the fixed monitor sensor in building environment, which can work for up to 16 hours without ambient energy input. For the on-body area application, the flexible coils are employed in the WPT system because of the comfort requirement. The coils are printed on 65/35 polyester/cotton textile with a Fabink-UV-IF1 interface layer coating. The interface layer provides a relatively flat and smooth surface to prevent the permeation of the conductive paste into the textile and allows the printing of finer profile coils, and the flexibility and breathability of textile can be remained. The measured inductances of the printed flexible coils are 3.9 ?H for single layer. The design of the printed coil minimises the coil's parasitic capacitance, which is less than 25 pF, and consequently increase the self-resonant frequency of the printed coil. A 5 V 1.51 W DC output has been achieved by a wireless power transfer system using the printed flexible coils with Qi standard circuitry; a DC-DC efficiency of 38% has been measured. It has been compared with the system employed with Qi standard wound copper coils which has the recorded 52% DC-DC efficiency.


The paper assesses the evolution of efficiency of Italian public universities for the period 2000–2010. It aims at investigating whether their levels of efficiency showed signs of convergence, and if the well-known disparity between northern and southern regions decreased. For this purpose, we use a refinement of data envelopment analysis, namely window analysis, which allows for measuring efficiency in cross-sectional and time-varying data. We find that the efficiency of most universities registered only marginal changes in the period, although a notable re-ranking occurred. However, changes in the management of universities, consequential to the reform processes, did not affect the long-run tendencies, such as the persisting difference in performance between north and south.


Underpotential deposition (upd) has been a hotspot in the field of electrochemical research throughout the years owing to its significant theoretical and applied research value. Theoretical research on upd primarily centers around the relations and rules of interaction among deposition substrates, deposition species, and anions (or other organic additives) during upd process. In this paper, the developments in theoretical research in recent years on upd on both the local and international levels are systematically summarized mainly from two viewpoints, namely, thermodynamics and kinetics. With regard to the thermodynamics of upd process, introductory comments and mathematical formulas are summarized from four aspects, i.e., underpotential shift (ΔEupd), electrosorption valency (γ), influence of temperature, and electrochemical adsorption isotherms. The applications and analyses of those related mathematical formulas are also presented in detail. In terms of the kinetics of upd process, nucleation and growth phenomena are mainly presented. We summarize the relevant mathematical models, and additionally introduce research studies on the characteristics of upd kinetics based on these mathematical models. Furthermore, this paper presents an outline of computational chemistry methods and application achievements concerning upd research. Finally, the theoretical research status of upd is presented, giving an overall view of the development trend.


Cross-linguistically, affix order is commonly determined by semantic scope (Rice, 2006) or a morphological template. Less frequently, affix order is free, which means that suffixes can be reordered without a concomitant change in scope. To address the question of what gives rise to and constrains free affix order (FAO), I present a case study of Paraguayan Guaraní (or PG, Tupí-Guaraní, Paraguay, iso 639-3: gug). I argue that FAO in PG should be analyzed as driven by prosodic factors. The prosodic analysis has previously been proposed only for Chintang (Bickel et al., 2007). Two major analyses of FAO see the phenomenon as driven by either morphology (e. g. Ryan, 2010) or prosody (Bickel et al., 2007). The morphological analysis proposes that FAO is a consequence of free variation within the morphological template. The phonological analysis models FAO with prosodic subcategorization for phonologically prominent positions. I argue that the two analyses make different predictions as to the preconditions for and the extent of FAO. I show that both the morphological and the prosodic profile of FAO are attested. I propose that FAO in PG is an instance of the latter. Thus, I demonstrate that FAO is not a unified phenomenon, but rather should be typologized as driven by either morphological or prosodic factors.


The current work focuses on the application of a.c. impedance spectroscopy techniques to cemenfltlOus systems while still in the liquid state (i.e. during the dormant period). A variety of formats of data presentation are presented and exploited to understand the origins of polarization processes within these systems. The theoretical treatment also allows simulation of the experimental data to provide an interpretation of the bulk impedance response. Data are obtained over the frequency range 1 Hz to 20 MHz, but interpretation and analysis is focused, in the main, on the range 1 kHz to 1 MHz.


The aim of this article is to review the utility of elastography in the day-to-day clinical practice of the urologist. An electronic database search was performed on PubMed and Cochrane Library with a date range between January 2000 and December 2021. The search yielded 94 articles that passed the inclusion and exclusion criteria. The articles were reviewed and discussed by organ, pathology and according to the physical principle underlying the elastographic method. Elastography was used in the study of normal organs, tumoral masses, chronic upper and lower urinary tract obstructive diseases, dysfunctions of the lower urinary tract and the male reproductive system, and as a pre- and post-treatment monitoring tool. Elastography has numerous applications in urology, but due to a lack of standardization in the methodology and equipment, further studies are required.


The fluffy brown sparrows are 15cm in length and distributed all over India up to 4000m in the Himalayas. The disappearance of sparrows has been widely reported in India. The sparrow population in Andhra Pradesh alone had dropped by 80 per cent, and in other states like Kerala, Gujarat and Rajasthan, it had dipped by 20 per cent, while the decline in coastal areas was as sharp as 70 to 80 per cent. But reliable information on sparrow populations is not available. No one is actually counting and keeping a record of the sparrows. The spread of diseases due to decline in sparrow population is an alarming danger. Introduction of unleaded petrol, use of chemically treated seeds, flow of electromagnetic waves from cellphone towers, reducing areas of free growing weeds or reducing numbers of badly maintained buildings, competition for food by other species etc. are possible reasons for this disappearance. The BirdLife International, Royal Society for the Protection of Birds (RSPB), a UK-based organisation and the Bombay Natural History Society (BNHS) have taken plan for the protection of sparrow population.


Background: Better nutrition is a prime entry point to ending the malnutrition maelstrom. Better health means stronger immune systems which mean less illness. Healthy people feel stronger, can work better and may have more earning opportunities to gradually lift them out of both poverty and malnutrition. Healthier, more productive societies are a potential outcome. Protein energy malnutrition has been identified as one of the major nutritional problem among children in India. Since mothers were the primary care takers of children, if they possess adequate knowledge on food and nutrition of children, they can be prevented from protein energy malnutrition. The aim of the study is to assess the effectiveness of planned teaching programme on knowledge regarding Protein energy malnutrition among mothers of under-five children in a selected rural community in Kodoli. Objectives: 1) To determine the pre-test level of knowledge of mothers of under-five children regarding protein energy malnutrition. 2) To evaluate the effectiveness of planned teaching programme on knowledge regarding protein energy malnutrition among mothers of under-five children. 3) To find the association between mean pre-test knowledge score and selected demographic variables. Methodology: A pre-experimental one group pre-test – post-test design was used for the study. The sample consisted of 30 subjects. Mothers of under-five children were selected by purposive sampling technique. The study was conducted in a rural area at Kodoli from 1-08-2018 to 30-08-2019. The investigator obtained written permission from concerned authority prior to the study and written consent was obtained from mothers and assured confidentiality of information. Data was collected by structured interview schedule. After the pre-test a PTP was administered to the subjects and on the seventh day post-test was conducted with the same questionnaire. The collected data was analyzed by using descriptive and inferential statistics. Result: In the pre-test none of the mothers had good knowledge 60% had poor knowledge and 40% had average knowledge whereas in the posttest 33.3% had good knowledge and 66.7% had average knowledge. The mean post test knowledge scores obtained by subjects (13.86) was higher than the mean pre-test knowledge score (9.1). Paired 't' test was done to find out the difference between the mean pre-test and post test knowledge score and statistically it was highly significant (t=9.69, p<0.05). There was no significant association between the mean pre-test knowledge score and the selected variables like age of mother in years (χ2=0.008) educational status of mother (χ2=0.027) family income/month (χ2=0.165) number of children (χ2=0.128) religion (χ2=0.212) type of family (χ2 = 0.0382). Conclusion: PTP was an effective strategy for providing information and to improve knowledge of mothers which was well appreciated and accepted by mothers.


Dinosaur bonebeds with amber content, yet scarce, offer a superior wealth and quality of data on ancient terrestrial ecosystems. However, the preserved palaeodiversity and/or taphonomic characteristics of these exceptional localities had hitherto limited their palaeobiological potential. Here we describe the amber from the Lower Cretaceous dinosaur bonebed of Ariño (Teruel, Spain) using a multidisciplinary approach. Amber is found in both a root layer with amber strictly in situ and a litter layer namely composed of aerial pieces unusually rich in bioinclusions, encompassing 11 insect orders, arachnids, and a few plant and vertebrate remains, including a feather. Additional palaeontological data ‒ charophytes, palynomorphs, ostracods‒ are provided. Ariño arguably represents the most prolific and palaeobiologically diverse locality in which fossiliferous amber and a dinosaur bonebed have been found in association, and the only one known where the vast majority of the palaeontological assemblage suffered no or low-grade pre-burial transport. That has enabled unlocking unprecedentedly complete and reliable palaeoecological data out of two complementary windows of preservation from the same site.


In chronic medical conditions remote patient monitoring (RPM), is beneficial to empower both medical providers and patients. RPM supports medical care and early interventions to potentially promote patient's disease management and improve outcomes. In heart failure, although RPM holds significant promise, published trials provide evidence regarding historical success and failures that inform future efforts. Heart failure has increased in incidence and prevalence during the past years, leading to significant cost. We must find alternate ways to monitor daily disease progression and symptomatology to allow the patient and their health provider react to not only reduce cardiovascular outcomes but reduce hospitalizations and readmission rates. Here we display most up to date studies and analysis of our perspective on the role of RPM in heart failure.


The nuclear meltdowns at Fukushima in the spring of 2011, according to countless media and government analyses, were a failure of Japan: collusive ties between regulators and industry prevented proper enforcement, the nation's nuclear engineers embodied a culture of hubris, and the state prevented the media from raising critical perspectives. This analysis is usefully understood as a narrative. Like all narratives, it reveals certain issues and masks others. One of the limitations of the "failure of Japan" narrative is that its national focus ignores causes and consequences at local and international scales. In this article, we offer a broader view of Fukushima by presenting a series of alternative narratives that draw out local, national, and international dimensions. Casting our gaze beyond the dominant narrative allows us to direct attention to actors and issues often overlooked, such as Cold War politics, international flows of knowledge and materials, global consumers, nation building, villagers in Ōkuma and Futaba, and laborers at the Fukushima Daiichi power plant. In particular, we highlight several significant ways in which narratives at different scales intersect, overlap, and reinforce each other. To make sense of the complex forces that brought about the nuclear meltdowns and myriad impacts they will have, we need more stories, not a single narrative.


Covid-19 was first discovered in Wuhan, Hubei Province in China at the end of 2019 to be precise in December. The entry of Covid in the middle of our lives, we are preoccupied with a series of dense activities in the days that we pass, Covid-19 changes all the structures of our lives and our patterns of life, from Covid-19 we are able to learn to be more careful, we are required to continue live a healthy life, wash your hands more actively and maintain a healthy diet and sleep. The method used in this research is qualitative, using a content analysis approach in its presentation using descriptive methods. In this study, researchers used documents in the form of text, images, symbols, news, and newspapers as sources of research data. By using this analysis, it is used to obtain data information that comes from online news. This research was conducted by collecting data in the media or online news related to changes in society after the Covid-19 pandemic in Malang. Persons' thinking is the existence of a process of differentiation, which assumes that every society is composed of a set of different subsystems based on its structure and functionalism for the wider community. Social changes in society due to Covid-19 have resulted in changes in behavior.Talcott Parsons gave birth to a Functional theory of change. As has been argued by his predecessors, Parsons also makes an analogy of social change in society, such as growth in living things.


Drawing from in situ fieldwork in Longyearbyen, Svalbard, the northernmost settlement on Earth, these notes bring out the affective, ambient, and atmospheric power of extended darkness during the polar night, when the sun does not appear above the horizon for several months at a time. Each entry is composed of 113 words to reflect the number of days without light in Longyearbyen during the winter of my visit. Through a mixture of ethnographic observations, researched academic scholarship, and some endeavors of poetic worldmaking, these notes attempt to evoke the ineffable force of global warming by performing the sort of acutely observed and felt attentiveness to planetary being that is needed for our time.


Understanding the nature of the interaction between small molecules and G-quadruplex DNA is crucial for the development of novel anticancer drugs. In this paper, we present the first data on time-resolved fluorescence anisotropy study on the interaction between a water-soluble cationic porphyrin H(2)TMPyP4 and four distinct G-quadruplex DNAs, that is, AG(3)(T(2)AG(3))(3), thrombin-binding aptamer (TBA), (G(4)T(4)G(4))2, and (TG(4)T)4. The anisotropy decay curves show the monoexponential for free H(2)TMPyP4 and the biexponential upon binding to the excess amount of G-quadruplex DNAs. The biexponential anisotropy decay can be well interpreted using a wobbling-in-the-cone model. The orientational diffusion of the bound H(2)TMPyP4 is initially restricted to a limited cone angle within the G-quadruplex DNAs, and then an overall orientational relaxation of the G-quadruplex DNA-H(2)TMPyP4 complexes occurs in a longer time scale. It was found that the dynamics of the restricted internal rotation of bound H(2)TMPyP4 strongly depends on the ending structures of the G-quadruplex DNAs. According to the order parameter (Q) calculated from the wobbling-in-the-cone model, we deduce that the degree of restriction around the bound H(2)TMPyP4 follows the order of TBA > (TG(4)T)4 > AG(3)(T(2)AG(3))(3) > (G(4)T(4)G(4))2. Especially, based on the maximum order parameter (Q) of bound H(2)TMPyP4 within TBA, a new sandwich-type binding mode for TBA-H(2)TMPyP4 complex was proposed in which both terminal G-quartet and T*T base pair stack on the porphyrin ring through pi-pi interaction. This study thus provides a new insight into the interaction between G-quadruplex DNAs and H(2)TMPyP4.


With the recent emergence of multicore architectures, the age of multicore computing might have already dawned upon us. This shift might have triggered the evolution of von Neumann architecture towards a parallel processing paradigm. Cellular Automata- inherently decentralized spatially extended systems consisting of large numbers of simple and identical components with local connectivity, also proposed by von Neumann in 1950s, is the potential candidate among the parallel processing alternatives. The spatial parallelism available on field programmable gate arrays make them the ideal platform to investigate the cellular automata systems as potential parallel processing paradigm on multicore architectures. The authors have been experimenting with this idea for quite some time now and report their progress from a single to a dual FPGA chip based cellular automata accelerator implementation. For D2Q9 Lattice Boltzmann method implementation, we were able to achieve an overall speed-up of 2.3 by moving our Fortran implementation to our single FPGA-based implementations. Further, with our dual FPGA-based implementation, we achieved a speed-up close to 1.8 compared to our single FPGA-based implementation.


Nowadays, surgical operations are impossible to imagine without general anaesthesia, which involves loss of consciousness, immobility, amnesia and analgesia. Understanding mechanisms underlying each of these effects guarantees well-controlled medical treatment.

Our work focuses on analgesia effect of general anaesthesia, more specifically, on patients reaction on nociception stimuli. The study was conducted on dataset consisting of 230 EEG signals: pre- and post-incisional recordings for 115 patients, who received desflurane and propofol [1].

Initial analysis was performed by power spectral analysis, which is a widespread approach in signal processing. Power spectral information was described by fitting the background activity and measuring power contained in delta and alpha bands according to power of background activity. The fact that power spectrum of background activity decays as frequency increasing is well known and thoroughly studied [2]. Here, traditional 1/f^α behaviour of the decay was replaced by a Lorentzian model to describe the power spectrum of background activity.

Due to observed non-stationary nature of EEG signals spectral analysis does not suffice to reveal significant changes between two states. A further improvement was done by expanding spectra with time information. To obtain time-frequency representations of the signals conventional spectrograms were used as well as a spectrogram reassignment technique [3]. The latter allows to ameliorate readability of a spectrogram by reassigning energy contained in spectrogram to more precise positions.

Subsequently, obtained spectrograms were used in recurrence analysis [4] and its quantification by complexity measure. Recurrence analysis allows to describe and visualise dynamics of a system and discover structural patterns contained in the data. Structure of each recurrence plot is characterised by Lempel–Ziv complexity measure [5], which shows a difference between pre- and post-incision.

References:
1. James W. Sleigh, Leslie, K. & Voss, L. The effect of skin incision on the electroencephalogram during general anesthesia maintained with propofol or desflurane. Journal of clinical monitoring and computing 24, 307–18 (2010), 10.1007/s10877-010-9251-3
2. Bedard, C. & Destexhe, A. Macroscopic Models of Local Field Potentials and the Apparent 1/f Noise in Brain Activity. Biophysical Journal 96, 2589–2603 (2009), 10.1016/j.bpj.2008.12.3951
3. Auger, F. et al. Time-Frequency Reassignment and Synchrosqueezing: An Overview. IEEE Signal Processing Magazine 30, 32–41 (2013), 10.1109/MSP.2013.2265316
4. Marwan, N., Carmenromano, M., Thiel, M. & Kurths, J. Recurrence plots for the analysis of complex systems. Physics Reports 438, 237–329 (2007), 10.1016/j.physrep.2006.11.001
5. Zhang, X.-S., Roy, R. J. & Jensen, E. W. EEG complexity as a measure of depth of anesthesia for patients. Biomedical Engineering, IEEE Transactions on 48, 1424–1433 (2001), 10.1109/10.966601


We present the LATE algorithm, an asynchronous variant of the Earley algorithm for parsing context-free grammars. The Earley algorithm is naturally task-based, but is difficult to parallelize because of dependencies between the tasks. We present the LATE algorithm, which uses additional data structures to maintain information about the state of the parse so that work items may be processed in any order. This property allows the LATE algorithm to be sped up using task parallelism. We show that the LATE algorithm can achieve a 120x speedup over the Earley algorithm on a natural language task.


This research study intends to investigate the tourist satisfaction as a mediating variable in the relationship between the Islamic attributes, service quality and destination loyalty among Malaysian Muslim tourists in the Padang city. A self survey was implemented as the means to attain the primary data among the 160 Malaysian Muslim tourists visiting the Padang city . The sample of 119 usable responses were collected from the 160. To analyze the model, Partial Least Squares structural equation modeling was utilized. The statistical outcomes established the positive and significant influence of the service quality, the Islamic attributes and the tourist satisfaction on destination loyalty. The results also established that tourist satisfaction were positively and significantly influenced by the service quality and the Islamic attributes. Along with it, tourist satisfaction mediated significantly in the relationship between the Islamic attribute, the service quality and the destination loyalty among the Malaysian Muslim tourists visiting in Padang city.


In the last few years, a new area has emerged in economic theory, which goes under the heading of 'incomplete contracting'. However, almost since its inception, the theory has been under attack for its lack of rigorous foundations. In this paper we evaluate some of the criticisms that have been made of the theory, in particular, those in Maskin and Tirole (1998a). In doing so, we develop a model that provides a rigorous foundation for the idea that contracts are incomplete.


Although acute laryngitis is common, it is often managed by primary physicians. Therefore, video images documenting its signs are scarce. This series includes 7 professional voice users who previously had undergone baseline strobovideolaryngscopy (SVL) during routine examinations or during evaluations for other complaints and who returned with acute laryngitis. Sequential SVL showed not only the expected erythema, edema, cough, and dysphonia, but also new masses in 5 of the 7 subjects. All the signs returned to baseline. This series is reported to highlight the reversible structural changes that can be expected in patients with acute laryngitis and the value of conservative management.


This report describes a rare case of congenital syphilis in a two-month-old Romanian infant. Diagnosis was possible when the baby showed decrease in the left upper limb movements and a papular rash. Her father had been infected and transmitted the infection to the mother, who had two non-treponemal serological tests during pregnancy, both with negative results. Congenital syphilis was confirmed by serological tests and the newborn was successfully treated. A global overview on diagnosis and treatment of children with suspected congenital syphilis is presented.


This paper uses unit record data from the Household Income and Labour Dynamics in Australia (HILDA) survey. The HILDA Project was initiated by the Australian Government Department of Families, Community Services and Indigenous Affairs (FaCSIA) and is managed by the Melbourne Institute for Economic and Social Research (MIAESR). The findings and views reported in this paper, however, are those of the author and should not be attributed to either FaCSIA or the MIAESR.


Today, manufacturers in the automotive industry have to find a compromise between ensuring maximum safety for passengers, which is achieved by the use of high stiffness materials, and a minimum CO2 footprint. These aims are achieved primarily by the usage of lightweight designs. With respect to the car body, high-strength steels—such as the manganese boron steel MBW® 1500 (22MnB5)—fulfil these requirements. Workpieces made of 22MnB5 have a high tensile strength of about 1500 MPa, respectively, enabling reduction of the sheet thickness. However, this high strength is not favorable in all sections of a part, especially those which are relevant for safety. In order to locally adjust the mechanical properties of MBW 1500, a laser-based heat treatment process has been developed to meet the requirements of high ductility in the deformation zones for better crash performance and in joining areas. By means of laser radiation, the brittle martensitic microstructure of MBW 1500 is either tempered or transformed into a ferrite/perlite-dominated microstructure. While the feasibility of the laser softening of high-strength steels with diode laser systems using a tophat intensity profile at a maximum feed rate of 1.0 m/min has already been shown, the present work focuses on the increase in the feed rate of laser softening using an adapted intensity distribution. This distribution is generated using a free-form optics and is designed in such a way that a homogeneous temperature profile on the workpiece's surface is induced. As a result, the feed rate can be increased maintaining homogeneous softening across the sheet thickness.Today, manufacturers in the automotive industry have to find a compromise between ensuring maximum safety for passengers, which is achieved by the use of high stiffness materials, and a minimum CO2 footprint. These aims are achieved primarily by the usage of lightweight designs. With respect to the car body, high-strength steels—such as the manganese boron steel MBW® 1500 (22MnB5)—fulfil these requirements. Workpieces made of 22MnB5 have a high tensile strength of about 1500 MPa, respectively, enabling reduction of the sheet thickness. However, this high strength is not favorable in all sections of a part, especially those which are relevant for safety. In order to locally adjust the mechanical properties of MBW 1500, a laser-based heat treatment process has been developed to meet the requirements of high ductility in the deformation zones for better crash performance and in joining areas. By means of laser radiation, the brittle martensitic microstructure of MBW 1500 is either tempered or transformed int...


We report of a fetus who was ultrasonographically shown to have growth retardation, oligohydramnios and a pericardial effusion without other components of a hydrops fetalis at 28 weeks' gestation. At 29 weeks' gestation the child was born by cesarean section of pathological CTG. A congenital cytomegaly was diagnosed. The etiological role of the infection for the development of the pericardial effusion is discussed.


Fractal Brownian motion, also called fractional Brownian motion (fBm), is a class of stochastic processes characterized by a single parameter called the Hurst parameter, which is a real number between zero and one. fBm becomes ordinary standard Brownian motion when the parameter has the value of one‐half. In this manner, it generalizes ordinary standard Brownian motion. Here, we precisely define fBm, compare it with Brownian motion, and describe its unique mathematical and statistical properties, including fractal behavior. Ideas of how such properties make these stochastic processes useful models of natural or man‐made systems in life are described. We show how to use these processes as unique random noise representations in state equation models of some systems. We finally present statistical state equation estimation techniques where such processes replace traditional Gaussian white noises. WIREs Comp Stat 2011 3 149–162 DOI: 10.1002/wics.142


In New Zealand the number of gym and fitness training related injuries dominate over every other sport. In 2020 it was reported they surpassed the number of claims for NZ's national sport, rugby [1]. A recent Accident Compensation Corporation [ACC] report showed an 18% increase in gym injuries in the period between 2015-2020 with the cost of support rising by 43% [2].  An epidemiology analysis of 10 years of ACC injury data found that the exercises which led to the greatest number of injuries were the bench press, deadlift, and shoulder press [3]. The aim of this doctoral research is to trial the feasibility of a digital system to coach technique. We are recruiting 200 female inexperienced gym-users for an initial biomechanics screening using motion capture software to assess participants' technique during bench press, deadlift, and shoulder press resistance exercises conducted using free weights, resistance machines and a TONAL strength training device.  A survey assessment will be carried out concurrently to understand the participants' knowledge, attitudes, and behaviours (KAB) towards strength training and injury. Based on the biomechanics screening, 30 participants with poor technique will be identified and invited to participate in a 4-week study to understand the feasibility of a digital system to coach strength training and improve their technique. The knowledge gained in the study will enable education of gym users to prevent further injury via the ACC SportSmart program, with the potential to integrate digital gym instruction by development of a mobile application. In this poster presentation, I will present the findings of my epidemiology analysis and outline the practical aspects of the project, including the biomechanics screening, tools and follow-up study. There will be an opportunity for visitors to the symposium to find out more information about the study and express their interest to participate.


Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC

The anti-angiogenic approach is traditionally considered for solid malignancies, but increasing evidence has also highlighted its involvement in the progression of hematological oncologies. Angiogenesis, including expression of key proteins, is aberrant in blood cancers such as leukemias, lymphomas, and myelomas, in addition to many solid malignancies, including pancreatic cancer. The most critical mediator of oncogenic angiogenesis is vascular endothelial growth factor (VEGF), which is recognized by two high-affinity receptor tyrosine kinases, VEGFR1 and VEGFR2 (KDR gene). VEGFR2 is necessary for the survival, growth, and differentiation of endothelial cells as its downstream effects include activation of the MAPK and the PI3K pathways, and its upregulation is observed under conditions of pathological angiogenesis. While VEGF/VEGFR2 signaling is known to act in a paracrine manner on endothelial cells, autocrine signaling has been observed in both malignant cells and hematopoietic stem cells. For endothelial and hematological malignancies, both autocrine and paracrine pathways can be targeted with anti-VEGFR2 therapies, potentially doubling the clinical efficacy. Intriguingly, the promoter region of KDR contains a GC-rich region of DNA within its the core promoter located −120 to −31 basepairs (bp) upstream of the transcriptional start site (TSS), putatively able to form several G-quadruplexes. These are unique DNA secondary structures that often serve as transcriptional silencer elements. In the present study, G-quadruplex formation has been isolated −80 to −38 bp upstream of the TSS, which contains five strings of guanines that form a mixed parallel/anti-parallel G-quadruplex, as determined by circular dichroism. The cleavage pattern of DMS footprinting and the major stop product of the polymerase stop assay confirmed that the dominant isoform is a parallel G-quadruplex occurring within the four 3' runs of guanines. Mutant studies were performed to further determine guanines integral to G-quadruplex formation. An electrophoretic mobility shift assay was used to confirm the formation of a biologically relevant intramolecular structure. High-throughput screening identified a novel KDR-interactive agent, NSC643735, which thermally stabilized the G-quadruplex. This compound is currently being tested in vitro, and has high potential to transcriptionally downregulate KDR mRNA and, subsequently, VEGFR2 protein. These data characterizing the formation of a unique secondary structure in an important oncogene are promising to develop novel and specific anti-KDR therapy for the treatment of hematological and solid malignancies.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1386.


Individuals who regularly consume excessive quantities of alcohol are at a greater risk of developing various cancers such as esophageal, pharyngeal and lung cancers compared to normal populations if they are deficient in ALDH2 enzyme activity. We evaluated oxidative DNA damage in the liver, brain, and lung tissues of Aldh2 +/+ and Aldh2 -/- mice after they had been subjected to acute ethanol exposure. The 8-hydroxydeoxyguanosine (8-OHdG) level in each tissue was evaluated as a biomarker of oxidative DNA damage. The 8-OHdG level in the liver, brain, and lung tissues was significantly increased following ethanol treatment. In addition, the level of 8-OHdG in the liver and lung tissues was affected by ALDH2 enzyme activity. This result suggests that ALDH2-deficient individuals may be more susceptible than wild-type ALDH2 individuals to ethanol-mediated diseases, including cancer.


We study the effects of the Point Spread Function (PSF) on the performance of the Objective Crystal Spectrometer (OCS) of the SODART telescope. The advantage of OCS/SODART over XMM and AXAF instruments in studying of the diffuse sources is illustrated by modelling of the OCS/SODART observation of Tycho and Cas A Supernova Remnants (SNR).


Expensive data movement makes the optimal target-specific selection of data-locality transformations essential. Loop fusion and tiling are the most important data-locality transformations. Their optimal selection is hard since good tile size choices inherently depend on the fusion choices and vice versa. Existing approaches avoid this difficulty by optimizing independent analytical models or by reverting to heuristics. Absinthe formulates the first unified linear optimization problem to derive single shot fusion and tile size decisions for stencil codes. At the core of our optimization problem, we place a learned analytic performance model that captures the characteristics of the target system. The tuned application kernels demonstrate excellent performance within 10% of exhaustively auto-tuned versions and up to 74% faster than the results of independent optimization with max fusion heuristic and Absinthe tile size selection. While the full search space is non-linear, bounding it to relevant solutions enables the efficient exploration of the exponential search space using linear solvers. As a result, the tuning of our application kernels takes less than one minute. Our approach thus establishes the foundations for next-generation compilers, which exploit empirical information to guide target-specific code transformations.


ABSTRACT: Peritendinous adhesions are a significant problem in tendon surgery. One of the most preferred methods for preventing adhesion formation is anti-adhesive applications. This study aimed to investigate the efficacy of natural synovial fluid as an alternative viscoelastic agent for preventing adhesion in the healing period compared to hyaluronic acid. Thirty adult New Zealand rabbits were used in the study to form three experimental models. In all groups, a rupture was induced in the Achilles tendons. Following tenorrhaphy, hyaluronic acid was applied in one group and synovial fluid in the other group for anti-adhesive purposes. In the control group, no viscoelastic application was made. Bandage was applied to the operated extremities for three weeks post-operatively. At the end of five weeks, euthanasia was performed on the animals using pentobarbital sodium. Surgical sites in all groups were macroscopically examined for healing status as well as the presence and extent of adhesions. Biomechanical tests and histopathological examinations were then performed on the tendons in all groups. Findings established once again the positive contribution of hyaluronic acid to preventing adhesion formation as well as to healing and tensile strength in tendon surgery. Although, we found that it is possible to use synovial fluid, which is a natural source of hyaluronic acid, as a viscoelastic material, it is not superior to commercial hyaluronic acid preparation.


Stratum corneum (SC) bilayer lipids, specifically fatty acids, ceramides and cholesterol, contribute to the permeability barrier function of the skin. Normal skin cleansing is associated with damage to the SC lipids because cleanser surfactants, in addition to providing the desired effect of solubilizing and facilitating the removal of sebum and skin soils, have a propensity to disrupt bilayer lipids by extracting endogenous skin lipids or intercalating into the bilayer. Disrupted SC lipids are associated with a variety of pathological skin conditions, as well as with dry skin induced by harsh cleansing. In an attempt to preserve the barrier and mitigate the damage caused by frequent normal cleansing, the incorporation of physiologically relevant lipids into skin cleansers has become common in leading cleansing products. It has been noted that fatty acids are more susceptible to surfactant‐induced removal than other lipids (eg, ceramides), an observation that may form the basis for a critically important strategy for replenishing SC lipids. This review will focus on the role of fatty acids in the structure and function of the SC, and the rationale for incorporation of stearic acid into moisturizing body cleansers to minimize their extraction by surfactants and replenish lost fatty acids to promote skin barrier preservation.


The narrow host range of infection and lack of suitable tissue culture systems for the propagation of hepatitis B and C viruses are limitations that have prevented a more thorough understanding of persistent infection and the pathogenesis of chronic liver disease. Despite decades of intensive research and significant progresses in understanding of viral hepatitis, many basic questions and clinical problems still await to be resolved. For example, the HBV cellular receptor and related mechanisms of viral entry have not yet been identified. Little is also known about the function of certain non-structural viral products, such as the hepatitis B e antigen and the X protein, or about the role of excess hepadnavirus subviral particles circulating in the blood stream during infection. Furthermore, the molecular mechanisms involved in the development of hepatocellular carcinoma and the role of the immune system in determining the fate of infection are not fully understood. The reason for these drawbacks is essentially due to the lack of reliable cell-based in vitro infection systems and, most importantly, convenient animal models. This lack of knowledge has been partially overcome for hepatitis B virus (HBV), by the discovery and characterization of HBV-like viruses in wild animals while for hepatitis C virus (HCV), related flaviviruses have been used as surrogate systems. Other laboratories have developed transgenic mice that express virus gene products and/or support virus replication. Some HBV transgenic mouse models develop fulminant hepatitis, acute hepatitis, or chronic liver disease after adoptive transfer, and others spontaneously develop hepatocellular carcinoma (HCC). Among HCV transgenic mice, most develop no disease, but acute hepatitis has been observed in one model, and HCC in another. Although mice are not susceptible to HBV and HCV, their ability to replicate these viruses and to develop liver diseases characteristic of human infections provides opportunities to study pathogenesis and develop novel therapeutics In the search for the mechanism of hepatocarcinogenesis in hepatitis viral infection, two viral proteins, the core protein of hepatitis C virus (HCV) and the HBx protein of hepatitis B virus (HBV), have been shown to possess oncogenic potential through transgenic mouse studies, indicating the direct involvement of the hepatitis viruses in hepatocarcinogenesis. This may explain the very high frequency of HCC in patients with HCV or HBV infection. Chimpanzees remain the only recognized animal model for the study of hepatitis C virus (HCV). Studies performed in chimpanzees played a critical role in the discovery of HCV and are continuing to play an essential role in defining the natural history of this important human pathogen. In the absence of a reproducible cell culture system, the infectivity titer of HCV challenge pools can be determined only in chimpanzees. Recent studies in chimpanzees have provided new insight into the nature of host immune responses-particularly the intrahepatic responses-following primary and secondary experimental HCV infections. The immunogenicity and efficacy of vaccine candidates against HCV can be tested only in chimpanzees. Finally, it would not have been possible to demonstrate the infectivity of infectious clones of HCV without chimpanzees. Chimpanzees became infected when RNA transcripts from molecular clones were inoculated directly into the liver. The infection generated by such transfection did not differ significantly from that observed in animals infected intravenously with wild-type HCV. It furthermore permits true homologous challenge in studies of protective immunity and in testing the efficacy of vaccine candidates. Finally, this in vivo transfection system has made it possible to test for the first time the importance of genetic elements for HCV infectivity. Although chimpanzees are the only animals fully permissive for HBV infection, their use for research purpose is severely limited by the high costs and strong ethical constrains. The only alternative source of HBV-permissive hepatocytes is the Asian tree shrew Tupaia belangeri. Though experimental infection of these squirrel-like mammals, phylogenetically related to primates, results only in a mild, transient replication, primary hepatocytes isolated from T. belangeri turned out to be a reliable tool for in vitro HBV infection experiments. Along with invaluable infection studies in chimpanzees, avian and mammalian HBV-related viruses continue to offer ample opportunities for studies in naturally occurring hosts. In general, most of our progresses in hepatitis B virus research are based on infection studies with two HBV-related animal viruses: the woodchuck HBV (WHV), which infects the Eastern American woodchuck (Marmota monax), and the duck HBV (DHBV), which infects Peking ducks. Both animal models have been essential for understanding various steps of viral life-cycle and factors involved in establishment of virus infection, persistence and hepatocarcinogenesis. Studies performed over the last ten years with HBV-replicating transgenic mice demonstrated that this small animal model is suitable to evaluate the impact of antiviral treatment strategies on HBV replication and for immunological studies upon induction of cytokines or adoptive transfer of HBV-specific cytotoxic T lymphocytes (CTLs). More recently, mouse models, based on transfection of recombinant adenoviral vector or hydrodynamic injection of naked DNA, have been developed to investigate mechanisms of viral clearance. Compared with transgenic mice, in vivo transfection systems should enable fast comparison of viral mutants for their replication competence. Nevertheless, for various reasons none of the above mentioned models are ideal, since all natural hosts of HBV-related viruses are of out-bred origin and their immune systems have not been characterized.


Modern internal therapy of skin diseases is based on a knowledge of pharmacology and biochemical pharmacology. The importance of the cytochrome P 450 system and its changes during treatment are referred to. Standard treatment in dermatology is not discussed but the literature is mentioned here. Treatment with glucocorticosteroids and non-steroidal anti-inflammatory substances are discussed in detail. The treatment of porphyria cutanea tarda with chloroquine shows good success. The results of carotinoid therapy of erythropoietic protoporphyria and non-porphyrin induced photodermatoses are debated.