Genetic diversity of EBV-encoded LMP1 in the Swiss HIV Cohort Study and implication for NF-Κb activation

Epstein-Barr virus (EBV) is associated with several types of cancers including Hodgkin's lymphoma (HL) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane protein 1 (LMP1), a multifunctional oncoprotein, is a powerful activator of the transcription factor NF-κB, a property that is essential for EBV-transformed lymphoblastoid cell survival. Previous studies reported LMP1 sequence variations and induction of higher NF-κB activation levels compared to the prototype B95-8 LMP1 by some variants. Here we used biopsies of EBV-associated cancers and blood of individuals included in the Swiss HIV Cohort Study (SHCS) to analyze LMP1 genetic diversity and impact of sequence variations on LMP1-mediated NF-κB activation potential. We found that a number of variants mediate higher NF-κB activation levels when compared to B95-8 LMP1 and mapped three single polymorphisms responsible for this phenotype: F106Y, I124V and F144I. F106Y was present in all LMP1 isolated in this study and its effect was variant dependent, suggesting that it was modulated by other polymorphisms. The two polymorphisms I124V and F144I were present in distinct phylogenetic groups and were linked with other specific polymorphisms nearby, I152L and D150A/L151I, respectively. The two sets of polymorphisms, I124V/I152L and F144I/D150A/L151I, which were markers of increased NF-κB activation in vitro, were not associated with EBV-associated HL in the SHCS. Taken together these results highlighted the importance of single polymorphisms for the modulation of LMP1 signaling activity and demonstrated that several groups of LMP1 variants, through distinct mutational paths, mediated enhanced NF-κB activation levels compared to B95-8 LMP1.

The Supportive Role of the Family in Solving Real and Projected Problems of Everyday Life

In this research the supportive role of the family in coping with everyday problems was studied using two large data sets. The results show the importance of the structural aspect of social support. Mapping individual preferences to support referents showed the crucial role of spouse and parents in solving everyday problems. The individual choices of particular support referents could be fairly accurately predicted from knowledge of the composition of the family, in both categorical regression and logit models. The far lower predictability of the criterion variable was shown using a wide range of socioeconomic, social and demographic indicators. Residence in small cities and indicators of extreme occupational strata were particularly predictive of the choice of support referent. The supportive role of the family was also traced in the personal projects of young adults, which were seen as ecological, natural and dynamic middle-level units of analysis of personality. Different aspects of personal projects, including reliance on social support referents, turned out to be highly interrelated. One the one hand, expectations of support were determined by the content of the project, and on the other, expected social support also influences the content of the project. Sivuha sees this as one of the ways others can enter self-structures.

Problem of Tragedy and Tragic Consciousness in Russia at the turn of the 19th Century

This project intertwines philosophical and historico-literary themes, taking as its starting point the concept of tragic consciousness inherent in the epoch of classicism. The research work makes use of ontological categories in order to describe the underlying principles of the image of the world which was created in philosophical and scientific theories of the 17th century as well as in contemporary drama. Using these categories brought Mr. Vilk to the conclusion that the classical picture of the world implied a certain dualism; not the Manichaean division between light and darkness but the discrimination between nature and absolute being, i.e. God. Mr. Vilk begins with an examination of the philosophical essence of French classical theatre of the XVII and XVIII centuries. The history of French classical tragedy can be divided into three periods: from the mid 17th to early 19th centuries when it triumphed all over France and exerted a powerful influence over almost all European countries; followed by the period of its rejection by the Romantics, who declared classicism to be "artificial and rational"; and finally our own century which has taken a more moderate line. Nevertheless, French classical tragedy has never fully recovered its status. Instead, it is ancient tragedy and the works of Shakespeare that are regarded to be the most adequate embodiment of the tragic. Consequently they still provoke a great number of new interpretations ranging from specialised literary criticism to more philosophical rumination. An important feature of classical tragedy is a system of rules and unities which reveals a hidden ontological structure of the world. The ontological picture of the dramatic world can be described in categories worked out by medieval philosophy - being, essence and existence. The first category is to be understood as a tendency toward permanency and stability (within eternity) connected with this or that fragment of dramatic reality. The second implies a certain set of permanent elements that make up the reality. And the third - existence - should be understood as "an act of being", as a realisation of permanently renewed processes of life. All of these categories can be found in every artistic reality but the accents put on one or another and their interrelations create different ontological perspectives. Mr. Vilk plots the movement of thought, expressed in both philosophical and scientific discourses, away from Aristotle's essential forms, and towards a prioritising of existence, and shows how new forms of literature and drama structured the world according to these evolving requirements. At the same time the world created in classical tragedy fully preserves another ontological paradigm - being - as a fundamental permanence. As far as the tragic hero's motivations are concerned this paradigm is revealed in the dedication of his whole self to some cause, and his oath of fidelity, attitudes which shape his behaviour. It may be the idea of the State, or personal honour, or something borrowed from the emotional sphere, passionate love. Mr. Vilk views the conflicting ambivalence of existence and being, duty as responsibility and duty as fidelity, as underlying the main conflict of classical tragedy of the 17th century. Having plotted the movement of the being/existence duality through its manifestations in 17th century tragedy, Mr. Vilk moves to the 18th century, when tragedy took a philosophical turn. A dualistic view of the world became supplanted by the Enlightenment idea of a natural law, rooted in nature. The main point of tragedy now was to reveal that such conflicts as might take place had an anti-rational nature, that they arose as the result of a kind of superstition caused by social reasons. These themes Mr. Vilk now pursues through Russian dramatists of the 18th and early 19th centuries. He begins with Sumarakov, whose philosophical thought has a religious bias. According to Sumarakov, the dualism of the divineness and naturalness of man is on the one hand an eternal paradox, and on the other, a moral challenge for humans to try to unite the two opposites. His early tragedies are not concerned with social evils or the triumph of natural feelings and human reason, but rather the tragic disharmony in the nature of man and the world. Mr Vilk turns next to the work of Kniazhnin. He is particularly keen to rescue his reputation from the judgements of critics who accuse him of being imitative, and in order to do so, analyses in detail the tragedy "Dido", in which Kniazhnin makes an attempt to revive the image of great heroes and city-founders. Aeneas represents the idea of the "being" of Troy, his destiny is the re-establishment of the city (the future Rome). The moral aspect behind this idea is faithfulness, he devotes himself to Gods. Dido is also the creator of a city, endowed with "natural powers" and abilities, but her creation is lacking internal stability grounded in "being". The unity of the two motives is only achieved through Dido's sacrifice of herself and her city to Aeneus. Mr Vilk's next subject is Kheraskov, whose peculiarity lies in the influence of free-mason mysticism on his work. This section deals with one of the most important philosophical assumptions contained in contemporary free-mason literature of the time - the idea of the trinitarian hierarchy inherent in man and the world: body - soul - spirit, and nature - law - grace. Finally, Mr. Vilk assess the work of Ozerov, the last major Russian tragedian. The tragedies which earned him fame, "Oedipus in Athens", "Fingal" and "Dmitri Donskoi", present a compromise between the Enlightenment's emphasis on harmony and ontological tragic conflict. But it is in "Polixene" that a real meeting of the Russian tradition with the age-old history of the genre takes place. The male and female characters of "Polixene" distinctly express the elements of "being" and "existence". Each of the participants of the conflict possesses some dominant characteristic personifying a certain indispensable part of the moral world, a certain "virtue". But their independent efforts are unable to overcome the ontological gap separating them. The end of the tragedy - Polixene's sacrificial self-immolation - paradoxically combines the glorification of each party involved in the conflict, and their condemnation. The final part of Mr. Vilk's research deals with the influence of "Polixene" upon subsequent dramatic art. In this respect Katenin's "Andromacha", inspired by "Polixene", is important to mention. In "Andromacha" a decisive divergence from the principles of the philosophical tragedy of Russian classicism and the ontology of classicism occurs: a new character appears as an independent personality, directed by his private interest. It was Katenin who was to become the intermediary between Pushkin and classical tragedy.

Semiparametric Methods for Semi-competing Risks Problem with Censoring and Truncation

Studies of chronic life-threatening diseases often involve both mortality and morbidity. In observational studies, the data may also be subject to administrative left truncation and right censoring. Since mortality and morbidity may be correlated and mortality may censor morbidity, the Lynden-Bell estimator for left truncated and right censored data may be biased for estimating the marginal survival function of the non-terminal event. We propose a semiparametric estimator for this survival function based on a joint model for the two time-to-event variables, which utilizes the gamma frailty specification in the region of the observable data. Firstly, we develop a novel estimator for the gamma frailty parameter under left truncation. Using this estimator, we then derive a closed form estimator for the marginal distribution of the non-terminal event. The large sample properties of the estimators are established via asymptotic theory. The methodology performs well with moderate sample sizes, both in simulations and in an analysis of data from a diabetes registry.

Hamilton-Waterloo problem with triangle and C9 factors

The Hamilton-Waterloo problem and its spouse-avoiding variant for uniform cycle sizes asks if Kv, where v is odd (or Kv - F, if v is even), can be decomposed into 2-factors in which each factor is made either entirely of m-cycles or entirely of n-cycles. This thesis examines the case in which r of the factors are made up of cycles of length 3 and s of the factors are made up of cycles of length 9, for any r and s. We also discuss a constructive solution to the general (m,n) case which fixes r and s.

A Study and Application of the Process of Supergene Enrichment of Silver Ores.

In many deposits of silver ores the grade of the ore de­creases considerably a few hundred feet below the surface. It is believed that in many cases the better ores owe their richness in part to the process of sulphide enrichment. It is recognized, however, that many rich silver ores are hypogene deposits that have been affected very little, if any, by processes of enrichment.

Study and Correlation of Belt and Cambrian Arkoses near Limespur, Montana

In the vicinity of Limespur, Montana, a siding along the Northern Pacific Railroad near Whitehall, Montana, occurs a characteristic type of arkose where­ in many small red mineral grains are distributed throughout the rock mass. It is in this respect that this arkose differs from other arkoses in the surrounding region.

Ein neues psychoendokrin-validiertes Verfahren zur Erfassung von Stressbewältigungsfertigkeiten (ISBF)

Background: We previously found good psychometric properties of the Inventory for assessment of stress management skills (German translation: Inventar zur Erfassung von Stressbewältigungsfertigkeiten), ISBF, a short questionnaire for combined assessment of different perceived stress management skills in the general population. Here, we investigate whether stress management skills as measured by ISBF relate to cortisol stress reactivity in two independent studies, a laboratory study (study 1) and a field study (study 2). Methods: 35 healthy non-smoking and medication-free men in study 1 (age mean±SEM:38.0±1.6) and 35 male and female employees in study 2 (age mean±SEM:32.9±1.2) underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. We assessed stress management skills (ISBF) and measured salivary cortisol before and after stress and several times up to 60 min (study 2) and 120 min (study 1) thereafter. Potential confounders were controlled. Results:. General linear models controlling for potential confounders revealed that in both studies, higher stress management skills (ISBF total score) were independently associated with lower cortisol levels before and after stress (main effects ISBF: p’s<.055) and lower cortisol stress reactivity (interaction ISBF-by-stress: p’s<.029). Post-hoc-testing of ISBF subscales suggest lower cortisol stress reactivity with higher “relaxation abilities” (both studies) and higher scores in the scale “cognitive strategies and problem solving” (study 2). Conclusions: Our findings suggest blunted increases in cortisol following stress with increasing stress management skills as measured by ISBF. This suggests that the ISBF not only relates to subjective psychological but also objective physiological stress indicators which may further underscore the validity of the questionnaire.

Casting materials and their application in research and teaching

From a biological point of view, casting refers to filling of anatomical and/or pathological spaces with extraneous material that reproduces a three-dimensional replica of the space. Casting may be accompanied by additional procedures such as corrosion, in which the soft tissue is digested out, leaving a clean cast, or the material may be mixed with radiopaque substances to allow x-ray photography or micro computed topography (µCT) scanning. Alternatively, clearing of the surrounding soft tissue increases transparency and allows visualization of the casted cavities. Combination of casting with tissue fixation allows anatomical dissection and didactic surgical procedures on the tissue. Casting materials fall into three categories namely, aqueous substances (India ink, Prussian blue ink), pliable materials (gelatins, latex, and silicone rubber), or hard materials (methyl methacrylates, polyurethanes, polyesters, and epoxy resins). Casting has proved invaluable in both teaching and research and many phenomenal biological processes have been discovered through casting. The choice of a particular material depends inter alia on the targeted use and the intended subsequent investigative procedures, such as dissection, microscopy, or µCT. The casting material needs to be pliable where anatomical and surgical manipulations are intended, and capillary-passable for ultrastructural investigations.

Fatal contact shot to the chest caused by the gas jet from a muzzle-loading pistol discharging only black powder and no bullet: case study and experimental simulation of the wounding effect.

In modern medico-legal literature, only a small number of publications deal with fatal injuries from black powder guns. Most of them focus on the morphological features such as intense soot soiling, blast tattooing and burn effects in close-range shots or describe the wound ballistics of spherical lead bullets. Another kind of "unusual" and potentially lethal weapons are handguns destined for firing only blank cartridges such as starter and alarm pistols. The dangerousness of these guns is restricted to very close and contact range shots and results from the gas jet produced by the deflagration of the propellant. The present paper reports on a suicide committed with a muzzle-loading percussion pistol cal. 45. An unusually large stellate entrance wound was located in the precordial region, accompanied by an imprint mark from the ramrod and a faint greenish discoloration (apparently due to the formation of sulfhemoglobin). Autopsy revealed an oversized powder cavity, multiple fractures of the anterior thoracic wall as well as ruptures of the heart, the aorta, the left hepatic lobe and the diaphragm. In total, the zone of mechanical destruction had a diameter of approx. 15 cm. As there was no exit wound and no bullet lodged in the body, the injury was caused exclusively by the inrushing combustion gases of the propellant (black powder) comparable with the gas jet of a blank cartridge gun. In contact shots to ballistic gelatine using the suicide's pistol loaded with black powder but no projectile, the formation of a nearly spherical cavity could be demonstrated by means of a high-speed camera. The extent of the temporary cavity after firing with 5 g of black powder roughly corresponded to the zone of destruction found in the suicide's body.