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\"There are certain things that Yuri Zipit knows: That being official food-taster for the leader of the Soviet Union requires him to drink too much vodka for a 12-year-old. That you do not have to be an Elephantologist to see that the great leader is dying. That Marshal Bruhah has been known to eat his own children, while Comrade Krushka is only fit to run a slaughterhouse, and that one of them has Yuri's father somewhere here in the Dacha. That it's a crime to love your family more than you love Socialism, the Party, or the Motherland. That, because of his damaged mind, everyone thinks Yuri is a fool. But Yuri isn't. He sits quietly through another excessive state dinner and witnesses it all--betrayals, body doubles, buffoonery. He's starting to get the hang of this politics thing, but there's so much to learn. Who knew that a man could be in five places at once? That someone could break your nose as a sign of friendship? That people could be disinvented? The Zoo is a cutting satire, told through the refreshing voice of one gutsy boy who will not give up on hope.\"-- Provided by publisher.

Aims: To improve multidisciplinary team awareness of doctor availability within the East-North-East Leeds Community Learning Disability Team. To create and implement a resource listing accurate availability per half-day, contact details, and named cover in cases of absence. To improve team communication, reduce uncertainty, and streamline contact and escalation processes. To utilise baseline and post-intervention outcome measures to assess improvements in practice. Methods: This project was formulated following reports of uncertainty around doctor availability, inefficient methods of contact attempts, and with no current effective rota system in place. A Plan-Do-Study-Act (PDSA) approach was taken to assess and adopt continuous improvement throughout. Baseline questionnaires were distributed to staff to assess current levels of awareness of doctor availability, escalation pathways, and perceived usefulness of a planned resource. Key stakeholders (consultants, resident doctors, managers, senior administrators) were engaged to adapt and expand a current limited senior doctor rota, to include all doctors, named cover, enhanced contact methods, and a wider audience. This utilised Outlook calendars, was displayed in the team office, and was updated weekly. Post-intervention questionnaires were circulated to assess the impact of the intervention. Further procedures were implemented to sustain this change, including commitments from permanent staff to take responsibility in maintaining the resource, standard operating procedures formulated for administrative and medical teams, and safeguards created to identify future issues encountered. Results: Response rates from staff were 32% and 36% pre- and post-intervention respectively. Staff confidence in knowing which doctors were available and when rose from 22% to 91%. Staff knowledge of how to immediately contact an available doctor rose from 44% to 91%. Staff knowledge of how to further escalate concerns rose from 67% to 91%. 91% of staff reported using the resource, 91% found it useful, and 82% found it accurate. Further adaptations were made as the project progressed and in response to feedback and issues encountered. Conclusion: This project successfully resulted in improving awareness of doctor availability in all domains measured, and was well received. By developing a clear, accessible rota and engaging staff in its use, staff confidence and team communication improved. This project led to lasting changes in practice, ensuring ongoing effectiveness sustained beyond the project’s conclusion. Key points of discussion include engagement of key stakeholders in planning, implementing, and sustaining improvement, ensuring feasibility and longevity. Furthermore, reflecting on the effective use of PDSA principles with simple, measurable changes, and implementing ongoing review processes.

Bdelloid rotifers are a class of microscopic invertebrates that have existed for millions of years apparently without sex or meiosis. They inhabit a variety of temporary and permanent freshwater habitats globally, and many species are remarkably tolerant of desiccation. Bdelloids offer an opportunity to better understand the evolution of sex and recombination, but previous work has emphasised desiccation as the cause of several unusual genomic features in this group. Here, we present high-quality whole-genome sequences of 3 bdelloid species: Rotaria macrura and R. magnacalcarata, which are both desiccation intolerant, and Adineta ricciae, which is desiccation tolerant. In combination with the published assembly of A. vaga, which is also desiccation tolerant, we apply a comparative genomics approach to evaluate the potential effects of desiccation tolerance and asexuality on genome evolution in bdelloids. We find that ancestral tetraploidy is conserved among all 4 bdelloid species, but homologous divergence in obligately aquatic Rotaria genomes is unexpectedly low. This finding is contrary to current models regarding the role of desiccation in shaping bdelloid genomes. In addition, we find that homologous regions in A. ricciae are largely collinear and do not form palindromic repeats as observed in the published A. vaga assembly. Consequently, several features interpreted as genomic evidence for long-term ameiotic evolution are not general to all bdelloid species, even within the same genus. Finally, we substantiate previous findings of high levels of horizontally transferred nonmetazoan genes in both desiccating and nondesiccating bdelloid species and show that this unusual feature is not shared by other animal phyla, even those with desiccation-tolerant representatives. These comparisons call into question the proposed role of desiccation in mediating horizontal genetic transfer.

Design History Beyond the Canon subverts hierarchies of taste which have dominated traditional narratives of design history. The book explores a diverse selection of objects, spaces and media, ranging from high design to mass-produced and mass-marketed objects, as well as counter-cultural and sub-cultural material.0The authors' research highlights the often marginalised role of gender and racial identity in the production and consumption of design, the politics which underpins design practice and the role of designed objects as pathways of nostalgia and cultural memory. While focused primarily on North American examples from the early 20th century onwards, this collection also features essays examining European and Soviet design history, as well as the influence of Asia and Africa on Western design practice. The book is organised in three thematic sections: Consumers, Intermediaries and Designers. The first section analyses a range of designed objects and spaces through the experiences and perspectives of users. The second section considers intermediaries from both technology and the culture industries, as well as the hidden labour within the design process itself by way of patents. The final section focuses on designers from multiple design disciplines including high fashion, industrial design, interior design, graphic design and design history pedagogy. The essays in all three sections utilise different research methods and a wide range of theoretical approaches, including feminist theory, critical race theory, spatial theory, material culture studies, science and technology studies and art history. Design History Beyond the Canon brings together the most recent research which reaches beyond the traditional canon and looks to interdisciplinary methodologies to better understand the practice and consumption of design.

Key Points Gene expression is regulated by transcription factors in concert with epigenetic modifications (such as DNA methylation, post-translational histone modifications, the position and compaction of nucleosomes and higher-order structural organization) at the gene regulatory elements where these factors can bind. Epigenetic modifications are heritable but plastic, thereby allowing cells to modify their gene expression patterns in response to changing contexts, as CD4 + T cells do in response to infection with different types of pathogen. The pace of discovery in the field of epigenetics is accelerating through the application of new genomic approaches, which are yielding new insights on the gene regulatory mechanisms in T helper (T H ) cells and other cell types. Compelling evidence indicates that epigenetic modifications at T H -cytokine and transcription factor gene loci work in concert with lineage-restricted transcription factors to govern cytokine expression and to stabilize lineage commitment. During T H 2-cell differentiation, GATA-binding protein 3 (GATA3) is necessary and apparently sufficient to induce T H 2-type cytokine expression, as well as most, if not all, of the favourable epigenetic modifications to the T H 2-cytokine locus and repressive modifications to the Ifng (interferon-γ) locus. Following these modifications, GATA3 contributes importantly to maintenance of the complete T H 2-cell phenotype but is not absolutely essential for the maintenance of Il4 (interleukin-4) expression. T-bet acts in concert with signal transducer and activator of transcription 4 (STAT4) during T H 1-cell differentiation to induce IFNg expression and epigenetic remodelling of the Ifng locus, and to repress T H 2-cytokine expression directly and through the inhibition of GATA3. The expression of T-bet does not seem to be essential for the maintenance of IFNg expression, but it is required to maintain certain other aspects of the T H 1-cell phenotype. The three-dimensional architecture of the T H 2-cytokine and Ifng loci is modified by 'chromatin looping', which brings distal gene regulatory elements in proximity with genes they help to regulate in appropriate cell types. Additional work is needed to determine how specific combinations of epigenetic modifications are established by networks of lineage-specifying transcription factors, whether, when and how they can later be removed or selectively modified, and their causal contribution to the stability or plasticity of T H -cell lineage specification. Numerous lineage-specific transcription factors have been linked with T-helper-cell subset specification. But, as discussed here, epigenetic modifications at the gene regulatory elements where these factors bind can also contribute to the regulation of T-helper-cell differentiation and function. Naive CD4 + T cells give rise to T-helper-cell subsets with functions that are tailored to their respective roles in host defence. The specification of T-helper-cell subsets is controlled by networks of lineage-specifying transcription factors, which bind to regulatory elements in genes that encode cytokines and other transcription factors. The nuclear context in which these transcription factors act is affected by epigenetic processes, which allow programmes of gene expression to be inherited by progeny cells that at the same time retain the potential for change in response to altered environmental signals. In this Review, we describe these epigenetic processes and discuss how they collaborate to govern the fate and function of T helper cells.

This text analyses co-operation between universities and regional authorities.

In this review, we provide an overview of the US Food and Drug Administration (FDA)-approved clinical uses of vagus nerve stimulation (VNS) as well as information about the ongoing studies and preclinical research to expand the use of VNS to additional applications. VNS is currently FDA approved for therapeutic use in patients aged >12 years with drug-resistant epilepsy and depression. Recent studies of VNS in in vivo systems have shown that it has anti-inflammatory properties which has led to more preclinical research aimed at expanding VNS treatment across a wider range of inflammatory disorders. Although the signaling pathway and mechanism by which VNS affects inflammation remain unknown, VNS has shown promising results in treating chronic inflammatory disorders such as sepsis, lung injury, rheumatoid arthritis (RA), and diabetes. It is also being used to control pain in fibromyalgia and migraines. This new preclinical research shows that VNS bears the promise of being applied to a wider range of therapeutic applications.

ظلت سيرة كريستوف كولومبوس وشخصيته محل نقاش وبحني وتنقيب، ليس فقط في أوروبا بل في جميع الأوساط المعرفية والثقافية والحضارية في العالم. ومع ذلك، مازالت لهذه الشخصية ألغازها ومازالت الأسئلة الحارقة تؤرق الباحثين والدارسين وتملأ رفوف جميع المكتبات في العالم ولعل هذا الكتاب الذي بين أيدينا، من بين أهم الكتب التي أحدثت ثورة فكرية في الآونة الأخيرة، ليس في الأوساط الأكاديمية فحسب بل في عقول القراء للهتمين بأميرال المحيط وبتاريخه الذي كتبت عنه آلاف الكتب. لعل أهم كتاب أعاد الاشتغال على موروث هيرناندو وعلاقته بوالدير كولومبوس هو كتاب \"مكتبة كولومبوس الضائعة\"، حيث اشتغل إدوارد ولسون لي على شخصيتين رئيسيتين، أو ربما يمكننا القول إنه اشتغل على موروث كولومبوس العام انطلاقا من عائلته ومحيطه. ولنكون أكثر دقة، اشتغل الباحث على شخصيتين أساسيتين في شخصية هيرناندو كولون - الذي سوف يأخذ القسط الأكبر من الكتاب. ووالدة کریستوف كولومبوس. فالأول كان مدخلا للحديبي عن الثاني، فكان مؤرا لرحلات والدي ومصدرا لحقائق مهمة تكشف لأول مرة عن الحالة الذي جاب البحار وكان الفاتحة الأولى لبروز مفاهیم کالعالم الجديد والاستعمار والتوسع.

Humans can identify visual objects independently of view angle and lighting, words independently of volume and pitch, and smells independently of concentration. The computational principles underlying invariant object recognition remain mostly unknown. Here we propose that, in olfaction, a small and relatively stable set comprised of the earliest activated receptors forms a code for concentration-invariant odor identity. One prediction of this “primacy coding” scheme is that decisions based on odor identity can be made solely using early odor-evoked neural activity. Using an optogenetic masking paradigm, we define the sensory integration time necessary for odor identification and demonstrate that animals can use information occurring <100 ms after inhalation onset to identify odors. Using multi-electrode array recordings of odor responses in the olfactory bulb, we find that concentration-invariant units respond earliest and at latencies that are within this behaviorally-defined time window. We propose a computational model demonstrating how such a code can be read by neural circuits of the olfactory system. Odor identity remains stable despite changes in concentration yet the neural mechanisms are relatively unknown. Here the authors test a primacy coding model using an optogenetic masking paradigm in mice to show that a set of earliest activated receptors are sufficient to make decisions about odor identity across concentrations.