Immunometabolism, vascular function and atherosclerosis

Cardiovascular disease (CVD) is among the leading causes of death worldwide and atherosclerosis is the primary underlying cause. Several studies in humans have shown that elevated blood leukocytes increase CVD risk. Pathways that regulate cholesterol accumulation in hematopoietic stem cells (HSCs) or macrophages, or hyperglycemia, affect the production of leukocytes, and may thus affect atherogenesis. We found that disturbances in intracellular cholesterol trafficking in Niemann-Pick type C1 (NPC1) disease, an inborn error of metabolism, promote HSCs mobilization to the spleen, likely contributing to splenomegaly, an early symptom of NPC1 disease. We showed that fasting-induced hypoglycemia in a mouse model for glycogen storage disease type Ia (GSD Ia), also an inborn error of metabolism, decreases pro-inflammatory Ly6Chi monocytes upon fasting and proposed that this may explain the limited atherogenesis in GSD Ia patients. We also investigated whether cholesterol accumulation in smooth muscle cells (SMCs) affected vascular function and atherogenesis. SMCs are located in the media of arteries and regulate vasoconstriction via α1-adrenergic receptor (α1-AR) signaling. We found that SMC cholesterol accumulation increased α1-AR dependent vasoconstriction in mice in vivo. While we did not find effects on atherosclerosis, we found that SMC cholesterol accumulation increases bladder size dramatically, in part due to increased SMC constriction. We propose that SMC cholesterol accumulation mechanistically links hypercholesterolemia and bladder outlet obstruction in humans

The Political Economy of Urban Land Reform in Hawaii

In the mid 1960s there were about 22,000 single-family leasehold homes in Honolulu. Dissatisfaction with leasehold led to reform legislation in 1967, allowing lessees to buy leased land. By 1991 less than 5000 lessees remained. This paper examines why landowners elected to lease rather than sell land and attributes the rise of leasehold to legal constraints on land sales by large estates, duties of estate trustees and the federal tax code. Idelogical forces initiated land reform in 1967, but rent-seeking forces captured the process in the mid 1970s. It is concluded that Hawaii's experiment with leasehold was a failure due to the difficulties associated with specifying and enforcing long-term contracts in residential land.

Predator Recognition Behaviors and Stress Hormones in an Endangered Captive Mammal: Implications for Reintroduction

One purpose of captive breeding programs for endangered species is the potential reestablishment of wild populations. However, behavioral problems resulting from relaxed selection or adaptation to captivity can lead to decreased predator recognition and increased mortality in reintroduced individuals. Predator training of prey animals can reduce this mortality, but a species must have some instinctual response to the signs of predators as a prerequisite for successful training. The Tadjik markhor (Capra falconeri heptneri) is one of the most endangered mammals in the world and may be reintroduced to portions of its former range in the future. We assessed the potential of captive Tadjik markhor to recognize signs from their natural predators using visual and olfactory cues, and compared their behavior and stress hormone levels to baseline levels and to novel but non-threatening cues. Mean percent time in vigilance behavior did not differ between predator and control cues, but both were higher than baseline (ANOVA; P \u3c 0.001). However, markhor exhibited more alarm calls and ear flicks when faced with predator cues than when faced with control cues or during baseline observations (MRPP, P \u3c 0.001). We found no difference, however, in fecal glucocorticoid (GC) levels among the three treatment types. These results suggest that captive markhor have not entirely lost their ability to recognize threats from potential predators and may respond to pre-release training in the event of a reintroduction program that uses captive-raised individuals

The benefit of guest loyalty programmes

The aim of this research is to find out what kind of guest loyalty programme Apollo Hotels and Resorts should implement for their individual leisure guests in order to gain more loyal leisure guests. In the literature review of this research, the following aspects are discussed: a loyalty programme and its use; the sort of loyalty programmes; the effects of a loyalty programme; and the wishes and needs of a leisure guest. Surveys were divided among 46 leisure guests of Apollo Hotels and Resorts in order to collect data on consumer demand for a guest loyalty programme. The data shows that it is highly recommended for Apollo Hotels and Resorts to implement a leisure guest loyalty programme based on tiers, with the possibility to redeem the saved credits for discounts at Apollo Hotels and Resorts. Furthermore, the data shows it is important that members of the guest loyalty programme receive special services not available to non-members.Keywords: guest loyalty programme, leisure guests, loyalty programme based on tiers, discounts, personal servic

Molecular dynamics of C-peptide of ribonuclease A studied by replica-exchange Monte Carlo method and diffusion theory

Generalized-ensemble algorithm and diffusion theory have been combined in order to compute the dynamical properties monitored by nuclear magnetic resonance experiments from efficient and reliable evaluation of statistical averages. Replica-exchange Monte Carlo simulations have been performed with a C-peptide analogue of ribonuclease A, and Smoluchowski diffusion equations have been applied. A fairly good agreement between the calculated and measured $^1$H-NOESY NMR cross peaks has been obtained. The combination of these advanced and continuously improving statistical tools allows the calculation of a wide variety of dynamical properties routinely obtained by experiments.Comment: 17 pages, 5 figures, (LaTeX); Chemical Physics Letters, in pres

Implementing social health insurance in Ireland: Report of a meeting and workshop held in Dublin, on December 6th 2010

We considered two basic questions, 'Is it possible to implement Social Health Insurance in Ireland?', and 'How can this be done?'. Can Social Health Insurance be implemented in Ireland? Our answer is a very definite yes. Furthermore, there would be many opportunities, while working towards this end, to improve the performance of our health care system. How can it be implemented? This process will need to be actively managed. There are many difficulties in the Irish health services, but also many opportunities. The greatest strengths are the talented, well-trained and very committed staff. Getting and keeping the support of these staff, for the necessary changes in service delivery, will be critical. Ireland has the capacity to make these changes, but without high quality management, a detailed focussed plan for change, and political support, little will happen. Each step in the change needs to be planned to maintain services, improve service delivery, improve service accountability, and improve service governance. Each sector of the service will need someone to lead the change, and mind that service during the change. Primary care remains under-developed. The HSE plan to develop primary care teams (PCT) has not succeeded. There are several established PCTs which work well. In other areas there are informal arrangements for collaboration, which work well. Overall, there are many useful lessons to learn from the experience so far. Future developments will need to place general practice at the centre of primary care. The mechanisms for doing this will vary from place to place, but need to be developed urgently. Acute hospitals face a crisis of governance. Maurice Hayes' (1) recent report on Tallaght hospital gives an idea of the scale of the changes needed. Tallaght is, we believe, not atypical, and is reputed to be by no means the worst governed hospital in the system. This, alone, should provide a pressing motive for change. Redesigning Irish hospitals to a new mission of supporting primary care, of supporting care in the community where possible can, and must, be done. Long-term care for older people is also a challenge. We advise moving to an integrated needs based system with smooth transitions between different degrees of support at home, and different degrees of support in specialized housing facilities including nursing homes. A similar model should apply to other forms of long-term care, for example for people with a substantial disability. Information systems and management processes both need a major overhaul. The health service remains strikingly under-managed, and fixing this will need a substantial culture change within the services. Wide use of standardized formal project management processes will be vital. There is a separate plan being developed to improve health service IT systems, and implementing this needs to be a high priority. We have not considered other key sectors, for example mental health, disability services, and social services. This does not mean that these are unimportant, merely that we had limited time, and a great deal to cover

Regional perturbation of gene transcription is associated with intrachromosomal rearrangements and gene fusion transcripts in high grade ovarian cancer.

Genomic rearrangements are a hallmark of cancer biology and progression, allowing cells to rapidly transform through alterations in regulatory structures, changes in expression patterns, reprogramming of signaling pathways, and creation of novel transcripts via gene fusion events. Though functional gene fusions encoding oncogenic proteins are the most dramatic outcomes of genomic rearrangements, we investigated the relationship between rearrangements evidenced by fusion transcripts and local expression changes in cancer using transcriptome data alone. 9,953 gene fusion predictions from 418 primary serious ovarian cancer tumors were analyzed, identifying depletions of gene fusion breakpoints within coding regions of fused genes as well as an N-terminal enrichment of breakpoints within fused genes. We identified 48 genes with significant fusion-associated upregulation and furthermore demonstrate that significant regional overexpression of intact genes in patient transcriptomes occurs within 1 megabase of 78 novel gene fusions that function as central markers of these regions. We reveal that cancer transcriptomes select for gene fusions that preserve protein and protein domain coding potential. The association of gene fusion transcripts with neighboring gene overexpression supports rearrangements as mechanism through which cancer cells remodel their transcriptomes and identifies a new way to utilize gene fusions as indicators of regional expression changes in diseased cells with only transcriptomic data

Politics, Improvisation, and Musicking in Frederic Rzewski\u27s Which Side Are You On? from \u3ci\u3eNorth American Ballads\u3c/i\u3e

Discussions of the role of politics in Frederic Rzewski\u27s music generally stop at surface elements: the title of the work, the use of a particular song, and guesses as to what left-leaning audience the piece is directed at. Similarly, discussion of the role of improvisation in Rzewski\u27s work begins and ends simply at the mention of its existence. Using transcription and analysis of improvisations from recordings of Which Side Are You On? from North American Ballads combined with ideas about modeling from Christian Asplund, musicking from Christopher Small, dialogue from David Bohm, and Rzewski\u27s own writings about music, I demonstrate how the political manifests at every level of the music, enabling listeners and performers to experience a socio-political situation beyond mere sloganeering, and the essential role improvisation plays in creating that experience

Grunt Work for the Avant-Garde

grunt work for the avant-garde is an original, four-movement composition for solo trombone, clarinet, violin, cello, and accordion