Definition of Mafa-A and -B haplotypes in pedigreed cynomolgus macaques (Macaca fascicularis)

The major histocompatibility complex (MHC) class I B gene/allelic repertoire was investigated in a pedigreed population of cynomolgus macaques of mixed Indonesian/Malaysian origin. The Mafa-B alleles detected in this cohort are mostly specific for a given geographic area, and only a small number of alleles appears to be shared with other populations. This suggests the fast evolution of Mafa-B alleles due to adaptation to new environments. In contrast to humans, the B locus in Old World monkeys displays extensive copy number variation. The Mafa-B and previously defined -A gene combinations segregate in families and thus allowed the definition of extended haplotypes. In many cases it was possible to assign a particular Mafa-I allele to one of these Mafa-A/B haplotypes as well. The presence of a large number of stable haplotypes in this cohort of animals, which was pedigreed for up to eight generations, looks promising for developing discriminative MHC typing tools that are less cumbersome. Furthermore, the discovery of 53 unreported Mafa-B sequences expands the lexicon of alleles significantly, and may help in understanding the complex organisation of the macaque B region

Effective peer-to-peer support for young people with end-stage renal disease: a mixed methods evaluation of Camp COOL

__Abstract__ __Background__ The Camp COOL programme aims to help young Dutch people with end-stage renal disease (ESRD) develop self-management skills. Fellow patients already treated in adult care (hereafter referred to as ‘buddies’) organise the day-to-day program, run the camp, counsel the attendees, and also participate in the activities. The attendees are young people who still have to transfer to adult care. This study aimed to explore the effects of this specific form of peer-to-peer support on the self-management of young people (16–25 years) with ESRD who participated in Camp COOL (CC) (hereafter referred to as ‘participants’). __Methods__ A mixed methods research design was employed. Semi-structured interviews (n = 19) with initiators/staff, participants, and healthcare professionals were conducted. These were combined with retrospective and pre-post surveys among participants (n = 62), and observations during two camp weeks. __Results__ Self-reported effects of participants were: increased self-confidence, more disease-related knowledge, feeling capable of being more responsible and open towards others, and daring to stand up for yourself. According to participants, being a buddy or having one positively affected them. Self-efficacy of attendees and independence of buddies increased, while attendees’ sense of social inclusion decreased (measured as domains of health-related quality of life). The buddy role was a pro-active combination of being supervisor, advisor, and leader. __Conclusions__ Camp COOL allowed young people to support each other in adjusting to everyday life with ESRD. Participating in the camp positively influenced self-management in this group. Peerto- peer support through buddies was much appreciated. Support from young adults was not only beneficial for adolescent attendees, but also for young adult buddies. Paediatric nephrologists are encouraged to refer patients to CC and to facilitate such initiatives. Together with nephrologists in adult care, they could take on a role in selecting buddies

Cottrell Scholars Collaborative New Faculty Workshop: Professional Development for New Chemistry Faculty and Initial Assessment of Its Efficacy

The Cottrell Scholars Collaborative New Faculty Workshop (CSC NFW) is a professional development program that was initiated in 2012 to address absences in the preparation of chemistry faculty at research universities as funded researchers and educators (i.e., teacher–scholars). The primary focus of the workshop is an introduction to evidence-based teaching methods; other topics including mentoring, work–life balance, time management, and grant writing are also addressed. A longer-term aim of the workshop is to develop lifelong teacher–scholars by encouraging workshop participants to engage with teaching-focused faculty learning communities through the CSC NFW and at their institutions. The workshop also provides a platform to investigate the adoption of student-centered pedagogies among new faculty, and a study of that process was initiated concurrently. Thus, the aim of the workshop program is to address professional development needs as well as understand the efficacy of that effort

Human monoclonal antibodies targeting carbonic anhydrase IX for the molecular imaging of hypoxic regions in solid tumours

BACKGROUND: Hypoxia, which is commonly observed in areas of primary tumours and of metastases, influences response to treatment. However, its characterisation has so far mainly been restricted to the ex vivo analysis of tumour sections using monoclonal antibodies specific to carbonic anhydrase IX (CA IX) or by pimonidazole staining, after the intravenous administration of this 2-nitroimidazole compound in experimental animal models.METHODS: In this study, we describe the generation of high-affinity human monoclonal antibodies (A3 and CC7) specific to human CA IX, using phage technology.RESULTS: These antibodies were able to stain CA IX ex vivo and to target the cognate antigen in vivo. In one of the two animal models of colorectal cancer studied (LS174T), CA IX imaging closely matched pimonidazole staining, with a preferential staining of tumour areas characterised by little vascularity and low perfusion. In contrast, in a second animal model (SW1222), distinct staining patterns were observed for pimonidazole and CA IX targeting. We observed a complementary pattern of tumour regions targeted in vivo by the clinical-stage vascular-targeting antibody L19 and the anti-CA IX antibody A3, indicating that a homogenous pattern of in vivo tumour targeting could be achieved by a combination of the two antibodies.CONCLUSION: The new human anti-CA IX antibodies are expected to be non-immunogenic in patients with cancer and may serve as broadly applicable reagents for the non-invasive imaging of hypoxia and for pharmacodelivery applications. British Journal of Cancer (2009) 101, 645-657. doi: 10.1038/sj.bjc.6605200 www.bjcancer.com Published online 21 July 2009 (C) 2009 Cancer Research U

Genomic plasticity of the MHC class I A region in rhesus macaques: extensive haplotype diversity at the population level as revealed by microsatellites

The Mamu-A genes of the rhesus macaque show different degrees of polymorphism, transcription level variation, and differential haplotype distribution. Per haplotype, usually one “major” transcribed gene is present, A1 (A7), in various combinations with “minor” genes, A2 to A6. In silico analysis of the physical map of a heterozygous animal revealed the presence of similar Mamu-A regions consisting of four duplication units, but with dissimilar positions of the A1 genes on both haplotypes, and in combination with different minor genes. Two microsatellites, D6S2854 and D6S2859, have been selected as potential tools to characterize this complex region. Subsequent analysis of a large breeding colony resulted in the description of highly discriminative patterns, displaying copy number variation in concert with microsatellite repeat length differences. Sequencing and segregation analyses revealed that these patterns are unique for each Mamu-A haplotype. In animals of Indian, Burmese, and Chinese origin, 19, 15, or 9 haplotypes, respectively, could be defined, illustrating the occurrence of differential block duplications and subsequent rearrangements by recombination. The haplotypes can be assigned to 12 unique combinations of genes (region configurations). Although most configurations harbor two transcribed A genes, one or three genes per haplotype are also present. Additionally, haplotypes lacking an A1 gene or with an A1 duplication appear to exist. The presence of different transcribed A genes/alleles in monkeys from various origins may have an impact on differential disease susceptibilities. The high-throughput microsatellite technique will be a valuable tool in animal selection for diverse biomedical research projects

Securitization, Deregulation, Economic Stability, And Financial Crisis, Part II - Deregulation, the Financial Crisis, and Policy Implications

This study analyzes the trends in the financial sector over the past 30 years, and argues that unsupervised financial innovations and lenient government regulation are at the root of the current financial crisis and recession. Combined with a long period of economic expansion during which default rates were stable and low, deregulation and unsupervised financial innovations generated incentives to make risky financial decisions. Those decisions were taken because it was the only way for financial institutions to maintain market share and profitability. Thus, rather than putting the blame on individuals, this paper places it on an economic setup that requires the growing use of Ponzi processes during enduring economic expansion, and on a regulatory system that is unwilling to recognize (on the contrary, it contributes to) the intrinsic instability of market mechanisms. Subprime lending, greed, and speculation are merely aspects of the larger mechanisms at work. It is argued that we need to change the way we approach the regulation of financial institutions and look at what has been done in other sectors of the economy, where regulation and supervision are proactive and carefully implemented in order to guarantee the safety of society. The criterion for regulation and supervision should be neither Wall Street’s nor Main Street’s interests but rather the interests of the socioeconomic system. The latter requires financial stability if it’s to raise, durably, the standard of living of both Wall Street and Main Street. Systemic stability, not profits or homeownership, should be the paramount criterion for financial regulation, since systemic stability is required to maintain the profitability - and ultimately, the existence - of any capitalist economic entity. The role of the government is to continually counter the Ponzi tendencies of market mechanisms, even if they are (temporarily) improving standards of living, and to encourage economic agents to develop safe and reliable financial practices. - See also, Working Paper No. 573.1, 'Securitization, Deregulation, Economic Stability, and Financial Crisis, Part I: The Evolution of Securitization.

Urinary pCO2 Monitoring System with a Planar Severinghaus Type Sensor

A urinary pCO2 measurement system with a miniature planar CO2 probe has been developed for monitoring pCO2 levels in the urine (U-pCO2) of catheterized septic shock patients. U-pCO2 may provide timely recognition of changes in the microcirculatory status of patients and used as an “early” warning of metabolic-cellular dysfunction. The utility of the U-pCO2 sensor has been demonstrated in monitoring experiments in a model bladder. The agreement between U-pCO2 values measured with the planar pCO2 probe and a commercial pCO2 probe in pooled urine samples projects the possibility of the implementation of the U-pCO2 measurement system for bedside monitoring

IMACCS: A Progress Report on NASA/GSFC's COTS-Based Ground Data Systems, and Their Extension into New Domains

International Telemetering Conference Proceedings / October 28-31, 1996 / Town and Country Hotel and Convention Center, San Diego, CaliforniaThe Integrated Monitoring, Analysis, and Control COTS System (IMACCS), a system providing real time satellite command and telemetry support, orbit and attitude determination, events prediction, and data trending, was implemented in 90 days at NASA Goddard Space Flight Center (GSFC) in 1995. This paper describes upgrades made to the original commercial, off-the-shelf (COTS)-based prototype. These upgrades include automation capability and spacecraft Integration and Testing (I&T) capability. A further extension to the prototype is the establishment of a direct RF interface to a spacecraft. As with the original prototype, all of these enhancements required lower staffing levels and reduced schedules compared to custom system development approaches. The team's approach to system development, including taking advantage of COTS and legacy software, is also described.International Foundation for TelemeteringProceedings from the International Telemetering Conference are made available by the International Foundation for Telemetering and the University of Arizona Libraries. Visit http://www.telemetry.org/index.php/contact-us if you have questions about items in this collection

PEDOT(PSS) as Solid Contact for Ion-Selective Electrodes: The Influence of the PEDOT(PSS) Film Thickness on the Equilibration Times

To understand the rate determining processes during the equilibration of poly(3,4-ethylenedioxythiophene):polystyrenesulfonate-based (PEDOT(PSS)-based) solid contact (SC) ion-selective electrodes (ISEs), the surfaces of Pt, Au, and GC electrodes were coated with 0.1, 1.0, 2.0, and 4.0 µm thick galvanostatically deposited PEDOT(PSS) films. Next, potential vs time transients were recorded with these electrodes, with and without an additional potassium ion-selective membrane (ISM) coating, following their first contact with 0.1 M KCl solutions. The transients were significantly different when the multilayered sensor structures were assembled on Au or GC compared to Pt. The differences in the rate of equilibration were interpreted as a consequence of differences in the hydrophilicity of PEDOT(PSS) in contact with the substrate electrode surfaces based on X-ray photoelectron spectroscopy (XPS) and synchrotron radiation-XPS (SR-XPS) analysis of 10-100 nm thick PEDOT(PSS) films. The influence of the layer thickness of the electrochemically deposited PEDOT(PSS)-films on the hydrophilicity of these films has been documented by contact angle measurements over PEDOT(PSS)-coated Au, GC, and Pt electrode surfaces. This study demonstrates that it is possible to minimize the equilibration (conditioning) time of SC ISEs with aqueous solutions before usage by optimizing the thickness of the SC layer with a controlled ISM thickness. PEDOT(PSS)-coated Au and GC electrodes exhibit a significant negative potential drift during their equilibration in an aqueous solution. By coating the PEDOT(PSS) surface with an ISM, the negative potential drift is compensated by a positive potential drift related to the hydration of the ISM and activity changes at the PEDOT(PSS)|ISM interface. The potential drifts related to activity changes in the ISM have been determined by a novel adaptation of the "sandwich membrane" method