Sequential dual site-selective protein labelling enabled by lysine modification.

Methods that allow for chemical site-selective dual protein modification are scarce. Here, we provide proof-of-concept for the orthogonality and compatibility of a method for regioselective lysine modification with strategies for protein modification at cysteine and genetically encoded ketone-tagged amino acids. This sequential, orthogonal approach was applied to albumin and a therapeutic antibody to create functional dual site-selectively labelled proteins

Report of the Task Force on the Special Educational Needs of Women

On January 17, 1972 an ad hoc committee was appointed to evaluate the special educational needs of women within the University of Maine at Orono/Bangor and in the larger community served by this University. This committee was chaired by Dr. Constance Carlson. PROBLEM : The intellectual, social and professional climate of the University does not encourage women students (undergraduate, graduate, CED, and special) to realize their full intellectual, social and professional potential. SOLUTION: The University environment must become a vital catalyst encouraging each woman student to make the most of the educational opportunity and cultural freedom available at Orono/Bangor thereby achieving her unique potential and developing a self-vision of herself as a responsible human being both in personal and in public life

Doing What You\u27re Told: Following Task Instructions in Changing, but Hospitable Environments

The AnimNL project (Anim ation from N atural L anguage) has as its goal the automatic creation of animated task simulations from natural-language instructions. The question addressed in this paper is how agents can perform tasks in environments about which they have only partial relevant knowledge. The solution we describe involves enabling such agents to * develop expectations through instruction understanding and plan inference, and use those expectations in deciding how to act; * exploit generalized abilities in order to deal with novel geometric situations. The AnimNL project builds on an animation system, Jack™, that has been developed at the Computer Graphics Research Lab at the University of Pennsylvania, and draws upon a range of recent work in Natural Language semantics, planning and plan inference, philosophical studies of intention, reasoning about knowledge and action, and subsumption architectures for autonomous agents

Envisioning the South End of Tomorrow: Live, Work and Recreate in a Transforming Neighborhood

ENVISIONING THE SOUTH END OF TOMORROW – Live, Work and Recreate in a Transforming Neighborhood Background and Challenges Downtown Springfield is currently undergoing a substantial change of the physical urban fabric. The most visible examples are the construction of the MGM Casino Resort and the renovated Union Station into a multimodal transportation hub. The MGM Casino Resort is the first one in the country that is integrated in a core downtown area. It is obvious that downtown and its adjacent districts will change substantially. How can different uses next to each other coexist productively or can negative influences be being mitigated? How can people that live in the South End benefit from urban development? Will their neighborhood become a healthier, more beautiful and more social place? How can the South End maintain its diversity while obtaining more space for expressing culture in a positive way? Method This design studio was a community service learning experience with goals and objectives that derived from informal interviews with people on the streets, stakeholder meetings, personal observations, sketching and case study research. The design solutions can be synthesized with these recommendations: Project Goals: • Create a multi-scalar greenway system for the whole neighborhood that creates a network of green squares and green streets. • Plant big street trees throughout the neighborhood to filter air and make the streets more walkable. • Create a system small places to sit and gather. • Redesign residential streets that prioritizes bicycle and foot traffic. • Create pedestrian crossings for Main Street and East Columbus Avenue to slow traffic down. • Design East and West Columbus Avenue as pedestrian-and bicycle-friendly corridors through a road diet and speed reduction. • Foster Connections underneath I-91 and across the Railroad to engage the Connecticut River and the Riverfront Park. • Create infill development on Main Street that supports local commerce and services. • Use vacant lots in the neighborhood for new housing that is green, innovative and attractive for diverse demographics. • Reduce the impact of stormwater runoff through swales along streets and underused land. • Address the diversity in the neighborhood and embrace the diversity of cultures through visual and performative art and ethnic food. Project Significance: This studio will advise the City of Springfield mitigating the impact of the casino through the media of Landscape Architecture

Inflammation in acute myocardial infarction: the good, the bad and the ugly.

Convergent experimental and clinical evidence have established the pathophysiological importance of pro-inflammatory pathways in coronary artery disease. Notably, the interest in treating inflammation in patients suffering acute myocardial infarction (AMI) is now expanding from its chronic aspects to the acute setting. Few large outcome trials have proven the benefits of anti-inflammatory therapies on cardiovascular outcomes by targeting the residual inflammatory risk (RIR), i.e. the smouldering ember of low-grade inflammation persisting in the late phase after AMI. However, these studies have also taught us about potential risks of anti-inflammatory therapy after AMI, particularly related to impaired host defence. Recently, numerous smaller-scale trials have addressed the concept of targeting a deleterious flare of excessive inflammation in the early phase after AMI. Targeting different pathways and implementing various treatment regimens, those trials have met with varied degrees of success. Promising results have come from those studies intervening early on the interleukin-1 and -6 pathways. Taking lessons from such past research may inform an optimized approach to target post-AMI inflammation, tailored to spare 'The Good' (repair and defence) while treating 'The Bad' (smouldering RIR) and capturing 'The Ugly' (flaming early burst of excess inflammation in the acute phase). Key constituents of such a strategy may read as follows: select patients with large pro-inflammatory burden (i.e. large AMI); initiate treatment early (e.g. ≤12 h post-AMI); implement a precisely targeted anti-inflammatory agent; follow through with a tapering treatment regimen. This approach warrants testing in rigorous clinical trials

Inflammation in acute myocardial infarction: the good, the bad and the ugly

Convergent experimental and clinical evidence have established the pathophysiological importance of pro-inflammatory pathways in coronary artery disease. Notably, the interest in treating inflammation in patients suffering acute myocardial infarction (AMI) is now expanding from its chronic aspects to the acute setting. Few large outcome trials have proven the benefits of anti-inflammatory therapies on cardiovascular outcomes by targeting the residual inflammatory risk (RIR), i.e. the smouldering ember of low-grade inflammation persisting in the late phase after AMI. However, these studies have also taught us about potential risks of anti-inflammatory therapy after AMI, particularly related to impaired host defence. Recently, numerous smaller-scale trials have addressed the concept of targeting a deleterious flare of excessive inflammation in the early phase after AMI. Targeting different pathways and implementing various treatment regimens, those trials have met with varied degrees of success. Promising results have come from those studies intervening early on the interleukin-1 and -6 pathways. Taking lessons from such past research may inform an optimized approach to target post-AMI inflammation, tailored to spare ‘The Good’ (repair and defence) while treating ‘The Bad’ (smouldering RIR) and capturing ‘The Ugly’ (flaming early burst of excess inflammation in the acute phase). Key constituents of such a strategy may read as follows: select patients with large pro-inflammatory burden (i.e. large AMI); initiate treatment early (e.g. ≤12 h post-AMI); implement a precisely targeted anti-inflammatory agent; follow through with a tapering treatment regimen. This approach warrants testing in rigorous clinical trials

The Impact of Adherence to Screening Guidelines and of Diabetes Clinics Referral on Morbidity and Mortality in Diabetes

Despite the heightened awareness of diabetes as a major health problem, evidence on the impact of assistance and organizational factors, as well as of adherence to recommended care guidelines, on morbidity and mortality in diabetes is scanty. We identified diabetic residents in Torino, Italy, as of 1st January 2002, using multiple independent data sources. We collected data on several laboratory tests and specialist medical examinations to compare primary versus specialty care management of diabetes and the fulfillment of a quality-of-care indicator based on existing screening guidelines (GCI). Then, we performed regression analyses to identify associations of these factors with mortality and cardiovascular morbidity over a 4 year- follow-up. Patients with the lowest degree of quality of care (i.e. only cared for by primary care and with no fulfillment of GCI) had worse RRs for all-cause (1.72 [95% CI 1.57–1.89]), cardiovascular (1.74 [95% CI 1.50–2.01]) and cancer (1.35 [95% CI 1.14–1.61]) mortality, compared with those with the highest quality of care. They also showed increased RRs for incidence of major cardiovascular events up to 2.03 (95% CI 1.26–3.28) for lower extremity amputations. Receiving specialist care itself increased survival, but was far more effective when combined with the fulfillment of GCI. Throughout the whole set of analysis, implementation of guidelines emerged as a strong modifier of prognosis. We conclude that management of diabetic patients with a pathway based on both primary and specialist care is associated with a favorable impact on all-cause mortality and CV incidence, provided that guidelines are implemented

Towards a more universal life detection strategy

This white paper argues for a more universal approach to life detection. We recommend that life detection missions focus on looking for signatures of life deemed to be shared by all possible types of life, independent of their specific biochemistries, rather than looking for signatures of life that could arguably be specific to Terran-life

Subsurface scientific exploration of extraterrestrial environments (MINAR 5): analogue science, technology and education in the Boulby Mine, UK

The deep subsurface of other planetary bodies is of special interest for robotic and human exploration. The subsurface provides access to planetary interior processes, thus yielding insights into planetary formation and evolution. On Mars, the subsurface might harbour the most habitable conditions. In the context of human exploration, the subsurface can provide refugia for habitation from extreme surface conditions. We describe the fifth Mine Analogue Research (MINAR 5) programme at 1 km depth in the Boulby Mine, UK in collaboration with Spaceward Bound NASA and the Kalam Centre, India, to test instruments and methods for the robotic and human exploration of deep environments on the Moon and Mars. The geological context in Permian evaporites provides an analogue to evaporitic materials on other planetary bodies such as Mars. A wide range of sample acquisition instruments (NASA drills, Small Planetary Impulse Tool (SPLIT) robotic hammer, universal sampling bags), analytical instruments (Raman spectroscopy, Close-Up Imager, Minion DNA sequencing technology, methane stable isotope analysis, biomolecule and metabolic life detection instruments) and environmental monitoring equipment (passive air particle sampler, particle detectors and environmental monitoring equipment) was deployed in an integrated campaign. Investigations included studying the geochemical signatures of chloride and sulphate evaporitic minerals, testing methods for life detection and planetary protection around human-tended operations, and investigations on the radiation environment of the deep subsurface. The MINAR analogue activity occurs in an active mine, showing how the development of space exploration technology can be used to contribute to addressing immediate Earth-based challenges. During the campaign, in collaboration with European Space Agency (ESA), MINAR was used for astronaut familiarization with future exploration tools and techniques. The campaign was used to develop primary and secondary school and primary to secondary transition curriculum materials on-site during the campaign which was focused on a classroom extra vehicular activity simulation

Identification of a Shared Genetic Susceptibility Locus for Coronary Heart Disease and Periodontitis

Recent studies indicate a mutual epidemiological relationship between coronary heart disease (CHD) and periodontitis. Both diseases are associated with similar risk factors and are characterized by a chronic inflammatory process. In a candidate-gene association study, we identify an association of a genetic susceptibility locus shared by both diseases. We confirm the known association of two neighboring linkage disequilibrium regions on human chromosome 9p21.3 with CHD and show the additional strong association of these loci with the risk of aggressive periodontitis. For the lead SNP of the main associated linkage disequilibrium region, rs1333048, the odds ratio of the autosomal-recessive mode of inheritance is 1.99 (95% confidence interval 1.33–2.94; P = 6.9×10−4) for generalized aggressive periodontitis, and 1.72 (1.06–2.76; P = 2.6×10−2) for localized aggressive periodontitis. The two associated linkage disequilibrium regions map to the sequence of the large antisense noncoding RNA ANRIL, which partly overlaps regulatory and coding sequences of CDKN2A/CDKN2B. A closely located diabetes-associated variant was independent of the CHD and periodontitis risk haplotypes. Our study demonstrates that CHD and periodontitis are genetically related by at least one susceptibility locus, which is possibly involved in ANRIL activity and independent of diabetes associated risk variants within this region. Elucidation of the interplay of ANRIL transcript variants and their involvement in increased susceptibility to the interactive diseases CHD and periodontitis promises new insight into the underlying shared pathogenic mechanisms of these complex common diseases