Sialic acids in biological and therapeutic processes: opportunities and challenges

It is now well documented that carbohydrates play multiple roles in biological processes, and hence are interesting targets for chemical biology and medicinal chemistry programmes. This review focuses on a subset of carbohydrates, specifically sialic acid containing carbohydrates. It highlights their occurrence and diversity, and presents evidence for their roles in a range of biological pathways. It illustrates that they are targets for novel medicinal chemistry strategies for a range of therapeutic areas, including cancer and immunity. Case studies highlight opportunities and challenges in this area, and sialic acid based drugs that have entered clinical practice, and are promising candidates for future disease intervention schemes, are discussed. The review concludes by highlighting perspectives and emerging roles for these targets

Moisture transport by Atlantic tropical cyclones onto the North American continent

Tropical Cyclones (TCs) are an important source of freshwater for the North American continent. Many studies have tried to estimate this contribution by identifying TC-induced precipitation events, but few have explicitly diagnosed the moisture fluxes across continental boundaries. We design a set of attribution schemes to isolate the column-integrated moisture fluxes that are directly associated with TCs and to quantify the flux onto the North American Continent due to TCs. Averaged over the 2004–2012 hurricane seasons and integrated over the western, southern and eastern coasts of North America, the seven schemes attribute 7 to 18 % (mean 14 %) of total net onshore flux to Atlantic TCs. A reduced contribution of 10 % (range 9 to 11 %) was found for the 1980–2003 period, though only two schemes could be applied to this earlier period. Over the whole 1980–2012 period, a further 8 % (range 6 to 9 % from two schemes) was attributed to East Pacific TCs, resulting in a total TC contribution of 19 % (range 17 to 22 %) to the ocean-to-land moisture transport onto the North American continent between May and November. Analysis of the attribution uncertainties suggests that incorporating details of individual TC size and shape adds limited value to a fixed radius approach and TC positional errors in the ERA-Interim reanalysis do not affect the results significantly, but biases in peak wind speeds and TC sizes may lead to underestimates of moisture transport. The interannual variability does not appear to be strongly related to the El Nino-Southern Oscillation phenomenon

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel. In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime, compute the two-point correlation functions of these perturbations and prove that Minkowski spacetime is a stable solution of semiclassical gravity. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a black hole and describe the metric fluctuations near the event horizon of an evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews in Relativity gr-qc/0307032 ; it includes new sections on the Validity of Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric Fluctuations of an Evaporating Black Hol

Instructional multimedia: An investigation of student and instructor attitudes and student study behavior

<p>Abstract</p> <p>Background</p> <p>Educators in allied health and medical education programs utilize instructional multimedia to facilitate psychomotor skill acquisition in students. This study examines the effects of instructional multimedia on student and instructor attitudes and student study behavior.</p> <p>Methods</p> <p>Subjects consisted of 45 student physical therapists from two universities. Two skill sets were taught during the course of the study. Skill set one consisted of knee examination techniques and skill set two consisted of ankle/foot examination techniques. For each skill set, subjects were randomly assigned to either a control group or an experimental group. The control group was taught with live demonstration of the examination skills, while the experimental group was taught using multimedia. A cross-over design was utilized so that subjects in the control group for skill set one served as the experimental group for skill set two, and vice versa. During the last week of the study, students and instructors completed written questionnaires to assess attitude toward teaching methods, and students answered questions regarding study behavior.</p> <p>Results</p> <p>There were no differences between the two instructional groups in attitudes, but students in the experimental group for skill set two reported greater study time alone compared to other groups.</p> <p>Conclusions</p> <p>Multimedia provides an efficient method to teach psychomotor skills to students entering the health professions. Both students and instructors identified advantages and disadvantages for both instructional techniques. Reponses relative to instructional multimedia emphasized efficiency, processing level, autonomy, and detail of instruction compared to live presentation. Students and instructors identified conflicting views of instructional detail and control of the content.</p

Internal and external forcing of multidecadal Atlantic climate variability over the past 1,200 years

The North Atlantic experiences climate variability on multidecadal scales, which is sometimes referred to as Atlantic multidecadal variability. However, the relative contributions of external forcing such as changes in solar irradiance or volcanic activity and internal dynamics to these variations are unclear. Here we provide evidence for persistent summer Atlantic multidecadal variability from AD 800 to 2010 using a network of annually resolved terrestrial proxy records from the circum-North Atlantic region. We find that large volcanic eruptions and solar irradiance minima induce cool phases of Atlantic multidecadal variability and collectively explain about 30% of the variance in the reconstruction on timescales greater than 30 years. We are then able to isolate the internally generated component of Atlantic multidecadal variability, which we define as the Atlantic multidecadal oscillation. We find that the Atlantic multidecadal oscillation is the largest contributor to Atlantic multidecadal variability over the past 1,200 years. We also identify coherence between the Atlantic multidecadal oscillation and Northern Hemisphere temperature variations, leading us to conclude that the apparent link between Atlantic multidecadal variability and regional to hemispheric climate does not arise solely from a common response to external drivers, and may instead reflect dynamic processes

Variation, variability, and the origin of the avian endocranium:Insights from the anatomy of alioramus altai (theropoda: Tyrannosauroidea)

The internal braincase anatomy of the holotype of Alioramus altai, a relatively small-bodied tyrannosauroid from the Late Cretaceous of Mongolia, was studied using high-resolution computed tomography. A number of derived characters strengthen the diagnosis of this taxon as both a tyrannosauroid and a unique, new species (e.g., endocranial position of the gasserian ganglion, internal ramification of the facial nerve). Also present are features intermediate between the basal theropod and avialan conditions that optimize as the ancestral condition for Coelurosauria--a diverse group of derived theropods that includes modern birds. The expression of several primitive theropod features as derived character states within Tyrannosauroidea establishes previously unrecognized evolutionary complexity and morphological plasticity at the base of Coelurosauria. It also demonstrates the critical role heterochrony may have played in driving patterns of endocranial variability within the group and potentially reveals stages in the evolution of neuroanatomical development that could not be inferred based solely on developmental observations of the major archosaurian crown clades. We discuss the integration of paleontology with variability studies, especially as applied to the nature of morphological transformations along the phylogenetically long branches that tend to separate the crown clades of major vertebrate groups

Risk propensity in the foreign direct investment location decision of emerging multinationals

A distinguishing feature of emerging economy multinationals is their apparent tolerance for host country institutional risk. Employing behavioral decision theory and quasi-experimental data, we find that managers’ domestic experience satisfaction increases their relative risk propensity regarding controllable risk (legally protectable loss), but decreases their tendency to accept non-controllable risk (e.g., political instability). In contrast, firms’ potential slack reduces relative risk propensity regarding controllable risk, yet amplifies the tendency to take non-controllable risk. We suggest that these counterbalancing effects might help explain observation that risk-taking in FDI location decisions is influenced by firm experience and context. The study provides a new understanding of why firms exhibit heterogeneous responses to host country risks, and the varying effects of institutions

Schools, teachers, and curriculum change: A balancing act?

Educational change is a fact of life for teachers across the world, as schools are subjected to constant and ubiquitous pressures to innovate. And, yet, many school practices remain remarkably persistent in the face of such innovation. This paradox of innovation without change is perplexing for policymakers and practitioners alike. This paper investigates the gap between policy and practice, between innovation and the changes in social practices that occur in response to such innovation. It draws upon empirical data from two case studies in Scotland &mdash; schools responding to new curriculum policy&mdash;exploring contrasting approaches to the management of innovation. One is a laissez faire approach, and the other a more directive managerial strategy. Through an analytical separation of culture, structure, and agency, derived from the social theory of Margaret Archer, the paper sheds light on the social processes that accompanied innovation in these two settings demonstrating how teacher culture and differing management styles impact upon externally initiated policy