How can I improve my life-affirming, need-fulfilling, and performance enhancing capacity to understand and model the meaning of educational quality?

Infectious pessimism, widespread apathy, and volatile relationships: these describe the high school culture I unwittingly adopted as a first-time principal at Potsdam High School in a rural suburban town in New England. I conducted a three-year intensive self-study and participatory action research project to challenge the status quo definition of educational quality in American public high school as a statistical tool of ranking, separating students, and compliance. I sought through co-investigation with beneficiaries and stakeholders of public high school a life-affirming, need-fulfilling and performance-enhancing meaning of quality to challenge the status quo Based on action research, I created a new meta-model of the meaning of quality to guide my leadership called Transformational Quality Theory (TQT). The thesis describes how using TQT theory influenced my improvement as a school leader and educational theorist, the learning and transformation of other people, and the impact it had on improving the academic and social milieu of an impoverished American high school

High sensitivity and specificity of a 5-analyte protein and microRNA biosignature for identification of active tuberculosis.

Objectives: Non-sputum-based tests to accurately identify active tuberculosis (TB) disease and monitor response to therapy are urgently needed. This study examined the biomarker capacity of a panel of plasma proteins alone, and in conjunction with a previously identified miRNA signature, to identify active TB disease. Methods: The expression of nine proteins (IP-10, MCP-1, sTNFR1, RANTES, VEGF, IL-6, IL-10, TNF and Eotaxin) was measured in the plasma of 100 control subjects and 100 TB patients, at diagnosis (treatment naïve) and over the course of treatment (1-, 2- and 6-month intervals). The diagnostic performance of the nine proteins alone, and with the miRNA, was assessed. Results: Six proteins were significantly up-regulated in the plasma of TB patients at diagnosis compared to controls. Receiver operator characteristic curve analysis demonstrated that IP-10 with an AUC = 0.874, sensitivity of 75% and specificity of 87% was the best single biomarker candidate to distinguish TB patients from controls. IP-10 and IL-6 levels fell significantly within one month of commencing treatment and may have potential as indicators of a positive response to therapy. The combined protein and miRNA panel gave an AUC of 1.00. A smaller panel of only five analytes (IP-10, miR-29a, miR-146a, miR-99b and miR-221) showed an AUC = 0.995, sensitivity of 96% and specificity of 97%. Conclusions: A novel combination of miRNA and proteins significantly improves the sensitivity and specificity as a biosignature over single biomarker candidates and may be useful for the development of a non-sputum test to aid the diagnosis of active TB disease

Laser cooling of a diatomic molecule

It has been roughly three decades since laser cooling techniques produced ultracold atoms, leading to rapid advances in a vast array of fields. Unfortunately laser cooling has not yet been extended to molecules because of their complex internal structure. However, this complexity makes molecules potentially useful for many applications. For example, heteronuclear molecules possess permanent electric dipole moments which lead to long-range, tunable, anisotropic dipole-dipole interactions. The combination of the dipole-dipole interaction and the precise control over molecular degrees of freedom possible at ultracold temperatures make ultracold molecules attractive candidates for use in quantum simulation of condensed matter systems and quantum computation. Also ultracold molecules may provide unique opportunities for studying chemical dynamics and for tests of fundamental symmetries. Here we experimentally demonstrate laser cooling of the molecule strontium monofluoride (SrF). Using an optical cycling scheme requiring only three lasers, we have observed both Sisyphus and Doppler cooling forces which have substantially reduced the transverse temperature of a SrF molecular beam. Currently the only technique for producing ultracold molecules is by binding together ultracold alkali atoms through Feshbach resonance or photoassociation. By contrast, different proposed applications for ultracold molecules require a variety of molecular energy-level structures. Our method provides a new route to ultracold temperatures for molecules. In particular it bridges the gap between ultracold temperatures and the ~1 K temperatures attainable with directly cooled molecules (e.g. cryogenic buffer gas cooling or decelerated supersonic beams). Ultimately our technique should enable the production of large samples of molecules at ultracold temperatures for species that are chemically distinct from bialkalis.Comment: 10 pages, 7 figure

Speech rhythm: a metaphor?

Is speech rhythmic? In the absence of evidence for a traditional view that languages strive to coordinate either syllables or stress-feet with regular time intervals, we consider the alternative that languages exhibit contrastive rhythm subsisting merely in the alternation of stronger and weaker elements. This is initially plausible, particularly for languages with a steep ‘prominence gradient’, i.e. a large disparity between stronger and weaker elements; but we point out that alternation is poorly achieved even by a ‘stress-timed’ language such as English, and, historically, languages have conspicuously failed to adopt simple phonological remedies that would ensure alternation. Languages seem more concerned to allow ‘syntagmatic contrast’ between successive units and to use durational effects to support linguistic functions than to facilitate rhythm. Furthermore, some languages (e.g. Tamil, Korean) lack the lexical prominence which would most straightforwardly underpin prominence alternation. We conclude that speech is not incontestibly rhythmic, and may even be antirhythmic. However, its linguistic structure and patterning allow the metaphorical extension of rhythm in varying degrees and in different ways depending on the language, and that it is this analogical process which allows speech to be matched to external rhythms

Block of death-receptor apoptosis protects mouse cytomegalovirus from macrophages and is a determinant of virulence in immunodeficient hosts.

The inhibition of death-receptor apoptosis is a conserved viral function. The murine cytomegalovirus (MCMV) gene M36 is a sequence and functional homologue of the human cytomegalovirus gene UL36, and it encodes an inhibitor of apoptosis that binds to caspase-8, blocks downstream signaling and thus contributes to viral fitness in macrophages and in vivo. Here we show a direct link between the inability of mutants lacking the M36 gene (ΔM36) to inhibit apoptosis, poor viral growth in macrophage cell cultures and viral in vivo fitness and virulence. ΔM36 grew poorly in RAG1 knockout mice and in RAG/IL-2-receptor common gamma chain double knockout mice (RAGγC(-/-)), but the depletion of macrophages in either mouse strain rescued the growth of ΔM36 to almost wild-type levels. This was consistent with the observation that activated macrophages were sufficient to impair ΔM36 growth in vitro. Namely, spiking fibroblast cell cultures with activated macrophages had a suppressive effect on ΔM36 growth, which could be reverted by z-VAD-fmk, a chemical apoptosis inhibitor. TNFα from activated macrophages synergized with IFNγ in target cells to inhibit ΔM36 growth. Hence, our data show that poor ΔM36 growth in macrophages does not reflect a defect in tropism, but rather a defect in the suppression of antiviral mediators secreted by macrophages. To the best of our knowledge, this shows for the first time an immune evasion mechanism that protects MCMV selectively from the antiviral activity of macrophages, and thus critically contributes to viral pathogenicity in the immunocompromised host devoid of the adaptive immune system

Denying reciprocity

When individuals receive benefits as a result of the burdens assumed by other people, they are expected to make a return in similar form. To do otherwise is considered as a failure to treat those other people with appropriate respect. It is this which justifies the expectation that individuals share in the labour that is necessary to preserve just institutions and productive practices that characterise complex schemes of social cooperation. In this paper, I argue that where benefits do not meet thresholds specifying the expected function and efficacy of those benefits, this does not simply issue in a ‘downward adjustment’ in the work expectations and reciprocal demands that are made of people. Rather, it legitimates refusal to engage in productive labour even where limited benefits are still being received. Other costs and obligations emerge that contribute to the creation of disruptive political, economic and social associations. These not only replace the demands of reciprocity but actively target and disrupt the practices and exchanges that give form to reciprocity

Mineral maturity and crystallinity index are distinct characteristics of bone mineral

The purpose of this study was to test the hypothesis that mineral maturity and crystallinity index are two different characteristics of bone mineral. To this end, Fourier transform infrared microspectroscopy (FTIRM) was used. To test our hypothesis, synthetic apatites and human bone samples were used for the validation of the two parameters using FTIRM. Iliac crest samples from seven human controls and two with skeletal fluorosis were analyzed at the bone structural unit (BSU) level by FTIRM on sections 2–4 lm thick. Mineral maturity and crystallinity index were highly correlated in synthetic apatites but poorly correlated in normal human bone. In skeletal fluorosis, crystallinity index was increased and maturity decreased, supporting the fact of separate measurement of these two parameters. Moreover, results obtained in fluorosis suggested that mineral characteristics can be modified independently of bone remodeling. In conclusion, mineral maturity and crystallinity index are two different parameters measured separately by FTIRM and offering new perspectives to assess bone mineral traits in osteoporosis

Reconfigurable self-assembly through chiral control of interfacial tension

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 481 (2012): 348–351, doi:10.1038/nature10769.From determining optical properties of simple molecular crystals to establishing preferred handedness in highly complex vertebrates, molecular chirality profoundly influences the structural, mechanical, and optical properties of both synthetic and biological matter at macroscopic lengthscales1,2. In soft materials such as amphiphilic lipids and liquid crystals, the competition between local chiral interactions and global constraints imposed by the geometry of the self-assembled structures leads to frustration and the assembly of unique materials3-6. An example of particular interest is smectic liquid crystals, where the 2D layered geometry cannot support twist, expelling chirality to the edges in a manner analogous to the expulsion of a magnetic field from superconductors7-10. Here, we demonstrate a previously unexplored consequence of this geometric frustration which leads to a new design principle for the assembly of chiral molecules. Using a model system of colloidal membranes11, we show that molecular chirality can control the interfacial tension, an important property of multi-component mixtures. This finding suggests an analogy between chiral twist which is expelled to the edge of 2D membranes, and amphiphilic surfactants which are expelled to oil-water interfaces12. Similar to surfactants, chiral control of interfacial tension drives the assembly of myriad polymorphic assemblages such as twisted ribbons with linear and circular topologies, starfish membranes, and double and triple helices. Tuning molecular chirality in situ enables dynamical control of line tension that powers polymorphic transitions between various chiral structures. These findings outline a general strategy for the assembly of reconfigurable chiral materials which can easily be moved, stretched, attached to one another, and transformed between multiple conformational states, thus enabling precise assembly and nano-sculpting of highly dynamical and designable materials with complex topologies.This work was supported by the National Science Foundation (NSF-MRSEC-0820492, NSF-DMR-0955776, NSF-MRI 0923057) and Petroleum Research Fund (ACS-PRF 50558-DNI7).2012-07-0

Setting the agenda for social science research on the human microbiome

The human microbiome is an important emergent area of cross, multi and transdisciplinary study. The complexity of this topic leads to conflicting narratives and regulatory challenges. It raises questions about the benefits of its commercialisation and drives debates about alternative models for engaging with its publics, patients and other potential beneficiaries. The social sciences and the humanities have begun to explore the microbiome as an object of empirical study and as an opportunity for theoretical innovation. They can play an important role in facilitating the development of research that is socially relevant, that incorporates cultural norms and expectations around microbes and that investigates how social and biological lives intersect. This is a propitious moment to establish lines of collaboration in the study of the microbiome that incorporate the concerns and capabilities of the social sciences and the humanities together with those of the natural sciences and relevant stakeholders outside academia. This paper presents an agenda for the engagement of the social sciences with microbiome research and its implications for public policy and social change. Our methods were informed by existing multidisciplinary science-policy agenda-setting exercises. We recruited 36 academics and stakeholders and asked them to produce a list of important questions about the microbiome that were in need of further social science research. We refined this initial list into an agenda of 32 questions and organised them into eight themes that both complement and extend existing research trajectories. This agenda was further developed through a structured workshop where 21 of our participants refined the agenda and reflected on the challenges and the limitations of the exercise itself. The agenda identifies the need for research that addresses the implications of the human microbiome for human health, public health, public and private sector research and notions of self and identity. It also suggests new lines of research sensitive to the complexity and heterogeneity of human–microbiome relations, and how these intersect with questions of environmental governance, social and spatial inequality and public engagement with science

Chaoborus and Gasterosteus Anti-Predator Responses in Daphnia pulex Are Mediated by Independent Cholinergic and Gabaergic Neuronal Signals

Many prey species evolved inducible defense strategies that protect effectively against predation threats. Especially the crustacean Daphnia emerged as a model system for studying the ecology and evolution of inducible defenses. Daphnia pulex e.g. shows different phenotypic adaptations against vertebrate and invertebrate predators. In response to the invertebrate phantom midge larvae Chaoborus (Diptera) D. pulex develops defensive morphological defenses (neckteeth). Cues originating from predatory fish result in life history changes in which resources are allocated from somatic growth to reproduction. While there are hints that responses against Chaoborus cues are transmitted involving cholinergic neuronal pathways, nothing is known about the neurophysiology underlying the transmission of fish related cues. We investigated the neurophysiological basis underlying the activation of inducible defenses in D. pulex using induction assays with the invertebrate predator Chaoborus and the three-spined stickleback Gasterosteus aculeatus. Predator-specific cues were combined with neuro-effective substances that stimulated or inhibited the cholinergic and gabaergic nervous system. We show that cholinergic-dependent pathways are involved in the perception and transmission of Chaoborus cues, while GABA was not involved. Thus, the cholinergic nervous system independently mediates the development of morphological defenses in response to Chaoborus cues. In contrast, only the inhibitory effect of GABA significantly influence fish-induced life history changes, while the application of cholinergic stimulants had no effect in combination with fish related cues. Our results show that cholinergic stimulation mediates signal transmission of Chaoborus cues leading to morphological defenses. Fish cues, which are responsible for predator-specific life history adaptations involve gabaergic control. Our study shows that both pathways are independent and thus potentially allow for adjustment of responses to variable predation regimes