GPCR production in a novel yeast strain that makes cholesterol-like sterols

The activities of many mammalian membrane proteins including G-protein coupled receptors are cholesterol-dependent. Unlike higher eukaryotes, yeast do not make cholesterol. Rather they make a related molecule called ergosterol. As cholesterol and ergosterol are biologically non-equivalent, the potential of yeast as hosts for overproducing mammalian membrane proteins has never been fully realised. To address this problem, we are trying to engineer a novel strain of Saccharomyces cerevisiae in which the cholesterol biosynthetic pathway of mammalian cells has been fully reconstituted. Thus far, we have created a modified strain that makes cholesterol-like sterols which has an increased capacity to make G-protein coupled receptors compared to control yeast.

Blobs versus bars:psychophysical evidence supports two types of orientation response in human color vision

The classic hypothesis of Livingstone and Hubel (1984, 1987) proposed two types of color pathways in primate visual cortex based on recordings from single cells: a segregated, modularpathway that signals color but provides little information about shape or form and a second pathway that signals color differences and so defines forms without the need to specify their colors. A major problem has been to reconcile this neurophysiological hypothesis with the behavioral data. A wealth of psychophysical studies has demonstrated that color vision has orientation-tuned responses and little impairment on form related tasks, but these have not revealed any direct evidence for nonoriented mechanisms. Here we use a psychophysical method of subthreshold summation across orthogonal orientations for isoluminant red-green gratings in monocular and dichoptic viewing conditions to differentiate between nonoriented and orientation-tuned responses to color contrast. We reveal nonoriented color responses at low spatial frequencies (0.25-0.375 c/deg) under monocular conditions changing to orientation-tuned responses at higher spatial frequencies (1.5 c/deg) and under binocular conditions. We suggest that two distinct pathways coexist in color vision at the behavioral level, revealed at different spatial scales: one is isotropic, monocular, and best equipped for the representation of surface color, and the other is orientation-tuned, binocular, and selective for shape and form. This advances our understanding of the organization of the neural pathways involved in human color vision and provides a strong link between neurophysiological and behavioral data. © 2013 ARVO.

The in vivo susceptibility of Leishmania donovani to sodium stibogluconate is drug specific and can be reversed by inhibiting glutathione biosynthesis

Resistance to pentavallent antimonial (Sb-v) agents such as sodium stibogluconate (SSG) is creating a major problem in the treatment of visceral leishmaniasis. In the present study the in vivo susceptibilities of Leishmania donovani strains, typed as SSG resistant (strain 200011) or SSG sensitive (strain 200016) on the basis of their responses to a single SSG dose of 300 mg of Sb-v/kg of body weight, to other antileishmanial drugs were determined. In addition, the role of glutathione in SSG resistance was investigated by determining the influence on SSG treatment of concomitant treatment with a nonionic surfactant vesicle formulation of buthionine sulfoximine (BSO), a specific inhibitor of the enzyme gamma-glutamylcysteine synthetase which is involved in glutathione biosynthesis, and SSG, on the efficacy of SSG treatment. L. donovani strains that were SSG resistant (strain 200011) and SSG sensitive (strain 200016) were equally susceptible to in vivo treatment with miltefosine, paromomycin and amphotericin B (Fungizone and AmBisome) formulations. Combined treatment with SSG and vesicular BSO significantly increased the in vivo efficacy of SSG against both the 200011 and the 200016 L. donovani strains. However, joint treatment that included high SSG doses was unexpectedly associated with toxicity. Measurement of glutathione levels in the spleens and livers of treated mice showed that the ability of the combined therapy to inhibit glutathione levels was also dependent on the SSG dose used and that the combined treatment exhibited organ-dependent effects. The SSG resistance exhibited by the L. donovani strains was not associated with cross-resistance to other classes of compounds and could be reversed by treatment with an inhibitor of glutathione biosynthesis, indicating that clinical resistance to antimonial drugs should not affect the antileishmanial efficacies of alternative drugs. In addition, it should be possible to identify a treatment regimen that could reverse antimony resistance.

Island diasporas: Perceptions of Indo-Caribbean protégés regarding the effects of their cross-cultural mentoring experiences in the United States

Mentoring is defined as an "intense caring relationship in which persons with more experience work with less experienced persons to promote both professional and personal development" (Caffarella, 1992, p. 38). It is "a powerful emotional, and passionate interaction whereby the mentor and protégé experience...intellectual growth and development" (Galbraith & Zelenak, 1991, p. 126). In cross-cultural mentoring, mentors and protégés from different cultures confront social and cultural identities, goals, expectations, values, and beliefs (Cross & Lincoln, 2005) to "achieve a higher level of potency in education and society" (Mullen, 2005, p. 6). Cross-cultural mentoring research explores attitudes, behaviors, linguistics and motivators of the more visible racial and ethnic groups in the U.S. (Elmer, 1986, Ulmer, 2008). The cross-cultural mentoring experiences of Indo-Caribbeans in the U.S. are obscured from the research despite their rich socio-historic culture. The purpose of this phenomenological study was to explore the perceptions of Indo-Caribbean protégés regarding the effects of their cross-cultural mentoring experiences in the United States. Phenomenology is "the systematic attempt to uncover and describe...the internal meaning structures, of lived experience [by studying the] particulars or instances as they are encountered" (Van Manen, 1990, p. 10). Criterion and snowball sampling were used to recruit 15 participants. A semi-structured interview guide was used to gather data and Creswell's (2007) simplified version of Moustakas's (1994) Modification of the Stevick-Colaizzi-Keen Method of Analysis of Phenomenological Data was used to analyze the data. Three themes emerged: (a) "Sitting at the feet of gurus" taught protégés how to accept guidance, (b) Guru-Shishya: Learning and Discipleship, ways that protégés perceived mentors' guidance related to work, skill acquisition, and social or emotional support, and (c) Samavartan sanskar: Building Coherence, helped protégés understand, manage and find meaning. Protégés' goals and professional expectations determined what they wanted from cross-cultural mentoring relationships and what they were willing to endure within those relationships. Since participants valued achievement and continuous improvement, mentor support was integral to making meaning and developing a sense of coherence in their lives. Implications regarding cross-cultural mentoring relationships together with recommendations for future research conclude the study.

A Cross-Generational Analysis of Spanish-to-English Lexico-Semantic Phenomena in Emerging Miami English

Sociolinguists have documented the substrate influence of various languages on the formation of dialects in numerous ethnic-regional setting throughout the United States. This literature shows that while phonological and grammatical influences from other languages may be instantiated as durable dialect features, lexical phenomena often fade over time as ethnolinguistic communities assimilate with contiguous dialect groups. In preliminary investigations of emerging Miami Latino English, we have observed that lexical forms based on Spanish lexical forms are not only ubiquitous among the speech of the first generation Cuban Americans but also of the second. Examples, observed in field work, casual observation, and studied formally in an experimental context include the following: “get down from the car,” which derives from the Spanish equivalent, bajar del carro instead of “get out of the car”. The translation task administered to thirty-one participants showed a variety lexical phenomena are still maintained at equal or higher frequencies.

Utilizing ICT to prevent loneliness and social isolation of the elderly. A literature review

Ageing of the population is a worldwide phenomenon. Numerous ICT-based solutions have been developed for elderly care but mainly connected to the physiological and nursing aspects in services for the elderly. Social work is a profession that should pay attention to the comprehensive wellbeing and social needs of the elderly. Many people experience loneliness and depression in their old age, either as a result of living alone or due to a lack of close family ties and reduced connections with their culture of origin, which results in an inability to participate actively in community activities (Singh & Misra, 2009). Participation in society would enhance the quality of life. With the development of information technology, the use of technology in social work practice has risen dramatically. The aim of this literature review is to map out the state of the art of knowledge about the usage of ICT in elderly care and to figure out research-based knowledge about the usability of ICT for the prevention of loneliness and social isolation of elderly people. The data for the current research comes from the core collection of the Web of Science and the data searching was performed using Boolean? The searching resulted in 216 published English articles. After going through the topics and abstracts, 34 articles were selected for the data analysis that is based on a multi approach framework. The analysis of the research approach is categorized according to some aspects of using ICT by older adults from the adoption of ICT to the impact of usage, and the social services for them. This literature review focused on the function of communication by excluding the applications that mainly relate to physical nursing. The results show that the so-called ‘digital divide’ still exists, but the older adults have the willingness to learn and utilise ICT in daily life, especially for communication. The data shows that the usage of ICT can prevent the loneliness and social isolation of older adults, and they are eager for technical support in using ICT. The results of data analysis on theoretical frames and concepts show that this research field applies different theoretical frames from various scientific fields, while a social work approach is lacking. However, a synergic frame of applied theories will be suggested from the perspective of social work.

Achievable sum-rate of multiuser massive MIMO downlink in ricean fading channels

We investigate the achievable ergodic sum-rate of multi-user multiple-input multiple-output systems in Ricean fading channels. We first derive a lower bound on the average signal-to-leakage-and-noise ratio by utilizing the Mullen's inequality, which is then used to analyze the effect of channel mean information on the achievable sum-rate. With these results, a novel statistical-eigenmode space-division multipleaccess downlink transmission scheme is proposed. For this scheme, we derive an exact closed-form expression for the achievable ergodic sum-rate. Our results show that the achievable ergodic sum-rate converges to a saturation value in the high signal-to-noise ratio (SNR) region and reaches to a lower limit value in the lower Ricean K-factor range. In addition, we present tractable upper and lower bounds, which are shown to be tight for any SNR and Ricean K-factor value. Finally, the theoretical analysis is validated via numerical simulations.

Thomson scattering on non-thermal atmospheric pressure plasma jets

To characterize non-thermal atmospheric pressure plasmas experimentally, a large variety of methods and techniques is available, each having its own specific possibilities and limitations. A rewarding method to investigate these plasma sources is laser Thomson scattering. However, that is challenging. Non-thermal atmospheric pressure plasmas (gas temperatures close to room temperature and electron temperatures of a few eV) have usually small dimensions (below 1 mm) and a low degree of ionization (below 10^-4). Here an overview is presented of how Thomson scattering can be applied to such plasmas and used to measure directly spatially and temporally resolved the electron density and energy distribution. A general description of the scattering of photons and the guidelines for an experimental setup of this active diagnostic are provided. Special attention is given to the design concepts required to achieve the maximum signal photon flux with a minimum of unwanted signals. Recent results from the literature are also presented and discussed.

A signaling visualization toolkit to support rational design of combination therapies and biomarker discovery: SiViT

Targeted cancer therapy aims to disrupt aberrant cellular signalling pathways. Biomarkers are surrogates of pathway state, but there is limited success in translating candidate biomarkers to clinical practice due to the intrinsic complexity of pathway networks. Systems biology approaches afford better understanding of complex, dynamical interactions in signalling pathways targeted by anticancer drugs. However, adoption of dynamical modelling by clinicians and biologists is impeded by model inaccessibility. Drawing on computer games technology, we present a novel visualisation toolkit, SiViT, that converts systems biology models of cancer cell signalling into interactive simulations that can be used without specialist computational expertise. SiViT allows clinicians and biologists to directly introduce for example loss of function mutations and specific inhibitors. SiViT animates the effects of these introductions on pathway dynamics, suggesting further experiments and assessing candidate biomarker effectiveness. In a systems biology model of Her2 signalling we experimentally validated predictions using SiViT, revealing the dynamics of biomarkers of drug resistance and highlighting the role of pathway crosstalk. No model is ever complete: the iteration of real data and simulation facilitates continued evolution of more accurate, useful models. SiViT will make accessible libraries of models to support preclinical research, combinatorial strategy design and biomarker discovery.

Mentoring : o caso Santander Totta

Mestrado em Ciências Empresariais

Electrical characterization of organic based transistors: stability issues

An investigation into the stability of metal insulator semiconductor (MIS) transistors based on alpha-sexithiophene is reported. In particular the kinetics of the threshold voltage shift upon application of a gate bias has been determined. The kinetics follow a stretched-hyperbola type behavior, in agreement with the formalism developed to explain metastability in amorphous-silicon thin film transistors. Using this model, quantification of device stability is possible. Temperature-dependent measurements show that there are two processes involved in the threshold voltage shift, one occurring at T approximate to 220 K and the other at T approximate to 300 K. The latter process is found to be sample dependent. This suggests a relation between device stability and alpha-sexithiophene deposition parameters. Copyright (c) 2005 John Wiley A Sons, Ltd.

Interface state mapping in a Schottky barrier of the organic semiconductor terrylene

In this work we quantitatively map interface states in energy in a Schottky barrier between aluminum and the vacuum sublimed organic semiconductor terrylene. The density map of these interface states was extracted from the, admittance spectroscopy data. They revealed an interface state density of 2 x 10(12). cm(-2)eV(-1) close to the valence band which decreases slightly towards midgap. Additional do measurements show that the semiconductor bulk activation energy is 0.33 eV which may correspond to an acceptor level. (C) 2002 Elsevier Science B.V. All rights reserved.

Determing the Effect of Thermal Treatment Timing on Ultra-High Performance Concrete Beams

The loss of prestressing force over time influences the long-term deflection of the prestressed concrete element. Prestress losses are inherently complex due to the interaction of concrete creep, concrete shrinkage, and steel relaxation. Implementing advanced materials such as ultra-high performance concrete (UHPC) further complicates the estimation of prestress losses because of the changes in material models dependent on curing regime. Past research shows compressive creep is "locked in" when UHPC cylinders are subjected to thermal treatment before being loaded in compression. However, the current precasting manufacturing process would typically load the element (through prestressing strand release from the prestressing bed) before the element would be taken to the curing facility. Members of many ages are stored until curing could be applied to all of them at once. This research was conducted to determine the impact of variable curing times for UHPC on the prestress losses, and hence deflections. Three UHPC beams, a rectangular section, a modified bulb tee section, and a pi-girder, were assessed for losses and deflections using an incremental time step approach and material models specific to UHPC based on compressive creep and shrinkage testing. Results show that although it is important for prestressed UHPC beams to be thermally treated, to "lock in" material properties, the timing of thermal treatment leads to negligible differences in long-term deflections. Results also show that for UHPC elements that are thermally treated, changes in deflection are caused only by external loads because prestress losses are "locked-in" following thermal treatment.

Effects of bubbles, cracks, and volcanic tephra on the spectral albedo of bare ice near the Transantarctic Mountains: Implications for sea glaciers on Snowball Earth

Spectral albedo was measured along a 6 km transect near the Allan Hills in East Antarctica. The transect traversed the sequence from new snow through old snow, firn, and white ice, to blue ice, showing a systematic progression of decreasing albedo at all wavelengths, as well as decreasing specific surface area (SSA) and increasing density. Broadband albedos under clear-sky range from 0.80 for snow to 0.57 for blue ice, and from 0.87 to 0.65 under cloud. Both air bubbles and cracks scatter sunlight; their contributions to SSA were determined by microcomputed tomography on core samples of the ice. Although albedo is governed primarily by the SSA (and secondarily by the shape) of bubbles or snow grains, albedo also correlates highly with porosity, which, as a proxy variable, would be easier for ice sheet models to predict than bubble sizes. Albedo parameterizations are therefore developed as a function of density for three broad wavelength bands commonly used in general circulation models: visible, near-infrared, and total solar. Relevance to Snowball Earth events derives from the likelihood that sublimation of equatorward-flowing sea glaciers during those events progressively exposed the same sequence of surface materials that we measured at Allan Hills, with our short 6 km transect representing a transect across many degrees of latitude on the Snowball ocean. At the equator of Snowball Earth, climate models predict thick ice, or thin ice, or open water, depending largely on their albedo parameterizations; our measured albedos appear to be within the range that favors ice hundreds of meters thick. Citation: