Gap junctions in isolated rat aorta: evidence for contractile responses that exhibit a differential dependence on intercellular communication

Connexin43 (Cx43) is a major gap junction protein present in the Fischer-344 rat aorta. Previous studies have identified conditions under which selective disruption of intercellular communication with heptanol caused a significant, readily reversible and time-dependent diminution in the magnitude of a1-adrenergic contractions in isolated rat aorta. These observations have indentified a significant role for gap junctions in modulating vascular smooth muscle tone. The goal of these steady-state studies was to utilize isolated rat aortic rings to further evaluate the contribution of intercellular junctions to contractions elicited by cellular activation in response to several other vascular spasmogens. The effects of heptanol were examined (0.2-2.0 mM) on equivalent submaximal (»75% of the phenylephrine maximum) aortic contractions elicited by 5-hydroxytryptamine (5-HT; 1-2 µM), prostaglandin F2a (PGF2a; 1 µM) and endothelin-1 (ET-1; 20 nM). Statistical analysis revealed that 200 µM and 500 µM heptanol diminished the maximal amplitude of the steady-state contractile responses for 5-HT from a control response of 75 ± 6% (N = 26 rings) to 57 ± 7% (N = 26 rings) and 34.9 ± 6% (N = 13 rings), respectively (P<0.05), and for PGF2a from a control response of 75 ± 10% (N = 16 rings) to 52 ± 8% (N = 19 rings) and 25.9 ± 6% (N = 18 rings), respectively (P<0.05). In contrast, 200 µM and 500 µM heptanol had no detectable effect on the magnitude of ET-1-induced contractile responses, which were 76 ± 5.0% for the control response (N = 38 rings), 59 ± 6.0% in the presence of 200 µM heptanol (N = 17 rings), and 70 ± 6.0% in the presence of 500 µM heptanol (N = 23 rings) (P<0.13). Increasing the heptanol concentration to 1 mM was associated with a significant decrease in the magnitude of the steady-state ET-1-induced contractile response to 32 ± 5% (21 rings; P<0.01); further increasing the heptanol concentration to 2 mM had no additional effect. In rat aorta then, junctional modulation of tissue contractility appears to be agonist-dependent.

Gap junctions in cells of the immune system: structure, regulation and possible functional roles

Gap junction channels are sites of cytoplasmic communication between contacting cells. In vertebrates, they consist of protein subunits denoted connexins (Cxs) which are encoded by a gene family. According to their Cx composition, gap junction channels show different gating and permeability properties that define which ions and small molecules permeate them. Differences in Cx primary sequences suggest that channels composed of different Cxs are regulated differentially by intracellular pathways under specific physiological conditions. Functional roles of gap junction channels could be defined by the relative importance of permeant substances, resulting in coordination of electrical and/or metabolic cellular responses. Cells of the native and specific immune systems establish transient homo- and heterocellular contacts at various steps of the immune response. Morphological and functional studies reported during the last three decades have revealed that many intercellular contacts between cells in the immune response present gap junctions or "gap junction-like" structures. Partial characterization of the molecular composition of some of these plasma membrane structures and regulatory mechanisms that control them have been published recently. Studies designed to elucidate their physiological roles suggest that they might permit coordination of cellular events which favor the effective and timely response of the immune system.

Gap junction modulation by extracellular signaling molecules: the thymus model

Gap junctions are intercellular channels which connect adjacent cells and allow direct exchange of molecules of low molecular weight between them. Such a communication has been described as fundamental in many systems due to its importance in coordination, proliferation and differentiation. Recently, it has been shown that gap junctional intercellular communication (GJIC) can be modulated by several extracellular soluble factors such as classical hormones, neurotransmitters, interleukins, growth factors and some paracrine substances. Herein, we discuss some aspects of the general modulation of GJIC by extracellular messenger molecules and more particularly the regulation of such communication in the thymus gland. Additionally, we discuss recent data concerning the study of different neuropeptides and hormones in the modulation of GJIC in thymic epithelial cells. We also suggest that the thymus may be viewed as a model to study the modulation of gap junction communication by different extracellular messengers involved in non-classical circuits, since this organ is under bidirectional neuroimmunoendocrine control.

Spectroscopic Studies of III-V Semiconductor Materials for Improved Devices

Defects in semiconductor crystals and at their interfaces usually impair the properties and the performance of devices. These defects include, for example, vacancies (i.e., missing crystal atoms), interstitials (i.e., extra atoms between the host crystal sites), and impurities such as oxygen atoms. The defects can decrease (i) the rate of the radiative electron transition from the conduction band to the valence band, (ii) the amount of charge carriers, and (iii) the mobility of the electrons in the conduction band. It is a common situation that the presence of crystal defects can be readily concluded as a decrease in the luminescence intensity or in the current flow for example. However, the identification of the harmful defects is not straightforward at all because it is challenging to characterize local defects with atomic resolution and identification. Such atomic-scale knowledge is however essential to find methods for reducing the amount of defects in energy-efficient semiconductor devices. The defects formed in thin interface layers of semiconductors are particularly difficult to characterize due to their buried and amorphous structures. Characterization methods which are sensitive to defects often require well-defined samples with long range order. Photoelectron spectroscopy (PES) combined with photoluminescence (PL) or electrical measurements is a potential approach to elucidate the structure and defects of the interface. It is essential to combine the PES with complementary measurements of similar samples to relate the PES changes to changes in the interface defect density. Understanding of the nature of defects related to III-V materials is relevant to developing for example field-effect transistors which include a III-V channel, but research is still far from complete. In this thesis, PES measurements are utilized in studies of various III-V compound semiconductor materials. PES is combined with photoluminescence measurements to study the SiO2/GaAs, SiNx/GaAs and BaO/GaAs interfaces. Also the formation of novel materials InN and photoluminescent GaAs nanoparticles are studied. Finally, the formation of Ga interstitial defects in GaAsN is elucidated by combining calculational results with PES measurements.

Inhibition of return, gap effect and saccadic reaction time to a visual target

Simple manual reaction time (MRT) to a visual target (S2) is shortened when a non-informative cue (S1) is flashed at the S2 location shortly before the onset of S2 (early facilitation). Afterwards, MRT to S2 appearing at the S1 location is lengthened (inhibition of return - IOR). Similar results have been obtained for saccadic reaction time (SRT). Moreover, when there is a temporal gap between offset of the fixation point (FP) and onset of a target (gap paradigm), SRT is shorter than SRT in an overlap paradigm (FP remains on). In the present study, we determined SRT to S2 (10º) after presenting S1 at the same eccentricity (10º) or at a parafoveal position (2º) in the same or in the opposite hemifield. In addition, we employed both gap and overlap paradigms. Twelve subjects were asked not to respond to S1 (2º or 10º) to the right or to the left of FP, but to respond by making a saccadic movement in response to S2. We obtained the following results: 1) a 40-ms gap effect, 2) an interaction between gap effect and IOR, 3) a 39-ms delay (IOR) when S2 appeared at the cued (S1) position, and 4) a smaller (17 ms) but significant inhibition when S1 occurred at 2º in the ipsilateral hemifield. Thus, a parafoveal (2º) S1 elicits an inhibition of SRT towards ipsilateral peripheral targets. Since an inhibition of the ipsilateral hemifield by a 1º eccentric cue has been reported to occur when manual responses are employed, we suggest that the postulated functional link between covert and overt orienting of attention is also valid for parafoveal cues.

From statin efficacy to everyday effectiveness: Studying the gap in between.

Statins are indicated for preventing cardiovascular disease events. Patients with diabetes have a risk of major cardiovascular events double the risk of their peers without diabetes. Thus, clinical treatment guidelines recommend statins for the management of diabetic dyslipidemia. The evidence base for statin use in cardiovascular disease derives from the randomized controlled statin trials designed to prove statin efficacy under ideal conditions, among a homogenous study population meeting strict trial eligibility criteria. This thesis was implemented as four pharmacoepidemiological statin studies using register data on realworld statin users. The overall purpose was to evaluate the trends, patterns and effectiveness of statin use in everyday life. More specifically, nationwide secular trends in statin use in Finland were analysed, especially among patient groups which had been underrepresented in the statin trials. Furthermore, the benchmarking statin trials in diabetes, the Heart Protection Study and the Collaborative Atorvastatin Diabetes Study, were evaluated for their representativeness for real-world diabetes care with the emphasis placed on adherence to statin use. The association between good adherence and the incidence of major cardiovascular events in the real-world was further investigated in diabetes. These studies demonstrate that statin initiations increased from 1995 to 2005 in Finland. The increase was most pronounced among those aged at least 75 years and was observed already before the publication of rigorous trial data conducted in elderly subjects. Thus, statins seem to have been initiated in clinical practice also going beyond the strict trial eligibility criteria. Nonetheless, low adherence to statin use among the real-world patients with diabetes was found not only to limit the representativeness of the trials for clinical care but also to attenuate in all likelihood their benefits in the real-world. In fact, good adherence to statin use was found to associate with a decreased risk for major cardiovascular events in patients with diabetes. In conclusion, these studies highlight the importance of good adherence to statin use in clinical practice in order to obtain the full therapeutic value demonstrated in the statin trials. Simply increasing the number of statin users will not alone suffice in sharing our common resources appropriately.

Looking for the GAP effect in manual responses and the role of contextual influences in reaction time experiments

When the offset of a visual stimulus (GAP condition) precedes the onset of a target, saccadic reaction times are reduced in relation to the condition with no offset (overlap condition) - the GAP effect. However, the existence of the GAP effect for manual responses is still controversial. In two experiments using both simple (Experiment 1, N = 18) and choice key-press procedures (Experiment 2, N = 12), we looked for the GAP effect in manual responses and investigated possible contextual influences on it. Participants were asked to respond to the imperative stimulus that would occur under different experimental contexts, created by varying the array of warning-stimulus intervals (0, 300 and 1000 ms) and conditions (GAP and overlap): i) intervals and conditions were randomized throughout the experiment; ii) conditions were run in different blocks and intervals were randomized; iii) intervals were run in different blocks and conditions were randomized. Our data showed that no GAP effect was obtained for any manipulation. The predictability of stimulus occurrence produced the strongest influence on response latencies. In Experiment 1, simple manual responses were shorter when the intervals were blocked (247 ms, P < 0.001) in relation to the other two contexts (274 and 279 ms). Despite the use of choice key-press procedures, Experiment 2 produced a similar pattern of results. A discussion addressing the critical conditions to obtain the GAP effect for distinct motor responses is presented. In short, our data stress the relevance of the temporal allocation of attention for behavioral performance.

Fundraising and investor relations in social enterprise: Marketing your way out of the pioneer gap in African off-grid renewable energy

Social enterprises apply the best of business for the pursuit of social or environmental mission while also generating revenues. Globally, nearly 1,3 billion people lack access to electricity, as well as another billion having access to only low quality and infrequent electricity. Off-grid renewable energy, like solar, will increasingly have a key role in the solution of the energy access issue. The pioneer gap in off-grid renewable energy consists of financing (or funding) gaps and capacity gaps, to do with both the early stage of the enterprises in question, as well as the early stage of the whole industry. The gaps are emphasised by specific characteristics of off-grid renewable energy business models and the requirements of operating in bottom-of-the-pyramid markets. The marketing perspective to fundraising is chosen to uncover the possible role enterprises themselves have in bridging the pioneer gap. The purpose of this thesis is to study how social enterprises operating in off-grid renewable energy in Africa utilise marketing activities in their investor relations in bridging the pioneer gap. This main research question is divided into the following sub-questions:  How does the pioneer gap affect fundraising for these enterprises?  How are the funding needs for these enterprises characterised?  How do these enterprises build trust in their investor relations? The theoretic framework is built on relationship marketing and investor relations, with an emphasis on creation of trust. The research is conducted as a thematical case study. Primary data is gathered via semi-structured interviews with six solar energy companies and two accelerators. According to the findings, the main components affecting trust-creation are diminished information asymmetry and perceived risk, mission alignment as well as a personal fit or relationship with the investor. Therefore, an enterprise can utilise e.g. the following marketing activities in their investor relations to bridge the pioneer gap: ensuring investor material, the enterprise story and presenting of them is clear, concise and complete to “package” the enterprise as an investment; taking investor needs and motivations into account as well as utilising existing investors as ambassadors.

Narrow Gap flux-cored arc welding of high strength shipbuilding steels

This thesis is part of the Arctic Materials Technologies Development –project. The research of the thesis was done in cooperation with Arctech Helsinki Shipyard, Lappeenranta University of Technology and Kemppi Oy. Focus of the thesis was to study narrow gap flux-cored arc welding of two high strength steels with three different groove angles of 20°, 10° and 5°. Welding of the 25 mm thick E500 TMCP and 10 mm thick EH36 steels was mechanized and Kemppi WisePenetration and WiseFusion processes were tested with E500 TMCP steel. EH36 steel test pieces were welded without Wise processes. Shielding gases chosen were carbon dioxide and a mixture of argon and carbon dioxide. Welds were tested with non-destructive and destructive testing methods. Radiographic, visual, magnetic particle and liquid penetrant testing proved that welds were free from imperfections. After non-destructive testing, welds were tested with various destructive testing methods. Impact strength, bending, tensile strength and hardess tests proved that mechanized welding and Wise processes produced quality welds with narrower gap. More inconsistent results were achieved with test pieces welded without Wise processes. Impact test results of E500 TMCP exceeded the 50 J limit on weld, set by Russian Maritime Register of Shipping. EH36 impact test results were much closer to the limiting values of 34 J on weld and 47 on HAZ. Hardness values of all test specimens were below the limiting values. Bend testing and tensile testing results fulfilled the the Register requirements. No cracking or failing occurred on bend test specimens and tensile test results exceeded the Register limits of 610 MPa for E500 TMCP and 490 MPa for EH36.

Neuropeptide Y, substance P, and human bone morphogenetic protein 2 stimulate human osteoblast osteogenic activity by enhancing gap junction intercellular communication

Bone homeostasis seems to be controlled by delicate and subtle “cross talk” between the nervous system and “osteo-neuromediators” that control bone remodeling. The purpose of this study was to evaluate the effect of interactions between neuropeptides and human bone morphogenetic protein 2 (hBMP2) on human osteoblasts. We also investigated the effects of neuropeptides and hBMP2 on gap junction intercellular communication (GJIC). Osteoblasts were treated with neuropeptide Y (NPY), substance P (SP), or hBMP2 at three concentrations. At various intervals after treatment, cell viability was measured by the MTT assay. In addition, cellular alkaline phosphatase (ALP) activity and osteocalcin were determined by colorimetric assay and radioimmunoassay, respectively. The effects of NPY, SP and hBMP on GJIC were determined by laser scanning confocal microscopy. The viability of cells treated with neuropeptides and hBMP2 increased significantly in a time-dependent manner, but was inversely associated with the concentration of the treatments. ALP activity and osteocalcin were both reduced in osteoblasts exposed to the combination of neuropeptides and hBMP2. The GJIC of osteoblasts was significantly increased by the neuropeptides and hBMP2. These results suggest that osteoblast activity is increased by neuropeptides and hBMP2 through increased GJIC. Identification of the GJIC-mediated signal transduction capable of modulating the cellular activities of bone cells represents a novel approach to studying the biology of skeletal innervation.

Hurry up and slow down : education to close the ingenuity gap /

To explore the idea of education to close the ingenuity gap I use Thomas Homer-Dixon's work to define ingenuity. The notion that the supply of ingenuity to solve our technical and social problems is not keeping pace with the ingenuity required to solve those problems is called the ingenuity gap. Man-made technological developments are increasing the density, intensity, and pace of globalisation. People must reorganise decision-making organisations and problem-solving methods to pragmatically combat the growing ingenuity gap. John Dewey's work illustrates the fundamental attitudes for the thinking and judgment associated with educating for ingenuity. Howard Gardner's idea that truth, beauty, and morality ought to form the core values and tenets of the philosophy of educating for ingenuity is integral to this thesis. The act of teaching facilitates the invitation to the communication necessary to foster ingenuity. John Novak-discusses the five relationships of educational leadership that enhance an environment of ingenuity. The International Baccalaureate (IB) is an existing model of global education, one that defines some of the school experiences and academic development of core values of educating for ingenuity. Expanding upon the structure of the IB and other research within this thesis, I speculate upon what my school, where educating for ingenuity so as to close the ingenuity gap is the goal, would be like.

Bridging the gap between post-secondary students with disabilities and faculty members with their perceptions of access and accommodation

The purpose of this study was to identify factors related to successful university course completion for students with disAbilities including the knowledge that faculty members and students with disAbilities have about accommodation issues; the accommodations that students with disAbilities and faculty use and find effective in the university setting; faculty members' perceptions of and attitudes toward students with disAbilities; and the attitudes that students with disAbilities have toward faculty. Fiftyseven participants were involved in the research, eight students with disabilities and forty-nine faculty members. The main objective of the research was to describe how the skills, knowledge, and attitudes of students and faculty members, and organizational supports interact to support students' academic success. The utilization and effectiveness of accommodations to overcome barriers associated with disAbility in a post-secondary setting are described in relation to students' and faculty members' perceptions of academic success.

Closing the summer learning gap for vulnerable junior kindergarten students

Under current academic calendars across North America, summer vacation creates a significant gap in the learning cycle. I t has been argued that this gap actually decreases student achievement levels over the course of the summer. In a synthesis of 39 studies Cooper, Nye, Charlton, Lindsay, & Greathouse (1996) indicated that summer learning loss equaled at least one month of instruction as measured by grade level equivalents on standardized test scores whereby children's test scores were at least one month lower when they returned to school in the fall than scores were when students left in the summer. Specifically, Cooper et aI., (1996) found that the summer learning loss phenomena may be particularly troublesome for less advantaged children including those with speech and language delays, children at-risk for reading disabilities, children from lower socio-economic backgrounds, and children learning English as a second language. In general, research illustrated clearly that the summer learning gap can be particularly problematic for vulnerable children and furthermore, that literacy skills may be the area of achievement that is most affected. A foundational pillar to this research project is including primary caregivers as authentic partners in a summer literacy program designed to support their children's literacy needs. This pillar led the research team to use the Learning Begins at Home: A Research-Based Family Literacy Program Curriculum designed by Antoinette Doyle, Kathleen Hipfner-Boucher, and Janette Pelletier from the Ontario Institute for the Studies of Education. The LBH program is designed to be flexibly adapted to suit the needs of each individual participating family. As indicated by Timmons (2008) literacy interventions are most powerful when they include authentic family involvement. Based on this research, a requirement for participating in the summer literacy program was involvement of a child and one of their primary caregivers. The participating caregiver was integrally involved in the program, participating in workshop activities prior to and following hands-on literacy work with their child. By including primary caregivers as authentic partners, the research team encouraged a paradigmatic shift in the family whereby literacy activities become routine within their household. 5 Participants in this study were 14 children from junior kindergarten classrooms within the Niagara Catholic District School Board. As children were referred to the program, they were assessed by a trained emergent literacy specialist (from Speech Services Niagara) to identify whether they met the eligibility requirements for participation in the summer program. To be eligible to participate, children demonstrated significant literacy needs (i.e. below 25%ile on the Test of Preschool Early Literacy described below). Children with low incidence disabilities (i.e. profound sensory impairments, severe intellectual impairments, developmental disabilities, etc) were excluded as participants. The research team used a standard pre- and posttest design whereby all participating children were assessed with the Test of Preschool Early Literacy (Lonigan et aI., 2007), and a standard measure of letter names and sounds. Pretests were administered two weeks prior to the commencement of the program and the first set of posttests was administered immediately following the program. A second set of posttests was administered in December 2009 to measure the sustainability of the program. As a result of the program, all children scored statistically significantly higher on their literacy scores at the post-program assessment point immediately following the program and also at the Dec-post-program assessment point. These results in general indicated that the summer family literacy program made an immediate impact on the emergent literacy skills of participating children. All participating children demonstrated significant increases in print and phonological awareness as well as their letter sound understanding.