Principal Candidate Research Articles

Micro-political analysis of the principal selection in a Taiwanese elementary school

This paper aims to investigate the micropolitical actions and strategies employed by the principal in the researched elementary school located in Northern Taiwan. Firstly, the author argues that the mechanism of the principal selection in Taiwan is the product of educational reform affected by policy borrowing. Secondly, drawing on ethnographic method the study illustrates the micropolitical dynamics of principal selection among the principal candidate, administrators and teachers. The research findings show that several micropolitical actions during the principal selection had been revealed, including the principal candidate seeking for internal teachers’ support, political competition between the principal candidate and the director in charge of academic affairs, building up guanxi from parents in the local community, and Confucian campus ethics as a major factor influencing the consequence of the principal selection. Key words: Micropolitics, principal selection, political competition, quanxi, Confucian ethics.

Human Simulated Studies of Aztreonam and Aztreonam-Avibactam To Evaluate Activity against Challenging Gram-Negative Organisms, Including Metallo-β-Lactamase Producers

Secondary to the stability of aztreonam against metallo-β-lactamases, coupled with avibatam's neutralizing activity against often coproduced extended-spectrum β-lactamases (ESBLs) or AmpC enzymes, the combination of aztreonam and avibactam has been proposed as a principal candidate for the treatment of infections with metallo-β-lactamase-producing Gram-negative organisms. Using the neutropenic-mouse thigh infection model, we evaluated the efficacy of human simulated doses of aztreonam-avibactam and aztreonam against 14 Enterobacteriaceae and 13 Pseudomonas aeruginosa isolates, of which 25 produced metallo-β-lactamases. Additionally, six P. aeruginosa isolates were also evaluated in immunocompetent animals. A humanized aztreonam dose of 2 g every 6 h (1-h infusion) was evaluated alone and in combination with avibactam at 375 or 600 mg every 6 h (1-h infusion), targeting the percentage of the dosing interval in which free-drug concentrations remained above the MIC (fT>MIC). Efficacy was evaluated as the change in bacterial density after 24 h compared with the bacterial density at the initiation of dosing. Aztreonam monotherapy resulted in reductions of two of the Enterobacteriaceae bacterial isolates (aztreonam MIC, ≤ 32 μg/ml; fT>MIC, ≥ 38%) and minimal activity against the remaining isolates (aztreonam MIC, ≥ 128 μg/ml; fT>MIC, 0%). Alternatively, aztreonam-avibactam therapy resulted in the reduction of all 14 Enterobacteriaceae isolates (aztreonam-avibactam MICs, ≤16 μg/ml; fT>MIC, ≥ 65%) and no difference between the 375- and 600-mg doses of avibactam was noted. Similar pharmacodynamically predictable activity against P. aeruginosa was noted in studies with neutropenic and immunocompetent mice, with activity occurring when the MICs were ≤ 16 μg/ml and variable efficacy noted when the MICs were ≥ 32 μg/ml. Again, no difference in efficacy between the 375- and 600-mg doses of avibactam was observed. Aztreonam-avibactam represents an attractive treatment option for infections with metallo-β-lactamase-producing Gram-negative pathogens that coproduce ESBLs or AmpC.

Uncovering the neurochemistry of reward and aversiveness

In a recent issue of Science was published an interesting report regarding the role of dopaminergic neurons on reward and aversiveness (Fiorillo, 2013). In contrast to what is claimed by some physiological and computational models (e.g., Schultz et al., 1997), the author provides a number of arguments to support the suggestion that reward and punishment have to be considered as two distinct neural dimensions. In particular, the author focuses on the evidence that dopaminergic neurons are selectively activated by rewarding outcomes, while these same neurons are insensitive to aversiveness. Thus, the author concludes a selective role for dopamine in detecting reward, and suggests that other (not dopaminergic) neurons should be sensitive to aversiveness. Recent insights suggest that these neurons may be serotonergic. For example, Limebeer et al. (2004) have shown that depletion of forebrain serotonin (5-HT) by 5,7 dihydroxytryptamine (5,7-DHT) lesions prevents induced conditioned disgust reactions such as “gaping,” the predominant conditioned rejection reaction (Parker, 2003) to “taste-related” aversive stimulation. Wright et al. (2010) have shown that learning to avoid odors associated with the malaise caused by ingesting toxins is mediated by serotonin. Moreover, it was recently demonstrated that partial depletion of 5-HT, in the insular cortex, prevents induced conditioned disgust reactions (Tuerke et al., 2012; see also Vicario, 2013, in press for a recent discussion about this issue). Finally, there is evidence of altered serotoninergic activity in Anorexia Nervosa (AN) (e.g., Jean et al., 2012), a psychiatric disorder characterized by a marked aversive sensitivity for food (Vicario, 2013, in press). The works mentioned above support the “two dimensions” hypothesis (Fiorillo, 2013) for reward and aversiveness. In particular, it is suggested that serotoninergic neurons could be the principal candidate of aversiveness processing. The evidence provided by these studies, which are based on the behavioral effects of block (removal) of serotonin, are difficult to interpret given the relevant number of variables that remains out of control. Thus, the definitive evidence could come from experiments that monitor activity of serotonin neurons on a fast timescale and relate it to reward and aversiveness in carefully controlled experiments. Moreover, future works might wish to investigate the existence of “ON” or “OFF” operating mechanism also for serotonin. In fact, if serotonin is the key neurotransmitter underlying aversiveness, there may be some serotonin neurons that signal aversive-ON (punishment) and others that signal aversive-OFF (absence of punishment and “negative reinforcement”).

HIV-1 V3 loop crown epitope-focused mimotope selection by patient serum from random phage display libraries: Implications for the epitope structural features

The crown region of the V3 loop in HIV-1 that contains the conserved amino acid sequence GPGR/G is known as the principal neutralizing determinant due to the extraordinary ability of antibodies to this region to neutralize the virus. To complement the existing peptide models of this epitope, we describe a family of 18 phage-displayed peptides, which include linear 12mer and constrained 7mer peptides that was selected by screening random libraries with serum from HIV-1 subtype B-infected patients. The 7mer constrained peptides presented two conserved amino acid sequences: PR-L in N-terminus and GPG in the C-terminus. On the basis of these peptides we propose a mimotope model of the V3 crown epitope in which the PR-L and GPG sequences represent the two known epitope binding sites. The GPG, has the same function as the V3 crown GPGR sequence but without the involvement of the “R” despite its being considered as the signature of the epitope in B-subtype viruses. The PR-L contains a proline not existing in the epitope that is postulated to induce kinks in the backbones of all peptides and create a spatial element mimicking the N-terminal conformationally variable binding site. Rabbit serum to these mimotopes recognized the V3 peptides and moderately decreased the fusion between HIV-1 Env- and CD4-expressing Jurkat cells. This study proposes the efficient generation by means of patient sera of V3 epitope mimics validated by interaction with the antibodies to contemporary viruses induced in patients. The serum antibody-selectable mimotopes are sources of novel information on the fine structure-function properties of HIV-1 principal neutralizing domain and candidate anti-HIV-1 immunogens.

Golgi Phosphoprotein 3 Determines Cell Binding Properties under Dynamic Flow by Controlling Golgi Localization of Core 2 N-Acetylglucosaminyltransferase 1

Core 2 N-acetylglucosaminyltransferase 1 (C2GnT1) is a key enzyme participating in the synthesis of core 2-associated sialyl Lewis x (C2-O-sLe(x)), a ligand involved in selectin-mediated leukocyte trafficking and cancer metastasis. To accomplish that, C2GnT1 needs to be localized to the Golgi and this step requires interaction of its cytoplasmic tail (CT) with a protein that has not been identified. Employing C2GnT1 CT as the bait to perform a yeast two-hybrid screen, we have identified Golgi phosphoprotein 3 (GOLPH3) as a principal candidate protein that interacts with C2GnT1 and demonstrated that C2GnT1 binds to GOLPH3 via the LLRRR(9) sequence in the CT. Confocal fluorescence microscopic analysis shows substantial Golgi co-localization of C2GnT1 and GOLPH3. Upon GOLPH3 knockdown, C2GnT1 is found mainly in the endoplasmic reticulum and decorated with complex-type N-glycans, indicating that the enzyme has been transported to the Golgi but is not retained. Also, we have found that a recombinant protein consisting of C2GnT1 CT(1-16)-Leu(17-32)-Gly(33-42)-GFP is localized to the Golgi although the same construct with mutated CT (AAAAA(9)) is not. The data demonstrate that the C2GnT1 CT is necessary and sufficient for Golgi localization of C2GnT1. Furthermore, GOLPH3 knockdown results in reduced synthesis of C2-O-sLe(x) associated with P-selectin glycoprotein ligand-1, reduced cell tethering to and rolling on immobilized P- or E-selectin, and compromised E-selectin-induced activation of spleen tyrosine kinase and cell adhesion to intercellular adhesion molecule-1 under dynamic flow. Our results reveal that GOLPH3 can regulate cell-cell interaction by controlling Golgi retention of C2GnT1.

Health Care Costs in End-of-Life and Palliative Care: The Quest for Ethical Reform

Health reform in the United States must address both access to medical services and universal insurance coverage, as well as health care cost containment. Uncontrolled health care costs will undermine improvements in access and coverage in the long-run, and will also be detrimental to other important social programs and goals. Accordingly, the authors offer an ethical perspective on health care cost control in the context of end-of-life and palliative care, an area considered by many to be a principal candidate for cost containment. However, the policy and ethical challenges may be more difficult in end-of-life care than in other areas of medicine. Here we discuss barriers to developing high quality, cost effective, and beneficial end-of-life care, and barriers to maintaining a system of decision making that respects the wishes and values of dying patients, their families, and caregivers. The authors also consider improvements in present policy and practice—such as increased timely access and referral to hospice and palliative care; improved organizational incentives and cultural attitudes to reduce the use of ineffective treatments; and improved communication among health professionals, patients, and families in the end-of-life care planning and decision-making process.

Development of high temperature gas-cooled reactor (HTGR) fuel in Japan

This paper describes experiences and present status of research and development works for the high temperature gas-cooled reactor (HTGR) fuel in Japan. Recently, Very High Temperature Reactor (VHTR) is evaluated highly worldwide, and is a principal candidate for the Generation IV reactor systems. In Japan, HTGR fuel fabrication technologies have been developed through the High Temperature Engineering Test Reactor (HTTR) project in Japan Atomic Energy Agency since 1960’s. In total about 2 tons of uranium of the HTTR fuel has been fabricated successfully and its excellent quality has been confirmed through the long-term high temperature operation. Based on the HTTR fuel technologies, SiC TRISO fuel has been newly developed for burnup extension targeted VHTR. For ZrC-TRISO coated fuel as an advanced fuel designs, R&Ds for fabrication and inspection have been carried out in JAEA. The irradiation with the Japanese uniform stoichiometric ZrC coating has been completed in the cooperation with Oak Ridge National Laboratory of the United States.

Long-Term Potentiation at CA3–CA1 Hippocampal Synapses with Special Emphasis on Aging, Disease, and Stress

Synaptic plasticity in the mammalian central nervous system has been the subject of intense investigation for the past four decades. Long-term potentiation (LTP), a major reflection of synaptic plasticity, is an activity-driven long-lasting increase in the efficacy of excitatory synaptic transmission following the delivery of a brief, high-frequency train of electrical stimulation. LTP is regarded as a principal candidate for the cellular mechanisms involved in learning and offers an attractive hypothesis of how memories are constructed. There are a number of exceptional full-length reviews published on LTP; the current review intends to present an overview of the research findings regarding hippocampal LTP with special emphasis on aging, diseases, and psychological insults.

P3.39 Ca2+-permeable channel TRPV2 as a promising therapeutic target for muscular dystrophy and cardiomyopathy

Disruption of dystrophin–glycoprotein complex caused by genetic defects of dystrophin or sarcoglycans results in muscular dystrophy and/or cardiomyopathy in human and animal models. Abnormal Ca2+ handling has been thought to be a key molecular event in the pathology of these diseases. However, the detailed mechanism for Ca2+ abnormality remains elusive. We have previously shown that the transient receptor potential cation channel TRPV2 is a principal candidate for Ca2+-entry pathways in dystrophic muscles.

Long-term potentiation (LTP) of human sensory-evoked potentials.

Long-term potentiation (LTP) is the principal candidate synaptic mechanism underlying learning and memory, and has been studied extensively at the cellular and molecular level in laboratory animals. Inquiry into the functional significance of LTP has been hindered by the absence of a human model as, until recently, LTP has only been directly demonstrated in humans in isolated cortical tissue obtained from patients undergoing surgery, where it displays properties identical to those seen in non-human preparations. In this brief review, we describe the results of paradigms recently developed in our laboratory for inducing LTP-like changes in visual-, and auditory-evoked potentials. We describe how rapid, repetitive presentation of sensory stimuli leads to a persistent enhancement of components of sensory-evoked potential in normal humans. Experiments to date, investigating the locus, stimulus specificity, and NMDA receptor dependence of these LTP-like changes suggest that they have the essential characteristics of LTP seen in experimental animals. The ability to elicit LTP from non-surgical patients will provide a human model system allowing the detailed examination of synaptic plasticity in normal subjects and may have future clinical applications in the assessment of cognitive disorders. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website.

Olanzapine-induced accumulation of adipose tissue is associated with an inflammatory state

Second-generation antipsychotics are widely used in the treatment of all forms of psychoses, but they often produce undesirable side effects, among which are weight gain and other elements of metabolic syndrome. The mechanisms of these adverse effects are not known. The liver and adipose tissue are the principal candidate organs implicated in the development of antipsychotic-induced metabolic adverse effects. The present study investigated in the rat the effects on liver and white adipose tissue of a chronic treatment (46 days) with olanzapine 2 mg/kg or haloperidol 1 mg/kg, as compared with a control solution. In the liver, the expression of key genes involved in glucose transport and lipid metabolism and of regulatory transcription factors, as well as the TNFα gene, was not altered in response to either antipsychotic. Similarly, key genes involved in glucose transport and lipid metabolism were not changed in adipose tissue. However, the white adipose tissue was inflammatory in olanzapine-treated rats, with extensive macrophage infiltration and a significant increase in TNFα expression. In the plasma, TNFα and IL-1β concentrations were slightly elevated. Chronic olanzapine treatment therefore produces a low-grade inflammatory state, likely initiated in the adipose tissue. Such an inflammatory state is known to be associated with an increased risk of insulin-resistance and cardiovascular diseases. This antipsychotic-induced inflammatory syndrome may participate in the inflammatory syndrome often observed in patients with schizophrenia. The strong and rather selective effect of olanzapine on TNFα expression may open new therapeutic opportunities for the prevention of olanzapine-induced metabolic abnormalities.

STRATEGI MEMPEROLEH SUMBERDAYA MANUSIA PENDIDIKAN YANG BERMUTU

Improving the quality ef education management begins with the improvement of human resources schools, principals as school managers need to have a high competence. To assume the principal's office is necessary to prepare the candidates who meet the qualifications and competence
 Goals of this study to obtain strategy to get quality education through ; first competency mapping pricipal candidate, second; competency mapping for the principal candidates in terms of the total competence of the principal, third competency mapping principal candidate from each principal aspects of competence.
 Surory approach use for this study data analysis with kuantitatif descriptive. Collecting data principal of competency with instmment by paper and pencil
 Result of this study to Mapping of Competence Principal Candidate, first Mapping competencies for prospective principals principals only 3% of the candidates included in the category of high competence, and 46% of the principal candidates have been category, 51 % belong to low or very low. Second mapping competencies of principal are acquired 63% of the principal candidates have mastered the managerial competence and social competence, for competence and personal entrepreneurship 4 3% of the principal candidates master the competence, the competence for supervision while the only 26% controlled by the principal candidate. Third Mapping competencies for managerial competence, entrepreneurship, personal, supervision and social, there are some competencies have mastery and any competece have not master.
 Based on mapping results, the implication of this study are : for the competence of managerial skills development priorities through education and training or workshop activities. For entrepreneurial competencies need to be trained to think of creative and innovative capabilities through case studies. For the supervision competencies need to be trained through simulation. For social competence and personality is only required to guide them through regular meetings.
 Keywords: Strategy, qualified human resources, headmaster competence-managerial personality-supervision-social entrepreneurship.

Superintendents’ Perceptions of the Principal Shortage

The research literature on the principal shortage is inconsistent regarding the actual scope of the shortage and a clear articulation of factors contributing to the successful recruitment and retention of today’s school leaders. Often, critical data related to the principal shortage are ignored, including the number of younger principals overlooked in a candidate job search or the number of credentialed principal candidates who ultimately withdraw from a search. This study is based on a survey of 197 superintendents concerning their views on the principal shortage and factors associated with influencing the recruitment and retention of school leaders. Some major findings are that superintendents often underestimate the principal candidate applicant pool in their own districts, compensation continues to be the primary method of attracting qualified principal applicants, and rural schools are at a distinct disadvantage compared with urban and suburban schools in their search for new school principals.

Enamel-free teeth: Tbx1 deletion affects amelogenesis in rodent incisors

TBX1 is a principal candidate gene for DiGeorge syndrome, a developmental anomaly that affects the heart, thymus, parathyroid, face, and teeth. A mouse model carrying a deletion in a functional region of the Tbx1 gene has been extensively used to study anomalies related to this syndrome. We have used the Tbx1 null mouse to understand the tooth phenotype reported in patients afflicted by DiGeorge syndrome. Because of the early lethality of the Tbx1−/− mice, we used long-term culture techniques that allow the unharmed growth of incisors until their full maturity. All cultured incisors of Tbx1−/− mice were hypoplastic and lacked enamel, while thorough histological examinations demonstrated the complete absence of ameloblasts. The absence of enamel is preceded by a decrease in proliferation of the ameloblast precursor cells and a reduction in amelogenin gene expression. The cervical loop area of the incisor, which contains the niche for the epithelial stem cells, was either severely reduced or completely missing in mutant incisors. In contrast, ectopic expression of Tbx1 was observed in incisors from mice with upregulated Fibroblast Growth Factor signalling and was closely linked to ectopic enamel formation and deposition in these incisors. These results demonstrate that Tbx1 is essential for the maintenance of ameloblast progenitor cells in rodent incisors and that its deletion results in the absence of enamel formation.

Strain-specific immunity may drive adaptive polymorphism in the merozoite surface protein 1 of the rodent malaria parasite Plasmodium chabaudi

Clinical immunity against malaria is slow to develop, poorly understood and strongly strain-specific. Understanding how strain-specific immunity develops and identifying the parasite antigens involved is crucial to developing effective vaccines against the disease. In previous experiments we have shown that strain-specific protective immunity (SSPI) exists between genetically distinct strains (cloned lines) of the rodent malaria parasite Plasmodium chabaudi chabaudi in mice [Cheesman, S., Raza, A., Carter, R., 2006. Mixed strain infections and strain-specific protective immunity in the rodent malaria parasite P. chabaudi chabaudi in mice. Infect. Immun. 74, 2996-3001]. In two subsequent studies, we identified the highly polymorphic Merozoite Surface Protein 1 (MSP-1) as being the principal candidate molecule for the control of SSPI against P. c. chabaudi malaria [Martinelli et al., 2005; Pattaradilokrat, S., Cheesman, S.J., Carter R., 2007. Linkage group selection: towards identifying genes controlling strain-specific protective immunity in malaria. PLoS ONE 2(9):e857]. In the present study, we sequenced the whole msp1 gene of several genetically distinct strains of P. chabaudi and found high levels of genetic diversity. Protein sequence alignments reveal extensive allelic polymorphism between the P. chabaudi strains, concentrated primarily within five regions of the protein. The 3′-end sequence region, encoding the C-terminal 21kDa region (MSP-121), which is analogous and homologous to MSP-119 of Plasmodium falciparum, appears to have been subject to balancing selection. We have found that the strains with the lowest sequence identity at MSP-121 (i.e. AS/CB and AJ/CB) induce robust and reciprocal SSPI in experimental mice. In contrast, two strains that do not induce reciprocal SSPI are identical at the 21kDa region. Final identification of the region(s) controlling SSPI will provide important information to help guide decisions about MSP-1 based vaccines.

Dominant-negative inhibition of Ca2+ influx via TRPV2 ameliorates muscular dystrophy in animal models

Muscular dystrophy is a severe degenerative disorder of skeletal muscle characterized by progressive muscle weakness. One subgroup of this disease is caused by a defect in the gene encoding one of the components of the dystrophin-glycoprotein complex, resulting in a significant disruption of membrane integrity and/or stability and, consequently, a sustained increase in the cytosolic Ca(2+) concentration ([Ca(2+)](i)). In the present study, we demonstrate that muscular dystrophy is ameliorated in two animal models, dystrophin-deficient mdx mice and delta-sarcoglycan-deficient BIO14.6 hamsters by dominant-negative inhibition of the transient receptor potential cation channel, TRPV2, a principal candidate for Ca(2+)-entry pathways. When transgenic (Tg) mice expressing a TRPV2 mutant in muscle were crossed with mdx mice, the [Ca(2+)](i) increase in muscle fibers was reduced by dominant-negative inhibition of endogenous TRPV2. Furthermore, histological, biochemical and physiological indices characterizing dystrophic pathology, such as an increased number of central nuclei and fiber size variability/fibrosis/apoptosis, elevated serum creatine kinase levels, and reduced muscle performance, were all ameliorated in the mdx/Tg mice. Similar beneficial effects were also observed in the muscles of BIO14.6 hamsters infected with adenovirus carrying mutant TRPV2. We propose that TRPV2 is a principal Ca(2+)-entry route leading to a sustained [Ca(2+)](i) increase and muscle degeneration, and that it is a promising therapeutic target for the treatment of muscular dystrophy.

Archaeal MCM has separable processivity, substrate choice and helicase domains

The mini-chromosome maintenance (MCM) complex is the principal candidate for the replicative helicase of archaea and eukaryotes. Here, we describe a functional dissection of the roles of the three principal structural modules of the homomultimeric MCM of the hyperthermophilic archaeon Sulfolobus solfataricus. Our results include the first analysis of the central AAA+ domain in isolation. This domain possesses ATPase and helicase activity, defining this as the minimal helicase domain. Reconstitution experiments show that the helicase activity of the AAA+ domain can be stimulated by addition of the isolated N-terminal half in trans. Addition of the N-terminus influences both the processivity of the helicase and the choice of substrate that can be melted by the ATPase domain. The degenerate helix-turn-helix domain at the C-terminus of MCM exerts a negative effect on the helicase activity of the complex. These results provide the first evidence for extensive regulatory inter-domain communication within the MCM complex.

The Poll Results Hypothesis

This empirical study seeks to broaden the interpretation of the rational voter model so as to reflect the potential impact of the results of polls of likely voters’ Presidential candidate preferences on the expected benefits of voting and hence on the voter participation rate. This study introduces the poll results hypothesis: in any given state, given the existence of the Electoral College, the greater the lead of a principal Presidential candidate over his/her closest rival as revealed in polls of likely voters, the lower, for at least some portion of prospective voters, the expected gross benefits of voting in that state and hence the lower the aggregate voter participation rate in that state. In a cross-section study of the 50 states during the 2004 general election, it is found, after allowing for a variety of other factors, that the greater the lead (as revealed in polls of likely voters) of either of the principal Presidential candidates over the other in any given state, the lower the voter turnout rate in that state.

Study on creep-fatigue life prediction methods for low-carbon nitrogen-controlled 316 stainless steel (316FR)

Low-carbon, nitrogen-controlled 316 stainless steel called 316FR was developed and is regarded as a principal candidate for a main structural material of liquid metal-cooled fast breeder reactor plants in Japan. To develop a creep-fatigue evaluation method suitable for this steel, a number of uniaxial creep-fatigue tests have been conducted for three products of this steel. Long-term data up to about 35,000 h were obtained and applicability of failure life prediction methods was studied based upon their results. Cruciform shaped specimens were also tested under biaxial loading conditions to examine the effect of stress multiaxiality on failure life under creep-fatigue condition.

Long-term creep rupture behavior of smoothed and notched bar specimens of low-carbon nitrogen-controlled 316 stainless steel (316FR) and their evaluation

Low-carbon, nitrogen-controlled 316 stainless steel is regarded as a principal candidate for a main structural material of future fast breeder reactor plants in Japan. To grasp creep deformation and rupture behavior of this steel whose modeling is indispensable in the design of high-temperature components, a number of uniaxial tensile creep tests have been conducted for four products of this steel at 550 °C and higher temperatures. Long-term creep rupture data up to about 94,000 h were obtained and used to examine the applicability of rupture and deformation estimation methods developed earlier. In addition, two tests were conducted using round-bar specimens with circumferential notches to make investigation of the effect of stress multiaxiality on creep damage.