15 research outputs found
G PROTEIN ACTIVATION OF A HORMONE-STIMULATED PHOSPHATASE IN HUMAN TUMOR CELLS
The growth-inhibiting peptide hormone somatostatin stimulates phosphotyrosine phosphatase activity in the human pancreatic cell line MIA PaCa-2. This hormonal activation was mediated by a pertussis toxin-sensitive guanosine 5'-triphosphate-binding protein (G protein) in the membranes of these cells. Activation of this G protein by somatostatin stimulated the dephosphorylation of exogenous epidermal growth factor receptor prepared from A-431 cells in vitro. This pathway may mediate the antineoplastic action of somatostatin in these cells and in human tumors and could represent a general mechanism of G protein coupling that is utilized by normal cells in the hormonal control of cell growt
The Construction of the Origami Level-n Menger Sponge Complement by the PJS Technique
In 2015, the author developed a new origami technique, called PJS technique (where PJS stands for “pleat and join strips”), by which we can construct polycubes, that are polyhedrons composed of elementary cubes, called units, connected face to face. Each strip, pleated in squares, has to cover four faces of a tower of stacked units, called a segment, having as length the number of units that form the tower. Each unit is composed by weaving together three paper strips in the three spatial directions and the length of each strip depends on the length of the segment in each respective direction. The PJS technique allowed the author to build, at the end of 2016, the first specimen of a level-4 origami Menger sponge and three yeas later, the first level-3 complement model. In this paper, we give a formula to compute the number of segments that make up a level-n Menger sponge complement in all directions and consequently, the number of modules needed for each length to build this polycube with the PJS technique
The Role of the Temporary Official (Pjs) of the Village Head in Carrying out the Main Duties and Functions in Sitoluama Village, Laguboti District, Toba Regency
81 HalamanPenelitian dilatarbelakangi oleh Peranan Pejabat Sementara (PJS) Kepala Desa Dalam Menjalankan Tugas Pokok Dan Fungsi Di Desa Sitoluama Kecamatan Laguboti Kabupaten Toba, dalam peranan Pejabat Sementara (PJS) belum sepenuhnya terlaksana Perannya sebagai pengganti Kepala desa, hal ini dapat dilihat dari Peranan sebagai hubungan Antar pribadi, Peranan yang berhubungan dengan informasi, Peranan sebagai Pembuat Keputusan adapun yang menjadi faktor penghambat dari permasalahan diantaranya mengenai Rendahnya sumberdaya Manusia, Minimnya fasilitas Kantor Kepala Desa Sitoluama, Kurangnya Bimbingan Aperatur desa Sitoluama. Penelitian ini bertujuan untuk mengetahui Peranan Pejabat Sementara (PJS) dalam menggantikan Kepala Desa Sitoluama dalam menjalankan Tugas Pokok dan Fungsinya, dan adapun tujuan lainnya ialah mengetahui apa saja faktor Penghambat yang dihadapi Pejabat Sementara (PJS) dalam tugasnya menggantikan Kepala Desa Sitoluama. Penelitian menggunakan Metode penelitian kualitatif pendekatan deskriptif. Sumber Data dikumpulkan berdasarkan teknik pengumpulan data yaitu observasi, wawancara, dokumentasi dan triangulasi data. Penulis mengambil teori dari Henry Mintzberg. Berdasarkan hasil penelitian yang dilakukan oleh Penulis maka hasil Skripsi peneliti ialah, sudah cukup membantu dan mampu melaksanakan Tugas dan Fungsinya sebagaimana Tugas yang diberikan Kepada Kepala Desa telah dikerjakan dengan cukup baik, namun belum maksimal menjalankan tugas dan fungsinya sebagai Pejabat Sementar Kepala desa Kedispilinan pada saat jam kerja, kurangnya bersosialisasi kepada masyarakat desa Sitoluama, dan juga kurang maksimal menyelesaikan masalah-masalah yang ada di desa Sitoluama. The research was motivated by the role of the Temporary Official (PJS) of the
Village Head in Carrying out the Main Duties and Functions in Sitoluama
Village, Laguboti District, Toba Regency, in the role of the Temporary Official
(PJS) the role of the village head was not fully implemented, this can be seen from
the role of interpersonal relationships , Roles related to information, Roles as
Decision Makers as for the inhibiting factors of the problems including the low
human resources, the lack of facilities for the Sitoluama village head office, the
lack of guidance from the Sitoluama village officials This study aims to determine
the role of Temporary Officials (PJS) in replacing the Sitoluama Village Head in
carrying out their Main Duties and Functions, and another objective is to find out
what are the inhibiting factors faced by Temporary Officials (PJS) in their duties
to replace the Sitoluama Village Head. The study used a descriptive qualitative
research method. Sources The data were collected based on data collection
techniques, namely observation, interviews, documentation and data
triangulation. The author takes the theory from Henry Mintzberg. Based on the
results of research conducted by the author on the Role of Temporary Officials
(PJS) of the Sitoluama Village Head in carrying out their main duties and
functions, the Role of Temporary Officials (PJS) in Sitoluama Village has been
quite helpful and able to carry out their duties and functions as the tasks given to
the Village Head have been done. quite well, but not yet maximally carrying out
his duties and functions as a Temporary Official for the Village Head of
Discipline during working hours, lack of socializing to the people of Sitoluama
village, and also less than optimal in solving problems that exist in Sitoluama
village
An empirical test of accreditation patient journey surveys: Randomized trial
Objective: To evaluate the effectiveness of utilizing the patient journey survey (PJS) method in healthcare accreditation processes. Design: Randomized trial of the PJS method in parallel with the current accreditation survey (CAS) method of the Australian Council on Healthcare Standards (ACHS). Setting: Acute healthcare organizations in Australia. Participants: Seventeen organizations, 28 organizational staff, nine surveyors and 38 patients. Main Outcome Measures: The results of each surveying method were compared. Participants provided feedback, via 18 interviews and 40 questionnaire surveys, about the benefits and disadvantages of a PJS compared to a CAS. Results: The PJS method is not as comprehensive as the CAS method for accreditation assessment. In matched assessments the majority of items were rated lower by the PJS method than by the CAS. PJSs were shown to be appropriate for assessing mandatory clinical criteria, but were less effective for assessing corporate and support criteria. The two methods diverged in their final assessments of which organizations met the accreditation threshold. Participants endorsed the use of PJSs within accreditation processes. Conclusions: The PJS methodology complements but is not a substitute for existing accreditation methods. There is significant stakeholder support for the inclusion of the PJS method within the current accreditation programme. © The Author 2012. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved
Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene
G protein-coupled receptor regulation of gene transcription primarily occurs through the phosphorylation of transcription factors by MAPKs. This requires transduction of an activating signal via scaffold proteins that can ultimately determine the outcome by binding signaling kinases and adapter proteins with effects on the target transcription factor and locus of activation. By investigating these mechanisms, we have elucidated how pituitary gonadotrope cells decode an input GnRH signal into coherent transcriptional output from the LH beta-subunit gene promoter. We show that GnRH activates c-Src and multiple members of the MAPK family, c-Jun NH2-terminal kinase 1/2, p38MAPK, and ERK1/2. Using dominant-negative point mutations and chemical inhibitors, we identified that calcium-dependent proline-rich tyrosine kinase 2 specifically acts as a scaffold for a focal adhesion/cytoskeleton-dependent complex comprised of c-Src, Grb2, and mSos that translocates an ERK-activating signal to the nucleus. The locus of action of ERK was specifically mapped to early growth response-1 (Egr-1) DNA binding sites within the LH beta-subunit gene proximal promoter, which was also activated by p38MAPK, but not c-Jun NH2-terminal kinase 1/2. Egr-1 was confirmed as the transcription factor target of ERK and p38MAPK by blockade of protein expression, transcriptional activity, and DNA binding. We have identified a novel GnRH-activated proline-rich tyrosine kinase 2-dependent ERK-mediated signal transduction pathway that specifically regulates Egr-1 activation of the LH beta-subunit proximal gene promoter, and thus provide insight into the molecular mechanisms required for differential regulation of gonadotropin gene expression
Novel serine/threonine kinase 11 gene mutations in Peutz-Jeghers syndrome patients and endoscopic management
Nagasaki University (長崎大学)博士(医学)AIM: To explore mutations in serine/threonine kinase 11 (STK11) gene in Peutz-Jeghers syndrome (PJS) with gastrointestinal (GI) hamartomatous polyps.
METHODS: Six Japanese PJS patients in 3 families were enrolled in this study. Each of the cases had hamartomatous polyposis in the gastrointestinal tract, including the small intestine, along with mucocutaneous hyperpigmentation. Narrow-band imaging (NBI)-magnification endoscopy was employed to detect microvascular and microsurface irregularities in the GI lesions. NBI magnification findings could be classified into three groups (type A, type B, or type C). Endoscopic polypectomy was performed using double-balloon enteroscopy or colonoscopy. Genomic DNA was extracted from a whole blood sample from each subject. All of the coding exons of STK11 gene, its boundary regions, and the promoter region containing the polymorphic regions were amplified by polymerase chain reaction, and direct sequencing was performed to assess the germline mutations.
RESULTS: NBI-magnification endoscopic observation could detect the abnormalities in microvessels and microsurface structures of GI polyps. Overall, we found 5 cases of type A and one case without the examination for the gastric polyps, while there were 4 cases of type B and 2 case of type A for the colorectal polyps. Seventy-nine small-bowel and 115 colorectal polyps over 27 sessions for each were resected endoscopically without significant complications. The only delayed complication included the occurrence of bleeding in a case, and this was successfully managed with hemoclips. Resected polyps contained no malignant components. Based on mutation analysis, all 3 cases in Family I exhibited the +658C>T nonsense mutation in exon 5, which resulted in the production of a truncated protein (Q220X). In Family II, a case had -252C>A and -193C>A in the promoter region. In Family III, a case was found to have the +1062C>G (F342L) mutation in exon 8.
CONCLUSION: We found two novel mutations of STK11 in association with PJS. Endoscopic polypectomy of GI polyps in PJS patients appears to be useful to prevent emergency laparotomies and reduce the cancer risk.長崎大学学位論文 学位記番号:博(医歯薬)甲第634号 学位授与年月日:平成25年10月2日Author: Hiroyuki Yajima, Hajime Isomoto, Hiroaki Nishioka, Naoyuki Yamaguchi, Ken Ohnita, Tatsuki Ichikawa, Fuminao Takeshima, Saburo Shikuwa, Masahiro Ito, Kazuhiko Nakao, Kazuhiro Tsukamoto and Shigeru KohnoCitation: World Journal of Gastrointest Endoscopy, 5(3): pp.102-110; 2013Nagasaki University (長崎大学), 博士(医学) (2013-10-02)doctoral thesi
Distribution and predictors of haemophilia-related costs in the United Kingdom: analysis of the CHESS I and CHESS II burden of illness studies
© The Author(s) 2024Background: Few studies have evaluated direct medical or societal costs of haemophilia in the United Kingdom (UK), and how patient characteristics impact future costs is uncertain. Cost predictors were identified and examined using cross-sectional data from the CHESS I and II studies. Methods: Patient- and physician-reported outcomes were analysed for UK adult males aged ≤ 65, with haemophilia A or B and no recent clinical trial participation. Demographics, haemophilia type and severity, inhibitors, annual bleed rate (ABR), problem joints (PJs), treatment type, and comorbidities, were utilised in regression analyses. Health-related quality of life was assessed using EQ-5D. Generalised linear models estimated expected non-drug haemophilia-related direct medical costs (DMC) and societal costs (non-drug DMC, direct non-medical and indirect costs). Average marginal effects (AMEs) determined predictors of cost. Results: Costs for 378 patients were analysed. Mean age was 33 years and 79% (299) had haemophilia A. Mean annual per-patient DMC were £165,001 (including factor treatment costs) and £4,091 when excluding factor replacement treatment costs (non-drug DMC). Mean annual per-patient non-treatment societal costs were £11,550 (standard deviation £20,171) among those with data available (n = 51). Number of PJs, ABR, and treatment regimen were significant determinants of haemophilia-related non-drug DMC (all P < 0.001). Non-drug DMC increased as ABR increased (AMEs were £2,018 for ABR 1–5, £3,101 for ABR 6–10 and £5,785 for ABR ≥ 11, vs. ABR 0) and by £1,869 per additional PJ. No significant predictors of non-drug haemophilia-related societal costs were identified. Mean EQ-5D score was 0.66, with lower scores observed for people with haemophilia B (0.48) compared with haemophilia A (0.71) and with increasing haemophilia severity. Conclusions: UK direct medical and societal costs of haemophilia are substantial. Non-drug DMC were particularly associated with ABR and number of PJs. These findings may be useful for real-world evaluations of the economic burden of haemophilia in the UK.Pfizer Ltd. CHESS II study was supported by unrestricted research grants from Sanofi, BioMarin and Takeda
The response of the tandem pore potassium channel TASK-3 (K2P9.1) to voltage : gating at the cytoplasmic mouth
Although the tandem pore potassium channel TASK-3 is thought to open and shut at its
selectivity filter in response to changes of extracellular pH, it is currently unknown whether the
channel also shows gating at its inner, cytoplasmic mouth through movements of membrane
helices M2 and M4.We used two electrode voltage clamp and single channel recording to show
that TASK-3 responds to voltage in a way that reveals such gating. In wild-type channels, Popen
was very low at negative voltages, but increased with depolarisation. The effect of voltage was
relatively weak and the gating charge small, ∼0.17.Mutants A237T (in M4) and N133A (in M2)
increased Popen at a given voltage, increasing mean open time and the number of openings per
burst. In addition, the relationship between Popen andvoltagewas shifted to lesspositive voltages.
Mutation of putative hinge glycines (G117A, G231A), residues that are conserved throughout
the tandem pore channel family, reduced Popen at a given voltage, shifting the relationship
with voltage to a more positive potential range. None of these mutants substantially affected
the response of the channel to extracellular acidification. We have used the results from single
channel recording to develop a simple kinetic model to show how gating occurs through two
classes of conformation change, with two routes out of the open state, as expected if gating
occurs both at the selectivity filter and at its cytoplasmic mouth
Analysis of the content of an interview survey of sugar babies(PJs) :What kind of act is sugar dating?
パパ活の実態を知るために、筆者は出会い系サイトやパパ活アプリに登録し、「パパ活女子」にインタビュー調査を行った。対面インタビューから、「パパ活女子」の生育歴、初体験と交際、パパ活の行為内容、パパ活のエピソード、トラブルとリスク管理、友達のパパ活、抱えている問題点、パパ活の継続意志などについて、項目ごとに情報を得た。また、これらインタビュー調査から得られたパパ活女性の類型を構築し、彼女たちが出会ってきたパパたちについての話から、「パパ」像の実態を記述した。結論的には、パパ活とは援助交際と変わらない行為であった。In order to understand the reality of sugar dating, the author registered on dating sites and apps, and interviewed “sugar babies”. From face-to-face interviews, the author obtained information on each of the following topics: upbringing history, first sexual experience and relationships, contents of sugar dating, episodes of daddies’ activities, troubles and risk management of sugar dating by sugar babies, friends’ sugar dating, problems they are facing, and their intention to continue their sugar dating. In addition, we constructed a typology of sugar babies obtained from these interviews, and described the actual image of “daddies” from the stories of the dadies they met. In conclusion, sugar dating was an act that was no different from compensated dating
Perancangan Sistem Informasi Pendataan Korban Bencana Alam Dan Bencana Sosial Di Dinas Sosial Kota Palembang Berbasis Website
Handling events that occur, by evacuating, meeting needs, protection are things that must be done by the government and local governments and emergency response. The Palembang City Social Service is a government institution that has many fields, one of which is PJS (Social Protection and Security) which has a Head of Social Protection for Natural and Social Disaster Victims (PSKBA / BS). In collecting data on victims of Natural and Social Disasters, the Social Service of Palembang City has used a computer in its data collection, but the data collection is still using MS Excel where the data can be lost at any time. Therefore, this study aims to design a web-based system that helps in collecting data on victims of natural and social disasters that can minimize data loss. In building information system software, the author uses an object-oriented method with a waterfall approach which consists of several stages, namely Requirements Analysis (requirements), System Design (design), System Implementation (implementation), System Testing (testing), and System Maintenance (maintenance). . The design of the Information System for Data Collection of Victims of Natural Disasters and Social Disasters at the Social Service of Palembang City is a system design process that can later be implemented in programming language which aims to make it easier for officers or admins to collect data and also recap reports quickly and accurately. The design of this system is based on the problems that exist at this time where the data collection process is still using Ms Excel which is considered to be still ineffective. The currently designed system is equipped with a menu of disaster data, command posts, victim data, officers, assistance, and a recap menu. Where these menus can support the system to be maximized and in accordance with user needs.Keywords : Information System, Waterfall, WebÂ
