200 research outputs found
How I treat thrombotic thrombocytopenic purpura and atypical haemolytic uraemic syndrome
No full textThrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS) are acute, rare life-threatening thrombotic microangiopathies that require rapid diagnosis and treatment. They are defined by microangiopathic haemolytic anaemia and thrombocytopenia, with renal involvement primarily in aHUS and neurological and cardiological sequelae in TTP. Prompt treatment for most cases of both conditions is with plasma exchange initially and monoclonal therapy (rituximab in TTP and eculizumab in aHUS) as the mainstay of therapy. Here we discuss the diagnosis and therapy for both disorders
Spectroscopic Study of the Organic Conductors:Charge-Transfer Salts of BDT-TTP and DMTSA
No full text総合研究大学院大学博士（理学）So many organic donor and acceptor molecules have been synthesized after the discovery of the superconductivity in the charge-transfer salts of BEDT-TTF. The molecules containing tetrathiapentalene (TTP) skeleton provide very stable organic metals. BDT-TTP (2, 5-bis(1, 4-dithiol-2-ylidene)-1, 3, 4, 6-tetrathiapentalene) is the most basic molecule among these TTPderivatives. The 2:1 charge-transfer salts such as (BDT-TTP)2X (X=SbF6, AsF6, CIO4, and ReO4) exhibit metallic behavior down to liquid helium temperature. This property is regarded as the result of the two-dimensional (2D) network of the conducting path in the solid state. According to the band calculation with the tight-binding approximation, (BDT-TTP)2SbF6 is predicted to have a closed Fermi surface. However, no direct experiment has been performed to prove this calculation. The first part of this thesis is concerned with this experiment. The charge-transfer salts of DMTSA (2,3-dimethyltetraselenoanthracene) show unusual electrical properties: The 1:1 salt DMTSA-BF4 shows a metallic conductivity, although a conventional 1:1 organic charge-transfer salt is regarded as a Molt insulator. For the elucidation of the metallic origin, the followings should be examined: the dimensionality of the conducting path, the possibility of the multiple bands, and the on-site Coulomb energy. In the second part this thesis, the author conduct a comparative study of the isostructural salts: metallic DMTSA-BF4 and non-metallic DMTTA-BF4 (DMTTA, 2, 3-dimethyltetrathioanthracene), and discuss their different electronic structure.
(BDT-TTP)2X (X=SbF6, AsF6) has β-type crystal structure. Strong dispersion with a significant anisotropy appears in the infrared region of E//a and E⊥a spectra. The plasma edges in both directions can be fitted by Drude model very well. These indicate a two-dimensional electronic structure with significant anisotropy in the crystals. The transfer integrals estimated from the plasma frequencies are ta=-0.259 and tp=-0.048eV for (BDT-TTP)2SbF6. The estimated ta is comparable with the calculated by the extended H〓 ckel method, while the estimated tp is almost half of the calculated. The Fermi surfaces of both compounds are open in the first Brillouin zone, in contrast to the closed Fermi surface of (BDT-TTP)2SbF6 proposed by the theoretical prediction. The anisotropy of the Fermi surface increases at low temperature. The CH stretching mode strongly appears at 3084cm-1 in E⊥a spectrum, suggesting that the conjugated HOMO electrons even extend to the hydrogen atoms.
The crystal structure of BDT-TTP analogue salts (ST-TTP)2AsF6 and (BDS-TTP)2AsF6 (ST-TTP: 2-(1, 3-diselenol-2-ylidene)-5-(1, 3-dithiol-2-ylidene)- 1, 3, 4, 6-tetrathiopentalene, BDS-TTP: 2, 5-bis(1, 3-diselenol-2-ylidene)-1, 3, 4, 6-tetrathiapentalene)) are iso-structural to (BDT-TTP)2X(X=SbF6, AsF6). The IR polarized reflection spectra resemble those of (BDT-TTP)2X (X=SbF6, AsF6). The estimated transfer integrals are ta=-0.24 1, tp=-0.042eV for (ST-TTP)2AsF6 and ta=-0.255, tp=-0,044eV for (BDS-TTP)2AsF6, which are smaller than BDT-TTP salts in spite of the introduction of the selenium atoms. The Fermi surfaces of both compounds are open as well. The infer-band electronic transition and the charge sensitive vibrational mode in the Raman spectrum shift to lower energy region on increasing selenium atoms in the donor molecule, while the Raman shift between the neutral molecule and the 2:1 salts does not vary.
The BDT-TTP molecules stack uniformly in (BDT-TTP)2Y (Y=ClO4, ReO4) crystal. The chemical ratio of BDT-TTP to ReO4 was expected not to be 1:0.5 but 1:0.36. However, the most charge sensitive vibrational mode of both compounds appears at 1480 cm-1 in the Raman spectrum, the same position as (BDT-TTP)2X (X =SbF6, AsF6), thereby indicating that the ratio of BDT-TTP to the anions is 2:1 in both compounds. The polarized reflection spectra resemble those of (BDT-TTP)2X (X=SbF6, AsF6). The Fermi surfaces of (BDT-TTP)2Y (Y =ClO4, ReO4) are open as well. The weak band at 8420cm-1 of E c spectrum is assigned to the infer-band transition of BDT-TTP monocation radical.
Different from (BDT-TTP)2X (X=SbF6, AsF6, CIO4 and ReO4) which are metallic down to liquid helium temperature, θ-(BDT-TTP)2Cu(NCS)2 is a semiconductor, although it is expected to be a two-dimensional metal from the calculation of the band structure. The phase transition is observed at ca. 250K in the electrical resistance measurement. The activation energy changes from 30-40meV before the phase transition to 100meV. The polarized reflection spectra suggest two dimensional electronic structure and larger infer-stack transfer integral than the intra-stack transfer integral. The spectroscopic weight of the CT band shifts to higher energy region below the phase transition temperature. The onset energy of the E//c CT band at 16K is comparable with the energy gap estimated from the resistance measurement. The charge sensitive mode in the Raman spectrum splits into several modes at low temperature, suggesting the charge disproportionation through the phase transition. The spin susceptibility increases on lowering temperature down to IOK, conforming the Curie-Weiss law with the magnetic moment of 0.62μB. The variations of the g-value and the linewidth of ESR signal with the temperature confirm the phase transition. All of these results show that θ-(BDT-TTP)2Cu(NCS)2 is a Molt insulator.
The polarized reflection spectra of DMTSA-BF4 and DMTTA-BF4 demonstrate that both compounds have a quasi-1D electronic structure. 1D metal DMTSA-BF4 shows a metal-insulator transition at ca. l50K. DMTTA-BF4 is a Mott insulator with U/4t〓0.8-1.2, and a magnetic phase transition takes place at ca. 100 K by the ESR experiment. The low-temperature reflection spectra of both compounds strongly suggest the breaking of screw-axis symmetry along the conducting axis. The phase transitions are regarded as the spin Peierls transition for DMTTA-BF4 and Peierls transition for DMTSA-BF4. Assuming a dimerized stack structure, the transfer integrals t1 and t2 are estimated as 0.25 and 0.21 eV from the 10K spectrum of DMTSA-BF4.
An interpretation is given to the broad absorption band at ca. 6900cm-1 in the E⊥c spectrum of DMTSA-BF4 single crystal. It is assigned to the infer-branch transition from the lower to the upper branch produced by folding the HOMO band at the zone boundary. According to the formulation of this optical transition, the transition probability originates from the zigzag stacking structure of DMTSA molecules in the crystal. The numerical calculation of the conductivity spectra of this transition agrees well with the observed conductivity spectrum.application/pdf総研大甲第423号thesi
The Combination of the Lactate Dehydrogenase/Hemoglobin Ratio with the PLASMIC Score Facilitates Differentiation of TTP from Septic DIC Without Identification of Schistocytes
No full textIn some cases, differentiating thrombotic thrombocytopenic purpura (TTP) from septic disseminated intravascular coagulation (DIC) without measuring ADAMTS13 activity is critical for urgent lifesaving plasma exchange. To investigate whether PLASMIC score without identifying the presence of schistocytes, D-dimer, fibrin/fibrinogen degradation products (FDP), FDP/D-dimer ratio, prothrombin time-international normalized ratio (PT-INR), lactate dehydrogenase (LD), hemoglobin (Hb), and LD/Hb ratio are useful in differentiating patients with TTP from those with septic DIC. Retrospective analysis was conducted on the medical records of the patients with septic DIC (32 patients) or TTP (16 patients). The PLASMIC score and other laboratory measurements all were helpful in differentiating TTP from septic DIC. When dichotomized between high risk (scores 6-7) and intermediate-low risk (scores 0-5), the PLASMIC score predicted TTP with a sensitivity of 75.0% and a specificity of 100%. However, 4 of 16 patients with TTP and 19 of 32 patients with septic DIC showed comparable PLASMIC scores of 4 or 5, making it difficult to distinguish between the two by PLASMIC score alone. Among the measurements examined, the LDH/Hb ratio was the most useful for differentiation. Receiver operating characteristic analysis of the LD/Hb ratio for predicting TTP revealed a cutoff of 53.7 (IU/10 g) (sensitivity 0.94, specificity 0.91). If the LD/Hb ratio was less than 53.7, it was unlikely that the patient had TTP. A combination of the LD/Hb ratio and the PLASMIC score may be useful for distinguishing between TTP and DIC and identifying patients who need rapid plasma exchange or caplacizumab administration.権利情報：Nishimura N, et al. The Combination of the Lactate Dehydrogenase/Hemoglobin Ratio with the PLASMIC Score Facilitates Differentiation of TTP from Septic DIC Without Identification of Schistocytes. Clinical and Applied Thrombosis-Hemostasis. 2023. 29:10760296231207629. Copyright © The Author(s) 2023. doi: 10.1177/1076029623120762
A Hierarchical Trusted Third-Party System for Secure Peer-to-Peer Transactions
No full textA peer-to-peer (P2P) network is a distributed network of peer computers loosely connected through the Internet. Transactions in a P2P network are often conducted on a no-security basis. Moreover, peer anonymity is often highly desirable, which makes security even more difficult to achieve. In most cases, a peer executes a transaction solely based on the faith that the other peer plays by the rules. Here we propose a hierarchical Trusted Third-Party (TTP) system that facilitates secure transactions between peers in an existing P2P network. This system is designed to provide mutual authentication by using public key cryptography for peers to authenticate the TTP system and by using symmetric key cryptography for the TTP system to authenticate peers. After logging into the system, two peers can obtain a shared secret key from the TTP system to form a secure channel over which all transactions are encrypted using the secret key. The TTP system is designed to operate as an independent entity that peers can choose to join independently of their P2P network and can remain anonymous among each other. In addition, a reputation scheme, in which peers rate each other, is employed in the TTP system. This self-policing system provides a relative measure of trust among peers so that a peer can decide whether to allow a transaction based on another peer’s rating. The anonymity of peers in P2P systems creates many difficulties for establishing an accurate rating system. However, we believe this is still achievable to a degree
The relationship between ADAMTS13 genotype and phenotype in congenital thrombotic thrombocytopenic purpura and characterisation of ADAMTS13 mutants
No full textCongenital thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy, usually involving ADAMTS13 gene defects. ADAMTS13 processes the multimeric plasma glycoprotein Von Willebrand factor making it less reactive to platelets. Patients differ in terms of disease severity and evidence suggests a relationship between ADAMTS13 genotype and disease phenotype. Over 140 mutations have been identified in patients but only ~30% of these has been expressed in vitro. The aim of this thesis was to study certain ADAMTS13 mutations identified in a homozygous form in congenital TTP patients to assess in vitro their effect on the secretion and activity of ADAMTS13 and to assess their contribution to disease phenotype. ADAMTS13 mutants (p.R102H, p.I143T and p.Y570C) and wild type (WT) were expressed in HEK293T cells. The p.R102H mutation partially affected the secretion of ADAMTS13 and reduced the catalytic efficiency of the mutant but not to the extent predicted based upon levels measured in patient plasma. Expressing this mutant with three ADAMTS13 polymorphisms (p.Q448E, p.P618A and p.A900V) which were also identified in the patient with this mutation further reduced the secretion and activity of ADAMTS13. When these three polymorphisms were expressed separately in WT ADAMTS13, the p.P618A polymorphism reduced the secretion and subsequently the activity of ADAMTS13 suggesting that this polymorphism in particular was responsible for the reduction observed. These results highlight the importance of ADAMTS13 polymorphisms. The p.I143T and p.Y570C mutations severely affected ADAMTS13 secretion. Immunofluorescence studies showed localisation of these mutants within the ER but less extensive localisation within the cis Golgi compared to WT ADAMTS13. The p.I143T mutant was characterised further and was shown to be degraded by the cell proteasome. Addition of a chemical chaperone (betaine) appeared to rescue the secretion defect caused by the p.I143T mutation. This may have future therapeutic implications for the treatment of some congenital TTP patients
A critical legal geography of "Territory of Traditional Nature-Use" (TTP) formation in the Sakha Republic (Yakutia), Russia
No full textIn Russia’s largest region, the Sakha Republic (Yakutia), Indigenous (KMNS) leaders and communities representing five different cultural groups have succeeded in preserving traditional ways of life, and particularly nomadic reindeer husbandry, through the enormous political, social, and environmental changes of the past century. To ensure continued cultural survival, Indigenous leaders have developed a wide range of political and legal instruments, processes, and bodies within and without Russian governance structures. Key among these instruments is the “Territory of Traditional Nature-Use” (TTP), a geographically bounded legal-cultural landscape within which dozens of normative republican and federal acts, constitutional laws, and codices regulate and protect traditional land-use, socioeconomic organization, and ways of life.sakha republicYakutiaIndigenous KMNSnomadic reindeer husbandryrussian governance structure
Tristetraprolin in Human Periodontal Health and Disease
No full textBackground: Tristetraprolin (TTP) is an RNA binding protein that tightly regulates target mRNA stability and translation through specific interactions with AU-rich regions of target mRNA 3’ untranslated region (UTR). TTP has been shown to play an important role involving decreased translation of important inflammatory cytokines in periodontal disease including TNF- , IL-6 and other immune mediators. The role of TTP was initially demonstrated in TTP knock- out mice that displayed systemic inflammatory conditions, including rheumatoid arthritis and dermatitis. The p38 MAPK cascade that is activated by bacterial-derived lipopolysaccharide (LPS) has been demonstrated to be part of the deactivation process of TTP. MAPK-activated protein kinase-2 (MK2), the immediate downstream kinase of p38 MAPK, directly deactivates TTP through phosphorylation, which allows increased mRNA stability and translation of target inflammatory mediators. Our goal of this study was to determine the amount of expression of proteins MK2, phosphor-MK2 (pMK2, the active form), and total TTP in human gingival tissues in health and disease. Materials and Methods: Human gingival tissues samples were collected from twenty-five periodontally healthy (control group) and twenty-five periodontal disease subjects (test group) in addition to clinical measurements. In order to test a true representation of periodontal health and disease, samples were removed due to clinical confounding factors and insufficient size tissues. Remaining samples were stained with hematoxylin and eosin (H&E) for histopathological analysis. Additionally, immunohistochemistry (IHC) staining was performed with specific antibodies against MK2, pMK2, and TTP. H&E inflammatory infiltrate scores, IHC intensity for all three proteins of interest, and IHC area scores were assigned to each sample by a blinded pathologist. Statistical analysis with Spearman Rank Correlation and Fisher’s Exact Test were performed to determine the relationship between the expression of the proteins and inflammatory scores and clinical measurements. Clinical measurements were represented by the periodontal inflammatory burden index (PIBI). Results: Mean values for all scores were higher for the test group compared to the control group. MK2 and TTP intensity, area, and composite scores had a statistically significant positive correlation to both H&E scores and PIBI shown from the results of the Spearman Rank Correlation. Intensity and composite scores for pMK2 also showed a positive correlation that was statistically significant. The area scores for pMK2 showed a significant relationship to H&E scores but not to PIBI. Findings from the Fisher Exact test stated that the H&E scores and all IHC values except for the pMK2 area score showed high predictability for periodontal disease status. Conclusion: There is an increased expression of MK2, pMK2, and TTP in periodontally diseased tissues when compared to the healthy samples. All three proteins showed a strong, positive correlation to inflammation and periodontal disease. The current TTP findings contrasted those found in previous studies, which can be explained by indiscriminate binding of the TTP antibody to all forms of TTP. Further investigations are necessary to understand the extent of TTP’s role in periodontitis and its potential as a target in treating periodontal disease
Giống ghẹ Charybdis (Crustacea: Portunidae) ở Việt Nam
No full text14 species of Charybdis were determinated in Vietnamese coastal waters, including two new records, all species were described, identified by key and illustrated on pictures.Publishe
Fulvestrant 500 mg in postmenopausal patients with metastatic breast cancer : the initial clinical experience
No full textBackground: Fulvestrant 500 mg is currently approved for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer after failure of prior endocrine therapies. Methods: A total of 117 postmenopausal women with metastatic breast cancer, who experienced progression after previous endocrine therapies, were treated with fulvestrant 500 mg between January 2012 and June 2014. Clinical response, time to progression (TTP) and adverse events were investigated. Results: Ninety-nine patients had recurrent breast cancer and 18 patients had stage IV disease. Patients had received a median of two endocrine therapies and a median of two chemotherapies, prior to fulvestrant. There were 10 patients with partial response, 39 patients with long stable disease, 18 patients with stable disease, and 50 patients with progressive disease, so that the objective response rate was 8.5 %, with a clinical benefit rate of 41.9 %. The median TTP was 6.1 months. The absence of liver metastases, a small number of previous chemotherapies, and the longer duration of first-line endocrine therapy were positively correlated with TTP in univariate analysis. In multivariate analysis, a significant association was observed between TTP and duration of first-line endocrine therapy. Serious adverse events were observed in one patient with pulmonary embolism and in one patient with psychiatric symptoms. Conclusions: Fulvestrant 500 mg is an effective and well-tolerated treatment for postmenopausal women with metastatic breast cancer that had progressed after prior endocrine therapies. Patients with acquired resistance to endocrine therapies might be good candidates for fulvestrant therapy regardless of the number of prior endocrine treatments
Synthesis and hydrolytic properties of iridium porphyrin alkyls
No full textM.Phil.The thesis focuses on the synthesis of iridium porphyrin alkyls and their hydrolytic properties. In the first part, alkylation of IrIII(ttp)(CO)Cl, iridium 5,10,15,20-tetrakistolylporphyrinato carbonyl chloride under basic conditions, with 1o, 2o alkyl halides is achieved to give IrIII(ttp)Rs (R = alkyl) in good yields. The reaction utilizes KOH as a cheap reducing agent in air and water compatible conditions. For 3o alkyl, IrIII(ttp)(adamantly) is obtained under N2 at 150 oC. Mechanistic investigations reveal a substrate dependent pathway of SN2 or halogen atom transfer (HAT). [Includes formula]In the second part, hydrolysis of IrIII(ttp)R (R = 1o, 2o alkyl) with water at 200 oC gives alkane (R-H), olefins (RCH=CH2) and IrIII(ttp)H as a major Ir(ttp) product. The alkane (R-H) product is rationalized from the hydrolysis of IrIII(ttp)R and bimolecular reductive elimination (BMRE) of IrIII(ttp)R and IrIII(ttp)H. The olefin (RCH=CH2) formation can be accounted via a β-H elimination of IrIII(ttp)R. The formation of R-H via BMRE is promoted and the olefin formation is suppressed upon addition of IrIII(ttp)H. The implication of the promoted BMRE for hydrogenation of IrIII(ttp)R supports and suggests the use of IrIII(ttp)H as a more efficient catalyst for carbon-carbon bond hydrogenation with water. [Includes formula]本論文主要討論銥卟啉烷基化合物的合成及其水解性質。 第一部分，羰基銥卟啉氯化物（IrIII(ttp)(CO)Cl）在鹼性條件下，與一級、二級鹵代烷烴化合物發生烷基化反應，可得到高產率的銥卟啉烷基化合物(IrIII(ttp)R)。該反應應用氫氧化鉀（KOH）作廉價還原劑，反應條件耐水耐氧。而三級烷基化合物，銥卟啉金剛烷(IrIII(ttp)-adamantyl)基化合物也在150 oC, 通氮氣的條件下獲得。機理研究表明，這是一個依據反應物選擇SN2 機理或鹵素原子遷移機理的反應。第二部分中，在 200 oC 水解一、二級銥卟啉烷基化合物可以得到烷烴（RH）、烯烴（RCH=CH2）以及主要金屬卟啉產物，銥卟啉氫化物（IrIII(ttp)H）。烷烴（RH）來源於銥卟啉烷基化合物的水解，以及銥卟啉氫化物和烷基化合物的雙分子還原(BMRE)。烯烴（RCH=CH2）產生來源於b位氫消除。雙分子還原可以提升烷烴產生速率，同時通過加銥卟啉氫化物抑制烯烴的產生。雙分子還原在加速銥卟啉烷基化合物水解的這一應用表明並支持了：銥卟啉氫化物是一種以水作氫化劑，高效催化氫化碳碳鍵斷裂的催化劑。Zuo, Huiping.Thesis M.Phil. Chinese University of Hong Kong 2017.Includes bibliographical references.Abstracts also in Chinese.Title from PDF title page (viewed on 04, February, 2020)
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