66,418 research outputs found
Effects of HO-1 overexpression on mitochondrial dysfunction and autophagy level in Lv-HO-1-H9c2 cells with H/R model.
(A) Cell viability was measured using the CCK-8 assay. The data are presented as means ± SE (N = 5). **p<0.01 vs corresponding Normoxia group; #p<0.05, vs corresponding Lv-scramble group. (B) Real-time quantitative PCR (RT q-PCR) analyses of HO-1 mRNA expression in lv-HO-1 H9c2 cells subjected to H/R relative to GAPDH expression (n = 3 wells per group). **p<0.01 vs. the normoxia group. (C) H/R-induced HO-1, p62, and LC-3 protein expression analyzed using western blots of lv-HO-1 H9c2 cells. GAPDH was used as a loading control (n = 3 wells per group). ##p<0.01 vs corresponding Lv-scramble group; ***p<0.001 vs. the corresponding normoxia group. (D) Representative confocal microscopy images and quantitative analysis of autophagosomes from 15 fields (n = 3 hearts per group). Scale bar = 500 nm. *p<0.05 vs. the corresponding normoxia group; ##p<0.01, vs corresponding Lv-scramble group. H/R, Hypoxia/reoxygenation; HO-1, heme oxygenase-1. (E,F) Flow cytometry detection of changes in JC-1 fluorescence color reflects changes in the mitochondrial membrane potential and mitochondrial ROS levels. #p<0.05, vs corresponding Lv-scramble group; **p<0.01 vs corresponding Normoxia group, #p<0.05, vs corresponding Lv-scramble group. (G) The apoptosis rate of the four groups. Cell identification and detection of apoptosis. **p<0.01 vs corresponding Normoxia group; ##p<0.01, vs corresponding Lv-scramble group.</p
Letter from A. F. Potter to John H. Page
Letter from A. F. Potter to John H. Page referring his request to build a railway to the District Forester at Albuquerque, New Mexico
Cooling rates of neutron stars and the young neutron star in the Cassiopeia A supernova remnant
We explore the thermal state of the neutron star in the Cassiopeia A supernova remnant using the recent result of Ho & Heinke that the thermal radiation of this star is well described by a carbon atmosphere model and the emission comes from the entire stellar surface. Starting from neutron star cooling theory, we formulate a robust method to extract neutrino cooling rates of thermally relaxed stars at the neutrino cooling stage from observations of thermal surface radiation. We show how to compare these rates with the rates of standard candles – stars with non-superfluid nucleon cores cooling slowly via the modified Urca process. We find that the internal temperature of standard candles is a well-defined function of the stellar compactness parameter x=rg/R, irrespective of the equation of state of neutron star matter (R and rg are circumferential and gravitational radii, respectively). We demonstrate that the data on the Cassiopeia A neutron star can be explained in terms of three parameters: f?, the neutrino cooling efficiency with respect to the standard candle; the compactness x; and the amount of light elements in the heat-blanketing envelope. For an ordinary (iron) heat-blanketing envelope or a low-mass (? 10?13 M?) carbon envelope, we find the efficiency f?? 1 (standard cooling) for x? 0.5 and f?? 0.02 (slower cooling) for a maximum compactness x? 0.7. A heat blanket containing the maximum mass (?10?8 M?) of light elements increases f? by a factor of 50. We also examine the (unlikely) possibility that the star is still thermally non-relaxe
The 1961 Kampong Bukit Ho Swee fire and the making of modern Singapore
By 1970, Singapore’s urban landscape was dominated by high-rise blocks of planned public housing built by the People’s Action Party government, signifying the establishment of a high modernist nation-state. A decade earlier, the margins of the City had been dominated by kampongs, home to semi-autonomous communities of low-income Chinese families which freely built, and rebuilt, unauthorised wooden houses. This change was not merely one of housing but belied a more fundamental realignment of state-society relations in the 1960s. Relocated in Housing and Development Board flats, urban kampong families were progressively integrated into the social fabric of the emergent nation-state. This study examines the pivotal role of an event, the great Kampong Bukit Ho Swee fire of 1961, in bringing about this transformation. The redevelopment of the fire site in the aftermath of the calamity brought to completion the British colonial regime’s ‘emergency’ programmes of resettling urban kampong dwellers in planned accommodation, in particular, of building emergency public housing on the sites of major fires in the 1950s. The PAP’s far greater political resolve, and the timing of and state of emergency occasioned by the scale of the 1961 disaster, enabled the government to rehouse the Bukit Ho Swee fire victims in emergency housing in record time. This in turn provided the HDB with a strategic platform for clearing other kampongs and for transforming their residents into model citizens of the nation-state. The 1961 fire’s symbolic usefulness extended into the 1980s and beyond, in sanctioning the PAP’s new housing redevelopment schemes. The official account of the inferno has also become politically useful for the government of today for disciplining a new generation of Singaporeans against taking the nation’s progress for granted. Against these exalted claims of the fire’s role in the Singapore Story, this study also examines the degree of actual change and continuity in the social and economic lives of the people of Bukit Ho Swee after the inferno. In some crucial ways, the residents continued to occupy a marginal place in society while pondering, too, over the unresolved question of the cause of the fire. These continuities of everyday life reflect the ambivalence with which the citizenry regarded the high modernist state in contemporary Singapore
Polly H. Carder Collection on George F. Root
George Frederick Root (1820-1895) was an American songwriter and music educator. He is perhaps best known for his song "The Battle Cry of Freedom," which was written and rose to popularity during the U.S. Civil War. The Polly H. Carder Collection on George F. Root contains original published scores and songbooks from the period 1852-1907 and photocopied scores collected by Polly H. Carder, author of the book George F. Root, Civil War Songwriter: A Biography. The collection also contains a short article, "The Last Days of George F. Root," written by Root's daughter, Clara Louise Burnham
Interphasma elongatum subsp. elongatum Ho 2017
Interphasma elongatum elongatum Ho, 2017 Type locality: China (Yuping, Pingbian, Yunnan). NOTE. No material examined.Published as part of Li, B. L., Shi, F. M. & Wang, H. J., 2021, Stick insects of the genus Interphasma Chen et He, 2008 (Phasmida: Phasmatidae) from China, pp. 24-32 in Far Eastern Entomologist 422 on page 26, DOI: 10.25221/fee.422.3, http://zenodo.org/record/716634
HMOX1 gene promoter alleles and high HO-1 levels are associated with severe malaria in Gambian children.
Heme oxygenase 1 (HO-1) is an essential enzyme induced by heme and multiple stimuli associated with critical illness. In humans, polymorphisms in the HMOX1 gene promoter may influence the magnitude of HO-1 expression. In many diseases including murine malaria, HO-1 induction produces protective anti-inflammatory effects, but observations from patients suggest these may be limited to a narrow range of HO-1 induction, prompting us to investigate the role of HO-1 in malaria infection. In 307 Gambian children with either severe or uncomplicated P. falciparum malaria, we characterized the associations of HMOX1 promoter polymorphisms, HMOX1 mRNA inducibility, HO-1 protein levels in leucocytes (flow cytometry), and plasma (ELISA) with disease severity. The (GT)(n) repeat polymorphism in the HMOX1 promoter was associated with HMOX1 mRNA expression in white blood cells in vitro, and with severe disease and death, while high HO-1 levels were associated with severe disease. Neutrophils were the main HO-1-expressing cells in peripheral blood, and HMOX1 mRNA expression was upregulated by heme-moieties of lysed erythrocytes. We provide mechanistic evidence that induction of HMOX1 expression in neutrophils potentiates the respiratory burst, and propose this may be part of the causal pathway explaining the association between short (GT)(n) repeats and increased disease severity in malaria and other critical illnesses. Our findings suggest a genetic predisposition to higher levels of HO-1 is associated with severe illness, and enhances the neutrophil burst leading to oxidative damage of endothelial cells. These add important information to the discussion about possible therapeutic manipulation of HO-1 in critically ill patients
Sung-Ho Jin
학위논문(박사)--아주대학교 일반대학원 :의학과,2014. 2ABSTRACT ⅰ
TABLE OF CONTENTS ⅲ
LIST OF FIGURES ⅴ
LIST OF TABLES ⅶ
Ⅰ. INTRODUCTION 1
A. Gastric Cancer and Malignant Ascites 1
B. Intraperitoneal Radioimmunotherapy 3
C. Purpose of the Study 6
Ⅱ. MATERIALS AND METHODS 7
A. Materials 7
1. Cell Lines 7
2. Subcutaneous Tumor and Malignant Ascites Mouse Models 7
3. Preparation of Radioimmunoconjugates 8
B. Methods 10
1. Western Immunoblot Analysis 10
2. Flow Cytometry Analysis 11
3. In vitro Cytotoxicity of Cetuximab 12
4. Immunofluorescence Microscopy 12
5. In vitro Stability Study of 64Cu-DOTA-Bn-NCS-Cetuximab 13
6. Immunoreactivity Assay 13
7. MicroPET Imaging 14
8. Biodistribution Studies 15
9. Peritoneal Membrane Autoradiography 15
10. Statistical Analysis 16
Ⅲ. RESULTS 17
A. EGFR Expression Levels in Gastric Carcinoma Cells 17
B. Subcellular Localization of Cetuximab-bound EGFR 19
C. Cetuximab Cytotoxicity in Gastric Cancer Cells 20
D. Conjugation and 64Cu Labeling 21
E. In Vitro Properties of 64Cu-DOTA-Cetuximab 23
F. Bilateral Subcutaneous Tumor and Malignant Ascites Mouse Models 26
G. PET Imaging of Bilateral Subcutaneous Tumor Model Mice 28
H. Biodistribution of 64Cu-DOTA-Cetuximab in Bilateral Subcutaneous Tumor Model Mice 29
I. EGFR expression level affected by incubation periods 33
J. PET Imaging of Malignant Ascites Model Mice after I.V. or I.P. Administration of 64Cu-DOTA-Cetuximab 35
K. Biodistribution of 64Cu-DOTA-Cetuximab in Malignant Ascites Model after I.V. or I.P. Administration 37
L. Localization of 64Cu-DOTA-Cetuximab in Peritoneal Seeding 43
Ⅳ. DISCUSSION 44
Ⅴ. CONCLUSION 49
REFERENCES 50
국문요약 61MasterIntraperitoneal (i.p.) radioimmunotherapy (RIT) may be a promising treatment strategy for intraperitoneally-confined malignant diseases including malignant ascites (MA) in gastric cancer. We conducted a comparative biodistribution study of 64Cu-DOTA-cetuximab in subcutaneous (SQ) tumor and MA mouse models.
A mouse xenograft model of bilateral SQ tumors that express epidermal growth factor receptor (EGFR) was established by SQ injections of NUGC-4 and MKN-45 gastric cancer cells into either shoulder of female BALB/c nude mice. The MA model was produced by i.p. injection of NUGC-4 cells. Cetuximab was conjugated to a bifunctional chelator (p-SCN-Bn-DOTA) and labeled with Copper-64 (T1/2 = 12.7 hours). Radiolabeled cetuximab was then administered intravenous (i.v.) or i.p. injection. Positron emission tomography (PET) imaging and biodistribution studies were conducted at the indicated time points.
In the bilateral SQ tumor model, the peak uptake of radiolabeled cetuximab in the NUGC-4 and MKN-45 tumors was detected at 24 h post-injection of 64Cu-DOTA-cetuximab by PET imaging and biodistribution analysis. NUGC-4 tumor uptake of radiolabeled cetuximab was significantly higher than MKN-45 tumor uptake at all time points. The EGFR expression levels of the two cell lines were similar according to in vitro experiments. However, based on flow cytometry analyses at different incubation times with primary antibody (cetuximab) ranging from 3 min to 3 h, the EGFR expression levels were increased over time, and the increasing slope was higher in NUGC-4 cells than in MKN-45 cells.
In the i.v.-induced MA model mice, the biodistribution of radiolabeled cetuximab in the blood pool and liver was high at 1 h and 3 h after i.v. injection and decreased over time. In the i.p.-induced MA model mice, the percent injected dose per gram (% ID/g) of ascites was very high and more than 8% at 1, 3, 24, and 48 h post injection; however, the % ID/g in all normal organs was equal to or less than 6% at all time points. In addition, all peak uptakes of normal organs and i.p.-induced NUGC-4 tumors appeared at 24 h after injection. In addition, the uptake ratios of tumor, peritoneum, and ascites to normal organs after i.p. injection were greater than after i.v. injection, particularly at the early time points. Finally, autoradiography studies using excised peritoneum and mesentery indicated several hot spots corresponding to peritoneal seeding.
The results suggest that using the i.p. route for RIT in malignant ascites models shows advantages over the i.v. route with regard to tumor targeting and half-life prolongation of radioimmunoconjugates in the peritoneal cavity
Thermochemistry of HO<sub>2</sub> + HO<sub>2</sub> → H<sub>2</sub>O<sub>4</sub>: Does HO<sub>2</sub> Dimerization Affect Laboratory Studies?
Self-reaction is an important sink
for the hydroperoxy radical
(HO<sub>2</sub>) in the atmosphere. It has been suggested (Denis,
P. A.; Ornellas, F. R. <i>J. Phys. Chem. A</i>, <b>2009</b>, <i>113</i> (2), 499–506) that the minor product
hydrogen tetroxide (HO<sub>4</sub>H) may act as a reservoir of HO<sub>2</sub>. Here, we compute the thermochemistry of HO<sub>2</sub> self-reactions
to determine if either HO<sub>4</sub>H or the cyclic hydrogen-bound
dimer (HO<sub>2</sub>)<sub>2</sub> can act as reservoirs. We computed
electronic energies using coupled-cluster calculations in the complete
basis set limit, CCSD(T)/CBS[45]//CCSD(T)/cc-pVTZ. Our model chemistry
includes corrections for vibrational anharmonicity in the zero-point
energy and vibrational partition functions, core–valence correlation,
scalar relativistic effects, diagonal Born–Oppenheimer, spin–orbit
splitting, and higher-order corrections. We compute the Gibbs energy
of dimerization to be (−20.1 ± 1.6) kJ/mol at 298.15 K
(2σ uncertainty), and (−32.3 ± 1.5) kJ/mol at 220
K. For atmospherically relevant [HO<sub>2</sub>] = 10<sup>8</sup> molecules
per cm<sup>3</sup>, our thermochemistry indicates that dimerization
will be negligible, and thus H<sub>2</sub>O<sub>4</sub> species are
atmospherically unimportant. Under conditions used in laboratory experiments
([HO<sub>2</sub>] > 10<sup>12</sup> molecules per cm<sup>3</sup>,
220 K), H<sub>2</sub>O<sub>4</sub> formation may be significant. We
compute two absorption spectra that could be used for laboratory detection
of HO<sub>4</sub>H: the OH stretch overtone (near-IR) and electronic
(UV) spectra
Elision of /h, ?/ in the Shirazi Dialect of Persian (SHDP): An Optimality Theory Based Analysis
Mnogi su se znanstvenici do danas bavili proučavanjem lenicije (oslabljivanja) kao jednog od najučestalijih fonoloških procesa. Elizija (ispuštanje) grkljanika (grkljanskog frikativa /h/ i grkljanskog prekidnika /?/) jedna je od najčešćih fonoloških alternacija u perzijskom Shirazi dijalektu (SHDP) koja je do danas, koliko je znanstvenicima poznato, neistražena. U radu se nastoje opisati činjenice o toj čestoj fonološkoj alternaciji u spomentom perzijskom regionalnom dijalektu te se naglašavaju osnovne razlike u nastupanju tih procesa u Shirazi dijalektu i standardnom perzijskom jeziku (SP). Analiza je rađena prema okviru optimalne teorije (Optimality theory) (McCarthy and Prince 1995., 2001.) prema kojoj su jezični oblici rezultat međudjelovanja prekršivih općih ograničenja. Istraživanjem se pokazalo da su spomenuti procesi brisanja suglasnika u Shirazi dijalektu ograničeni položajem u slogu te su uvjetovani položajem u kodi, između dvaju vokala ili u suglasničkom skupu. Uglavnom se ne ostvaruju u pristupu, iako postoje primjeri u kojima je gubljenje dopušteno i u pristupu naglašenog sloga. Stoga ovo istraživanje Shirazi dijalekt svrstava među jezike koji dopuštaju oslabljivanje u pristupu naglašenog sloga. Spomenuti procesi ispuštanja ne događaju se na početku riječi, a nakon ispuštanja grkljanika uvijek slijedi kompenzacijsko produljivanje (Compensatory lengthening – CL), čak i nakon ispuštanja u pristupu naglašenog sloga.Until recently, many researchers have shown interest in studying lenitions, which are examples of the most common universal types of phonological processes. Elision of laryngeals (glottal fricative /h/ and glottal stop /?/) is one of the most common phonological alternations exhibited in the Shirazi dialect of Persian (SHDP) which to the knowledge of the researchers, has not been studied to date. This paper seeks to provide a description of the facts about this common phonological alternation in the addressed regional dialect of Persian and points out some main differences between the behavior of these processes in SHDP and Standard Persian (SP). The analysis is cast in an Optimal Theoretic (OT) framework (McCarthy and Prince 1995, 2001), which holds that linguistic forms are the outcome of interaction among violable universal constraints. The present study shows that the addressed processes of consonant deletion in SHDP are restricted by syllabic position and are conditioned by coda position, intervocalic position or consonant clusters. They are usually blocked in the onset, but there are cases where reduction is allowed in the onset of the stressed syllable. Thus, the study adds SHDP to the list of languages which permit lenition in the onset of the stressed syllable. The addressed processes of elision are always blocked in word-initial position and laryngeal elision is always followed by Compensatory lengthening (CL), even after deletion from the onset of the stressed syllable
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