878 research outputs found

    A Study of Initialization in Linux and OpenBSD

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    The code that initializes a system can be notoriously difficult to understand. In secure systems, initialization is critical for establishing a starting state that is secure. This paper explores two architectures used for bringing an operating system to its initial state, once the operating system gains control from the boot loader. Specifically, the ways in which the OpenBSD and Linux operating systems handle initialization are dissected

    Inhibition of CLIC4 Enhances Autophagy and Triggers Mitochondrial and ER Stress-Induced Apoptosis in Human Glioma U251 Cells under Starvation

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    CLIC4/mtCLIC, a chloride intracellular channel protein, localizes to mitochondria, endoplasmic reticulum (ER), nucleus and cytoplasm, and participates in the apoptotic response to stress. Apoptosis and autophagy, the main types of the programmed cell death, seem interconnected under certain stress conditions. However, the role of CLIC4 in autophagy regulation has yet to be determined. In this study, we demonstrate upregulation and nuclear translocation of the CLIC4 protein following starvation in U251 cells. CLIC4 siRNA transfection enhanced autophagy with increased LC3-II protein and puncta accumulation in U251 cells under starvation conditions. In that condition, the interaction of the 14-3-3 epsilon isoform with CLIC4 was abolished and resulted in Beclin 1 overactivation, which further activated autophagy. Moreover, inhibiting the expression of CLIC4 triggered both mitochondrial apoptosis involved in Bax/Bcl-2 and cytochrome c release under starvation and endoplasmic reticulum stress-induced apoptosis with CHOP and caspase-4 upregulation. These results demonstrate that CLIC4 nuclear translocation is an integral part of the cellular response to starvation. Inhibiting the expression of CLIC4 enhances autophagy and contributes to mitochondrial and ER stress-induced apoptosis under starvation

    Living donor liver transplantation using sensitized lymphocytotoxic crossmatch positive graft

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    We describe a successful living donor liver transplantation (LDLT) using a lymphocytotoxic crossmatch highly positive graft. A 41-year-old woman with alcoholic liver cirrhosis was referred as a potential candidate for LDLT, and her husband was willing to donate his partial liver. As the T-lymphocytotoxic crossmatch titer was over 10,000×, the patient was first infused with rituximab for preoperative desensitization, and then five rounds of plasmapheresis were performed. After the third plasmapheresis, the lymphocytotoxic crossmatch test was negative. A left liver graft including the caudate lobe was implanted, and anti-CD25 antibody (basiliximab) was administered on postoperative days 1 and 4. The postoperative course was uneventful except for an episode of mild acute cellular rejection on postoperative day 27. Although the impact of a lymphocytotoxic crossmatch-positive liver graft on acute cellular rejection and graft survival in LDLT remains controversial, perioperative desensitization may provide benefits when using a highly sensitized liver graft

    The genome and transcriptome of Trichormus sp NMC-1: insights into adaptation to extreme environments on the Qinghai-Tibet Plateau

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    The Qinghai-Tibet Plateau (QTP) has the highest biodiversity for an extreme environment worldwide, and provides an ideal natural laboratory to study adaptive evolution. In this study, we generated a draft genome sequence of cyanobacteria Trichormus sp. NMC-1 in the QTP and performed whole transcriptome sequencing under low temperature to investigate the genetic mechanism by which T. sp. NMC-1 adapted to the specific environment. Its genome sequence was 5.9 Mb with a G+C content of 39.2% and encompassed a total of 5362 CDS. A phylogenomic tree indicated that this strain belongs to the Trichormus and Anabaena cluster. Genome comparison between T. sp. NMC-1 and six relatives showed that functionally unknown genes occupied a much higher proportion (28.12%) of the T. sp. NMC-1 genome. In addition, functions of specific, significant positively selected, expanded orthogroups, and differentially expressed genes involved in signal transduction, cell wall/membrane biogenesis, secondary metabolite biosynthesis, and energy production and conversion were analyzed to elucidate specific adaptation traits. Further analyses showed that the CheY-like genes, extracellular polysaccharide and mycosporine-like amino acids might play major roles in adaptation to harsh environments. Our findings indicate that sophisticated genetic mechanisms are involved in cyanobacterial adaptation to the extreme environment of the QTP

    A huge intraductal papillary mucinous carcinoma of the bile duct treated by right trisectionectomy with caudate lobectomy

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    <p>Abstract</p> <p>Background</p> <p>Because intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) is believed to show a better clinical course than non-papillary biliary neoplasms, it is important to make a precise diagnosis and to perform complete surgical resection.</p> <p>Case presentation</p> <p>We herein report a case of malignant IPMN-B treated by right trisectionectomy with caudate lobectomy and extrahepatic bile duct resection. Radiologic images showed marked dilatation of the left medial sectional bile duct (B4) resulting in a bulky cystic mass with multiple internal papillary projections. Duodenal endoscopic examination demonstrated very patulous ampullary orifice with mucin expulsion and endoscopic retrograde cholangiogram confirmed marked cystic dilatation of B4 with luminal filling defects. These findings suggested IPMN-B with malignancy potential. The functional volume of the left lateral section was estimated to be 45%. A planned extensive surgery was successfully performed. The remnant bile ducts were also dilated but had no macroscopic intraluminal tumorous lesion. The histopathological examination yielded the diagnosis of mucin-producing oncocytic intraductal papillary carcinoma of the bile duct with poorly differentiated carcinomas showing neuroendocrine differentiation. The tumor was 14.0 × 13.0 cm-sized and revealed no stromal invasiveness. Resection margins of the proximal bile duct and hepatic parenchyma were free of tumor cell. The patient showed no postoperative complication and was discharged on 10<sup>th </sup>postoperative date. He has been regularly followed at outpatient department with no evidence of recurrence.</p> <p>Conclusion</p> <p>Considering a favorable prognosis of IPMN-B compared to non-papillary biliary neoplasms, this tumor can be a good indication for aggressive surgical resection regardless of its tumor size.</p

    Quantum-squeezing effects of strained multilayer graphene NEMS

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    Quantum squeezing can improve the ultimate measurement precision by squeezing one desired fluctuation of the two physical quantities in Heisenberg relation. We propose a scheme to obtain squeezed states through graphene nanoelectromechanical system (NEMS) taking advantage of their thin thickness in principle. Two key criteria of achieving squeezing states, zero-point displacement uncertainty and squeezing factor of strained multilayer graphene NEMS, are studied. Our research promotes the measured precision limit of graphene-based nano-transducers by reducing quantum noises through squeezed states

    Evidence for the different physiological significance of the 6- and 2-minute walk tests in multiple sclerosis

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    <p>Abstract</p> <p>Background</p> <p>Researchers have recently advocated for the 2-minute walk (2MW) as an alternative for the 6-minute walk (6MW) to assess long distance ambulation in persons with multiple sclerosis (MS). This recommendation has not been based on physiological considerations such as the rate of oxygen consumption (V·O<sub>2</sub>) over the 6MW range.</p> <p>Objective</p> <p>This study examined the pattern of change in V·O<sub>2 </sub>over the range of the 6MW in a large sample of persons with MS who varied as a function of disability status.</p> <p>Method</p> <p>Ninety-five persons with clinically-definite MS underwent a neurological examination for generating an Expanded Disability Status Scale (EDSS) score, and then completion of the 6MW protocol while wearing a portable metabolic unit and an accelerometer.</p> <p>Results</p> <p>There was a time main effect on V·O<sub>2 </sub>during the 6MW (<it>p </it>= .0001) such that V·O<sub>2 </sub>increased significantly every 30 seconds over the first 3 minutes of the 6MW, and then remained stable over the second 3 minutes of the 6MW. This occurred despite no change in cadence across the 6MW (<it>p </it>= .84).</p> <p>Conclusions</p> <p>The pattern of change in V·O<sub>2 </sub>indicates that there are different metabolic systems providing energy for ambulation during the 6MW in MS subjects and steady state aerobic metabolism is reached during the last 3 minutes of the 6MW. By extension, the first 3 minutes would represent a test of mixed aerobic and anaerobic work, whereas the second 3 minutes would represent a test of aerobic work during walking.</p

    Recent advances in radiotherapy

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    Radiation therapy has come a long way from treatment planning based on orthogonal radiographs with large margins around tumours. Advances in imaging and radiation planning software have led to three-dimensional conformal radiotherapy and, further, to intensity modulated radiotherapy (IMRT). IMRT permits sparing of normal tissues and hence dose-escalation to tumours. IMRT is the current standard in treatment of head and prostate cancer and is being investigated in other tumour sites. Exquisitely sculpted dose distributions (increased geographical miss) with IMRT, plus tumour motion and anatomical changes during radiotherapy make image guided radiotherapy an essential part of modern radiation delivery. Various hardware and software tools are under investigation for optimal IGRT

    Estimating the lifetime economic burden of stroke according to the age of onset in South Korea: a cost of illness study

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    <p>Abstract</p> <p>Background</p> <p>The recently-observed trend towards younger stroke patients in Korea raises economic concerns, including erosion of the workforce. We compared per-person lifetime costs of stroke according to the age of stroke onset from the Korean societal perspective.</p> <p>Methods</p> <p>A state-transition Markov model consisted of three health states ('post primary stroke event', 'alive post stroke', and 'dead') was developed to simulate the natural history of stroke. The transition probabilities for fatal and non-fatal recurrent stroke by age and gender and for non-stroke causes of death were derived from the national epidemiologic data of the Korean Health Insurance Review and Assessment Services and data from the Danish Monitoring Trends in Cardiovascular Disease study. We used an incidence-based approach to estimate the long-term costs of stroke. The model captured stroke-related costs including costs within the health sector, patients' out-of-pocket costs outside the health sector, and costs resulting from loss of productivity due to morbidity and premature death using a human capital approach. Average insurance-covered costs occurring within the health sector were estimated from the National Health Insurance claims database. Other costs were estimated based on the national epidemiologic data and literature. All costs are presented in 2008 Korean currency values (Korean won = KRW).</p> <p>Results</p> <p>The lifetime costs of stroke were estimated to be: 200.7, 81.9, and 16.4 million Korean won (1,200 KRW is approximately equal to one US dollar) for men who suffered a first stroke at age 45, 55 and 65 years, respectively, and 75.7, 39.2, and 19.3 million KRW for women at the same age. While stroke occurring among Koreans aged 45 to 64 years accounted for only 30% of the total disease incidence, this age group incurred 75% of the total national lifetime costs of stroke.</p> <p>Conclusions</p> <p>A higher lifetime burden and increasing incidence of stroke among younger Koreans highlight the need for more effective strategies for the prevention and management of stroke especially for people between 40 and 60 years of ages.</p
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