Miracle-dz/UniFAR-FTUs huggingface dataset:
Activity of Plasma Membrane V-ATPases Is Critical for the Invasion of MDA-MB231 Breast Cancer Cells*

Background: The V-ATPase has been proposed to function at the plasma membrane in tumor cell invasion. Results: Inhibition of plasma membrane V-ATPases prevented invasion of MDA-MB-231 cells. Conclusion: Activity of plasma membrane V-ATPases is critical for breast cancer cell invasion. Significance: Plasma membrane V-ATPases are a possible therapeutic target to limit metastasis. The vacuolar (H+)-ATPases (V-ATPases) are a family of ATP-driven proton pumps that couple ATP hydrolysis with translocation of protons across membranes. Previous studies have implicated V-ATPases in cancer cell invasion. It has been proposed that V-ATPases participate in invasion by localizing to the plasma membrane and causing acidification of the extracellular space. To test this hypothesis, we utilized two separate approaches to specifically inhibit plasma membrane V-ATPases. First, we stably transfected highly invasive MDA-MB231 cells with a V5-tagged construct of the membrane-embedded c subunit of the V-ATPase, allowing for extracellular expression of the V5 epitope. We evaluated the effect of addition of a monoclonal antibody directed against the V5 epitope on both V-ATPase-mediated proton translocation across the plasma membrane and invasion using an in vitro Matrigel assay. The addition of anti-V5 antibody resulted in acidification of the cytosol and a decrease in V-ATPase-dependent proton flux across the plasma membrane in transfected but not control (untransfected) cells. These results demonstrate that the anti-V5 antibody inhibits activity of plasma membrane V-ATPases in transfected cells. Addition of the anti-V5 antibody also inhibited in vitro invasion of transfected (but not untransfected) cells. Second, we utilized a biotin-conjugated form of the specific V-ATPase inhibitor bafilomycin. When bound to streptavidin, this compound cannot cross the plasma membrane. Addition of this compound to MDA-MB231 cells also inhibited in vitro invasion. These studies suggest that plasma membrane V-ATPases play an important role in invasion of breast cancer cells.
Modeling and control of 4-phase floating interleaving boost converter

Fuel cell systems are current intensive sources, so that their output voltage must be increased to approximately a few hundred volts to be suitable for vehicles power trains or for any potential practical application. For this purpose, boost converter power electronic stages are required. In this paper, a small-signal ac model of high voltage ratio low input current ripple 4-phase Floating Interleaved Boost Converter (FIBC) using PWM switch method will be developed as well as controller design using frequency response techniques will be carried out. Simulation results of 4-phase FIBC using Simplorer will be presented to validate the small-signal ac model and the controller design.
Factors influencing care seeking for a self-defined worst panic attack.

OBJECTIVE Only 60 percent of persons who experience panic attacks seek treatment for them, many at the emergency department. The author documented care-seeking behaviors among persons living in the community who had experienced panic attacks and studied determinants of care seeking. METHODS In-depth structured interviews were conducted with 97 randomly selected community-dwelling adults who met DSM-III-R criteria for panic attacks. Participants were asked whether they had contemplated using or had actually used medical, alternative, and family sources of care when they had experienced their worst attack. RESULTS Seventy-seven participants (79 percent) had considered using a general medical or mental health site when they experienced their worst attack. Of these, 50 (52 percent) had actually used such a site. General medical sites were contemplated more often (72 percent of participants) than mental health sites (27 percent), particularly emergency departments (43 percent) and family physicians' offices (34 percent). Other sources, such as friends or family members, alternative sites, and self-treatment, were contemplated less often. Once contemplated, certain sources were readily used, such as ambulances, family members, and self-treatment. Several factors were significantly associated with whether a person contemplated seeking care: access or barriers to treatment, perception of symptoms and of the reasons for the panic attack, and family-related variables. CONCLUSIONS Contemplation and use of a mental health site after a panic attack was rare among the participants in this study. Further study of determinants of care seeking may help explain why persons who experience panic attacks fail to seek treatment or seek treatment from non-mental health sources.
A 1.27 GHz, All-Digital Spread Spectrum Clock Generator/Synthesizer in 65 nm CMOS

Spread spectrum clocking is an effective solution to reduce the electromagnetic interference produced by digital chips, using a clock signal with a frequency that is intentionally swept (frequency modulated) within a certain frequency range, with a predefined modulation profile. We present the implementation of an all-digital spread spectrum clock generator. The circuit is realized by using a design flow completely based on standard cells and is able to perform clock spreading with an arbitrary modulation profile and a modulation frequency up to 5 MHz. The circuit uses two digitally controlled delay lines driven by a digital modulator to synthesize the output waveform. A replica delay line is employed in a real-time measurement circuit to track process, voltage and temperature variations. A chip has been implemented in a 65 nm CMOS technology. The chip is able to generate signals up to 1.27 GHz. The measured peak level reduction of the clock spectrum, at 750 MHz output frequency, is 20.5 dB with a 6% modulation depth. The power dissipation is 44 mW @ 1.27 GHz.
VO2 slow component: physiological and functional significance.

This paper offers a brief synopsis of the five preceding papers which constitute the proceedings of the symposium "Mechanistic basis of the slow component of VO2 kinetics during heavy exercise. " The key features have been taken from each paper and a coherent position regarding the site and potential underlying mechanisms for the "excess" VO2 is presented. The hypothesis is developed that some aspect of fiber type recruitment patterns might be responsible for this phenomenon. Elucidation of the precise determinants of VO2 during heavy exercise is fundamental to our understanding of muscle energetics. Furthermore, certain patient populations, whose exercise tolerance is limited by impaired cardiovascular and/or respiratory capacity, may benefit from interventions designed to constrain the magnitude of the VO2 slow component.
Defective presentation of MHC class I‐restricted cytotoxic T‐cell epitopes in Burkitt's lymphoma cells

Defects of antigen processing/presentation have been suggested to play a role in the escape of Burkitt's lymphoma (BL) from cytotoxic T lymphocyte (CTL)‐mediated rejection. Impaired presentation of an immunodominant HLA AII‐restricted epitope from the resident or recombinant vaccinia virus‐expressed Epstein‐Barr virus nuclear antigen (EBNA)4 was demonstrated in the EBV‐positive E95B‐BL28 and its EBV‐negative parental BL28 cell lines. We have investigated whether this was due to (i) impaired production of the antigenic peptide, (ii) poor peptide translocation into the ER lumen or (iii) inefficient maturation and transport of the MHC‐peptide complexes at the cell surface. The defect was not overcome by cytosolic expression of a pre‐formed epitope, suggesting that presentation of EBNA4 is not limited by inefficient production of the antigenic peptide. BL28 expressed 5‐ to 10‐fold lower levels of the transporter associated with antigen presentation (TAP) 1 and TAP2 proteins and behaved poorly in a streptolysin‐O‐mediated peptide translocation assay, whereas E95B‐BL28 showed higher TAP expression and virtually normal transporter function. Up‐regulation of HLA AII and reconstitution of TAP activity by treatment with IFN‐γ did not restore presentation of the resident EBNA4 in E95B‐BL28 and did not enhance presentation of the vaccinia virus‐expressed intact protein or preformed epitope. Efficient maturation of class I molecules to Endo H‐resistant species was demonstrated in pulse‐chase experiments. Taken together, our findings identify a previously uncharacterized defect of antigen presentation which appears to affect events occurring after proteasomal degradation but before TAP‐dependent peptide transport and MHC class I assembly and maturation. © 1996 Wiley‐Liss, Inc.
Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases

A proper diagnosis of cirrhosis is essential for the management of patients with chronic liver diseases. We assessed the accuracy of liver stiffness measurement by Fibroscan for the diagnosis of cirrhosis in 1,257 patients with chronic liver diseases of various causes enrolled in a prospective multicenter study as well as clarified causes of discrepancies between liver histology and Fibroscan. One hundred thirty‐two patients had unsuitable biopsy specimens, and 118 had unreliable liver stiffness measurements. Because 232 patients overlapped with a previous study, analysis was performed in the 775 new patients then derived in the whole population (1,007; 165 cirrhosis). Diagnostic accuracy was assessed by receiver operator curve (ROC) analysis. Liver samples were re‐analyzed in case of discrepancies. The area under the ROC (AUROC) was 0.95 (95% CI, 0.93‐0.96) for the diagnosis of cirrhosis in either 775 or 1,007 patients. The cutoff value with optimal diagnosis accuracy was 14.6 kPa in 1,007 patients (positive and negative predictive values, 74% and 96%) with discrepancies among the etiological groups. Eighty patients were misclassified: (1) among 45 patients without cirrhosis with liver stiffness 14.6 kPa or greater, 27 (60%) had extensive fibrosis and 10 (22%) significant perisinusoidal fibrosis; and (2) among 35 patients with cirrhosis and liver stiffness less than 14.6 kPa, 10 (29%) had a macronodular pattern and 25 (71%) either none or mild activity. In conclusion, Fibroscan is a reliable method for the diagnosis of cirrhosis in patients with chronic liver diseases, better at excluding than at predicting cirrhosis using a threshold of 14.6 kPa. False‐negatives are mainly attributable to inactive or macronodular cirrhosis. (HEPATOLOGY 2006;44:1511–1517.)
The association of incident dementia with mortality in PD

Objective: To evaluate the association of incident dementia with mortality in a cohort of patients with idiopathic PD who were nondemented at baseline evaluation, controlling for extrapyramidal sign (EPS) severity at each study visit. Background: The development of dementia has been associated with reduced survival in PD. Because EPS severity is associated with both dementia and mortality in PD, the association of dementia with mortality may be confounded by disease severity. Methods: A cohort of patients with PD was followed annually with neurologic and neuropsychological evaluations. The association of incident dementia and the total Unified PD Rating Scale (UPDRS) motor score with mortality in PD was examined using Cox proportional hazards models with time-dependent covariates. All analyses were adjusted for age at baseline, sex, years of education, ethnicity, and duration of PD. Results: Of 180 PD patients, 41 (22.8%) died during a mean follow-up period of 3.9 ± 2.2 years. Among those who died during the study period, 48.8% (20 of 41) became demented during follow-up, as compared to 23.0% (32 of 139) of those who remained alive. Both incident dementia (RR: 2.2, 95% CI: 1.1 to 4.5, p = 0.04) and the total UPDRS motor score at each study visit (RR: 1.04, 95% CI: 1.02 to 1.07, p = 0.001) were associated with mortality in PD when included in the same Cox model. Conclusions: Incident dementia has an independent effect on mortality when controlling for EPS severity. The development of dementia is associated with a twofold increased mortality risk in PD.
Pancreas preserving total duodenectomy for complex duodenal injury.

CONTEXT To assess the feasibility and safety of a pancreas-preserving total duodenectomy in the management of severe duodenal injury caused by abdominal trauma. CASE REPORT Two patients with both extensive injury of the duodenum and diffuse peritonitis underwent pancreas preserving total duodenectomy at our tertiary care centre. These two young male patients (age 20 and 22 years) presented 2 days and 6 hours respectively following blunt abdominal trauma. The duodenum was almost completely separated from the pancreas. Ampulla was seen as a button on the pancreas. Following total duodenectomy, reconstruction was performed by suturing the jejunum to the head of the pancreas anteriorly and posteriorly away from the ampulla (invagination of the pancreas into the jejunum). There were no complications attributable to the procedure. Both patients are well on follow up. CONCLUSION A Pancreas-preserving total duodenectomy offers a safe alternative to the Whipple procedure in managing complex duodenal injury. This procedure avoids unnecessary resection of the adjacent pancreas and anastomosis to undilated hepatic and pancreatic ducts.
Interaction of the Saccharomyces cerevisiae alpha-factor with phospholipid vesicles as revealed by proton and phosphorus NMR.

Proton and phosphorus-31 nuclear magnetic resonance (1H and 31P NMR) studies of the interaction between a tridecapeptide pheromone, the alpha-factor of Saccharomyces cerevisiae, and sonicated lipid vesicles are reported. 31P NMR studies demonstrate that there is interaction of the peptide with the phosphorus headgroups, and quasielastic light scattering (QLS) studies indicate that lipid vesicles increase in size upon addition of peptide. Previous solution (aqueous and DMSO) studies from this laboratory indicate that alpha-factor is highly flexible with only one long-lived identifiable structural feature, a type II beta-turn spanning the central portion of the peptide. Two-dimensional (2D) 1H nuclear Overhauser effect spectroscopy (NOESY) studies demonstrate a marked ordering of the peptide upon interaction with lipid, suggesting a compact N-terminus, in addition to a stabilized beta-turn. In contrast to our results in both solution and lipid environment, Wakamatsu et al. [Wakamatsu, K. , Okada, A. , Suzuki, M. , Higashijima, T. , Masui, Y. , Sakakibara, S. , & Miyazawa, T. (1986) Eur. J. Biochem. 154, 607-615] proposed a lipid environment conformation, on the basis of one-dimensional transferred NOE studies in D2O, which does not include the beta-turn.
Effect of Total Spinal Anesthesia on Arterial and Venous Responses to Dopamine and Dobutamine

To test whether acute denervation alters the vascular effects of dopamine and dobutamine, we anesthetized 16 greyhounds and placed them on total cardiopulmonary bypass (CPB). Eight dogs received total spinal anesthesia before drug testing; eight dogs were tested in the absence of total spinal anesthesia. During dopamine and dobutamine infusions, venous capacitance [determined by the volume of the CPB venous reservoir (VR)] and mean arterial pressure (MAP) were monitored. The CPB pump flows remained constant throughout our studies. Every dog received six increasing doses of both drugs. In the absence of total spinal anesthesia, both dopamine and dobutamine increased VR (decreased venous capacitance) in a dose-dependent manner. Do but amine decreased MAP in a dose-related fashion but do pa mine had no significant effect on MAP. After total spinal anesthesia, both dopamine and do but amine produced greater dose-related increases in VR (i.e., decreases in venous capacitance) than in the absence of spinal anesthesia. Dopamine increased MAP but dobutamine had no significant effect. These data demonstrate how dopamine and dobutamine differ in their effects on the arterial circulation in the presence or absence of spinal anesthesia. The acute denervation of spinal anesthesia altered venous and arterial dose-response relationships of both drugs. Finally, our study demonstrates the effectiveness of dobutamine and, perhaps even more so, dopamine as possible alternatives to ephedrine for the pharmacologie correction of the non cardiac circulatory se quelae of spinal anesthesia.
Estimation of platelet-activating factor receptors in the endometrium of the pregnant rabbit: regulation of ligand availability and catabolism by bovine serum albumin.

High affinity receptors have been demonstrated for the potent phospholipid autacoid, platelet-activating factor (PAF C18:0; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) in a variety of tissues, including the endometrium. Because of the relative instability of PAF and our previous demonstration that lyso-PAF (1-O-alkyl-2-lyso-sn-glycero-3-phosphorylcholine), the major metabolite of PAF, displaced [3H]PAF from endometrial PAF receptor sites, we have examined the ability of bovine serum albumin (BSA) to prevent degradation of PAF and have characterized PAF and lyso-PAF binding sites in purified rabbit endometrial membranes isolated on Day 6 of pregnancy. In buffer containing the phospholipase A2 inhibitors, quinacrine (10 microM) and dibromoacetophenone (2 microM), and 0.25% BSA, 87.4 +/- 3.2% of added [3H]PAF C18:0 remained intact after incubation at 25 degrees C for 150 min. The metabolic products, lyso-PAF and 1-O-alkyl-2-acyl-sn-glycero-3-phosphorylcholine (alkylacyl-GPC), only amounted to 5.2 +/- 3.2 and 3.3 +/- 1.1, respectively. At the same concentration, rabbit serum albumin (RSA) also significantly protected [3H]PAF C18:0 from metabolism, but bovine gamma globulin (BGG) was ineffective. The presence of 0.25% BSA, however, did not protect [3H]lyso-PAF C18:0 from extensive catabolism: the major product formed was [3H]alkylacyl-GPC. Insignificant amounts of [3H]PAF were formed. Under the same conditions (25 degrees C, 150 min) in the presence of 0.25% BSA, saturation analysis revealed the presence of two types of PAF C18:0 receptors in the endometrial membranes. Type 1 sites had a Kd of 0.42 +/- 0.03 nM (mean +/- SD; n = 3) and binding capacity of 0.11 +/- 0.01 pmol/mg protein. Type 2 receptor sites had a Kd of 5.96 +/- 0.35 nM and a binding capacity of 1.59 +/- 0.22 pmol/mg protein. Thus, in the presence of BSA, the binding capacities of the two classes of receptors were markedly reduced compared to values generated previously in its absence. The Kd of the Type 1 sites was not significantly changed by the presence of BSA. A single class of saturable high-affinity binding sites was demonstrable for lyso-PAF C18:0: Kds ranged from 0.76 +/- 0.58 to 11.1 +/- 0.62 nM, depending on which method of analysis was used (Eadie-Hofstee, Scatchard-Rosenthal, or the Lundon nonlinear method). The binding capacities were equally varied, ranging from 0.15 +/- 0.08 to 15.17 +/- 4.95 pmol/mg protein. (ABSTRACT TRUNCATED AT 400 WORDS)
A common nonsense mutation in EphB2 is associated with prostate cancer risk in African American men with a positive family history

Background: The EphB2 gene was recently implicated as a prostate cancer (PC) tumour suppressor gene, with somatic inactivating mutations occurring in ∼10% of sporadic tumours. We evaluated the contribution of EphB2 to inherited PC susceptibility in African Americans (AA) by screening the gene for germline polymorphisms. Methods: Direct sequencing of the coding region of EphB2 was performed on 72 probands from the African American Hereditary Prostate Cancer Study (AAHPC). A case-control association analysis was then carried out using the AAHPC probands and an additional 183 cases of sporadic PC compared with 329 healthy AA male controls. In addition, we performed an ancestry adjusted association study where we adjusted for individual ancestry among all subjects, in order to rule out a spurious association due to population stratification. Results: Ten coding sequence variants were identified, including the K1019X (3055A→T) nonsense mutation which was present in 15.3% of the AAHPC probands but only 1.7% of 231 European American (EA) control samples. We observed that the 3055A→T mutation significantly increased risk for prostate cancer over twofold (Fisher’s two sided test, p = 0.003). The T allele was significantly more common among AAHPC probands (15.3%) than among healthy AA male controls (5.2%) (odds ratio 3.31; 95% confidence interval 1.5 to 7.4; p = 0.008). The ancestry adjusted analyses confirmed the association. Conclusions: Our data show that the K1019X mutation in the EphB2 gene differs in frequency between AA and EA, is associated with increased risk for PC in AA men with a positive family history, and may be an important genetic risk factor for prostate cancer in AA.
Sedation with propofol for interventional endoscopic procedures: A risk factor analysis

Objective. Propofol sedation for mainly diagnostic endoscopic procedures has proved safe in recent trials, with no need for endotracheal intubation. However, there is evidence that cardiorespiratory side effects occur more frequently and that assisted ventilation may be necessary if propofol sedation is performed for interventional endoscopic procedures. Material and methods. Over a 6-year period, all adverse events (defined as premature termination of the procedure due to sedation-related events or either the need for assisted ventilation or admission to ICU) occurring during 9547 endoscopic interventions (UGI, n=5.374, ERCP, n=3.937, EUS, n=236) under propofol sedation were assessed. Results. A total of 135 adverse events (1.4%) were documented. Assisted ventilation was necessary in 40 patients (0.4%); 9 patients required endotracheal intubation (0.09%); 28 needed further monitoring on the ICU (0.3%); and 4 patients died, 3 potentially due to sedation-related side effects (mortality, 0.03%). Independent risk factors for sedation-related side effects were emergency endoscopic examinations and a total propofol dose >100 mg. Conclusions. Interventional endoscopy under propofol sedation is not risk-free. Increased attention must be focused on close monitoring of vital parameters, particularly when undertaking long-lasting interventions and emergency procedures.
Design and Implementation of an Open Sourced Location Service System for the Aglets Mobile Agent System

Mobile agent technologies can be applied in many fields, including electronic commerce, personal assistance, secure brokering, distributed information retrieval, telecommunication network services, monitoring and notification, etc. Since most of the mobile agents rely on a location service system to communicate with each other in the network environment, the location service system must provide reliable location information and guarantee the message delivery. The aglets system is a popular open sourced Java-based mobile agent system, yet it current supports no complete location service solution. This work designs and implements an open sourced location service system for the aglets mobile agent system, which has four major advantages: easy to integrate for legacy applications, easy to join servers in a single region, easy to link among multi-regions for different laboratories, and easy to implement, thus making the range of applications more extensive. Finally, the experimental results demonstrate that our system is efficient in various network environments