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The lung, followed by regional lymph node and bone, is the most common site for extrahepatic metastasis of hepatocellular carcinoma (HCC). Metastatic skin lesion of HCC is rare, and it is a sign of poor prognosis, indicating the strong possibility of metastases in other regions of the body. We report the case of a 52-year-old male with multiple metastases, including skin metastasis of HCC, which were treated with multidisciplinary therapy.

Anti-icing system can reduce traffic accidents and congestion by quickly removing the frozen road surface area. there is no decision criteria for determining application of the Anti-icing system in Korea. In this study, we proposed the decision criteria for determining application of the anti-icing system based on weather and road conditions, i.e., geometric and topographic conditions. Regional climate survey, Solar Radiation analysis, and dynamic vehicle simulation considered road geometry was conducted to standardize the installation method of anti-icing system. Also, we have developed a software that can be determined an installation of anti-icing system.

This study aims to construct the performance data for smoke-control zone and realize the safety of injection and pressurization room which is composed of supply air pressure zone, vestibule, smoke-control zone and stairwell. To obtain this, smoke-control system and the device of the opening-closing force of fire door are manufactured. This subject is the analysis of the closing force, angular velocity and fire door size in the case of fixed volume flow rate. Based on the results, closing force increased as fire door size and closing angular velocity increases. Also, it is remark that there exists a critical angular velocity, which maintains constant maximum closing force even though the angular velocity increases more.

Acidic protein levels in the milk decrease markedly as lactation progresses, suggesting that it is an important part of the colostrum. However, little attention has been paid to their biological function. In this study, we isolated the acidic protein fraction of bovine colostrum (AFC, isoelectric point

This article discusses the current National Comprehensive Cancer Network guidelines and other available Western and Eastern guidelines for the surveillance of gastric cancer following surgical resection. It reviews the literature assessing the utility of intensive surveillance strategies for gastric cancer, which fails to show an improvement in survival. The unique issues relating to follow-up of early gastric cancer and after endoscopic resection of early gastric cancer are discussed. This article also reviews the available modalities for follow-up. In addition, it briefly discusses the advancements in treatment of recurrent and metastatic disease and the implications for gastric cancer survival and surveillance strategies.

Nervous necrosis viruses (NNV) cause serious economic losses in marine fish cultivation. The red-spotted grouper NNV (RGNNV) is the most common species of NNV worldwide. There have been many efforts to develop prophylactic NNV vaccines, and various types of vaccine candidate have been suggested. However, most were designed as injectable vaccines, which are not suitable for large-scale vaccination and cause too much stress to the fish. Oral vaccination through voluntary feeding is an ideal way to provide protective immunity to fish. In the present study, recombinant Saccharomyces cerevisiae producing RGNNV capsid protein was used as oral vaccine. The recombinant yeast was prepared in freeze-dried form after disruption. Convict groupers were divided into three groups, control, and oral and parenteral vaccination groups, each consisting of 700 fishes. The control group received no treatment, the parenteral group received one intraperitoneal injection of RGNNV virus-like particles, and the oral vaccination group consumed feed containing the lysed recombinant yeast; voluntary intake was allowed four times at one-week intervals. Both vaccination groups produced serum RGNNV neutralizing antibody titers of >103 (log 2, 9.96), sustained for at least 95days post-immunization. In addition, in response to challenge with RGNNV both groups suffered significantly reduced mortality and had reduced brain RGNNV titers. These results indicate that recombinant yeast-based oral fish vaccines have great potential for large-scale vaccination.

In this paper, effect of ultrafine ceria (UFC) particle of which size is as small as 20 nm on CMP performance was investigated. Compared to conventionally used 100 nm abrasive particle which is made by calcination process, almost 80% scratch reduction was obtained by using UFC. However, a UFC slurry showed unstable material removal rate behavior from less than 200 A/min to over 2000 A/min, depending on polishing pad surface characteristics. As pad surface roughness increases, oxide removal rate using UFC drops abruptly to less than 200 A/min. In order to use UFC for scratch reduction, the pad surface roughness optimization is necessary to avoid a sudden drop in the removal rate. This study gives a possible boundary for pad surface roughness for UFC application for CMP.

In this study, the effect of the friction and wear of a polishing pad on the material removal rate of a silicon oxide wafer was investigated during chemical mechanical polishing (CMP) with ceria slurry. Further, the effect of surface properties of the polishing pad, such as surface roughness and hardness, on the variation in the material removal rate was examined. From a tribological viewpoint, the in-situ friction force was monitored during the CMP process, and wear of the polishing pad was controlled by different types of conditioners. After CMP, the pad surface roughness was measured by optical profiling and scanning electron microscopy. Experimental results showed that the material removal rate was almost linearly proportional to the friction force between the pad and the wafer surface, irrespective of the properties of the pad. Experiments on the dependency of the pad wear rate on the material removal rate showed that the material removal rate increased with a decrease in the pad wear rate. Experiments and pad characterization confirmed that such a correlation was attributed to the pad surface roughness and the friction force.

When fire occurs in complex or building, toxic gas is important factor for evacuation because it cause death of evacuees. The effect of toxic gas which effects human motion is calculated using Purser's Fractional Effective Dose(FED). The FDS_EVAC is used for evacuation. However, FED of FDS_EVAC has some problem of application because it dose not considers evacuees's gender and age groups but using single subject. In this study, numerical analysis using modified FED which considers gender and age group of evacuees was performed. We investigate the effect of improved FED on the evacuation. We applied evacuation analysis to exhibition centre where the evacuees was set one thousand five hundred people. The FED is increasing with children 2%, male 17%, female 4%, adult 13% and elderly people 22%. Fatality is increasing due to increased FED. Key Words : FED, evacuation, FDS † Corresponding Author: Hong Sun Ryou, Tel : +82-2-820-5280, E-mail : cfdmec@cau.ac.krDepartment of Mechanical Engineering, Chung Ang University, 84, Heukseok-ro, Dongjak-Gu, Seoul 156-756, Korea

Total extracts of ginseng (the root of Panax ginseng C. A. MEYER) and saponin and polysaccharide fractions have been the main products used to investigate novel effects of ginseng over the last five decades. However, the differences if any between the pharmacological effects of total extract and saponin and polysaccharide fractions are largely unknown. In this study, we compared their effects on influenza A virus infection. Mice received total extract of Korean red ginseng (RG), and polysaccharide and saponin fractions of Korean RG, orally for 14 d prior to influenza A virus infection. Seventy eight percent of mice infected with 2× the 50% lethal dose (LD50) of virus survived when administered the polysaccharide fraction, compared to 67%, 56% and 17% when administered total extract, saponin fraction and phosphate-buffered saline (PBS), respectively. Moreover, body weight loss in mice given the polysaccharide fraction was significantly reduced while there was mild reduction in body weight loss in that receiving saponin fraction or total extract when mice were infected with 0.2× or 0.5×LD50 of virus. We also confirmed that the polysaccharide fraction was most effective in reducing the accumulation of tumor necrosis factor alpha (TNF-α)/inducible nitric oxide synthase (iNOS)-producing dendritic cells (tipDCs) in the mouse lungs. Our results indicate that the polysaccharides of RG have a pronounced beneficial effect on the symptoms of influenza virus infection.

This study examines the effectiveness of robotic pancreatoduodenectomy vs open pancreatoduodenectomy for clinically relevant pancreatic fistula occurrence and other major postoperative outcomes.

Distal cholangiocarcinoma (DC) and pancreatic ductal adenocarcinoma (PDAC) are often managed as 1 entity, yet direct comparisons are lacking. Our aim was to use 2 large multi-institutional databases to assess treatment, pathologic, and survival differences between these diseases.This study included patients with DC and PDAC who underwent curative-intent pancreaticoduodenectomy from 2000 to 2015 at 13 institutions comprising the US Extrahepatic Biliary Malignancy and Central Pancreas Consortiums. Primary endpoint was disease-specific survival (DSS).Of 1,463 patients, 224 (15%) had DC and 1,239 (85%) had PDAC. Compared with PDAC, DC patients were less likely to be margin-positive (19% vs 25%; p = 0.005), lymph node (LN)-positive (55% vs 69%; p0.001), and receive adjuvant therapy (57% vs 71%; p 0.001). Of DC patients treated with adjuvant therapy, 62% got gemcitabine alone and 16% got gemcitabine/cisplatin. Distal cholangiocarcinoma was associated with improved median DSS (40 months) compared with PDAC (22 months; p0.001), which persisted on multivariable analysis (hazard ratio 0.65; 95% CI 0.50 to 0.84; p = 0.001). Lymph node involvement was the only factor independently associated with decreased DSS for both DC and PDAC. The DC/LN-positive patients had similar DSS as PDAC/LN-negative patients (p = 0.74). Adjuvant therapy (chemotherapy ± radiation) was associated with improved median DSS for PDAC/LN-positive patients (21 vs 13 months; p = 0.001), but not for DC patients (38 vs 40 months; p = 0.62), regardless of LN status.Distal cholangiocarcinoma and pancreatic ductal adenocarcinoma are distinct entities. Distal cholangiocarcinoma has a favorable prognosis compared with PDAC, yet current adjuvant therapy regimens are only associated with improved survival in PDAC, not DC. Therefore, treatment paradigms used for PDAC should not be extrapolated to DC, despite similar operative approaches, and novel therapies for DC should be explored.

Background Pseudoviruses (PsVs) that encapsidate a reporter plasmid DNA have been used as surrogates for native human papillomavirus (HPV), whose continuous production is technically difficult. HPV PsVs have been designed to form capsids made up of the major capsid protein L1 and the minor capsid proteins L2. HPV PsVs have been produced in 293TT cells transfected with plasmid expressing L1 and L2 protein and plasmid containing the reporter gene. Several studies have suggested that naturally occurring HPV virions contain cellular histones, and histones have also been identified in mature HPV PsVs. However, the effect of the histones on the properties of the PsVs has not been investigated. Using heparin chromatography, we separated mature HPV type 16 PsVs into three fractions (I, II, and III) according to their heparin-binding affinities. Results The amounts of cellular histone and cellular nucleotides per PsV were found to increase in the order fraction I, II and III. It appeared that PsVs in fraction I contains just small amount of cellular histone in Western blot analysis. The proportions of the three fractions in PsV preparations were 83.4, 7.5, and 9.1 % for fraction I, II, and III PsVs, respectively. In the electron microscope PsVs in fraction I appeared to have a more condensed structure than those in fractions II and III. Under the electron microscope fraction II and III PsVs appeared to be covered by substantial amounts of cellular histone while there was no visible histone covering PsVs of fraction I. Also the levels of reporter gene expression in infections of fraction II and III PsVs to 293TT cells were significantly lower than those in infections of fraction I PsV, and fraction II and III particles had significantly reduced immunogenicity. Conclusions Our findings suggest that the involvement of large amounts of cellular histones during PsV formation interferes with the structural integrity of the PsVs and affects their immunogenicity. The fraction I particle therefore has the most suitable characteristics for use as an HPV PsV. Electronic supplementary material The online version of this article (doi:10.1186/s12896-016-0296-3) contains supplementary material, which is available to authorized users.

Charge variants (acidic and basic) of recombinant monoclonal antibodies (Mabs) have received much attention due to their potential biological effects. C-terminal lysine variants are common in Mabs and their proportion is affected by the manufacturing process. In the present study, changes of trastuzumab charge variants brought about by carboxypeptidase B treatment and subsequent storage at 8 or 37 °C for up to 24 h were monitored by cation-exchange chromatography analysis to investigate the effects of C-terminal lysine cleavage and its subsequent reaction at 8 or 37 °C. C-terminal lysine cleavage at 8 °C reduced the fraction of basic species and had little effect on the fraction of acidic species. Analysis of individual peaks demonstrated that C-terminal lysine cleavage induced both increases and decreases in individual acidic variants, with the result that there was little overall change in the overall proportion of acidic species. It appeared that most of the basic variant Mab molecules but only a fraction of the acidic variant molecules had C-terminal lysines. Increasing the temperature to 37 °C appeared to increase the fraction of acidic species and decrease main species significantly, without a similar change in basic species. These results indicate that length of exposure to elevated temperature is a critical consideration in charge variant analysis.

Post CMP defect is a critical process parameter to yield enhancement and device reliability in sub-14nm semiconductor manufacturing as "killing" particle size has shrunk according to device shrinkage. In order to improve defect at post CMP step, CMP has an in-situ cleaning module, commonly composed of megasonic cleaning, brush scrubber cleanings, fluid jet cleaning and their combination. Among the module, brush scrubber cleaning is the most effective method in particle removal due to its physical force. Although many studies have been conducted to optimize particle removal efficiency of brush cleaning, its cross contamination effect has not been considered for the optimization of post CMP defects. In this paper, effect of brush scrubber cleaning on the post CMP defect and its optimization process are explored. In addition to cross contamination effect, equipment aspect of optimization is also investigated. Chemical spray bar position to the wafer and mechanical operation are key controlling factors. Brush motor torque analysis suggests how to optimize brush operation. Experimental results in this paper provide insight into post CMP cleaning optimization.

Human respiratory syncytial virus (hRSV) is the most common cause of bronchiolitis and pneumonia in infants. The lack of proper prophylactics and therapeutics for controlling hRSV infection has been of great concern worldwide. Xylitol is a well-known sugar substitute and its effect against bacteria in the oral cavity is well known. However, little is known of its effect on viral infections. In this study, the effect of dietary xylitol on hRSV infection was investigated in a mouse model for the first time. Mice received xylitol for 14 d prior to virus challenge and for a further 3 d post challenge. Significantly larger reductions in lung virus titers were observed in the mice receiving xylitol than in the controls receiving phosphate-buffered saline (PBS). In addition, fewer CD3(+) and CD3(+)CD8(+) lymphocytes, whose numbers reflect inflammatory status, were recruited in the mice receiving xylitol. These results indicate that dietary xylitol can ameliorate hRSV infections and reduce inflammation-associated immune responses to hRSV infection.

Vaccination is the main strategy for preventing influenza infection. However, vaccine efficacy is influenced by several factors, including age and health status. The efficacy of the influenza vaccine is much lower (17% to 53%) in individuals over 65 yr of age compared with young adults (70% to 90%). Therefore, increasing vaccine efficacy remains a challenge for the influenza vaccine field. In this study, we investigated the impact of supplementing vaccination with the dietary intake of Korean red ginseng (RG) extract and RG saponin. Mice were immunized two times intranasally with inactivated influenza A (H1N1) virus. Mice received RG extract or RG saponin orally for 14 d prior to the primary immunization. After the primary immunization, mice continued to receive RG extract or RG saponin until the secondary immunization. Mice vaccinated in combination with dietary intake of RG extract and RG saponin showed elevated serum anti-influenza A virus IgG titers and improved survival rates in lethal influenza A virus infection: 56% and 63% of mice receiving RG extract or RG saponin survived, respectively, while 38% of mice that only received the vaccine survived. Moreover, mice receiving RG extract supplementation recovered their body weight more quickly than those not receiving RG extract supplementation. We propose that the dietary intake of RG extract and RG saponin enhances the vaccine-induced immune response and aids in providing protection against influenza virus infection.

Background Despite rigorous manual counting protocols and the classification of retained surgical items (RSIs) as potential "never events," RSIs continue to occur in approximately 1 per 1,000 to 18,000 operations. This study's goals were to evaluate the incorporation of a radiofrequency detection system (RFDS) into existing laparotomy sponge- and Raytec-counting protocols for the detection of RSIs and define associated risk factors. Study Design All patients undergoing surgery at the University of North Carolina Hospitals from September 2009 to August 2010 were enrolled consecutively. The performance of an RFDS-incorporated accounting protocol for detecting RSIs was prospectively evaluated. Several operative metrics were recorded to identify risk factors for miscounts. Results A total of 2,285 patients were enrolled. One near miss was detected by the RFDS. Thirty-five miscounts occurred, for a rate of 1.53%. The ultimate locations of miscounted items were surgical site (n = 11), within operative suite (n = 10), surgical drapes (n = 2), and emergency protocol deviations (n = 12). Perioperative variables associated with miscounts were higher estimated volume of blood lost, longer operations, higher number of laparotomy sponges used, open surgical approach, "after hours" operations, change of surgical team during operation, weekend or holiday operations, unanticipated changes in operative plan during surgery, and emergency operations. Body mass index was not associated with miscounts. Surveys completed by participating surgical staff suggested high confidence in the RFDS for prevention of RSIs. Conclusions The incorporation of the RFDS assisted in the resolution of a near-miss event (1 of 2,285) not detected by manual counting protocols and assisted in the resolution of 35 surgical-sponge miscounts. No known RSIs occurred during the study period. Risk factors for miscounts were identified and can help identify at-risk surgical populations.

Human papillomavirus (HPV) is the cause of most cases of cervical cancer. HPV type 58 (HPV58) is the second most frequent cause of cervical cancer and high-grade squamous intraepithelial lesions (HSIL) in Asia and South / Central America, respectively. However, there is no vaccine against HPV58, although there are commercially available vaccines against HPV16 and 18. In this study, we produced HPV58 L1 protein from Saccharomyces cerevisiae, and investigated its immunogenicity. We first determined the optimum period of culture for obtaining HPV58 L1. We found that a considerable portion of the HPV58 L1 resulting from 48 h culture cannot be recovered by purification, while the HPV58 L1 resulting from 144 h culture is recovered efficiently: the yield of HPV58 L1 finally recovered from 144 h culture was 2.3 times higher than that from 48 h culture, although the production level of L1 protein from 144 h culture was lower than that from 48 h culture. These results indicate that the proportion of functional L1 protein from 144 h-cultured cells is significantly higher than that of 48 h-cultured cells. The HPV58 L1 purified from the 144 h culture was correctly assembled into structures similar to naturally occurring HPV virions. Immunization with the HPV58 L1 efficiently elicited anti-HPV58 neutralizing antibodies and antigen-specific CD4+ and CD8+ T cell proliferations, without the need for adjuvant. Our findings provide a convenient method for obtaining substantial amounts of highly immunogenic HPV58 L1 from S. cerevisiae.

A general stoichiometric cation exchange mechanism does not fully explain the unique exchange behaviors of Na-4-mica, the most highly charged swelling 2:1 phyllosilicate. Herein, we present for the first time a novel model of hydronium-promoted equilibrium for the cation exchange reaction of highly charged swelling 2:1 phyllosilicates with alkali metal cations. The exchange reaction of Na-4-mica with alkali metal cations revealed that adsorbed cations undergo further exchange with hydronium ions to result in the unprecedented back-release and position rearrangement of adsorbed cations. During the exchange reaction, hydronium ions play a key role as not competitive but stabilizing cation. Stabilization is accomplished through replacing half of the adsorbed cations and consequently relocating their position. Therefore, this hydronium-promoted equilibrium mechanism would provide a novel intellectual framework not only for understanding cation exchange reactions of various highly charged phyllosilicates but a...

Micro-scratch formation on a post-chemical mechanical polishing (CMP) wafer surface is one of the critical problems that should be solved for miniaturization and reliability of a semiconductor device. In this study, the mechanism of micro-scratch formation during CMP was investigated through experiments and simulations. When a used pad was utilized in the experiments, it was found that micro-scratches could be generated by the polishing process that was done with DI water and additive only without abrasive particles. In order to analyze these micro-scratches under a used pad process, the change in surface properties of the polishing pad before and after the CMP was investigated using various surface sensitive techniques. In addition, 2-dimensional finite element analysis (FEA) of CMP process was performed to verify the experimental results. Especially, the FE model with a particle put inside a pad pore was considered to examine how it plays a role in micro-scratch generation. In summary, the scientific results from experiments and simulations in this study first revealed that the pad–particle mixture could be formed on the pad surface during CMP process, which would be one of the major factors leading to micro-scratch generation.

There is increasing demand for virus-like particles (VLPs) as a platform for prophylactic vaccine production. However, little attention has been paid to how downstream processing affects the structure and immunogenicity of the VLPs. In this study, we compared three methods of purifying human papillomavirus type 16 (HPV16) VLPs, each including the same cation-exchange chromatography (CEC) step. Method T-1 uses both ammonium sulfate precipitation (ASP) and a step to remove precipitated contaminating proteins (SRPC) prior to CEC, while T-2 uses only the SRPC step prior to CEC and T-3 includes neither step. We compared the structural integrity and immunogenicity of the HPV16 VLPs resulting from these three methods. All three preparations were highly pure. However, the final yields of the VLPs obtained with T-2 were 1.5 and 2 fold higher than with T-1 and T-3, respectively. With respect to structural integrity, T-1 and T-2 HPV16 VLPs had smaller hydrodynamic diameters and higher reactivity towards monoclonal anti-HPV16 neutralizing antibodies than T-3 VLPs, indicating higher potentials of T-1 and T-2 VLPs for eliciting anti-HPV16 neutralizing antibodies. Moreover, it was confirmed that the T-1 and T-2 HPV16 VLPs elicit anti-HPV16 neutralizing antibodies more efficiently than T-3 HPV16 VLPs do in mice immunizations: the abilities for eliciting neutralizing antibodies were in the order T-2 VLP > T-1 VLP > T-3 VLP. We conclude that the process design for purifying HPV VLPs is a critical determinant of the quality of the final product.

CIA05 is a toll-like receptor (TLR) 4 agonist derived from an Escherichia coli lipopolysaccharide (LPS) mutant and has been shown to have potential as a vaccine adjuvant. In this study, we investigated the immunopotentiating activity of the adjuvant system CIA06, which is comprised of CIA05 and aluminum hydroxide (alum), when used with the human papillomavirus (HPV) L1 virus-like particles (VLPs) vaccine. BALB/c mice were immunized intramuscularly three times at 2-week intervals with HPV16 L1 VLPs alone or in the presence of various combinations of CIA05 and alum, and the immune responses were assessed. We found that the combination of CIA05 and alum at a ratio of 1:50 (designated CIA06B) yielded the highest immune response in terms of serum anti-HPV L1 VLP IgG antibody titers, splenocyte interferon (IFN)-γ secretion, and antigen-specific memory B cell responses. The immunogenicity of the CIA06B-adjuvanted HPV16/18 L1 VLP vaccine was compared with that of the currently licensed HPV vaccine Cervarix™. The CIA06B-adjuvanted vaccine was similar to Cervarix™ with regard to eliciting serum antigen-specific IgG antibodies and virus-neutralizing antibodies but more effective at inducing splenic cytokine production and memory B cells. We also observed that the antigen-specific IgG antibody titers, splenic IFN-γ secretion and memory B cells induced by the CIA06B-adjuvanted HPV vaccine remained high up to 24 weeks post-immunization. Based on these data, we concluded that CIA06B may have potential as an adjuvant in a potent prophylactic vaccine against HPV infection.

hpb_432 228..235 Background: The effect of diabetes on survival after resection pancreatic ductal carcinoma (PDAC) is unclear. The present study was undertaken to determine whether pre-operative diabetes has any predictive value for survival. Methods: A retrospective review from seven centres was performed. Metabolic factors, tumour char- acteristics and outcomes of patients undergoing resection for PDAC were collected. Univariate and multivariable analyses were performed to determine factors associated with disease-free (DFS) and overall survival (OS). Results: Of the 509 patients in the present study, 31.2% had diabetes. Scoring systems were devised to predict OS and DFS based on a training set (n = 245) and were subsequently tested on an independent set (n = 264). Pre-operative diabetes (P 2c m (P = 0.001), metastatic nodal ratio >0.1 (P < 0.001) and R1 margin (P < 0.001) all correlated with DFS and OS on univariate analysis. Scoring systems were devised based on multivariable analysis of the above factors. Diabetes and the metastatic nodal ratio were the most important factors in each system, earning two points for OS and four points for DFS. These scoring systems significantly correlated with both DFS (P < 0.001) and OS (P < 0.001). Conclusion: Pre-operative diabetes status provides useful information that can help to stratify patients in terms of predicted post-operative OS and DFS.

The L1 protein is a major component of prophylactic human papillomavirus (HPV) vaccines. Little effort has been made to improve the productivity of L1 protein by optimizing cell culture conditions although the high price of the vaccines is considered one of the factors limiting its widespread use. In biopharmaceutical manufacturing, strategies for optimizing culture conditions tend to focus on improvements in upstream processing rather than final yield because of the complexities of purification procedures. In this study, we investigated L1 protein productivity as a function of the composition of the carbon source and the point of cell harvesting in the Saccharomyces cerevisiae expression system. We performed 44 series of purifications and achieved the highest productivity when the cells were cultured in a medium composed of 7% glucose and 1% galactose for 144 h. The final yield of L1 protein was markedly affected by the glucose: galactose ratio and the point at which cells were harvested: there was a 15-fold difference between the lowest and highest yields. We believe that optimization of the composition of the carbon source and the time of cell harvest have considerable potential for reducing the cost of production of HPV L1 protein.

We recently reported that a partner-assisted emotional disclosure intervention for gastrointestinal cancer led to improvements in relationship quality and intimacy for couples in which the patient initially reported higher levels of holding back from discussing cancer-related concerns. The purposes of the present study were to examine outcomes at 8-week follow-up and process variables that may influence treatment effects. One hundred thirty couples were randomly assigned to either partner-assisted emotional disclosure or an education/support control condition. Participants completed measures of relationship quality, intimacy, and psychological distress before randomization, post-treatment, and 8 weeks later. Patients in the disclosure intervention completed measures of negative affect immediately following each treatment session, and their level of expressiveness during the sessions was rated by trained observers. Data were analyzed using multilevel modeling. Among couples in which the patient initially reported higher levels of holding back, the disclosure intervention led to improvements in relationship quality and intimacy that were maintained at 8-weeks follow-up. High levels of patient expressiveness during the disclosure sessions were associated with improvements in relationship quality and intimacy, and high levels of patient negative affect immediately following the sessions were associated with reductions in psychological distress at the post-test assessment. For couples in which the patient tends to hold back from discussing concerns, partner-assisted emotional disclosure is a beneficial intervention leading to improvements in relationship functioning that maintain over time. Future research is needed to examine methods of enhancing intervention effects, including encouraging patient expressiveness and negative affect during the sessions.

The purpose of the study was to evaluate the utilization and morbidity associated with feeding jejunostomy tubes (JT) placed at the time of gastroesophageal resection (GER). Under institutional review board approval, a prospective database of patients undergoing GER from January 2004 to September 2010 was reviewed. Data analyzed included patient demographics, postoperative complications, JT use, and JT specific complications. Fisher’s exact tests explored associations with utilization of a JT following resection. Seventy-three patients (51 men, 22 women, median age of 59) underwent placement of a JT at the time of GER (total gastrectomy = 28, Ivor–Lewis = 28, subtotal gastrectomy = 8, proximal gastrectomy = 6, and transhiatal esophagectomy = 3) of both malignant (97%) and benign (3%) disease processes. Twenty-one JT specific complications (11 minor and 10 major) were identified. Reoperation was required in the management of two complications (small bowel obstructions), while all other complications were easily managed by an interventional radiologist (n = 8), bedside procedure (n = 5), or did not require intervention (n = 6). Eighty-six percent of patients were discharged tolerating a postgastrectomy diet, 10% nothing per orem, and 4% a liquid diet. Inpatient enteral nutrition (EN) was initiated in 68%, but continued on discharge in only 54% secondary to failure to thrive (54%), dysphagia (21%), anastomic leak (15%), chyle leak (3%), esophagostomy (3%), and duodenal stump leak (3%). The mean time to discontinuance of EN and removal of the JT was 44 days (range, 4–203) and 71 days (range, 15–337) respectively. Although only 13% (n = 5) of patients requiring adjuvant therapy were utilizing their JT at the commencement of therapy, 75% (n = 21) required EN during its course. The median time to adjuvant therapy was found to be slightly longer in those who required outpatient EN versus those who did not (61 vs. 90 days, p = 0.08). However, the median time to adjuvant therapy did not differ between those who were and were not receiving EN at the time of adjuvant therapy commencement (80 vs. 92 days, p = 0.2). Age (p = 0.4), number of co-morbidities (p = 0.2), preoperative percent body weight loss (p = 0.9), and clinical stage (p = 0.8) were not significantly associated with outpatient JT use. Patients who suffered a postoperative complication were most likely to require EN (p = 0.002), an association that strengthened as the number of complications increased (p = 0.0008). Although not statistically significant, a trend towards increased outpatient EN was noted in patients who underwent transhiatal esophagectomy and total gastrectomy (p = 0.06). JT placement carries a considerable morbidity in patients undergoing GER. However, because it is difficult to preoperatively ascertain who will need prolonged EN, the routine placement of a JT is recommended, particularly in those who will likely require adjuvant therapy or are at high risk for postoperative complications. Despite patient desires for early removal of an unused JT, caution should be taken if adjuvant therapy is being considered.

Purpose Rectal cancer is often clinically resistant to radiotherapy (RT) and identifying molecular markers to define the biologic basis for this phenomenon would be valuable. The nuclear factor κ-light chain-enhancer of activated B cells (NF-κB) is a potential anti-apoptotic transcription factor that has been associated with resistance to RT in model systems. The present study was designed to evaluate NF-κB activation in patients with rectal cancer undergoing chemoradiotherapy to determine whether NF-κB activity correlates with the outcome in rectal cancer patients. Methods and Materials A total of 22 patients underwent biopsy at multiple points in a prospective study and the data from another 50 were analyzed retrospectively. The pretreatment tumor tissue was analyzed for multiple NF-κB subunits by immunohistochemistry. Serial tumor biopsy cores were analyzed for NF-κB–regulated gene expression using reverse transcriptase polymerase chain reaction and for NF-κB subunit nuclear localization using immunohistochemistry. Results Several NF-κB target genes (Bcl-2, cellular inhibitor of apoptosis protein [cIAP]2, interleukin-8, and tumor necrosis factor receptor-associated-1) were significantly upregulated by a single fraction of RT at 24 h, demonstrating for the first time that NF-κB is activated by RT in human rectal tumors. The baseline NF-κB p50 nuclear expression did not correlate with the pathologic response to RT. However, an increasing baseline p50 level was prognostic for overall survival (hazard ratio, 2.15; p = .040). Conclusion NF-κB nuclear expression at baseline in rectal cancer was prognostic for overall survival but not predictive of the response to RT. Larger patient numbers are needed to assess the effect of NF-κB target gene upregulation on the response to RT. Our results suggest that NF-κB might play an important role in tumor metastasis but not to the resistance to chemoradiotherapy.

Background: Laparoscopic left pancreatectomy (LLP) is associated with favorable outcomes compared with open left pancreatectomy (OLP). However, it is unclear if the risk factors associated with operative morbidity differ between these two techniques. Guidelines for determining which patients should undergo OLP versus LLP do not exist. Methods: A multi-institutional analysis of OLP and LLP performed in 9 academic medical centers was undertaken. LLP cases were defined in an intent-to-treat manner. Perioperative variables were analyzed to identify factors associated with complications and pancreatic fistulae after OLP and LLP. In addition, complication and fistula rates for patients undergoing OLP and LLP were compared in matched cohorts to determine if one approach resulted in superior outcomes over the other. Results: Six hundred and ninety-three left pancreatectomy cases (439 OLP, 254 LLP) were analyzed. OLP and LLP cases were similar with respect to patient age and American Society of Anesthesiologists score. Body mass index (BMI) was higher in patients undergoing LLP. OLP was more often performed for adenocarcinoma and larger tumors, resulted in longer resected specimen lengths, and more commonly involved concomitant splenectomy. Estimated blood loss was higher and operative times were longer during OLP. On multivariate analysis, variables associated with major complications and clinically significant fistulae differed between OLP and LLP. Patients with body mass index ≤27, without adenocarcinoma, and with pancreatic specimen length ≤8.5 cm had significantly higher rates of significant fistulae after OLP than after LLP; in contrast, no preoperatively evaluable variables were associated with a higher likelihood of significant fistula after LLP versus OLP. Conclusions: Risk factors for complications and pancreatic fistulae after left pancreatectomy differ when open versus laparoscopic techniques are employed. Preoperative characteristics may identify cohorts of patients who will benefit more from LLP, and no patient cohorts had higher postoperative complication rates after LLP than OLP. These observations suggest that LLP may be the operative procedure of choice for most patients with left-sided pancreatic lesions; a more definitive prospective and randomized comparison may be warranted.

Korean red ginseng (RG), which is a ginseng treated by heating and steaming, has biological activity similar to Panax ginseng. The effect of ginseng on influenza infection has not been studied although it is known to have a broad range of biological activities. The aim of the study is to investigate the effect of RG extract on infl uenza A (H1N1) virus infection. We investigated the inhibitory effect of RG extract on plaque formation by infl uenza A virus in a cell-based plaque assay, and the effect of orally administered RG on infl uenza A virus infection in mice. RG extract, which was applied at a non-cytotoxic concentration, inhibited plaque formation by infl uenza A virus in the cell-based plaque assay. The orally administered RG extract ameliorated body weight loss and signifi cantly increased survival in mice infected with infl uenza A virus. Our results suggest that RG extract has components that reduce the severity of infection by infl uenza A virus and could potentially be used as a complement to treatment of infl uenza A virus infections.

The currently available purification protocol for human papillomavirus (HPV) pseudovirus (PsV), as a substitute for the native HPV virion, utilizes Optiprep gradients (OG), which require costly equipment such as ultracentrifuges, and 4-7 h of working time, and cannot cope with large PsV samples. To develop a convenient method for purifying HPV type 58 PsV (HPV58 PsV) we have examined the use of heparin chromatography (HC) and cation-exchange chromatography (CC), which utilize open column systems and do not require expensive equipment. We confirmed that the PsVs resulting from HC and CC have correctly assembled conformations and are neutralized by anti-HPV58 PsV mouse serum, indicating that their antigenic characteristics make them suitable to substitute for native HPV58 virion. The recoveries of infectious PsV resulting from HC and CC were 39% and 11%, respectively, while that from OG was 58%. The two new purification methods are advantageous with respect to working time (only 30 min) and expense over the OG method, and have considerable potential for large scale purification.

Background As compared with open distal pancreatectomy (ODP), laparoscopic distal pancreatectomy (LDP) affords improved perioperative outcomes. The role of LDP for patients with pancreatic ductal adenocarcinoma (PDAC) is not defined. Study Design Records from patients undergoing distal pancreatectomy (DP) for PDAC from 2000 to 2008 from 9 academic medical centers were reviewed. Short-term (node harvest and margin status) and long-term (survival) cancer outcomes were assessed. A 3:1 matched analysis was performed for ODP and LDP cases using age, American Society of Anesthesiologists (ASA) class, and tumor size. Results There were 212 patients who underwent DP for PDAC; 23 (11%) of these were approached laparoscopically. For all 212 patients, 56 (26%) had positive margins. The mean number of nodes (± SD) examined was 12.6 ±8.4 and 114 patients (54%) had at least 1 positive node. Median overall survival was 16 months. In the matched analysis there were no significant differences in positive margin rates, number of nodes examined, number of patients with at least 1 positive node, or overall survival. Logistic regression for all 212 patients demonstrated that advanced age, larger tumors, positive margins, and node positive disease were independently associated with worse survival; however, method of resection (ODP vs. LDP) was not. Hospital stay was 2 days shorter in the matched comparison, which approached significance (LDP, 7.4 days vs. ODP, 9.4 days, p=0.06). Conclusions LDP provides similar short- and long-term oncologic outcomes as compared with OD, with potentially shorter hospital stay. These results suggest that LDP is an acceptable approach for resection of PDAC of the left pancreas in selected patients.

Ischemia and reperfusion (I/R) injury is a major cause of hepatic failure after liver surgery, but no method could monitor or predict it real-time during surgery. We measured bioelectrical impedance (BEI) and cell viability to assess the usefulness of BEI during I/R in rat liver. A 70% partial liver ischemia model was used. BEI was measured at various frequencies. Adenosine triphosphate (ATP) content, and palmitic acid oxidation rate were measured, and histological changes were observed in order to quantify liver cell viability. BEI changed significantly during ischemia at low frequency. In the ischemia group, BEI increased gradually during 60 min of ischemia and had a tendency to plateau thereafter. The ATP content decreased below 20% of the baseline level. In the I/R group, BEI recovered to near baseline level. After 24 hr of reperfusion, the ATP contents decreased to below 50% in 30, 60 and 120 min of ischemia and the palmitic acid metabolic rates decreased to 91%, 78%, and 74%, respectively, compared with normal liver. BEI may be a good tool for monitoring I/R during liver surgery. The liver is relatively tolerant to ischemia, however after reperfusion, liver cells may be damaged depending upon the duration of ischemia.

Human papillomavirus (HPV) is the causative agent of cervical cancer, the second most common cause of cancer death in women worldwide. The licensed HPV vaccine Gardasil((R)) from Merck & Co. is a quadrivalent vaccine containing virus-like particles (VLPs) of the L1 proteins from HPV types 6, 11, 16, and 18 adsorbed on aluminum salts (alum). CIA07 is an immunostimulatory agent comprised of bacterial DNA fragments (CIA02) and a nontoxic derivative of lipopolysaccharide (CIA05) that has been shown to have antitumor activity and adjuvant activity for viral and bacterial vaccine antigens. We investigated whether these CIAs are capable of promoting the immune response to Gardasil. Balb/c mice were immunized intramuscularly twice three weeks apart with 1/20 human dose of Gardasil alone or in combination with CIA02, CIA05 or both, and immune responses were assessed. The serum anti-HPV16 L1 VLP IgG antibody titer was significantly higher in mice administered CIA05 or CIA05 plus CIA02, but not in those given CIA02, compared with mice given Gardasil alone. A secreted alkaline phosphatase (SEAP)-based pseudovirus neutralization assay showed increased neutralizing antibody titers in both CIA05 and CIA05 plus CIA02 groups. Coadministration of CIA05 with Gardasil led to a marked increase in serum IgG2a antibody titer and the percentage of interferon (IFN)-gamma(+) cells in the spleen, indicating that CIA05 effectively promotes Th1-type immune responses. These data indicate that CIA05, in synergy with alum, enhances the immune response to HPV L1 VLPs and suggest its potential as an adjuvant for the development of a potent prophylactic HPV vaccine.

Human papillomavirus (HPV) types 16 and 18 are the main targets in the field of prophylactic vaccines for preventing cervical cancer. L1 protein, the major capsid protein of HPV, selfassembles into virus-like particles (VLP), which are the major component of prophylactic vaccines. To obtain highly purified L1 protein, contaminants must be removed by several chromatography steps. However, this requires a great deal of time and labor, and results in loss of large amounts of the target protein. Therefore, we have sought to develop an efficient method for removing contaminants prior to chromatography during the purification of HPV18 L1 protein from Saccharomyces cerevisiae. For this purpose the contaminating proteins were removed by an ammonium sulfate precipitation step and further removed by a removal of precipitated contaminants step. Purification of the L1 protein by chromatography was significantly improved by the removal of precipitated contaminants step. In the present work we developed two one-step chromatography methods (heparin and cation-exchange chromatography), and HPV18 L1 proteins purified by both methods self-assembled into VLP. The two chromatographic purification methods are simpler and more convenient than previous methods and are widely applicable to work with VLPs.

Dynamic friction experiments between aluminum and steel were conducted using an explosively driven tribotester, which allows friction testing with high velocity and high pressure within a very short time. Characterization of the sliding surfaces showed material transfer, severe plastic deformation of the softer material, evidence of high strain and strain rate, and nanostructure formation at the surface and subsurface. Such friction-induced phenomena have frequently been reported. However experimental results obtained in a few microseconds are rarely described. In particular, formation of a thin (∼1 μm) and uniform nanostructure within such a short time suggests that a new mechanism is needed to explain the nanostructure formation. Molecular dynamics simulations of the sliding of hard/soft crystals reveal nanometer size vorticity at the sliding interface. This results in atomic-scale flow and mixing that contribute to a disordered and nanostructured surface layer, as observed in experiments.

Chronic kidney disease is often accompanied by hyperparathyroidism. Cinacalcet, a recent addition to the medical armamentarium, has proven efficacious. It is unclear whether cinacalcet use has any impact on the postoperative course in patients progressing to surgery. The records of 77 patients operated on for renal hyperparathyroidism were reviewed. Sixty-three were treated before the use of cinacalcet and 14 after. Ten subtotal and 67 total parathyroidectomies were performed. Mean nadir serum calcium was similar (6.6 ± 1.3 vs 6.2 ± 1.4 mg/dL). More patients taking cinacalcet preoperatively required intravenous calcium postoperatively (62%) than those treated before its use (41%), although this did not reach statistical significance ( P = 0.09). In those undergoing total parathyroidectomy, cinacalcet use preoperatively (n = 11) led to a lower postoperative nadir calcium (5.8 ± 1.7 vs 6.6 ± 1.3 mg/dL) as compared with those who did not receive it (n = 56) ( P = 0.05). This translated to a greater need for intravenous calcium infusion postoperatively (72 vs 38%) ( P = 0.03). These data suggest a somewhat more aggressive postoperative course in patients who fail calcimimetic and require surgery. This may be useful to inform physicians and patients of expectations postoperatively, although it is not likely to alter management.

Terminal sialylation of therapeutic glycoprotein is important for biological activity and in vivo stability. The enzyme α2,3-sialyltransferase is the key enzyme that links sialic acids to the termini of glycans in the Chinese hamster ovary (CHO) cell line. Terminal sialylation is affected by numerous factors, but the elements that regulate α2,3-sialyltransferase are not known. We investigated the relationship between α2,3-sialyltransferase activity, ammonium concentration, and cell attachment area-based cell concentration in a recombinant human erythropoietin (rhEPO)-producing CHO cell line. We found that ammonium in the culture medium had almost no effect on α2,3-sialyltransferase activity, but that the activity was affected by cell attachment area-based cell concentration; α2,3-sialyltransferase activity and terminal sialylation of rhEPO decreased with increasing the cell concentration. These results demonstrate that the cell attachment area-based cell concentration is an important factor that affects 2,3-sialyltransferase activity and terminal sialylation of CHO cells.

Self-contained Non-Equilibrium Molecular Dynamics (NEMD) simulations using Lennard-Jones potentials were performed to identify the origin and mechanisms of atomic scale interfacial behavior between sliding metals. The mixing sequence and velocity profiles were compared via MD simulations for three cases, viz.: sell-mated, similar and hard-softvcrystal pairs. The results showed shear instability, atomic scale mixing, and generation of eddies at the sliding interface. Vorticity at the interface suggests that atomic flow during sliding is similar to fluid flow under Kelvin-Helmholtz instability and this is supported by velocity profiles from the simulations. The initial step-function velocity profile spreads during sliding. However the velocity profile does not change much at later stages of the simulation and it eventually stops spreading. The steady state friction coefficient during simulation was monitored as a function of sliding velocity. Frictional behavior can be explained on the basis of plastic deformation and adiabatic effects. The mixing layer growth kinetics was also investigated.

Background The role of adjuvant chemoradiation therapy (CRT) in pancreatic cancer remains controversial. The primary aim of this study was to determine if CRT improved survival in patients with resected pancreatic cancer in a large, multiinstitutional cohort of patients. Study Design Patients undergoing resection for pancreatic adenocarcinoma from seven academic medical institutions were included. Exclusion criteria included patients with T4 or M1 disease, R2 resection margin, preoperative therapy, chemotherapy alone, or if adjuvant therapy status was unknown. Results There were 747 patients included in the initial evaluation. Primary analysis was performed between patients that had surgery alone (n=374) and those receiving adjuvant CRT (n=299). Median followup time was 12.2 months and 14.5 months for survivors. Median overall survival for patients receiving adjuvant CRT was significantly longer than for those undergoing operation alone (20.0 months versus 14.5 months, p=0.001). On subset and multivariate analysis, adjuvant CRT demonstrated a significant survival advantage only among patients who had lymph node (LN)-positive disease (hazard ratio 0.477, 95% CI 0.357 to 0.638) and not for LN-negative patients (hazard ratio 0.810, 95% CI 0.556 to 1.181). Disease-free survival in patients with LN-negative disease who received adjuvant CRT was significantly worse than in patients who had surgery alone (14.5 months versus 18.6 months, p=0.034). Conclusions This large multiinstitutional study emphasizes the importance of analyzing subsets of patients with pancreas adenocarcinoma who have LN metastasis. Benefit of adjuvant CRT is seen only in patients with LN-positive disease, regardless of resection margin status. CRT in patients with LN-negative disease may contribute to reduced disease-free survival.

Crankshaft, the core element of the engine of a vehicle, transforms the translational motion generated by combustion to rotational motion. Its failure will cause serious damage to the engine so its reliability verification must be performed. In this study, the S-N data of the bending fatigue limit of a crankshaft are derived. To evaluate the reliability of the crankshaft, reliability verification and analysis are performed. For the purpose of further evaluation, the bending test of the original crankshaft is carried out, and failure mode analysis is made. The appropriate number of samples, the applied load, and the test time are computed. On the basis of the test results, Weibull analysis for the shape and scale parameters of the crankshaft is estimated. Likewise, the B10 life under 50% of the confidence level and the MTTF are exactly calculated, and the groundwork for improving the reliability of the crankshaft is laid.

Phase II clinical trials of mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitors are ongoing and ERK1/2 activation is frequently used as a biomarker. In light of the mutational activation of BRAF and KRAS in colorectal cancer, inhibitors of the Raf-MEK-ERK mitogen-activated protein kinase are anticipated to be promising. Previous studies in pancreatic cancer have found little correlation between BRAF/KRAS mutation status and ERK1/2 activation, suggesting that identifying biomarkers of MEK inhibitor response may be more challenging than previously thought. The purpose of this study was to evaluate the effectiveness of MEK inhibitor therapy for colorectal cancer and BRAF/KRAS mutation status and ERK1/2 activation as biomarkers for MEK inhibitor therapy. First, we found that MEK inhibitor treatment impaired the anchorage-independent growth of nearly all KRAS/BRAF mutant, but not wild-type, colorectal cancer cells. There was a correlation between BRAF, but not KRAS, mutation status and ERK1/2 activation. Second, neither elevated ERK1/2 activation nor reduction of ERK1/2 activity correlated with MEK inhibition of anchorage-independent growth. Finally, we validated our cell line observations and found that ERK1/2 activation correlated with BRAF, but not KRAS, mutation status in 190 patient colorectal cancer tissues. Surprisingly, we also found that ERK activation was elevated in normal colonic epithelium, suggesting that normal cell toxicity may be a complication for colorectal cancer treatment. Our results suggest that although MEK inhibitors show promise in colorectal cancer, KRAS/BRAF mutation status, but not ERK activation as previously thought, may be useful biomarkers for MEK inhibitor sensitivity. [Mol Cancer Ther 2009;8(4):834–43]

The aim of the study was to investigate the seroprevalence to HPV type 16 in Korean women with precancerous and cancerous lesions of the uterine cervix. The cases were 173 Korean women of whom 130 had high-grade cervical intraepithelial neoplasias (CIN), 43 cervical carcinomas and the control group was 106 women showing normal cervical cytology. Serologic assays were performed using HPV-16 VLPs as antigen in an ELISA. Specific antibodies against HPV-16 VLP were detected in 59.2% (77/130) of the patients with high-grade CIN, in 67.4% (29/43) of the patients with cervical cancer and in 20.8% (22/106) of control subjects. No difference of serologic response was found between high-grade CIN and cancer. HPV-16 seropositivity showed the significant association with patients' age and preoperative HPV DNA infection. Recurrence of high-grade CIN was not affected by the VLP-16 seropositivity. Recurrence of carcinoma showed the borderline association with HPV-16 seropositivity (P=0.06). The association between the cancer recurrence and seropositivity was not found in the logistic regression analysis. Two patients dying of cancer during the follow-up period were both seronegative (P=0.01). In conclusion, serologic testing for HPV-16 VLP antibody provides a disease indicator of cervical lesions and potential prognostic parameter of cervical carcinoma.

In this paper, an evaluation model of disaster management system which is developed by using GRI G3 version and BCP process for the sustainability management of small and middle enterprises was proposed. The proposed evaluation model can be used to evaluate the disaster management system directly, and to establish the disaster management system as an index. Also, the rules obtained by pattern analysis using fuzzy ID3 for the proposed evaluation model are expected to use the guideline effectively for self evaluation in the small and middle enterprises.

The terminal sialic acid of human erythropoietin (hEPO) is essential for in vivo activity. The current resorcinol and HPLC methods for analyzing α2,3-linked sialic acid require more than a microgram of purified rhEPO, and purification takes a great deal of time and labor. In this study, we assessed the use of an antibody-based enzyme-linked lectin assay (ABELLA) for analyzing non-purified recombinant hEPO (rhEPO). The major problem of this method was the high background due to terminal sialylation of components of the assay (antibody and bovine serum albumin) other than rhEPO. To solve this problem, we used a monoclonal antibody (Mab 287) to capture the rhEPO, and oxidized the bovine serum albumin used for blocking with meta-periodate. The sialic acid content of non-purified rhEPO measured by ABELLA was similar to that obtained by the resorcinol method on purified rhEPO. ABELLA has advantages such as adaptability and need for minimal amounts of rhEPO (40 ng/ml). Our observations suggest that ABELLA should reduce the time and labor needed to improve culture conditions so as to increase protein sialylation, and also facilitate the study of sialylation mechanisms.