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The forest biomass dynamics in boreal forests has a significant effect on global carbon cycles. Biomass estimates provide insight into the carbon balance of forest vegetation in Siberia. This paper discusses the methods used in modern studies (2010–2021) to estimate aboveground forest biomass on the basis of radar remote sensing data. Biomass estimation methodologies are described, including field data collection, data preprocessing, and modeling of relationships between remote sensing (RS) data and biomass. In terms of forest biomass estimation, radar sensing has limited capabilities determined by the characteristics of the survey equipment and parameters of studied forest stands. Modern studies combine optical and radar RS data to estimate forest biomass more accurately using regression models, machine learning, and special techniques (BIOMASAR, SWCM, and MaxEnt). Vegetation optical depth values estimated on the basis of microwave surveys make it possible to solve the saturation problem hindering the estimation of large amounts of biomass. It is difficult to compare the accuracy of biomass estimation methods due to the lack of uniform approaches to experimental and error computation procedures. Errors in biomass estimates produced on the basis of optical and radar data vary considerably (~25% on average). The small amount of reference field data complicates biomass estimations in boreal forests of Siberia. It is believed that the application of machine learning algorithms to remote sensing data collected by the Sentinel-1 and ALOS-PALSAR satellites will make it possible to estimate the biomass of boreal forests with a high spatial resolution. [ABSTRACT FROM AUTHOR]

Currently, desalination is limited by high energy consumption and high operational and maintenance costs. In this study, a new concept of a hollow fiber forward osmosis (HFFO)-based infinity desalination process with minor environmental impacts (free-energy intake and no pretreatment or brine discharge) is suggested. To evaluate the concept, an element-scale HFFO was conducted in both conventional FO and pressure-assisted FO modes, simulating a submerged HFFO operation. In the HFFO test, the impacts of several operating conditions on the performance of the HFFO were investigated to select the best case. Based on these results, the energy costs were calculated and compared with those of a hybrid FO–seawater reverse osmosis (SWRO) process. The HFFO showed a high dilution rate of the draw solution (up to approximately 400%), allowing the downstream SWRO process to operate at 25 bar with the same permeate volume production (recovery rate of 60%). Consequently, the HFFO-based infinity desalination process has an annual energy revenue of 183.83 million USD, compared with a stand-alone two-stage RO process based on a 100,000 m3/day plant. [ABSTRACT FROM AUTHOR]

The radial increment of Abies sibirica Ledeb. and mortality dynamics of fir stands in the mountain forests of the Eastern Sayan (Stolby State Nature Reserve) have been analyzed. The unprecedented decline in fir stands is caused by water stress due to an increase in air temperature and synergy with the impact of the Polygraphus proximus Blandford. This xylophage was not previously observed in the Abies sibirica range. In the initial phase of climate warming, an increase in radial increment was observed, which was replaced by a depression in 1985–2017. The declining of fir trees was preceded by an increase in the relationship between growth index and SPEI, as well as between the growth index and root-zone moisture content. At the same time, the growth index of the declining cohort was more closely associated with the root zone moisture content (r2 = 0.56) and SPEI (r2 = 0.74) than the growth index of the surviving cohort (r2 = 0.15 and r2 = 0.39, respectively). The decline in fir began in the 2000s, when Polygraphus proximus Blandford attacked trees Abies sibirica. During this period, dead stands were localized mainly on the relief elements with the highest probability of water stress (steep slopes located in a "rain shadow"). By 2017, the decline spread throughout the entire territory of fir stands, which led to the mortality of ~75% of fir stands. During the period of tree decline, a close relationship was observed between growth index and fir mortality (r = –0.79). The surviving trees grew under conditions of a higher root-zone humidity (compared to declining trees). The proximity of growth-index trajectories of cohorts of declining and surviving trees, which indicates the probability of mortality of surviving trees in the context of a predicted climate aridity increase, is noteworthy. [ABSTRACT FROM AUTHOR]

A nonparametric algorithm of automatic classification of large arrays of statistical data is considered. Its synthesis is based on decomposition of initial data. The results of decomposition form a set of centers of multidimensional intervals and the corresponding frequencies of occurrence of values of random variables. Based on information obtained, classes corresponding to single-mode fragments of the probability density of features of examined objects are detected. The spatial interpretation of automatic classification results is analyzed. The nonparametric algorithms developed in the study are important tools of processing of data obtained by remote sensing of natural resources. [ABSTRACT FROM AUTHOR]

The influence of climate changes on larch (Larix sibirica Ledeb.) radial increment under conditions of a limited (forest steppe) and sufficient (high-altitude Kuznetsk Alatau, floodplain stands) humidification is considered. The relationship between growth index of larch trees (N = 257) and ecological and climatic variables is analyzed. In the forest steppe, with the onset of warming, a decrease in the aridity of the climate, an increase in the duration of the growing season (1980s), and an increase in the larch growth index followed by its depression in the 1990s have been observed. Radial-increment depression is caused by an increase in vapor-pressure deficit and arid climate due to a rising air temperature. In the 2000s, radial-increment fluctuations with average values not exceeding those before the beginning of current climate warming period occurred. In the highlands, since the 1970s, there has been a general increase in the larch radial increment closely associated with the main limiting factor of growth—air temperature. At the same time, in arid years, the radial-increment depression of larch trees in highland and floodplain larch forests is also noted. When implementing “hard” climate scenarios (RCP 6.0 and RCP 8.5), it is likely that the larch growth index in a forest steppe will decrease further and its increase in areas of sufficient moisture will be observed. [ABSTRACT FROM AUTHOR]

Climate changes have induced the northward migration of outbreaks of the Siberian silk moth (Dendrolimus sibiricus Tschetv.), one of the most dangerous pests in the taiga. The initial outbreak of the Siberian silk moth began in 2014 in Siberian pine-fir stands within the Yenisei Plain on the southwestern flat slopes at elevations up to 200 m above sea level. Further, the outbreak extended to the parts of the forest with higher humidity, the northern slopes, and Yenisei Ridge at low and middle elevations. The northern limit of the outbreak zone shifted to 50 km (to 60°26' N) northward from the historical boundary of formerly observed outbreaks. The outbreak was incited by an increase in aridity, the sum of positive temperatures (t > +10°C), and a decrease in soil moisture. It extended to an area of 800000 ha. Stand mortality was accompanied by the activation of secondary pests, including aggressive bark beetle species Polygraphus proximus. The outbreak under study is part of the panzonal outbreak that occurred in 2014-2017 on the territory of Siberia in Krasnoyarsk krai and Tomsk, Kemerovo, and Irkutsk oblasts. The increase in warming, aridity, and vegetative period provides opportunities for the Siberian silk moth to migrate to the northern dark-conifer taiga. [ABSTRACT FROM AUTHOR]

Summary: In non-osteoporotic postmenopausal women with breast cancer, aromatase inhibitors (AIs) negatively affected bone mineral density (BMD), lumbar spine trabecular bone score (TBS) as a bone microarchitecture index, and hip geometry as a bone macroarchitecture index. Introduction: AIs increase the risk of fracture in patients with breast cancer. Therefore, we aimed to evaluate the long-term skeletal effects of AIs in postmenopausal women with primary breast cancer. Methods: We performed a retrospective longitudinal observational study in non-osteoporotic patients with breast cancer who were treated with AIs for ≥3 years (T-score >−2.5). Patients with previous anti-osteoporosis treatment or those who were given bisphosphonate during AI treatment were excluded from the analysis. We serially assessed BMD, lumbar spine TBS, and hip geometry using dual-energy X-ray absorptiometry. Results: BMD significantly decreased from baseline to 5 years at the lumbar spine (−6.15%), femur neck (−7.12%), and total hip (−6.35%). Lumbar spine TBS also significantly decreased from baseline to 5 years (−2.12%); this change remained significant after adjusting for lumbar spine BMD. The annual loss of lumbar spine BMD and TBS slowed after 3 and 1 year of treatment, respectively, although there was a relatively constant loss of BMD at the femur neck and total hip for up to 4 years. The cross-sectional area, cross-sectional moment of inertia, minimal neck width, femur strength index, and section modulus significantly decreased, although the buckling ratio increased over the treatment period (all P < 0.001); these changes were independent of total hip BMD. Conclusions: Long-term adjuvant AI treatment negatively influenced bone quality in addition to BMD in patients with breast cancer. This study suggests that early monitoring and management are needed in non-osteoporotic patients with breast cancer who are starting AIs. [ABSTRACT FROM AUTHOR]

The reasons for the decline in Siberian pine and fir in the Baikal Region (Khamar-Daban) were analyzed using remote sensing techniques, dendrochronology and GIS-technology methods, and in situ observations. It is found that a decrease in the value of the growth index ( R = 0.69) and an decrease in the SPEI drought index (Standardized Precipitation-Evapotranspiration Index) ( R = 0.72) has been observed since the 1980s. In the mid-2000s, the increase in aridity led to the division of Siberian pine trees into two cohorts: 'survivors' and 'decliners.' The spatial distribution of these cohorts is different: dead and declining stands are localized mainly on relief elements with increased risk of water stress (steep and convex slopes of southwestern exposure). The growth index of the trees is closely related to the dryness index in June ( r = 0.55). Along with water stress, declining trees were also exposed to stem pests and plant pathogens. The primary cause of Siberian pine decline is water stress due to the increasing climate aridity. The weakened waterstressed trees were sensitized to pathogens. The synergism of climatic and biotic effects led to the decline of Siberian pine stands. On the whole, heavily damaged and declining stands (over 50% of dead and declining trees) within the Khamar-Daban ridge are 8-10% of the total area of dark coniferous forests. [ABSTRACT FROM AUTHOR]

The compressor of an automotive proton exchange membrane fuel cell requires severe dynamic performance under normal driving patterns. Because the air flow demand of the automotive fuel cell requires steep increase/decrease, it is very important to understand the air flow trajectory of the centrifugal compressor to avoid the compressor surge. In this study, a simulation model of an automotive fuel cell system with a dynamic compressor was developed to investigate the proper trajectory of air flow rate on a performance map of an air compressor. The dynamic response of the compressor shows that the cathode inlet and exit valves have a significant effect on surge evolution. In particular, the results showed that a proper combination of valve opening areas is required to avoid compressor surge. In this study, the original two valve approach was reduced to a single cathode exit valve control with fixed cathode inlet orifice. A surge rejection algorithm was also developed, based on the comparison of surge protection envelope pressure with actual measured pressure. The results show that surge evolution is effectively avoided by controlling the cathode exit valve. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the expression of c-Met, and to investigate correlations between the expression of c-Met, clinicopathologic variables, and survival in patients undergoing curative surgery followed by adjuvant chemoradiotherapy for extrahepatic bile duct (EHBD) cancer. Methods: Ninety EHBD cancer patients who underwent curative resection followed by adjuvant chemoradiotherapy were enrolled. Expression of c-Met was assessed with immunohistochemical staining on tissue microarray. The correlation between clinicopathologic variables and survival outcomes was evaluated using Kaplan-Meier method and Cox proportional hazard model. Results: On univariate analysis, 66 patients (76.7 %) showed c-Met expression. c-Met expression had a significant impact on 5-year overall survival (OS) (43.0 % in c-Met(+) vs. 25.0 % in c-Met(−), p = 0.0324), but not on loco-regional relapse-free survival or distant metastasis-free survival (DMFS). However, on multivariate analysis incorporating tumor location and nodal involvement, survival difference was not maintained ( p = 0.2940). Tumor location was the only independent prognostic factor predicting OS ( p = 0.0089). Hilar location tumors, nodal involvement, and poorly differentiated tumors were all identified as independent prognostic factors predicting inferior DMFS ( p = 0.0030, 0.0013, and 0.0037, respectively). Conclusions: This study showed that c-Met expression was not associated with survival outcomes in EHBD cancer patients undergoing curative resection followed by adjuvant chemoradiotherapy. Further studies are needed to fully elucidate the prognostic value of c-Met expression in these patients. [ABSTRACT FROM AUTHOR]

The decline of spruce stands in Belarus has been analyzed in relation to the dynamics of climatic variables. The results show that this process is correlated with the amount of precipitation, moisture deficit, index of aridity, relative air humidity, and evapotranspiration. Frosts at the onset of the growing season enhance tree die-off, while increase in cloud cover has a favorable effect on the state of spruce stands. Damage to trees occurs mainly in areas with elevated and convex topography and slopes of southwestern aspect, increasing on steeper slopes. The level of die-off is most closely correlated with conditions of the previous year, which is explained by the impact of biological factors (pest insects and phytopathogens) on tree stands already affected by water stress. The decline of spruce stands on a mass scale is also observed in neighboring regions of Russia and counties of East Europe, which is evidence for a low adaptability of spruce to current climate change, including the increasing frequency and severity of dry periods. [ABSTRACT FROM AUTHOR]

The GRACE gravimetric survey is applied to analyze the equivalent water mass anomalies (EWMAs) in the permafrost zone of Central Siberia. Variations in EWMAs are related to precipitation, air temperature, potential evapotranspiration, and soil composition (drainage conditions). The EWMA dynamics demonstrates two periods. The period of 2003-2008 is characterized by a positive trend. The one of 2008-2012 shows a decrease in the trend with a simultaneous increase by 30-70% of EWMA dispersion in the background of growth (up to 40%) of precipitation variability. The rate of water mass increment demonstrates a positive correlation with the sand and gravel contents in soil ( r = 0.72) and a negative one with clay content ( r =-0.69 to-0.77). For Taimyr Peninsula, there is a deficit of residual water mass (~250 mm for the period of 2012-2013) indicating the deeper thawing of permafrost soils. In the Central Siberian Plateau, the indicator of more intensive permafrost thawing (and that of an increase in active layer thickness) is a considerable trend of water mass increase (2003-2008). The increasing trend of the largest Siberian rivers (Yenisei and Lena) is revealed in the period of 2003-2012. [ABSTRACT FROM AUTHOR]

Quantitative dynamics, water surface area, and water level of lakes in the Trans-Baikal forest-steppe zone have been studied by spectroradiometry (Landsat satellite), gravimetry (GRACE satellite), and altimetry (Envisat satellite). The number of lakes and their water surface area correlated with precipitation ( r = 0.84-0.85), summer and annual temperature ( r =-0.77 to-0.9), and drought index ( r = 0.95-0.97). During extremely dry periods (2006-2010), the number of lakes decreased by four (compared to 1989) and their water surface area decreased by three (compared to 2000). The rate of change in the water level of the lakes (periods of ~29 years) was determined. [ABSTRACT FROM AUTHOR]

In recent decades there has been an increase in the radial growth of Larix sibirica Ledeb., Pinus sibirica Du Tour, and Abies sibirica in the Kuznetsk Alatau alpine forest-tundra ecotone. Larch growth correlates positively with summer temperatures; cedar and fir growth is determined by temperature, precipitation, and sunshine duration. It is shown that the current growth of maturing larch trees is about 55% higher than that of a similar age group observed 200 years ago. The rate of larch advancement along the height gradient is estimated at 1 m/10 years. A periodical limitation of the radial growth in fir by winter and summer temperatures is found; the strongest correlation is revealed with summer temperatures ( r = 0.9). The growth rate of all conifers correlates highly with the concentration of CO in the atmosphere ( r = 0.42-0.84). Increased winter temperatures induce the transformation of the elfin forms in larch and cedar (the early 1970s) and later fir (the early 1980s) into vertical forms. [ABSTRACT FROM AUTHOR]

Background:Epidermal growth factor receptor (EGFR) is overexpressed in a subset of human epidermal growth factor receptor 2 (HER2)-positive breast cancers, and coexpression of HER2 and EGFR has been reported to be associated with poor clinical outcome. Moreover, interaction between HER2 and EGFR has been suggested to be a possible basis for trastuzumab resistance.Methods:We analysed the clinical significance of EGFR overexpression and EGFR gene copy number alterations in 242 HER2-positive primary breast cancers. In addition, we examined the correlations between EGFR overexpression, trastuzumab response and clinical outcome in 447 primary, and 112 metastatic HER2-positive breast cancer patients treated by trastuzumab.Results:Of the 242 primary cases, the level of EGFR overexpression was 2+ in 12.7% and 3+ in 11.8%. High EGFR gene copy number was detected in 10.3%. Epidermal growth factor receptor overexpression was associated with hormone receptor negativity and high Ki-67 proliferation index. In survival analyses, EGFR overexpression, but not high EGFR copy number, was associated with poor disease-free survival in all patients, and in the subgroup not receiving adjuvant trastuzumab. In 447 HER2-positive primary breast cancer patients treated with adjuvant trastuzumab, EGFR overexpression was also an independent poor prognostic factor. However, EGFR overexpression was not associated with trastuzumab response, progression-free survival or overall survival in the metastatic setting.Conclusions:Epidermal growth factor receptor overexpression, but not high EGFR copy number, is a poor prognostic factor in HER2-positive primary breast cancer. Epidermal growth factor receptor overexpression is a predictive factor for trastuzumab response in HER2-positive primary breast cancer, but not in metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2 (HER2)-directed treatment using trastuzumab has shown clinical benefit in HER2-positive gastric cancer. Clinical trials using lapatinib in HER2-positive gastric cancer are also currently underway. As with other molecularly targeted agents, the emergence of acquired resistance to HER2-directed treatment is an imminent therapeutic problem for HER2-positive gastric cancer. In order to investigate the mechanisms of acquired resistance to HER2-directed treatment in gastric cancer, we generated lapatinib-reslstant gastric cancer cell lines (SNU216 LR) in vitro by chronic exposure of a HER2-positive gastric cancer cell line (SNU216) to lapatinib. The resultant SNU216 LR cells were also resistant to gefitinib, cetuximab, trastuzumab, afatinlb and dacomitinib. Interestingly, SNU216 LR cells displayed an epithelial-mesenchymal transition (EMT) phenotype and maintained the activation of MET, HER3, Stat3, Akt and mitogen-activated protein kinase signaling in the presence of lapatinib. Using gene expression arrays, we identified the upregulation of a variety of EMT-related genes and extracellular matrix molecules, such as Testican-1, in SNU216 LR cells. We showed that the Inhibition of Testican-1 by small interfering RNA decreased Testican-1-induced, MET-dependent, downstream signaling, and restored sensitivity to lapatinib in these cells. Furthermore, treatment with XAV939 selectively inhibited β-catenin-mediated transcription and Testican-1-induced EMT signaling, leading to Gl arrest. Taken together, these data support the potential role of EMT in acquired resistance to HER2-directed treatment in HER2-positive gastric cancer, and provide insights into strategies for preventing and/or overcoming this resistance in patients. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the lake sediment budget of land use changes using the Universal Soil Loss Equation (USLE), sediment delivery ratio (SDR), and trap efficiency (TE). The geographic information system was combined with the USLE to estimate the soil erosion of the Lake Asan watershed. Spatial data for each of the USLE factors were obtained from the land use, soil, and 1/25,000 scale digital contour maps. Landsat-5 TM images were selected for analyzing soil erosion changes due to land use changes. The sediment yield to Lake Asan was estimated using the SDR and TE. The estimated sediment budget was compared with observed data from the Lake Asan watershed between 1974 and 2003. The total estimated annual mean sediment budgets from Lake Asan in 1986, 1992, and 2000 were 0.267, 0.301, and 0.339 × 10 ton, respectively, with an average of 0.302 × 10 ton. The average measured sediment budget was 3.15 × 10 ton year. The average estimated value shows reasonable agreement with the observed sediment balance. The average estimated and measured sediment budgets contain uncertainties due to both the methods and the approach used by the observers. The simulated results indicated that soil erosion in the Lake Asan watershed increased at a rate of approximately 2 % per year from 1986 to 2000 due to land use change. This study may be useful for managers to identify reservoir rehabilitation management methods for stable irrigation water supply. [ABSTRACT FROM AUTHOR]

Background:In preclinical gastric cancer (GC) models, FGFR2 amplification was associated with increased tumour cell proliferation and survival, and drugs targeting this pathway are now in clinical trials.Methods:FGFR2 FISH was performed on 961 GCs from the United Kingdom, China and Korea, and the relationship with clinicopathological data and overlap with HER2 amplification were analysed.Results:The prevalence of FGFR2 amplification was similar between the three cohorts (UK 7.4%, China 4.6% and Korea 4.2%), and intratumoral heterogeneity was observed in 24% of FGFR2 amplified cases. FGFR2 amplification was associated with lymph node metastases (P<0.0001). FGFR2 amplification and polysomy were associated with poor overall survival (OS) in the Korean (OS: 1.83 vs 6.17 years, P=0.0073) and UK (OS: 0.45 vs 1.9 years, P<0.0001) cohorts, and FGFR2 amplification was an independent marker of poor survival in the UK cohort (P=0.0002). Co-amplification of FGFR2 and HER2 was rare, and when high-level amplifications did co-occur these were detected in distinct areas of the tumour.Conclusion:A similar incidence of FGFR2 amplification was found in Asian and UK GCs and was associated with lymphatic invasion and poor prognosis. This study also shows that HER2 and FGFR2 amplifications are mostly exclusive. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this research was to analyze the relationship between dose-volumetric parameters and the development of diabetes mellitus (DM) in patients treated with chemoradiotherapy (CRT) following curative resection for upper gastrointestinal (GI) cancers.Patients and Methods: Medical records of patients who underwent postoperative CRT following curative resection, either pancreaticoduodenectomy (PD) or pylorus preserving pancreaticoduodenectomy (PPPD) for upper GI cancers including pancreas, biliary, ampullary, and duodenal cancers, between January 2006 and December 2008 were retrospectively reviewed. A total of 42 patients who were regularly followed for at least 2 years were included for analysis. Dose-volumetric parameters such as remnant pancreatic volume, mean dose, maximum dose (Dmax), and percentage of volume receiving specific dose or more were obtained from pre- and postoperative CT scan images and treatment plan.Results: Dmax and V50 (percentage of volume receiving at least 50 Gy) were statistically significant factors for the development of DM (p = 0.013, p = 0.031, respectively). The sensitivity and specificity of Dmax was 0.875 and 0.559, with cut-off value of 51.1 Gy, respectively. V50 had sensitivity of 0.875 and specificity of 0.618 for cut-off value of 16 %. No patient-related factor other than pretreatment cerebrovascular events was associated with the development of DM. On multivariate analysis, V50 was the only factor with statistical significance (p = 0.028), whereas Dmax showed borderline significance (p = 0.079).Conclusion: V50 was the only independent factor associated with the development of diabetes and may function as guideline to predict the development of DM in patients receiving CRT following curative resection. [ABSTRACT FROM AUTHOR]

Background:There have been controversies in prognostic impact of mucinous histology on colorectal cancer, and its implication in patients treated with adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is unclear.Methods:Stage II and III colorectal cancer patients who underwent curative resection followed by adjuvant FOLFOX were included. Patients were grouped according to the mucinous content: >50%, mucinous adenocarcinoma (MAC); <50%, adenocarcinoma with intermediated mucinous component (AIM); and without any mucinous component, non-MAC (NMA). Clinicopathological features and disease-free survival (DFS) were compared.Results:Among a total of 521 patients, 27 patients (5.2%) had MAC, 41 patients (7.9%) had AIM, and 453 patients (86.9%) had NMA. Mucinous adenocarcinoma and AIM had higher frequency of proximal location and microsatellite instability, but lower frequency of angiolymphatic invasion. Disease-free survival was significantly worse in the MAC compared with NMA (3-year DFS 57% and 86%, respectively; P<0.001) and AIM (3-year DFS 87%, P=0.01 vs MAC). Multivariate analysis revealed MAC as an independent negative prognostic factor of DFS (adjusted hazard ratio 7.96, 95% confidence interval 3.76-16.8).Conclusion:Adenocarcinoma with intermediated mucinous component and MAC have distinct clinicopathological features compared with NMA. Mucinous adenocarcinoma has an adverse prognostic impact on stage II or III colorectal cancer treated with adjuvant FOLFOX. [ABSTRACT FROM AUTHOR]

Background:We aimed to determine the role of palliative resection in metastatic colorectal cancer (mCRC) and ascertain which patient populations would benefit most from this treatment.Methods:A total of 1015 patients diagnosed with mCRC at Seoul National University Hospital between 2000 and 2009 were retrospectively studied.Results:Of the 1015 patients, 168 patients with only liver and/or lung metastasis received curative resection. The remaining 847 patients were treated with palliative chemotherapy and/or palliative resection combined with best supportive care. Palliative resection was performed in 527 (62.2%) cases (complete resection with negative margin (R0) in 93, R1/2 in 434). Resected patients had a more prolonged median overall survival (OS) than unresected patients (21.3 vs 14.1 months; P<0.001). In multivariate analysis, R0 resection was found to be associated with a superior OS compared with R1/2 resection (51.3 vs 19.1 months; P<0.001) and no resection (51.3 vs 14.1 months; P<0.001). When we performed propensity score matching, palliative resection was found to be related to prolonged OS (hazard ratio=0.72, 95% confidence interval=0.59-0.89; P=0.003).Conclusion:Palliative resection without residual disease and chemotherapy confers a longer-term survival outcome than palliative chemotherapy alone in mCRC patient subset. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Transcription factor E3 (TFE3) has been shown to increase insulin sensitivity by activating insulin-signalling pathways. However, the role of TFE3 in glucose homeostasis is not fully understood. Here, we explored the possible therapeutic potential of TFE3 for the control of hyperglycaemia using a streptozotocin-induced mouse model of diabetes. Methods: We achieved overabundance of TFE3 in streptozotocin mice by administering an adenovirus (Ad) or adeno-associated virus serotype 2 (AAV2). We also performed an oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). To explore molecular mechanisms of blood glucose control by TFE3, transcriptional studies on the regulation of genes involved in hepatic glucose metabolism were performed using quantitative real-time PCR and chromatin immunoprecipitation assay. The binding site of TFE3 in the liver Gck gene promoter was identified using deletion and site-specific mutation studies. Results: Overabundance of TFE3 resulted in reduced hyperglycaemia as shown by the OGTT and ITT in streptozotocin-treated mice. We observed that TFE3 can upregulate Gck in a state of insulin deficiency. However, glucose-6-phosphatase and cytosolic phosphoenolpyruvate carboxykinase mRNA levels were decreased by Ad-mediated overexpression of Tcfe3. Biochemical studies revealed that the anti-hyperglycaemic effect of TFE3 is due to the upregulation of Gck. In primary cultured hepatocytes, TFE3 increased expression of Gck mRNA. Conversely, small interfering RNA-mediated knockdown of TFE3 resulted in a decrease in Gck mRNA. Conclusions/interpretation: This study demonstrates that TFE3 counteracts hyperglycaemia in streptozotocin-treated mice. This effect could be due to the upregulation of Gck by binding of TFE3 to its cognitive promoter region. [ABSTRACT FROM AUTHOR]

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To elucidate the location of motor entry points (MEPs) and intramuscular nerve endings of the hamstring muscles. We dissected 50 cadaveric lower extremities to identify the MEPs, where the nerve branch first pierced the muscle belly, and the proximal and distal limit points (PLPs and DLPs, respectively) of the terminal intramuscular nerve endings. These points were measured in relation to a reference line, expressed in x-coordinate, which connected the superior medial aspect of ischial tuberosity to the proximal aspect of the medial femoral epicondyle. We also expressed the MEP in y-coordinate, which is perpendicular to the x-coordinate connecting the superior medial aspect of ischial tuberosity to the lateral aspect of the greater trochanter. Finally, these distances were translated into percentage distances in relation to the total length of the reference lines and their mean values were calculated. For the long head of biceps femoris muscles, the MEPs were located at 41.5 and 36.3% distance of the x and y coordinates, while the PLP and DLP were located at 39.7 and 72.9% distance of the x-coordinate. For the short head, the corresponding data were 56.2, 59.7, 58.9 and 80.2%. The semitendinosus showed two innervations zones; the data for the upper and lower zones were 20.3, 18.9, 18.6, 36.8% and 59.9, 21.4, 56.6, 79.1%, respectively. For the semimembranosus, the data were 62.2, 18.8, 55.9 and 89.1%. The parameters provided from this study should help increase the efficacy and precision of motor point injections to the hamstring muscles. [ABSTRACT FROM AUTHOR]

statistical downscaling known for producing station-scale climate information from GCM output was preferred to evaluate the impacts of climate change within the Mount Makiling forest watershed, Philippines. The lumped hydrologic BROOK90 model was utilized for the water balance assessment of climate change impacts based on two scenarios (A1B and A2) from CGCM3 experiment. The annual precipitation change was estimated to be 0.1–9.3% increase for A1B scenario, and −3.3 to 3.3% decrease/increase for the A2 scenario. Difference in the mean temperature between the present and the 2080s were predicted to be 0.6–2.2°C and 0.6–3.0°C under A1B and A2 scenarios, respectively. The water balance showed that 42% of precipitation is converted into evaporation, 48% into streamflow, and 10% into deep seepage loss. The impacts of climate change on water balance reflected dramatic fluctuations in hydrologic events leading to high evaporation losses, and decrease in streamflow, while groundwater flow appeared unaffected. A study on the changes in monthly water balance provided insights into the hydrologic changes within the forest watershed system which can be used in mitigating the effects of climate change. [ABSTRACT FROM AUTHOR]

Corneal neovascularization can reduce visual acuity. GA-binding protein (GABP) is a transcription factor that regulates the expression of target genes including vascular endothelial growth factor (VEGF) and roundabout4 (Robo4), which participate in pathologic angiogenesis. We assessed whether intraocular injection of the GABP gene affects the growth of new corneal blood vessels in a mouse ocular neovascularization model. Transfection of human GABPα and GABPβ gene (GABPα/β) into human conjunctival epithelial cells resulted in decreased VEGF and Robo4 expression. Three groups of mice underwent chemical and mechanical denudation of the corneal epithelium. Subsequently, two groups were administered subconjunctival injection of lipoplexes carrying plasmid DNA encoding for human GABPα/β or an empty plasmid DNA at 1-week intervals. The third group served as an experimental control. In vivo delivery of human GABPα/β into mouse neovascularized cornea reduced VEGF and Robo4 gene expression. Biomicroscopic examination showed that, at 1 week after one or two injections, GABPα/β-treated eyes had significantly less neovascularized corneal area than did eyes treated with the empty vector. Histologic examination showed significantly less vascularized area and fewer blood vessels in the GABP-treated group at 1 week after injections. However, these angiosuppressive effects were weakened at 2 weeks after injections. Our results indicate that subconjunctival GABP gene delivery delays corneal neovascularization for up to 2 weeks in a mouse model of deliberate corneal injury.Gene Therapy (2009) 16, 973–981; doi:10.1038/gt.2009.50; published online 7 May 2009 [ABSTRACT FROM AUTHOR]

The purpose of this study is to understand the operational characteristics of a diesel engine that uses BD20 reformed by ultrasonic energy irradiation. In particular we study the effects of tuning injection delay and EGR rate. BD containing about 10% oxygen has attracted attention due to soaring crude oil prices and environmental pollution. This oxygen decreases soot by promoting combustion, but it also increases NOx. To solve this problem, injection timing may be delayed or an EGR system may be applied. These adjustments normally lower engine power and increase exhaust emission but, in using fuel reformed by ultrasonic energy irradiation (which is changed physically and chemically to promote combustion), we may hope to circumvent this problem. To control the duration of the ultrasonic energy irradiation, the capacity of the chamber in an ultrasonic energy fuel supply system was tested at 550cc and 1100cc capacities. As for the results of the experiment, we could identify the optimum EGR rate by investigating the engine performance and the characteristics of exhaust emissions according to the injection timing and the EGR rate while ultrasonically irradiated BD20 was fed to a commercial diesel engine. With UBD20 (at an injection timing of BTDC 16°), the optimum EGR rate, giving satisfactory engine performance and exhaust emissions characteristics, was in the range of 15∼20%. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse the impact of epidermal growth factor receptor (EGFR), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), aurora kinase (ARK) A/B, and excision repair cross-complementing gene 1 (ERCC1) on the efficacy of adjuvant chemotherapy with 5-fluorouracil and cisplatin (FP) after curative gastric resection. Normal and cancer tissue were separately obtained from gastrectomy samples of 153 patients with AJCC stage III-IV (M0) who subsequently treated with adjuvant FP chemotherapy. TS, DPD, TP, ERCC1, and ARK proteins were measured by immunohistochemistry (IHC). EGFR expression was investigated using a standardized IHC with the EGFR PharmDx assay. Amplification of EGFR gene was analysed using fluorescent in situ hybridisation (FISH). In multivariate analysis, stage, ratio of positive to removed lymph nodes, and EGFR expression were significant prognostic factors for overall survival. Patients with higher EGFR expression had better overall survival than those with lower expression (relative risk: 0.475 (95% confidence interval, 0.282-0.791, P=0.005). Low EGFR expression might be a predictive marker for relapse in curative resected stage III-IV (M0) gastric cancer patients who received adjuvant FP chemotherapy. [ABSTRACT FROM AUTHOR]

This prospective study was conducted with the Korean Cancer Study Group to evaluate the efficacy and safety of cetuximab combined with modified FOLFOX6 (mFOLFOX6) as first-line treatment in recurrent or metastatic gastric cancer and to identify potential predictive biomarkers. Patients received cetuximab 400 mg m(-2) at week 1 and 250 mg m(-2) weekly thereafter until disease progression. Oxaliplatin (100 mg m(-2)) and leucovorin (100 mg m(-2)) were administered as a 2-h infusion followed by a 46-h continuous infusion of 5-fluorouracil (2400 mg m(-2)) every 2 weeks for a maximum of 12 cycles. Biomarkers potentially associated with efficacy were analysed. Among 38 evaluable patients, confirmed response rate (RR) was 50.0% (95% CI 34.1-65.9). Median time-to-progression (TTP) was 5.5 months (95% CI 4.5-6.5) and overall survival (OS) 9.9 months. Eleven patients having tumour EGFR expression by immunohistochemistry with low serum EGF and TGF-alpha levels showed a 100% RR compared to 37.0% in the remaining 27 patients (P<0.001). Moreover, ligand level increased when disease progressed in seven out of eight patients with EGFR expression and low baseline ligand level. No patient exhibited EGFR amplification or K-ras mutations. Gastric cancer patients with EGFR expression and low ligand levels had better outcomes with cetuximab/mFOLFOX6 treatment. [ABSTRACT FROM AUTHOR]

To understand patients' perceptions of clinical trials (CTs) is the principal step in the enrollment of patients to CTs. However, these perceptions in eastern countries are very rare. From 12 February 2007 to 13 April 2007, we consecutively distributed the questionnaire to 842 cancer patients who initiated a first cycle of chemotherapy regardless of each treatment step in the Seoul National University Hospital. Younger age, higher educational degree, higher economic status, and possession of private cancer insurance were related with significantly higher awareness of CTs (P=0.001, P=0.006, P=0.002, and P=0.009, respectively). However, unlike awareness, perceptions on benefits of CTs were not changed according to age, educational degree, and economic status (P=0.709, P=0.920, and P=0.847, respectively). Willingness was also not changed according to age, educational degree, economic status, and private cancer insurance (P=0.381, P=0.775, P=0.887, and P=0.392, respectively). Instead, males and heavily treated patients had more positive perceptions on benefits (P=0.002 and P=0.001, respectively) and more willingness to participate in CTs (OR=1.17, 1.14-2.75: OR=1.59, 1.01-2.51, respectively). In summary, cancer patients' awareness of CTs, perceptions on the benefit in CTs, and willingness to participate are differently influenced by diverse medical and social conditions. This information would be very helpful for investigators to properly conduct CTs in eastern cancer patients. [ABSTRACT FROM AUTHOR]

Groundwater recharge and base flow using different investigated methods are simulated in the 15-ha Bukmoongol small-forested watershed located at the southern part of Korea. The WHAT system, PART, RORA, PULSE, BFI, and RAP software are used to estimate groundwater recharge or base flow and base flow index from the measured streamflow. Results show that about 15–31 per cent of annual rainfall might be contributed for base flow. The watershed groundwater recharge proportions are computed to about 10–21 per cent during the wet period and 23–32 per cent for the remainder periods. Mean annual base flow indices vary from 0.25 to 0.76 estimated using different methods. However, the study found out that all methods were significantly correlated with each other. The similarity of various methods is expressed as a weighted relationship provided by the matrix product from the principal component analysis. Overall, the BFI and WHAT software appeared consistent in estimating recharge or base flow, and base flow index under Korea’s conditions. The case study recommends the application of different models to other watersheds as well as in low-lying areas where most observation groundwater wells are located with available streamflow data. [ABSTRACT FROM AUTHOR]

The purpose of this study is to understand the physical and chemical characteristics of biodiesel blended fuel reformed by ultrasonic energy irradiation. To do this, a mixture of commercial diesel fuel and biodiesel was compared and analyzed according to whether or not ultrasonic energy irradiation was performed and the duration of irradiation. The results of the experiments indicate that when ultrasonic energy irradiation was performed on biodiesel blended fuel, its viscosity decreased by 3–7%. In the case of BD20, when ultrasonic energy irradiation was performed, its Sauter mean diameter (SMD) dropped by 12% on average. As the irradiation duration increased, the volume ratio of olefins increased up to a maximum of 2.7%, and the higher heating value increased to a maximum of 5.8%. On the contrary, the ratio of aromatics decreased by a maximum of 2.7%, and BI decreased by a maximum of 7%. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the prognostic value of tumour-associated macrophages with a focus on micro-anatomical localisation and determine whether molecular changes of the epidermal growth factor receptor (EGFR) are related to macrophage infiltration in resected non-small cell lung cancer (NSCLC). One hundred and forty-four patients were included in this study. Immunohistochemistry was used to identify CD68+ macrophages in the tumour islet and surrounding stroma. Epidermal growth factor receptor mutations were studied by direct sequencing. The EGFR gene copy number and protein expression were analysed by fluorescence in situ hybridisation and immunohistochemistry. Patients with a high tumour islet macrophage density survived longer than did the patient with a low tumour islet macrophage density (5-year overall survival rate was 63.9 vs 38.9%, P=0.0002). A multivariate Cox proportional hazard analysis revealed that the tumour islet macrophage count was an independent prognostic factor for survival (hazard ratio 0.471, 95% confidence interval 0.300-0.740). However, EGFR mutations, gene copy number, and protein expression were not related to the macrophage infiltration. In conclusion, tumour islet macrophage infiltration was identified as a strong favourable independent prognostic marker for survival but not correlated with the molecular changes of the EGFR in patients with resected NSCLC. [ABSTRACT FROM AUTHOR]

This study was performed to investigate the therapeutic effect of umbilical cord serum eyedrops on dry eye associated with graft-versus-host disease (GVHD). Twenty-four eyes of 12 patients with severe dry eye syndrome associated with GVHD were treated with 20% umbilical cord serum eyedrops. Symptom scoring, corneal sensitivity test, tear film break up time (BUT), Schirmer test, tear clearance rate (TCR), and corneal fluorescein staining were performed before and 2 and 6 months after treatment. Six months after treatment, significant improvement was observed in symptom score (from 3.83±0.38 to 0.83±0.57, P<0.01), corneal sensitivity (from 52.08±6.06 mm to 57.50±3.00 mm, P<0.01), tear film BUT (from 2.50±0.91 s to 5.71±1.04 s, P<0.01), and keratoepitheliopathy score (from 7.42±2.02 to 1.29±0.46, P<0.01). There was no siginificant change in Schirmer test and TCR results. No significant complications associated with the use of the eyedrops were observed. Umbilical cord serum eyedrops are safe and may be an effective way to treat severe dry eye associated with GVHD.Bone Marrow Transplantation (2007) 39, 231–235. doi:10.1038/sj.bmt.1705566; published online 8 January 2007 [ABSTRACT FROM AUTHOR]

Despite recent advances in the chemotherapy of chronic hepatitis B (CHB), an effective viral suppression after cessation of therapy has not yet been achieved. To investigate whether hepatitis B virus (HBV)-specific T-cell responses are inducible and can contribute to the viral suppression after cessation of the therapy, we conducted a proof-of-concept study with a DNA vaccine comprising of most HBV genes plus genetically engineered interleukin-12 DNA (IL-12N222L) in 12 CHB carriers being treated with lamivudine (LAM). When the ex vivo and/or cultured IFN-γ enzyme-linked immunospot (ELISPOT) assay was performed, the detectable HBV-specific IFN-γ secreting T-cell responses were observed at the end of treatment and during a follow-up. These type 1T-cell responses, particularly CD4+ memory T-cell responses could be maintained for at least 40 weeks after the therapy and correlated with virological responses, but not with alanine aminotransferase elevation. Moreover, DNA vaccination under LAM treatment appeared to be well-tolerated and showed 50% of virological response rate in CHB carriers. Thus, a combination therapy of the DNA vaccine with chemotherapy may be one of new immunotherapeutic methods for the cure of CHB.Gene Therapy (2006) 13, 1110–1117. doi:10.1038/sj.gt.3302751; published online 9 March 2006 [ABSTRACT FROM AUTHOR]

We have prepared pentacene films on Si, Al2O3, and glass substrates by thermal evaporation and have investigated their optical properties at room temperature over a wide range of frequencies from infrared to ultraviolet (5 meV to 6.5 eV). A series of optical phonon modes and electronic transitions have been observed. The internal vibrational modes in the infrared region match well their molecular counterparts but the electronic transitions show substantial changes from those of a free pentacene molecule. The HOMO–LUMO gap energy of the pentacene films deposited on Al2O3 and glass substrates is 1.85 eV. [ABSTRACT FROM AUTHOR]

Increased expression of VEGF in several types of tumours has been shown to correlate with poor prognosis. We used a replication-deficient adenoviral vector containing antisense VEGF cDNA (Ad5CMV-αVEGF) to down-regulate VEGF expression and increase the efficiency of delivery of the antisense sequence in the human breast cancer cell line MDA231-MB. Transfection of these cells with Ad5CMV-αVEGF in vitro reduced secreted levels of VEGF protein without affecting cell growth. Moreover, injection of the Ad5CMV-αVEGF vector into intramammary xenografts of these cells established in nude mice inhibited tumour growth and reduced the amount of VEGF protein and the density of microvessels in those tumours relative to tumours treated with the control vector Ad5(dl312). Our results showed that antisense VEGF[SUB165] cDNA was efficiently delivered in vivo via an adenoviral vector and that this treatment significantly inhibited the growth of established experimental breast tumours. The Ad5CMV-αVEGF vector may be useful in targeting the tumour vasculature in the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

The Reproducing Kernel Particle Method (RKPM), one of the major meshfree methods, is applied to the analysis of shear localization problem. The total Lagrangian formulation of RKPM and explicit time integration are employed in order to simulate the adiabatic shear band formation in a thermo-viscoplastic material. The multiresolution study based on multiple-scale RKPM is then accomplished and an efficient measure of the high-scale component is accordingly proposed for meshfree adaptive procedures. A time-marching strategy is also suggested and successfully implemented for the process of transient adaptive refinement. Numerical examples are finally presented to demonstrate the performance of meshfree adaptivity and to ensure the feasibility of the high-scale detector for multiple-scale refinements. [ABSTRACT FROM AUTHOR]

The effect of orientation in the amorphous and crystalline regions on the biodegradability of PTMS [poly(tetramethylene succinate)] was studied using the amorphous orientation function, birefringence, and crystallinity. The crystalline and amorphous intrinsic lateral sonic moduli, E and E, were 2.61 × 103 and 0.41 × 103 MPa, respectively. Using the data on birefringence, crystalline and amorphous orientation function ( f∈ and fam), crystallinity, and sonic modulus of the oriented PTMS fibers, the intrinsic birefringence of the crystalline (Δ) and amorphous (Δ) regions were evaluated to be 0.0561 and 0.0634, respectively. The biodegradabilities of oriented PTMS films were reduced as the elongation increased, i.e., the amorphous orientation increased. At low elongation (100 and 150%), however, biodegradabilities remained unchanged when the degradation test was performed in activated sludge, which was attributed to the amorphous orientation occurring even at 100% elongation, though the amorphous orientation direction was perpendicular to the fiber axis. [ABSTRACT FROM AUTHOR]

Metastable pseudomorphic GeSi layers grown by chemical vapor deposition or by molecular beam epitaxy on Si(100) substrates were implanted at room temperature. The implantations were performed with 90 keV As ions to a dose of 1 x 1013 cm-2 for Ge0.08Si0.92 layers and 70 keV BF2 ions to a dose of 3x 1013 cm-2 for Ge0.06Si0.94 layers. The samples were subsequently annealed for short 10–40 s durations in a lamp furnace with a nitrogen ambient, or for a long 30 min period in a vacuum tube furnace. For Ge0.08Si0.92 samples annealed for a 30 min-long duration at 700°C, the dopant activation can only reach 50% without introducing significant strain relaxation, whereas samples annealed for short 40 s periods (at 850°C) can achieve more than 90% activation without a loss of strain. For Ge0.06Si0.94 samples annealed for either 40 s or 30 min at 800°C, full electrical activation of the boron is exhibited in the GeSi epilayer without losing their strain. However, when annealed at 900°C, the strain in both implanted and unimplanted layers is partly relaxed after 30 min, whereas it is not visibly relaxed after 40 s. [ABSTRACT FROM AUTHOR]

A procedure of genetic evaluation of reproductive traits such as litter size and survival in a polytocous species under the assumption of polygenic inheritance is described. Conditional distributions of these traits are assumed to be Poisson and Bernoulli, respectively. Using the concept of generalized linear models, logarithmic (litter size) and probit (survival) functions are described as linear combinations of 'nuisance' environmental effects and of transmitting abilities of sires or individual breeding values. The liability of survival is expressed conditionally to the logarithm of litter size. Inferences on location parameters are based on the mode of their joint posterior density assuming a prior multivariate normal distribution. A method of estimation of the dispersion parameters is also presented. The use of a 'truncated' Poisson distribution is suggested to account for missing records on litter size. [ABSTRACT FROM AUTHOR]

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Based upon the method of eigenfunction expansion and Leknitskii's complex-variable potentials for the generalized plane deformation, the singular stress field near transverse cracks is examined for cross-ply composite laminates under two types of deformation, extension and in-plane shear. The stress singularity for each deformation is obtained from the eigenvalue equation resulting from appropriate near field conditions. It is found that the stress singularity for in-plane shear deformation is much stronger than for extension. To compute the stress intensity, use is made of the asymptotic representation for the stress and displacement field in conjunction with the singular hybrid finite element method. The numerical results are confirmed through comparison to those from other numerical techniques such as the boundary collocation method. [ABSTRACT FROM AUTHOR]

Four hundred and ninety-five sera from 325 patients from whom Pseudomonas aeruginosa had been isolated and 86 control sera were tested for antibody by indirect haemagglutination tests (HAT) and complement fixation tests (CFT) using a polyvalent pseudomonas serotype-specific vaccine antigen, PEV-02. Sera were also tested by countercurrent immunoelectrophoresis (CIE) for precipitins to a species-specific protein antigen. Control sera gave titres of 160 or less by HAT and 20 or less by CFT. 2-Mercaptoethanol resistant antibody titres (immunoglobulin G) were below 40 for all control sera and none of the latter contained precipitins to common antigen. Of 325 patients, 156 (48%) gave titres of 320 or greater by HAT and of these, 114 (73%) showed elevated immunoglobulin G titres. Less patients with positive blood cutures than expected were positive by HAT and more patients with bone infections gave raised immunoglobulin G titres than expected. Cystic fibrosis patients were invariably seropositive by all tests. There was a correlation between positive CIE and CFT tests, especially in patients who were positive by HAT. Approximately half of 83 patients tested gave a serotype-specific antibody response. The tests were of little value in confirming clinically evident acute infections, but in cases of doubtful infection they did provide confirmatory evidence of an antibody response in approximately one-third of patients culture-positive for Pseudomonas aeruginosa. [ABSTRACT FROM AUTHOR]

The morphological changes of Poly(tetramethylene succinate) single crystal lamellae by hydrolysis are investigated, using TEM, WAXD and SAXS. And the morphology of PTMS spherulites was also observed by optical microscopy after treatments as well as single crystal lamellae. The edge region of single crystal lamella can be most easily affected in the initial stage of hydrolysis. As the hydrolysis time increases, the lamellae are separated into small fragments which may be started from the uneven or irregular parts of the surface. The WAXD results showed that crystallinity were increased with increasing of treatment time. The lamellar thickness decreased at the initial stage of hydrolysis and increased again. There were cracks on the surface of spherulites after hydrolysis and the direction of cracks were tangential direction of spherulites. This result was thought to be from the uniformity of molecular arrangement in the crystallographic unit cell. [ABSTRACT FROM AUTHOR]