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Background: Diarrheagenic Escherichia coli (DEC) strains are predominant cause of gastrointestinal tract illnesses. The main objective of the study was to determine antibiotic resistance in various types of DEC isolated from chicken broilers farmed in Pakistan. Methods: A total of 200 feces and 200 meat samples from broiler chickens were collected from the slaughtering shops in Southern Punjab, Pakistan. The confirmed fecal (n=150) and meat (n=150) E. coli isolates were investigated against 16 antibiotics. Fourteen virulence genes specific for Enteropathogenic (EPEC), Shiga Toxin-producing (STEC), Enteroinvasive (EIEC), Enteroaggregative (EAEC), and Enterotoxigenic (ETEC) E. coli were identified using Polymerase Chain Reaction. Results: EPEC was the most detected pathotype in both feces (76%) and meat (90%) samples, followed by STEC, EIEC, and ETEC. The highest resistance (40-90%) was observed against penicillin, oxytetracycline, and nalidixic acid in fecal isolates. More than 50% EPEC and EAEC fecal isolates, and 60% EAEC meat isolates were simultaneously resistant to 6 or more antibiotics. Conclusion: Conclusively, the broiler meat sold in open markets of Pakistan was considerably contaminated with multi-drug resistant DEC. To mitigate the issue, the gov- ernment should regulate the use of antibiotics at poultry farms and monitor slaughtering practices in slaughterer houses.

Objective The morphological data of the second thoracic vertebra and the third lumbar vertebra were measured by computerized tomography （CT）. The sex differences were analyzed and the discrimination equation was obtained. Methods The data of 274 adults （203 cases from experimental group and 69 cases from validation group） from central China were collected. Four linear data （maximum transverse length of vertebral body, maximum longitudinal length of vertebral body, maximum transverse length of vertebral foramen, maximum longitudinal length of vertebral foramen）, one angle data （angle between spinous processes） and two area （vertebral foramen area, total cross-sectional area of vertebral body） data of the second thoracic vertebra and the third lumbar vertebra were collected, respectively. Then three ratios ［maximum transverse length/ maximum longitudinal length of vertebral body, maximum transverse length/ maximum longitudinal length of vertebral foramen, vertebral foramen area/ （total cross-sectional area of vertebral body-vertebral foramen area）］ and one angle （angle between spinous processes） were obtained. The discriminant equation was established for sexual discriminant analysis. Results The morphology of the second thoracic vertebra and the third lumbar vertebra was related with gender. Four single index discriminant formulae and eleven multi-index discriminant formulae were established. The 69 validation group samples were substituted into the formula for testing, and the maximum discriminant accuracy rate of the single-index discriminant formula was 75%. The maximum discriminant accuracy rate of multi-index discriminant formula was 83%. Conclusion It is feasible to conduct individual sex analysis by the morphological indexes of second thoracic vertebra and the third lumbar vertebra. The indexes have important application values in practice.基于CT测量典型椎体形态的华中地区成年人性别判别.目的 通过计算机体层成像（computerized tomography，CT）技术测量第2胸椎与第3腰椎的形态学相关数据，分析其性别差异并建立性别判别分析方程。 方法 采集华中地区成年人影像资料样本274例（实验组203例，验证组69例），分别对第2胸椎与第3腰椎的4个线性数据（椎体横向最大长度、纵向最大长度、椎孔横向最大长度、椎孔纵向最大长度）、1个角度数据（棘突间夹角）、2个面积数据（椎孔面积、椎体横断面总面积）进行测量，得出3个比值［椎体横向最大长度/纵向最大长度、椎孔横向最大长度/纵向最大长度、椎孔面积/（椎体横断面总面积-椎孔面积）］及1个角度（棘突间夹角），建立判别方程进行性别判别分析。 结果 第2胸椎与第3腰椎形态与性别存在相关性，建立了4个单指标判别公式及11个多指标判别公式。验证组代入公式检验，得到单指标判别方程的最大判别准确率为75%，多指标判别方程的最大判别准确率为83%。 结论 利用第2胸椎与第3腰椎的形态学指标进行个体性别分析具有一定可行性。.法医人类学；胸椎；腰椎；性别判别；计算机体层成像.

The standard of care for early postmenopausal ERα+ breast cancer patients is adjuvant endocrine therapy, typically an aromatase inhibitor or tamoxifen, and endocrine therapy with or without a CDK 4/6 inhibitor in the metastatic setting. However, a number of these patients are not sensitive to endocrine therapy or experience breast cancer recurrence 10 to 15 years after endocrine treatment, and all eventually progress in the metastatic setting. Metastasis of ER+ therapy-resistant breast cancer correlates with the acquisition of ESR1 activating mutations in up to 40% or more of affected patients. The two most common ERα mutations are Y537S and D538G, both of which confer ERα constitutive activity. Lasofoxifene is a SERM originally developed to treat vulvovaginal atrophy and osteoporosis. In this study, we analyzed the efficacy of lasofoxifene in the treatment of MCF7 tumor explant models that were engineered with CRISPR/Cas9 to express Y537S or D538G ERα. To better mimic the natural micro-environment of infiltrating ductal breast cancer, we used the mammary intraductal mouse model (MIND), in which tumor cells are introduced into the ducts via the nipple. Three MCF7 cell variants, MCF7 WT, MCF7 Y537S and MCF7 D538G were injected into the mammary ducts of NSG mice. Prior to injection, cells were labeled with a luciferase reporter to monitor tumor growth in vivo using a Xenogen IVIS imager. Mice were treated with three different doses of lasofoxifene (1, 5 and 10mg/kg; 5days/wk SQ), vehicle, or the SERD, fulvestrant, (5 mg SQ once per week = 250 mg/kg). After 70 days of treatment, primary tumor growth, as measured by endpoint tumor weight, of MCF7 WT, D538G and Y537S explants was significantly inhibited versus vehicle by 10 mg/kg lasofoxifene and fulvestrant. Compared to fulvestrant, lasofoxifene was significantly more effective at 5 and 10 mg/kg for the MCF7 Y537S and D538G tumors. Notably, the two MCF7 mutants metastasized to the lung and liver, whereas WT MCF-7 cells were only very weakly metastatic by the end of the study. Lasofoxifene significantly inhibited the metastasis of both MCF7 Y537S and D538G to the lungs and liver at 5 and 10 mg/ml. In contrast, fulvestrant only inhibited metastasis of the MCF7 D538G mutant to both organs. In a follow-up combination therapy study of MCF-7 WT and Y537S tumor explants, in which mice were co-treated with either fulvestrant and palbociclib or lasofoxifene and palbociclib, lasofoxifene plus palbociclib demonstrated a better outcome than fulvestrant and palbociclib in terms of primary tumor weight inhibition. Results for lung and liver metastasis inhibition are forthcoming. In conclusion, these data suggest that lasofoxifene may have the potential to be utilized as a treatment for metastatic breast cancers, including those that express constitutively active ERα mutations, including D538G and Y537S, and warrants further study. Citation Format: Laine M, Greene M, Chang Y-F, Phung L, Hiipakka R, Komm B, Greene GL. Lasofoxifene decreases breast cancer lung and liver metastasis in a mammary intraductal (MIND) xenograft model of mutant ERα+ breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD7-09.

Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancer cases and is more prevalent among young women and African American women. Metastasis and chemoresistance remain significant challenges in TNBC. The development of targeted therapies for TNBC may dramatically improve the survival of patients and the quality of life. An adaptor protein, Src Homology 2 Domain Containing Transforming Protein 1 (SHC1) and steroid receptor coactivator-3 (NCOA3) are found to be overexpressed in breast cancers and important in the regulation of tumor progression and metastasis and drug resistance in ER+ breast cancer. The elevated SHC1 or NCOA3 correlates with poor prognosis in breast cancer patients. However, the biological significance of SHC1 and NCOA3 in TNBC is not well known. In this study, we performed siRNA-mediated knockdown to determine the importance of SHC1 and NCOA3 in the cell proliferation and death of TNBC. The effect of siSHC1 or siNCOA3 on the invasion and chemoresistance was also assayed in vitro. We found that although SHC1 and NCOA3 knockdown slightly inhibited the tumor growth of TNBC cells (MDA-MB-231, BT549, and HS578T), siSHC1 + paclitaxel and siNCOA3 + paclitaxel significantly decreased cell proliferation and increased caspase-3/7 activity in vitro, compared to drug alone. In vivo studies using MDA-MB-231 xenografts and a TNBC PDX model also showed that siSHC1 and siNCOA3 significantly augmented paclitaxel-induced tumor shrinkage. In invasion assays, SHC1 and NCOA3 knockdown significantly decreased the invasion of TNBC cells. These results suggest that targeting SHC1 and NCOA3 is worth investigating for the treatment of TNBC. Citation Format: Chang Y-F, Wang Y, Greene GL. Src homology 2 domain containing transforming protein 1 and steroid receptor coactivator-3 as novel targets for triple-negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-11-14.

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The potential contribution of surface and ground water to overall nitrous oxide emissions from irrigated production systems has not yet been quantified. In this study we have used the International Panel on Climate Change (IPPC) emission factor five (EF5) to determine the indirect emissions from the irrigation water surface and from the ground water when it is pumped back onto the surface for irrigation. The additional land surface emission from the irrigation water source N was also calculated and termed the “indirect land surface emission”. The study primarily used data collected (2000–2010) from the Australian Cotton Research Institute, Narrabri, Australia to calculate indirect and direct farm emissions during the cotton production season from the research station. The average annual direct and indirect N2O-N emissions are 0.90 kg N2O-N ha−1 yr−1 direct; 0.30 kg N2O-N ha−1 yr−1 indirect emissions from the land surface; 0.08kg N2O-N ha−1 yr−1 from the head ditch; 0.03 kg N2O-N yr−1 from the tail drain. In total 26% of the emissions could be potentially emitted via the indirect pathway at the farm scale using river water for irrigation. If ground water with a concentration of (1.0 NO3-N mg L−1) was used to irrigate the crop then in total ∼1.4% of the emissions would be emitted via the indirect pathway at the farm scale. But further refinement of the indirect emission factor and improved monitoring of temporal and spatial surface and ground water total N concentrations are required for mass balance calculations. Direct measurement of the N2O-N water surface emissions is required to validate the IPCC calculated values.

Furrow irrigation in cotton growing vertosols is the most preferred method in Australia. After fertilisation, irrigation water interacts with the soil which can dissolve nitrogen (N) compounds into the run-off water. The run-off or tail water that leaves the field is enriched with N and can reduce crop N use efficiency. During 2014−2015 and 2015−2016 N solute concentration in the irrigation water and run-off was measured in a tillage cropping rotation experiment. In the continuous cotton treatments (2014−2015) when urea was broadcast on the surface of furrow irrigated cotton system, 11 % of the applied fertiliser (260 kg N ha−1) was lost from the field in the tail water. Most of the losses from the soil occurred during the first irrigation as nitrate and urea. The irrigation water supplied 10 kg dissolved organic nitrogen (DON) kg N ha−1 to the field. During 2015−2016, when subsurface banding of the urea was used, losses equated to 5 % of applied N, in irrigated continuous cotton treatments. In a second crop treatment, an irrigated maize rotation, the broadcasted urea was leached into the soil by rainfall before a 100 mm irrigation event. The run-off losses were less than the sub surface urea banding and in this treatment were 0.5 % of the applied fertiliser. The study shows that DON-N, NO3-N, NH4-N, Urea-N are dissolved from the soil in cotton production systems and lost to furrow irrigation run-off. This dissolved N maybe denitrified in the cotton irrigation network if the tail water is not reused quickly. The results show that N contributions from irrigation water need to be accounted for overall N budget of the cotton farm to improve the N use efficiency.

In this research, TRACE code with the interface code-SNAP was used to simulate and analyze the SBO (station blackout) accident which occurred in Maanshan PWR (pressurized water reactor) nuclear power plant (NPP). There are four main steps in this research. First, the SBO accident data of Maanshan NPP were collected. Second, the TRACE/SNAP model of Maanshan NPP was established by using these data. Third, this TRACE/SNAP model was used to perform the simulation and analysis of SBO accident. Finally, the simulation and analysis of SBO with mitigation equipments was performed. The analysis results of TRACE are consistent with the data of Maanshan NPP. The mitigation equipments of Maanshan can maintain the safety of Maanshan in the SBO according to the TRACE predictions.

A number of clinical guidelines on nutrition therapy in cancer patients have been published by national and international societies; however, most of the reviewed data focused on gastrointestinal cancer or non-cancerous abdominal surgery. To collate the corresponding data for esophageal cancer (EC), a consensus panel was convened to aid specialists from different disciplines, who are involved in the clinical nutrition care of EC patients. The literature was searched using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the ISI Web of Knowledge. We searched for the best evidence pertaining to nutrition therapy in the case of EC. The panel summarized the findings in 3 sections of this consensus statement, based on which, after the diagnosis of EC, an initial distinction is made between the patients, as follows: (1) Assessment; (2) Therapy in patients with resectable disease; patients receiving chemotherapy or chemoradiotherapy prior to resection, and patients with unresectable disease, requiring chemoradiotherapy or palliative therapy; and (3) Formula. The resulting consensus statement reflects the opinions of a multidisciplinary group of experts, and a review of the current literature, and outlines the essential aspects of nutrition therapy in the case of EC. The statements are: Patients with EC are among one of the highest risk to have malnutrition. Patient generated suggestive global assessment is correlated with performance status and prognosis. Nutrition assessment for patients with EC at the diagnosis, prior to definitive therapy and change of treatment strategy are suggested and the timing interval can be two weeks during the treatment period, and one month while the patient is stable. Patients identified as high risk of malnutrition should be considered for preoperative nutritional support (tube feeding) for at least 7-10 days. Various routes for tube feedings are available after esophagectomy with similar nutrition support benefits. Limited intrathoracic anastomotic leakage postesophagectomy can be managed with intravenous antibiotics and self-expanding metal stent (SEMS) or jejunal tube. Enteral nutrition in patients receiving preoperative chemotherapy or chemoradiation provides benefits of maintaining weight, decreasing toxicity, and preventing treatment interruption. Tube feeding or SEMS can offer nutrition support in patients with unresectable esophageal cancer, but SEMS is not recommended for those with neoadjuvant chemoradiation before surgery. Enteral immunonutrition may preserve lean body mass and attenuates stress response after esophagectomy. Administration of glutamine may decrease the severity of chemotherapy induced mucositis. Enteral immunonutrition achieves greater nutrition status or maintains immune functions during concurrent chemoradiation.

Objective To study the change trend, distribution characteristics and causes of medical malpractices in 18 years, through retrospective analysis of 1 900 cases of medical malpractices, in order to provide guidance for the precaution and the treatment of medical malpractices. Methods A thousand and nine hundred medical malpractice cases that were accepted by Hunan Xiangya Judical Identification Center from 2000 to 2017 were collected. Statistical analysis on the caseloads, the clients, the department distributions, the levels of the hospital and the causes of medical malpractices, etc were conducted. Results The number of cases commissioned by third-party accreditation agencies for medical fault identification was on the rise; The clients of medical malpractices changed significantly in 18 years. Most of the medical malpractice cases occurred in secondary and tertiary hospitals, significantly more in surgery, obstetrics and gynecology. The occurrence of medical malpractices was related to the doctor's insufficient prediction of the severity of the disease and the possible complications, and failure to fully inform the relevant duty of care, etc. Conclusion China's medical malpractice solutions and medical fault identification procedures are gradually improving. Strengthening the medical malpractice precaution awareness of medical workers in surgery, obstetrics and gynecology will be conducive to resolution of medical malpractices.1 900例医疗损害鉴定的回顾性分析.目的 通过对1 900例医疗损害案件进行回顾性分析，研究18年间医疗损害案件的变化趋势、分布特点和发生原因，为医疗损害的预防和处理提供指导。 方法 选择湖南省湘雅司法鉴定中心2000—2017年受理的1 900例医疗损害鉴定案件，对每年的案件量、委托方、科室分布、医院等级、发生原因等数据进行统计。 结果 委托第三方鉴定机构进行医疗过错鉴定的案件数量呈上升趋势，医疗损害鉴定的委托单位在18年间发生了显著变化。医疗损害以二级和三级医院发生较多，在外科和妇产科明显偏多。医疗损害的发生与医方对病情严重性及可能出现的并发症预见不足、未尽到充分告知相关注意义务等有关。 结论 我国医疗损害案件的解决途径和医疗过错鉴定程序在逐步完善，加强外科、妇产科医护人员医疗损害防范意识有利于医疗损害的解决。.法医学；回顾性研究；医疗损害；案例分析.

To establish a mathematical model of stature estimation for Sichuan Han females on the basis of the relationship between lower limbs and individual height, thus to provide evidence for forensic identification.Samples were collected from 171 Sichuan Han females. Large flat panel multi-function digital photography system was used to take the full-body X-ray films of the lower limbs. Indexes of long bones and stature of the subjects were measured, respectively. A linear regression analysis was carried out on the correlation between them, and a mathematical model of the stature calculation was established. Then the mathematical model was used to calculate the stature of another 29 Sichuan Han females to test its accuracy.The maximum length of femur （The stature estimation is high by using the long bones of the lower limbs has high accuracy.全下肢直接数字X线摄影推算四川汉族女性身高.探究下肢长骨与个体身高的关系，建立当代四川汉族女性身高推算的数学模型，为法医学个体识别提供依据。.收集171例四川汉族女性个体，应用大平板多功能数字化摄影系统采集全下肢正位X线片，测量下肢长骨相关指标，同时测量被研究者的身高，对下肢长骨各指标与身高的相关性进行线性回归分析，建立身高推算的数学模型。同时，运用该数学模型，对另外29例四川汉族女性的身高进行推算，以检验上述身高推算模型的准确性。.股骨最大长（利用下肢长骨进行身高推算准确性较高。.法医人类学；X线；身高；下肢骨；四川；女性.

The analysis aimed to identify the treatment gaps in current fracture liaison services (FLS) and to provide recommendations for best practice establishment of future FLS across the Asia-Pacific region. The findings emphasize the unmet need for the implementation of new programs and provide recommendations for the refinement of existing ones. The study’s objectives were to evaluate fracture liaison service (FLS) programs in the Asia-Pacific region and provide recommendations for establishment of future FLS programs. A systematic literature review (SLR) of Medline, PubMed, EMBASE, and Cochrane Library (2000–2017 inclusive) was performed using the following keywords: osteoporosis, fractures, liaison, and service. Inclusion criteria included the following: patients ≥ 50 years with osteoporosis-related fractures; randomized controlled trials or observational studies with control groups (prospective or retrospective), pre–post, cross-sectional and economic evaluation studies. Success of direct or indirect interventions was assessed based on patients’ understanding of risk, bone mineral density assessment, calcium intake, osteoporosis treatment, re-fracture rates, adherence, and mortality, in addition to cost-effectiveness. Overall, 5663 unique citations were identified and the SLR identified 159 publications, reporting 37 studies in Asia-Pacific. These studies revealed the unmet need for public health education, adequate funding, and staff resourcing, along with greater cooperation between departments and physicians. These actions can help to overcome therapeutic inertia with sufficient follow-up to ensure adherence to recommendations and compliance with treatment. The findings also emphasize the importance of primary care physicians continuing to prescribe treatment and ensure service remains convenient. These findings highlight the limited evidence supporting FLS across the Asia-Pacific region, emphasizing the unmet need for new programs and/or refinement of existing ones to improve outcomes. With the continued increase in burden of fractures in Asia-Pacific, establishment of new FLS and assessment of existing services are warranted to determine the impact of FLS for healthcare professionals, patients, family/caregivers, and society.

The last decade has witnessed great interest in research on content-based image retrieval (CBIR). In 2009, Lin et al. proposed a smart CBIR system based on colour and texture feature. Their system has a high detection rate except the cases where image objects have similar shapes. To enhance the detection rate a shape-based image feature called object-moment is proposed in this paper. Object-moment uses the moment of force to compute the object edge feature by calculating the distance from each edge pixel to the axis, and adding them up as a feature. Besides, we integrate the colour features (NSOM, CSOM) and the texture features (CCM, DBPSP) to enhance image detection rate and simplify computation of image retrieval. A series of analyses and comparisons are performed in our experiments to demonstrate that our proposed method improves the retrieval accuracy significantly.

Intrinsic and acquired resistance to antineoplastic agents continues to be a major clinical impediment to successful treatment of cancer in general, and breast cancer in particular. For example, about 40% of ER-positive metastatic breast tumors fail to respond to tamoxifen therapy, and of those that initially respond many will eventually develop resistance. Similarly, taxanes used as a first-line chemotherapy agent will have a response rate of 50%, which comes down to 20–30% in second- or third-line chemotherapy; nearly half of the treated subjects do not respond to it and suffer side effects. These facts underscore the importance of understanding the mechanism of resistance, which is crucial for the optimal systemic therapy of breast cancer. Unfortunately, in spite of extensive inquiry in this field, little is known about the key molecules/signaling pathways that regulate this phenomenon. Recently, we have discovered that small non-coding RNAs, i.e. microRNA (miRNAs), may play a critical role in mediating drug resistance in breast cancers. We have identified miRNAs that are differentially expressed between drug-resistant and sensitive breast cancer cells. Specifically, we have combined a high-throughput screening platform with a library of chemically synthesized inhibitors for all known human miRNAs and identified specific miRNA that selectively sensitize/de-sensitize drug-resistant breast cancer cells to either tamoxifen or trastuzumab (herceptin), drugs that are commonly used as a first line treatment for ER-positive and Her2-positive breast cancers, respectively. We identified 10 and 12 miRNA inhibitors that sensitized resistant cells to tamoxifen and trastuzumab, respectively. Interestingly, expression of cognate miRNA/s that sensitize resistant tumors to drug-induced cell death in our screen was found to be lower in relapsed (drug-resistant) metastatic breast cancer patients compared to normal matched control. In addition to tumor tissues, the levels of sensitizer miRNA/s in the blood sera of relapsed metastatic breast cancer patients was found to be dramatically lower than that of normal healthy individual. These findings are significant as it suggests that miRNAs can be efficiently detected in blood serum and therefore, can be used as a potential biomarker for predicting treatment outcomes. In addition, miRNAs may provide novel therapeutic tools for the treatment of drug-resistant breast cancers. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-07-10.

Intrinsic and acquired resistance to antineoplastic agents continues to be a major clinical impediment to successful treatment of cancer in general, and breast cancer in particular. For example, about 40% of ER-positive breast tumors fail to respond to tamoxifen therapy, and of those that initially respond many will eventually develop resistance. Similarly, taxanes used as a first-line chemotherapy agent will have a response rate of 50%, which comes down to 20–30% in second- or third-line chemotherapy; nearly half of the treated subjects do not respond to it and suffer side effects. These facts underscore the importance of understanding the mechanism of resistance, which is crucial for better management of breast cancer. Unfortunately, in spite of extensive inquiry in this field, little is known about the key molecules/signaling pathways that regulate this phenomenon. Recently, we have discovered that small non-coding RNAs, i.e. microRNA (miRNAs), may play a critical role in mediating drug resistance in breast cancers. We have identified miRNAs that are differentially expressed between chemoresistant and sensitive breast cancer cells. Specifically, we have combined a high-throughput screening platform with a library of chemically synthesized inhibitors for all known human miRNAs and identified specific miRNA that selectively sensitize/de-sensitize drug-resistant breast cancer cells to either tamoxifen or trastuzumab (herceptin), drugs that are commonly used as a first line treatment for ER-positive and Her2-positive breast cancers, respectively. Interestingly, we identified 10 and 12 miRNA inhibitors that sensitized resistant cells to tamoxifen and trastuzumab, respectively. Interestingly, expression of cognate miRNA/s that sensitize resistant tumors to drug-induced cell death in our screen was found to be lower in relapsed (drug resistant) metastatic breast cancer patients compared to normal matched control. In addition to tumor tissues, the levels of sensitizer miRNA/s in the blood sera of relapsed metastatic breast cancer patients was found to be dramatically lower than that of normal healthy individual. These findings are significant as it suggests that miRNAs can be efficiently detected in blood serum and therefore, can be used as a potential biomarker for predicting treatment outcomes. In addition, miRNAs may provide novel therapeutic tools for the treatment of drug-resistant breast cancers. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-10-14.

Approximately 15–20% of all breast cancers account for triple negative breast cancers (TNBCs) that exhibit an aggressive, distinct metastatic pattern and poor prognosis resulting in a disproportionate number of breast cancer deaths. More than 50% of patients with TNBC develop chemoresistance and do not respond to chemotherapeutic drugs, leading to early relapse and shorter survival. Understanding the mechanisms underlying such resistance is therefore crucial for the development of new, efficacious cancer drugs. In spite of extensive inquiry in this field, little is known about the key molecules/signaling pathways that regulate this phenomenon. Recently, we have discovered that small non-coding RNAs-miRNAs play critical roles in mediating drug sensitivity/resistance in TNBCs. We have identified miRNAs that are differentially expressed between chemo-resistant and sensitive breast cancer cells. In particular, through high-throughput miRNA inhibitor library screens, we have identified miRNA inhibitors that sensitize resistant TNBC cells to paclitaxel, a drug commonly used to treat triple negative breast cancers. Interestingly, our studies revealed that specific miRNAs including miR-185 (patent pending) that sensitize resistant TNBCs to paclitaxel are expressed at significantly lower levels in relapsed metastatic TNBC patient sera compared to sera from their healthy siblings. Furthermore, using liposome- or biocompatible PLGA nanoparticle-based approaches, we show that systemic delivery of one of the sensitizer miRNAs suppresses breast cancer lung metastasis without any hepatotoxicity in preclinical mouse tumor models. Importantly, we show that one of the mechanisms by which sensitizer miRNAs regulate paclitaxel sensitivity is by targeting Stathmin, a microtubule destabilizer protein that can bind to tubulin dimers and stimulate microtubule destabilization. These findings suggest that tumor-specific miRNAs render selective cell cytotoxicity in a drug-specific manner, that these miRNAs may serve as detection markers for identifying patients who might benefit most from specific drug treatment, and that these miRNAs may represent novel therapeutic tools for the treatment of the TNBCs. Since miRNAs are endogenously expressed and can be easily manipulated using synthetic oligoribonucleotides, we believe that they represent more attractive targets than the single gene or gene product targeted by conventional cancer treatments that are typically prone to drug resistance. Since paclitaxel is used for the treatment of many cancers, the long-term implications of this study are likely not limited to breast cancer alone but may apply to other tumor types. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-10-16.

We demonstrate an extended reach 60 km coarse wavelength division multiplexing (CWDM)-time division multiple access (TDMA) passive optical network (PON) with 40 Gb/s capacity for both down and upstream directions. The system leverages existing 10 Gb/s TDMA PON technologies and incorporates various subsystems such as volume manufacturable optical transmitters, a prototype 10 Gb/s burst-mode receiver, hybrid semiconductor optical amplifier-Raman amplifiers, and a cyclic CWDM multiplexer. We confirm that this 32-user system has sufficient power margin to accommodate 128 users.

Background and context: Since 1982, cancer has been the leading cause of death in Taiwan, claiming more than 40,000 lives each year. This not only caused huge medical expenses, but also affected the quality of life of patients and their families. However, many cancer survivors and their caregivers do not fully understand lifestyle advice, including nutrition and dietary behaviors, to lower the progression of the disease. Due to cancer and painstaking treatment, cancer patients often suffer from inadequate calories intake and serious body weight (BW) loss, which is highly related to malnutrition or cancer cachexia. After they leave the hospital, they still need nutritional guidance; therefore, the importance of providing nutrition services in the community should be emphasized. Aim: To help cancer survivors achieve better nutritional status by teaching them how to have adequate calories intakes and maintain BW that they're supposed to have better quality of life. Strategy/Tactics: (1) Cancer survivors with nutritional needs were referred from 66 cooperative cancer resources centers of hospitals nationwide. (2) Dietitians assess their nutritional conditions and provide nutritional guidance. (3) Deliver free nutritional supplements to the cancer survivors who are financially disadvantaged or have dysphagia problems. Program/Policy process: The registered dietitians conducted nutritional education through nutrition counseling and guidance. For those who are financially disadvantaged or have dysphagia problems, the 24-hour dietary recall and PG-SGA scale were used to assess the survivors' nutritional status, including BW and calories intake, then free nutritional supplements according to their needs and a regular follow-up to collect their BW and nutritional information changes after our interventions were done. Outcomes: From 2016 to 2017, a total of 434 of cancer survivors who have financial difficulties or dysphagia problems accepted the free nutritional supplements and nutritional guidance services. 178 survivors completed follow-up and collected nutritional information. 40.4% of them are head and neck cancers, 38.2% are digestive system-related cancers that were in poor eating conditions. After our interventions, 70.2% of these survivors can maintain or increase their BW with average BW 57.9 ± 12.8 kg; and 77.0% can maintain or increase the calories intake, which average increased from 1798 ± 252.5 kcal/day to 1541.6 ± 347.9 kcal/day. What was learned: We can effectively help cancer survivors achieve adequate calories intakes and maintain BW to prevent the occurrence of malnutrition by providing the services of nutritional supplements and nutritional guidance.

In order to measure 182Hf by accelerator mass spectrometry (AMS), a chemical procedure for separation of hafnium from tungsten has been developed by extraction chromatography. The extraction chromatographic behavior of hafnium and tungsten has been studied using tri-n-octylamine (TOA) as the stationary phase, HCl–H2O2 mixture and NH3·H2O as the mobile phase. The effects of H2O2 concentration, column loading and column dimensions are investigated. Hf and W with microgram amounts are successfully separated on a chromatographic column (O5 × 196 mm), on which Hf is hardly retained after completely eluted with 6 M HCl–1% H2O2 and W strongly adsorbed is then eluted with 3 M NH3·H2O. The decontamination factor for tungsten is 3.0 × 105 and the recovery of hafnium is better than 99% using a single column separation.

In this paper, a new data hiding scheme for halftone images by pixel swapping is proposed, and the decryption process needs no computation. The proposed scheme generates a halftone stego-image with high visual quality, and the secret can be revealed in human vision system by stacking the stego-image with another designated halftone image. The quality of the revealed secret image is better than other existing schemes. In addition, the proposed scheme can cooperate with other existing data hiding schemes for halftone images to further increase the revealed secret quality without losing the characteristic of the original stego-image.

Supplier selection is a critical multi-criterion decision-making activity for suc- cessful supply chain management. This study involved developing an integrated supplier selection methodology, which is constructed using analytic network process, data envelop- ment analysis, and multiple objective particle swarm optimization. The proposed integrated methodology can account for multiple supplier selection criteria and set boundaries on weight value for multiple objective data envelopment analysis inputs and outputs. To solve the data envelopment analysis model, a new algorithm based on multiple objective particle swarm optimization is introduced, which embeds with tabu list and group mechanisms, and then, it is found to be superior to the compared algorithms in solving performance on three test functions and the illustrative case. In addition, the proposed integrated method- ology was applied to a supplier selection problem of sphygmomanometer manufacturer in Taiwan to verify its applicability of decision-making process. The results show that the methodology can be implemented as an effective decision aid for supplier selection under multiple criteria with weight restrictions.

A method of efficiency calibration for the measurement of 88Kr and 138Xe by HPGe γ-spectrometer is proposed in the present paper. The question for the efficient calibration is, how to achieve homogeneous sources of 88Kr-88Rb and 138Xe-138Cs. The fission product gases were obtained by irradiating a precisely measured amount of U3O8 (90% 235U) filled in a quartz glass ampoule. Source cell was first filled up with stearic acid, and then the fission product gases were charged into it. Xenon and krypton are not adsorbed on stearic acid, therefore, homogeneous sources of 88Kr-88Rb and 138Xe-138Cs can be prepared. The results of the experiment demonstrate that the method is feasible and successful.

This paper reports on the characterization of the nano-wool fibrous materials that were obtained by using a patent pending technology to pulverise natural wool fibers into nano-scale particles in terms of morphology. After three steps pulverization, the nano-wool particles are in fibrous shape with length of around 80–300 nm, diameter of 10–80 nm and the mode particle size was around 100 nm. The surfaces of cotton fiber in a fabric treated with the nano-wool fibrous materials were covered a film of nano-wool fibrous materials, which change the water absorbency, thermal conductivity and Qmax values of the fabric significantly. These results indicate that the nano-wool fibrous materials can be used as a functional material for cotton fabrics treatment.

1 Department of Bioenvironmental Engineering, Chung Yuan Christian University, 200, Chung-Pei Road, Chung-Li 320, Taiwan 2 Department of Environmental Engineering and Science, Chia-Nan University of Pharmacy and Science, Tainan 717, Taiwan 3 Department of Environmental Engineering and Management, Chaoyang University of Technology, Wufong, Taichung 413, Taiwan 4 Department of Tourism Management, Chia-Nan University of Pharmacy and Science, Tainan 717, Taiwan

The search for flavonoids with novel therapeutic effects has been intense. Wogonin, as a naturally existing monoflavonoid, has been shown to have therapeutic potential in vitro and in vivo. Methods for its extraction from herbs and its chemical synthesis have been developed. Pharmacokinetic studies have shown a rapid tissue distribution and prolonged plasma elimination phase of wogonin. It has been shown experimentally that wogonin exerts anti‐oxidant activity, which may, in part, underlie its antiinflammatory, anti‐cancer, antiviral and neuroprotective actions. The recent discovery of its anxiolytic activity suggests a new mechanism of action, involving interaction with the benzodiazepine (BZD) binding site of the GABA(A) receptor and modulation of this receptor activity. Although the safety record of wogonin is remarkable and voluminous literature about its pharmacological effects is available, it has not been used in Western medicine in the form of a pure chemical. In this article we review its therapeutic effects, its sources and pharmacokinetic profile to highlight its therapeutic potential.

We develop a 2-D discrete model to simulate malignant cells growing in healthy tissues using a thermodynamic method on the basis of Potts model. After introducing a malignant seed in a healthy tissue, we use a set of adjustment factors, including the interaction between cells and nutrient, to simulate the growth of malignant cells under different environments. This allows us to investigate the effects of environment on malignant cell growth and the formation of cancer.

A diamantane derivative 1,6-Bis [4-(4-amino-3-hydroxyphenoxy) phenyl] diamantane (DPD) was found to inhibit the growth of several cancer cell lines in the National Cancer Institute (NCI) Anticancer Drug Screen system. In this study, we examined the in vitro and in vivo effects of DPD on human colon cancer cells. DPD exerted growth inhibitory activities in vitro against three human colon cancer cell lines (Colo 205, HT-29, and HCT-15). DPD-treated cells were arrested at G(0)/G(1) as analysed by flow cytometric analysis. The expression of cyclin D was decreased in DPD-treated cells. The differentiation markers of carcinoembryonic antigen and fibronectin were significantly increased in colon cancer cells after treatment with DPD. The epithelium-like brush borders on HT-29 cell surface were also demonstrated at 1 week after withdrawal from DPD treatment. The DPD-induced cell growth inhibition and differentiation were irreversible after removal of DPD. The in vivo effect of tumour growth suppression by DPD was also observed in mouse xenografts. No acute toxicity was observed after an intraperitoneal challenge of DPD in BALB/c-nude mice weekly. These results suggest that DPD appears to be a new potentially less toxic modality of cancer therapy.

Aims To estimate the prevalence of blindness and partial sight in the general and diabetic populations and to measure the impact of ethnicity and gender on these rates. Methods Data on visual impairment in the population to be studied was obtained from the Royal Leicestershire Rutland and Wycliffe Society for the Blind (RLRWSB). Using the validated technique of capture-mark-recapture (CMR), a census day was set and data from four sources collected: hospital admissions data, GP returns, wards, and mass media. Computer cross-linkage to Leicestershire Health Authority data ensured patients were alive and resident in Leicestershire at the census date. Estimates of diabetes, ethnicity and gender prevalence were calculated using the 1991 census. Results CMR calculations revealed that there was under ascertainment of visual impairment in the RLRWSB data. The CMR calculations with direct age standardization estimate the prevalence of blindness and partial sight in the general and diabetic populations to be 51.8/10 000 (CI 50.6–53.0) and 148.8/10 000 (CI 122.1–175.5), respectively. In the diabetic population there was a higher proportion of visually impaired females than males (P

The partially cured unsaturated polyester (UPE)/styrene resins with various degrees of conversion lower than gel conversion blended with PVAc and 2-fluorotoluene solvent were investigated using both static and dynamic light scattering (SLS and DLS). The solvent (i.e., 2-fluorotoluene) is isorefractive with PVAc; thus, one sees only primary and partially cured UPEs in light-scattering experiments. DLS was used to follow the variations of primary UPE and UPE microgel particle sizes, and SLS was used to follow the variations of UPE molecular weight, second virial coefficient (A2), anisosymmetry (ρv), and differential index refraction (dn/dC) with degree of UPE conversion and PVAc concentration. The experimental data showed that, at a fixed degree of UPE/styrene conversion, increasing PVAc concentration in the UPE/styrene system caused decreases in dn/dC, A2, ρv, and particle sizes of UPE microgels. These results suggest that mixing PVAc into UPE/styrene resins causes an increase in the compactness of UPE coils and favors intramolecular UPE/styrene cyclization in the early stage of curing. Thus A2, ρv, and particle sizes of microgels decreased with increasing PVAc concentration. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 79: 1439–1449, 2001

Accumulating evidence shows that miRNAs play a role in drug resistance. Despite these observations, little is known about the identities of the miRNAs involved in drug resistance and their downstream targets. In the present study, we identified miR-296-5p for which a tumor suppressive role has been previously described, as a miRNA that is involved in paclitaxel drug resistance in triple negative breast cancer (TNBC) cells. Enforced expression of miR-296-5p suppressed cell growth, migration, and invasion in MDA-MB-231 breast cancer cells. Using a microarray approach, we identified BCL2-related Ovarian Killer (BOK), a pro-apoptotic gene as a target of miR-296-5p. BOK levels were validated BOK levels in miR-296-5p transfected MDA-MB-231 and MDA-MB-468 cells using real-time PCR and Western blot. Our results demonstrated that over-expression of miR-296-5p down-regulated BOK expression in TNBC cells. Transfection of miR-296-5p significantly suppressed luciferase reporters containing wild-type BOK-3'-UTR constructs. In contrast, mutant BOK-3'-UTR constructs were unaffected by ectopic miR-296-5p. Furthermore, BOK expression was induced in the presence of paclitaxel, but ectopic miR-296-5p significantly suppressed BOK induction by paclitaxel treatment compared to the control cells. These data provide new insights on the role of miRNAs in drug resistance and suggests that therapeutic strategies against miR-296-5p may be warranted. Citation Format: Onyeagucha BC, Rajamanickam S, Subbarayalu P, Bansal B, Bansal H, Chang Y-F, Timilsina S, Abdelfaltah N, Eedunuri VK, Rao MK. Down-regulation of Bcl2-related ovarian killer (BOK) by miR-296-5p protects breast cancer cells from paclitaxel-induced apoptosis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-03-04.

Oscillations of a SDOF piecewise linear system subjected to forced excitations with two harmonic fequencies has been investigated. A J integral was applied to determine the response types and to construct the bifurcation diagrams. Phenomena including jump behavior, subharmonics of various orders, period doubling, and intermittency to chaos were observed by the J bifurcation. Also, frequency locked oscillations, quasi periodic oscillations, and chaotic motions have been distinguished

Selectins participate in the initial events leading to leukocyte extravasation from the blood into tissues. Thus the selectins have generated much interest as targets for antiinflammatory agents. Therapeutic molecules based on the monomeric carbohydrate ligand sialyl Lewis X (SLe(X)) have low affinities and are not specific for a given selectin. Using SELEX (Systematic Evolution of Ligands by EXponential Enrichment) technology, we have generated aptamers specific for L-selectin that require divalent cations for binding and have low nanomolar affinity. In vitro, the deoxyoligonucleotides inhibit L-selectin binding to immobilized SLe(X) in static assays and inhibit L-selectin-mediated rolling of human lymphocytes and neutrophils on cytokine-activated endothelial cells in flow-based assays. These aptamers also block L-selectin-dependent lymphocyte trafficking in vivo, indicating their potential utility as therapeutics.

This paper explores the importance of the N loss pathways relative to the immobilisation and soil mineral N supply during a cotton season. Despite using an agronomic practice of splitting urea application to reduce losses and an optimal rate (232kg urea-N ha–1) for the experiment, the average fertiliser recovery was 32%, which indicates that soil N mineralisation is a key source of N for irrigated cotton production systems. A large amount of the fertiliser (62kgNha–1) was immobilised in the soil at the end of the season and during the season the soil supplied 159kgNha–1 to the plant via mineralisation. During the season, large N losses occurred from the field via the atmospheric, deep drainage and surface run-off pathways (143kgNha–1). The losses occurred directly after fertilisation, predominantly at the start of the season when the majority of the urea fertiliser was applied (180kg urea-N ha–1). This indicates that the form, placement and timing of the fertiliser did not synchronise with soil and crop N dynamics and irrigation practice. Over the course of the measurement season, based on the N inputs, losses and storage budget, a 42kgNha–1 soil deficit was observed. Further longer term work is required to quantify the magnitude and significance of the soil N stock across different systems.

In this paper, we present an effective block-based digital fragile watermarking scheme for image tamper detection and recovery. The proposed scheme embeds watermarks consisting of the authentication data and the recovery data into image blocks. It adopts parity check and the intensity-relation check to thwart various malicious attacks. In the tamper detection process, instead of independently testing the embedded authentication data of each block, we take the block-neighbourhood into account and utilize a hierarchical structure to determine the legitimacy of image blocks. Experimental results show that the proposed scheme can effectively resist collage attack, vector quantization (VQ) attack and constant-average attack, while sustaining superior accuracy of tamper localization. Furthermore, the results reveal that the tampered images can be successfully self-recovered with acceptable visual quality.

This paper reports performance tests on a DC-coupled 10Gb/s burst-mode receiver with on-chip reset, designed for 10G-GPONs. Record short 2R settling time, high sensitivity and large loud/soft ratio is demonstrated in burst-mode operations at 2.5G/5G/10Gb/s.

Taylor series methods compute a solution to an initial value problem in ordinary differential equations by expanding each component of the solution in a long Taylor series. The series terms are generated recursively using the techniques of automatic differentiation. The ATOMFT system includes a translator to transform statements of the system of ODEs into a FORTRAN 77 object program that is compiled, linked with the ATOMFT runtime library, and run to solve the problem. We review the use of the ATOMFT system for nonstiff and stiff ODEs, the propagation of global errors, and applications to differential algebraic equations arising from certain control problems, to boundary value problems, to numerical quadrature, and to delay problems.