It is believed that the solar energy is the ultimate clean energy source to meet global human energy consumption demand. However, The harvesting of solar energy in a clean and sustainable fashion and the storage and transport of the electricity could be challenges precluding practical scaling up of solar energy applications. Photoelectrochemical (PEC) water splitting using semiconducting materials is the most attractive approach of the solar energy applications because it efficiently converts solar energy, with high efficacy, to storable and transportable hydrogen fuel through an environmentally benign process (reaction with water and with hydrocarbon and oxygen as by-products). However, the good chemical and electrochemical stability and high overall energy conversion efficiency, in addition to low cost, are current challenges for the use of large scale PEC for practical and sustainable solar fuel production. The focus of this thesis is to develop economically competitive and efficient PEC water splitting cells by selecting low cost and earth abundant semiconductors and developing cheap and facile scalable processing for photoelectrode fabrication. Two systems, three dimensional branched nanowire heterostructures and metal coating enabled planar Si structures, are studied in details. This dissertation is structured in the following: after a briefly introduction of the principle of photoelectrochemical (PEC) water splitting cells in chapter 1, TiO₂ nanowires and TiO₂/Si branched nanostructures are discussed in chapters 2 and 3. As a low cost material, TiO₂ nanowire structure is prepared by a hydrothermal method and further modified by different post growth treatments to improve light absorption and kinetic properties and investigated their effects on PEC water splitting performances. The results show that types and sequences of post growth treatments should be carefully considered to improve the properties and performances of TiO₂ NWs. Also, hierarchically heterogeneous integrated TiO₂/Si nanostructures such as core/shell and multibranched nanowire structures are fabricated by a combination of nanoimprint lithography, reactive ion etch, and hydrothermal reactions. The structures have increased surface area for enhanced light absorption and more reaction sites and short diffusion length of minority carriers for higher reaction rate. Their PEC performances and the associated charge transfer at heterojunction interface are studied showing that photo current of TiO₂/Si heterojunction structure is limited by the recombination at the TiO₂/Si junctions or the properties of TiO₂. In chapter 4, metal-Si (MS) and metal- insulator-Si (MIS) structures, which have been studied in photovoltaic cells, are employed to developed cost- effective and efficient Si-based photoelectrodes. Earth abundant Ni film is selected as an oxygen evolution electrocatlayst for PEC photoanode, which can provide a junction voltage and protect Si surface, and applied to MS and MIS structures to compare their PEC performances and investigate the effects of insulating layer. Furthermore, MS and MIS structures are used to fabricate PEC photocathode with bimetal layer and the study is discussed in chapter 5. Bimetal layer can decouple catalytic reaction part from photovoltaic part. We design different patterned bimetal layers to improve the amount of light absorption of Si substrate and investigate the effects of MS or MIS contact, differently prepared insulator and bimetal thickness ratio on PEC water splitting performances. Finally, a summary on the major accomplishments and perspectives on future improvements are presented in Chapter 6

Drug resistance is a major obstacle in cancer treatment: A case in point is the failure of cancer patients to respond to tyrosine kinase inhibitors (TKI) of EGFR, a receptor that is highly expressed in many cancers. Identification of the targets and delineation of mechanisms of drug resistance remain major challenges. Traditional pharmacological assays of drug resistance measure the response of tumor cells using cell proliferation or cell death as readouts. These assays performed using traditional plastic tissue culture plates (2D) do not translate to in vivo realities. Here, we describe a genetic screen based on phenotypic changes that can be completed over a period of 1-1½ months using functional endpoints in physiologically relevant 3D culture models. This phenotype-based assay could lead to the discovery of previously unknown therapeutic targets and could explain the source of the resistance and relapse. As a proof of principle, we performed our 3D culture assay with a small cDNA library in that yielded five unknown intermediates in EGFR and PI3K signaling pathways. Here, we describe the screening method and the characterization of one of the five molecules, but this approach could be easily expanded for a high-throughput screening to identify or evaluate many more unknown intermediates in oncogenic signaling pathways.

Building on diversity literature, the present study examines the distinct effects of workforce diversity in various attributes on internal processes and performance at the organization level. Focusing on the status-relatedness of diversity dimensions, we propose thenegative effects of diversity in hierarchical position, and the positive effects of diversity in gender, age and education. We further identify innovative climate, employee competence, and employee satisfaction as the mediating mechanisms that account for the relationships between workforce diversity and organizational performance. The present hypotheses were empirically validated using time-lagged, multi-source data collected from 256 Koreanmanufacturing companies at two time points over a two-year period. Hierarchical position diversity was negatively related to employee competence and satisfaction, thus negatively affecting operational performance. Education diversity showed positive effects on innovativeclimate, employee competence, and employee satisfaction, which in turn increased the innovation and operational efficiency of the organization. A series of structural equation models also confirmed the negative direct effect of age diversity and the positive direct effect of education diversity on innovative performance. The present study elaborated the distinctimplications of diversity dimensions with different levels of status-relatedness, and offered empirical contributions that highlight mediating mechanisms between workforce diversity and performance at the organization level.

Approximately 60% of VACTERL (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with atresia, renal defects/radial limb dysplasia) patients have renal anomalies that can be associated with chronic kidney disease (CKD). With improved medical care, a large proportion of these patients survive into adulthood. Longitudinal follow-up data regarding the management of kidney disease in these children is lacking. Twelve VACTERL patients with CKD stage 2–5 and 12 age-matched controls with similar urologic anomalies and CKD [mean follow-up period 15.0 ± 1.4 (SE) and 11.9 ± 2.1 years, respectively] were identified in a single center. Eight VACTERL patients progressed to end-stage renal disease (ESRD) compared to four controls (66.7 vs. 33.3%, respectively). Six VACTERL patients were dialyzed pre-transplant. Of the four patients on peritoneal dialysis (PD), three had to be switched to hemodialysis due to complications, whereas two of the three controls on PD did not experience significant problems. Seven VACTERL patients underwent renal transplantation compared to four controls. Mean creatinine clearance 2 years post-transplant was 65.8 ± 6.3 in VACTERL patients vs. 87.8 ± 7.1 ml/min per 1.73 m2 in controls (p = 0.03). VACTERL patients had a significantly lower mean height standard deviation score than the controls (−2.34 ± 0.41 vs. −1.27 ± 0.24, respectively; p < 0.05). Based on these results, VACTERL patients with CKD develop ESRD more frequently, experience more complications with dialysis, may have a poorer transplant outcome, and have more severe growth failure than controls.

People are increasingly involved in the self-management of their own health, including chronic conditions. With technology advances, the choice of self-management practices, tools, and technologies has never been greater. The studies reported here investigated the information seeking practices of two different chronic health populations in their quest to manage their health conditions. Migraine and diabetes patients and clinicians in the UK and the US were interviewed about their information needs and practices, and representative online communities were explored to inform a qualitative study. We found that people with either chronic condition require personally relevant information and use a broad and varied set of practices and tools to make sense of their specific symptoms, triggers, and treatments. Participants sought out different types of information from varied sources about themselves, their medical condition, and their peers' experiences of the same chronic condition. People with diabetes and migraine expended great effort to validate their personal experiences of their condition and determine whether these experiences were 'normal'. Based on these findings, we discuss the need for future personal health technologies that support people in engaging in meaningful and personalised data collection, information seeking, and information sharing with peers in flexible ways that enable them to better understand their own condition.

Previously, we reported that overexpression of AtRH17, an Arabidopsis DEAD-box RNA helicase gene, confers salt stress-tolerance via a pathway other than the well-known salt stress-responsive pathways. To decipher the salt stress-responsive pathway in AtRH17-overexpressing transgenic plants (OXs), we performed RNA-Sequencing and identified 397 differentially expressed genes between wild type (WT) and AtRH17 OXs. Among them, 286 genes were upregulated and 111 genes were downregulated in AtRH17 OXs relative to WT. Gene ontology annotation enrichment and KEGG pathway analysis showed that the 397 upregulated and downregulated genes are involved in various biological functions including secretion, signaling, detoxification, metabolic pathways, catabolic pathways, and biosynthesis of secondary metabolites as well as in stress responses. Genevestigator analysis of the upregulated genes showed that nine genes, namely, LEA4-5, GSTF6, DIN2/BGLU30, TSPO, GSTF7, LEA18, HAI1, ABR, and LTI30, were upregulated in Arabidopsis under salt, osmotic, and drought stress conditions. In particular, the expression levels of LEA4-5, TSPO, and ABR were higher in AtRH17 OXs than in WT under salt stress condition. Taken together, our results suggest that a high AtRH17 expression confers salt stress-tolerance through a novel salt stress-responsive pathway involving nine genes, other than the well-known ABA-dependent and ABA-independent pathways.

The development of novel targeted therapies for cancer treatment requires identification of reliable targets. FAM83 ('family with sequence similarity 83') family members A, B, and D were shown recently to have oncogenic potential. However, the overall oncogenic abilities of FAM83 family genes remain largely unknown. Here, we used a systematic and integrative genomics approach to investigate oncogenic properties of the entire FAM83 family members. We assessed transcriptional expression patterns of eight FAM83 family genes (FAM83A-H) across tumor types, the relationship between their expression and changes in DNA copy number, and the association with patient survival. By comparing the gene expression levels of FAM83 family members in cancers from 17 different tumor types with those in their corresponding normal tissues, we identified consistent upregulation of FAM83D and FAM83H across the majority of tumor types, which is largely driven by increased DNA copy number. Importantly, we found also that a higher expression level of a signature of FAM83 family members was associated with poor prognosis in a number of human cancers. In breast cancer, we found that alterations in FAM83 family genes correlated significantly with TP53 mutation, whereas significant, but inverse correlation was observed with PIK3CA and CDH1 (E-cadherin) mutations. We also identified that expression levels of 55 proteins were significantly associated with alterations in FAM83 family genes including a decrease in GATA3, ESR1, and PGR proteins in tumors with alterations in FAM83. Our results provide strong evidence for a critical role of FAM83 family genes in tumor development, with possible relevance for therapeutic target development.

Breast cancer is a complex and multifactorial disease. Tumors have a heterogeneous microenvironment, which have multiple interactions with other cell types, greatly influencing the behavior of tumor cells and response to therapy. The 3D culture mimics the microenvironment better found in vivo and is more appropriated than the traditional 2D culture made from plastic to test the cellular response to drugs. To investigate the effects of [10]-gingerol on breast tumor cells, we used physiologically relevant three-dimensional (3D) cultures of malignant and non-malignant human breast cells grown in laminin-rich extracellular matrix gels (lr-ECM). Our results showed selective cytotoxicity of [10]-gingerol against the malignant T4-2 breast cancer cell line compared to non-malignant S1 cells. The compound reverted the malignant phenotype of the cancer cells, downregulating the expression of epidermal growth factor receptor (EGFR) and β1-integrin. Moreover, [10]-gingerol induced apoptosis in this cell line. These results suggest that [10]-gingerol may be an effective compound to use as adjuvant therapy in breast cancer treatment. J. Cell. Biochem. 118: 2693-2699, 2017. © 2017 Wiley Periodicals, Inc.

Objective

Studies evaluating major amputation after initial minor amputation are few with rates of subsequent major amputation ranging from 14% to 35% with limited understanding of associated comorbidities and time to limb loss. The aim of this study is to determine the major amputation rates for patients who had already undergone an initial minor amputation and determine which factors are associated with the need for subsequent major amputation.

Methods

Using statewide data between 2005 and 2013, patients with peripheral artery disease (PAD), diabetes mellitus (DM), and combined PAD/DM who had a lower extremity ulcer and who had also undergone a minor amputation were identified. These patients were evaluated for the rate of subsequent major amputation and competing risk Cox proportional hazards modeling was used to study which factors were associated with the risk of subsequent limb loss.

Results

The cohort consisted of 11,597 patients (DM, n = 4254; PAD, n = 2142; PAD/DM, n = 5201) with lower extremity ulcers who underwent an initial minor amputation. The rate of any subsequent amputation was highest in patients with PAD/DM (23% vs DM = 17%, PAD = 17%; P = not statistically significant). The rate of subsequent minor amputation was 16% in the PAD/DM versus 15.2% in PAD and 12.2% in patients with DM (P < .001). Patients with PAD/DM had the highest rate of subsequent major amputation (6.3% vs DM = 5.2%, PAD = 2.1%; P < .001). There was no statistically significant difference in the median time to major amputation among the three groups (PAD/DM, 13 months; DM, 14 months; PAD, 8.6 months; P = NS). Patients who were revascularized before a repeat minor amputation had a decreased risk of a major amputation compared with those who were intervened on after a repeat minor amputation (hazard ratio, 0.002; 95% confidence interval, 0-0.22). Patients treated completely in the outpatient setting were also less likely to undergo subsequent major amputation (hazard ratio, 0.7; 95% confidence interval, 0.5-0.98) compared with those who required hospitalization or presented to the emergency room.

Conclusions

Patients with ulcers and combined PAD and DM have a higher risk for secondary major and minor amputation than patients with either disease alone with half of the limb loss occurring at approximately 1 year after the initial minor amputation. Additionally, early diagnosis and appropriate referral may result in decreased limb loss for these patients.