Assessing the technical and economic viability of peer-to-peer energy sharing in off-grid environments

This thesis introduces the concept of peer-to-peer energy sharing in off-grid environment and analyze the technical and economic feasibility of this energy model. In the traditional power main network, many remote areas have difficulties in electricity, and P2P energy sharing discussed in this thesis is very suitable for this environment. In this thesis, P2P energy sharing technology is proven economically and technically feasible. However, it still faces many challenges, and we need more attempts and cases to promote its development

Impact of Scleroderma‐Associated Autoantibodies on Clinical Outcome Assessments: Post Hoc Analysis From a Randomised, Double‐blind, Placebo‐controlled, Phase 3 Trial of Tocilizumab in Scleroderma

Objective Scleroderma‐associated autoantibodies (SSc‐Abs) are specific in participants (pts) with systemic sclerosis and are associated with organ involvement. Our objective was to assess the influence of baseline SSc‐Abs on the trajectories of the clinical outcome assessments (COAs) in a phase III randomized controlled trial. Methods We used data on both the groups who received placebo (Pbo) and tocilizumab from the focuSSced trial. The SSc‐Ab panel was assessed centrally. We analyzed four groups with SSc‐Abs: anti–topoisomerase 1 antibody (ATA), anti–RNA polymerase 3 antibody (RNAP3), anti‐centromere antibody, and negative for all three (triple negative). We assessed the impact of baseline SSc‐Abs on six COAs: modified Rodnan skin score (mRSS), forced vital capacity (FVC%), Health Assessment Questionnaire Disability Index, patient and clinical global assessments, and American College of Rheumatology (ACR) Composite Response Index in Systemic Sclerosis (CRISS). Results We observed that all COAs, except for FVC%, improved for the group who received Pbo during the 48‐week period. For mRSS, pts with RNAP3 showed the largest Pbo effect (7.20 per year, n = 14) and smallest for ATA (3.28 per year, n = 49). This trend was also seen for the ACR CRISS (0.00–1.00 scale), with median improvement at week 48 of 0.94 for RNAP3 versus 0.01 for ATA. ATA enriched for FVC% decline of 7.34% per year versus 2.54% per year for RNAP3. In the group who received tocilizumab, similar changes were seen in the mRSS and ACR CRISS with preservation of lung function, irrespective of SSc‐Ab type. Conclusion Our result shows a differential effect of SSc‐Abs on the trajectories of COAs over 48 weeks in group who received Pbo. These findings highlight the importance of incorporating SSc‐Abs in trial design, either as a stratification factor or limiting the SSc‐Abs that are included in the trials

Prognostic and predictive markers of systemic sclerosis-interstitial lung disease in a clinical trial and long-term observational cohort

OBJECTIVES: Explore prognostic and predictive markers of systemic sclerosis-associated interstitial lung disease (SSc-ILD) outcomes in a phase 3 trial (focuSSced) and prognostic markers in a real-world cohort (SMART). METHODS: The focuSSced SSc-ILD subgroup included 68 of 106 placebo-treated and 68 of 104 tocilizumab-treated patients. The SMART cohort included 505 patients with SSc-ILD. Linear mixed-effect models were used to identify factors associated with change in forced vital capacity (FVC). Kaplan-Meier estimation and Cox regression were used for time-to-event analyses. RESULTS: In placebo-treated focuSSced patients, sex was a significant prognostic factor for FVC decline; males had increased risk for absolute decline ≥10% in percent-predicted FVC (ppFVC) and 0.22% faster weekly FVC decline than females (P = 0.0001). FVC was 9.8% lower in patients with C-reactive protein >6 mg/ml versus those with C-reactive protein ≤6 mg/ml (P = 0.0059). Tocilizumab reduced the risk for ≥10% decline in ppFVC in patients who were male, had earlier disease (<2 years duration), had interleukin-6 levels <10 pg/ml, or had anti-topoisomerase antibodies (ATA). In the SMART cohort, prognostic factors for ppFVC <70% were male sex, ATA, and low baseline FVC. Males had 3.3% lower FVC 1 year after disease onset (P < 0.001) and 0.6% faster yearly decline (P = 0.03) than females. CONCLUSION: Prognostic markers in SSc-ILD were similar between focuSSced and SMART. Male sex and inflammatory markers were associated with lower FVC but interleukin-6 ≥ 10 pg/ml was not predictive of response to tocilizumab. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02453256

A Large-Scale Zebrafish Gene Knockout Resource for the Genome-Wide Study of Gene Function

With the completion of the zebrafish genome sequencing project, it becomes possible to analyze the function of zebrafish genes in a systematic way. The first step in such an analysis is to inactivate each protein-coding gene by targeted or random mutation. Here we describe a streamlined pipeline using proviral insertions coupled with high-throughput sequencing and mapping technologies to widely mutagenize genes in the zebrafish genome. We also report the first 6144 mutagenized and archived F1’s predicted to carry up to 3776 mutations in annotated genes. Using in vitro fertilization, we have rescued and characterized ~0.5% of the predicted mutations, showing mutation efficacy and a variety of phenotypes relevant to both developmental processes and human genetic diseases. Mutagenized fish lines are being made freely available to the public through the Zebrafish International Resource Center. These fish lines establish an important milestone for zebrafish genetics research and should greatly facilitate systematic functional studies of the vertebrate genome

Mutational analysis of the tyrosine kinome in serous and clear cell endometrial cancer uncovers rare somatic mutations in TNK2 and DDR1

Background: Endometrial cancer (EC) is the 8th leading cause of cancer death amongst American women. Most ECs are endometrioid, serous, or clear cell carcinomas, or an admixture of histologies. Serous and clear ECs are clinically aggressive tumors for which alternative therapeutic approaches are needed. The purpose of this study was to search for somatic mutations in the tyrosine kinome of serous and clear cell ECs, because mutated kinases can point to potential therapeutic targets. Methods: In a mutation discovery screen, we PCR amplified and Sanger sequenced the exons encoding the catalytic domains of 86 tyrosine kinases from 24 serous, 11 clear cell, and 5 mixed histology ECs. For somatically mutated genes, we next sequenced the remaining coding exons from the 40 discovery screen tumors and sequenced all coding exons from another 72 ECs (10 clear cell, 21 serous, 41 endometrioid). We assessed the copy number of mutated kinases in this cohort of 112 tumors using quantitative real time PCR, and we used immunoblotting to measure expression of these kinases in endometrial cancer cell lines. Results: Overall, we identified somatic mutations in TNK2 (tyrosine kinase non-receptor, 2) and DDR1 (discoidin domain receptor tyrosine kinase 1) in 5.3% (6 of 112) and 2.7% (3 of 112) of ECs. Copy number gains of TNK2 and DDR1 were identified in another 4.5% and 0.9% of 112 cases respectively. Immunoblotting confirmed TNK2 and DDR1 expression in endometrial cancer cell lines. Three of five missense mutations in TNK2 and one of two missense mutations in DDR1 are predicted to impact protein function by two or more in silico algorithms. The TNK2P761Rfs*72 frameshift mutation was recurrent in EC, and the DDR1R570Q missense mutation was recurrent across tumor types. Conclusions: This is the first study to systematically search for mutations in the tyrosine kinome in clear cell endometrial tumors. Our findings indicate that high-frequency somatic mutations in the catalytic domains of the tyrosine kinome are rare in clear cell ECs. We uncovered ten new mutations in TNK2 and DDR1 within serous and endometrioid ECs, thus providing novel insights into the mutation spectrum of each gene in EC

Predisposition to Cancer Caused by Genetic and Functional Defects of Mammalian Atad5

ATAD5, the human ortholog of yeast Elg1, plays a role in PCNA deubiquitination. Since PCNA modification is important to regulate DNA damage bypass, ATAD5 may be important for suppression of genomic instability in mammals in vivo. To test this hypothesis, we generated heterozygous (Atad5+/m) mice that were haploinsuffficient for Atad5. Atad5+/m mice displayed high levels of genomic instability in vivo, and Atad5+/m mouse embryonic fibroblasts (MEFs) exhibited molecular defects in PCNA deubiquitination in response to DNA damage, as well as DNA damage hypersensitivity and high levels of genomic instability, apoptosis, and aneuploidy. Importantly, 90% of haploinsufficient Atad5+/m mice developed tumors, including sarcomas, carcinomas, and adenocarcinomas, between 11 and 20 months of age. High levels of genomic alterations were evident in tumors that arose in the Atad5+/m mice. Consistent with a role for Atad5 in suppressing tumorigenesis, we also identified somatic mutations of ATAD5 in 4.6% of sporadic human endometrial tumors, including two nonsense mutations that resulted in loss of proper ATAD5 function. Taken together, our findings indicate that loss-of-function mutations in mammalian Atad5 are sufficient to cause genomic instability and tumorigenesis

Association Between Transient Elastography and Controlled Attenuated Parameter and Liver Ultrasound in Children With Cystic Fibrosis

Methods to identify children with cystic fibrosis (CF) at risk for development of advanced liver disease are lacking. We aim to determine the association between liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) with research ultrasound (US) patterns and conventional hepatic markers as a potential means to follow liver disease progression in children with CF. ELASTIC (Longitudinal Assessment of Transient Elastography in CF) is a nested cohort of 141 patients, ages 7-21, enrolled in the Prediction by US of Risk of Hepatic Cirrhosis in CF (PUSH) Study. We studied the association between LSM with research-grade US patterns (normal [NL], heterogeneous [HTG], homogeneous [HMG], or nodular [NOD]) and conventional hepatic markers. In a subgroup (n = 79), the association between controlled attenuation parameter (CAP) and US pattern was explored. Among 133 subjects undergoing VCTE, NOD participants (n = 26) had a significantly higher median (interquartile range) LSM of 9.1 kPa (6.3, 15.8) versus NL (n = 72, 5.1 kPa [4.2, 7.0]; P < 0.0001), HMG (n = 17, 5.9 kPa [5.2, 7.8]; P = 0.0013), and HTG (n = 18, 6.1 kPa [4.7, 7.0]; P = 0.0008) participants. HMG participants (n = 14) had a significantly higher mean CAP (SD) (270.5 dB/m [61.1]) compared with NL (n = 40, 218.8 dB/m [46.5]; P = 0.0027), HTG (n = 10, 218.1 dB/m [60.7]; P = 0.044), and NOD (n = 15, 222.7 dB/m [56.4]; P = 0.041) participants. LSM had a negative correlation with platelet count (rs = − 0.28, P = 0.0071) and positive correlation with aspartate aminotransferase-to-platelet ratio index (rs = 0.38, P = 0.0002), Fibrosis-4 index (rs = 0.36, P = 0.0007), gamma-glutamyltransferase (GGT; rs = 0.35, P = 0.0017), GGT-to-platelet ratio (rs = 0.35, P = 0.003), and US spleen size z-score (rs = 0.27, P = 0.0073). Conclusion: VCTE is associated with US patterns and conventional markers in patients with liver disease with CF

The World of Eurydice

As a creative project with an exhibition as its final presentation, my graduation project is a series of explorations of people trapped in private space, memory, and daily prayer psychology under the epidemic situation. My project consists of two parts. The first part, including drawings on paper and a foam sculpture, is the construction of the hell of memory, which explores the relationship between mourning and consumption. The second part is about the relationship between human spiritual desires and everyday objects. It is mainly an installation work, including some paintings, sculptures, and a short film played by a projector. Through the transformation and sanctifying of everyday objects, I explore the early witchcraft consciousness of human prayer rituals, restore religion and witchcraft rituals to the original prayer paradigm, and suggest the metaphorical connection between private apartment space and the closed spiritual world of individuals under the epidemic