From Home Energy Audit to Retrofit and Beyond

Many in Michigan, like countless others across the United States, live in energy inefficient, detached single-family homes. There is an enormous opportunity to decrease state residential energy consumption and its subsequent greenhouse gas emissions, improve occupant comfort, and bolster home values by auditing and retrofitting these homes with more efficient energy systems. In accordance with Michigan state law PA 295, DTE Energy maintains an energy optimization (EO) program aimed at conserving electricity and gas. Under this program, the utility company offers residential customers several options and incentives to invest in energy saving measures. However, participation by homeowners has been limited. Through collaboration between the University of Michigan and DTE Energy, this project sought to evaluate the effectiveness of the utility’s audit-to-retrofit programs and overall residential EO program. Software tools—including MySQL (a relational database management system), R (a statistical analysis package), ArcGIS (a geographic information system), and SurveyGizmo (an online survey development platform) — facilitated quantitative and qualitative program evaluation. These findings informed actionable recommendations to increase program participation, improve customer satisfaction, and target future EO participants. This comprehensive assessment examined both temporal and spatial scales and should help create better mechanisms for data storage, manipulation, and visualization. Largescale data analysis in the context of residential energy efficiency is becoming increasingly necessary and important for utilities. An integrated approach such as the one laid out in this report could improve the way utilities like DTE Energy implement home energy efficiency programs, assess these programs, and help increase participation for future programs.Master of ScienceNatural Resources and EnvironmentUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/97777/4/From_Home_Energy_Audit_to_Retrofit_and_Beyond.May_2013.V22.pd

Overexpression of EPHB4 Is associated with poor survival of patients with gastric cancer

Background: Increased expression of erythropoietin-producing human hepatoma (EPHB4) leads to enhanced cell migration, growth and adhesion in tumor cells. However, little is known regarding the effects of EPHB4 in gastric cancer. The present study aimed to examine the clinical relevance of EPHB4 and its association with the prognosis of gastric cancer. Materials and Methods: EPHB4 transcript expression in 324 gastric cancer samples with paired adjacent normal gastric tissues was determined using quantitative polymerase chain reaction and the results were statistically analyzed against patient clinicopathological data. AGS and HGC27 cell lines were transfected with EPHB4 siRNA and the effects examined by functional analysis. Results: EPHB4 mRNA levels in gastric cancer tissues were significantly elevated when compared to non-cancerous tissues (p=0.0110). Tissue samples from male patients exhibited lower expression than those from female patients (p=0.0110). Non-cardiac gastric tumors (fundus, corpus and pylorus) expressed a higher number of EPHB4 transcripts in comparison to cardiac gastric tumors (p<0.001). Increased expression of EPHB4 was significantly associated with poorer overall (p=0.0051) and progression-free (p=0.0262) survival. EPHB4 knockdown appeared to reduce post-wound migration of AGS cells (p=0.0057) and increase migration of HGC27 cells (p=0.0337). EPHB4 knockdown significantly increased adhesive ability in HGC27 (p<0.0001). Conclusion: The expression of EPHB4 was increased in gastric cancer and increased EPHB4 expression was correlated with poor survival. Knockdown of EPHB4 promoted adhesion and exerted diverse effects on migration of gastric cancer cells. Further investigations may highlight its predictive and therapeutic potential in gastric cancer

Psoriasin overexpression confers drug resistance to cisplatin by activating ERK in gastric cancer

Psoriasin, a member of the S100 multigenic family, which is aberrantly expressed in a variety of human tumors, is considered as an attractive molecular target for cancer treatment. The present study aimed to characterize the role of psoriasin in gastric cancer (GC), the associated pathways through which it contributes to cancer development and progression, and the effect of psoriasin on cellular response to pre-operative chemotherapy in patients with GC. Expression of psoriasin mRNA and protein were analyzed using quantitative polymerase chain reaction and immunohistochemistry of gastric cancer cohorts, respectively. Gastric cancer cell models with differential expression of psoriasin were generated using stable cell lines that overexpressed psoriasin. The in vitro biological functions of the cells in response to psoriasin overexpression and to chemotherapeutic agents were assessed using various cell-based assays. Psoriasin was overexpressed in patients with advanced GC, and high psoriasin levels led to poor clinical outcomes. Increasing psoriasin expression in GC cell lines promoted cell proliferation, migration and invasion in vitro. Furthermore, psoriasin overexpression caused alterations in the levels of epithelial-mesenchymal transition-associated proteins, and activated the extracellular signal-regulated kinase signaling pathway. Additionally, higher levels of psoriasin expression were significantly associated a lack of response to neoadjuvant chemotherapy in patients with GC. Psoriasin overexpression tended to decrease the sensitivity of GC cells to cisplatin, potentially by inhibiting apoptosis or increasing the S-phase population. Taken together, these results indicate that psoriasin may be a promising therapeutic target for GC treatment, and a potential molecular marker to predict patient response to pre-operative chemotherapy

EphB2 represents an independent prognostic marker in patients with gastric cancer and promotes tumour cell aggressiveness

Dysregulated expression of ephrin type-B receptor 2 (EphB2) has been linked with development and progression of solid tumours. In the current study we attempted to investigate the clinical relevance in GC and the effect of EphB2 expression on gastric cancer (GC) cells. EphB2 protein levels in GC and benign gastric tissues were determined using immunohistochemistry. EphB2 transcript expression in a GC cohort with GC tissue samples (n=171) and paired adjacent normal gastric tissues (n=97) was determined using qPCR. The EphB2 expression was over-activated using a CRISPR activator for the investigation of its cellular function. The expression levels of the EphB2 protein in the tumour tissues of tissue arrays were higher than the benign non-cancerous gastric tissues (P<0.05). EphB2 mRNA expression in GC tissues was also significantly elevated when compared with adjacent non-cancerous tissues (P<0.01). EphB2 activation promoted the migration and invasion abilities of the GC cell lines (P<0.01, respectively). In contrast, EphB2 activation significantly decreased the adhesion in GC cells (P<0.0001, respectively). The enrichment analysis of the correlated genes in a GC cohort indicates that EphB2 may function through mediating the cytokine-cytokine interaction, JAK-STAT and TP53 signaling pathways. In conclusion, EphB2 represents as a novel independent prognostic marker in GC. And activation of the EphB2 gene expression elevated the levels of migration and invasion, but suppressed adhesion of GC cells, indicating that EphB2 may act as a tumour promotor in GC. Our findings thus provide fundamental evidence for the consideration of the therapeutic potential of targeting EphB2 in GC

Polyclonal antibody against the DPV UL46M protein can be a diagnostic candidate

<p>Abstract</p> <p>Background</p> <p>The duck plague virus (DPV) UL46 protein (VP11/12) is a 739-amino acid tegument protein encoded by the <it>UL46 </it>gene. We analyzed the amino acid sequence of UL46 using bioinformatics tools and defined the main antigenic domains to be between nucleotides 700-2,220 in the <it>UL46 </it>sequence. This region was designated UL46M. The DPV <it>UL46 </it>and <it>UL46M </it>genes were both expressed in <it>Escherichia coli </it>Rosetta (DE3) induced by isopropy1-β-<smcaps>D</smcaps>-thiogalactopyranoside (IPTG) following polymerase chain reaction (PCR) amplification and subcloning into the prokaryotic expression vector pET32a(+). The recombinant proteins were purified using a Ni-NTA spin column and used to generate the polyclonal antibody against UL46 and UL46M in New Zealand white rabbits. The titer was then tested using enzyme-linked immunosorbent assay (ELISA) and agar diffusion reaction, and the specificity was tested by western blot analysis. Subsequently, we established Dot-ELISA using the polyclonal antibody and applied it to DPV detection.</p> <p>Results</p> <p>In our study, the DPV UL46M fusion protein, with a relative molecular mass of 79 kDa, was expressed in <it>E. coli </it>Rosetta (DE3). Expression of the full <it>UL46 </it>gene failed, which was consistent with the results from the bioinformatic analysis. The expressed product was directly purified using Ni-NTA spin column to prepare the polyclonal antibody against UL46M. The titer of the anti-UL46M antisera was over 1:819,200 as determined by ELISA and 1:8 by agar diffusion reaction. Dot-ELISA was used to detect DPV using a 1:60 dilution of anti-UL46M IgG and a 1:5,000 dilution of horseradish peroxidase (HRP)-labeled goat anti-rabbit IgG.</p> <p>Conclusions</p> <p>The anti-UL46M polyclonal antibody reported here specifically identifies DPV, and therefore, it is a promising diagnostic tool for DPV detection in animals. UL46M and the anti-UL46M antibody can be used for further clinical examination and research of DPV.</p

Podwyższone stężenia lipokaliny-2 w surowicy krwi są związane ze wskaźnikami metabolizmu glukozy i metabolizmu kostnego w przebiegu cukrzycy typu 2

Introduction: The role of lipocalin 2 (LCN2) in type 2 diabetes mellitus (T2DM) needs to be fully elucidated. Moreover, bone has been demonstrated to modulate glucose metabolism via LCN2. We thus performed this study to investigate the associations of LCN2 with indexes of glucose metabolism in T2DM. The associations of LCN2 with bone metabolism were examined concurrently. Material and methods: Total 288 Chinese Han subjects entered in this study including 146 patients with T2DM and 142 subjects with normal glucose tolerance. Insulin resistance was assessed by HOMA-IR andWstęp: Wyjaśnienie roli lipokaliny-2 (lipocalin 2; LCN2) w przebiegu cukrzycy typu 2 jest niezbędne, w szczególności, że zostało dowiedzione, iż kość moduluje metabolizm glukozy za pośrednictwem LCN2. Niniejsze badanie przeprowadzono, aby zbadać, w jaki sposób LCN2 jest powiązana ze wskaźnikami metabolizmu glukozy w przebiegu cukrzycy typu 2. Jednocześnie zbadano powiązania LCN2 z metabolizmem kostnym. Materiał i metody: W badaniu wzięło udział 288 Chińczyków Han, w tym 146 pacjentów z cukrzycą typu 2 i 142 pacjentów z prawidłową tolerancją glukozy. Insulinooporność oceniano za pomocą wskaźnika HOMA-IR, natomiast funkcję komórek beta trzustki za pomocą HOMA-β. W przypadku pacjentów z cukrzycą typu 2 oznaczano również markery obrotu kostnego, N-końcowy propeptyd prokolagenu typu I, C-końcowy usieciowany telopeptyd łańcucha alfa kolagenu typu I, gęstość mineralną kości (bone mineral density; BMD) odcinka lędźwiowego kręgosłupa i szyjki kości udowej. Wyniki: Stężenia LCN2 w surowicy krwi w przebiegu cukrzycy typu 2 były wyższe niż u osób z prawidłową tolerancją glukozy (p = 0,005). Ponadto, LCN2 była dodatnio skorelowana ze stężeniem insuliny w surowicy krwi na czczo (r = 0,262, p = 0,001), wskaźnikiem HOMA-IR (r = 0,185, p = 0,026) i HOMA-β (r = 0,306, p &lt; 0,001), odpowiednio, oraz ujemnie skorelowana z osoczowym stężeniem glukozy na czczo (r = –0,218, p = 0,006). Dodatkowo, BMD szyjki kości udowej (β = –0,176, p = 0,033), N-końcowy propeptyd prokolagenu typu I (β = 0,181, p = 0,026) oraz C-końcowy usieciowany telopeptyd łańcucha alfa kolagenu typu I (β = –0,168, p = 0,037) były niezależnymi czynnikami predykcyjnymi dla LCN2 w przebiegu cukrzycy typu 2. Wnioski: Lipokalina-2 była powiązana ze wskaźnikami metabolizmu glukozy. Ponadto, BMD oraz markery obrotu kostnego były nie­zależnymi czynnikami predykcyjnymi dla LCN2 w przebiegu cukrzycy typu 2. Można sądzić, że LCN2 może odgrywać rolę w procesie wzajemnego wpływu homeostazy kości i homeostazy glukozy

Unraveling the transcriptome-based network of tfh cells in primary sjogren syndrome: insights from a systems biology approach

BackgroundPrimary Sjogren Syndrome (pSS) is an autoimmune disease characterized by immune cell infiltration. While the presence of follicular T helper (Tfh) cells in the glandular microenvironment has been observed, their biological functions and clinical significance remain poorly understood.MethodsWe enrolled a total of 106 patients with pSS and 46 patients without pSS for this study. Clinical data and labial salivary gland (LSG) biopsies were collected from all participants. Histological staining was performed to assess the distribution of Tfh cells and B cells. Transcriptome analysis using RNA-sequencing (RNA-seq) was conducted on 56 patients with pSS and 26 patients without pSS to uncover the underlying molecular mechanisms of Tfh cells. To categorize patients, we employed the single-sample gene set enrichment analysis (ssGSEA) algorithm, dividing them into low- and high-Tfh groups. We then utilized gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and deconvolution tools to explore functional and immune infiltration differences between the low- and high-Tfh groups.ResultsPatients with pSS had a higher positive rate of the antinuclear antibody (ANA), anti-Ro52, anti-SSA, anti-SSB and hypergammaglobulinaemia and higher levels of serum IgG compared to the non-pSS. Histopathologic analyses revealed the presence of Tfh cells (CD4+CXCR5+ICOS+) in germinal centers (GC) within the labial glands of pSS patients. GSEA, WGCNA, and correlation analysis indicated that the high-Tfh group was associated with an immune response related to virus-mediated IFN response and metabolic processes, primarily characterized by hypoxia, elevated glycolysis, and oxidative phosphorylation levels. In pSS, most immune cell types exhibited significantly higher infiltration levels in the high-Tfh group compared to the low-Tfh group. Additionally, patients in the Tfh-high group demonstrated a higher positive rate of the ANA, rheumatoid factor (RF), and hypergammaglobulinaemia, as well as higher serum IgG levels.ConclusionOur study suggests that Tfh cells may play a crucial role in the pathogenesis of pSS and could serve as potential therapeutic targets in pSS patients

Characterisation of macrophage infiltration and polarisation based on integrated transcriptomic and histological analyses in Primary Sjögren’s syndrome

BackgroundPrimary Sjögren’s syndrome (pSS) is a progressive inflammatory autoimmune disease. Immune cell infiltration into glandular lobules and ducts and glandular destruction are the pathophysiological hallmarks of pSS. Macrophages are one of the most important cells involved in the induction and regulation of an inflammatory microenvironment. Although studies have reported that an abnormal tissue microenvironment alters the metabolic reprogramming and polarisation status of macrophages, the mechanisms driving macrophage infiltration and polarisation in pSS remain unclear.MethodsImmune cell subsets were characterised using the single-cell RNA sequencing (scRNA-seq) data of peripheral blood mononuclear cells (PBMCs) from patients with pSS (n = 5) and healthy individuals (n = 5) in a public dataset. To evaluate macrophage infiltration and polarisation in target tissues, labial salivary gland biopsy tissues were subjected to histological staining and bulk RNA-seq (pSS samples, n = 24; non-pSS samples, n = 12). RNA-seq data were analysed for the construction of macrophage co-expression modules, enrichment of biological processes and deconvolution-based screening of immune cell types.ResultsDetailed mapping of PBMCs using scRNA-seq revealed five major immune cell subsets in pSS, namely, T cells, B cells, natural killer (NK) cells, dendritic cells (DCs) and monocyte-macrophages. The monocyte-macrophage subset was large and had strong inflammatory gene signatures. This subset was found to play an important role in the generation of reactive oxygen species and communicate with other innate and adaptive immune cells. Histological staining revealed that the number of tissue-resident macrophages was high in damaged glandular tissues, with the cells persistently surrounding the tissues. Analysis of RNA-seq data using multiple algorithms demonstrated that the high abundance of pro-inflammatory M1 macrophages was accompanied by the high abundance of other infiltrating immune cells, senescence-associated secretory phenotype and evident metabolic reprogramming.ConclusionMacrophages are among the most abundant innate immune cells in PBMCs and glandular tissues in patients with pSS. A bidirectional relationship exists between macrophage polarisation and the inflammatory microenvironment, which may serve as a therapeutic target for pSS