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This paper focused on the relationship between gender and emotion. It had been stereotyped that woman would sense more sadness than men when facing sad situations, while men would be more outraged than women in angry circumstances. To test our hypothesis, this work recruited a total sample size of 420 people to watch two video clips (angry and sad videos) and completed a survey about the pictures. Their emotional states were unconsciously reflected by their attitudes towards the video clips. Excel and a t-test were implemented to analyze the emotional differences between males and females under each condition (sadness and anger). The result corresponded to our speculationwomen tended to feel more despairing than men when watching sad video clips, while men tended to be more irritated than women after watching angry videos.

Breast milk is the main source of nutrition for infants; it contains considerable microflora that can be transmitted to the infant endogenously or by breastfeeding, and it plays an important role in the maturation and development of the immune system. In this study, we isolated and identified lactic acid bacteria (LAB) from human colostrum, and screened 2 strains with probiotic potential. The LAB isolated from 40 human colostrum samples belonged to 5 genera: Lactobacillus, Bifidobacterium, Streptococcus, Enterococcus, and Staphylococcus. We also isolated Propionibacterium and Actinomyces. We identified a total of 197 strains of LAB derived from human colostrum based on their morphology and 16S rRNA sequence, among them 8 strains of Bifidobacterium and 10 strains of Lactobacillus, including 3 Bifidobacterium species and 4 Lactobacillus species. The physiological and biochemical characteristics of strains with good probiotic characteristics were evaluated. The tolerances of some of the Bifidobacterium and Lactobacillus strains to gastrointestinal fluid and bile salts were evaluated in vitro, using the probiotic strains Bifidobacterium lactis BB12 and Lactobacillus rhamnosus GG as controls. Among them, B. lactis Probio-M8 and L. rhamnosus Probio-M9 showed survival rates of 97.25 and 78.33% after digestion for 11 h in artificial gastrointestinal juice, and they exhibited growth delays of 0.95 and 1.87 h, respectively, in 0.3% bile salts. These two strains have the potential for application as probiotics and will facilitate functional studies of probiotics in breast milk and the development of human milk-derived probiotics.

The antigenic targets of immunity and the role of vaccination in breast cancer are unknown. We performed a phase I study of an autologous GM-CSF-secreting breast cancer vaccine in patients with metastatic and stage II-III breast cancer.Tumor cells from patients with metastatic (n = 15) and stage II-III (n = 7) disease were transduced with a replication-defective adenoviral vector encoding GM-CSF, and then irradiated. Twelve and seven patients with metastatic and stage II-III disease, respectively, received weekly vaccination for three weeks, followed by every other week until disease progression or vaccine supply was exhausted (metastatic) or until six total vaccine doses were administered (stage II-III).Among those patients with metastatic disease who received vaccinations, eight had progressive disease at two months, three had stable disease for 4-13 months, and one has had no evidence of disease for 13 years. Of the patients with stage II-III disease, five died of metastatic disease between 1.16 and 8.49 years after the start of vaccinations (median 6.24 years) and two are alive as of September 2021. Toxicities included injection site reactions, fatigue, fever, upper respiratory symptoms, joint pain, nausea, and edema. Four of five evaluable patients with metastatic disease developed a skin reaction with immune cell infiltration after the fifth injection of unmodified, irradiated tumor cells.We conclude that tumor cells can be harvested from patients with metastatic or stage II-III breast cancer to prepare autologous GM-CSF-secreting vaccines that induce coordinated immune responses with limited toxicity. TRIAL REGISTRATION AND DATE OF REGISTRATION: clinicaltrials.gov, NCT00317603 (April 25, 2006) and NCT00880464 (April 13, 2009).

Background: We tested the feasibility of determining the prevalence and epidemiology of antibiotic resistance in rural China and investigated patterns and drivers of antibiotic use for common respiratory and urinary tract infections (RTI/UTI). Methods: (i) Observations and exit interviews in eight village clinics and township health centres and 15 retail pharmacies; (ii) Urine, throat swab and sputum samples from patients to identify potential pathogens and test susceptibility; (iii) 103 semi-structured interviews with doctors, patients, pharmacy workers and antibiotic-purchasing customers; (iv) Assessment of completeness and accuracy of electronic patient records through comparison with observational data. Results: 87.9% of 1123 recruited patients were prescribed antibiotics, most of whom had RTIs. Antibiotic prescribing for RTIs was not associated with presence of bacterial pathogens but with longer duration of infection (OR=3.33) and presence of sore throat (OR=1.64). Fever strongly predicted prescription of intravenous antibiotics (OR=2.87). Resistance rates in bacterial pathogens isolated were low compared with national data. 25.8% of patients reported antibiotics use pre-clinic visit. Only 56.2% of clinic patients and 53% of pharmacy customers could confirm their prescription included antibiotics. Diagnostic uncertainty, economic need, understanding of antibiotics as anti-inflammatory and limited doctor-patient communication were identified as drivers of antibiotic use. Completion and accuracy of e-records was variable. Conclusions: Despite high levels of antibiotic prescribing and self-medication, prevalence of antibiotic resistance in this rural population is currently relatively low. More systematic use of e-records could improve antibiotic surveillance in rural facilities.

Light plays a direct crucial role in the switch between sleep and arousal and the regulation of physiology and behaviour, such as circadian rhythms and emotional change. Artificial lights, which are different from natural light sources with a continuous light spectrum, are composed of three single-colour lights and are increasingly applied in modern society. However, in vivo research on the mechanisms of blue light-regulated sleep and arousal is still insufficient. In this work, we detected the effects of inserting white or blue light for 1 h during the dark period on the wheel-running activity and sucrose preference of C57 mice. The results showed that blue light could induce delays in sleep and arousal-promoting responses. Furthermore, this lighting pattern, including blue light alone, induced depressive-like emotions. The c-fos expression in the blue light group was significantly higher in the arcuate hypothalamic nucleus (Arc) and significantly lower in the cingulate cortex (Cg) and anterior part of the paraventricular thalamic nucleus (PVA) than in the white light group. Compared with the white light group, the phospho-ERK expression in the paraventricular hypothalamic nucleus (PVN) and PVA was lower in the blue light group. These molecular changes indicated that certain brain regions are involved in blue light-induced response processes. This study may provide useful information to explore the specific mechanism of special light-regulated physiological function.

Smart and interactive textiles have been attracted great attention in recent years. This research explored three different techniques and processes in developing textile-based conductive coils that are able to embed in a garment layer. Coils made through embroidery and screen printing have good dimensional stability, although the resistance of screen printed coil is too high due to the low conductivity of the print ink. Laser cut coil provided the best electrical conductivity; however, the disadvantage of this method is that it is very difficult to keep the completed coil to the predetermined shape and dimension. The tested results show that an electromagnetic field has been generated between the textile-based conductive coil and an external coil that is directly powered by electricity. The magnetic field and electric field worked simultaneously to complete the wireless charging process.

An SS31 prodrug improved AKI therapy via rapid distribution in the kidney and long-term retention in the renal tubule., The development of drugs with rapid distribution in the kidney and long-term retention in the renal tubule is a breakthrough for enhanced treatment of acute kidney injury (AKI). Here, l-serine–modified chitosan (SC) was synthesized as a potential AKI kidney–targeting agent due to the native cationic property of chitosan and specific interaction between kidney injury molecule–1 (Kim-1) and serine. Results indicated that SC was rapidly accumulated and long-term retained in ischemia-reperfusion–induced AKI kidneys, especially in renal tubules, which was possibly due to the specific interactions between SC and Kim-1. SC-TK-SS31 was then prepared by conjugating SS31, a mitochondria-targeted antioxidant, to SC via reactive oxygen species (ROS)–sensitive thioketal linker. Because of the effective renal distribution combined with ROS-responsive drug release behavior, the administration of SC-TK-SS31 led to an enhanced therapeutic effect of SS31 by protecting mitochondria from damage and reducing the oxidative stress, inflammation, and cell apoptosis.

The amplification of chromosome 9p24.1 encoding PD-L1, PD-L2, and JAK2 has been reported in multiple types of cancer and is associated with poor outcome, upregulation of PD-L1, and activation of the JAK/STAT pathway. We have developed a novel fluorescence in situ hybridization assay which combines 3 probes mapping to 9p24.1 with a commercial chromosome 9 centromere (CEN9) probe for detection of the JAK2/9p24.1 amplification. JAK2 fluorescence in situ hybridization was compared with array-based comparative genomic hybridization in 34 samples of triple negative breast cancer tumor. By array-based comparative genomic hybridization, 15 had 9p24.1 copy-number gain (log2ratio>0.3) and 19 were classified as non-gain (log2ratio≤0.3). Copy-number gain was defined as JAK2/CEN9 ratio ≥1.1 or average JAK2 signals≥3.0. Twelve of 15 samples with copy-number gain by array-based comparative genomic hybridization were also detected by fluorescence in situ hybridization. Eighteen of 19 samples classified as copy-number non-gain by array-based comparative genomic hybridization were concordant by array-based comparative genomic hybridization. The sensitivity and specificity of the fluorescence in situ hybridization assay was 80% and 95%, respectively (P=0.02). The sample with the highest level of amplification by array-based comparative genomic hybridization (log2ratio=3.6) also scored highest by fluorescence in situ hybridization (ratio=8.2). There was a correlation between the expression of JAK2 and amplification status (Mean 633 vs 393, P=0.02), and there was a trend of association with PD-L1 RNA expression (Mean 46 vs 22, P=0.11). No significant association was observed between PD-L1 immunohistochemistry expression and copy-number gain status. In summary, the novel array-based comparative genomic hybridization assay for detection of chromosome 9p24.1 strongly correlates with the detection of copy-number gain by array-based comparative genomic hybridization. In triple negative breast cancer, this biomarker may identify a relevant subset of patients for targeted molecular therapies.

We make three arguments in this review of the literature on rural welfare governance in Vietnam and China. First, welfare restructuring in these countries has gone through two overlapping processes of contraction and expansion, underlined by changing politics of needs and shifting modes of governance since their shift from state to market socialism. Such politics are the outcome of the Communist party-state’s dual project of legitimation and control, as widespread social conflicts challenge its legitimacy. Secondly, the dislocations and inequalities induced by marketization have been coupled with greater involvement of a broad range of social actors in welfare provision. Thirdly, the rise of social protection is shaped by state control, wealth disparities between regions and social classes, and a care politics deeming certain groups as failing to meet the human capital requirements of the new economy. While providing some buffer against destitution, existing forms of social protection do little to alleviate the social exclusion and inequality resulting from post-reform dispossession.

Introduction: Preclinical data suggests that priming T cell immunity to mutated or overexpressed proteins can induce tumor rejection, and may potentiate the effects of checkpoint blockade. PIK3CA and p53 are the most commonly mutated genes in breast cancer, and are enriched in high-grade and metastatic tumors. Here, we evaluated the immunogenicity of neo-epitopes derived from common PIK3CA and p53 mutations. Methods: We applied a custom informatics pipeline, EpitopeHunter, to predict neo-epitopes (8-11mers) from twelve PIK3CA and ten p53 mutations restricted to thirty-nine MHC class I alleles. We selected high affinity neo-epitopes (IEDB score < 500) with predicted poor binding of the matched wild type epitope. We used the predicted peptides to stimulate PBMC from healthy donors in vitro, and measured T cell immunity by interferon-γ ELISPOT. We compared the T cell specificity of mutant vs wild type epitopes. A positive response to an epitope was defined as a response that met both of the following criteria: 1) net number of spots (after subtracting background) was >5 spots/50,000 cells and 2) net number of spots exceeded the background spots plus two SDs. Results: In total, 1,824 PIK3CA and 1,520 p53 derived peptide sequences were generated. Of these, 42 PIK3CA (2%) and 45 p53 (3%) peptides were predicted to bind to the HLA class I molecules included in our study. Over 90% of the neo-epitopes were 9- and 10-mers, and the predicted neo-epitopes varied across mutations (range 2-10 per mutation). PIK3CAH1047L and p53R248W had the highest number of potential binding neo-epitopes (n=10 each). We successfully generated T cell lines specific for A*0201 PIK3CAH1047L, A*1101 PIK3CAH1047L, A*1101 PIK3CAE542K and A*0201 p53R248W. Conclusions: Common mutations of PIK3CA and p53 can lead to the generation of potential HLA class I restricted neo-epitopes. We identified four immunogenic neo-epitopes, which may serve as candidates for targeted immunotherapy in breast cancer. Citation Format: Chen M, Yuvaraj P, Sharma AA, Narang P, Wilson Sayres MA, Anderson KS. Targeting neo-epitopes from PIK3CA and p53 mutations for immunotherapy of 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 P4-06-04.

A new SMART fabric concept is reported in which visual changes of the material are designed to influence different human emotions. This is achieved by developing a novel electrochromic composite yarn, knitted into pattern-changing fabrics, which has high response in temperature change and uniform contrast. The influence of these pattern-changing effects on the response of the human visual brain is investigated further by using event-related potential (ERP). Four SMART pattern-changing fabric pairs were used in this experiment. Each fabric presents two patterns interactively with different, but complementary or opposing, pattern attributes. 20 participants took part in the experiment, in which they were exposed to the patterns, while their visual brain activities were recorded. Comparisons of the three prominent ERP components; P1, N1, and P2 that correspond to the two patterns of each fabric have shown significant differences in the latency and amplitude of these components. These differences show that patterns and pattern-changing cause different visual impacts and that these changes influence our level of attention and processing effort. The study concludes that with the pattern changing ability of these thermochromic hybrid materials we can create designs with attributes that can directly manipulate user emotions, which we like to call ‘psychotextiles’. Our study also poses much wider questions of our image processing process in relation to design and art.

Antimicrobial resistance is widely recognised as a global threat to human health. This paper explores the mobilisation of biomedical concepts and technologies within local semantic registers and addresses the implications of translation and knowledge complexity for attempts to mitigate the problem of antibiotic resistance. In China, antibiotics are frequently prescribed for common complaints and are widely available without prescription. Drawing on field research in three rural counties of one province, we show that current patterns of antibiotic use are the result of sociocultural, economic and systems drivers within a medical context that draws on precepts from both biomedicine and Chinese medical knowledge. Comparative analysis with European settings suggests that pathogenicity, the set of explanatory frameworks regarding the production of disease, varies socio-temporally in the causal mechanisms that are prioritised. Incorporated within diagnostic strategies that direct treatment towards the bodily response to infection rather than to the infecting pathogen, ‘anti-inflammatory medicine’ as the popular term for antibiotics in parts of Asia foregrounds physiological process over microbial invasion. We examine the articulation of biomedical knowledge paradigms within a non-Pasteurian milieu in relation to socio-historical process, including hybridisation between ontologically distinct medical traditions and the heterogeneity of scientific knowledge claims that underpin contemporary practices of antibiotic prescribing. We conclude that the concept of inflammation functions as a boundary object which effectively mediates the interfaces between popular knowledges, biomedical sciences and local medical practices. Our analysis may have wide relevance because popular and scientific understandings of inflammation alike draw on metaphors grounded in universal sensory experience that provides a common basis for culturally diverse conceptual elaboration. Situated understandings of inflammation and associated treatment preferences constitute a contextually coherent response to available medical technologies in community health care. Our analysis also calls into question simplistic interpretations of antibiotic use for non-bacterial conditions as deriving from lack of education or public awareness and suggests a need to reconsider current public health knowledge translation strategies.

Background Cancer immunotherapy with immune checkpoint blockade (CKB) is now standard of care for multiple cancers. The clinical response to CKB is associated with T cell immunity targeting cancer-induced mutations that generate novel HLA-binding epitopes (neoepitopes). Methods Here, we developed a rapid bioinformatics pipeline and filtering strategy, EpitopeHunter, to identify and prioritize clinically relevant neoepitopes from the landscape of somatic mutations. We used the pipeline to determine the frequency of neoepitopes from the TCGA dataset of invasive breast cancers. We predicted HLA class I-binding neoepitopes for 870 breast cancer samples and filtered the neoepitopes based on tumor transcript abundance. Results We found that the total mutational burden (TMB) was highest for triple-negative breast cancer, TNBC, (median = 63 mutations, range: 2–765); followed by HER-2(+) (median = 39 mutations, range: 1–1206); and lowest for ER/PR(+)HER-2(−) (median = 32 mutations, range: 1–2860). 40% of the nonsynonymous mutations led to the generation of predicted neoepitopes. The neoepitope load (NEL) is highly correlated with the mutational burden (R2 = 0.86). Conclusions Only half (51%) of the predicted neoepitopes are expressed at the RNA level (FPKM≥2), indicating the importance of assessing whether neoepitopes are transcribed. However, of all patients, 93% have at least one expressed predicted neoepitope, indicating that most breast cancer patients have the potential for neo-epitope targeted immunotherapy. Electronic supplementary material The online version of this article (10.1186/s12885-019-5402-1) contains supplementary material, which is available to authorized users.

Delta opioids are thought to relieve ischemic injury and have tissue-protective properties. However, the detailed mechanisms of delta opioids have not been well identified. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), have been shown to mediate downstream signals of δ opioid receptor (δOR) activation through the metalloproteinase (MMP)-dependent EGF-like growth factor (HB-EGF) excretion pathway, which is called transactivation. In this study, to investigate the role of EGFR in δOR-induced anti-ischemic effects in the brain, we applied the middle cerebral artery occlusion (MCAO) model followed by reperfusion to mimic ischemic stroke injury in rats. Pre-treatment with the δOR agonist [D-ala2, D-leu5] enkephalin (DADLE) improved the neurologic deficits and the decreased infarct volume caused by cerebral ischemia/reperfusion injury, which were blocked by the EGFR inhibitor AG1478 and the MMP inhibitor GM6001, respectively. Further results indicated that DADLE activated EGFR, Akt and ERK1/2 and upregulated EGFR expression in the hippocampus in a time-dependent manner, which were inhibited by AG1478 and GM6001. The enzyme-linked immunosorbent assay (ELISA) results showed that δOR activation led to an increase in HB-EGF release, but HB-EGF in tissue was downregulated at the mRNA and protein levels. Moreover, this protective action caused by δOR agonists may involve attenuated hippocampal cellular apoptosis. Overall, these results demonstrate that MMP-mediated transactivation of EGFR is essential for δOR agonist-induced MCAO/reperfusion injury relief. These findings provide a potential molecular mechanism for the neuroprotective property of δOR and may add new insight into mitigating or preventing injury.

Introduction: Immune checkpoint blockade is an effective immunotherapy for multiple cancers, including a subset of TNBCs. The clinical response to checkpoint blockade correlates with high tumor mutational burden. Cancer-induced mutations are predicted to generate new HLA-binding epitopes (neo-epitopes), which are potential targets of T cells. To determine the neo-epitope load in breast cancer, we developed a rapid bioinformatics pipeline and filtering strategy, EpitopeHunter, to identify and prioritize clinically relevant neo-epitopes from the landscape of somatic mutations. Here, we determined the specificity and frequency of neo-epitopes from the TCGA dataset of invasive breast cancers. Methods: We analyzed 842 tumor and normal breast cancer exome sequencing from the TCGA dataset. Subgroup analysis was performed based on the IHC status of ER, PR and HER2: (i) TNBC (n=98); (ii) ER and/or PR(+), Her2(-) (n=604); and (iii) ER and PR(+/-), Her-2(+) (n=140). Cancer specific mutations were called uniformly for the aligned tumor and normal pairs using VarScan2. For each annotated non-synonymous mutation, we generated all possible neo-epitopes (up to 11-mers) including the mutant amino acid. HLA typing of A, B and C MHC class I genes of each patient was determined using the POLYSOLVER algorithm. We selected high affinity binding epitopes using the IEDB prediction algorithm based on the known epitopes to identify likely binding of each neo-epitope within the suite of patient-specific HLA alleles (IEDB score < 500). We then filtered the epitopes based on tumor transcript abundance using RNAseq expression for 837/842 patients. An expression value of FPKM > 2 was used as a cut-off for the expressed neo-epitopes. Results: Total mutational burden was highest for TNBC (median=53, range: 2-1162); followed by ER and PR(+/-), Her-2(+) (median=40, range: 6-4983); and lowest for ER and/or PR (+), Her-2(-) (median=30, range: 0-5515). About 15% of the nonsynonymous mutations led to the generation of neo-epitopes. The neo-epitope load (high affinity neo-epitopes with IEDB score Conclusions: We have developed a rapid bioinformatics pipeline, EpitopeHunter, for the identification of neo-epitopes from tumor sequencing data. Eighty percent of breast cancer patients have at least one expressed neo-epitope, which may serve as candidates for targeted immunotherapy. Citation Format: Narang P, Chen M, Sharma AA, Anderson KS, Wilson Sayres MA. The neo-epitope landscape of breast cancer: Implications for immunotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-13.

Figure S9. Kaplan-Meier estimates for high and low mutation burden. KM survival curves are shown for (A) disease-free survival and (B) overall survival between cases with high and low mutation (MB) burden, the upper and lower quartiles, in each subtype of breast cancer. Here we defined the top quartile of mutation burden as high and the bottom quartile as low (PDF 903 kb)

Figure S3. Correlation of number of potential binding neoepitopes with number of nonsynonymous mutations. The number of potential binding neoepitopes (IEDB scoreâ â ¤â 500) are highly correlated with the number of nonsynonymous mutations for all three subtypes of breast cancer. In all the plots, a linear regression model is used to fit the data; the fitted line is shown in red and 95% CIs are shown as grey shaded area around the line (PDF 268 kb)

Figure S7. Expression analysis for the high affinity neoepitopes (FPKM ≥2). (A) The number of the expressed neoepitopes (normalized by total number of samples in each breast cancer subtype) is shown for each FPKM range. 51% (8927/17518) of predicted neoepitopes are expressed with an FPKM threshold of ≥2. (B) Number of neoepitopes (normalized by the number of samples in each breast cancer subtype) with the highest expressed neoepitope for each patient as shown. 93% (762/815) of patients have at least one potential binding epitope.

Figure S2. Comparison of mutations called by the current protocol versus cBioportal ( http://www.cbioportal.org ). The total number of mutations called by the current protocol (in blue) is comparable to the mutations called from cBioportal (in orange) across all three classifications of breast cancer subtype (PDF 425 kb)

Figure S6. Correlation of number of potential binding neoepitopes with number of expressed (FPKM≥2) neoepitopes. The number of potential binding neoepitopes (IEDB score ≤ 500) are highly correlated with the number of expressed neoepitopes (FPKM≥2) for all three subtypes of breast cancer. In all the plots a linear regression model is used to fit the data; the fitted line is shown in red and 95% CIs are shown in grey (PDF 255 kb)

Figure S5. Expressed neoepitopes (FPKM≥5) in subtypes of breast cancer. The range of expressed neoepitopes (with FPKM≥5) is highest for the TNBC, followed by HER-2(+); and lowest for the ER/PR(+)HER-2(−) subtype of breast cancer. The median and range of the number of expressed neoepitopes are: 4 (0–131) in ER/PR(+)HER-2(−), 3 (0–82) in HER-2(+) and 8 (0–230) in TNBC. The number of samples in each case are: 583 (ER/PR(+)HER-2(−)), 138 (HER-2(+)), 92 (TNBC). Significant differences between reported FPKM values are computed pairwise for each breast cancer subtype using a Wilcox rank sum test, *** P

Figure S4. Length of potential binding neoepitopes in breast cancer. The number of potential binding neoepitopes (IEDB â ¤500) are plotted against peptide sizes (8, 9, 10, 11 mers). 4% of the predicted neoepitopes are 8-mers, 57% of the predicted neoepitopes are 9-mer, 33% of the predicted neoepitopes are 10-mers and 6% are 11mers (PDF 101 kb)

Table S2. Patient and tumor characteristics. Demographic data for patients and clinical measurements for tumors are included in the table below for each category of breast cancer (PDF 58 kb)

Background Elevated PD-L1 expression on tumor cells, a context associated with an adaptive immune response, has been linked to the total burden of copy number variants (CNVs) in aneuploid tumors, to microsatellite instability (MSI), and to specific genomic driver lesions, including loss of PTEN, MYC amplification, and activating mutations in driver oncogenes such as KRAS and PIK3CA. Triple-negative breast cancers (TNBCs) typically have high levels of CNVs and diverse driver lesions in their genomes. Thus, there is significant interest in exploiting genomic data to develop predictive immunotherapy biomarkers for patients with TNBC. Methods Whole tissue samples from 55 resected TNBCs were screened by immunohistochemistry (IHC) for PD-1 and PD-L1 by using validated antibodies and established scoring methods for staining of tumor and non-tumor cells. In parallel, we interrogated biopsies from each resection with DNA content flow cytometry and sorted the nuclei of diploid, tetraploid, and aneuploid cell populations. CNVs were mapped with CNV oligonucleotide arrays by using purified (>95%) tumor populations. We generated whole exome data for 12 sorted tumor samples to increase the resolution within loci of interest and to incorporate somatic mutations into our genomic signatures. Results and Conclusions PD-L1 staining was detected on tumor cells in 29 out of 54 (54%) evaluable cases and was associated with increased overall survival (P = 0.0024). High levels of PD-1 and PD-L1 (IHC ≥4) were present in 11 out of 54 (20%) and 20 out of 54 (37%) cases with staining of PD-L1 primarily on tumor cells for 17 out of 20 (85%) cases. The latter included tumors with both high (>50) and low (

Figure S4. FISH validation of high-level 9p24.1 amplicon. A) DNA content histogram of flow-sorted TNBC-11. B) Chromosome 9 Comparative Genomic Hybridization plot with high-level (log2 ratio >4) gain of JAK2 locus (arrow) at 9p24.1. C) Multi-color FISH assay [5′JAK2[9p24](green)/ 3′JAK2[9p24](red)/CEN 9(aqua)] image indicates more than 21 intact JAK2 signals and 1–3 CEN 9 signals. Abbreviations: FISH fluorescence in situ hybridization, TNBC triple-negative breast cancer. (PPTX 948 kb)

Figure S7. TNBC with JAK1 homozygous deletion. A) DNA content histogram of flow-sorted TNBC-51. B) Whole genome CNV profile of 3.5Â N aneuploid TNBC-51 genome. C) Homozygous deletion at 1p31.3 includes the JAK1 locus. Red shaded area denotes ADM2-defined CNV interval. Abbreviations: CNV copy number variant, TNBC triple-negative breast cancer. (PPTX 226 kb)

Figure S6. FISH validation of 9p24.1 copy number loss. A) DNA content histogram of flow-sorted TNBC-8. B) Chromosome 9 Comparative Genomic Hybridization plot with (log2 ratio − 1) loss of JAK2 locus (arrow) at 9p24.1. C) Multi-color FISH assay [5′JAK2[9p24](green)/ 3′JAK2[9p24](red)/CEN 9(aqua)] image indicates 0–2 intact JAK2 signals and 1–4 CEN 9 signals. Abbreviations: FISH fluorescence in situ hybridization, TNBC triple-negative breast cancer. (PPTX 700 kb)

Figure S5. FISH validation of 9p24.1 amplicon. A) DNA content histogram of flow-sorted TNBC-29. B) Chromosome 9 Comparative Genomic Hybridization plot with (log2 ratio >1) gain of JAK2 locus (arrow) at 9p24.1. C) Multi-color FISH assay [5′JAK2[9p24](green)/ 3′JAK2[9p24](red)/CEN 9(aqua)] image indicates 3–5 intact JAK2 signals and 2–3 CEN 9 signals. Abbreviations: FISH fluorescence in situ hybridization, TNBC triple-negative breast cancer. (PPTX 776 kb)

Background Activation of the JAK/STAT pathway is common in triple-negative breast cancer (TNBC) and affects the expression of genes controlling immune signaling. A subset of TNBC cases will have somatic amplification of chromosome 9p24.1, encoding PD-L1, PD-L2, and JAK2, which has been associated with decreased survival. Materials and Methods Eleven TNBC cell lines were evaluated using array comparative genomic hybridization. A copy number gain was defined as an array comparative genomic hybridization log2 ratio of ≥ 1. Cell surface expression of programmed cell death ligand 1 (PD-L1) was detected using flow cytometry and compared with the median fluorescence intensity of isotype control immunoglobulin. To selectively inhibit JAK2, lentiviral vectors encoding 2 different short hairpin RNA (shRNA) were generated. JAK2, STAT1, STAT3, phosphorylated (p) STAT1, and pSTAT3 expression were measured by immunoblot. Statistical significance was defined as P Results The cell line HCC70 had 9p24.1 copy number amplification that was associated with both increased JAK2 and pSTAT3; however, knockdown of JAK2 inhibited cell growth independently of 9p24.1 copy number status. In TNBC cell lines with 9p24.1 gain or amplification, PD-L1 expression rapidly and strikingly increased 5- to 38-fold with interferon-γ (P Conclusion These data suggest that the JAK2/STAT1 pathway in TNBC might regulate the dynamic expression of PD-L1 that is induced in the setting of an inflammatory response. Inhibition of JAK2 might provide a synergistic therapy when combined with other immunotherapies in the subset of TNBC with 9p24.1 amplification.

Great challenges has been put on ancillary services in electric power system, especially with the penetration of renewable energy generation. Bulk battery energy storage systems (ESS) has gain a worldwide population due to its high quality of regulation in recent years. In this paper, we focus on design of regulation service contract market, which is applicable for both traditional generators and ESS. To guarantee market fairness and make full use of high quality regulation resources, group bidding is introduced, meaning that resource acquisition is carried out through several bidding sections with different requirements for regulation performance. Transaction model in each section is established. Then, iterative bidding mechanism is also used so that market members are licensed to negotiate with each other, which makes final market clearing prices close to real regulation cost. A numeral example is studied to illustrate feasibility and merits of the proposed market mechanism, and then market benefit under this market mechanism for BESS is analyzed briefly.

As energy shortages and pollution problems become more severe, as well as the increasing demand from users, conventional energy has shown a lot of shortcomings. The introduction of photovoltaic-energy storage system (PESS) can effectively take advantage of renewable photovoltaic power system, guarantee power quality and reduce environmental pollution. In this paper, the comprehensive economy and technology evaluation index system and evaluation method of PESS are studied. Firstly, the comprehensive evaluation index system of PESS was constructed from the aspects of economy, the reliability of power supply, the friendliness of the source and network, and the environmental benefits. Secondly, based on DEMATEL-ANP-Anti-Entropy and the improved grey correlation method, the weight of each assessment factor is determined; then the evaluation function of the index system of PESS can be formulated based on polynomial interpolation method; finally, the PESS which actually operates in a commercial park is comprehensively evaluated, the results of the study verify the feasibility and validity of the proposed index system and evaluation methods.

This work is an intelligent voice control lighting device based on Arduino UNO microcontroller. It will save a lot of time and bring more convenience to life, work and study. When using, need to speak to desk lamp only "turn on the lamp", "turn off the lamp" can realize the switch of intelligent desk lamp. Say "up", "down", "left" and "right" to control the direction of the light. At the same time, it also has the function of small night lamp night closed room fluorescent lamp, desk lamp on the photosensitive intelligent components will sense if the change of light intensity, light up to 10 seconds automatically, can prevent to turn off the lights after walking knock against. In addition, we added clock on the panel, using DS1302 clock module to save time, and can be saved without power. Increased the practical use of intelligent desk lamp, more optimized movement inconvenient people to use.

Background: Checkpoint blockade (CKB) are in clinical trials in breast cancer, but responses may be limited by the low tumor micro-immune profile and somatic mutation burden. Oncolytic viruses may function by activating the immune microenvironment, and improve clinical responses when combined with CKB against cancers like melanoma. In this study, we evaluate the synergy of cytotoxic T lymphocytes (CTLs) combined with oncolytic myxoma virus in an in vitro model of human breast cancer. Method: BMLF1-CTLs were generated from human HLA-A*02 PBMCs, which were stimulated with antigen presenting cells pulsed with the EBV BMLF1 HLA-A*02 peptide (GLCTLVAML). MCF-7 was engineered to express the full-length BMLF1 gene from EBV. To assess the impact of myxoma virus infection on CTL cytotoxicity, target MCF-7 cells (+/- BMLF1) were co-cultured with BMLF1-CTLs (E:T ratio=5:1) and myxoma virus vMyx-M135KO-GFP (vMyx135KO), at multiplicity of infection (MOI) ranges from 0.1 to 10 ffu/cell, in vitro for 48 hours. Cytotoxicity was measured by flow cytometry with propidium iodide (PI). Cell surface expression of MHC class I and class II were measured by flow cytometry. Statistical comparisons were performed using an unpaired t-test and variation among and between groups was calculated using ANOVA. Statistical significance was defined as p Results: At the highest MOI (10 ffu/cell), cell surface MHC class I expression on MDA-MB-231 was decreased 38-fold (p Conclusions: Oncolytic myxoma virus infection can decrease the MHC class I expression in human breast cancer cell lines, but only at high multiplicities of infection. At low level of virus, myxoma virus infection can enhance CTL cytotoxcity of breast cancer cell line. Citation Format: Meixuan Chen, Ana L. Matos, Padhmavathy Yuvaraj, Laura Belmont, Grant McFadden, Karen S. Anderson. Synergy of CTL tumor cytotoxicity with myxoma oncolytic virotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4093.

Introduction: Previously, we detected amplification of chromosome 9p24.1 encoding PDL1, PDL2, and JAK2 (the PDJ amplicon) in up to 25% of triple negative breast cancers (TNBC) using oligonucleotide CGH arrays (aCGH). Amplification was associated with poor outcome and activation of the JAK/STAT pathway. Here, we have developed a novel fluorescence in situ hybridization (FISH) for detection of the JAK2/PDL1 amplification. Methods: We selected five 9p24.1-amplified and five non-amplified paraffin embedded TNBC tumor samples, defined by aCGH log2ratio>2.0 as amplified for FISH validation. 5' JAK2 DNA labeled with SpectrumGreen dUTP, 3' JAK2 DNA labeled in SpectrumOrange dUTP and a commercially available chromosome 9 centromeric probe (Spectrum Aqua) were combined as one probe set. The break-apart (BAP) probe set was applied to individual slides, hybridized, and washed, 50 events/sample were counted. We defined 9p24.1 amplification by FISH as the ratio of average JAK2 score/ average centromere 9 (CEN 9) score >1.1. Nonparametric student's t-test was used for statistical analysis. Results: In the amplified subgroup (n=5), JAK2 amplification was detected by FISH with the range from 1.89 to 21.0 (mean, 6.76). To adjust for aneuploidy, the ratio of JAK2 to CEN 9 was measured with the range from 1.02 to 9.21 (mean ratio, 2.9). The sample with highest level of amplification (aCGH log2ratio =4) detected by aCGH also scored highest by FISH (FISH ratio=9.21). One case with JAK2 amplification (aCGH log2ratio =3) was not detected by FISH (ratio, 1.02), but had low tumor cell content. In the non-amplification subgroup (n=5), JAK2 amplification was detected by FISH with the range from 0.98 to 3.54 (mean, 1.8), the ratio of JAK2 to CEN 9 was measured with the range from 0.48 to1.05 (mean, 0.73). Of note, two tumors with copy number loss by aCGH were confirmed by FISH (ratio 0.48, 0.56). In total, the 9p24.1 amplification was detected in 4 out 5 (80%) amplified samples defined by aCGH and 5 out 5 not amplified. A significant difference in JAK2: CEN 9 ratio (p=0.03) was observed between the amplified and non-amplified subgroups but not in JAK2 absolute scores (p=0.095). Conclusion: In this study, we have developed a novel FISH assay for detection of the 9p24.1 amplification in TNBC, encoding JAK2, PD-L1, and PD-L2. The FISH assay correlates with detection of the amplification by aCGH, but is less sensitive, in particular in tissue with lower tumor cell content. We predict that 9p24.1 amplification will be a clinically relevant biomarker in TNBC. Citation Format: Chen M, Andreozzi M, Pockaj B, Barrett MT, Ocal IT, McCullough AE, Anderson KS. A novel fluorescence in situ hybridization assay to detect 9p24.1 amplification in 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 P6-07-17.