Films for optical use and methods of making such films

Films for optical use, articles containing such films, methods for making such films, and systems that utilize such films, are disclosedPublished versio

Time-Optimal Path Planning for Heterogeneous Robots in Swarm Manufacturing

Time-optimal path planning is a critical problem in any system employing mobile robots. Much of the literature on this problem operates under two major assumptions: the environment is static, and the robots’ effective shapes are constant and discretized either as a circle or a sphere, disregarding the impact of the robot’s orientation on the overall task. These assumptions are restrictive in swarm manufacturing, where the environment is dynamically changing and manufacturing robots have geometric constraints for operation. For example, robots can not only move but also change their effective shapes depending on the parts they carry or the material deposited. These variations can significantly impact the path-planning solution. In this paper, we propose a methodology to find time-optimal paths in swarm manufacturing while explicitly considering the effective and changing shapes of mobile robots and the dynamic obstacles surrounding them.Mechanical Engineerin

Including diverse and admixed populations in genetic epidemiology research

The inclusion of ancestrally diverse participants in genetic studies can lead to new discoveries and is important to ensure equitable health care benefit from research advances. Here, members of the Ethical, Legal, Social, Implications (ELSI) committee of the International Genetic Epidemiology Society (IGES) offer perspectives on methods and analysis tools for the conduct of inclusive genetic epidemiology research, with a focus on admixed and ancestrally diverse populations in support of reproducible research practices. We emphasize the importance of distinguishing socially defined population categorizations from genetic ancestry in the design, analysis, reporting, and interpretation of genetic epidemiology research findings. Finally, we discuss the current state of genomic resources used in genetic association studies, functional interpretation, and clinical and public health translation of genomic findings with respect to diverse populations

Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study

Objective: Serum α-fetoprotein (AFP) is the most commonly used biomarker for screening hepatocellular carcinoma (HCC) but fails to detect about half of the patients. Thus, we investigated if circulating microRNAs (miRNAs) could outperform AFP for HCC detection. Design: A retrospective cohort study. Setting: Two clinical centres in China. Participants: The exploration phase included 96 patients with HCC who received primary curative hepatectomy, and the validation phase included 29 hepatitis B carriers, 57 patients with HCC and 30 healthy controls. Main outcome measures: Expression of miRNAs was measured by real-time quantitative reverse transcription-PCR. Areas under receiver operating characteristic curves were used to determine the feasibility of using serum miRNA concentration as a diagnostic marker for defining HCC. A multivariate logistic regression analysis was used to evaluate performances of combined serum miRNAs. Results: In the exploration phase, miRNA profiling on resected tumour/adjacent non-tumour tissues identified miR-15b, miR-21, miR-130b and miR-183 highly expressed in tumours. These miRNAs were also detectable in culture supernatants of HCC cell lines and in serum samples of patients. Remarkably, these serum miRNAs were markedly reduced after surgery, indicating the tumour-derived source of these circulating miRNAs. In a cross-centre validation study, combined miR-15b and miR-130b demonstrated as a classifier for HCC detection, yielding a receiver operating characteristic curve area of 0.98 (98.2% sensitivity and 91.5% specificity). The detection sensitivity of the classifier in a subgroup of HCCs with low AFP (<20 ng/ml) was 96.7%. The classifier also identified early-stage HCC cases that could not be detected by AFP. Conclusion: The combined miR-15b and miR-130b classifier is a serum biomarker with clinical value for HCC screening.published_or_final_versio

Sensitivity to measurement perturbation of single atom dynamics in cavity QED

We consider continuous observation of the nonlinear dynamics of single atom trapped in an optical cavity by a standing wave with intensity modulation. The motion of the atom changes the phase of the field which is then monitored by homodyne detection of the output field. We show that the conditional Hilbert space dynamics of this system, subject to measurement induced perturbations, depends strongly on whether the corresponding classical dynamics is regular or chaotic. If the classical dynamics is chaotic the distribution of conditional Hilbert space vectors corresponding to different observation records tends to be orthogonal. This is a characteristic feature of hypersensitivity to perturbation for quantum chaotic systems.Comment: 11 pages, 6 figure

Deletion of either the regulatory gene ara1 or metabolic gene xki1 in Trichoderma reesei leads to increased CAZyme gene expression on crude plant biomass.

BackgroundTrichoderma reesei is one of the major producers of enzymes for the conversion of plant biomass to sustainable fuels and chemicals. Crude plant biomass can induce the production of CAZymes in T. reesei, but there is limited understanding of how the transcriptional response to crude plant biomass is regulated. In addition, it is unknown whether induction on untreated recalcitrant crude plant biomass (with a large diversity of inducers) can be sustained for longer. We investigated the transcriptomic response of T. reesei to the two industrial feedstocks, corn stover (CS) and soybean hulls (SBH), over time (4&nbsp;h, 24&nbsp;h and 48&nbsp;h), and its regulatory basis using transcription factor deletion mutants (Δxyr1 and Δara1). We also investigated whether deletion of a xylulokinase gene (Δxki1) from the pentose catabolic pathway that converts potential inducers could lead to increased CAZyme gene expression.ResultsBy analyzing the transcriptomic responses using clustering as well as differential and cumulative expression of plant biomass degrading CAZymes, we found that corn stover induced a broader range and higher expression of CAZymes in T. reesei, while SBH induced more pectinolytic and mannanolytic transcripts. XYR1 was the major TF regulating CS utilization, likely due to the significant amount of d-xylose in this substrate. In contrast, ARA1 had a stronger effect on SBH utilization, which correlates with a higher abundance of l-arabinose in SBH that activates ARA1. Blocking pentose catabolism by deletion of xki1 led to higher expression of CAZyme encoding genes on both substrates at later time points. Surprisingly, this was also observed for Δara1 at later time points. Many of these genes were XYR1 regulated, suggesting that inducers for this regulator accumulated over time on both substrates.ConclusionOur data demonstrates the complexity of the regulatory system related to plant biomass degradation in T. reesei and the effect the feedstock composition has on this. Furthermore, this dataset provides leads to improve the efficiency of a T. reesei enzyme cocktail, such as by the choice of substrate or by deleting xki1 to obtain higher production of plant biomass degrading CAZymes

Cinnamic Acid and Sorbic acid Conversion Are Mediated by the Same Transcriptional Regulator in Aspergillus niger

Cinnamic acid is an aromatic compound commonly found in plants and functions as a central intermediate in lignin synthesis. Filamentous fungi are able to degrade cinnamic acid through multiple metabolic pathways. One of the best studied pathways is the non-oxidative decarboxylation of cinnamic acid to styrene. In Aspergillus niger, the enzymes cinnamic acid decarboxylase (CdcA, formally ferulic acid decarboxylase) and the flavin prenyltransferase (PadA) catalyze together the non-oxidative decarboxylation of cinnamic acid and sorbic acid. The corresponding genes, cdcA and padA, are clustered in the genome together with a putative transcription factor previously named sorbic acid decarboxylase regulator (SdrA). While SdrA was predicted to be involved in the regulation of the non-oxidative decarboxylation of cinnamic acid and sorbic acid, this was never functionally analyzed. In this study, A. niger deletion mutants of sdrA, cdcA, and padA were made to further investigate the role of SdrA in cinnamic acid metabolism. Phenotypic analysis revealed that cdcA, sdrA and padA are exclusively involved in the degradation of cinnamic acid and sorbic acid and not required for other related aromatic compounds. Whole genome transcriptome analysis of ΔsdrA grown on different cinnamic acid related compounds, revealed additional target genes, which were also clustered with cdcA, sdrA, and padA in the A. niger genome. Synteny analysis using 30 Aspergillus genomes demonstrated a conserved cinnamic acid decarboxylation gene cluster in most Aspergilli of the Nigri clade. Aspergilli lacking certain genes in the cluster were unable to grow on cinnamic acid, but could still grow on related aromatic compounds, confirming the specific role of these three genes for cinnamic acid metabolism of A. niger.Peer reviewe

A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors

Background LY3022855 is a recombinant, immunoglobulin, human monoclonal antibody targeting the colony-stimulating factor-1 receptor. This phase 1 trial determined the safety, pharmacokinetics, and antitumor activity of LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid cancers who had received standard anti-cancer treatments. Methods In Part A (dose-escalation), patients received intravenous (IV) LY3022855 25/50/75/100 mg once weekly (QW) combined with durvalumab 750 mg once every two weeks (Q2W) IV or LY3022855 50 or 100 mg QW IV with tremelimumab 75/225/750 mg once every four weeks. In Part B (dose-expansion), patients with non-small cell lung cancer (NSCLC) or ovarian cancer (OC) received recommended phase 2 dose (RP2D) of LY3022855 from Part A and durvalumab 750 mg Q2W. Results Seventy-two patients were enrolled (median age 61 years): PartA = 33, Part B = 39. In Part A, maximum tolerated dose was not reached, and LY3022855 100 mg QW and durvalumab 750 mg Q2W was the RP2D. Four dose-limiting equivalent toxicities occurred in two patients from OC cohort. In Part A, maximum concentration, area under the concentration-time curve, and serum concentration showed dose-dependent increase over two cycles of therapy. Overall rates of complete response, partial response, and disease control were 1.4%, 2.8%, and 33.3%. Treatment-emergent anti-drug antibodies were observed in 21.2% of patients. Conclusions LY3022855 combined with durvalumab or tremelimumab in patients with advanced NSCLC or OC had limited clinical activity, was well tolerated. The RP2D was LY3022855 100 mg QW with durvalumab 750 mg Q2W