Single-beam three-dimensional optical trapping at extremely low insertion angles via optical fiber optimization

Employing optical fiber to deliver the trapping laser to the sample chamber significantly reduces the size and costs of optical tweezers (OT). The utilization of fiber decouples the OT from the microscope, providing scope for system portability, and the potential for uncomplicated integration with other advanced microscopy systems. For use with an atomic force microscope, the fiber must be inserted at an angle of 10 deg to the plane of the sample chamber floor. However, the literature states that optical trapping with a single fiber inserted at an angle ≤20 deg is not possible. This paper investigates this limitation and proposes a hypothesis that explains it. Based on this explanation, a tapered-fiber optical tweezer system is developed. This system demonstrates that such traps can indeed be made to function in three-dimensions (3-D) at insertion angles of ≤10 deg using relatively low optical powers, provided the fiber taper is optimized. Three such optimized tapered fiber tips are presented, and their ability to optically trap both organic and inanimate material in 3-D is demonstrated. The near-horizontal insertion angle introduced a maximum trapping range (MTR). The MTR of the three tips is determined empirically, evaluated against simulated data, and found to be tunable through taper optimization

Recombinant Incretin-Secreting Microbe Improves Metabolic Dysfunction in High-Fat Diet Fed Rodents

peer-reviewedThe gut hormone glucagon-like peptide (GLP)-1 and its analogues represent a new generation of anti-diabetic drugs, which have also demonstrated propensity to modulate host lipid metabolism. Despite this, drugs of this nature are currently limited to intramuscular administration routes due to intestinal degradation. The aim of this study was to design a recombinant microbial delivery vector for a GLP-1 analogue and assess the efficacy of the therapeutic in improving host glucose, lipid and cholesterol metabolism in diet induced obese rodents. Diet-induced obese animals received either Lactobacillus paracasei NFBC 338 transformed to express a long-acting analogue of GLP-1 or the isogenic control microbe which solely harbored the pNZ44 plasmid. Short-term GLP-1 microbe intervention in rats reduced serum low-density lipoprotein cholesterol, triglycerides and triglyceride-rich lipoprotein cholesterol substantially. Conversely, extended GLP-1 microbe intervention improved glucose-dependent insulin secretion, glucose metabolism and cholesterol metabolism, compared to the high-fat control group. Interestingly, the microbe significantly attenuated the adiposity associated with the model and altered the serum lipidome, independently of GLP-1 secretion. These data indicate that recombinant incretin-secreting microbes may offer a novel and safe means of managing cholesterol metabolism and diet induced dyslipidaemia, as well as insulin sensitivity in metabolic dysfunction

Diphacinone and coumatetralyl persistence in deer and implications for wildlife management

Eason, C.T., Murphy, E., Ross, J.G., Hix, S., Arthur, D., MacMorran, D., Broome, K., Fairweather, A

Integrating Multiple Sources of Knowledge for the Intelligent Detection of Anomalous Sensory Data in a Mobile Robot

For service robots to expand in everyday scenarios they must be able to identify and manage abnormal situations intelligently. In this paper we work at a basic sensor level, by dealing with raw data produced by diverse devices subjected to some negative circumstances such as adverse environmental conditions or difficult to perceive objects. We have implemented a probabilistic Bayesian inference process for deducing whether the sensors are working nominally or not, which abnormal situation occurs, and even to correct their data. Our inference system works by integrating in a rigorous and homogeneous mathematical framework multiple sources and modalities of knowledge: human expert, external information systems, application-specific and temporal. The results on a real service robot navigating in a structured mixed indoor-outdoor environment demonstrate good detection capabilities and set a promising basis for improving robustness and safety in many common service tasks.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

The Suzaku X-ray spectrum of NGC 3147. Further insights on the best "true" Seyfert 2 galaxy candidate

NGC 3147 is so far the most convincing case of a "true" Seyfert 2 galaxy, i.e. a source genuinely lacking the Broad Line Regions. We obtained a Suzaku observation with the double aim to study in more detail the iron line complex, and to check the Compton-thick hypothesis for the lack of observed optical broad lines. The Suzaku XIS and HXD/PIN spectra of the source were analysed in detail. The line complex is composed of at least two unresolved lines, one at about 6.45 keV and the other one at about 7 keV, most likely identified with Fe XVII/XIX, the former, and Fe XXVI, the latter. The high-ionization line can originate either in a photoionized matter or in an optically thin thermal plasma. In the latter case, an unusually high temperature is implied. In the photoionized model case, the large equivalent width can be explained either by an extreme iron overabundance or by assuming that the source is Compton-thick. In the Compton-thick hypothesis, however, the emission above 2 keV is mostly due to a highly ionized reflector, contrary to what is usually found in Compton-thick Seyfert 2s, where reflection from low ionized matter dominates. Moreover, the source flux varied between the XMM-Newton and the Suzaku observations, taken 3.5 years apart, confirming previous findings and indicating that the size of the emitting region must be smaller than a parsec. The hard X-ray spectrum is also inconclusive on the Compton-thick hypothesis. Weighting the various arguments, a "true" Seyfert 2 nature of NGC 3147 seems to be still the most likely explanation, even if the "highly ionized reflector" Compton-thick hypothesis cannot at present be formally rejected.Comment: 6 pages, accepted for publication in Astronomy & Astrophysic

Optimal treatment allocations in space and time for on-line control of an emerging infectious disease

A key component in controlling the spread of an epidemic is deciding where, whenand to whom to apply an intervention.We develop a framework for using data to informthese decisionsin realtime.We formalize a treatment allocation strategy as a sequence of functions, oneper treatment period, that map up-to-date information on the spread of an infectious diseaseto a subset of locations where treatment should be allocated. An optimal allocation strategyoptimizes some cumulative outcome, e.g. the number of uninfected locations, the geographicfootprint of the disease or the cost of the epidemic. Estimation of an optimal allocation strategyfor an emerging infectious disease is challenging because spatial proximity induces interferencebetween locations, the number of possible allocations is exponential in the number oflocations, and because disease dynamics and intervention effectiveness are unknown at outbreak.We derive a Bayesian on-line estimator of the optimal allocation strategy that combinessimulation–optimization with Thompson sampling.The estimator proposed performs favourablyin simulation experiments. This work is motivated by and illustrated using data on the spread ofwhite nose syndrome, which is a highly fatal infectious disease devastating bat populations inNorth America

Pharmacologic treatment with CPI-613 and PS48 decreases mitochondrial membrane potential and increases quantity of autolysosomes in porcine fibroblasts

A metabolic phenomenon known as the Warburg effect has been characterized in certain cancerous cells, embryonic stem cells, and other rapidly proliferative cell types. Previously, our attempts to induce a Warburg-like state pharmaceutically via CPI-613 and PS48 treatment did augment metabolite production and gene expression; however, this treatment demonstrated a Reverse Warburg effect phenotype observed in cancer-associated stroma. In the current study, we inquired whether the mitochondria were affected by the aforementioned pharmaceutical treatment as observed in cancerous stromal fibroblasts. While the pharmaceutical agents decreased mitochondrial membrane potential in porcine fetal fibroblasts, the number and size of mitochondria were similar, as was the overall cell size. Moreover, the fibroblasts that were treated with CPI-613 and PS48 for a week had increased numbers of large autolysosome vesicles. This coincided with increased intensity of LysoTracker staining in treated cells as observed by flow cytometry. Treated fibroblasts thus may utilize changes in metabolism and autophagy to mitigate the damage of treatment with pharmaceutical agents. These findings shed light on how these pharmaceutical agents interact and how treated cells augment metabolism to sustain viability. c2019, The Author(s).Includes bibliographical references

Clinical actionability of comprehensive genomic profiling for management of rare or refractory cancers

Background. The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important. Methods. A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors. The primary objectives were to assess utility, feasibility, and limitations of genomic sequencing for genomically guided therapy or other clinical purpose in the setting of a multidisciplinary molecular tumor board. Results. Of the tumors from the 92 patients with sufficient tissue, 88 (96%) had at least one genomic alteration (average 3.6, range 0–10). Commonly altered pathways included p53 (46%), RAS/RAF/MAPK (rat sarcoma; rapidly accelerated fibrosarcoma; mitogen-activated protein kinase) (45%), receptor tyrosine kinases/ligand (44%), PI3K/AKT/mTOR (phosphatidylinositol-4,5-bisphosphate 3-kinase; protein kinase B; mammalian target of rapamycin) (35%), transcription factors/regulators (31%), and cell cycle regulators (30%). Many low frequency but potentially actionable alterations were identified in diverse histologies. Use of comprehensive profiling led to implementable clinical action in 35% of tumors with genomic alterations, including genomically guided therapy, diagnostic modification, and trigger for germline genetic testing. Conclusion. Use of targeted next-generation sequencing in the setting of an institutional molecular tumor board led to implementable clinical action in more than one third of patients with rare and poor-prognosis cancers. Major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access. Early and serial sequencing in the clinical course and expanded access to genomically guided early-phase clinical trials and targeted agents may increase actionability. Implications for Practice: Identification of key factors that facilitate use of genomic tumor testing results and implementation of genomically guided therapy may lead to enhanced benefit for patients with rare or difficult to treat cancers. Clinical use of a targeted next-generation sequencing assay in the setting of an institutional molecular tumor board led to implementable clinical action in over one third of patients with rare and poor prognosis cancers. The major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access both on trial and off label. Approaches to increase actionability include early and serial sequencing in the clinical course and expanded access to genomically guided early phase clinical trials and targeted agents