A paperfluidic platform to detect Neisseria gonorrhoeae in clinical samples

Globally, the microbe Neisseria gonorrhoeae (NG) causes 106 million newly documented sexually transmitted infections each year. Once appropriately diagnosed, NG infections can be readily treated with antibiotics, but high-risk patients often do not return to the clinic for treatment if results are not provided at the point of care. A rapid, sensitive molecular diagnostic would help increase NG treatment and reduce the prevalence of this sexually transmitted disease. Here, we report on the design and development of a rapid, highly sensitive, paperfluidic device for point-of-care diagnosis of NG. The device integrates patient swab sample lysis, nucleic acid extraction, thermophilic helicase-dependent amplification (tHDA), an internal amplification control (NGIC), and visual lateral flow detection within an 80 min run time. Limits of NG detection for the NG/NGIC multiplex tHDA assay were determined within the device, and clinical performance was validated retroactively against qPCR-quantified patient samples in a proof-of-concept study. This paperfluidic diagnostic has a clinically relevant limit of detection of 500 NG cells per device with analytical sensitivity down to 10 NG cells per device. In triplicate testing of 40 total urethral and vaginal swab samples, the device had 95% overall sensitivity and 100% specificity, approaching current laboratory-based molecular NG diagnostics. This diagnostic platform could increase access to accurate NG diagnoses to those most in need.This work was funded by the National Institute of Health National Institute of Allergy and Infectious Diseases award number R01 AI113927 to Boston University and the NIH National Institute of Biomedical and Bioengineering award number U54 EB007958 to Johns Hopkins University. (R01 AI113927 - National Institute of Health National Institute of Allergy and Infectious Diseases; U54 EB007958 - NIH National Institute of Biomedical and Bioengineering)Accepted manuscrip

Analysis of imatinib in bone marrow and plasma samples of chronic myeloid leukaemia patients using solid phase extraction LC-ESI-MS

The LC-ESI-MS was developed and validated for the analysis of imatinib in plasma and bone marrow samples using deuterated imatinib (D(8)-IM) as an internal standard. The biological samples were extracted using Strata-X-C SPE cartridges and separated on C<sub>8</sub> column (50 x 3 mm, 3 µm), and methanol: 0.1% formic acid (70:30) was delivered at the rate of 0.7 ml/min as a mobile phase. Imatinib was quantified in samples by monitoring the ions m/z 494.3 for imatinib and 502.3 for D<sub>8</sub>-imatinib on mass spectrometer. The method was linear in the concentration range of 1-1500 ng/250 µl in spiked human plasma samples and limit of quantification was 5 ng/mL. Inter-day and intra-day variations in spiked human plasma spiked with 50, 250 and 500 ng /mL were less than 3.16%. The repeatability and reproducibility and other parameters of the methods were also validated. The method was employed for the analysis of the imatinib in human plasma and bone marrow samples. The drug levels in bone marrow and plasma samples were correlated to the degree of cytogenetic response. No significant difference of imatinib level between blood and bone marrow in IM-treated patients dosed to steady state was observed

The complement of the Bowditch space in the SL(2,C) character variety

Let ${\mathcal X}$ be the space of type-preserving \SL(2,C) characters of the punctured torus $T$. The Bowditch space ${\mathcal X}_{BQ}$ is the largest open subset of ${\mathcal X}$ on which the mapping class group acts properly discontinuously, this is characterized by two simple conditions called the $BQ$-conditions. In this note, we show that $[\rho]$ is in the interior of the complement of ${\mathcal X}_{BQ}$ if there exists an essential simple closed curve $X$ on $T$ such that $|{\rm tr} \rho(X)|<0.5$.Comment: 6 page

New business and economic models in the connected digital economy

This paper discusses business models as a systemic phenomenon as opposed to traditional reductionistic approaches of business disciplines. It presents the ways connectivity change economic models due to the availability of consumption data as an economic resource, markets forming at consumption spaces, and how industries could disrupt one another when connected through consumption technologies. The paper further suggests that the challenges posed by connectivity results in the redrawing of traditional firm and market boundaries. It proposes for more research into modularity, transaction costs, the future role of the firm, and the necessary transformation of businesses to stay agile in a connected digital economy

Walang Himala?: Pagsusuri sa mga Tala ni Pedro Chirino, SJ Tungkol sa mga Himalang Dulot ng Pagbibinyag Noong Ika-16 Hanggang Ika-17 Siglo sa Pilipinas

Sa akdang Relación de las Islas Filipinas, isinalaysay ni Pedro Chirino, SJ ang mga milagrosong pagbibinyag na nakapagpagaling ng mga karamdaman (“medicinal baptism”) ng mga katutubo sa pamamagitan ng hiwaga ng agua bendita. Sinusuri sa sanaysay na ito ang wika ng mga himala na ginamit ni Chirino sa kaniyang mga salaysay. Inilalahad sa sanaysay ang ilang posibleng sanhi ng paggaling ng mga karamdamang binigyang-lunas ng mga misyonerong Heswita, bukod sa tinukoy nilang kapangyarihan ng Diyos at hiwaga ng tubig. Iminumungkahi ng pag-aaral na ang integrasyon ng mga elemento ng dayuhan at katutubong pananampalataya ang nagpatibay ng paniniwala ng mga katutubo na ang kanilang mga sakit ay mabibigyang-lunas o ang kanilang resistensiya ay mapalalakas laban sa mga epidemya at malubhang sakit. Isinisiwalat din sa sanaysay ang kaalaman ng mga misyonero hinggil sa mga halamang-gamot at mga paraan ng paghahanda ng mga ito upang maging gamot para sa mga sakit ng mga katutubo. Tinatalakay rin sa sanaysay ang posibleng kaugnayan ng lubos na pagbibigay-diin ni Chirino sa mga himalang dulot ng pagbibinyag sa apela noon ng mga Heswita sa Pilipinas na itatag at kilalanin na ang bise-probinsiya ng Pilipinas (“Philippine vice-province”) bilang isang hiwalay na probinsiya ng Kapisanan ni Hesus (“full-fledged province of the Society of Jesus”) upang magkaroon sila ng higit na awtonomiya at kapangyarihan sa pangangasiwa ng kanilang mga lugar ng misyon sa Pilipinas

Quantification of neurodegeneration by measurement of brain-specific proteins

Quantification of neurodegeneration in animal models is typically assessed by time-consuming and observer-dependent immunocytochemistry. This study aimed to investigate if newly developed ELISA techniques could provide an observer-independent, cost-effective and time-saving tool for this purpose. Neurofilament heavy chain (NfH(SM135)), astrocytic glial fibrillary acidic protein (GFAP), S100B and ferritin, markers of axonal loss, gliosis, astrocyte activation and microglial activation, respectively, were quantified in the spinal cord homogenates of mice with chronic relapsing experimental allergic encephalomyelitis (CREAE, n=8) and controls (n=7). Levels of GFAP were found to be threefold elevated in CREAE (13 ng/mg protein) when compared to control animals (4.5 ng/mg protein, p<0.001). The inverse was observed for NfH(SM135) (21 ng/mg protein vs. 63 ng/mg protein, p<0.001), ferritin (542 ng/mg protein vs. 858 ng/mg protein, p<0.001) and S100B (786 ng/mg protein vs. 2080 ng/mg protein, N.S.). These findings were confirmed by immunocytochemistry, which demonstrated intense staining for GFAP and decreased staining for NfH(SM135) in CREAE compared to control animals. These findings indicate that axonal loss and gliosis can be estimated biochemically using the newly developed ELISA assays for NfH(SM135) and GFAP. These assays may facilitate the quantification of pathological features involved in neurodegeneration

Multispectral Deep Neural Networks for Pedestrian Detection

Multispectral pedestrian detection is essential for around-the-clock applications, e.g., surveillance and autonomous driving. We deeply analyze Faster R-CNN for multispectral pedestrian detection task and then model it into a convolutional network (ConvNet) fusion problem. Further, we discover that ConvNet-based pedestrian detectors trained by color or thermal images separately provide complementary information in discriminating human instances. Thus there is a large potential to improve pedestrian detection by using color and thermal images in DNNs simultaneously. We carefully design four ConvNet fusion architectures that integrate two-branch ConvNets on different DNNs stages, all of which yield better performance compared with the baseline detector. Our experimental results on KAIST pedestrian benchmark show that the Halfway Fusion model that performs fusion on the middle-level convolutional features outperforms the baseline method by 11% and yields a missing rate 3.5% lower than the other proposed architectures.Comment: 13 pages, 8 figures, BMVC 2016 ora

Solid state morphology and band gap studies of ETS-10 supported CdS nanoparticles

Engelhard titanosilicate (ETS-10) supported cadmium sulphide (CdS) nanoparticles were synthesized and characterized by various solid state techniques including: XRD, DR UV-Vis, TEM and FESEM. The effect of different synthesis routes of CdS nanoparticles on its physicochemical character was studied. It was observed that CdS nanoparticles prepared by both in situ sulphur reduction (CdS-IS) and reverse micelle (CdS-RM) methods showed similar properties. However, CdS-IS nanoparticles are more feasible and economically practical. The reflectance measurements of the as-synthesized CdS nanoparticles are apparently blue-shifted compared to bulk CdS. This phenomenon of blue-shifted absorption edge has been ascribed to an increase in bandgap energy with a decrease in particle sizes. The bandgap of the as-synthesized CdS samples was calculated from the linear correlation of [F(R) h?]2 and h?. The bandgap of CdS in ETS-10 was noticeably slightly reduced when compared with the as-synthesized CdS (8 nm) due to the formation of cluster arrays on the pores of ETS-10

Emerging landscape of oncogenic signatures across human cancers.

Cancer therapy is challenged by the diversity of molecular implementations of oncogenic processes and by the resulting variation in therapeutic responses. Projects such as The Cancer Genome Atlas (TCGA) provide molecular tumor maps in unprecedented detail. The interpretation of these maps remains a major challenge. Here we distilled thousands of genetic and epigenetic features altered in cancers to ∼500 selected functional events (SFEs). Using this simplified description, we derived a hierarchical classification of 3,299 TCGA tumors from 12 cancer types. The top classes are dominated by either mutations (M class) or copy number changes (C class). This distinction is clearest at the extremes of genomic instability, indicating the presence of different oncogenic processes. The full hierarchy shows functional event patterns characteristic of multiple cross-tissue groups of tumors, termed oncogenic signature classes. Targetable functional events in a tumor class are suggestive of class-specific combination therapy. These results may assist in the definition of clinical trials to match actionable oncogenic signatures with personalized therapies

The Effects of Social Stress on Voluntary Running Behavior in Female Mice

Regular physical activity (PA) positively impacts physical and mental health outcomes. However, there is a reciprocal relationship wherein stress significantly reduces healthy levels of routine PA. We showed previously that voluntary running behavior of male mice essentially ceases following exposure to a resident-intruder social stress. Here we examined female mice. Female mice were divided into four groups (n=8/group): sedentary/control, voluntary running/control, sedentary/stress, and voluntary running/stress. Running groups were given unlimited access to a running wheel in the home cage for 9 weeks with a nightly average of 6.86 ± 2.5 km. During the ninth week, stress groups were exposed to a single, 6-hour bout of a female-specific, resident-intruder social stress. Plasma corticosterone significantly increased following stress (34.56 ± 13 ng/ml basal to 330.5 ± 95 ng/ml immediately post-stress). Nightly running dropped significantly to 1.72 ± 0.9 km. Unlike male mice where running levels were slow to recover, voluntary running in these female mice returned to normal levels by the second night (5.01 ± 2.5 km). This study shows the sensitivity of habitual running behavior to stress exposure and suggests the utility of this mouse model in exploring the means by which stress negatively impacts routine PA