Refinement of eDNA as an early monitoring tool at the landscape-level: study design considerations.

Natural resource managers use data on the spatial range of species to guide management decisions. These data come from survey or monitoring efforts that use a wide variety of tools. Environmental DNA (eDNA) is a surveillance tool that uses genetic markers for detecting species and holds potential as a tool for large-scale monitoring programs. Two challenges of eDNA-based studies are uncertainties created by imperfect capture of eDNA in collection samples (e.g., water field samples) and imperfect detection of eDNA using molecular methods (e.g., quantitative PCR). Occurrence models can be used to address these challenges, thus we use an occurrence model to address two objectives: first, to determine how many samples were required to detect species using eDNA; second, to examine when and where to take samples. We collected water samples from three different habitat types in the Upper Mississippi River when both Bighead Carp and Silver Carp were known to be present based on telemetry detections. Each habitat type (backwater, tributary, and impoundment) was sampled during April, May, and November. Detections of eDNA for both species varied across sites and months, but were generally low, 0-19.3% of samples were positive for eDNA. Overall, we found that eDNA-based sampling holds promise to be a powerful monitoring tool for resource managers; however, limitations of eDNA-based sampling include different biological and ecological characteristics of target species such as seasonal habitat usage patterns as well as aspects of different physical environments that impact the implementation of these methods such as water temperature.

Pathway-based analysis of GWAs data identifies association of sex determination genes with susceptibility to testicular germ cell tumors.

Genome-wide association (GWA) studies of testicular germ cell tumor (TGCT) have identified 18 susceptibility loci, some containing genes encoding proteins important in male germ cell development. Deletions of one of these genes, DMRT1, lead to male-to-female sex reversal and are associated with development of gonadoblastoma. To further explore genetic association with TGCT, we undertook a pathway-based analysis of SNP marker associations in the Penn GWAs (349 TGCT cases and 919 controls). We analyzed a custom-built sex determination gene set consisting of 32 genes using three different methods of pathway-based analysis. The sex determination gene set ranked highly compared with canonical gene sets, and it was associated with TGCT (FDRG = 2.28 × 10(-5), FDRM = 0.014 and FDRI = 0.008 for Gene Set Analysis-SNP (GSA-SNP), Meta-Analysis Gene Set Enrichment of Variant Associations (MAGENTA) and Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS) analysis, respectively). The association remained after removal of DMRT1 from the gene set (FDRG = 0.0002, FDRM = 0.055 and FDRI = 0.009). Using data from the NCI GWA scan (582 TGCT cases and 1056 controls) and UK scan (986 TGCT cases and 4946 controls), we replicated these findings (NCI: FDRG = 0.006, FDRM = 0.014, FDRI = 0.033, and UK: FDRG = 1.04 × 10(-6), FDRM = 0.016, FDRI = 0.025). After removal of DMRT1 from the gene set, the sex determination gene set remains associated with TGCT in the NCI (FDRG = 0.039, FDRM = 0.050 and FDRI = 0.055) and UK scans (FDRG = 3.00 × 10(-5), FDRM = 0.056 and FDRI = 0.044). With the exception of DMRT1, genes in the sex determination gene set have not previously been identified as TGCT susceptibility loci in these GWA scans, demonstrating the complementary nature of a pathway-based approach for genome-wide analysis of TGCT.

A Height Estimation Approach for Terrain Following Flights from Monocular Vision.

In this paper, we present a monocular vision-based height estimation algorithm for terrain following flights. The impressive growth of Unmanned Aerial Vehicle (UAV) usage, notably in mapping applications, will soon require the creation of new technologies to enable these systems to better perceive their surroundings. Specifically, we chose to tackle the terrain following problem, as it is still unresolved for consumer available systems. Virtually every mapping aircraft carries a camera; therefore, we chose to exploit this in order to use presently available hardware to extract the height information toward performing terrain following flights. The proposed methodology consists of using optical flow to track features from videos obtained by the UAV, as well as its motion information to estimate the flying height. To determine if the height estimation is reliable, we trained a decision tree that takes the optical flow information as input and classifies whether the output is trustworthy or not. The classifier achieved accuracies of 80 % for positives and 90 % for negatives, while the height estimation algorithm presented good accuracy.

Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23.

Genome-wide association studies (GWASs) have identified multiple common genetic variants associated with an increased risk of testicular germ cell tumors (TGCTs). A previous GWAS reported a possible TGCT susceptibility locus on chromosome 1q23 in the UCK2 gene, but failed to reach genome-wide significance following replication. We interrogated this region by conducting a meta-analysis of two independent GWASs including a total of 940 TGCT cases and 1559 controls for 122 single-nucleotide polymorphisms (SNPs) on chromosome 1q23 and followed up the most significant SNPs in an additional 2202 TGCT cases and 2386 controls from four case-control studies. We observed genome-wide significant associations for several UCK2 markers, the most significant of which was for rs3790665 (PCombined = 6.0 × 10(-9)). Additional support is provided from an independent familial study of TGCT where a significant over-transmission for rs3790665 with TGCT risk was observed (PFBAT = 2.3 × 10(-3)). Here, we provide substantial evidence for the association between UCK2 genetic variation and TGCT risk.

A marked paucity of granule cells in the developing cerebellum of the Npc1(-/-) mouse is corrected by a single injection of hydroxypropyl-ß-cyclodextrin.

In this study we show that postnatal development of cerebellar granule neurons (GNs) is defective in Npc1(-/-) mice. Compared to age-matched wild-type littermates, there is an accelerated disappearance of the external granule layer (EGL) in these mice. This is due to a premature exit from the cell cycle of GN precursors residing at the level of the EGL. As a consequence, the size of cerebellar lobules of these mice displays a 20%-25% reduction compared to that of age-matched wild-type mice. This size reduction is detectable at post-natal day 28 (PN28), when cerebellar GN development is completed while signs of neuronal atrophy are not yet apparent. Based on the analysis of EGL thickness and the determination of proliferating GN fractions at increasing developmental times (PN8-PN14), we trace the onset of this GN developmental defect during the second postnatal week. We also show that during this developmental time Shh transcripts undergo a significant reduction in Npc1(-/-) mice compared to age-matched wild-type mice. In light of the mitogenic activity of Shh on GNs, this observation further supports the presence of defective GN proliferation in Npc1(-/-) mice. A single injection of hydroxypropyl-ß-cyclodextrin at PN7 rescues this defect, restoring the normal patterns of granule neuron proliferation and cerebellar lobule size. To our knowledge, these findings identify a novel developmental defect that was underappreciated in previous studies. This defect was probably overlooked because Npc1 loss-of-function does not affect cerebellar foliation and causes the internal granule layer and molecular layer to decrease proportionally, giving rise to a normally appearing, yet harmoniously smaller, cerebellum.

The effects of lebrikizumab in patients with mild asthma following whole lung allergen challenge.

BACKGROUND: Interleukin 13 (IL13) is a T-helper type 2 (Th2) cytokine associated with inflammation and pathology in allergic diseases such as bronchial asthma. We have shown that treatment with lebrikizumab, an anti-IL13 monoclonal antibody, significantly improves prebronchodilator forced expiratory volume in 1 s (FEV(1)) in a subset of subjects with uncontrolled asthma. OBJECTIVE: To evaluate efficacy and safety of lebrikizumab in subjects with mild asthma who underwent bronchial allergen challenge. METHODS: Twenty-nine subjects were randomized 1 : 1-5 mg/kg lebrikizumab (n = 13) or placebo (n = 16) administered subcutaneously every 4 weeks over 12 weeks, a total of four doses. Primary efficacy outcome was late asthmatic response (LAR) at Week 13, defined as area under the curve of FEV1 measured 2-8 h following inhaled allergen challenge. Serum biomarkers were measured to verify IL13 pathway inhibition and identify patients with an increased response to lebrikizumab. RESULTS: At Week 13, the LAR in lebrikizumab subjects was reduced by 48% compared with placebo subjects, although this was not statistically significant (95% confidence interval, -19%, 90%). Exploratory analysis indicated that lebrikizumab-treated subjects with elevated baseline levels of peripheral blood eosinophils, serum IgE, or periostin exhibited a greater reduction in LAR compared with subjects with lower baseline levels of these biomarkers. Lebrikizumab exerted systemic effects on markers of Th2 inflammation, reducing serum immunoglobulin E (IgE), chemokine ligands 13 and 17 by approximately 25% (P < 0.01). Lebrikizumab was well tolerated. CONCLUSION AND CLINICAL RELEVANCE: Lebrikizumab reduced the LAR in subjects with mild asthma. Clinical trial number NCT00781443.

Frequency comb generation in superconducting resonators.

We have generated frequency combs spanning 0.5 to 20 GHz in superconducting λ/2 resonators at T=3 K. Thin films of niobium-titanium nitride enabled this development due to their low loss, high nonlinearity, low frequency dispersion, and high critical temperature. The combs nucleate as sidebands around multiples of the pump frequency. Selection rules for the allowed frequency emission are calculated using perturbation theory, and the measured spectrum is shown to agree with the theory. Sideband spacing is measured to be accurate to 1 part in 10(8). The sidebands coalesce into a continuous comb structure observed to cover at least several frequency octaves.

Next generation sequencing is here now.

The availability of massively parallel DNA sequencers has brought the cost of sequencing genes to affordable levels but the cost of analyzing the huge amount of data has not decreased to the same extent. Thus, only analyzing the sequences of the genes relevant to the patient's condition makes the cost manageable. A panel of genes relevant to lymphedematous conditions is described.

A novel FLT4 mutation identified in a patient with Milroy disease.

Milroy disease is an autosomal dominant disorder generally presenting with below the knee lymphedema at birth. It is linked to mutations in the tyrosine kinase domain of the VEGFR3 protein which is encoded in the FLT4 gene. Here we report a case of Milroy disease in a patient with a dominant pattern of inheritance, classical physical findings, and lymphatic system imaging demonstrating lack of tracer transport in the lower limbs. Genetic analysis revealed a novel missense mutation compared to a summary of reported mutations causing Milroy Disease.

X-linked CHARGE-like Abruzzo-Erickson syndrome and classic cleft palate with ankyloglossia result from TBX22 splicing mutations.

X-linked cleft palate (CPX) is caused by mutations in the gene encoding the TBX22 transcription factor and is known to exhibit phenotypic variability, usually involving either a complete, partial or submucous cleft palate, with or without ankyloglossia. This study hypothesized a possible involvement of TBX22 in a family with X-linked, CHARGE-like Abruzzo-Erickson syndrome, of unknown etiology. The phenotype extends to additional features including sensorineural deafness and coloboma, which are suggested by the Tbx22 developmental expression pattern but not previously associated in CPX patients. A novel TBX22 splice acceptor mutation (c.593-5T>A) was identified that tracked with the phenotype in this family. A novel splice donor variant (c.767+5G>A) and a known canonical splice donor mutation (c.767+1G>A) affecting the same exon were identified in patients with classic CPX phenotypes and were comparatively analyzed using both in silico and in vitro splicing studies. All three variants were predicted to abolish normal mRNA splicing and an in vitro assay indicated that use of alternative splice sites was a likely outcome. Collectively, the data showed the functional effect of several novel intronic splice site variants but most importantly confirms that TBX22 is the gene underlying Abruzzo-Erickson syndrome, expanding the phenotypic spectrum of TBX22 mutations.

Cholesterol metabolism-associated molecules in late onset Alzheimer's disease.

Alzheimer’s disease (AD) is the most common cause of dementia and, with an aging population, poses a huge public health problem. Although a small per cent is caused by single gene changes, most AD is sporadic and unexplained. Of many modifying factors, changes in brain cholesterol homeostasis are the best studied. We present a review of the role of altered cholesterol metabolism and hypercholesterolemia in APP processing and Abeta generation. We also provide an overview of the potential pharmacological modulation of cholesterol homeostasis in the brain by cholesterol-lowering agents and beta-cyclodextrins.

Wear rates of resin composites.

SUMMARY A laboratory study was conducted to examine the wear of resin composite materials using a generalized wear simulation model. Ten specimens each of five resin composites (Esthet•X [EX], Filtek Supreme Plus [SP], Filtek Z250 [Z2], Tetric EvoCeram [EC], and Z100 Restorative [Z1]) were subjected to wear challenges of 100,000, 400,000, 800,000, and 1,200,000 cycles. The materials were placed in cylinder-shaped stainless-steel fixtures, and wear was generated using a flat stainless-steel antagonist in a slurry of polymethylmethacrylate beads. Wear (mean facet depth [µm] and volume loss [mm(3)]) was determined using a noncontact profilometer (Proscan 2000) with Proscan and ProForm software. Statistical analysis of the laboratory data using analysis of variance and Tukey's post hoc test showed a significant difference (p<0.05) for mean wear facet depth and volume loss for both the number of cycles and resin composite material. Linear regression analysis was used to develop predictive wear rates and volume loss rates. Linear wear was demonstrated with correlation coefficients (R(2)) ranging from 0.914 to 0.995. Mean wear values (mean facet depth [µm]) and standard deviations (SD) for 1200K cycles were as follows: Z1 13.9 (2.0), Z2 26.7 (2.7), SP 30.1 (4.1), EC 31.8 (2.3), and EX 67.5 (8.2). Volume loss (mm(3)) and SDs for 1200K cycles were as follows: Z1 0.248 (0.036), Z2 0.477 (0.044), SP 0.541 (0.072), EC 0.584 (0.037), and EX 1.162 (0.139). The wear rate (µm) and volume loss rate (mm(3)) per 100,000 cycles for the five resin composites were as follows: wear rate Z1 0.58, EC 1.27, Z2 1.49, SP 1.62, and EX 4.35, and volume loss rate Z1 0.009, EC 0.024, Z2 0.028, SP 0.029, and EX 0.075. The generalized wear model appears to be an excellent method for measuring relative wear of resin composite materials.

The Re-Discovery of Dural (Meningeal) Lymphatics: Amnesia or Ambition?

In 2015 the discovery of meningeal (dural) lymphatics was announced to much fanfare. The journal Science named this the second most important discovery of the year! Yet, they had actually been well described two and a quarter centuries earlier, in Italy, England, and Holland. However, there was controversy about their existence because of the difficulties in studying them, also addressed two and a quarter centuries earlier. Their study had generated a very large literature and they were "textbook" knowledge. The reasons for this neglect are discussed emphasizing the current scientific milieu and the changing modes of evaluating scientists.

Text-Driven Video Acceleration: A Weakly-Supervised Reinforcement Learning Method.

The growth of videos in our digital age and the users' limited time raise the demand for processing untrimmed videos to produce shorter versions conveying the same information. Despite the remarkable progress that summarization methods have made, most of them can only select a few frames or skims, creating visual gaps and breaking the video context. This paper presents a novel weakly-supervised methodology based on a reinforcement learning formulation to accelerate instructional videos using text. A novel joint reward function guides our agent to select which frames to remove and reduce the input video to a target length without creating gaps in the final video. We also propose the Extended Visually-guided Document Attention Network (VDAN+), which can generate a highly discriminative embedding space to represent both textual and visual data. Our experiments show that our method achieves the best performance in Precision, Recall, and F1 Score against the baselines while effectively controlling the video's output length.

Childhood infections, orchitis and testicular germ cell tumours: a report from the STEED study and a meta-analysis of existing data.

BACKGROUND: Similarities between the age-specific incidence pattern of testicular germ cell tumours (TGCTs) and the age-specific incidence pattern of cancers of viral origin prompted us to evaluate the relationship between common infections occurring during childhood or young adult life and TGCT using existing data from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) case-control study. METHODS: TGCT cases diagnosed between 2002 and 2005 (n=767) were matched on age, race and serum draw date to at least one control (n=929). RESULTS: None of the infections evaluated were associated with TGCT risk. Further, a meta-analysis of mumps and mumps orchitis or orchitis infection did not support an association with TGCT (mumps pooled odds ratio (OR): 1.03, 95% confidence interval (CI): 0.89-1.20; mumps orchitis or orchitis pooled OR: 1.80, 95% CI: 0.74-4.42). CONCLUSION: Based on our evaluation of childhood and early life infections and meta-analyses of mumps and mumps orchitis and/or orchitis, TGCT does not appear to be associated with common childhood infections.

LYMPHSPIRATION: The importance of the study of dermatoglyphics for lymphologists.

A recent genome-wide association study (GWAS) looking for the genes determining fingerprint and palmar crease patterns disclosed one gene, among many others, which causes lymphedema (CELSR1) while others influencing tissue growth. Since digital fluid influences the height of the volar pads, influences of lymphedema on dermatoglyphics should be sought.

Centrifugal Versus Centripetal Origin(s) of the Lymphatic System: Controversy (Mostly) Resolved?

New findings reopen the controversy about centrifugal vs. centripetal origin of the lymphatic system and support that the latter may be the predominant source of lymphatic endothelial cells from mesenchymal lymphangioblasts.

Lack of embryonic homozygous or adult heterozygous lymphatic phenotypes for a Sos1 mutation and lack of lymphatic embryonic phenotypes for a homozygous Cx47 mutation in mice.

We have studied the lymphatic phenotypes of 2 mutations, known to cause abnormalities of lymphatics in humans, in mice. The Cx47 R260C mutation (variably penetrant in humans heterozygous for it and causing limb lymphedema) had an adult mouse phenotype of hyperplasia and increased lymph nodes only in homozygous condition but we did not find any anatomical phenotype in day 16.5 homozygous embryos. Mice harboring the Sos1 mutation E846K (causing Noonan's in man which occasionally shows lymphatic dysplasia) had no adult heterozygous phenotype in lymphatic vessel appearance and drainage (homozygotes are early embryonic lethals) while day 16.5 heterozygous embryos also had no detectable anatomical phenotype.

Human chromosome map of lymphedema-lymphangiogenesis genes: Template for current and future discovery.

We have created a human chromosomal map of the location of known and candidate genes involved in primary lymphedema (PLE). This should facilitate further discovery and provide a basis for understanding microdeletions which cause lymphedema.

A Sparse Sampling-Based Framework for Semantic Fast-Forward of First-Person Videos.

Technological advances in sensors have paved the way for digital cameras to become increasingly ubiquitous, which, in turn, led to the popularity of the self-recording culture. As a result, the amount of visual data on the Internet is moving in the opposite direction of the available time and patience of the users. Thus, most of the uploaded videos are doomed to be forgotten and unwatched stashed away in some computer folder or website. In this paper, we address the problem of creating smooth fast-forward videos without losing the relevant content. We present a new adaptive frame selection formulated as a weighted minimum reconstruction problem. Using a smoothing frame transition and filling visual gaps between segments, our approach accelerates first-person videos emphasizing the relevant segments and avoids visual discontinuities. Experiments conducted on controlled videos and also on an unconstrained dataset of First-Person Videos (FPVs) show that, when creating fast-forward videos, our method is able to retain as much relevant information and smoothness as the state-of-the-art techniques, but in less processing time.