Macropinocytotic uptake and infection of human epithelial cells with species B2 adenovirus type 35

The human adenovirus serotype 35 (HAdV-35, short Ad35) causes kidney and urinary tract infections, and infects respiratory organs of immunocompromised individuals. Unlike other adenoviruses, Ad35 has a low seroprevalence which makes Ad35-based vectors promising candidates for gene therapy. Ad35 utilizes CD46 and integrins as receptors for infection of epithelial and hematopoietic cells. Here, we show that infectious entry of Ad35 into HeLa, human kidney HK-2 cells and normal human lung fibroblasts strongly depended on CD46 and integrins but not heparan sulfate, and variably required the large GTPase dynamin. Ad35 infections were independent of expression of the carboxy-terminal domain of AP180 which effectively blocks clathrin-mediated uptake. Ad35 infections were inhibited by small chemicals against the serine/threonine kinase Pak1 (p21-activated kinase), protein kinase C (PKC), sodium-proton exchangers, actin and acidic organelles. Remarkably, the F-actin inhibitor jasplakinolide, the Pak1 inhibitor IPA-3 or the sodium-proton exchange inhibitor EIPA blocked the endocytic uptake of Ad35. Dominant-negative proteins or small interfering RNAs against factors driving macropinocytosis, including the small GTPase Rac1, Pak1 or the Pak1 effector C-terminal binding protein 1 (CtBP1) potently inhibited Ad35 infection. Confocal laser scanning microscopy, electron microscopy and live cell imaging showed that Ad35 colocalized with fluid phase markers in large endocytic structures that were positive for CD46, alpha v integrins and also CtBP1. Our results extend earlier observations with HAdV-3 (Ad3), and establish macropinocytosis as an infectious pathway for species B human adenoviruses in epithelial and hematopoietic cells

Use of remote sensing‑derived fPAR data in a grapevine simulation model for estimating vine biomass accumulation and yield variability at sub‑field level

Grapevine simulation models are mostly used to estimate plant development, growth and yield at plot scale. However, the spatial variability of pedologic and micro-climatic conditions can influence vine growth, leading to a sub-field heterogeneity in plant vigor and final yield that may be better estimated through the assimilation of high spatial resolution data in crop models. In this study, the spatial variability of grapevine intercepted radiation at fruit-set was used as input for a grapevine simulation model to estimate the variability in biomass accumulation and yield in two Tuscan vineyards (Sites A and B). In Site A, the model, forced with intercepted radiation data as derived from the leaf area index (LAI), measured at canopy level in three main vigor areas of the vineyard, provided a satisfactory simulation of the final pruning weight (r2 = 0.61; RMSE = 19.86 dry matter g m−2). In Site B, Normalized Difference Vegetation Index (NDVI) from Sentinel-2A images was firstly re-scaled to account for canopy fraction cover over the study areas and then used as a proxy for grapevine intercepted radiation for each single pixel. These data were used to drive the grapevine simulation model accounting for spatial variability of plant vigor to reproduce yield variability at pixel scale (r2 = 0.47; RMSE = 75.52 dry matter g m−2). This study represents the first step towards the realization of a decision tool supporting winegrowers in the selection of the most appropriate agronomic practices for reducing the vine vigor and yield variability at sub-field level

Total knee replacements using rotating hinge implants in polio patients: clinical and functional outcomes

Little evidences are available in the literature concerning the outcomes of total knee replacement (TKR) in poliomyelitis patients with severe knee deformities or degeneration. Encouraging results have been reported concerning the use of constrained implants, i.e., rotating hinge knee prosthesis (RHK), compared to less constrained ones. The purpose of this paper is to report our experience with rotating hinge total knee replacement, using only RHK prosthesis, to determine functional results, complications, and survival of TKR in poliomyelitis patients. We performed a retrospective chart review of 14 patients with a history of knee osteoarthritis following poliomyelitis that underwent primary TKR, for a total of 15 surgical procedure (one bilateral case). Preoperative and postoperative clinical measurements have been conducted for all patients using the Knee Society Score (KSS). Hip-knee angle, recurvatum knee angle, and Insall-Salvati index were evaluated with full weight-bearing panoramic view X-ray preoperatively and postoperatively. The 2-year postoperative clinical KSS significantly improved from the preoperative scores. The average clinical KSS improved from 32,9 (range 3-48) preoperatively to 77,4 (range 60-88) postoperatively (P value < 0.005). The average functional KSS improved from 32,5 (range 10-60) preoperatively to 59,4 (range 30-95) postoperatively (P value < 0.005). TKR is a successful treatment in improving knee function and patient's quality of life. Using constrained implants, especially rotating hinge implants in polio patients with a quadriceps muscle weakness, could be a good alternative to maintain a physiological kinematics and reducing the revision rate due to knee instability

Improving procedural fidelity of behavioural interventions for people with intellectual and developmental disabilities: A systematic review

Background: Despite its importance within behavioural intervention, it remains unclear how best to achieve high procedural fidelity. This paper reviewed studies on improving procedural fidelity of behavioural interventions for individuals with intellectual and developmental disabilities (IDD). Method: A systematic literature search was conducted, which identified 20 studies meeting inclusion criteria. Data were extracted on study design, participant characteristics, intervention, target behaviours, effect sizes, maintenance, generalisation, and social validity. A quality rating was also applied. Results: A total of 100 participants took part in the included studies. Most participants were teachers working with children in school settings. There was a significant positive correlation between level of procedural fidelity and client outcomes. Feedback was the most commonly employed intervention to improve procedural fidelity. Conclusions: More research should be conducted in environments with high levels of variability such as community homes to determine how to reach and maintain high levels of procedural fidelity

Biomarker phenotyping drives clinical management in axillary sentinel node: A retrospective study on women with primary breast cancer in 2002

The current study examined if cancer biomarker phenotyping could predict the clinical/pathological status of axillary nodes in women with primary breast cancer. Primary breast cancers from 2002 were analyzed for tumor size, estrogen receptor (ER), progesterone receptor (PgR), Ki.67MIB expression and Her2/neu amplification. Relationships between the clinical and pathological status of the axilla and the biological subtypes classification were analyzed using univariate, multivariate and regression tree analysis. A total of 65% of women with axillary nodes clinically involved had complete axillary node dissection (ALND) while 705 women with clinically negative axillary underwent sentinel lymph node biopsy (SLNB), 18.5% of the latter had at least one pathologically SLNB involved node. Multivariate analysis revealed that the Luminal A subtype was significantly associated (OR 0.62; P<10-9) with clinical negative axilla while HER2pos/not Luminal was associated with clinical positivity (OR 1.71; P<0.01). No significant association between biological subtypes and SLNB status was demonstrated. Regression tree analysis revealed that subgroups with significantly different probability of SLNB status were separated according to tumor size and PgR values. In conclusion, the current study demonstrated that biomarker breast cancer phenotyping is significantly associated with clinical status of axillary nodes but not with pathological involvement of nodes at SLNB. Regression tree analysis could represent a valid attempt to individualize some patients subgroups candidate to different surgical axilla approaches

Measurement of the angular correlation between the two gamma rays emitted in the radioactive decays of a 60^{60}Co source with two NaI(Tl) scintillator

We implemented a didactic experiment to study the angular correlation between the two gamma rays emitted in typical $^{60}$Co radioactive decays. We used two NaI(Tl) scintillators, already available in our laboratory, and a low-activity $^{60}$Co source. The detectors were mounted on two rails, with the source at their center. The first rail was fixed, while the second could be rotated around the source. We performed several measurements by changing the angle between the two scintillators in the range from $90^\circ$ to $180^\circ$. Dedicated background runs were also performed, removing the source from the experimental setup. We found that the signal rate increases with the angular separation between the two scintillators, with small discrepancies from the theoretical expectations.Comment: 15 pages, 12 figure

Weak Lensing from Space I: Instrumentation and Survey Strategy

A wide field space-based imaging telescope is necessary to fully exploit the technique of observing dark matter via weak gravitational lensing. This first paper in a three part series outlines the survey strategies and relevant instrumental parameters for such a mission. As a concrete example of hardware design, we consider the proposed Supernova/Acceleration Probe (SNAP). Using SNAP engineering models, we quantify the major contributions to this telescope's Point Spread Function (PSF). These PSF contributions are relevant to any similar wide field space telescope. We further show that the PSF of SNAP or a similar telescope will be smaller than current ground-based PSFs, and more isotropic and stable over time than the PSF of the Hubble Space Telescope. We outline survey strategies for two different regimes - a ``wide'' 300 square degree survey and a ``deep'' 15 square degree survey that will accomplish various weak lensing goals including statistical studies and dark matter mapping.Comment: 25 pages, 8 figures, 1 table, replaced with Published Versio

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead