Prenatal Vitamin D deficiency induces an early and more severe experimental autoimmune encephalomyelitis in the second generation

In a previous study, we demonstrated that mouse adult F(1) offspring, exposed to a vitamin d deficiency during pregnancy, developed a less severe and delayed Experimental Autoimmune Encephalomyelitis (EAE), when compared with control offspring. We then wondered whether a similar response was observed in the subsequent generation. To answer this question, we assessed F(2) females whose F(1) parents (males or females) were vitamin d-deprived when developing in the uterus of F(0) females. Unexpectedly, we observed that the vitamin d deficiency affecting the F(0) pregnant mice induced a precocious and more severe EAE in the F(2) generation. This paradoxical finding led us to assess its implications for the epidemiology of Multiple Sclerosis (MS) in humans. Using the REFGENSEP database for MS trios (the patient and his/her parents), we collected the parents' dates of birth and assessed a potential season of birth effect that could potentially be indicative of the vitamin d status of the pregnant grandmothers. A trend for a reduced number of births in the Fall for the parents of MS patients was observed but statistical significance was not reached. Further well powered studies are warranted to validate the latter finding.

The effect of exercise repetition on the frequency characteristics of motor output force : Implications for Achilles tendinopathy rehabilitation

Objectives: To investigate the frequency characteristics of the ground reaction force (GRF) recorded throughout the eccentric Achilles tendon rehabilitation programme described by Alfredson. Design: Controlled laboratory study, longitudinal. Methods: Nine healthy adult males performed six sets (15 repetitions per set) of eccentric ankle exercise. Ground reaction force was recorded throughout the exercise protocol. For each exercise repetition the frequency power spectrum of the resultant ground reaction force was calculated and normalised to total power. The magnitude of peak relative power within the 8-12 Hz bandwidth and the frequency at which this peak occurred was determined. Results: The magnitude of peak relative power within the 8-12 Hz bandwidth increased with each successive exercise set and following the 4th set (60 repetitions) of exercise the frequency at which peak relative power occurred shifted from 9 to 10 Hz. Conclusions: The increase in magnitude and frequency of ground reaction force vibrations with an increasing number of exercise repetitions is likely connected to changes in muscle activation with fatigue and tendon conditioning. This research illustrates the potential for the number of exercise repetitions performed to influence the tendons' mechanical environment, with implications for tendon remodelling and the clinical efficacy of eccentric rehabilitation programmes for Achilles tendinopathy.

Utilizing least significant bit-planes of RONI pixels for medical image watermarking

We propose a computationally efficient image border pixel based watermark embedding scheme for medical images. We considered the border pixels of a medical image as RONI (region of non-interest), since those pixels have no or little interest to doctors and medical professionals irrespective of the image modalities. Although RONI is used for embedding, our proposed scheme still keeps distortion at a minimum level in the embedding region using the optimum number of least significant bit-planes for the border pixels. All these not only ensure that a watermarked image is safe for diagnosis, but also help minimize the legal and ethical concerns of altering all pixels of medical images in any manner (e.g, reversible or irreversible). The proposed scheme avoids the need for RONI segmentation, which incurs capacity and computational overheads. The performance of the proposed scheme has been compared with a relevant scheme in terms of embedding capacity, image perceptual quality (measured by SSIM and PSNR), and computational efficiency. Our experimental results show that the proposed scheme is computationally efficient, offers an image-content-independent embedding capacity, and maintains a good image quality

Effect of heat treatment and bend strain on the Jc of Ag-sheathed Bi-2212 tape

Bi-2212 tapes were fabricated using a powder-in-tube method and their superconducting properties were measured as a function of heat treatment. The tapes were heated to temperature, T1 (884-915 °C), and kept at that temperature for 20 min to induce partial (incongruent) melting. The samples were cooled to T2 with a ramp rate of 120 °C h-1 and then slowly cooled to T3 with a cooling rate, R2, and from T3 to T4 with a cooling rate, R3. The tapes were kept at the temperature T4 for P1 hours and then cooled to room temperature. Both R1 and R2 were chosen between 2 and 8 °C h-1. It was found that the structure and Jc of the tapes depend on the sintering conditions, i.e. T1-4, R1-3 and P1. The highest Jc of 5800 Å cm-2 was obtained at 77 K in a self-field with heat treatment where T1 = 894 and 899 °C, R1 = R2 = 5 °C h-1 and P1 = 6 h were employed. When 0.7% of bend strain, which is equivalent to a bend radius of 5 mm, was applied to the tape, 80% of the initial Jc was sustained.

Endothelin-1 is a novel prognostic factor in non-small cell lung cancer

Endothelin-1 (ET-1) is a potent vasoactive peptide and a hypoxia-inducible angiogenic growth factor associated with the development and growth of solid tumours. This study evaluated the expression of big endothelin-1 (big ET-1), a stable precursor of ET-1, and ET-1 in non-small cell lung cancer (NSCLC). Big ET-1 expression was evaluated in paraffin-embedded tissue sections from 10 NSCLC tumours using immunohistochemistry and in situ hybridisation. The production of big ET-1 and ET-1 was studied in six established NSCLC cell lines. The plasma concentrations of big ET-1 were measured in 30 patients with proven NSCLC prior to chemotherapy by means of a sandwich enzyme-linked immunoassay and compared to levels in 20 normal controls. Big ET-1 immunostaining was detected in the cancer cells of all tumours studied. Using in situ hybridisation, tumour cell big ET-1 mRNA expression was demonstrated in all samples. All six NSCLC cell lines expressed ET-1, with big ET-1 being detected in three. The median big ET-1 plasma level in patients with NSCLC was 5.4 pg/mL (range 0-22.7 pg/mL) and was significantly elevated compared to median big ET-1 plasma levels in controls, 2.1 pg/mL (1.2-13.4 pg/mL) (p=0.0001). Furthermore, patients with plasma big ET-1 levels above the normal range (upper tertile) had a worse outcome (p=0.01). In conclusion, big ET-1/ET-1 is expressed by resected NSCLC specimens and tumour cell lines. Plasma big ET-1 levels are elevated in NSCLC patients compared to controls with levels >7.8 pg/mL being associated with a worse outcome. The development of selective ET-1 antagonists such as Atrasentan indicates that ET-1 may be a therapeutic target in NSCLC. © 2004 Wichtig Editore.

Why are there Different Age Related Trends for Different Chemicals?

Persistent organic pollutants (POPs) such as dioxins, PCBs, persistent organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs) as well as perfluorinated compounds (PFCs) and triclosan are ubiquitous in the human population. In Australia, we have pooled and subsequently analysed over 10 000 human serum samples for the determination of these chemicals by age group (0–0.5; 0.6–1; 1.1–1.5; 1.6–2; 2.1–2.5; 2.6–3; 3.1–3.5; 3.6–4; 4.1–6; 6.1–9; 9.1–12; 12.1–15; 16–30; 31–45; 46–60 and >60 years) and gender. The results of this analysis were then used to assess the trends of these different chemicals as a function of age, gender and to a lesser extent region. Our data demonstrate clear chemical specific age trends. In particular we demonstrate that for the traditional POPs there is an increase in body burden with age whereas the opposite is true for chemicals such as PBDEs. For PFCs we find chemical specific age trends that vary from compound to compound. For triclosan we show that no apparent age trend is observable. The results of the study and its implications to the collection and archiving of samples for retrospective analysis are discussed.

Regulation of ROCK1 via Notch1 during breast cancer cell migration into dense matrices

Background The behaviour of tumour cells depends on factors such as genetics and the tumour microenvironment. The latter plays a crucial role in normal mammary gland development and also in breast cancer initiation and progression. Breast cancer tissues tend to be highly desmoplastic and dense matrix as a pre-existing condition poses one of the highest risk factors for cancer development. However, matrix influence on tumour cell gene expression and behaviour such as cell migration is not fully elucidated. Results We generated high-density (HD) matrices that mimicked tumour collagen content of 20 mg/cm3 that were ~14-fold stiffer than low-density (LD) matrix of 1 mg/cm3. Live-cell imaging showed breast cancer cells utilizing cytoplasmic streaming and cell body contractility for migration within HD matrix. Cell migration was blocked in the presence of both the ROCK inhibitor, Y-27632, and the MMP inhibitor, GM6001, but not by the drugs individually. This suggests roles for ROCK1 and MMP in cell migration are complicated by compensatory mechanisms. ROCK1 expression and protein activity, were significantly upregulated in HD matrix but these were blocked by treatment with a histone deacetylase (HDAC) inhibitor, MS-275. In HD matrix, the inhibition of ROCK1 by MS-275 was indirect and relied upon protein synthesis and Notch1. Inhibition of Notch1 using pooled siRNA or DAPT abrogated the inhibition of ROCK1 by MS-275. Conclusion Increased matrix density elevates ROCK1 activity, which aids in cell migration via cell contractility. The upregulation of ROCK1 is epigenetically regulated in an indirect manner involving the repression of Notch1. This is demonstrated from inhibition of HDACs by MS-275, which caused an upregulation of Notch1 levels leading to blockade of ROCK1 expression.

Machine learning for activity recognition : hip versus wrist data

Problem addressed Wrist-worn accelerometers are associated with greater compliance. However, validated algorithms for predicting activity type from wrist-worn accelerometer data are lacking. This study compared the activity recognition rates of an activity classifier trained on acceleration signal collected on the wrist and hip. Methodology 52 children and adolescents (mean age 13.7 +/- 3.1 year) completed 12 activity trials that were categorized into 7 activity classes: lying down, sitting, standing, walking, running, basketball, and dancing. During each trial, participants wore an ActiGraph GT3X+ tri-axial accelerometer on the right hip and the non-dominant wrist. Features were extracted from 10-s windows and inputted into a regularized logistic regression model using R (Glmnet + L1). Results Classification accuracy for the hip and wrist was 91.0% +/- 3.1% and 88.4% +/- 3.0%, respectively. The hip model exhibited excellent classification accuracy for sitting (91.3%), standing (95.8%), walking (95.8%), and running (96.8%); acceptable classification accuracy for lying down (88.3%) and basketball (81.9%); and modest accuracy for dance (64.1%). The wrist model exhibited excellent classification accuracy for sitting (93.0%), standing (91.7%), and walking (95.8%); acceptable classification accuracy for basketball (86.0%); and modest accuracy for running (78.8%), lying down (74.6%) and dance (69.4%). Potential Impact Both the hip and wrist algorithms achieved acceptable classification accuracy, allowing researchers to use either placement for activity recognition.

The effect of topical adrenergic and anticholinergic agents on the choroidal thickness of young healthy adults

The human choroid is capable of rapidly changing its thickness in response to a variety of stimuli. However little is known about the role of the autonomic nervous system in the regulation of the thickness of the choroid. Therefore, we investigated the effect of topical parasympatholytic and sympathomimetic agents upon the choroidal thickness and ocular biometrics of young healthy adult subjects. Fourteen subjects (mean age 27.9 ± 4 years) participated in this randomized, single-masked, placebo-controlled study. Each subject had measurements of choroidal thickness (ChT) and ocular biometrics of their right eye taken before, and then 30 and 60 min following the administration of topical pharmacological agents. Three different drugs: 2% homatropine hydrobromide, 2.5% phenylephrine hydrochloride and a placebo (0.3% hydroxypropyl methylcellulose) were tested in all subjects; each on different days (at the same time of the day) in randomized order. Participants were masked to the pharmacological agent being used at each testing session. The instillation of 2% homatropine resulted in a small but significant increase in subfoveal ChT at 30 and 60 min after drug instillation (mean change 7 ± 3 μm and 14 ± 2 μm respectively; both p < 0.0001). The parafoveal choroid also exhibited a similar magnitude, significant increase in thickness with time after 2% homatropine (p < 0.001), with a mean change of 7 ± 0.3 μm and 13 ± 1 μm (in the region located 0.5 mm from the fovea center), 6 ± 1 μm and 12.5 ± 1 μm (1 mm from the fovea center) and 6 ± 2 μm and 12 ± 2 μm (1.5 mm from the fovea center) after 30 and 60 min respectively. Axial length decreased significantly 60 min after homatropine (p < 0.01). There were also significant changes in lens thickness (LT) and anterior chamber depth (ACD) (p < 0.05) associated with homatropine instillation. No significant changes in choroidal thickness, or ocular biometrics were found after 2.5% phenylephrine or placebo at any examination points (p > 0.05). In human subjects, significant increases in subfoveal and parafoveal choroidal thickness occurred after administration of 2% homatropine and this implies an involvement of the parasympathetic system in the control of choroidal thickness in humans.

Programmable digital signal averager.

A high speed digital signal averager with programmable features for the sampling period, for the number of channels and for the number of sweeps is described. The system implements a stable averaging algorithm (Deadroff and Trimble 1968) to provide a stable, calibrated display. The performance of the instrument has been evaluated for the reduction of random noise and for comb-filter action. Special uses of the instrument as a box-car integrator and as a transient recorder are also indicated.

An Algorithm to Decide Feasibility of Linear Integer Constraints Occurrng in Decision Tables

Abstract-To detect errors in decision tables one needs to decide whether a given set of constraints is feasible or not. This paper describes an algorithm to do so when the constraints are linear in variables that take only integer values. Decision tables with such constraints occur frequently in business data processing and in nonnumeric applications. The aim of the algorithm is to exploit. the abundance of very simple constraints that occur in typical decision table contexts. Essentially, the algorithm is a backtrack procedure where the the solution space is pruned by using the set of simple constrains. After some simplications, the simple constraints are captured in an acyclic directed graph with weighted edges. Further, only those partial vectors are considered from extension which can be extended to assignments that will at least satisfy the simple constraints. This is how pruning of the solution space is achieved. For every partial assignment considered, the graph representation of the simple constraints provides a lower bound for each variable which is not yet assigned a value. These lower bounds play a vital role in the algorithm and they are obtained in an efficient manner by updating older lower bounds. Our present algorithm also incorporates an idea by which it can be checked whether or not an (m - 2)-ary vector can be extended to a solution vector of m components, thereby backtracking is reduced by one component.

X-ray studies on crystalline complexes involving amino acids and peptides. Part XIV: Closed conformation and head-to-tail arrangement in a new crystal form of L-histidine L-aspartate monohydrate

A new form of L-histidine L-aspartate monohydrate crystallizes in space group P22 witha = 5.131(1),b = 6.881(1),c= 18.277(2) Å,β= 97.26(1)° and Z = 2. The structure has been solved by the direct methods and refined to anR value of 0.044 for 1377 observed reflections. Both the amino acid molecules in the complex assume the energetically least favourable allowed conformation with the side chains staggered between the α-amino and α-scarboxylate groups. This results in characteristic distortions in some bond angles. The unlike molecules aggregate into alternating double layers with water molecules sandwiched between the two layers in the aspartate double layer. The molecules in each layer are arranged in a head-to-tail fashion. The aggregation pattern in the complex is fundamentally similar to that in other binary complexes involving commonly occurring L amino acids, although the molecules aggregate into single layers in them. The distribution of crystallographic (and local) symmetry elements in the old form of the complex is very different from that in the new form. So is the conformation of half the histidine molecules. Yet, the basic features of molecular aggregation, particularly the nature and the orientation of head-to-tail sequences, remain the same in both the forms. This supports the thesis that the characteristic aggregation patterns observed in crystal structures represent an intrinsic property of amino acid aggregation.

Evaluation of Ustilago sporoboli-indici as a classical biological control agent for invasive Sporobolus grasses in Australia

Sporobolus pyramidalis, S. africanus, S. natalensis, S. fertilis and S. jacquemontii, known collectively as the weedy Sporobolus grasses, are exotic weeds causing serious economic losses in grazing areas along Australia's entire eastern coast. In one of the first attempts to provide biological control for a grass, the potential of a smut, Ustilago sporoboli-indici, as a biological control agent for all five weedy Sporobolus spp. found in Australia was evaluated in glasshouse studies. Application of basidiospores to 21-day-old Sporobolus seedlings and subsequent incubation in a moist chamber (26 °C, 90% RH, 48 h) resulted in infection of S. pyramidalis, S. africanus, S. natalensis and S. fertilis but not S. jacquemontii. Host-range trials with 13 native Australian Sporobolus spp. resulted in infection of four native species. Evaluation of damage caused by the smut on two Australian native and two weedy Sporobolus spp. showed that the total numbers of flowers infected for the four grasses were in the following order: S. creber > S. fertilis > S. elongatus > S. natalensis with percentage flower infections of 21%, 14%, 12% and 3%, respectively. Significant differences (P = 0.001) were found when the numbers of infected flowers caused by each treatment were compared. The infection of the four native Sporobolus spp. by the smut indicated that it was not sufficiently host specific for release in Australia and the organism was rejected as a potential biological control agent. The implications of these results are discussed.

Identification of putative virulence-associated genes of Haemophilus parasuis through suppression subtractive hybridization.

Haemophilus parasuis is the causative agent of Glässer's disease. Up to now 15 serovars of H. parasuis have been identified, with significant differences existing in virulence between serovars. In this study, suppression subtractive hybridization (SSH) was used to identify the genetic difference between Nagasaki (H. parasuis serovar 5 reference strain, highly virulent) and SW114 (H. parasuis serovar 3 reference strain, non-virulent). A total of 191 clones were obtained from the SSH library. Using dot hybridization and PCR, 15 clones were identified containing fragments that were present in the Nagasaki genome while absent in the SW114 genome. Among these 15 fragments, three fragments (ssh1, ssh13, ssh15) encode cell surface-associated components; three fragments (ssh2, ssh5, ssh9) are associated with metabolism and stress response; one fragment (ssh8) is involved in assembly of fimbria and one fragment (ssh6) is a phage phi-105 ORF25-like protein. The remaining seven fragments are hypothetical proteins or unknown. Based on PCR analysis of the 15 serovar reference strains, eight fragments (ssh1, ssh2, ssh3, ssh6, ssh8, ssh10, ssh11 and ssh12) were found in three to five of most virulent serovars (1, 5, 10, 12, 13 and 14), zero to two in three moderately virulent serovars (2, 4 and 15), but absent in the low virulent serovar (8) and non-virulent serovars (3, 6, 7, 9 and 11). In vivo transcription fragments ssh1, ssh2, ssh8 and ssh12 were identified in total RNA samples extracted from experimental infected pig lung by RT-PCR. This study has provided some evidence of genetic differences between H. parasuis strains of different virulence.