Intermittent Hypoxic Therapy Inhibits Allogenic Bone-Graft Resorption by Inhibition of Osteoclastogenesis in a Mouse Model

Systemic Intermittent Hypoxic Therapy (IHT) relies on the adaptive response to hypoxic stress. We investigated allogenic bone-graft resorption in the lumbar spine in 48 mice. The mice were exposed to IHT for 1 week before surgery or 1 week after surgery and compared with controls after 1 and 4 weeks. Complete graft resorption was observed in 33–36% of the animals in the control group, but none in the preoperative IHT group. Increased bone-graft volume was demonstrated by micro-computed tomography in the preoperative IHT group after 1 week (p = 0.03) while a non-significant difference was observed after 4 weeks (p = 0.12). There were no significant differences in the postoperative IHT group. Increased concentration of immune cells was localized in the graft area, and more positive tartrate-resistant acid phosphatase (TRAP) staining was found in controls compared with IHT allogenic bone grafts. Systemic IHT resulted in a significant increase of the major osteoclast inhibitor osteoprotegerin as well as osteogenic and angiogenic regulators Tgfbr3, Fst3l, Wisp1, and Vegfd. Inflammatory cytokines and receptor activator of nuclear factor kappa-B ligand (RANKL) stimulators IL-6, IL-17a, IL-17f, and IL-23r increased after 1 and 4 weeks, and serum RANKL expression remained constant while Ccl3 and Ccl5 decreased. We conclude that the adaptive response to IHT activates numerous pathways leading to inhibition of osteoclastic activity and inhibition of allogenic bone-graft resorption.     

Gaucher Disease Diagnosis Using Lyso-Gb1 on Dry Blood Spot Samples: Time to Change the Paradigm?

For years, the gold standard for diagnosing Gaucher disease (GD) has been detecting reduced β-glucocerebrosidase (GCase) activity in peripheral blood cells combined with GBA1 mutation analysis. The use of dried blood spot (DBS) specimens offers many advantages, including easy collection, the need for a small amount of blood, and simpler transportation. However, DBS has limitations for measuring GCase activity. In this paper, we recount our cross-sectional study and publish seven years of experience using DBS samples and levels of the deacylated form of glucocerebroside, glucosylsphingosine (lyso-Gb1), for GD diagnosis. Of 444 screened subjects, 99 (22.3%) were diagnosed with GD at a median (range) age of 21 (1–78) years. Lyso-Gb levels for genetically confirmed GD patients vs. subjects negative to GD diagnosis were 252 (9–1340) ng/mL and 5.4 (1.5–16) ng/mL, respectively. Patients diagnosed with GD1 and mild GBA1 variants had lower median (range) lyso-Gb1, 194 (9–1050), compared to GD1 and severe GBA1 variants, 447 (38–1340) ng/mL, and neuronopathic GD, 325 (116–1270) ng/mL (p = 0.001). Subjects with heterozygous GBA1 variants (carrier) had higher lyso-Gb1 levels, 5.8 (2.5–15.3) ng/mL, compared to wild-type GBA1, 4.9 (1.5–16), ng/mL (p = 0.001). Lyso-Gb1 levels, median (range), were 5 (2.7–10.7) in heterozygous GBA1 carriers with Parkinson’s disease (PD), similar to lyso-Gb1 levels in subjects without PD. We call for a paradigm change for the diagnosis of GD based on lyso-Gb1 measurements and confirmatory GBA1 mutation analyses in DBS. Lyso-Gb1 levels could not be used to differentiate between heterozygous GBA1 carriers and wild type.     

A rheo-optical apparatus for real time kinetic studies on shear-induced alignment of self-assembled soft matter with small sample volumes

In soft materials, self-assembled nanoscale structures can allow new functionalities but a general problem is to align such local structures aiming at monodomain overall order. In order to achieve shear alignment in a controlled manner, a novel type of rheo-optical apparatus has here been developed that allows small sample volumes and in situ monitoring of the alignment process during the shear. Both the amplitude and orientation angles of low level linear birefringence and dichroism are measured while the sample is subjected to large amplitude oscillatory shear flow. The apparatus is based on a commercial rheometer where we have constructed a flow cell that consists of two quartz teeth. The lower tooth can be set in oscillatory motion whereas the upper one is connected to the force transducers of the rheometer. A custom made cylindrical oven allows the operation of the flow cell at elevated temperatures up to 200 degrees C. Only a small sample volume is needed (from 9 to 25 mm(3)), which makes the apparatus suitable especially for studying new materials which are usually obtainable only in small quantities. Using this apparatus the flow alignment kinetics of a lamellar polystyrene-b-polyisoprene diblock copolymer is studied during shear under two different conditions which lead to parallel and perpendicular alignment of the lamellae. The open device geometry allows even combined optical/x-ray in situ characterization of the alignment process by combining small-angle x-ray scattering using concepts shown by Polushkin et al. [Macromolecules 36, 1421 (2003)].     

Search for Superconductivity in Lithium

We report on the results of a search for superconductivity in Li. We find no evidence for the predicted transition to superconductivity at any temperature down to 5 mK in magnetic fields down to 0.4 T. However, an unexpected Curie–Weiss temperature dependence in the magnetic susceptibility is observed. We discuss the possibility that this signal arises from the Li itself, the possibility that it arises from Kondo behavior, and the implications of the effect for the predicted T_c of Li.     

Simultaneous ac Susceptibility and Specific Heat Measurements of YBCO Ceramics

Simultaneous ac magnetic susceptibility and specific heat studies of YBCO ceramics permitted the correct correlation of the corresponding critical temperatures. The midpoint of the real component () and the maximum of the imaginary component () of ac susceptibility curves confirmed the T _c = 92 K critical temperature value determined by dc resistance measurements. The specific heat maximum's temperature (T _cc 93.6 K)—-taken as the calorimetric critical one—fell between T _c and T* (the pseudogap onset temperature). We suggest that T _cc signals the appearance of the first localized coherent pairs, while the temperature T _c marks their percolation. The existence of two different critical temperature values confirms the coexistence of partial coherent and coherent electron pairing phenomena in the region below T _cc of the superconducting phase diagram.     

Does increased confidence among novice drivers imply a decrease in safety? The effects of skid training on slippery road accidents

Finnish driver training was renewed in 1990 with the inclusion of a compulsory skid training course in the curriculum. The study evaluated the renewal's effect on accidents in slippery road conditions. A questionnaire was sent by mail to 41000 novice drivers who were randomly selected from the official register of driving licences. It included questions on driving exposure and the accidents the drivers had been involved in during 6-18 months following licensing. The rate of return was 74.7%. Half of the drivers had received their licence in 1989 and had, therefore, not received any skid training. The other half had received their licence in 1990 after the introduction of the skid training course. The results showed no effects of the renewal on slippery road accidents for either male or female drivers. Another questionnaire was sent to 1300 old and new curriculum drivers immediately after licensing and a second time 1/2-1 year later, both with questions about skills, worries and perceived risks regarding driving in slippery conditions. The new curriculum drivers showed higher confidence in their skills and they were less afraid to drive in slippery conditions than the old curriculum drivers. This increase in confidence as a result of skid training is discussed. It is argued that high confidence in one's personal skills does not necessarily imply negative safety. The crucial factor is how these skills are used, and for what purpose.     

Approximating the Advertisement Placement Problem

The advertisement placement problem deals with space and time sharing by advertisements on the Internet. Consider a Web page containing a rectangular display area (e.g., a banner) in which advertisements may appear. The display area can be utilized efficiently by allowing several small ads to appear simultaneously side by side, as well as by cycling through a schedule of ads, allowing different ads to be displayed at different times. A customer wishing to purchase advertising space specifies an ad size and a display count, which is the number of times their ad should appear during each cycle. The scheduler may accept or reject any given advertisement, but must be able to schedule all accepted ads within the given time and space constraints. Each advertisement has a non-negative profit associated with it, and the objective is to schedule a maximum-profit subset of ads. We present a (3 + )-approximation algorithm for the general problem, as well as (2 + )-approximation algorithms for two special cases.     

Financing cleaner production investments—UNEP experience

Cleaner production (CP) can be good business. To address constraints related to financing CP and to look for ways to overcome them, the United Nations Environment Programme, Division of Technology, Industry and Economic (UNEP/DTIE), has been implementing since 1999 a project "Strategies and mechanisms for promoting cleaner production investment in developing countries". The project is coming to an end in February 2003. Through field testing and adaptation and in partnership with experts in industrialised and developing countries and economies in transition, it has generated a series of guides, checklists and training packages. Over 3,000 persons attended the over 100 1- or 2-day courses delivered by national institutions in five demonstration countries. The project has also contributed to making preventive approaches and efficient resource management part of awareness raising and training activities by some development finance institutions and the UNEP Finance Initiatives. Proposals on innovative financing schemes have been made in several workshops for banks and donors in 2002. In addition to the special financing issue of the Journal of Cleaner Production (published in March 2003), articles on links between CP, financing and accounting have been contributed to professional publications.Although the project's demonstration activities have focused on five countries in Africa, Asia and Central America, its conclusions, recommendations and outputs are of direct relevance also to other developing countries and economies in transition. The integration of preventive strategies into investment decision making processes is a challenge both in the industrialised and in developing countries in the region. This paper summarises the lessons learned through the project and presents the recommendations, tools and instruments available for adaptation and use by CP promoters, financial institutions and business schools.     

Pricing based adaptive scheduling method for bandwidth allocation

In this paper we present a packet scheduling method which guarantees bandwidth of the connection and optimizes revenue of the network service provider. A closed form formula for updating the adaptive weights of a packet scheduler is derived from a revenue-based optimization problem. The weight updating procedure is fast and independent on the assumption of the connections’ statistical behavior. The features of the algorithm are simulated and analyzed with and without a call admission control (CAC) mechanism. We also show in context with the CAC procedure a mechanism for guaranteeing a specified mean bandwidth for different service classes.