Relativistic diffusion processes and random walk models

The nonrelativistic standard model for a continuous, one-parameter diffusion process in position space is the Wiener process. As well-known, the Gaussian transition probability density function (PDF) of this process is in conflict with special relativity, as it permits particles to propagate faster than the speed of light. A frequently considered alternative is provided by the telegraph equation, whose solutions avoid superluminal propagation speeds but suffer from singular (non-continuous) diffusion fronts on the light cone, which are unlikely to exist for massive particles. It is therefore advisable to explore other alternatives as well. In this paper, a generalized Wiener process is proposed that is continuous, avoids superluminal propagation, and reduces to the standard Wiener process in the non-relativistic limit. The corresponding relativistic diffusion propagator is obtained directly from the nonrelativistic Wiener propagator, by rewriting the latter in terms of an integral over actions. The resulting relativistic process is non-Markovian, in accordance with the known fact that nontrivial continuous, relativistic Markov processes in position space cannot exist. Hence, the proposed process defines a consistent relativistic diffusion model for massive particles and provides a viable alternative to the solutions of the telegraph equation.Comment: v3: final, shortened version to appear in Phys. Rev.

Controlled surface-associated delivery of genes and oligonucleotides

A system and methods for controlled gene delivery comprising condensed nucleic acids complexed with polylinkers, wherein the complexes are covalently and/or noncovalently bound to the surface of a substrate capable of supporting cell adhesion. The gene delivery system achieves temporal and spatial control of nucleic acid delivery to a target cell or cells through control of complex density on the surface of the support substrate, and reversibility of the attachment of the polylinker to the support substrate. The system and method of the invention can be used to create spatial patterns of gene expression, and in tissue engineering, high throughput screening, and gene therapy applications. What is claimed is: 1. A method for increasing transgene expression, comprising making a controlled nucleic acid delivery system, said system comprising forming nucleic acid polylinker complexes capable of being delivered to cells cultured on a support substrate, wherein said complexes are formed prior to being covalently or non-covalently immobilized to the surface of a support substrate, and wherein said method comprises: a) contacting a nucleic acid with a polylinker to form a nucleic acid-polylinker complex, said complex being formed prior to attachment to a support substrate; and b) immobilizing the nucleic acid-polylinker complex to a support substrate; and wherein said cells are added to the support substrate after immobilization of the nucleic acid-polylinker complex to the support substrate. 2. The method of claim 1, further comprising modification of the support substrate with serum prior to addition of the nucleic acid-polylinker complex, and wherein said modification allows for an increase in transgene expression. 3. The method of claim 1, wherein the extent of transgene expression is dependent upon substrate modification and complex formation. 4. The method of claim 1, wherein said nucleic acid polylinker complexes are polyplexes or lipoplexes. 5. The method of claim 1, wherein said support substrate is polystyrene, gold, hyaluronic acid collagen hydrogels or polylactide-co-glycolide (PLG). 6. The method of claim 2, wherein said substrate modification is made by treatment with serum. 7. The method of claim 1, wherein delivery of the nucleic acid-polylinker complexes to cells occurs from a polystyrene surface treated with serum, and wherein said delivery results in similar or greater percentage of transfected cells relative to bolus delivery. 8. The method of claim 1, said method further comprising release of the nucleic acid from the nucleic acid-polylinker complexes, wherein said release is maximized when the support substrate is treated with serum. 9. A method for increasing transgene expression, comprising making a controlled nucleic acid delivery system, said system comprising forming nucleic acid polylinker complexes capable of being delivered to cells cultured on a support substrate, wherein said complexes are covalently or non-covalently immobilized to the surface of a support substrate, and wherein said method comprises: a) contacting a nucleic acid with a polylinker to form a nucleic acid-polylinker complex; b) immobilizing the nucleic acid-polylinker complex to a support substrate; and c) adding cells to the support substrate after immobilization of the nucleic acid-polylinker complex to the support substrate, wherein the release of nucleic acid from the nucleic acid-polylinker complexes is further enhanced when the support substrate containing the complexes is treated with serum or is incubated in conditioned medium. 10. The method of claim 2, wherein the delivery of the nucleic acid-polylinker complexes to cells from a serum-modified support substrate results in higher cellular association of the nucleic acid-polylinker complexes with the support substrate. 11. A method for increasing transgene expression, comprising the steps of: a) making a controlled nucleic acid delivery system by contacting a nucleic acid with a polylinker to form a nucleic acid-polylinker complex, wherein said complex is formed prior to addition to a support substrate; b) immobilizing the nucleic acid-polylinker complex to a support substrate; wherein said immobilizing is accomplished by covalent or non-covalent means, and c) adding the cells into which transgene expression is desired to the support substrate after immobilization of the nucleic acid-polylinker complex to the support substrate. 12. The method of claim 11, wherein said support substrate comprises a biodegradable or non-biodegradable material. 13. The method of either one of claim 1 or 11, wherein said complexes are formed prior to attachment to the solid support substrate. 14. The method of claim 12, wherein said biodegradable material is a hydrogel and said non-biodegradable material is polystyrene or gold. 15. The method of claim 12, wherein said hydrogel comprises a mixture of hyaluronic acid and collagen. 16. A method for increasing transgene expression, wherein said method promotes transfection of primary cells, comprising the steps of: a) making a controlled nucleic acid delivery system by contacting a nucleic acid with a polylinker to form a nucleic acid-polylinker complex; b) immobilizing the nucleic acid-polylinker complex to a support substrate; wherein said immobilizing is accomplished by covalent or non-covalent means, and c) adding the cells into which transgene expression is desired to the support substrate after immobilization of the nucleic acid-polylinker complex to the support substrate, wherein the biodegradable material is a hydrogel and the non-biodegradable material is polystyrene or gold, and wherein the hvdrogel comprises a mixture of hyaluronic acid and collagen. 17. The method of either one of claim 1 or 11, wherein said nucleic acid polylinker complexes are immobilized to the support substrate using biotin and avidin, or an avidin derivative, or by non-specific adsorption. 18. The method of claim 17, wherein said avidin derivative is streptavidin or neutravidin. 19. The method of any one of claim 11–15, wherein the method further comprises controlling the size of the nucleic acid polylinker complex by regulating the salt content during complex formation. 20. The method of claim 19, wherein controlling the size of said complex formation is accomplished by the presence or absence of salt during the formation of the complexes, wherein the forming of large diameter complexes in the presence of salt results in increased transgene expression, and wherein the forming of small diameter complexes in the absence of salt results in a greater percentage of cells being transfected. 21. The method of claim 19, wherein the salt is sodium chloride. 22. A method for increasing transgene expression, comprising the steps of: a) making a controlled nucleic acid delivery system by contacting a nucleic acid with a polylinker to form a nucleic acid-polylinker complex; b) immobilizing the nucleic acid-polylinker complex to a support substrate; wherein said immobilizing is accomplished by covalent or non-covalent means, and c) adding the cells into which transgene expression is desired to the support substrate after immobilization of the nucleic acid-polylinker complex to the support substrate, wherein said method further comprises release of the nucleic acid from the substrate, wherein the release is optimized by using conditioned medium. 23. The method of claim 11, wherein said method further comprises biotinylation of said complex to enhance release of said complex from said substrate. 24. The method of either of claim 1 or 11, wherein the nucleic acid is DNA, RNA or an oligonucleotide. 25. The method of claim 24, wherein said oligonucleotide is an antisense oligonucleotide or a catalytic RNA capable of interfering with the expression of a gene. 26. The controlled nucleic acid delivery system of either of claim 1 or 11, wherein the polylinker is a cationic polymer, cationic lipid, cationic protein, or cationic peptide

Intramuscular myxoid lipoma in the proximal forearm presenting as an olecranon mass with superficial radial nerve palsy: a case report

<p>Abstract</p> <p>Background</p> <p>Extremity lipomas may occur in any location, including the proximal forearm. We describe a case of a patient with an intramuscular lipoma presenting as an unusual posterior elbow mass.</p> <p>Case presentation</p> <p>We discuss the case of a 57-year-old Caucasian man who presented with a tender, posterior elbow mass initially diagnosed as chronic olecranon bursitis. A minor sensory disturbance in the distribution of the superficial radial nerve was initially thought to be unrelated, but was likely caused by mass effect from the lipoma. No pre-operative advanced imaging was obtained because the diagnosis was felt to have already been made. At the time of surgery, a fatty mass originating in the volar forearm muscles was found to have breached the dorsal forearm fascia and displaced the olecranon bursa. Tissue diagnosis was made by histopathology as a myxoid lipoma with no aggressive features. Post-operative recovery was uneventful.</p> <p>Conclusion</p> <p>We present a case of an unusual elbow mass presenting with symptoms consistent with chronic olecranon bursitis, a relatively common condition. The only unexplained pre-operative finding was the non-specific finding of a transient superficial radial nerve deficit. We remind clinicians to be cautious when diagnosing soft tissue masses in the extremities when unexplained physical findings are present.</p

Correlation between Compact Radio Quasars and Ultra-High Energy Cosmic Rays

Some proposals to account for the highest energy cosmic rays predict that they should point to their sources. We study the five highest energy events (E>10^20 eV) and find they are all aligned with compact, radio-loud quasars. The probability that these alignments are coincidental is 0.005, given the accuracy of the position measurements and the rarity of such sources. The source quasars have redshifts between 0.3 and 2.2. If the correlation pointed out here is confirmed by further data, the primary must be a new hadron or one produced by a novel mechanism.Comment: 8 pages, 3 tables, revtex. with some versions of latex it's necessary to break out the tables and latex them separately using article.sty rather than revtex.st

Distribution of lipids in the grain of wheat (cv Hereward) determined by lipidomic analysis of milling and pearling fractions

Lipidomic analyses of milling and pearling fractions from wheat grain were carried out to determine differences in composition which could relate to the spatial distribution of lipids in the grain. Free fatty acids and triacylglycerols were major components in all fractions, but the relative contents of polar lipids varied, particularly lysophosphatidyl choline and digalactosyldiglyceride, which were enriched in flour fractions. By contrast, minor phospholipids were enriched in bran and offal fractions. The most abundant fatty acids in the analysed acyl lipids were C16:0 and C18:2 and their combinations, including C36:4 and C34:2. Phospholipids and galactolipids have been reported to have beneficial properties for bread making, while free fatty acids and triacylglycerols are considered detrimental. The subtle differences in the compositions of fractions determined in the present study could therefore underpin the production of flour fractions with optimised compositions for different end uses

Causas de Morte em Doentes com Hemofilia: Estudo Retrospectivo de 1979 a 2007, no Serviço de Imunohemoterapia do HSJ

Neurokinin A (NKA) induces bronchoconstriction mediated by tachykinin NK2 receptors in animals and humans, and may be increased in asthma. Because beta(2)-adrenoceptor agonists are the most widely used bronchodilators in asthma, we investigated the effects of the beta(2)-adrenoceptor agonist fenoterol on NK2 receptor messenger RNA (mRNA) and receptor density as well as the functional responses of bovine tracheal smooth muscle to the NK2 receptor agonist [beta-Ala(8)]-NKA(4-10) in vitro, using Northern blot analysis, receptor binding, and organ bath studies. Incubation with fenoterol induced a time- and concentration-dependent upregulation of NK2 receptor mRNA (71% increase after 12 h at 10(-7) M fenoterol), which was abolished by propranolol (a nonselective beta-adrenoceptor agonist) and ICI118551 (a selective beta(2)-adrenoceptor antagonist), but not by CGP20712A (a selective beta(1)-adrenoceptor antagonist), indicating that fenoterol acts via beta(2)-adrenoceptors. These effects were mimicked by forskolin and prostaglandin E-2 (PGE,), both agents that increase cyclic adenosine monophosphate (cAMP), and by the cAMP analogue 8-bromo-cAMP. The upregulation was blocked by cycloheximide, indicating that it requires new protein synthesis, and was accompanied by an increase in both the stability of NK2 receptor mRNA and the rate of NK2 receptor gene transcription. Radioligand binding assay using the selective NK2 receptor antagonist [H-3]SR48968 showed a significant increase in the number of receptor binding sites after 12 h and 18 h, which was accompanied by an increased contractile responsiveness to the NK2 receptor agonist [beta-Ala(8)]-NKA(4-10). Dexamethasone completely prevented the fenoterol-induced increase in NK2 receptor mRNA and in the contractile response. We conclude that beta(2)-adrenoceptor agonists induce upregulation of functional NK2 receptors in airway smooth muscle by increasing cAMP, and that this can be prevented by a corticosteroid. The increased responsiveness could be relevant to asthma control and mortality

Synergies for Improving Oil Palm Production and Forest Conservation in Floodplain Landscapes

Lowland tropical forests are increasingly threatened with conversion to oil palm as global demand and high profit drives crop expansion throughout the world’s tropical regions. Yet, landscapes are not homogeneous and regional constraints dictate land suitability for this crop. We conducted a regional study to investigate spatial and economic components of forest conversion to oil palm within a tropical floodplain in the Lower Kinabatangan, Sabah, Malaysian Borneo. The Kinabatangan ecosystem harbours significant biodiversity with globally threatened species but has suffered forest loss and fragmentation. We mapped the oil palm and forested landscapes (using object-based-image analysis, classification and regression tree analysis and on-screen digitising of high-resolution imagery) and undertook economic modelling. Within the study region (520,269 ha), 250,617 ha is cultivated with oil palm with 77% having high Net-Present-Value (NPV) estimates ($413/ha?yr–$637/ha?yr); but 20.5% is under-producing. In fact 6.3% (15,810 ha) of oil palm is commercially redundant (with negative NPV of $-299/ha?yr-$-65/ha?yr) due to palm mortality from flood inundation. These areas would have been important riparian or flooded forest types. Moreover, 30,173 ha of unprotected forest remain and despite its value for connectivity and biodiversity 64% is allocated for future oil palm. However, we estimate that at minimum 54% of these forests are unsuitable for this crop due to inundation events. If conversion to oil palm occurs, we predict a further 16,207 ha will become commercially redundant. This means that over 32,000 ha of forest within the floodplain would have been converted for little or no financial gain yet with significant cost to the ecosystem. Our findings have globally relevant implications for similar floodplain landscapes undergoing forest transformation to agriculture such as oil palm. Understanding landscape level constraints to this crop, and transferring these into policy and practice, may provide conservation and economic opportunities within these seemingly high opportunity cost landscapes

PhotoAffinity bits : a photoaffinity-based fragment screening platform for efficient identification of protein ligands

Advances in genomic analyses enable the identification of new proteins that are associated with disease. To validate these targets, tool molecules are required to demonstrate that a ligand can have a disease-modifying effect. Currently, as tools are reported for only a fraction of the proteome, platforms for ligand discovery are essential to leverage insights from genomic analyses. Fragment screening offers an efficient approach to explore chemical space, however, it remains challenging to develop techniques that are both sufficiently high-throughput and sensitive. We present a fragment screening platform, termed PhABits (PhotoAffinity Bits), which utilises a library of photoreactive fragments to covalently capture fragment-protein interactions. Hits can be profiled to determine potency and site of crosslinking, and subsequently developed as reporters in a competitive displacement assay to identify novel hit matter. We envision that the PhABits will be widely applicable to novel protein targets, identifying starting points in the development of therapeutic

Long-lived states in synchronized traffic flow. Empirical prompt and dynamical trap model

The present paper proposes a novel interpretation of the widely scattered states (called synchronized traffic) stimulated by Kerner's hypotheses about the existence of a multitude of metastable states in the fundamental diagram. Using single vehicle data collected at the German highway A1, temporal velocity patterns have been analyzed to show a collection of certain fragments with approximately constant velocities and sharp jumps between them. The particular velocity values in these fragments vary in a wide range. In contrast, the flow rate is more or less constant because its fluctuations are mainly due to the discreteness of traffic flow. Subsequently, we develop a model for synchronized traffic that can explain these characteristics. Following previous work (I.A.Lubashevsky, R.Mahnke, Phys. Rev. E v. 62, p. 6082, 2000) the vehicle flow is specified by car density, mean velocity, and additional order parameters $h$ and $a$ that are due to the many-particle effects of the vehicle interaction. The parameter $h$ describes the multilane correlations in the vehicle motion. Together with the car density it determines directly the mean velocity. The parameter $a$, in contrast, controls the evolution of $h$ only. The model assumes that $a$ fluctuates randomly around the value corresponding to the car configuration optimal for lane changing. When it deviates from this value the lane change is depressed for all cars forming a local cluster. Since exactly the overtaking manoeuvres of these cars cause the order parameter $a$ to vary, the evolution of the car arrangement becomes frozen for a certain time. In other words, the evolution equations form certain dynamical traps responsible for the long-time correlations in the synchronized mode.Comment: 16 pages, 10 figures, RevTeX