The hard-particle model for a dense granular flow down an inclined plane

Perfectly hard particles are those which experience an infinite repulsive force when they overlap, and no force when they do not overlap. In the hard-particle model, the only static state is the isostatic state where the forces between particles are statically determinate. In the flowing state, the interactions between particles are instantaneous because the time of contact approaches zero in the limit of infinite particle stiffness. Here, we discuss the development of a hard particle model for a realistic granular flow down an inclined plane, and examine its utility for predicting the salient features both qualitatively and quantitatively. We first discuss Discrete Element simulations, that even very dense flows of sand or glass beads with volume fraction between 0.5 and 0.58 are in the rapid flow regime, due to the very high particle stiffness. An important length scale in the shear flow of inelastic particles is the `conduction length' delta = (d/(1 - e(2))(1/2)), where d is the particle diameter and e is the coefficient of restitution. When the macroscopic scale h (height of the flowing layer) is larger than the conduction length, the rates of shear production and inelastic dissipation are nearly equal in the bulk of the flow, while the rate of conduction of energy is O((delta/h)(2)) smaller than the rate of dissipation of energy. Energy conduction is important in boundary layers of thickness delta at the top and bottom. The flow in the boundary layer at the top and bottom is examined using asymptotic analysis. We derive an exact relationship showing that the a boundary layer solution exists only if the volume fraction in the bulk decreases as the angle of inclination is increased. In the opposite case, where the volume fraction increases as the angle of inclination is increased, there is no boundary layer solution. The boundary layer theory also provides us with a way of understanding the cessation of flow when at a given angle of inclination when the height of the layer is decreased below a value h(stop), which is a function of the angle of inclination. There is dissipation of energy due to particle collisions in the flow as well as due to particle collisions with the base, and the fraction of energy dissipation in the base increases as the thickness decreases. When the shear production in the flow cannot compensate for the additional energy drawn out of the flow due to the wall collisions, the temperature decreases to zero and the flow stops. Scaling relations can be derived for h(stop) as a function of angle of inclination.

The Far Eastern Question at the Washington Conference (1921-1922) with an outline of its implications for internal politics in China

This dissertation is a narrative account of the negotiations concerning the question of the Far East and the Shandong issue at the Washington Conference, leading to treaties, agreements and resolutions. In this dissertation, a certain stress is laid on the interaction between the Conference and the internal situation in China, particularly concerning the question of the implications of the Conference for Cabinet politics in Peking. Through the narrative account of the Conference, the general aim is an attempt to reassess the achievements of the Washington Conference. Too often the Washington Conference has been viewed negatively. The political aim behind the legal framework was to open the door to China as a sovereign State member of the international community whose territorial integrity was internationally recognized, despite its chaotic internal situation. It is undeniable that the Washington Conference opened a new chapter in modern Chinese history. The violations of the agreements concerning China that occurred in the 1930s should not lead to the belief that these agreements were of no value. Peace may not be lasting and evolves according to circumstances; agreements are transitory, and new situations need new arrangements. This dissertation tries to demonstrate that the agreements in themselves were not the cause of their failure, but the failure was due to the lack of determination on the part of the Signatories Powers to defend them.

T-type calcium channel:from physiological function to therapeutical targeting – Exploring neuronal development

Tämän tutkimuksen tarkoitus oli tutkia T-tyypin kalsiumkanavan toimintaa ja sen mahdollista roolia neuronaalisten kantasolujen migraatiossa. T-tyypin kalsiumkanavan tehtävän kehittyneissä aivoissa tiedetään olevan elektroenkefalografisten oskillaatioiden tuottaminen. Nämä taas ovat eräiden fysiologisten ja patofysiologisten tapahtumien säätelyssä avainasemassa. Tällaisia tapahtumia ovat uni, muisti, oppiminen ja epileptiset poissaolokohtaukset. Näiden lisäksi T-tyypin kalsiumkanavalla on myös periferaalisia vaikutuksia, mutta tämä tutkielma keskittyy sen neuronaalisiin toimintoihin. Tämän matalan jännitteen säätelemän kanavan toiminta neurogeneesin aikana on vähemmän tutkittua ja tunnettua kuin sen vaikutukset kehittyneissä aivoissa. T-tyypin kalsiumkanavan tiedetään edistävän kantasolujen proliferaatiota ja erilaistumista neurogeneesiksen aikana, mutta vaikutukset niiden migraatioon ovat vähemmän tunnetut. Tämä tutkimus näyttää T-tyypin kalsiumkanavan todennäköisesti osallistuvan neuronaaliseen migraatioon hiiren alkion subventrikkeli alueelta eristetyillä kanta- tai progeniittorisoluilla tehdyissä kokeissa. Selektiiviset T-tyypin kalsiumkanavan antagonistit, etosuksimidi, nikkeli ja skorpionitoksiini, kurtoxin hidastivat migraatiota erilaistuvissa progeniittorisoluissa. Tämä tutkimus koostuu kirjallisuuskatsauksesta ja kokeellisesta osasta. Tämän tutkimuksen toinen tarkoitus oli esitellä vaihtoehtoinen lähestymistapa invasiiviselle kantasoluterapialle, joka vaatii kantasolujen viljelyä ja siirtämistä ihmiseen. Tämä toinen tapa on endogeenisten kantasolujen eiinvasiivinen stimulointi, jolla ne saadaan migratoitumaan kohdekudokseen, erilaistumaan siellä ja tehtävänsä suoritettuaan lopettamaan jakaantumisen. Non-invasiivinen kantasoluterapia on vasta tiensä alussa, ja tarvitsee farmakologista osaamista kehittyäkseen. Joitain onnistuneita ei-invasiivisia hoitoja on jo tehty selkärangan vaurioiden korjaamisessa. Vastaavanlaisia menetelmiä voitaisiin käyttää myös keskushermoston vaurioiden ja neurodegeneratiivisten sairauksien hoidossa. Näiden menetelmien kehittäminen vaatii endogeenisten kantasoluja inhiboivien ja indusoivien mekanismien tuntemista. Yksi tärkeä kantasolujen erilaistumista stimuloiva tekijä on kalsiumioni. Jänniteherkät kalsiumkanavat osallistuvat kaikkiin neurogeneesiksen eri vaiheisiin. T-tyypin kalsiumkanava, joka ekspressoituu suuressa määrin keskushermoston kehityksen alkuvaiheessa ja vähenee neuronaalisen kehityksen edetessä, saattaa olla oleellisessa asemassa progeniittorisolujen ohjaamisessa.

Töhry- vai taidepolitiikkaa? Diskurssiteoreettinen tarkastelu graffitin artikulaatioista suhteessa kaupunkitilaan Helsingissä 1995– 2010

Graffitit ja katutaide vaikuttavat visuaaliseen ympäristöömme ja ovat viime vuosina herättäneet vilkasta keskustelua kaupunkitilan sallitun käytön rajoista. Helsingissä oli vuosina 1998–2008 käynnissä siistiin kaupunkikuvaan tähtäävä Stop töhryille -projekti. Projekti herätti vastustusta ja politisoitui: keskusteluun nousivat graffitien ja töhryjen lisäksi esimerkiksi julkisen tilan arvot, kaupunkitilan estetiikka, nuorten oikeus kaupunkiin ja taiteen rajat. Tässä tutkielmassa tarkastellaan vallankäyttöä kaupunkitilassa graffitien ja katutaiteen ympärillä käydyn keskustelun kautta. Tutkimus keskittyy yhden kaupungin, Helsingin, tarjoamaan esimerkkiin. Tutkimuksen tavoitteena on selvittää millaisia diskursseja graffiteista esitetään, kuinka puhe graffitien ympärillä politisoituu ja miten graffitin diskurssit liittyvät julkiseen tilaan. Kaupunki ja julkinen tila ymmärretään tässä tutkimuksessa Henri Lefebvren ja Doreen Masseyn teorioiden pohjalta sosiaalisena tuotteena ja siten poliittisena käsitteenä. Tutkimuksen pääasiallisen aineiston muodostavat Helsingin Sanomien aihepiiriä käsittelevät lehtitekstit vuosilta 1995–2010, analyysin apuna käytetään lisäksi kaupungin omia asiakirjoja, Internet-sivuja ja valokuvia. Tutkimustehtävää lähestytään Ernesto Laclaun ja Chantal Mouffen diskurssiteorian kautta. Laclau ja Mouffe ymmärtävät sosiaaliset merkitykset aina diskursiivisesti rakentuneiksi ja selittävät diskurssien muutosta poliittisen ontologian avulla. Tässä tutkimuksessa diskurssiteorian tarjoamista analyyttisista käsitteistä tärkeiksi nousevat diskurssi, tyhjät ja kelluvat merkitsijät, hegemonia ja sosiaalinen antagonismi. Aineiston perusteella näyttää siltä, että graffitien ympärillä Helsingissä vuosina 1995–2010 käyty keskustelu kiertyy karkeasti arvioiden kahden diskurssin ympärille ja jakaantuu kolmeen vaiheeseen. Kaksi läpi koko aineiston kulkevaa diskurssia, joiden osana graffitit artikuloidaan, nimetään tässä tutkimuksessa ”töhryn” ja ”taiteen” diskursseiksi. Keskustelun ensimmäisessä vaiheessa (1995–2000) Helsingin kaupunkikuvan töhriminen näyttäytyy vakavana ongelmana, joka vaatii hallinnolta ja poliitikoilta toimenpiteitä: graffitien torjumiseen tähtäävä Stop töhryille -projekti aloitetaan vuonna 1998. Keskustelun toisessa vaiheessa (2000–2007) Stop töhryille -projekti ja graffitit politisoituvat: projektista ja graffitien luvallisista tekopaikoista keskustellaan valtuustossa lähes vuosittain. Näkyville nousee antagonistinen jakolinja töhryn ja kaupunkitaiteen välillä: julkisuudessa esitetty kritiikki siirtyy töhritystä kaupunkikuvasta kohti Stop töhryille -projektia. Vuosi 2008, jolloin Stop töhryille -projekti loppuu, näyttäytyy dislokaation hetkenä. Kaupunginvaltuustossa graffitit artikuloidaan taiteena ja kaupunkikulttuurina; graffiteille löytyy nyt myös luvallista tilaa kaupungista. Diskurssiteorian käsittein voidaan ajatella töhryjen ja taiteen diskurssin taistelevan graffitikeskustelun hegemonisesta asemasta. Julkinen tila on molemmille diskursseille tärkeä, sillä kamppaillessaan graffitien määritelmästä ne kamppailevat jatkuvasti myös julkisesta tilasta ja sen määrittelemisen vallasta kaupungissa. Julkinen tila on paitsi materiaalista myös jatkuvasti debatissa syntyvää: sosiaalinen tuote. Graffitikeskustelussa syntyvä sosiaalinen antagonismi on tärkeä myös siinä mielessä, että sen kautta esiin nousevat esiin erilaiset näkemykset paitsi julkisesta tilasta myös taiteesta ja kulttuurista kaupungissa.

Ultimate Strength of RC Wall Panels with Openings

Test results of 12 reinforced concrete (RC) wall panels with openings are presented. The panels have been subjected to in-plane vertical loads applied at an eccentricity to represent possible accidental eccentricity that occurs in practice due to constructional imperfections. The 12 specimens consist of two identical groups of six panels each. One group of panels is tested in one-way in-plane action (i.e., supported at top and bottom edges against lateral displacement). The second group of panels is tested in two-way in-plane action (i.e., supported on all the four edges against lateral displacement). Openings in the panels represent typical door and window openings. Cracking loads, ultimate loads, crack patterns, and lateral deflections of the panels are studied. Empirical methods have been developed for the prediction of ultimate load. Also, lateral deflections, cracking loads, and ultimate loads of identical loads tested under one-way and two-way action are compared.

NK-and T-cell function in chronic myeloid leukemia patients treated with interferon-? monotherapy

Chronic myeloid leukemia (CML) is one of the most studied human malignancies. It is caused by an autonomously active tyrosine kinase BCR-ABL, which is a result from a translocation between chromosomes 9 and 22 in the hematopoietic stem cell. As an outcome, a Philadelphia (Ph) chromosome is formed. BCR-ABL causes disturbed cell proliferation among other things. Although targeted tyrosine kinase inhibitor therapy has been developed in the beginning of the millenium and the survival rate has increased significantly, it is still not known why some patients benefit more from the treatment than others. Furthermore, the therapy is not considered to be curative. Before the era of tyrosine kinase inhibitors, the first-line treatment for CML was interferon-? (IFN-?). However, only a small proportion of patients benefitted from the treatment. Of these patients, a few were able to discontinue the treatment without renewal of the disease. The mechanism of IFN-? is not completely understood, but it is believed that differences in the immune system can be one of the reasons why some patients have better therapy response. Kreutzman, Rohon et al. have recently discovered that patients who have been able to stop IFN-? treatment have an increased number of NK- and T-cells. They also have a unique clonal T-cell population and more cytotoxic CD8+ T-cells and less CD4+ T-cells. The aim of this master’s thesis was to study the function of T- and NK-cells in IFN-? treated patients. Although it was shown earlier that IFN-? treated patients have increased NK-cell count, the function of these cells was unknown. Therefore, we have now investigated the killing potential of patients’ NK-cells, their activation status and cell surface antigen expression. In addition, we have also studied the activation status of patients’ T-cells and their cytotoxic properties. We observed that NK-cells from patients treated with IFN-? are unable to kill leukemic cells (K562) than NK-cells from healthy controls. In addition, patients on IFN-? treatment have more active T-cells and their NK-cells have an undifferentiated immunoregulatory phenotype. Patients that have been able to stop the treatment have anergic T-and NK-cells. As a conclusion our results suggest that IFN-? therapy induces increased NK-cell count, NK-cell immunoregulatory functions and more active T-cells. After stopping IFN-? therapy, NK- and T-cells from CML patients restore anergy typical for CML.

Continuity of plastic strain rate in stress relaxation tests

Stress relaxation testing is often utilised for determining whether athermal straining contributes to plastic flow; if plastic strain rate is continuous across the transition from tension to relaxation then plastic strain is fully thermally activated. This method was applied to an aged type 316 stainless steel tested in the temperature range 973–1123 K and to a high purity Al in the recrystallised annealed condition tested in the temperature range 274–417 K. The results indicated that plastic strain is thermally activated in these materials at these corresponding test temperatures. For Al, because of its high strain rate sensitivity, it was necessary to adopt a back extrapolation procedure to correct for the finite period that the crosshead requires to decelerate from the constant speed during tension to a dead stop for stress relaxation.

The function and regulation of the U11-48K protein in U12-dependent splicing

The removal of noncoding sequences, or introns, from the eukaryotic messenger RNA precursors is catalyzed by a ribonucleoprotein complex known as the spliceosome. In most eukaryotes, two distinct classes of introns exist, each removed by a specific type of spliceosome. The major, U2-type introns account for over 99 % of all introns, and are almost ubiquitous. The minor, U12-type introns are found in most but not all eukaryotes, and reside in conserved locations in a specific set of genes. Due to their slow excision rates, the U12-type introns are expected to be involved in the regulation of the genes containing them by inhibiting the maturation of the messenger RNAs. However, little information is currently available on how the activity of the U12-dependent spliceosome itself is regulated. The levels of many known splicing factors are regulated through unproductive alternative splicing events, which lead to inclusion of premature STOP codons, targeting the transcripts for destruction by the nonsense-mediated decay pathway. These alternative splice sites are typically found in highly conserved sequence elements, which also contain binding sites for factors regulating the activation of the splice sites. Often, the activation is achieved by binding of products of the gene in question, resulting in negative feedback loops. In this study, I show that U11-48K, a protein factor specific to the minor spliceosome, specifically recognizes the U12-type 5' splice site sequence, and is essential for proper function of the minor spliceosome. Furthermore, the expression of U11-48K is regulated through a feedback mechanism, which functions through conserved sequence elements that activate alternative splicing and nonsense-mediated decay. This mechanism is conserved from plants to animals, highlighting both the importance and early origin of this mechanism in regulating splicing factors. I also show that the feedback regulation of U11-48K is counteracted by a component of the major spliceosome, the U1 small nuclear ribonucleoprotein particle, as well as members of the hnRNP F/H protein family. These results thus suggest that the feedback mechanism is finely tuned by multiple factors to achieve precise control of the activity of the U12-dependent spliceosome.

Structural proteins of mycobacteriophage I3: cloning, expression and sequence analysis of a gene encoding a 70-kDa structural protein

The structural proteins of mycobacteriophage I3 have been analysed by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis (SDS-PAGE), radioiodination and immunoblotting. Based on their abundance the 34- and 70-kDa bands appeared to represent the major structural proteins. Successful cloning and expression of the 70-kDa protein-encoding gene of phage I3 in Escherichia coli and its complete nucleotide sequence determination have been accomplished, A second (partial) open reading frame following the stop codon for the 70-kDa protein was also identified within the cloned fragment. The deduced amino-acid sequence of the 70-kDa protein and the codon usage patterns indicated the preponderance of codons, as predicted from the high G+C content of the genomic DNA of phage I3.

Wave dispersion in a cellular composite with modulated microstructure

In this paper we report a modeling technique and analysis of wave dispersion in a cellular composite laminate with spatially modulated microstructure, which can be modeled by parameterization and homogenization in an appropriate length scale. Higher order beam theory is applied and the system of wave equations are derived. Homogenization of these equations are carried out in the scale of wavelength and frequency of the individual wave modes. Smaller scale scattering below the order of cell size are filtered out in the present approach. The longitudinal dispersion relations for different values of a modulation parameter are analyzed which indicates the existence of stop and pass band patterns. Dispersion relations for flexural-shear case are also analyzed which indicates a tendency toward forming the stop and pass bands for increasing values of a shear stiffness modulation parameter. The effect the phase angle (θ) of the incident wave indicates the existence more number of alternative stop bands and pass bands for θ = 45°.

Higgs Working Group Summary Report

Report of the Higgs working group for the Workshop "Physics at TeV Colliders", Les Houches, France 8-18 June 1999. It contains 6 separate sections: 1. Measuring Higgs boson couplings at the LHC. 2. Higgs boson production at hadron colliders at NLO. 3. Signatures of Heavy Charged Higgs Bosons at the LHC. 4. Light stop effects and Higgs boson searches at the LHC. 5. Double Higgs production at TeV Colliders in the MSSM. 6. Programs and Tools for Higgs Bosons.

Open source drug discovery- A new paradigm of collaborative research in tuberculosis drug development

It is being realized that the traditional closed-door and market driven approaches for drug discovery may not be the best suited model for the diseases of the developing world such as tuberculosis and malaria, because most patients suffering from these diseases have poor paying capacity. To ensure that new drugs are created for patients suffering from these diseases, it is necessary to formulate an alternate paradigm of drug discovery process. The current model constrained by limitations for collaboration and for sharing of resources with confidentiality hampers the opportunities for bringing expertise from diverse fields. These limitations hinder the possibilities of lowering the cost of drug discovery. The Open Source Drug Discovery project initiated by Council of Scientific and Industrial Research, India has adopted an open source model to power wide participation across geographical borders. Open Source Drug Discovery emphasizes integrative science through collaboration, open-sharing, taking up multi-faceted approaches and accruing benefits from advances on different fronts of new drug discovery. Because the open source model is based on community participation, it has the potential to self-sustain continuous development by generating a storehouse of alternatives towards continued pursuit for new drug discovery. Since the inventions are community generated, the new chemical entities developed by Open Source Drug Discovery will be taken up for clinical trial in a non-exclusive manner by participation of multiple companies with majority funding from Open Source Drug Discovery. This will ensure availability of drugs through a lower cost community driven drug discovery process for diseases afflicting people with poor paying capacity. Hopefully what LINUX the World Wide Web have done for the information technology, Open Source Drug Discovery will do for drug discovery. (C) 2011 Elsevier Ltd. All rights reserved.

Pickup and delivery problem using metaheuristics techniques

Dial-a-ride problem (DARP) is an optimization problem which deals with the minimization of the cost of the provided service where the customers are provided a door-to-door service based on their requests. This optimization model presented in earlier studies, is considered in this study. Due to the non-linear nature of the objective function the traditional optimization methods are plagued with the problem of converging to a local minima. To overcome this pitfall we use metaheuristics namely Simulated Annealing (SA), Particle Swarm Optimization (PSO), Genetic Algorithm (GA) and Artificial Immune System (AIS). From the results obtained, we conclude that Artificial Immune System method effectively tackles this optimization problem by providing us with optimal solutions. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.

Aquatic Ecosystems: Conservation, Restoration and Management

Aquatic Ecosystems perform numerous valuable environmental functions. They recycle nutrients, purify water, recharge ground water, augment and maintain stream flow, and provide habitat for a wide variety of flora and fauna and recreation for people. A rapid population increase accompanied by unplanned developmental works has led to the pollution of surface waters due to residential, agricultural, commercial and industrial wastes/effluents and decline in the number of water bodies. Increased demands for drainage of wetlands have been accommodated by channelisation, resulting in further loss of stream habitat, which has led to aquatic organisms becoming extinct or imperiled in increasing numbers and to the impairment of many beneficial uses of water, including drinking, swimming and fishing. Various anthropogenic activities have altered the physical, chemical and biological processes within aquatic ecosystems. An integrated and accelerated effort toward environmental restoration and preservation is needed to stop further degradation of these fragile ecosystems. Failure to restore these ecosystems will result in sharply increased environmental costs later, in the extinction of species or ecosystem types, and in permanent ecological damage.

Effect of base dissipation on the granular flow down an inclined plane

The effect of base dissipation on the granular flow down an inclined plane is examined by altering the coefficient of restitution between the moving and base particles in discrete element (DE) simulations. The interaction laws between two moving particles are kept fixed, and the coefficient of restitution (damping constant in the DE simulations) between the base and moving particles are altered to reduce dissipation, and inject energy from the base. The energy injection does result in an increase in the strain rate by up to an order of magnitude, and the temperature by up to two orders of magnitude at the base. However, the volume fraction, strain rate and temperature profiles in the bulk (above about 15 particle diameters from the base) are altered very little by the energy injection at the base. We also examine the variation of h(stop), the minimum height at the cessation of flow, with energy injection from the base. It is found that at a fixed angle of inclination, h(stop) decreases as the energy dissipation at the base decreases.