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.

Työhön liittyvä kilpailu 18 - 65-vuotiaiden pyhtääläisten kuvaamana

Tutkimuksen kohteena olivat Pyhtään työikäisten asukkaiden näkemykset ja kokemukset työssä esiintyvästä kilpailusta Tutkimusongelma oli työhön liittyvän kilpailun ilmiön hahmottaminen. Tutkimuksen tarkoitus oli valottaa työhön liittyvän kilpailun moninaisuutta antaen esimerkkejä sen eri muodoista, esittäen ajatuksia uusien tulkintojen tekemiselle ja herättäen ideoita kilpailun eri muotojen soveltamiselle työn ja työilmapiirin tutkimuksissa. Tavoitteena oli tutkia haastatteluissa esiintyviä tapoja käsittää työhön liittyvä kilpailu ja sitä, missä määrin eri ammateissa kuvattiin sosiaalista kilpailua verrattuna välineelliseen kilpailuun. Työyhteisöön samastumista tarkasteltiin kilpailun ja koetun oikeudenmukaisuuden näkökulmista. Työn arvostusta käsiteltiin tarkastellen haastateltujen käsitystä ammattinsa yleisestä arvostuksesta sekä haastateltujen omia arvioita ammatistaan, sekä millä tavalla ammattirooli nousi esiin haastateltujen itsen kuvauksissa. Työpaikan ihmissuhteita ja valtaa tarkasteltiin kohdistamalla huomio työtovereiden kanssa toimeen tulemiseen ja työpaikan ihmissuhteiden aiheuttamaan stressiin sekä haastateltujen työssään kokeman oman vaikutusvallan, tasavertaisuuden, epäreiluuden, arvostuksen ja kilpailun määrään. Selvitettiin myös miten vallankäyttöä ja kiusaamista kuvattiin ja millä tavalla vallankäytön ja kiusaamisen katsottiin edesauttavan tavoitteiden saavuttamisessa. Lopuksi tarkastelun kohteina olivat ongelmien käsittely, työssä viihtyminen ja viihtymiseen vaikuttavat seikat. Aineisto kerättiin Pyhtäällä kesällä 2007. Vastaajia oli yhteensä 245 ja vastausprosentti oli 50. Tutkimuksessa mukana olivat kalkki työilmapiiriä ja työpaikan ihmissuhteita koskeviin kysymyksiin vastanneet haastatellut (N = 167). Suurimmaksi osaksi tutkimus oli kuvailevaa, mutta siinä oli myös kvantitatiivista kysymyksenasettelua. Tutkimuksessa käytettiin sekä kvalitatiivisia että kvantitatiivisia analyysimenetelmiä. Puolistrukturoiduissa yksilöhaastatteluissa hyödynnettiin tulkitsevaa fenomenologista analyysia. Kirjattuja avovastauksia tutkittiin luokittavalla ja tulkitsevalla sisällönanalyysilla. Lisäksi laskettiin tilastollisia merkitsevyyksiä Työpaikalla esiintyvä kilpailu nähtiin haastateltujen selonteoissa hyvin moninaisena, sekä myönteisenä että haitallisena. Siihen ymmärrettiin kuuluvan niin resursseihin, työtehtäviin, tuloksiin ja palkkioihin liittyvää välineellistä kilpailua, kuin ihmisten välistä sosiaalista valtataisteluakin. Suhteessa välineelliseen kilpailuun sosiaalista kilpailua kuvattiin eniten hoiva- ja sosiaalialan ammateissa. Suhteessa sosiaaliseen kilpailuun välineellistä kilpailua kuvasivat eniten yrittäjät Vastausten perusteella suun kilpailun määrä korreloi työpaikan ihmissuhteiden aiheuttamaan stressiin, mutta vain silloin, kun kokemus työpaikan oikeudenmukaisuudesta oli matala. Kilpailun eri muotojen (kilpailu omien tavoitteiden saavuttamisesta vs. kilpailu organisaation tavoitteiden saavuttamisesta) väliset yhteydet työyhteisöön samastumiseen eivät aineistossa olleet tilastollisesti merkitseviä. Haastatellun arvio oman ammattinsa arvostuksesta ei myöskään ennustanut haastatellun todennäköisyyttä esittää itsensä ammattikuntansa edustajana avoimen itsen kuvauksen tilanteessa. Koettu oikeudenmukaisuus kuitenkin korreloi työyhteisöön samastumiseen. Mitä oikeudenmukaisempana haastatellut työpaikkaansa pitivät, sitä tärkeämmäksi samastumiskohteeksi he sen tyypillisesti arvioivat. Myös työssä viihtymisen ja työpaikan koetun oikeudenmukaisuuden välinen korrelaatio oli aineistossa voimakas. Lisäksi silloin, kun kokemus oikeudenmukaisuudesta oli matalalla tasolla, oli myös työpaikan ihmissuhteiden aiheuttama stressi yhteydessä vähäiseen työssä viihtymiseen. Tärkeimmät läheet tutkimuksessa olivat: Turner. John C 1975. Social comparison and social identity. Some prospects for intergroup behaviour. European Journal of Social Psychology, 5(1), 5-34. Haslam, S. Alexander 2004. Psychology in organizalions. The social identity approach Second Edition. London: SAGE Publications. Tyler, Tom - Blader. Steven 2000. Cooperation in Groups: Procedural Justice, Social Identity, and Behavioural Engagement. Essays in Social Psychology. Philadelphia: Psychology Press / Taylor & Francis Group. Kantolahti, T. - Tikander, T. 2010. Puheenvuoroja työn kuormittavuudesta. Sosiaali- ja terveysministeriön selvityksiä 2010:17

Hierarchies of circuit classes that are closed under complement

We examine three hierarchies of circuit classes and show they are closed under complementation. (1) The class of languages recognized by a family of polynomial size skew circuits with width O(w), are closed under complement. (2) The class of languages recognized by family of polynomial size circuits with width O(w) and polynomial tree-size, are closed under complement. (3) The class of languages recognized by a family of polynomial size, O(log(n)) depth, bounded AND fan-in with OR fan-in f (f⩾log(n)) circuits are closed under complement. These improve upon the results of (i) Immerman (1988) and Szelepcsenyi (1988), who show that 𝒩L𝒪𝒢 is closed under complementation, and (ii) Borodin et al. (1989), who show that L𝒪𝒢𝒞ℱL is closed under complement

Fast edge splitting and Edmonds' arborescence construction for unweighted graphs

Given an unweighted undirected or directed graph with n vertices, m edges and edge connectivity c, we present a new deterministic algorithm for edge splitting. Our algorithm splits-off any specified subset S of vertices satisfying standard conditions (even degree for the undirected case and in-degree ≥ out-degree for the directed case) while maintaining connectivity c for vertices outside S in Õ(m+nc2) time for an undirected graph and Õ(mc) time for a directed graph. This improves the current best deterministic time bounds due to Gabow [8], who splits-off a single vertex in Õ(nc2+m) time for an undirected graph and Õ(mc) time for a directed graph. Further, for appropriate ranges of n, c, |S| it improves the current best randomized bounds due to Benczúr and Karger [2], who split-off a single vertex in an undirected graph in Õ(n2) Monte Carlo time. We give two applications of our edge splitting algorithms. Our first application is a sub-quadratic (in n) algorithm to construct Edmonds' arborescences. A classical result of Edmonds [5] shows that an unweighted directed graph with c edge-disjoint paths from any particular vertex r to every other vertex has exactly c edge-disjoint arborescences rooted at r. For a c edge connected unweighted undirected graph, the same theorem holds on the digraph obtained by replacing each undirected edge by two directed edges, one in each direction. The current fastest construction of these arborescences by Gabow [7] takes Õ(n2c2) time. Our algorithm takes Õ(nc3+m) time for the undirected case and Õ(nc4+mc) time for the directed case. The second application of our splitting algorithm is a new Steiner edge connectivity algorithm for undirected graphs which matches the best known bound of Õ(nc2 + m) time due to Bhalgat et al [3]. Finally, our algorithm can also be viewed as an alternative proof for existential edge splitting theorems due to Lovász [9] and Mader [11].

Zero momentum gluons and the total pp and pbarp cross-sections

We describe a QCD motivated model for total cross-sections which uses the eikonal representation and incorporates QCD mini-jets to drive the rise with energy of the cross-section, while the impact parameter distribution is obtained through the Fourier transform of the transverse momentum distribution of soft gluons emitted in the parton-parton interactions giving rise to mini-jets in the final state. A singular but integral expression for the running coupling constant in the infrared region is part of this model.

Nonstandard, strongly interacting spin one $t \bar t$ resonances

Examining theories with an extended strong interaction sector such as axigluons or flavour universal colorons, we find that the constraints obtained from the current data on $t \bar t$ production at the Tevatron are in the range of $\sim {\cal O}$ TeV and thus competitive with those obtained from the dijet data. We point out that for large axigluon/coloron masses, the limits on the coloron mass may be different than those for the axigluon even for $\cot \xi = 1$. We also compute the expected forward-backward asymmetry for the case of the axigluons which would allow it to be discriminated against the SM as also the colorons. We further find that at the LHC, the signal should be visible in the $t \bar t$ invariant mass spectrum for a wide range of axigluon and coloron masses that are still allowed. We point out how top polarisation may be used to further discriminate the axigluon and coloron case from the SM as well as from each other.

Efficient Algorithms for Computing All Low s-t Edge Connectivities and Related Problems

Given an undirected unweighted graph G = (V, E) and an integer k ≥ 1, we consider the problem of computing the edge connectivities of all those (s, t) vertex pairs, whose edge connectivity is at most k. We present an algorithm with expected running time Õ(m + nk3) for this problem, where |V| = n and |E| = m. Our output is a weighted tree T whose nodes are the sets V1, V2,..., V l of a partition of V, with the property that the edge connectivity in G between any two vertices s ε Vi and t ε Vj, for i ≠ j, is equal to the weight of the lightest edge on the path between Vi and Vj in T. Also, two vertices s and t belong to the same Vi for any i if and only if they have an edge connectivity greater than k. Currently, the best algorithm for this problem needs to compute all-pairs min-cuts in an O(nk) edge graph; this takes Õ(m + n5/2kmin{k1/2, n1/6}) time. Our algorithm is much faster for small values of k; in fact, it is faster whenever k is o(n5/6). Our algorithm yields the useful corollary that in Õ(m + nc3) time, where c is the size of the global min-cut, we can compute the edge connectivities of all those pairs of vertices whose edge connectivity is at most αc for some constant α. We also present an Õ(m + n) Monte Carlo algorithm for the approximate version of this problem. This algorithm is applicable to weighted graphs as well. Our algorithm, with some modifications, also solves another problem called the minimum T-cut problem. Given T ⊆ V of even cardinality, we present an Õ(m + nk3) algorithm to compute a minimum cut that splits T into two odd cardinality components, where k is the size of this cut.

A Kinematic Theory for Planar Hoberman and Other Novel Foldable Mechanisms

In this paper, we present a kinematic theory for Hoberman and other similar foldable linkages. By recognizing that the building blocks of such linkages can be modeled as planar linkages, different classes of possible solutions are systematically obtained including some novel arrangements. Criteria for foldability are arrived by analyzing the algebraic locus of the coupler curve of a PRRP linkage. They help explain generalized Hoberman and other mechanisms reported in the literature. New properties of such mechanisms including the extent of foldability, shape-preservation of the inner and outer profiles, multi-segmented assemblies and heterogeneous circumferential arrangements are derived. The design equations derived here make the conception of even complex planar radially foldable mechanisms systematic and easy. Representative examples are presented to illustrate the usage of the design equations and the kinematic theory.

Simultaneous Geometry Optimization and Material Selection for Truss Structures

In this work, we explore simultaneous design and material selection by posing it as an optimization problem. The underlying principles for our approach are Ashby's material selection procedure and structural optimization. For the simplicity and ease of initial implementation of the general procedure, truss structures under static load are considered in this work in view of maximum stiffness, minimum weight/cost and safety against failure. Along the lines of Ashby's material indices, a new design index is derived for trusses. This helps in choosing the most suitable material for any design of a truss. Using this, both the design space and material database are searched simultaneously using optimization algorithms. The important feature of our approach is that the formulated optimization problem is continuous even though the material selection is an inherently discrete problem.

An Objective Evaluation of Displacement-Amplifying Compliant Mechanisms for Sensor Applications

Displacement-amplifying compliant mechanisms (DaCMs) reported in literature are mostly used for actuator applications. This paper considers them for sensor applications that rely on displacement measurement, and evaluates them objectively. The main goal is to increase the sensitivity under constraints imposed by several secondary requirements and practical constraints. A spring-mass-lever model that effectively captures the addition of a DaCM to a sensor is used in comparing eight DaCMs. We observe that they significantly differ in performance criteria such as geometric advantage, stiffness, natural frequency, mode amplification, factor of safety against failure, cross-axis stiffness, etc., but none excel in all. Thus, a combined figure of merit is proposed using which the most suitable DaCM could be selected for a sensor application. A case-study of a micro machined capacitive accelerometer and another case-study of a vision-based force sensor are included to illustrate the general evaluation and selection procedure of DaCMs with specific applications. Some other insights gained with the analysis presented here were the optimum size-scale for a DaCM, the effect on its natural frequency, limits on its stiffness, and working range of the sensor.

Topology Optimization of Micromachined Structures with Surface Micromachining Manufacturing Constraints

Topology optimization methods have been shown to have extensive application in the design of microsystems. However, their utility in practical situations is restricted to predominantly planar configurations due to the limitations of most microfabrication techniques in realizing structures with arbitrary topologies in the direction perpendicular to the substrate. This study addresses the problem of synthesizing optimal topologies in the out-of-plane direction while obeying the constraints imposed by surface micromachining. A new formulation that achieves this by defining a design space that implicitly obeys the manufacturing constraints with a continuous design parameterization is presented in this paper. This is in contrast to including manufacturing cost in the objective function or constraints. The resulting solutions of the new formulation obtained with gradient-based optimization directly provide the photolithographic mask layouts. Two examples that illustrate the approach for the case of stiff structures are included.

Topology Optimization of Electrostatically Actuated Micromechanical Structures with Accurate Electrostatic Modeling of the Interpolated Material Model

In this paper, we present a novel formulation for performing topology optimization of electrostatically actuated constrained elastic structures. We propose a new electrostatic-elastic formulation that uses the leaky capacitor model and material interpolation to define the material state at every point of a given design domain continuously between conductor and void states. The new formulation accurately captures the physical behavior when the material in between a conductor and a void is present during the iterative process of topology optimization. The method then uses the optimality criteria method to solve the optimization problem by iteratively pushing the state of the domain towards that of a conductor or a void in the appropriate regions. We present examples to illustrate the ability of the method in creating the stiffest structure under electrostatic force for different boundary conditions.

Amphiphilic poly(meta-phenylene)s: A novel conjugated polysoap; A possible foldamer?

Novel amphiphilic poly(meta-phenylene)s were prepared by an oxidative coupling approach. These polymers were synthesized to shed light on their solution properties with special emphasis on aggregation and folding behavior. The polymers were characterized by NMR spectroscopy and molecular weights were determined by Gel Permeation Chromatography using Universal calibration. Literature studies revealed that the backbone of these PMPs can be helical moreover, the light emitting properties of this conjugated polymer can be used as a handle to study the possible aggregation or self-assembling behavior. In this report we show the synthesis, characterization and preliminary aggregation properties that points out that one of the synthesized PMP behave as a polysoap.

Atomic layer deposition of ZrO2 thin films: Study of growth kinetics and dielectric behaviour

Thin films of ZrO2 have been deposited by ALD on Si(100) and SIMOX using two different metalorganic complexes of Zr as precursors. These films are characterized by X-ray diffraction, transmission and scanning electron microscopies, infrared spectroscopy, and electrical measurements. These show that amorphous ZrO2 films of high dielectric quality may be grown on Si(100) starting about 400degreesC. As the growth temperature is raised, the films become crystalline, the phase formed and the microstructure depending on precursor molecular structure. The phase of ZrO2 formed depends also on the relative duration of the precursor and oxygen pulses. XPS and IR spectroscopy show that films grown at low temperatures contain chemically unbound carbon, its extent depending on the precursor. C-V measurements show that films grown on Si(100) have low interface state density, low leakage current, a hysteresis width of only 10-250 mV and a dielectric constant of similar to16-25.