Comparison of Pedestrian Fundamental Diagram Across Cultures

The relation between speed and density is connected with every self-organization phenomenon of pedestrian dynamics and offers the opportunity to analyze them quantitatively. But even for the simplest systems, like pedestrian streams in corridors, this fundamental relation isn't completely understood. Specifications of this characteristic in guidelines and text books differ considerably reflecting the contradictory database and the controversial discussion documented in the literature. In this contribution it is studied whether cultural influences and length of the corridor can be the causes for these deviations. To reduce as much as possible unintentioned effects, a system is chosen with reduced degrees of freedom and thus the most simple system, namely the movement of pedestrians along a line under closed boundary conditions. It is found that the speed of Indian test persons is less dependent on density than the speed of German test persons. Surprisingly the more unordered behaviour of the Indians is more effective than the ordered behaviour of the Germans. Without any statistical measure one cannot conclude about whether there are differences or not. By hypothesis test it is found quantitatively that these differences exist, suggesting cultural differences in the fundamental diagram of pedestrians.Comment: 12 pages, 7 figure

Novel tools for identification of oncogenic driver mutations

Genetic alterations contribute to the development and pathogenesis of several human cancers. These mutations accumulate in a cancer tissue over the course of time due to the instability of the cancer genome. Large-scale sequencing efforts have enabled identification of an abundance of these somatic mutations, and the amount of data is constantly increasing due to the improved accessibility of next-generation sequencing technologies. From this multitude of cancer-associated somatic mutations, a large majority are predicted to be inconsequential “passenger” mutations, (i.e., mutations which do not confer a selective growth advantage to the cancer cells); and only a handful have been validated as “driver” mutations (i.e., mutations playing a critical role in the development or maintenance of cancer). These driver mutations also function as predictive markers for survival, therapeutic efficacy, and often make the cancer cells susceptible to therapeutic intervention. Identification of driver mutations is an integral part of biomarker discovery in cancer research, and my thesis aimed to address this by developing a screening platform and a database. The in vitro Screen for Activating Mutations (iSCREAM) is a high-throughput screening workflow which was established with Epidermal Growth Factor Receptor (EGFR) as a model. The screen was validated by detection of known activating mutations like EGFR L858R. A previously known EGFR variant of unknown significance (VUS), EGFR A702V, was discovered in the screen and was functionally characterized to be an activating mutation. The iSCREAM screening methodology was further used to systematically study ERBB4, another gene in the EGFR family of receptor tyrosine kinases. We detected ERBB4 VUS R687K, and E715K in the screen and identify them as activating mutations. The ERBB4 mutations were characterized for their effect on ERBB4 phosphorylation, their sensitivity to various tyrosine kinase inhibitors, and their tumorigenicity was evaluated with in vivo allografts. The Database Of Recurrent Mutations (DORM), was prepared by analyzing a public registry of somatic mutations and preparing a catalog of the mutations identified from genome-wide studies to recapitulate the “real-world” frequency of all the recurrent (n > 1) somatic mutations. DORM allows limiting the scope of search to 38 tissue types and supports advanced queries using regular expressions. The easy-to-use database and its backend are written to be very responsive and fast in comparison to contemporary public cancer databases. Taken together, the findings and resources presented in this thesis establish grounds for further studies with other tyrosine kinases and potentially enable diversification into new niches.Uusia työkaluja syöpää aiheuttavien mutaatioiden tunnistamiseksi Geneettiset muutokset vaikuttavat useiden ihmisen syöpien syntyyn ja kehittymiseen. Syöpäkudokseen geenimutaatioita kertyy yhä enemmän ajan kuluessa syövän genomisen instabiliteetin vuoksi. Laajamittaisten sekvensointihankkeiden avulla on pystytty tunnistamaan paljon erilaisia somaattisia eli hankinnallisia mutaatioita ja sekvensointitulosten määrä kasvaa jatkuvasti uuden sukupolven sekvensointitekniikoiden (engl. next generation sequencing, NGS) paremman saatavuuden ansiosta. Näistä lukuisista syöpään liittyvistä somaattisista mutaatioista suurin osa on potilaan ennusteen kannalta merkityksettömiä "matkustajamutaatioita" (engl. passenger mutation) eli mutaatioita, jotka eivät anna valikoivaa kasvuetua syöpäsoluille. Vain muutamia somaattisia mutaatioita on validoitu "ajajamutaatioiksi" (engl. driver mutation) eli mutaatioiksi, joilla on kriittinen rooli syövän kehittymisessä tai ylläpitämisessä. Nämä ajajamutaatiot toimivat usein eloonjäämisen sekä hoidon tehon ennusteellisina markkereina ja usein myös herkistävät syöpäsoluja hoidoille. Ajajamutaatioiden tunnistaminen on olennainen osa syövän biomarkkereiden tutkimusta. Väitöskirjatyöni tavoitteena oli kehittää ajajamutaatioiden seulonta-alusta ja tietokanta. Aktivoivien mutaatioiden in vitro -seulonta (engl. in vitro Screen for Activating Mutations, iSCREAM) on tehoseulontamenetelmä, jonka kehittämistyössä käytettiin mallina epidermaalista kasvutekijäreseptoria (EGFR) koodaavaa geeniä iSCREAM-seulonnalla tunnistettiin jo tunnettuja aktivoivia EGFR-mutaatioita, kuten L858R, mikä validoi menetelmän toimivuuden. Seulontamenetelmällä tunnistettiin ja karakterisoitiin myös uusi EGFR-geenin aktivoiva mutaatio, A702V, jonka oletettu toimintamekanismi selvitettiin. iSCREAM-seulontamenetelmää hyödynnettiin tässä työssä myös EGFR-reseptorityrosiinikinaasiperheen toisen geenin, ERBB4-geenin, systemaattiseen tutkimiseen, jonka avulla löydettiin uusina aktivoivina mutaatioina ERBB4 R687K ja E715K. Näiden ERBB4-mutaatioiden vaikutusta ERBB4:n fosforylaatioon ja lääkeherkkyyteen erilaisille tyrosiinikinaasiestäjille karakterisoitiin, ja niiden tuumorigeenisyys validoitiin in vivo -allografteissa. Toistuvien mutaatioiden tietokanta (engl. Database Of Recurrent Mutations, DORM) luotiin analysoimalla somaattisten mutaatioiden julkista rekisteriä ja laatimalla luettelo genominlaajuisissa tutkimuksissa tunnistetuista mutaatioista, jotta kaikkien toistuvien (n > 1) somaattisten mutaatioiden "todellinen" esiintymistiheys voitaisiin laskea. DORM mahdollistaa haun rajoittamisen 38:aan kudostyyppiin ja tukee edistyneempiä kyselyjä säännöllisten lausekkeiden (engl. regular expression) avulla. Helppokäyttöinen tietokanta ja sen taustajärjestelmä kehitettiin hyvin reagoivaksi ja nopeaksi nykyisiin julkisiin syöpätietokantoihin verrattuna. Tässä työssä esitetyt havainnot ja resurssit luovat yhdessä perustan jatkotutkimuksille muilla tyrosiinikinaaseilla ja ovat mahdollisesti laajennettavissa muillekin tutkimusalueille

Solving Fuzzy Quadratic Programming Problems with a Proposed Algorithm

The theory of fuzzy mathematics has been proven very effective for defining and solving optimization problems. Fuzzy quadratic programming (FQP) is a consequence of this approach. In this paper, an algorithm has been proposed to solve FQP with coefficients as triangular fuzzy numbers (TFN). The proposed algorithm converts FQP into two parametric quadratic programming (QP) problems. These QP solutions provide a lower and upper bound on the objective function of FQP. When these two values coincide, an optimal solution is achieved. This algorithm has been analyzed using a numerical example and compared with existing methods

ANALYSIS OF BEHAVIOUR OF T JUNCTIONS BY VARYING ANGLES AND TYPE OF FLOW.

T-junctions are one of the most difficult pipe fitting in terms of calculation of the head loss occurring through it. Various attempts have been made to derive the value of loss coefficients of the two branches of the tjunctions. Some formulas which involve area ratios and flow ratios are available. However, the use of these coefficients has to be further scrutinized. The erroneous effect of the use of constant loss co-efficients needed to understood and reviewed. This has been done, through the use of a standard network and the simplest network having one T-junction. Further efforts have been made to minimize the losses occurred at t-junctions and the implications of it in engineering design have been discussed

Organizational learning - aiming the unreached

Organizational learning - aiming the unreache

Capacity-building strategy for Watsan reform

Capacity-building strategy for Watsan refor

Newer methods of stainless steel production and their impact on ferroalloy consumption pattern

The conventional method of stainless steel making through the electric arc furnace has got several limitat-ions such as restricted use of low cost high carbon ferro-alloys and lower productivity. In recent times a number of secondary steelmaking methods viz AOD, VOD etc. have been developed to overcome the shortcomings of the conventional method. The paper describes the various new secondary steel making processes for stainless steel making. All these new processes have a substantial flexibility regard-ing the input materials usage. As a result considerable scope exists in these processes for the use of low cost ferroalloys. Based on the material balance of these proc-ess, typical examples are given in the paper on the cons-umption pattern, of the input materials. The situation in these context of the Indian stainless steelmaking industry has been reviewed