The directional contact distance of two ellipsoids: Coarse-grained potentials for anisotropic interactions

Copyright @ 2005 American Institute of Physics.We obtain the distance of closest approach of the surfaces of two arbitrary ellipsoids valid at any orientation and separation measured along their intercenter vector. This directional distance is derived from the elliptic contact function. The geometric meaning behind this approach is clarified. An elliptic pair potential for modeling arbitrary mixtures of elliptic particles, whether hard or soft, is proposed based on this distance. Comparisons with Gay-Berne potentials are discussed. Analytic expressions for the forces and torques acting on the elliptic particles are given.This research has been supported by GlaxoSmith-Klin

Targeting Somatostatin Receptors with Peptide-functionalized Silica Nanoparticles

ABSTRACT Nano-sized synthetic drug carriers comprise a valuable addition to oncology armaments, opening new avenues for improved delivery of anticancer therapies. Nanocarriers designed to bind surface receptors of tumor cells by virtue of bearing cognate high affinity ligands, also called as actively-targeted nanocarriers, have drawn a lot of attention during the last decade, promising to enable selective tumor accumulation via ligand-receptor interactions. The present work encompasses development and early in vitro evaluation efforts with a particular type of such a targeted nanocarrier [nanoparticles of mesoporous silica (SiO2), MSN], functionalized with short peptide ligands of somatostatin receptors (SSTR), frequently abundant in tumors. The synthesized targeted MSN, as well as control inactive peptide–functionalized counterparts, were characterized by physicochemical means and evaluated for their ability to bind to SSTR and enter living cells in vitro. We sequentially studied MSN in protein-depleted and serumenriched media – the latter condition involved adsorption of proteins to MSN surface (formation of the so-called protein corona), which invariably happens in vivo and affects cellular interactions of nanomaterials. We demonstrate that the targeted MSN can bind SSTR not only under the rectified conditions, but also in the presence of protein adsorption. Ultimately, we show that SSTR targeting leads to a decreased cellular accumulation of MSN with protein corona, which highlights the complexity of nanobiointeractions and urges to re-consider the applicability of the conventional model of tumor receptor targeting with nanocarriers to somatostatin receptors. The work covers a number of chemical (MSN design, synthesis and surface functionalization) and molecular biology (in vitro targetability evaluation and generation of relevant tools, receptor signaling, endocytosis) aspects of high relevance for development and characterization of targeted nanocarriers and as such should be of interest to the broad community working with nanomedicines and targeted delivery. The discussion of the original experimental evidence is preceded by a critical literature review, introducing the current concepts of nanocarriermediated delivery in oncology. KEYWORDS: nanocarrier, tumor receptor targeting, ligand-receptor interaction, nanoparticle corona, mesoporous silica nanoparticle, somatostatin receptor, cAMP.TIIVISTELMÄ Nanokokoiset lääkkeiden kantajat avaavat uusia keinoja syöpähoitojen parantamiseksi. Nanokantajat, joiden pinnalla olevat korkean affiniteetin ligandit ovat suunniteltu sitomaan tuumorisolujen pintareseptoreita (ns. aktiivisesti kohdennetut nanokantajat), mahdollistavat nanohiukkasten selektiivisen kertymisen syöpäkasvaimeen ligandi-reseptori-vuorovaikutusten kautta. Tämä työ kattaa kehityksen ja varhaiset in vitro-kokeet kohdennetulla nanokantajahiukkasella [mesohuokoisen piidioksidin (SiO2) nanohiukkaset, MSN], jotka on funktionalisoitu somatostatiinireseptorien lyhyillä peptidiligandeilla (SSTR), joita esiintyy usein runsaasti kasvaimissa. Syntetisoidut kohdennetut MSN-hiukkaset sekä kontrollina käytetyt inaktiiviset peptidifunktionaaliset vastineet karakterisoitiin fysikaaliskemiallisilla menetelmillä sekä arvioitiin niiden kykyä sitoutua SSTR:ään ja päästä eläviin soluihin in vitro. Tutkimus suoritettiin MSN-hiukkasilla sekä proteiinipitoisessa että seerumilla rikastetussa ravintoliuoksessa – jälkimmäisessä tapauksessa proteiinit kiinnittyivät MSN:n pinnalle (ns. proteiinikoronan muodostuminen), joka tapahtuu in vivo ja vaikuttaa nanomateriaalin ja solun väliseen vuorovaikutukseen. Osoitamme, että kohdennettu MSN voi sitoa SSTR:ää paitsi puhdistetuissa olosuhteissa, myös proteiinikoronan läsnäollessa. Lopuksi osoitamme, että SSTR-kohdennuksessa proteiinikorona vähentää MSN:n kertymistä soluihin, mikä korostaa nanobiovuorovaikutusten monimutkaisuutta, ja kyseenalaistaa nanokantajien kanssa käytetyn tavanomaisen kasvainreseptorikohdennusmallin soveltuvuutta somatostatiinireseptoreihin. Työssä käytettiin kemiallisia (MSN-suunnittelu, synteesi ja pinnan funktionalisointi) ja molekyylibiologisia (kohdennettavuuden arviointi in vitro, työkalujen luominen, reseptorisignalointi ja endosytoosi) menetelmiä, jotka ovat olennaisia kohdennettujen nanokantajien kehitykselle ja karakterisoinnille. Tulosten oletetaan kiinnostavan laajaa yhteisöä, joka työskentelee nanolääkkeiden ja niiden kohdentamisen parissa. Kokeellista osuutta edeltää kirjallisuuskatsaus, jossa esitellään nanokantaja-välitteisen kuljetuksen nykyiset käsitteet syöpäbiologiassa. AVAINSANAT: nanokantaja, kasvainreseptorikohdistus, ligandi-reseptorivuorovaikutus, nanohiukkasen korona, mesohuokoinen piidioksidi-nanopartikkeli, somatostatiinireseptori, cAMP

Analytic pulse design for selective population transfer in many-level quantum systems: maximizing amplitude of population oscillations

State selective preparation and manipulation of discrete-level quantum systems such as atoms, molecules or quantum dots is a the ultimate tool for many diverse fields such as laser control of chemical reactions, atom optics, high-precision metrology and quantum computing. Rabi oscillations are one of the simplest, yet potentially quite useful mechanisms for achieving such manipulation. Rabi theory establishes that in the two-level systems resonant drive leads to the periodic and complete population oscillations between the two system levels. In this paper an analytic optimization algorithm for producing Rabi-like oscillations in the general discrete many-level quantum systems is presented.Comment: Published in Phys.Rev.A. This is the final published versio

A novel design process of low cost 3D printed ambidextrous finger designed for an ambidextrous robotic hand

This paper presents the novel mechanical design of an ambidextrous finger specifically designed for an ambidextrous anthropomorphic robotic hand actuated by pneumatic artificial muscles. The ambidextrous nature of design allows fingers to perform both left and right hand movements. The aim of our design is to reduce the number of actuators, increase the range of movements with best possible range ideally greater than a common human finger. Four prototypes are discussed in this paper; first prototype is focused on the choice of material and to consider the possible ways to reduce friction. Second prototype is designed to investigate the tendons routing configurations. Aim of third and fourth prototype is to improve the overall performance and to maximize the grasping force. Finally, a unified design (Final design) is presented in great detail. Comparison of all prototypes is done from different angles to evaluate the best design. The kinematic features of intermediate mode have been analysed to optimize both the flexibility and the robustness of the system, as well as to minimize the number of pneumatic muscles. The final design of an ambidextrous finger has developed, tested and 3D printed

State-Selective Control For Vibrational Excitation and Dissociation of Diatomic Molecules With Shaped Ultrashort Laser Pulses

Ultrafast state-selective dynamics of diatomic molecules in the electronic ground state under the control of infrared picosecond and femtosecond shaped laser pulses is investigated for the discrete vibrational bound states and for the dissociative continuum states. Quantum dynamics in a classical laser field is simulated for a one-dimensional nonrotating dissociative Morse oscillator, representing the local OH bond in the H2O and HOD molecules. Computer simulations are based on two approaches - exact treatment by the time-dependent Schrödinger equation and approximate treatment by integro-differential equations for the probability amplitudes of the bound states only. Combination of these two approaches is useful to reveal mechanisms underlying selective excitation of the continuum states and above-threshold dissociation in a single electronic state and for designing optimal laser fields to control selective preparation of the high-lying bound states and the continuum states. Optimal laser fields can be designed to yield almost 100% seletive preparation of any prescribed bound state, including those close to the dissociation threshold. State-selective preparation of the highest bound state may be accompanied by the appearance of a quasi-bound molecular state in the continuum with the kinetic energy of the fragments being close to zero. The respective above-threshold dissociation spectrum containes an additional, zero-order peak. The laser-induced dissociation from selectively prepared high-lying bound states is shown to be very efficient, with the dissociation probability approaching the maximal value. Flexible tools of state-selective laser control are developed which enable one to achieve selective control of the dissociation spectra resulting in time-selective and space-selective control of the dissociation fragments

The analysis of size-segregated cloud condensation nuclei counter (CCNC) data and its implications for cloud droplet activation

Ambient aerosol, CCN (cloud condensation nuclei) and hygroscopic properties were measured with a size-segregated CCNC (cloud condensation nuclei counter) in a boreal environment of southern Finland at the SMEAR (Station for Measuring Ecosystem-Atmosphere Relations) II station. The instrumental setup operated at five levels of supersaturation <i>S</i> covering a range from 0.1–1% and measured particles with a size range of 20–300 nm; a total of 29 non-consecutive months of data are presented. The median critical diameter <i>D</i>_c ranged from 150 nm at <i>S</i> of 0.1% to 46 nm at <i>S</i> of 1.0%. The median aerosol hygroscopicity parameter &kappa; ranged from 0.41 at <i>S</i> of 0.1% to 0.14 at <i>S</i> of 1.0%, indicating that ambient aerosol in Hyytiälä is less hygroscopic than the global continental or European continental averages. It is, however, more hygroscopic than the ambient aerosol in an Amazon rainforest, a European high Alpine site or a forested mountainous site. A fairly low hygroscopicity in Hyytiälä is likely a result of a large organic fraction present in the aerosol mass comparative to other locations within Europe. A considerable difference in particle hygroscopicity was found between particles smaller and larger than ~100 nm in diameter, possibly pointing out to the effect of cloud processing increasing &kappa; of particles > 100 nm in diameter. The hygroscopicity of the smaller, ~50 nm particles did not change seasonally, whereas particles with a diameter of ~150 nm showed a decreased hygroscopicity in the summer, likely resulting from the increased VOC emissions of the surrounding boreal forest and secondary organic aerosol (SOA) formation. For the most part, no diurnal patterns of aerosol hygroscopic properties were found. Exceptions to this were the weak diurnal patterns of small, ~50 nm particles in the spring and summer, when a peak in hygroscopicity around noon was observed. No difference in CCN activation and hygroscopic properties was found on days with or without atmospheric new particle formation. During all seasons, except summer, a CCN-inactive fraction was found to be present, rendering the aerosol of 75–300 nm in diameter as internally mixed in the summer and not internally mixed for the rest of the year

The influence of corrosion on reliability and inspection program for fatigue‐prone airframe structures

This paper is devoted to a discussion and solution of the following problems: Determination of mean value and variance of estimates of parameters of fatigue crack growth model for both the corroded and non‐corroded types of specimens; Inspection modeling with the use of the Monte Carlo method for calculation of probability of fatigue failure as a function of inspection number; Determination of the number of inspections required for the limitation of fatigue failure probability; Comparison of required reliability for corroded and non‐corroded cases. Special programs have been developed for necessary calculations. It was confirmed that the influence of corrosion has a great impact on the required number of inspections. First Published Online: 14 Oct 201