Adaptive executions of hyperbolic block-structured AMR applications on GPU systems

A block-structured adaptive mesh refinement (AMR) technique has been used to obtain numerical solutions for many scientific applications. Some block-structured AMR approaches have focused on forming patches of non-uniform sizes where the size of a patch can be tuned to the geometry of a region of interest. In this paper, we develop strategies for adaptive execution of block-structured AMR applications on GPUs, for hyperbolic directionally split solvers. While effective hybrid execution strategies exist for applications with uniform patches, our work considers efficient execution of non-uniform patches with different workloads. Our techniques include bin-packing work units to load balance GPU computations, adaptive asynchronism between CPU and GPU executions using a knapsack formulation, and scheduling communications for multi-GPU executions. Our experiments with synthetic and real data, for single-GPU and multi-GPU executions, on Tesla S1070 and Fermi C2070 clusters, show that our strategies result in up to a 3.23 speedup in performance over existing strategies.

Dynamics of Cricket Sound Production

The clever designs of natural transducers are a great source of inspiration for man-made systems. At small length scales, there are many transducers in nature that we are now beginning to understand and learn from. Here, we present an example of such a transducer that is used by field crickets to produce their characteristic song. This transducer uses two distinct components-a file of discrete teeth and a plectrum that engages intermittently to produce a series of impulses forming the loading, and an approximately triangular membrane, called the harp, that acts as a resonator and vibrates in response to the impulse-train loading. The file-and-plectrum act as a frequency multiplier taking the low wing beat frequency as the input and converting it into an impulse-train of sufficiently high frequency close to the resonant frequency of the harp. The forced vibration response results in beats producing the characteristic sound of the cricket song. With careful measurements of the harp geometry and experimental measurements of its mechanical properties (Young's modulus determined from nanoindentation tests), we construct a finite element (FE) model of the harp and carry out modal analysis to determine its natural frequency. We fine tune the model with appropriate elastic boundary conditions to match the natural frequency of the harp of a particular species-Gryllus bimaculatus. We model impulsive loading based on a loading scheme reported in literature and predict the transient response of the harp. We show that the harp indeed produces beats and its frequency content matches closely that of the recorded song. Subsequently, we use our FE model to show that the natural design is quite robust to perturbations in the file. The characteristic song frequency produced is unaffected by variations in the spacing of file-teeth and even by larger gaps. Based on the understanding of how this natural transducer works, one can design and fabricate efficient microscale acoustic devices such as microelectromechanical systems (MEMS) loudspeakers.

Dynamics of Glass Forming Liquids with Randomly Pinned Particles

It is frequently assumed that in the limit of vanishing cooling rate, the glass transition phenomenon becomes a thermodynamic transition at a temperature T-K. However, with any finite cooling rate, the system falls out of equilibrium at temperatures near T-g(> T-K), implying that the very existence of the putative thermodynamic phase transition at T-K can be questioned. Recent studies of systems with randomly pinned particles have hinted that the thermodynamic glass transition may be observed for liquids with randomly pinned particles. This expectation is based on the results of approximate calculations that suggest that the thermodynamic glass transition temperature increases with increasing concentration of pinned particles and it may be possible to equilibrate the system at temperatures near the increased transition temperature. We test the validity of this prediction through extensive molecular dynamics simulations of two model glass-forming liquids in the presence of random pinning. We find that extrapolated thermodynamic transition temperature T-K does not show any sign of increasing with increasing pinning concentration. The main effect of pinning is found to be a rapid decrease in the kinetic fragility of the system with increasing pin concentration. Implications of these observations for current theories of the glass transition are discussed.

NANOLOCALIZED SINGLE CELL MEMBRANE NANOELECTROPORATION

Today single cell research is a great interest to analyze cell to cell or cell to environment behavior with their intracellular compounds, where bulk measurement can provide average value. To deliver biomolecules precise and localized way into single living cell with high transfection rate and high cell viability is a challenging and promisible task for biological and therapeutic research. In this report, we present a nano-localized single cell nano-electroporation technique, where electroporation take place in a very precise and localized area on a single cell membrane to achieve high efficient delivery with high cell viability. We fabricated 60nm gap with 40 nm triangular Indium Tin Oxide (ITO) based nano-eletcrode tip, which can intense electric field in a nano-localized area of a single cell to permeabilize cell membrane and deliver exogenous biomolecules from outside to inside of the cell. This device successfully deliver dyes, proteins into single cell with high cell viability (98%). The process not only control precise delivery mechanism into single cell with membrane reversibility, but also it can provide special, temporal and qualitative dosage control, which might be beneficial for therapeutic and biological cell studies.

Role Of Vertical Component Of Surface Tension Of The Droplet On The Elastic Deformation Of Pdms Membrane

Poly(dimethylsiloxane) (PDMS) has been widely used in lab-on-a-chip and micro- total analysis systems (mu-TAS), thus wetting and electrowetting behaviors of PDMS are of great importance in these devices. PDMS is a kind of soft polymer material, so the elastic deformation of PDMS membrane by a droplet cannot be neglected due to the vertical component of the interfacial tension between the liquid and vapor, and this vertical component of liquid-vapor surface tension is also balanced by the stress distribution within the PDMS membrane. Such elastic deformation and stress distribution not only affect the exact measurement of contact angle, but also have influence on the micro-fluidic behavior of the devices. Using ANSYS code, we simulated numerically the elastic deformation and stress distribution of PDMS membrane on a rigid substrate due to the liquid-vapor surface tension. It is found that the vertical elastic deformation of the PDMS membrane is on the order of several tens of nanometers due to the application of a droplet with a diameter of 2.31 mm, which is no longer negligible for lab-on-a-chip and mu-TAS. The vertical elastic deformation increases with the thickness of the PDMS membrane, and there exists a saturated membrane thickness, regarded as a semi-infinite membrane thickness, and the vertical elastic deformation reaches a limiting value when the membrane thickness is equal to or thicker than such saturated thickness. (C) Koninklijke Brill NV, Leiden, 2008.

A dynamical systems analysis of vortex pinch-off

Vortex rings constitute the main structure in the wakes of a wide class of swimming and flying animals, as well as in cardiac flows and in the jets generated by some moss and fungi. However, there is a physical limit, determined by an energy maximization principle called the Kelvin-Benjamin principle, to the size that axisymmetric vortex rings can achieve. The existence of this limit is known to lead to the separation of a growing vortex ring from the shear layer feeding it, a process known as `vortex pinch-off', and characterized by the dimensionless vortex formation number. The goal of this thesis is to improve our understanding of vortex pinch-off as it relates to biological propulsion, and to provide future researchers with tools to assist in identifying and predicting pinch-off in biological flows.

To this end, we introduce a method for identifying pinch-off in starting jets using the Lagrangian coherent structures in the flow, and apply this criterion to an experimentally generated starting jet. Since most naturally occurring vortex rings are not circular, we extend the definition of the vortex formation number to include non-axisymmetric vortex rings, and find that the formation number for moderately non-axisymmetric vortices is similar to that of circular vortex rings. This suggests that naturally occurring vortex rings may be modeled as axisymmetric vortex rings. Therefore, we consider the perturbation response of the Norbury family of axisymmetric vortex rings. This family is chosen to model vortex rings of increasing thickness and circulation, and their response to prolate shape perturbations is simulated using contour dynamics. Finally, the response of more realistic models for vortex rings, constructed from experimental data using nested contours, to perturbations which resemble those encountered by forming vortices more closely, is simulated using contour dynamics. In both families of models, a change in response analogous to pinch-off is found as members of the family with progressively thicker cores are considered. We posit that this analogy may be exploited to understand and predict pinch-off in complex biological flows, where current methods are not applicable in practice, and criteria based on the properties of vortex rings alone are necessary.

Pharmacology and pore-forming domains of the cystic fibrosis transmembrane conductance regulator

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel member of the ATP-binding cassette (ABC) superfamily of membrane proteins. CFTR has two homologous halves, each consisting of six transmembrane spanning domains (TM) followed by a nucleotide binding fold, connected by a regulatory (R) domain. This thesis addresses the question of which domains are responsible for Cl^- selectivity, i.e., which domains line the channel pore.

To address this question, novel blockers of CFTR were characterized. CFTR was heterologously expressed in Xenopus oocytes to study the mechanism of block by two closely related arylaminobenzoates, diphenylamine-2-carboxylic acid (DPC) and flufenamic acid (FFA). Block by both is voltage-dependent, with a binding site ≈ 40% through the electric field of the membrane. DPC and FFA can both reach their binding site from either side of the membrane to produce a flickering block of CFTR single channels. In addition, DPC block is influenced by Cl^- concentration, and DPC blocks with a bimolecular forward binding rate and a unimolecular dissociation rate. Therefore, DPC and FFA are open-channel blockers of CFTR, and a residue of CFTR whose mutation affects their binding must line the pore.

Screening of site-directed mutants for altered DPC binding affinity reveals that TM-6 and TM-12 line the pore. Mutation of residue 5341 in TM-6 abolishes most DPC block, greatly reduces single-channel conductance, and alters the direction of current rectification. Additional residues are found in TM-6 (K335) and TM-12 (T1134) whose mutations weaken or strengthen DPC block; other mutations move the DPC binding site from TM-6 to TM-12. The strengthened block and lower conductance due to mutation T1134F is quantitated at the single-channel level. The geometry of DPC and of the residues mutated suggest α-helical structures for TM-6 and TM-12. Evidence is presented that the effects of the mutations are due to direct side-chain interaction, and not to allosteric effects propagated through the protein. Mutations are also made in TM-11, including mutation S1118F, which gives voltage-dependent current relaxations. The results may guide future studies on permeation through ABC transporters and through other Cl^- channels.

Coupled effects of mechanics, geometry, and chemistry on bio-membrane behavior

Lipid bilayer membranes are models for cell membranes--the structure that helps regulate cell function. Cell membranes are heterogeneous, and the coupling between composition and shape gives rise to complex behaviors that are important to regulation. This thesis seeks to systematically build and analyze complete models to understand the behavior of multi-component membranes.

We propose a model and use it to derive the equilibrium and stability conditions for a general class of closed multi-component biological membranes. Our analysis shows that the critical modes of these membranes have high frequencies, unlike single-component vesicles, and their stability depends on system size, unlike in systems undergoing spinodal decomposition in flat space. An important implication is that small perturbations may nucleate localized but very large deformations. We compare these results with experimental observations.

We also study open membranes to gain insight into long tubular membranes that arise for example in nerve cells. We derive a complete system of equations for open membranes by using the principle of virtual work. Our linear stability analysis predicts that the tubular membranes tend to have coiling shapes if the tension is small, cylindrical shapes if the tension is moderate, and beading shapes if the tension is large. This is consistent with experimental observations reported in the literature in nerve fibers. Further, we provide numerical solutions to the fully nonlinear equilibrium equations in some problems, and show that the observed mode shapes are consistent with those suggested by linear stability. Our work also proves that beadings of nerve fibers can appear purely as a mechanical response of the membrane.

Structural and mechanistic motifs in membrane proteins: the three-dimensional modelling of rhodopsin, band 3, and the nicotinic acetylcholine receptor

Because so little is known about the structure of membrane proteins, an attempt has been made in this work to develop techniques by which to model them in three dimensions. The procedures devised rely heavily upon the availability of several sequences of a given protein. The modelling procedure is composed of two parts. The first identifies transmembrane regions within the protein sequence on the basis of hydrophobicity, β-turn potential, and the presence of certain amino acid types, specifically, proline and basic residues. The second part of the procedure arranges these transmembrane helices within the bilayer based upon the evolutionary conservation of their residues. Conserved residues are oriented toward other helices and variable residues are positioned to face the surrounding lipids. Available structural information concerning the protein's helical arrangement, including the lengths of interhelical loops, is also taken into account. Rhodopsin, band 3, and the nicotinic acetylcholine receptor have all been modelled using this methodology, and mechanisms of action could be proposed based upon the resulting structures.

Specific residues in the rhodopsin and iodopsin sequences were identified, which may regulate the proteins' wavelength selectivities. A hinge-like motion of helices M3, M4, and M5 with respect to the rest of the protein was proposed to result in the activation of transducin, the G-protein associated with rhodopsin. A similar mechanism is also proposed for signal transduction by the muscarinic acetylcholine and β-adrenergic receptors.

The nicotinic acetylcholine receptor was modelled with four trans-membrane helices per subunit and with the five homologous M2 helices forming the cation channel. Putative channel-lining residues were identified and a mechanism of channel-opening based upon the concerted, tangential rotation of the M2 helices was proposed.

Band 3, the anion exchange protein found in the erythrocyte membrane, was modelled with 14 transmembrane helices. In general the pathway of anion transport can be viewed as a channel composed of six helices that contains a single hydrophobic restriction. This hydrophobic region will not allow the passage of charged species, unless they are part of an ion-pair. An arginine residue located near this restriction is proposed to be responsible for anion transport. When ion-paired with a transportable anion it rotates across the barrier and releases the anion on the other side of the membrane. A similar process returns it to its original position. This proposed mechanism, based on the three-dimensional model, can account for the passive, electroneutral, anion exchange observed for band 3. Dianions can be transported through a similar mechanism with the additional participation of a histidine residue. Both residues are located on M10.

Carbon-carbon bond forming reactions from bis(carbene)-platinum(II) complexes and olefin polymerization and oligomerization using group 4 post-metallocene complexes

A long-standing challenge in transition metal catalysis is selective C–C bond coupling of simple feedstocks, such as carbon monoxide, ethylene or propylene, to yield value-added products. This work describes efforts toward selective C–C bond formation using early- and late-transition metals, which may have important implications for the production of fuels and plastics, as well as many other commodity chemicals.

The industrial Fischer-Tropsch (F-T) process converts synthesis gas (syngas, a mixture of CO + H₂) into a complex mixture of hydrocarbons and oxygenates. Well-defined homogeneous catalysts for F-T may provide greater product selectivity for fuel-range liquid hydrocarbons compared to traditional heterogeneous catalysts. The first part of this work involved the preparation of late-transition metal complexes for use in syngas conversion. We investigated C–C bond forming reactions via carbene coupling using bis(carbene)platinum(II) compounds, which are models for putative metal–carbene intermediates in F-T chemistry. It was found that C–C bond formation could be induced by either (1) chemical reduction of or (2) exogenous phosphine coordination to the platinum(II) starting complexes. These two mild methods afforded different products, constitutional isomers, suggesting that at least two different mechanisms are possible for C–C bond formation from carbene intermediates. These results are encouraging for the development of a multicomponent homogeneous catalysis system for the generation of higher hydrocarbons.

A second avenue of research focused on the design and synthesis of post-metallocene catalysts for olefin polymerization. The polymerization chemistry of a new class of group 4 complexes supported by asymmetric anilide(pyridine)phenolate (NNO) pincer ligands was explored. Unlike typical early transition metal polymerization catalysts, NNO-ligated catalysts produce nearly regiorandom polypropylene, with as many as 30-40 mol % of insertions being 2,1-inserted (versus 1,2-inserted), compared to <1 mol % in most metallocene systems. A survey of model Ti polymerization catalysts suggests that catalyst modification pathways that could affect regioselectivity, such as C–H activation of the anilide ring, cleavage of the amine R-group, or monomer insertion into metal–ligand bonds are unlikely. A parallel investigation of a Ti–amido(pyridine)phenolate polymerization catalyst, which features a five- rather than a six-membered Ti–N chelate ring, but maintained a dianionic NNO motif, revealed that simply maintaining this motif was not enough to produce regioirregular polypropylene; in fact, these experiments seem to indicate that only an intact anilide(pyridine)phenolate ligated-complex will lead to regioirregular polypropylene. As yet, the underlying causes for the unique regioselectivity of anilide(pyridine)phenolate polymerization catalysts remains unknown. Further exploration of NNO-ligated polymerization catalysts could lead to the controlled synthesis of new types of polymer architectures.

Finally, we investigated the reactivity of a known Ti–phenoxy(imine) (Ti-FI) catalyst that has been shown to be very active for ethylene homotrimerization in an effort to upgrade simple feedstocks to liquid hydrocarbon fuels through co-oligomerization of heavy and light olefins. We demonstrated that the Ti-FI catalyst can homo-oligomerize 1-hexene to C₁₂ and C₁₈ alkenes through olefin dimerization and trimerization, respectively. Future work will include kinetic studies to determine monomer selectivity by investigating the relative rates of insertion of light olefins (e.g., ethylene) vs. higher α-olefins, as well as a more detailed mechanistic study of olefin trimerization. Our ultimate goal is to exploit this catalyst in a multi-catalyst system for conversion of simple alkenes into hydrocarbon fuels.

Synthetic, kinetic and mechanistic studies in early transition metal systems. I. α- and β-hydrogen elimination reactions in derivatives of permethyltitanocene, -zirconocene, and -hafnocene. II. The reactions of aluminum alkyls with derivatives of permethylniobocene

The thermal decomposition of Cp*Ti(CH_3)_2 (Cp*≡ ƞ^5-C_5Me_5) toluene solution follows cleanly first-order kinetics and produces a single titanium product Cp*(C_5Me_4CH_2)Ti(CH_3) concurrent with the evolution of one equivalent of methane. Labeling studies using Cp*_2Ti- (CD_3)_2 and (Cp*-d_(15))_2Ti(CH_3)_2 show the decomposition to be intramolecular and the methane to be produced by the coupling of a methyl group with a hydrogen from the other TiCH_3 group. Activation parameters, ΔH^‡ and ΔS^‡, and kinetic deuterium isotope effects have been measured. The alternative decomposition pathways of α-hydrogen abstraction and a-hydrogen elimination, both leading to a titanium-methylidene intermediate, are discussed.

The insertion of unactivated acetylenes into the metal-hydride bonds of Cp*_2MH_2 (M = Zr, Hf) proceeds rapidly at low temperature to form monoand/ or bisinsertion products, dependent upon the steric bulk of the acetylene substituents. Cp*_2M(H)(C(Me)=CHMe), Cp*_2M(H)(CH=CHCMe_3), Cp*_2M(H)-(CH=CHPh), Cp*_2M(CH=CHPh)_2, Cp*_2M(CH=CHCH_3)_2 and Cp*_2Zr- (CH=CHCH_2CH_3)_2 have been isolated and characterized. To extend the study of unsaturated-carbon ligands, Cp*_2M(C≡CCH_3)_2 have been prepared by treating Cp*_2MCl_2 with LiC≡CCH_3. The reactivity of many of these complexes with carbon monoxide and dihydrogen is surveyed. The mono(2- butenyl) complexes Cp*_2M(H)(C(Me)=CHMe) rearrange at room temperature, forming the crotyl-hydride species Cp*_2M(H)(ƞ^3-C_4H_7). The bis(propenyl) and bis(l-butenyl) zirconium complexes Cp*_2Zr(CH=CHR)_2 (R = CH_3, CH_2CH_3) also rearrange, forming zirconacyclopentenes. Labeling studies, reaction chemistry, and kinetic measurements, including deuterium isotope effects, demonstrate that the unusual 6-hydrogen elimination from an sp^2-hybridized carbon is the first step in these latter rearrangements but is not observed in the former. Details of these mechanisms and the differences in reactivity of the zirconium and hafnium complexes are discussed.

The reactions of hydride- and alkyl-carbonyl derivatives of permethylniobocene with equimolar amounts of trialkylaluminum reagents occur rapidly producing the carbonyl adducts Cp*_2Nb(R)(COAlR'_3) (R = H, CH_3, CH_2CH_3, CH_2CH_2Ph, C(Me)=CHMe; R' = Me, Et). The hydride adduct Cp*_2NbH_3•AlEt_3 has also been formed. In solution, each of these compounds exists in equilibrium with the uncomplexed species. The formation constants for Cp*_2Nb(H)(COA1R'_R) have been measured. They indicate the steric bulk of the Cp* ligands plays a deciding factor in the isolation of the first example of an aluminum Lewis acid bound to a carbonyl-oxygen in preference to a metalhydride. Reactions of Cp*_2Nb(H)CO with other Lewis acids and of the one:one adducts with H_2, CO and C_2H_4 are also discussed.

Cp*_2Nb(H)(C_2H_4) also reacts with equimolar amounts of trialkylaluminum reagents, forming a one:one complex that ^1H NMR spectroscopy indicates contains a Nb-CH_2CH_2-Al bridge. This adduct also exists in equilibrium with the uncomplexed species in solution. The formation constant for Cp*_2N+/b(H)(CH_2CH_2ĀlEt_3) has been measured. Reactions of Cp*_2Nb(H)(C_2H_4) with other Lewis acids and the reactions of Cp*_2N+b(H)- (CH_2CH_2ĀlEt_3) with CO and C_2H_4 are described, as are the reactions of Cp_*2Nb(H)(CH_2=CHR) (R = Me, Ph), Cp*_2Nb(H)(CH_3C≡CCH_3) and Cp*_2Ti-(C_2H_4) with AlEt_3.

The Get3 ATPase drives unidirectional targeting of tail-anchored membrane proteins

Efficient and accurate localization of membrane proteins is essential to all cells and requires a complex cascade of interactions between protein machineries. This is exemplified in the recently discovered Guided Entry of Tail-anchored protein pathway, in which the central targeting factor Get3 must sequentially interact with three distinct binding partners (Get4, Get1 and Get2) to ensure the targeted delivery of Tail-anchored proteins to the endoplasmic reticulum membrane. To understand the molecular and energetic principles that provide the vectorial driving force of these interactions, we used a quantitative fluorescence approach combined with mechanistic enzymology to monitor the effector interactions of Get3 at each stage of Tail-anchored protein targeting. We show that nucleotide and membrane protein substrate generate a gradient of interaction energies that drive the cyclic and ordered transit of Get3 from Get4 to Get2 and lastly to Get1. These data also define how the Get3/Tail-anchored complex is captured, handed over, and disassembled by the Get1/2 receptor at the membrane, and reveal a novel role for Get4/5 in recycling Get3 from the endoplasmic reticulum membrane at the end of the targeting reaction. These results provide general insights into how complex cascades of protein interactions are coordinated and coupled to energy inputs in biological systems.

Chemical studies of viral entry mechanisms: I. Hydrophobic protein-lipid interactions during sendai virus membrane fusion. II. Kinetics of bacteriophage λ DNA injection.

Viruses possess very specific methods of targeting and entering cells. These methods would be extremely useful if they could also be applied to drug delivery, but little is known about the molecular mechanisms of the viral entry process. In order to gain further insight into mechanisms of viral entry, chemical and spectroscopic studies in two systems were conducted, examining hydrophobic protein-lipid interactions during Sendai virus membrane fusion, and the kinetics of bacteriophage λ DNA injection.

Sendai virus glycoprotein interactions with target membranes during the early stages of fusion were examined using time-resolved hydrophobic photoaffinity labeling with the lipid-soluble carbene generator3-(trifluoromethyl)-3-(m-^(125 )I] iodophenyl)diazirine (TID). The probe was incorporated in target membranes prior to virus addition and photolysis. During Sendai virus fusion with liposomes composed of cardiolipin (CL) or phosphatidylserine (PS), the viral fusion (F) protein is preferentially labeled at early time points, supporting the hypothesis that hydrophobic interaction of the fusion peptide at the N-terminus of the F_1 subunit with the target membrane is an initiating event in fusion. Correlation of the hydrophobic interactions with independently monitored fusion kinetics further supports this conclusion. Separation of proteins after labeling shows that the F_1 subunit, containing the putative hydrophobic fusion sequence, is exclusively labeled, and that the F_2 subunit does not participate in fusion. Labeling shows temperature and pH dependence consistent with a need for protein conformational mobility and fusion at neutral pH. Higher amounts of labeling during fusion with CL vesicles than during virus-PS vesicle fusion reflects membrane packing regulation of peptide insertion into target membranes. Labeling of the viral hemagglutinin/neuraminidase (HN) at low pH indicates that HN-mediated fusion is triggered by hydrophobic interactions, after titration of acidic amino acids. HN labeling under nonfusogenic conditions reveals that viral binding may involve hydrophobic as well as electrostatic interactions. Controls for diffusional labeling exclude a major contribution from this source. Labeling during reconstituted Sendai virus envelope-liposome fusion shows that functional reconstitution involves protein retention of the ability to undergo hydrophobic interactions.

Examination of Sendai virus fusion with erythrocyte membranes indicates that hydrophobic interactions also trigger fusion between biological membranes, and that HN binding may involve hydrophobic interactions as well. Labeling of the erythrocyte membranes revealed close membrane association of spectrin, which may play a role in regulating membrane fusion. The data show that hydrophobic fusion protein interaction with both artificial and biological membranes is a triggering event in fusion. Correlation of these results with earlier studies of membrane hydration and fusion kinetics provides a more detailed view of the mechanism of fusion.

The kinetics of DNA injection by bacteriophage λ. into liposomes bearing reconstituted receptors were measured using fluorescence spectroscopy. LamB, the bacteriophage receptor, was extracted from bacteria and reconstituted into liposomes by detergent removal dialysis. The DNA binding fluorophore ethidium bromide was encapsulated in the liposomes during dialysis. Enhanced fluorescence of ethidium bromide upon binding to injected DNA was monitored, and showed that injection is a rapid, one-step process. The bimolecular rate law, determined by the method of initial rates, revealed that injection occurs several times faster than indicated by earlier studies employing indirect assays.

It is hoped that these studies will increase the understanding of the mechanisms of virus entry into cells, and to facilitate the development of virus-mimetic drug delivery strategies.

Deep near-infrared spectroscopy of high-redshift galaxies: the physical growth of passive systems

The assembly history of massive galaxies is one of the most important aspects of galaxy formation and evolution. Although we have a broad idea of what physical processes govern the early phases of galaxy evolution, there are still many open questions. In this thesis I demonstrate the crucial role that spectroscopy can play in a physical understanding of galaxy evolution. I present deep near-infrared spectroscopy for a sample of high-redshift galaxies, from which I derive important physical properties and their evolution with cosmic time. I take advantage of the recent arrival of efficient near-infrared detectors to target the rest-frame optical spectra of z > 1 galaxies, from which many physical quantities can be derived. After illustrating the applications of near-infrared deep spectroscopy with a study of star-forming galaxies, I focus on the evolution of massive quiescent systems.

Most of this thesis is based on two samples collected at the W. M. Keck Observatory that represent a significant step forward in the spectroscopic study of z > 1 quiescent galaxies. All previous spectroscopic samples at this redshift were either limited to a few objects, or much shallower in terms of depth. Our first sample is composed of 56 quiescent galaxies at 1 < z < 1.6 collected using the upgraded red arm of the Low Resolution Imaging Spectrometer (LRIS). The second consists of 24 deep spectra of 1.5 < z < 2.5 quiescent objects observed with the Multi-Object Spectrometer For Infra-Red Exploration (MOSFIRE). Together, these spectra span the critical epoch 1 < z < 2.5, where most of the red sequence is formed, and where the sizes of quiescent systems are observed to increase significantly.

We measure stellar velocity dispersions and dynamical masses for the largest number of z > 1 quiescent galaxies to date. By assuming that the velocity dispersion of a massive galaxy does not change throughout its lifetime, as suggested by theoretical studies, we match galaxies in the local universe with their high-redshift progenitors. This allows us to derive the physical growth in mass and size experienced by individual systems, which represents a substantial advance over photometric inferences based on the overall galaxy population. We find a significant physical growth among quiescent galaxies over 0 < z < 2.5 and, by comparing the slope of growth in the mass-size plane dlogR_e/dlogM_∗ with the results of numerical simulations, we can constrain the physical process responsible for the evolution. Our results show that the slope of growth becomes steeper at higher redshifts, yet is broadly consistent with minor mergers being the main process by which individual objects evolve in mass and size.

By fitting stellar population models to the observed spectroscopy and photometry we derive reliable ages and other stellar population properties. We show that the addition of the spectroscopic data helps break the degeneracy between age and dust extinction, and yields significantly more robust results compared to fitting models to the photometry alone. We detect a clear relation between size and age, where larger galaxies are younger. Therefore, over time the average size of the quiescent population will increase because of the contribution of large galaxies recently arrived to the red sequence. This effect, called progenitor bias, is different from the physical size growth discussed above, but represents another contribution to the observed difference between the typical sizes of low- and high-redshift quiescent galaxies. By reconstructing the evolution of the red sequence starting at z ∼ 1.25 and using our stellar population histories to infer the past behavior to z ∼ 2, we demonstrate that progenitor bias accounts for only half of the observed growth of the population. The remaining size evolution must be due to physical growth of individual systems, in agreement with our dynamical study.

Finally, we use the stellar population properties to explore the earliest periods which led to the formation of massive quiescent galaxies. We find tentative evidence for two channels of star formation quenching, which suggests the existence of two independent physical mechanisms. We also detect a mass downsizing, where more massive galaxies form at higher redshift, and then evolve passively. By analyzing in depth the star formation history of the brightest object at z > 2 in our sample, we are able to put constraints on the quenching timescale and on the properties of its progenitor.

A consistent picture emerges from our analyses: massive galaxies form at very early epochs, are quenched on short timescales, and then evolve passively. The evolution is passive in the sense that no new stars are formed, but significant mass and size growth is achieved by accreting smaller, gas-poor systems. At the same time the population of quiescent galaxies grows in number due to the quenching of larger star-forming galaxies. This picture is in agreement with other observational studies, such as measurements of the merger rate and analyses of galaxy evolution at fixed number density.

Physico-chemical interactions between compartment-forming lipids and other prebiotically relevant biomolecules

Lipids are essential constituents of contemporary living cells, serving as structural molecules that are necessary to form membranous compartments. Amphiphilic lipid-like molecules may also have contributed to prebiotic chemical evolution by promoting the synthesis, aggregation and cooperative encapsulation of other biomolecules. The resulting compartments would allow systems of molecules to be maintained that represent microscopic experiments in a natural version of combinatorial chemistry. Here we address these possibilities and describe recent results related to interactions between amphiphiles and other biomolecules during early evolution toward the first living cells.