Secure Compute-and-Forward in a Bidirectional Relay

We consider the basic bidirectional relaying problem, in which two users in a wireless network wish to exchange messages through an intermediate relay node. In the compute-and-forward strategy, the relay computes a function of the two messages using the naturally occurring sum of symbols simultaneously transmitted by user nodes in a Gaussian multiple-access channel (MAC), and the computed function value is forwarded to the user nodes in an ensuing broadcast phase. In this paper, we study the problem under an additional security constraint, which requires that each user's message be kept secure from the relay. We consider two types of security constraints: 1) perfect secrecy, in which the MAC channel output seen by the relay is independent of each user's message and 2) strong secrecy, which is a form of asymptotic independence. We propose a coding scheme based on nested lattices, the main feature of which is that given a pair of nested lattices that satisfy certain goodness properties, we can explicitly specify probability distributions for randomization at the encoders to achieve the desired security criteria. In particular, our coding scheme guarantees perfect or strong secrecy even in the absence of channel noise. The noise in the channel only affects reliability of computation at the relay, and for Gaussian noise, we derive achievable rates for reliable and secure computation. We also present an application of our methods to the multihop line network in which a source needs to transmit messages to a destination through a series of intermediate relays.

Quercetin, a Natural Flavonoid Interacts with DNA, Arrests Cell Cycle and Causes Tumor Regression by Activating Mitochondrial Pathway of Apoptosis

Naturally occurring compounds are considered as attractive candidates for cancer treatment and prevention. Quercetin and ellagic acid are naturally occurring flavonoids abundantly seen in several fruits and vegetables. In the present study, we evaluate and compare antitumor efficacies of quercetin and ellagic acid in animal models and cancer cell lines in a comprehensive manner. We found that quercetin induced cytotoxicity in leukemic cells in a dose-dependent manner, while ellagic acid showed only limited toxicity. Besides leukemic cells, quercetin also induced cytotoxicity in breast cancer cells, however, its effect on normal cells was limited or none. Further, quercetin caused S phase arrest during cell cycle progression in tested cancer cells. Quercetin induced tumor regression in mice at a concentration 3-fold lower than ellagic acid. Importantly, administration of quercetin lead to -5 fold increase in the life span in tumor bearing mice compared to that of untreated controls. Further, we found that quercetin interacts with DNA directly, and could be one of the mechanisms for inducing apoptosis in both, cancer cell lines and tumor tissues by activating the intrinsic pathway. Thus, our data suggests that quercetin can be further explored for its potential to be used in cancer therapeutics and combination therapy.

Potential Application of Adsorptive Media to Enhance Phosphorus Uptake in Stormwater Basins and Wetlands at Lake Tahoe : literature review. Report to the University of California Davis Tahoe Research Group

Phosphorus removal by wetlands and basins in Lake Tahoe may be improved through designing these systems to filter storm water through media having higher phosphorus removal capabilities than local parent material. Substrates rich in iron, aluminum and calcium oftentimes have enhanced phosphorus removal. These substrates can be naturally occurring, byproducts of industrial or water treatment processes, or engineered. Phosphorus removal fundamentally occurs through chemical adsorption and/or precipitation and much of the phosphorus can be irreversibly bound. In addition to these standard media, other engineered substrates are available to enhance P removal. One such substrate is locally available in Reno and uses lanthanum coated diatomaceous earth for arsenate removal. This material, which has a high positive surface charge, can also irreversibly remove phosphorus. Physical factors also affect P removal. Specifically, specific surface area and particle shape affect filtration capacity, contact area between water and the surface area, and likelihood of clogging and blinding. A number of substrates have been shown to effectively remove P in case studies. Based upon these studies, promising substrates include WTRs, blast furnace slag, steel furnace slag, OPC, calcite, marble Utelite and other LWAs, zeolite and shale. However, other nonperformance factors such as environmental considerations, application logistics, costs, and potential for cementification narrow the list of possible media for application at Tahoe. Industrial byproducts such as slags risk possible leaching of heavy metals and this potential cannot be easily predicted. Fly ash and other fine particle substrates would be more difficult to apply because they would need to be blended, making them less desirable and more costly to apply than larger diameter media. High transportation costs rule out non-local products. Finally, amorphous calcium products will eventually cementify reducing their effectiveness in filtration systems. Based upon these considerations, bauxite, LWAs and expanded shales/clays, iron-rich sands, activated alumina, marble and dolomite, and natural and lanthanum activated diatomaceous earth are the products most likely to be tested for application at Tahoe. These materials are typically iron, calcium or aluminum based; many have a high specific surface area; and all have low transportation costs. (PDF contains 21 pages)

Topics in bifurcation theory

I. Existence and Structure of Bifurcation Branches

The problem of bifurcation is formulated as an operator equation in a Banach space, depending on relevant control parameters, say of the form G(u,λ) = 0. If dimN(G_u(u_O,λ_O)) = m the method of Lyapunov-Schmidt reduces the problem to the solution of m algebraic equations. The possible structure of these equations and the various types of solution behaviour are discussed. The equations are normally derived under the assumption that G^O_λεR(G^O_u). It is shown, however, that if G^O_λεR(G^O_u) then bifurcation still may occur and the local structure of such branches is determined. A new and compact proof of the existence of multiple bifurcation is derived. The linearized stability near simple bifurcation and "normal" limit points is then indicated.

II. Constructive Techniques for the Generation of Solution Branches

A method is described in which the dependence of the solution arc on a naturally occurring parameter is replaced by the dependence on a form of pseudo-arclength. This results in continuation procedures through regular and "normal" limit points. In the neighborhood of bifurcation points, however, the associated linear operator is nearly singular causing difficulty in the convergence of continuation methods. A study of the approach to singularity of this operator yields convergence proofs for an iterative method for determining the solution arc in the neighborhood of a simple bifurcation point. As a result of these considerations, a new constructive proof of bifurcation is determined.

Unnatural amino acids in the synthesis and semisynthesis of metalloprotein motifs

The design, synthesis, and characterization of two novel metalloprotein motifs is presented. The first project involved the design and construction of a protein motif which was programmed to form a tetradentate metal complex upon the addition of metal cations. The overall structure of the motif was based on a ββ super-secondary structure consisting of a flexible peptide sequence flanked by metal binding regions located at the carboxy and amino termini. The metal binding region near the amino terminus was constructed from a reverse turn motif with two metal ligating residues, (2R, 3R)-β-methyl-cysteine and histidine. Selection of the peptide sequence for this region was based on the conformational analysis of a series of tetrapeptides designed to form reverse turns in solution.

The stereospecific syntheses of a series of novel bipyridyl- and phenanthrolylsubstituted amino acids was carried out to provide ligands for the carboxy terminus metal binding region. These residues were incorporated into peptide sequences using solid phase peptide synthesis protocols, and metal binding studies indicated that the metal binding properties of these ligands was dictated by the specific regioisomer of the heteroaromatic ring and the peptide primary sequence.

Finally, a peptide containing optimized components for the metal binding regions was prepared to test the ability of the compound to form the desired intramolecular peptide:metal cation complexes. Metal binding studies demonstrated that the peptide formed monomeric complexes with very high metal cation binding affinities and that the two metal binding regions act cooperatively in the metal binding process. The use of these systems in the design of proteins capable of regulating naturally occurring proteins is discussed.

The second project involved the semisynthesis of two horse heart cytochrome c mutants incorporating the bipyridyl-amino acids at position 72 of the protein sequence. Structural studies on the proteins indicated that the bipyridyl amino acids had a neglible effect on the protein structure. One of the mutants was modified with Ru(bpy)_2^(+2) to form a redox-active protein, and the modified protein was found to have enhanced electron transfer properties between the heme and the introduced metal site.

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.

The short-timescale behavior of glacial ice

Glaciers are often assumed to deform only at slow (i.e., glacial) rates. However, with the advent of high rate geodetic observations of ice motion, many of the intricacies of glacial deformation on hourly and daily timescales have been observed and quantified. This thesis explores two such short timescale processes: the tidal perturbation of ice stream motion and the catastrophic drainage of supraglacial meltwater lakes. Our investigation into the transmission length-scale of a tidal load represents the first study to explore the daily tidal influence on ice stream motion using three-dimensional models. Our results demonstrate both that the implicit assumptions made in the standard two-dimensional flow-line models are inherently incorrect for many ice streams, and that the anomalously large spatial extent of the tidal influence seen on the motion of some glaciers cannot be explained, as previously thought, through the elastic or viscoelastic transmission of tidal loads through the bulk of the ice stream. We then discuss how the phase delay between a tidal forcing and the ice stream’s displacement response can be used to constrain in situ viscoelastic properties of glacial ice. Lastly, for the problem of supraglacial lake drainage, we present a methodology for implementing linear viscoelasticity into an existing model for lake drainage. Our work finds that viscoelasticity is a second-order effect when trying to model the deformation of ice in response to a meltwater lake draining to a glacier’s bed. The research in this thesis demonstrates that the first-order understanding of the short-timescale behavior of naturally occurring ice is incomplete, and works towards improving our fundamental understanding of ice behavior over the range of hours to days.

Sterochemically modified polyamides for recognition in the minor groove of DNA

The design of synthetic molecules that recognize specific sequences of DNA is an ongoing challenge in molecular medicine. Cell-permeable small molecules targeting predetermined DNA sequences offer a potential approach for offsetting the abnormal effects of misregulated gene-expression. Over the past twenty years, Professor Peter B. Dervan has developed a set of pairing rules for the rational design of minor groove binding polyamides containing pyrrole (Py), imidazole (Im), and hydroxypyrrole (Hp). Polyamides have illustrated the capability to permeate cells and inhibit transcription of specific genes in vivo. This provides impetus to identify structural elements that expand the repetoire of polyamide motifs with recognition properties comparable to naturally occurring DNA binding proteins. Through the introduction of chiral amino acids, we have developed chiral polyamides with stereochemically regulated binding characteristics. In addition, chiral substituents have facilitated the development of new polyamide motifs that broaden binding site sizes targetable by this class of ligands.

Cleavage of DNA by polyamide-seco-CBI conjugates

Small molecules that bind to any predetermined DNA sequence in the human genome are potentially useful tools for molecular biology and human medicine. Polyamides containing N-methylimidazole (Im) N-methylpyrrole (Py) are cell permeable small molecules that bind DNA according to a set of "pairing rules" with affinities and specificities similar to many naturally occurring DNA binding proteins. Py-Im polyamides offer a general approach to the chemical regulation of gene expression. We demonstrate here that polyamide containing a DNA alkylating moiety seco-CBI can specifically direct sequence specific DNA alkylation. We can also control the strand of DNA that is alkylated, depending on the enantiomer of seco-CBI used and the orientation of the polyamide relative to the alkylation site (Chapter 2). This class of molecules has been applied to a gene repair system in collaboration with the Baltimore group at Caltech (Chapter 3). Also reported are additional seco-CBI polyamide conjugates synthesized to study other systems (HIV-1 and COX-2) (Appendix 1).

Computational design of self-assembling proteins and protein-DNA nanowires

Computational protein design (CPD) is a burgeoning field that uses a physical-chemical or knowledge-based scoring function to create protein variants with new or improved properties. This exciting approach has recently been used to generate proteins with entirely new functions, ones that are not observed in naturally occurring proteins. For example, several enzymes were designed to catalyze reactions that are not in the repertoire of any known natural enzyme. In these designs, novel catalytic activity was built de novo (from scratch) into a previously inert protein scaffold. In addition to de novo enzyme design, the computational design of protein-protein interactions can also be used to create novel functionality, such as neutralization of influenza. Our goal here was to design a protein that can self-assemble with DNA into nanowires. We used computational tools to homodimerize a transcription factor that binds a specific sequence of double-stranded DNA. We arranged the protein-protein and protein-DNA binding sites so that the self-assembly could occur in a linear fashion to generate nanowires. Upon mixing our designed protein homodimer with the double-stranded DNA, the molecules immediately self-assembled into nanowires. This nanowire topology was confirmed using atomic force microscopy. Co-crystal structure showed that the nanowire is assembled via the desired interactions. To the best of our knowledge, this is the first example of a protein-DNA self-assembly that does not rely on covalent interactions. We anticipate that this new material will stimulate further interest in the development of advanced biomaterials.

Sequence-function relationships in E. coli transcriptional regulation

Understanding how transcriptional regulatory sequence maps to regulatory function remains a difficult problem in regulatory biology. Given a particular DNA sequence for a bacterial promoter region, we would like to be able to say which transcription factors bind there, how strongly they bind, and whether they interact with each other and/or RNA polymerase, with the ultimate objective of integrating knowledge of these parameters into a prediction of gene expression levels. The theoretical framework of statistical thermodynamics provides a useful framework for doing so, enabling us to predict how gene expression levels depend on transcription factor binding energies and concentrations. We used thermodynamic models, coupled with models of the sequence-dependent binding energies of transcription factors and RNAP, to construct a genotype to phenotype map for the level of repression exhibited by the lac promoter, and tested it experimentally using a set of promoter variants from E. coli strains isolated from different natural environments. For this work, we sought to ``reverse engineer'' naturally occurring promoter sequences to understand how variations in promoter sequence affects gene expression. The natural inverse of this approach is to ``forward engineer'' promoter sequences to obtain targeted levels of gene expression. We used a high precision model of RNAP-DNA sequence dependent binding energy, coupled with a thermodynamic model relating binding energy to gene expression, to predictively design and verify a suite of synthetic E. coli promoters whose expression varied over nearly three orders of magnitude.

However, although thermodynamic models enable predictions of mean levels of gene expression, it has become evident that cell-to-cell variability or ``noise'' in gene expression can also play a biologically important role. In order to address this aspect of gene regulation, we developed models based on the chemical master equation framework and used them to explore the noise properties of a number of common E. coli regulatory motifs; these properties included the dependence of the noise on parameters such as transcription factor binding strength and copy number. We then performed experiments in which these parameters were systematically varied and measured the level of variability using mRNA FISH. The results showed a clear dependence of the noise on these parameters, in accord with model predictions.

Finally, one shortcoming of the preceding modeling frameworks is that their applicability is largely limited to systems that are already well-characterized, such as the lac promoter. Motivated by this fact, we used a high throughput promoter mutagenesis assay called Sort-Seq to explore the completely uncharacterized transcriptional regulatory DNA of the E. coli mechanosensitive channel of large conductance (MscL). We identified several candidate transcription factor binding sites, and work is continuing to identify the associated proteins.

Structure-Guided Design and Biophysical Characterization of Novel Anti-HIV Reagents

Despite over 30 years of effort, an HIV-1 vaccine that elicits protective antibodies still does not exist. Recent clinical studies have identified that during natural infection about 20% of the population is capable of mounting a potent and protective antibody response. Closer inspection of these individuals reveal that a subset of these antibodies, recently termed potent VRC01-like (PVL), derive exclusively from a single human germline heavy chain gene. Induced clonal expansion of the B cell encoding this gene is the first step through which PVL antibodies may be elicited. Unfortunately, naturally occurring HIV gp120s fail to bind to this germline, and as a result cannot be used as the initial prime for a vaccine regimen. We have determined the crystal structure of an important germline antibody that is a promising target for vaccine design efforts, and have set out to engineer a more likely candidate using computationally-guided rational design.

In addition to prevention efforts on the side of vaccine design, recently characterized broadly neutralizing anti-HIV antibodies have excellent potential for use in gene therapy and passive immunotherapy. The separation distance between functional Fabs on an antibody is important due to the sparse distribution of envelop spikes on HIV compared to other viruses. We set out to build and characterize novel antibody architectures by incorporating structured linkers into the hinge region of an anti-HIV antibody b12. The goal was to observe whether these linkers increased the arm-span of the IgG dimer. When incorporated, flexible Gly4Ser repeats did not result in detectable extensions of the IgG antigen binding domains, by contrast to linkers including more rigid domains such as β2-microglobulin, Zn-α2-glycoprotein, and tetratricopeptide repeats (TPRs). This study adds an additional set of linkers with varying lengths and rigidities to the available linker repertoire, which may be useful for the modification and construction of antibodies and other fusion proteins.

Evaluación del impacto radiológico ambiental de una industria NORM

[ES]El proceso de soldadura más común es la soldadura por arco metálico con electrodos revestidos. A veces ese revestimiento contiene materiales radiactivos de origen natural (NORMs). En España los electrodos más utilizados son los recubiertos de rutilo mezclado con otros materiales. El rutilo contiene algunos radionúclidos naturales detectables, por lo que puede ser considerado como un NORM. Este trabajo principalmente se centra en la aplicación de la metodología expuesta en la Guía de Seguridad 11.3 del Consejo de Seguridad Nuclear (Metodología para la evaluación del impacto radiológico en las industrias NORM), como una herramienta para obtener las dosis en una fábrica que produce este tipo de electrodo y evaluar el impacto radiológico en una instalación específica. Para ello, se aplicaron en dicha instalación los pasos requeridos por la metodología para su cumplimiento. Se analizaron los beneficios inherentes al estudio y se identificaron las zonas de radiación más altas así como la posición de los trabajadores. Habiendo hecho uso de evaluaciones de dosis llevadas a cabo con anterioridad por otros procedimientos, métodos de simulación, se establecieron las pautas de protección radiológica a seguir para el cumplimiento de dicha guía, mediante la colocación de dosímetros personales y monitores de radiación.

Investigation of taste tainting in salmon flesh in the Ribble catchment

This report presents the findings of the first phase of an investigation into the cause(s) of taints in salmonid fish in the River Ribble, commissioned by the North West Region of the Environment Agency. There have been reports of tainting in fish taken from both the estuary and the freshwater river for many years, but the contaminants involved and their source and transport pathway are unknown. Tainting by phenols has been of specific concern in the past. The work programme comprised: examination of tainting reports; collection of salmonids; their submission for taste testing; literature review; analysis of fish flesh using gas chromatography-mass spectrometry (GCMS) and analysis of river bed sediments. From enquiries, three common descriptors of the 'taint' were identified: disinfectanty; diesely; and muddy. The incidence of taints appears transient/irregular and may therefore relate to the incidence of discharges and specific threshold concentrations of pollutants. The literature review showed that a wide range of organic compounds including many industrial chemicals, and others which are naturally occurring, can taint fish flesh. Taste testing confirmed the presence of tainted salmon and trout in the Ribbie Catchment. It identified a low incidence of 'untainted' fish but demonstrated the 'taint' to be not specific to one tainting substance. Differences were found both between the species and fish from different parts of the catchment. Overall, most fish exhibited an unpleasant flavour, though this may have been influenced to some extent by the fact that most were sexually mature. The worst tainting was found in trout from the river Calder: a soapy/chemical aftertaste. An unpleasant earthy/musty flavour distinguished the salmon from the trout. Phenol was shown to have been a minor issue during the present study, whilst no hydrocarbon taints were identified. Examination of tissue from the eight salmon exhibiting the worst taints revealed the presence of aromatic hydrocarbons, but no phenolic compounds. Other notable substances present in the fish were siioxanes and benzophenone. Data from sediment analysis is presented which shows the main compounds present to be aromatic and polyaromatic hydrocarbons, that concentrations at two locations R. Darwen and R. Calder were significantly higher than at other sites, and that some phenolic compounds were detected at low levels. A paucity of fish flesh taste descriptors linked to specific compounds prevented an obvious correlation to be made between the tastes observed and the organic compounds detected. Descriptors frequently used by the taste testing panel (e.g. earthy, musty, astringency, chemical) cannot be linked to any of the compounds identified in the tissue analyses. No taste information was available from the literature on siioxanes. Aromatic hydrocarbons though present in tissue and sediments were not identified as tainting.

Community-based fish culture in seasonal floodplains

During the rainy season in extensive river floodplains and deltaic lowlands, floods render the land unavailable for crop production for several months each year. These waters are considerably underutilized in terms of managed aquatic productivity. This raises the opportunity to enclose parts of these floodwater areas to produce a crop of specifically stocked aquatic organisms aside from the naturally occurring ‘wild’ species that are traditionally fished and are not affected by the culture activity, resulting in more high-quality, nutrient-dense food production and enhanced farm income for all stakeholders, notably the poor. The WorldFish Center and its national partners recently tested the concurrent rice-fish culture in the shallower flooded areas and the alternating rice-fish culture in the deep-flooded areas of Bangladesh and Viet Nam through a community-based management system. Results indicate that community-based fish culture in rice fields can increase fish production by about 600 kg/ha/year in shallow flooded areas and up to 1.5 t/ha/year in deep-flooded areas, without a reduction in the rice yield or wild fish catch.