Academic literature on the topic 'PHAST Library'

Oggigiorno, le architetture parallele sono ovunque: computer desktop, dispositivi mobile, workstation ad alte prestazioni e server sono solo alcuni esempi. Oltre ai classici multi-core, anche GPU, FPGA, TPU e altri dispositivi vengono utilizzati in un ampio spettro di applicazioni. In questa era post-PC, i programmatori devono necessariamente sfruttare l'eterogeneità per utilizzare pienamente l'hardware e raggiungere prestazioni senza precedenti. Scrivere codice eterogeneo può essere difficile: ogni dispositivo può avere i suoi linguaggi, i suoi framework e i suoi stili di programmazione. Pertanto, per essere produttivi, bisognerebbe preferire degli approcci eterogenei che consentano la scrittura di codice una volta sola. Questi approcci devono fornire come minimo la portabilità del codice tra dispositivi, ma anche la portabilità delle prestazioni, così da ridurre la necessità di programmare e ottimizzare diverse architetture in maniera specifica. Nonostante l'ampia diffusione di dispositivi eterogenei, tali framework sono ancora di là da venire. Questa tesi di Dottorato presenta il mio contributo alla programmazione parallela ed eterogenea. In una prima parte viene discusso approfonditamente lo stato dell'arte dell'ambito di appartenenza. In seguito viene presentato un framework che mira a porsi come punto di riferimento, tentando di conciliare i punti forti delle diverse soluzioni concorrenti, limitandone le debolezze. Questo framework, dal nome PHAST Library, è una libreria di programmazione single-source in C++ moderno che fornisce produttività e portabilità di codice e prestazioni tra dispositivi paralleli. In questo lavoro si discutono le caratteristiche in maniera approfondita e se ne valuta il valore tramite confronto con altri framework eterogenei ad alto livello di astrazione, sia da un punto di vista prestazionale che di produttività. Dal confronto, che annovera esempi semplici e applicazioni reali, emerge che il framework è maturo. Inoltre, PHAST Library rappresenta un miglioramento misurabile dello stato dell'arte e perciò può essere utilizzato per lo sviluppo di applicazioni parallele ed eterogenee in maniera produttiva e portabile. La tesi si conclude con la discussione delle sue possibili evoluzioni.<br>Nowadays, parallel architectures are everywhere: desktop computers, mobile devices, high-performance workstations, and servers are just a few examples. Not only multi-core microprocessors, but also GPUs, FPGAs, TPUs, and other computing devices are widely used in a broad range of applications. Programmers willing to code in this post-PC era need to take advantage of heterogeneity in order to fully utilize these devices and reach unprecedented performance. Programming heterogeneity can be difficult: each device can have its own languages, frameworks, and coding styles. Heterogeneous approaches that let programmers code once must be preferred for productivity reasons. They must provide portability as a minimum requirement, but also performance portability to reduce the need of device-specific coding and tuning. Despite the wide diffusion of heterogeneous computing devices, frameworks with these facilities are yet to come. This Ph.D. thesis presents my contribution to parallel and heterogeneous programming. After presenting an in-depth study of the state-of-the-art programming approaches for heterogeneous devices, it presents a programming framework that aims at embodying their strengths while limiting their weaknesses. This framework, called PHAST Library, is a modern C++ single-source programming library that provides near-native performance, productivity, portability, and performance portability across parallel computing devices. This thesis discusses it in-depth and evaluates it against other productive heterogeneous frameworks from both performance and productivity points of view. The comparison is done in the case of various toy and real-world applications, which shows that the framework is mature. It also improves the state-of-the-art in a measurable way, and thus its use can help programmers to write high-level, high-performance parallel heterogeneous code. In conclusion, a possible evolution of the framework is presented.

Thesis: S.B., Massachusetts Institute of Technology, Department of Materials Science and Engineering, 2018.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references (page 39).<br>An experimental study was performed to determine the effects on Corona Phase Molecular Recognition (CoMoRe) of bioconjugating a host of small molecules to DNA wrapped single-walled carbon nanotubes. In addition, the study observed the effects of the DNA sequence length on the subsequent effectiveness of the small molecules to alter the corona phase. The conjugation of small molecules was shown to alter both the intensity and the position of the fluorescence and absorbance profile. The length of the DNA sequence was found to change the small molecule's ability to alter the fluorecence spectra of the wrapped nanotubes. The EDC/sulfo-NHS reaction was done to conjugate the small molecules to two identical DNA sequences with varying lengthes. Through the methods of ultraviolet-visibile-near infrared absorption spectroscopy, near infrared fluorescence spectroscopy, and high-performance liquid chromatography characterization and structural analysis were performed. The results showed the successful conjugation of the small molecules to the amino-modified DNA and an alteration in the corona phase. The small molecules were found to bind to the DNA at multiple locations and the length of the sequence was found to have an effect on the corona phase.<br>by Jasmine K. Harris.<br>S.B.

Les dendrimères sont très prometteurs du fait de leur structure unique et de leur multivalence. Cependant, leur synthèse souffre de problèmes de défauts de structure et de présence de produits secondaires très similaires. Des approches synthétiques alternatives sont donc fortement désirées. L'objectif de ma thèse consiste à explorer la synthèse sur support solide et l’approche d'autoassemblage pour la préparation de dendrimères.La première partie de ma thèse se concentre sur la synthèse de dendrimères en phase solide. Nous avons tout d'abord développé une méthode de synthèse pour les dendrimères poly(amidoamines) basée sur la chimie des peptides. Nous avons ensuite construit une petite bibliothèque de dendrimères de type triazine en faisant varier la taille et la terminaison des dendrimères pour créer une variété de dendrimères. Nous avons aussi tenté de synthétiser des dendrimères poly(aminoesters) bien que nous n'ayons pu les obtenir du fait du caractère labile de ces dendrimères.La deuxième partie de ma thèse vise à appliquer l’approche d'autoassemblage pour la construction de dendrimères supramoléculaires comme théranostiques combinant l'imagerie et la thérapie. Nous avons synthétisé un petit dendrimère amphiphile portant DOTA pour chélater le Gd (III). Ce dendrimère est capable de s'autoassembler en supramolécule et d’encapsuler l’agent anticancéreux doxorubicine, pour construire des agents théranostiques à base de dendrimères multivalents.L’ensemble de ma thèse se consacre au développement de stratégies en phase solide et de l'autoassemblage pour construire des dendrimères pour les applications dans les domaines biomédicaux et des matériaux<br>Dendrimers hold great promise for wide applications thanks to their unique structural architecture and multivalent cooperativity. However, dendrimer synthesis often suffers from structural defects caused by incomplete reactions and difficulties associated with purification. Consequently, alternative synthetic approaches to overcome the limitations of current dendrimer synthesis are in high demand.My first PhD project mainly focuses on establishing novel strategies and methodologies for solid-phase dendrimer synthesis with advantages of convenient complete synthesis and easy purification procedures. We first developed a new and concise solid-phase synthesis of PAMAM dendrimers based on the adoption of peptide synthesis chemistry. We then constructed a small library of triazine dendrimers varying in generations and surface groups with a view to rapidly synthesizing dendrimers with structural diversity. We also strived to synthesize poly(aminoester) dendrimers although we had difficult to get it thorough.My second PhD program aims to apply the self-assembly approach for constructing supramolecular dendrimer theranostics. A small DOTA-conjugated amphiphilic dendrimer with Gd(III)-chelation was synthesized and self-assembled into supramolecular nanomicelles to encapsulate the anticancer drug doxorubicin. The obtained system constitutes a multivalent nanotheranostic to combine imaging purpose with therapeutic utility.In summary, my PhD program mainly contributes to elaborating strategies for dendrimer synthesis using both solid-phase method and self-assembly approach in the view to realizing and broadening their applications in the arenas of biomedical and material sciences

Pin1 is a peptidyl prolyl isomerase (PPIase) enzyme with two domains, the catalytic domain and the WW domain. Both domains specifically bind pSer/pThrâ Pro motifs. Pin1 plays an important role in regulating the cell cycle, and it is involved in many diseases, such as cancer, HIV-1, Alzheimerâ s disease, asthma, hepatitis B, and rheumatoid arthritis. Pin1 is a very promising target for new drug development. Three stereoisomers: (R,S)-, (S,R)- and (S,S)-Acâ pSerâ Ψ[(Z)CH=C]â Pipâ 2-(2-naphthyl)ethylamine were synthesized as inhibitors binding to the Pin1 catalytic domain. The (R,S)- and (S,R)-isomers were synthesized via a 13-step route, with overall yields of 2.0% and 1.4%, respectively. The newly formed stereogenic center in the piperidyl ring was introduced by a Luche reduction, followed by a stereoselective [2,3]-Still-Wittig rearrangement. The configuration of the stereocenter was determined by NOESY of a bicyclic derivative. The (Z)- to (E)-alkene ratio in the rearrangement was (5.5:1). The (S,S)-isomer was obtained as the epimerized by-product resulting from the (S,R)-isomer in the Na/NH3 deprotection step. The IC50 values for Pin1 inhibition were: 52, 85, and 141 μM, respectively. We concluded that in this Z-alkene isostere, the R-configuration would be preferred at both stereogenic centers, as mimics of L-Ser and L-Pip, to improve the affinity. Combinatorial chemistry is a powerful method to discover biologically active compounds, and solid-phase synthesis is most commonly used to synthesize combinatorial libraries. To identify ligands for the Pin1 WW domain, a library, R1COâ pSerâ Proâ NHR2, was designed. A new solid-phase phosphorylating reagent (SPPR) containing a phosphoramidite function was synthesized in one step from commercially available Wang resin. The SPPR was applied in the preparation of a designed library through parallel synthesis. The library contained 357 members (17 à 21), and was screened by an enzyme-linked enzyme binding assay (ELEBA). The best hits were resynthesized, and the competitive dissociation constants, Kd-rel, were measured by ELEBA, with a Kd-rel value of 130 μM for the best ligand. The absolute dissociation constants will be measured by our collaborator, Prof. Jefferey Peng, University of Notre Dame, using NMR methods. Besides the identification of the Pin1 WW domain ligands, I created a practical method for solid-phase synthesis of phosphopeptides.<br>Ph. D.

This thesis describes different aspects of protein interactions. Initially the function of peptides and their conjugates with small molecule inhibitors on the surface of Human Carbonic Anhydrase isoenzyme II (HCAII) is evaluated. The affinities for HCAII of the flexible, synthetic helix-loop-helix motif conjugated with a series of spacered inhibitors were measured by fluorescence spectroscopy and found in the best cases to be in the low nM range. Dissociation constants show considerable dependence on linker length and vary from 3000 nM for the shortest spacer to 40 nM for the longest with a minimum of 5 nM for a spacer with an intermediate length. A rationale for binding differences based on cooperativity is presented and supported by affinities as determined by fluorescence spectroscopy. Heteronuclear Single Quantum Correlation Nuclear Magnetic Resonance (HSQC) spectroscopic experiments with 15N-labeled HCAII were used for the determination of the site of interaction. The influence of peptide charge and hydrophobicity was evaluated by surface plasmon resonance experiments. Hydrophobic sidechain branching and, more pronounced, peptide charge was demonstrated to modulate peptide – HCAII binding interactions in a cooperative manner, with affinities spanning almost two orders of magnitude. Detailed synthesis of small molecule inhibitors in a general lead discovery library as well as a targeted library for inhibition of α-thrombin is described. For the lead discovery library 160 members emanate from two N4-aryl-piperazine-2-carboxylic acid scaffolds derivatized in two dimensions employing a combinatorial approach on solid support. The targeted library was based on peptidomimetics of the D-Phe-Pro-Arg showing the scaffolds cyclopropane-1R,2R-dicarboxylic acid and (4-amino-3-oxo-morpholin-2-yl)- acetic acid as proline isosters. Employing 4-aminomethyl-benzamidine as arginine mimic and different hydrophobic amines and electrophiles as D-phenylalanine mimics resulted in 34 compounds showing IC50 values for α-thrombin ranging more than three orders of magnitude with the best inhibitor showing an IC50 of 130 nM. Interestingly, the best inhibitors showed reversed stereochemistry in comparison with a previously reported series employing a 3-oxo-morpholin-2-yl-acetic acid scaffold.

The thesis describes the development of new and improved methods for analyzing degradation markers from organophosphorus Chemical Warfare Agents (CWAs). Paper I and II describes an innovative and significantly improved method for the enrichment, derivatization (trimethysilylation) and GC-MS analysis of a broad range of organophosphorus CWAs degradation markers, namely the alkylphosphonic acids and a zwitterionic compound. That was achieved using solid phase disc extraction in combination with solid phase derivatization. The new method overcomes most limitations observed with existing techniques: it offers almost 100 % recoveries, requires no elution or evaporation steps, facilitates miniaturization of the solid sorbent and reagent, is compatible with in-vial derivatization, and minimizes the chromatographic background due to the use of a highly selective anion exchange sorbent disc. Paper III describes the development of new fluorinated diazomethane derivatization reagents and their evaluation for rapid and high sensitivity screening and identification of nerve agent degradation markers. The reagents are water-tolerant to some extent, which simplifies the derivatization step. The best reagent identified was 3,5-bis(trifluoromethyl)benzyl diazomethane, which outperformed the other reagent isomers tested and also the established commercial alternative, pentafluorobenzylbromide, allowing for the rapid (5 min) and direct derivatization of a 25 μL aqueous sample in acetonitrile. The spectra of the formed derivatives (high-energy collision induced fragmentation MS/MS) were used to construct a database (Paper IV) that proved to be superior in terms of match factor and probability compared to EI data gathered for trimethylsilyl derivatives. The study also focused on efforts towards achieving detailed structure information on the alkyl chains of the compounds in question using diagnostic ion interpretation. The final paper (paper V) describes the first rapid direct derivatization method for analyzing nerve agent metabolites in urine at trace levels. The method is based on the derivative from the paper III and the unambiguous identification was proven using a combination of low resolution and high resolution negative ion chemical ionization selected ion monitoring techniques. Novel results presented in these papers include: the first in-situ derivatization of alkylphosphonic acids on an SPE disc; the first direct derivatization of nerve agent markers in water and biomedical samples; the first high sensitivity GC-MS screening for these markers; and the first highly reproducible high-energy isomer specific CID MS/MS library. Overall, the results presented in this thesis represent significant contributions to the analysis of nerve agent degradation products.