Human cytomegalovirus inhibits antigen presentation by a sequential multistep process.

The human cytomegalovirus (HCMV) genomic unique short (US) region encodes a family of homologous genes essential for the inhibition of major histocompatibility complex (MHC) class I-mediated antigen presentation during viral infection. Here we show that US3, the only immediate early (IE) gene within the US region, encodes an endoplasmic reticulum-resident glycoprotein that prevents intracellular transport of MHC class I molecules. In contrast to the rapid degradation of newly synthesized MHC class I heavy chains mediated by the early gene product US11, we found that US3 retains stable MHC class I heterodimers in the endoplasmic reticulum that are loaded with peptides while retained in the ER. Consistent with the expression pattern of US3 and US11, MHC class I molecules are retained but not degraded during the IE period of infection. Our data identify the first nonregulatory role of an IE protein of HCMV and suggest that HCMV uses different T-cell escape strategies at different times during the infectious cycle.

A sequential dimerization mechanism for erythropoietin receptor activation.

We have probed the interaction of human erythropoietin (EPO) with its receptor (EPO-R) by analyzing a panel of 17 EPO mutants in a variety of in vitro assays. Mutant proteins were expressed in 293s cells and quantified by using an N-terminal epitope tag in conjunction with a surface plasmon resonance assay. Receptor binding was studied using both a soluble form of the EPO-R extracellular domain in an ELISA-format binding competition assay and full-length EPO-R in transfected BaF3 cells. Proliferative activity of the mutants was also determined in the BaF3-derived cell line and was correlated with the results from binding assays. Based on the results of these assays, we identified two distinct receptor binding sites on the EPO molecule. We propose that one site, containing residues Arg-150 and Lys-152, binds initially to EPO receptor on the cell surface. A second site, containing Arg-103 and Ser-104 (and possibly Arg-14), is involved in binding a second EPO-R at the cell surface, thus forming a homodimeric receptor complex. Furthermore, we demonstrate that one EPO mutant (R103A), which has previously been shown to lack proliferative function, is in fact an EPO antagonist. Taken together, these data support a sequential dimerization mechanism of EPO-R activation.

Sequential choice from several populations.

We consider the problem of sampling sequentially from two or more populations in such a way as to maximize the expected sum of outcomes in the long run.

Sequential cytokine dynamics in chronic rejection of rat renal allografts: roles for cytokines RANTES and MCP-1.

Chronic rejection, the most important cause of long-term graft failure, is thought to result from both alloantigen-dependent and -independent factors. To examine these influences, cytokine dynamics were assessed by semiquantitative competitive reverse transcriptase-PCR and by immunohistology in an established rat model of chronic rejection lf renal allografts. Isograft controls develop morphologic and immunohistologic changes that are similar to renal allograft changes, although quantitatively less intense and at a delayed speed; these are thought to occur secondary to antigen-independent events. Sequential cytokine expression was determined throughout the process. During an early reversible allograft rejection episode, both T-cell associated [interleukin (IL) 2, IL-2 receptor, IL-4, and interferon gamma] and macrophage (IL-1 alpha, tumor necrosis factor alpha, and IL-6) products were up-regulated despite transient immunosuppression. RANTES (regulated upon activation, normal T-cell expressed and secreted) peaked at 2 weeks; intercellular adhesion molecule (ICAM-1) was maximally expressed at 6 weeks. Macrophage products such as monocyte chemoattractant protein (MCP-1) increased dramatically (to 10 times), presaging intense peak macrophage infiltration at 16 weeks. In contrast, in isografts, ICAM-1 peaked at 24 weeks. MCP-1 was maximally expressed at 52 weeks, commensurate with a progressive increase in infiltrating macrophages. Cytokine expression in the spleen of allograft and isograft recipients was insignificant. We conclude that chronic rejection of kidney allografts in rats is predominantly a local macrophage-dependent event with intense up-regulation of macrophage products such as MCP-1, IL-6, and inducible nitric oxide synthase. The cytokine expression in isografts emphasizes the contribution of antigen-independent events. The dynamics of RANTES expression between early and late phases of chronic rejection suggest a key role in mediating the events of the chronic process.

Human Trafficking for sexual exploitation in Europe. Towards a true “EU approach”?

La presente tesi analizza il reato di traffico di esseri umani in Europa, con particolare attenzione al fenomeno dello sfruttamento sessuale. La ricerca è stata condotta in parte nell’ambito del progetto “FIDUCIA. New European crimes and trust-based policy” (www.fiduciaproject.eu). La tesi è composta da 5 capitoli. Il primo capitolo introduce il reato di tratta di esseri umani, a livello globale e, successivamente, nello specifico, in Europa. Vengono presentati i fattori determinanti e le origini del fenomeno. Inoltre, ne vengono fornite le definizioni e le principali caratteristiche, in linea con i più importanti documenti internazionali sul tema. Il capitolo si chiude con una panoramica statistica, che affronta anche le criticità della raccolta di dati relativi ai reati. Il secondo capitolo analizza l’approccio correntemente adottato a livello domestico ed europeo contro la tratta. Le misure vengono presentate prima dal punto di vista teorico; successivamente ne vengono forniti esempi concreti, ad esempio convenzioni internazionali, direttive, ma anche progetti di ricerca, collaborazioni internazionali tra autorità ed ONG. Il terzo capitolo si concentra sulla tratta a fini di sfruttamento sessuale. Vengono analizzati il potenziale legame con la prostituzione, e l’approccio europeo. Segue un approfondimento dei modelli legali implementati a livello europeo ed uno studio comparato di cinque paesi membri, rappresentativi dei vari modelli di regolamentazione della prostituzione (Italia, Belgio, Polonia, Germania e Svezia). Il quarto capitolo raccoglie le interviste condotte con diversi esperti che si occupano di contrasto alla tratta: ONG italiane e straniere, referenti nazionali anti-tratta di Italia, Belgio e Germania, FRONTEX, membri del Parlamento Europeo. Nelle conclusioni, vengono proposte prima una valutazione complessiva del quadro attuale, e poi alcune raccomandazioni ai governi nazionali e agli organismi sopranazionali. In particolare, visto l’obiettivo di un contrasto omogeneo e coordinato della tratta (per sfruttamento sessuale specificamente) a livello europeo, si ritiene che un modello regolamentare uniforme della prostituzione negli stati membri possa contribuire a migliorare uniformità ad efficacia dell’approccio europeo alla tratta.

Human Motion Analysis Based on Sequential Modeling of Radar Signal and Stereo Image Features

Falls are one of the greatest threats to elderly health in their daily living routines and activities. Therefore, it is very important to detect falls of an elderly in a timely and accurate manner, so that immediate response and proper care can be provided, by sending fall alarms to caregivers. Radar is an effective non-intrusive sensing modality which is well suited for this purpose, which can detect human motions in all types of environments, penetrate walls and fabrics, preserve privacy, and is insensitive to lighting conditions. Micro-Doppler features are utilized in radar signal corresponding to human body motions and gait to detect falls using a narrowband pulse-Doppler radar. Human motions cause time-varying Doppler signatures, which are analyzed using time-frequency representations and matching pursuit decomposition (MPD) for feature extraction and fall detection. The extracted features include MPD features and the principal components of the time-frequency signal representations. To analyze the sequential characteristics of typical falls, the extracted features are used for training and testing hidden Markov models (HMM) in different falling scenarios. Experimental results demonstrate that the proposed algorithm and method achieve fast and accurate fall detections. The risk of falls increases sharply when the elderly or patients try to exit beds. Thus, if a bed exit can be detected at an early stage of this motion, the related injuries can be prevented with a high probability. To detect bed exit for fall prevention, the trajectory of head movements is used for recognize such human motion. A head detector is trained using the histogram of oriented gradient (HOG) features of the head and shoulder areas from recorded bed exit images. A data association algorithm is applied on the head detection results to eliminate head detection false alarms. Then the three dimensional (3D) head trajectories are constructed by matching scale-invariant feature transform (SIFT) keypoints in the detected head areas from both the left and right stereo images. The extracted 3D head trajectories are used for training and testing an HMM based classifier for recognizing bed exit activities. The results of the classifier are presented and discussed in the thesis, which demonstrates the effectiveness of the proposed stereo vision based bed exit detection approach.

All the rest is merely exploitation and perseverance : the poster art of Frank Kozik

"The history of poster art tends to focus on the art of Henri Toulouse-Latrec, Jules Cheret, and Alfonse Mucha, while leaving out or barely mentioning the work of artists such as Wes Wilson, Stanley Mouse, and Alton Kelley. The aim of this thesis is to widen the gaze of poster art by centering on a contemporary rock poster artist: Frank Kozik. By focusing on formal and sociological analysis ofa number of Kozik's posters, I illustrate how he not only fits in with the arc of poster art development, but also influences it into the next century"

Sequential and parallel synchronous alternating iterative methods

The so-called parallel multisplitting nonstationary iterative Model A was introduced by Bru, Elsner, and Neumann [Linear Algebra and its Applications 103:175-192 (1988)] for solving a nonsingular linear system Ax = b using a weak nonnegative multisplitting of the first type. In this paper new results are introduced when A is a monotone matrix using a weak nonnegative multisplitting of the second type and when A is a symmetric positive definite matrix using a P -regular multisplitting. Also, nonstationary alternating iterative methods are studied. Finally, combining Model A and alternating iterative methods, two new models of parallel multisplitting nonstationary iterations are introduced. When matrix A is monotone and the multisplittings are weak nonnegative of the first or of the second type, both models lead to convergent schemes. Also, when matrix A is symmetric positive definite and the multisplittings are P -regular, the schemes are also convergent.

Synthesis of Dihydroisobenzofurans via Palladium-Catalyzed Sequential Alkynylation/Annulation of 2-Bromobenzyl and 2-Chlorobenzyl Alcohols under Microwave Irradiation

The palladium-catalyzed synthesis of dihydroisobenzofurans has been performed by sequential Sonogashira cross-coupling/cyclization reactions between terminal alkynes and 2-(hydroxymethyl)bromo- and chlorobenzenes in methanol as solvent at 130 °C under microwave irradiation. A 4,4′-dichlorobenzophenone oxime-derived chloro-bridged palladacycle is an efficient pre-catalyst to perform this tandem process using 2-dicyclohexylphosphanyl-2′,4′,6′-triisopropylbiphenyl (Xphos) as ancillary ligand and potassium hydroxide as base in the absence of a copper cocatalyst. Under these conditions, functionalized 2-bromo- and 2-chlorobenzaldehydes are also suitable partners in the domino process affording phthalans in good yields. All the reactions can be performed under air and employing reagent-grade chemicals under low loading conditions (1 mol% Pd).

A Sequential Algorithm for the Rigorous Design of Thermally Coupled Distillation Sequences

A sequential design method is presented for the design of thermally coupled distillation sequences. The algorithm starts by selecting a set of sequences in the space of basic configurations in which the internal structure of condensers and reboilers is explicitly taken into account and extended with the possibility of including divided wall columns (DWC). This first stage is based on separation tasks (except by the DWCs) and therefore it does not provide an actual sequence of columns. In the second stage the best arrangement in N-1 actual columns is performed taking into account operability and mechanical constraints. Finally, for a set of candidate sequences the algorithm try to reduce the number of total columns by considering Kaibel columns, elimination of transfer blocks or columns with vertical partitions. An example illustrate the different steps of the sequential algorithm.