On Coordinating Personalized Web Services using COOPS

This paper presents CooPS, which is a method for Coordinating Personalized Services. These services are primarily offered to mobile users. Very little has been done so far regarding first, personalizing Web services for the benefit of mobile users and second, providing the methodological support to designers who specify the operations of personalization. Various obstacles still exist such as lack of techniques for modeling and specifying the integration of personalization into Web services, and existing approaches for Web services composition typically facilitate orchestration only, while neglecting contextual information on users and Web services

A novel technique for evaluating and selecting logistics service providers based on the logistics resource view

The increasing importance of logistics outsourcing and availability of logistics services providers (LSPs) highlights the significance and complexity of the LSP evaluation and selection process. Most existing LSP evaluation and selection studies use historical performance data and assume independence among decision criteria. This paper proposes an integrated logistics outsourcing approach to evaluate and select LSPs based on their logistics resources and capabilities. This novel approach combines a fuzzy decision making trial, valuation laboratory (FDEMATEL) and fuzzy techniques to order preferences by similarity to ideal solution (FTOPS IS) methods. The new multi-criteria decision making (MCDM) model addresses the impact relationships between decision criteria and ranks LSP alternatives against weighted resources and capabilities. The effectiveness of this approach is demonstrated through a real case study and a two-phase sensitivity analysis confirms its robustness

Polimerne mješavine obložene Eudragitom: Potencijalni sustav za kontroliranu peroralnu isporuku teofilina

Sustained release (SR) dosage forms enable prolonged and continuous deposition of the drug in the gastrointestinal (GI) tract and improve the bioavailability of medications characterized by a narrow absorption window. In this study, a new strategy is proposed for the development of SR dosage forms for theophylline (TPH). Design of the delivery system was based on a sustained release formulation, with a modified coating technique and swelling features aimed to extend the release time of the drug. Different polymers, such as Carbopol 71G (CP), sodium carboxymethylcellulose (SCMC), ethylcellulose (EC) and their combinations were tried. Prepared matrix tablets were coated with a 5 % (m/m) dispersion of Eudragit (EUD) in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for drug concentration and in vitro drug release. It was found that the in vitro drug release rate decreased with increasing the amount of polymer. Coating with EUD resulted in a significant lag phase in the first two hours of dissolution in the acidic pH of simulated gastric fluid (SGF) due to decreased water uptake, and hence decreased driving force for drug release. Release became faster in the alkaline pH of simulated intestinal fluid (SIF) owing to increased solubility of both the coating and matrixing agents. The optimized formulation was subjected to in vivo studies in rabbits and the pharmacokinetic parameters of developed formulations were compared with the commercial (Asmanyl®) formulation. Asmanyl® tablets showed faster absorption (tmax 4.0 h) compared to the TPH formulation, showing a tmax value of 8.0 h. The cmax and AUC values of TPH formulation were significantly (p < 0.05) higher than those for Asmanyl®, revealing relative bioavailability of about 136.93 %. Our study demonstrated the potential usefulness of eudraginated polymers for the oral delivery of the sparingly soluble drug theophylline.Pripravci za produljeno oslobađanje (SR) omogućavaju produljeno i kontinuirano oslobađanje lijeka u gastrointestinalnom (GI) traktu i poboljšavaju bioraspoloživost lijekova s uskim apsorpcijskim prozorom. U radu se predlaže nova strategija za razvoj formulacija s produljenim oslobađanjem teofilina (TPH), koja se temelji na sustavu za produljeno oslobađanje, kojem je u svrhu produljenja vremena oslobađanja modificiran način oblaganja i bubrenja. Korišteni su različiti polimeri, kao što su Carbopol 71G (CP), natrijeva karboksimetilceluloza (SCMC), etilceluloza (EC) i njihove kombinacije. Pripravljene matriks tablete obložene su 5-postotnom (m/m) disperzijom Eudragita (EUD) kako bi se postiglo produljeno oslobađanje tijekom 24 h. U pripravljenim formulacijama određena je koncentracija lijeka i in vitro oslobađanje. Rezultati pokazuju da se povećanjem udjela polimera smanjuje brzina oslobađanja in vitro. Oblaganje s EUD značajno je produljilo lag fazu tijekom prva 2 sata otapanja u kiselom pH simuliranog želučanog soka (SGF). Naime, oblaganje usporava ulazak vode i tako smanjuje pogonsku silu za oslobađanje lijeka. Zbog povećane topljivosti obložnog sloja i matriksa u lužnatom mediju, oslobađanje u simuliranoj intestinalnoj tekućini (SIF) je brže. Optimizirana formulacija ispitana je in vivo na zečevima. Farmakokinetički parametri novih formulacija uspoređivani su s komercijalnim pripravkom Asmanyl®. Asmanyl® tablete pokazuju bržu apsorpciju (tmax 4,0 h) u odnosu na TPH formulaciju (tmax 8,0 h). cmax i AUC vrijednosti TPH formulacije bile su značajno (p < 0,05) više od onih za Asmanyl®, što ukazuje na relativnu bioraspoloživost od oko 136,93 %. Stoga smatramo da su polimeri obloženi eudragitom potencijalno korisni za oralnu upotrebu teško topljivog lijeka teofilina

Factors influencing patient satisfaction with dental appearance and treatments they desire to improve aesthetics

Background: We assessed factors influencing patients’ satisfaction with their dental appearance and the treatments they desired to improve dental aesthetics. Methods: A cross-sectional study was performed out among 235 adult patients who visited the Hospital Universiti Sains Malaysia dental clinic. A structured, interviewer-guided questionnaire was used to identify patient satisfaction with their general dental appearance, cosmetic elements and desired treatments. Results: The 235 patients consisted of 70 males (29.8%) and 165 females (70.2%), of mean age 31.5 years (SD 13.0). Of these patients, 124 (52.8%) were not satisfied with their general dental appearance. In addition, 132 patients (56.2%) were not happy with the color of their teeth, 76 (32.3%), regarded their teeth were poorly aligned, 62 (26.4%), as crowded and 56 (23.4%) protruded. Dissatisfaction with tooth color was significantly higher in female than in male patients (odds ratio [OR] of 1.99 (95% confidence interval [CI] 1.13-3.50). Tooth whitening was the treatment most desired by patients (48.1%). Results of multiple logistic regression analysis showed that patient dissatisfaction with general dental appearance was significantly associated with female gender (OR = 2.18; 95% CI: 1.18-4.03), unhappiness with tooth color (OR = 3.05; 95% CI: 1.74-5.34) and the opinion that their teeth protruded (OR = 2.91, 95% CI: 1.44-5.91)

A Novel CCR5 Mutation Common in Sooty Mangabeys Reveals SIVsmm Infection of CCR5-Null Natural Hosts and Efficient Alternative Coreceptor Use In Vivo

In contrast to HIV infection in humans and SIV in macaques, SIV infection of natural hosts including sooty mangabeys (SM) is non-pathogenic despite robust virus replication. We identified a novel SM CCR5 allele containing a two base pair deletion (Δ2) encoding a truncated molecule that is not expressed on the cell surface and does not support SIV entry in vitro. The allele was present at a 26% frequency in a large SM colony, along with 3% for a CCR5Δ24 deletion allele that also abrogates surface expression. Overall, 8% of animals were homozygous for defective CCR5 alleles and 41% were heterozygous. The mutant allele was also present in wild SM in West Africa. CD8+ and CD4+ T cells displayed a gradient of CCR5 expression across genotype groups, which was highly significant for CD8+ cells. Remarkably, the prevalence of natural SIVsmm infection was not significantly different in animals lacking functional CCR5 compared to heterozygous and homozygous wild-type animals. Furthermore, animals lacking functional CCR5 had robust plasma viral loads, which were only modestly lower than wild-type animals. SIVsmm primary isolates infected both homozygous mutant and wild-type PBMC in a CCR5-independent manner in vitro, and Envs from both CCR5-null and wild-type infected animals used CXCR6, GPR15 and GPR1 in addition to CCR5 in transfected cells. These data clearly indicate that SIVsmm relies on CCR5-independent entry pathways in SM that are homozygous for defective CCR5 alleles and, while the extent of alternative coreceptor use in SM with CCR5 wild type alleles is uncertain, strongly suggest that SIVsmm tropism and host cell targeting in vivo is defined by the distribution and use of alternative entry pathways in addition to CCR5. SIVsmm entry through alternative pathways in vivo raises the possibility of novel CCR5-negative target cells that may be more expendable than CCR5+ cells and enable the virus to replicate efficiently without causing disease in the face of extremely restricted CCR5 expression seen in SM and several other natural host species

The HIV Envelope but Not VSV Glycoprotein Is Capable of Mediating HIV Latent Infection of Resting CD4 T Cells

HIV fusion and entry into CD4 T cells are mediated by two receptors, CD4 and CXCR4. This receptor requirement can be abrogated by pseudotyping the virion with the vesicular stomatitis virus glycoprotein (VSV-G) that mediates viral entry through endocytosis. The VSV-G-pseudotyped HIV is highly infectious for transformed cells, although the virus circumvents the viral receptors and the actin cortex. In HIV infection, gp120 binding to the receptors also transduces signals. Recently, we demonstrated a unique requirement for CXCR4 signaling in HIV latent infection of blood resting CD4 T cells. Thus, we performed parallel studies in which the VSV-G-pseudotyped HIV was used to infect both transformed and resting T cells in the absence of coreceptor signaling. Our results indicate that in transformed T cells, the VSV-G-pseudotyping results in lower viral DNA synthesis but a higher rate of nuclear migration. However, in resting CD4 T cells, only the HIV envelope-mediated entry, but not the VSV-G-mediated endocytosis, can lead to viral DNA synthesis and nuclear migration. The viral particles entering through the endocytotic pathway were destroyed within 1–2 days. These results indicate that the VSV-G-mediated endocytotic pathway, although active in transformed cells, is defective and is not a pathway that can establish HIV latent infection of primary resting T cells. Our results highlight the importance of the genuine HIV envelope and its signaling capacity in the latent infection of blood resting T cells. These results also call for caution on the endocytotic entry model of HIV-1, and on data interpretation where the VSV-G-pseudotyped HIV was used for identifying HIV restriction factors in resting T cells

The TA Framework: Designing Real-time Teaching Augmentation for K-12 Classrooms

Recently, the HCI community has seen increased interest in the design of teaching augmentation (TA): tools that extend and complement teachers' pedagogical abilities during ongoing classroom activities. Examples of TA systems are emerging across multiple disciplines, taking various forms: e.g., ambient displays, wearables, or learning analytics dashboards. However, these diverse examples have not been analyzed together to derive more fundamental insights into the design of teaching augmentation. Addressing this opportunity, we broadly synthesize existing cases to propose the TA framework. Our framework specifies a rich design space in five dimensions, to support the design and analysis of teaching augmentation. We contextualize the framework using existing designs cases, to surface underlying design trade-offs: for example, balancing actionability of presented information with teachers' needs for professional autonomy, or balancing unobtrusiveness with informativeness in the design of TA systems. Applying the TA framework, we identify opportunities for future research and design.Comment: to be published in Proceedings of the 2020 CHI Conference on Human Factors in Computing Systems, 17 pages, 10 figure

Exposure to Apoptotic Activated CD4+ T Cells Induces Maturation and APOBEC3G- Mediated Inhibition of HIV-1 Infection in Dendritic Cells

Dendritic cells (DCs) are activated by signaling via pathogen-specific receptors or exposure to inflammatory mediators. Here we show that co-culturing DCs with apoptotic HIV-infected activated CD4+ T cells (ApoInf) or apoptotic uninfected activated CD4+ T cells (ApoAct) induced expression of co-stimulatory molecules and cytokine release. In addition, we measured a reduced HIV infection rate in DCs after co-culture with ApoAct. A prerequisite for reduced HIV infection in DCs was activation of CD4+ T cells before apoptosis induction. DCs exposed to ApoAct or ApoInf secreted MIP-1α, MIP-1β, MCP-1, and TNF-α; this effect was retained in the presence of exogenous HIV. The ApoAct-mediated induction of co-stimulatory CD86 molecules and reduction of HIV infection in DCs were partially abrogated after blocking TNF-α using monoclonal antibodies. APOBEC3G expression in DCs was increased in co-cultures of DCs and ApoAct but not by apoptotic resting CD4+ T cells (ApoRest). Silencing of APOBEC3G in DC abrogated the HIV inhibitory effect mediated by ApoAct. Sequence analyses of an env region revealed significant induction of G-to-A hypermutations in the context of GG or GA dinucleotides in DNA isolated from DCs exposed to HIV and ApoAct. Thus, ApoAct-mediated DC maturation resulted in induction of APOBEC3G that was important for inhibition of HIV-infection in DCs. These findings underscore the complexity of differential DC responses evoked upon interaction with resting as compared with activated dying cells during HIV infection

HIV-2 interaction with cell coreceptors: amino acids within the V1/V2 region of viral envelope are determinant for CCR8, CCR5 and CXCR4 usage

© 2014 Santos-Costa et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Human immunodeficiency virus 1 and 2 (HIV-1 and HIV-2) use cellular receptors in distinct ways. Besides a more promiscuous usage of coreceptors by HIV-2 and a more frequent detection of CD4-independent HIV-2 isolates, we have previously identified two HIV-2 isolates (HIV-2MIC97 and HIV-2MJC97) that do not use the two major HIV coreceptors: CCR5 and CXCR4. All these features suggest that in HIV-2 the Env glycoprotein subunits may have a different structural organization enabling distinct - although probably less efficient - interactions with cellular receptors. Results: By infectivity assays using GHOST cell line expressing CD4 and CCR8 and blocking experiments using CCR8-specific ligand, I-309, we show that efficient replication of HIV-2MIC97 and HIV-2MJC97 requires the presence of CCR8 at plasma cell membrane. Additionally, we disclosed the determinants of chemokine receptor usage at the molecular level, and deciphered the amino acids involved in the usage of CCR8 (R8 phenotype) and in the switch from CCR8 to CCR5 or to CCR5/CXCR4 usage (R5 or R5X4 phenotype). The data obtained from site-directed mutagenesis clearly indicates that the main genetic determinants of coreceptor tropism are located within the V1/V2 region of Env surface glycoprotein of these two viruses. Conclusions: We conclude that a viral population able to use CCR8 and unable to infect CCR5 or CXCR4-positive cells, may exist in some HIV-2 infected individuals during an undefined time period, in the course of the asymptomatic stage of infection. This suggests that in vivo alternate molecules might contribute to HIV infection of natural target cells, at least under certain circumstances. Furthermore we provide direct and unequivocal evidence that the usage of CCR8 and the switch from R8 to R5 or R5X4 phenotype is determined by amino acids located in the base and tip of V1 and V2 loops of HIV-2 Env surface glycoprotein.This work was supported by grants from: Fundação para a Ciência e Tecnologia (FCT; PPCDT/SAU-IMI/55726/2004); Fundação para a Ciência e Tecnologia and Ministério da Saúde de Portugal (VIH/SAU/0006/2011); and from Gilead Sciences Portugal (Programa Gilead Génese).info:eu-repo/semantics/publishedVersio