Locally class-presentable and class-accessible categories

We generalize the concepts of locally presentable and accessible categories. Our framework includes such categories as small presheaves over large categories and ind-categories. This generalization is intended for applications in the abstract homotopy theory

Brown representability for space-valued functors

In this paper we prove two theorems which resemble the classical cohomological and homological Brown representability theorems. The main difference is that our results classify small contravariant functors from spaces to spaces up to weak equivalence of functors. In more detail, we show that every small contravariant functor from spaces to spaces which takes coproducts to products up to homotopy and takes homotopy pushouts to homotopy pullbacks is naturally weekly equivalent to a representable functor. The second representability theorem states: every contravariant continuous functor from the category of finite simplicial sets to simplicial sets taking homotopy pushouts to homotopy pullbacks is equivalent to the restriction of a representable functor. This theorem may be considered as a contravariant analog of Goodwillie's classification of linear functors.Comment: 19 pages, final version, accepted by the Israel Journal of Mathematic

Sporadic calcitonin-negative medullary thyroid carcinoma is not more aggressive than its classic counterpart: case report and review of the literature

Objective: medullary thyroid carcinoma (MTC) with normal serum basal calcitonin (calcitonin-negative MTC) is uncommon. The exact mechanism for this paradox is unclear. It has been suggested that the loss of ability to secrete calcitonin is due to tumor cell dedifferentiation and may confer a worse prognosis. Methods: we describe a 45-year-old woman with a sporadic 4.5-cm well-differentiated MTC, who despite having normal preoperative serum basal calcitonin and poor calcitonin immunostaining in tumor cells, remains in remission 5 years after total thyroidectomy with bilateral central neck dissection. Out of the 20 patients with calcitonin-negative MTC reported to date, we include 16 patients with clinical disease at presentation to determine if they fare worse than their classic MTC counterparts. We try to correlate the extent of calcitonin immunostaining with the degree of tumor differentiation to determine if poor tumor calcitonin immunoreactivity is an indicator of tumor cell dedifferentiation. Results: Seven and 9 patients with calcitonin-negative MTC had poorly-differentiated and well-differentiated tumors, respectively. Four patients in the former group died from metastatic MTC within 3 years of the diagnosis. The status of the 2 living patients with known follow-up information was one with N1 disease and one in remission. In the well-differentiated group, 2 patients had N1M1 disease and 7 patients were in remission. According to the number of tumor cells immunoreactive to calcitonin, the 15 patients with known data were classified in 3 groups: 1+ group (only few tumor cells stained weakly for calcitonin), 7 patients; 2+ group (many tumor cells stained focally for calcitonin), 2 patients; and 3+ group (most tumor cells stained strongly for calcitonin), 6 patients. The level of calcitonin immunoreactivity did not correlate with the patient’s clinical status. Conclusion: the degree of tumor differentiation is a far better predictor of outcome than the extent of calcitonin immunoreactivity and poor tumor calcitonin staining is not necessarily an indicator of tumor cell dedifferentiation

Hausdorff dimension of operator semistable L\'evy processes

Let $X=\{X(t)\}_{t\geq0}$ be an operator semistable L\'evy process in \rd with exponent $E$, where $E$ is an invertible linear operator on \rd and $X$ is semi-selfsimilar with respect to $E$. By refining arguments given in Meerschaert and Xiao \cite{MX} for the special case of an operator stable (selfsimilar) L\'evy process, for an arbitrary Borel set B\subseteq\rr_+ we determine the Hausdorff dimension of the partial range $X(B)$ in terms of the real parts of the eigenvalues of $E$ and the Hausdorff dimension of $B$.Comment: 23 page

Nanomedical Theranostics in Cardiovascular Disease

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. New diagnostic and therapeutic strategies are needed to mitigate this public health issue. Advances in nanotechnology have generated innovative strategies for diagnosis and therapy in a variety of diseases, foremost in cancer. Based on these studies, a novel concept referred to as nanomedical theranostics, or the combinatory application of nanoparticulate agents to allow diagnostic therapy, is being explored to enable image-guided, personalized, or targeted treatment. Preclinically, theranostics have been gradually applied to CVD with several interesting and encouraging findings. This article summarizes studies and challenges of nanotheranostic strategies in CVD. It also evaluates nanotheranostic strategies that may potentially be utilized to benefit patients

The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells

© 2016 Chorny et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).Pentraxin 3 (PTX3) is a fluid-phase pattern recognition receptor of the humoral innate immune system with ancestral antibody-like properties but unknown antibody-inducing function. In this study, we found binding of PTX3 to splenic marginal zone (MZ) B cells, an innate-like subset of antibody-producing lymphocytes strategically positioned at the interface between the circulation and the adaptive immune system. PTX3 was released by a subset of neutrophils that surrounded the splenic MZ and expressed an immune activation-related gene signature distinct from that of circulating neutrophils. Binding of PTX3 promoted homeostatic production of IgM and class-switched IgG antibodies to microbial capsular polysaccharides, which decreased in PTX3-deficient mice and humans. In addition, PTX3 increased IgM and IgG production after infection with blood-borne encapsulated bacteria or immunization with bacterial carbohydrates. This immunogenic effect stemmed from the activation of MZ B cells through a neutrophil-regulated pathway that elicited class switching and plasmablast expansion via a combination of T cell-independent and T cell-dependent signals. Thus, PTX3 may bridge the humoral arms of the innate and adaptive immune systems by serving as an endogenous adjuvant for MZ B cells. This property could be harnessed to develop more effective vaccines against encapsulated pathogens.This study was supported by European Advanced grant ERC-2011-ADG-20110310, Ministerio de Ciencia e Innovación grant SAF2011-25241, and Marie Curie reintegration grant PIRG-08-GA-2010-276928 to A. Cerutti; Sara Borrell post-doctoral fellowships to A. Chorny; and US National Institutes of Health grants R01 AI57653, U01 AI95613, P01 AI61093, and U19 096187 to A. Cerutti. C. Cunha and A. Carvalho were funded by grants from Fundação para a Ciência e Tecnologia, co-funded by Programa Operacional Regional do Norte (ON.2—O Novo Norte)., and from the Quadro de Referência Estratégico Nacional (SFRH/BPD/96176/2013 to C. Cunha and grant IF/00735/2014 to A. Carvalho) through the Fundo Europeu de Desenvolvimento Regional and Projeto Estratégico (LA 26 – 2013–2014; PEst-C/SAU/LA0026/2013). The financial support of the European Commission (FP7-HEALTH-2011-ADITEC-No.280873 and ERC-PHII-669415) to A. Mantovani is gratefully acknowledged.info:eu-repo/semantics/publishedVersio

Co-encapsulation of human serum albumin and superparamagnetic iron oxide in PLGA nanoparticles: Part I. Effect of process variables on the mean size

PLGA (poly d,l-lactic-co-glycolic acid) nanoparticles (NPs) encapsulating magnetite nanoparticles (MNPs) along with a model drug human serum albumin (HSA) were prepared by double emulsion solvent evaporation method. This Part I will focus on size and size distribution of prepared NPs, whereas encapsulation efficiency will be discussed in Part II. It was found that mean hydrodynamic particle size was influenced by five important process variables. To explore their effects, a five-factorial, three-level experimental design and statistical analysis were carried out using STATISTICA® software. Effect of process variables on the mean size of nanoparticles was investigated and finally conditions to minimize size of NPs were proposed. GAMS™/MINOS software was used for optimization. The mean hydrodynamic size of nanoparticles ranged from 115 to 329 nm depending on the process conditions. Smallest possible mean particle size can be achieved by using low polymer concentration and high dispersion energy (enough sonication time) along with small aqueous/organic volume ratio

Predicting In Vivo Efficacy of Potential Restenosis Therapies by Cell Culture Studies: Species-Dependent Susceptibility of Vascular Smooth Muscle Cells

Although drug-eluting stents (DES) are successfully utilized for restenosis therapy, the development of local and systemic therapeutic means including nanoparticles (NP) continues. Lack of correlation between in vitro and in vivo studies is one of the major drawbacks in developing new drug delivery systems. The present study was designed to examine the applicability of the arterial explant outgrowth model, and of smooth muscle cells (SMC) cultures for prescreening of possible drugs. Elucidation of different species sensitivity (rat, rabbit, porcine and human) to diverse drugs (tyrphostins, heparin and bisphsophonates) and a delivery system (nanoparticles) could provide a valuable screening tool for further in vivo studies. The anticipated sensitivity ranking from the explant outgrowth model and SMC mitotic rates (porcine>rat>>rabbit>human) do not correlate with the observed relative sensitivity of those animals to antiproliferative therapy in restenosis models (rat≥rabbit>porcine>human). Similarly, the inhibitory profile of the various antirestenotic drugs in SMC cultures (rabbit>porcine>rat>>human) do not correlate with animal studies, the rabbit- and porcine-derived SMC being highly sensitive. The validity of in vitro culture studies for the screening of controlled release delivery systems such as nanoparticles is limited. It is suggested that prescreening studies of possible drug candidates for restenosis therapy should include both SMC cell cultures of rat and human, appropriately designed with a suitable serum

The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells

Pentraxin 3 (PTX3) is a fluid-phase pattern recognition receptor of the humoral innate immune system with ancestral antibody-like properties but unknown antibody-inducing function. In this study, we found binding of PTX3 to splenic marginal zone (MZ) B cells, an innate-like subset of antibody-producing lymphocytes strategically positioned at the interface between the circulation and the adaptive immune system. PTX3 was released by a subset of neutrophils that surrounded the splenic MZ and expressed an immune activation–related gene signature distinct from that of circulating neutrophils. Binding of PTX3 promoted homeostatic production of IgM and class-switched IgG antibodies to microbial capsular polysaccharides, which decreased in PTX3-deficient mice and humans. In addition, PTX3 increased IgM and IgG production after infection with blood-borne encapsulated bacteria or immunization with bacterial carbohydrates. This immunogenic effect stemmed from the activation of MZ B cells through a neutrophil-regulated pathway that elicited class switching and plasmablast expansion via a combination of T cell–independent and T cell–dependent signals. Thus, PTX3 may bridge the humoral arms of the innate and adaptive immune systems by serving as an endogenous adjuvant for MZ B cells. This property could be harnessed to develop more effective vaccines against encapsulated pathogens.European Advanced grant ERC-2011-ADG-20110310, Ministerio de Ciencia e Innovación grant SAF2011-25241, and Marie Curie reintegra -tion grant PIRG-08-GA-2010-276928 to A. Cerutti; Sara Borrell post-doctoral fellow -ships to A. Chorny; and US National Institutes of Health grants R01 AI57653, U01 AI95613, P01 AI61093, and U19 096187 to A. Cerutti. C. Cunha and A. Carvalho were funded by grants from Fundação para a Ciência e Tecnologia, co-funded by Programa Operacional Regional do Norte (ON.2—O Novo Norte)., and from the Quadro de Referência Estratégico Nacional (SFRH/BPD/96176/2013 to C. Cunha and grant IF/00735/2014 to A. Carvalho) through the Fundo Europeu de Desenvolvimento Regional and Projeto Estratégico (LA 26 – 2013–2014; PEst-C/SAU/LA0026/2013