Estimation of the angle between ultrasound beam and blood velocitythrough correlation functions

Correlation functions, calculated on the ultrasonic echoes scattered by blood, provide a rich harvest of information concerning the local speed, which has often been underestimated; in particular, blood flow measurement usually yields only the longitudinal component of the velocity, even if significant information about the speed direction can be extracted. In this paper it is shown how correlation functions, calculated on the dependency of both time and space displacements, allow us to evaluate the angle Θ between ultrasound beam and blood flow; when straight vessels are considered, this single parameter, combined with the longitudinal velocity profile, permits the complete hemodynamic characterization. The underlying theory is developed and preliminary experimental results are presented     

Membrane traffic in polarized neurons

The plasma membrane of neurons can be divided into two domains, the soma-dendritic and the axonal. These domains perform different functions: the dendritic surface receives and processes information while the axonal surface is specialized for the rapid transmission of electrical impulses. This functional specialization is generated by sorting and anchoring mechanisms that guarantee the correct delivery and retention of specific membrane proteins. Our understanding of neuronal membrane protein sorting is primarily based on studies of protein overexpression in cultured neurons. These studies revealed that newly synthesized membrane proteins are segregated in the Golgi apparatus in the cell body from where they are transported to the axonal or dendritic surface. Such segregation presumably depends on sorting motifs in the proteins' primary structure. They appear to be located in the cytoplasmic tail for dendritic proteins and in the transmembrane-ectodomain for axonal proteins. Recent studies on neurotransmitter segregation suggest that anchoring in the correct subdomain of the plasma membrane also requires cytoplasmic tail information for binding to the cytoskeleton either directly or by linker proteins. Both mechanisms, sorting and retention, gradually mature during neural development. Young neurons appear to develop initial polarity by other mechanisms, presumably analogous to the mechanisms used by migrating cells.     

Main and interactive effects of shiftwork, age and work stress on health in an Italian sample of healthcare workers

Among healthcare workers, shiftwork (mostly if nightwork is also included), ageing and work-related stress may be factors leading to impaired health. Such risk factors may also operate in interaction, resulting in an even increased harm for health. The present study aims at evaluating these relationships in a sample of 1842 hospital workers in Northern Italy. Subjects were mainly women, 33.1% were aged > or = 45 yr, and they were almost evenly distributed between dayworkers and rotating shiftworkers (nights included). Shiftwork was associated with poor sleep, while it was protective against gastrointestinal disorders, poor work ability and job dissatisfaction. Work stress was the risk factor with the highest relevance for poor health. Ageing was associated with lower physical health. Few significant interactions were observed. Shiftwork with nights and high work stress significantly interacted in increasing the risk for poor sleep. The "healthy worker effect" may have played a strong role in study findings.     

Platelet lysate and adipose mesenchymal stromal cells on silk fibroin nonwoven mats for wound healing

In this work platelet lysate (PL) and adipose‐derived mesenchymal stromal cells (ASCs) seeded on nonwoven fibroin mats were in vitro and in vivo evaluated for tissue regenerative applications. Nonwoven mats obtained by a large scale water entanglement technique were characterized for their physico‐chemical properties. Results indicated a high purity of fibroin fibers, their stability after sterilization process and appropriate technological properties suitable for tissue engineering. Moreover, the scaffolds in vitro supported adhesion and migration of ASCs and the presence of PL improved the cell proliferation. The products were then applied on epithelial/dermal wounds carried out on the dorsal surface of rabbit: the skin reparative process was solved in 9 days, with a completely restitutio ad integrum of the epithelium in animals treated with PL alone; ASCs did not further improve the wound healing. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42942.     

Verifying Object-based Graph Grammars

The development of concurrent and reactive systems is gaining importance since they are well-suited to modern computing platforms, such as the Internet. However, the development of correct concurrent and reactive systems is a non-trivial task. Object-based graph grammar (OBGG) is a visual formal language suitable for the specification of this class of systems. In previous work, a translation from OBGG to PROMELA (the input language of the SPIN model checker) was defined, enabling the verification of OBGG models using SPIN. In this paper we extend this approach in two different ways: (1) the approach for property specification is improved, enabling to prove properties not only about possible OBGG derivations, but also about the internal state of involved objects; (2) an approach is defined to interpret PROMELA races as OBGG derivations, generating graphical counter-examples for properties that are not true for a given OBGG model. Another contribution of this paper is (3) the definition of a method for model checking partial systems (isolated objects or a set of objects) using an assume-guarantee approach. A gas station system modeled with OBGGs is used to illustrate the contributions.This work is partially sponsored by projects IQ-MObile (CNPq-Brazil/CNR-Italy) and PLATUS (CNPq).Osmar Marchi dos Santos is partially sponsored by CAPES-Brazil.     

Large-matrix-ordering technique with applications to transposition

An important class of data-order variations that can be accomplished by means of read-write routines between the main memory and external-storage devices is simply described in terms of a symbol string, called an `order key?. Optimum procedures for ordering matrices larger than the available main storage are presented.     

Photothermal Therapy Promotes Tumor Infiltration and Antitumor Activity of CAR T Cells

Chimeric antigen receptor (CAR)‐redirected T lymphocytes (CAR T cells) show modest therapeutic efficacy in solid tumors. The desmoplastic structure of the tumor and the immunosuppressive tumor microenvironment usually account for the reduced efficacy of CAR T cells in solid tumors. Mild hyperthermia of the tumor reduces its compact structure and interstitial fluid pressure, increases blood perfusion, releases antigens, and promotes the recruitment of endogenous immune cells. Therefore, the combination of mild hyperthermia with the adoptive transfer of CAR T cells can potentially increase the therapeutic index of these cells in solid tumors. It is found that the chondroitin sulfate proteoglycan‐4 (CSPG4)‐specific CAR T cells infused in Nod scid gamma mice engrafted with the human melanoma WM115 cell line have superior antitumor activity after photothermal ablation of the tumor. The findings suggest that photothermal therapy facilitates the accumulation and effector function of CAR T cells within solid tumors.     

Delivery Techniques for Enhancing CAR T Cell Therapy against Solid Tumors

Chimeric antigen receptor (CAR) T cells exhibit promising results for cancer immunotherapy. However, the clinical success is still restricted to certain types of blood cancers, while in solid tumors the clinical activity is modest and potential toxicities remain a concern. There are various barriers that prevent CAR T cells from combating solid tumors. Therefore, distinct strategies have been explored to augment CAR T cell proliferative capacity, persistence, and effector function. Altering the tumor microenvironment, and in particular its physiochemical properties and immunosuppressive milieu, is of great significance to facilitate CAR T cell therapy. In this article, emerging strategies implemented to overcome the barriers of CAR T cell therapy in solid tumors are reviewed. Enhancing infiltration, activation, and persistence of CAR T cells has been addressed in several preclinical models. The future development of this field to promote innovation and clinical translation is also discussed.     

Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant

mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE.