Чисельний аналіз полів в околі вершини тріщини у двоконсольному балочному тришаровому зразку, що навантажений згинальними моментами

The paper presents an interfacial crack problem adopted for studying fracture toughness and debonding tolerance of sandwich composite materials. A specific example of the fracture sandwich specimens such as a double cantilever sandwich beam subjected to uneven bending moments (DCB-UBM) is considered. A finite element modelling of this test method is carried out using the ABAQUS™ code. Atwo-dimensional (2-D) model has been developed to highlight the distribution of stress and displacement fields and to calculate the energy release rate (ERR) and the phase angle at the interface crack between two dissimilar orthotropic materials. The J − integral approach built-in ABAQUS code and the crack surface displacement method programmed as an add-on subroutine within the Matlab® environment are used for computing those fracture parameters. The influence of different moment ratios on the near crack tip stress state, the ERR, and phase angle fracture parameters is estimated.Представлено проблему міжфазної тріщини, за допомогою якої вивчаються в’язкість руйнування та стійкість до відшарування у тришарових композиційних матеріалах. Розглянуто конкретний приклад тришарового зразка на руйнування – двохконсольна тришарова балка, яка навантажена згинальними моментами. Скінчено елементне моделювання цього тесту здійснюється за допомогою програми ABAQUS™. Двовимірна модель була розроблена для виявлення розподілу полів напружень та переміщень, а також для розрахунку швидкості вивільнення енергії руйнування та фазового кута міжфазної тріщини поміж двома різними ортотропними матеріалами. J − інтеграл підхід, який є вбудованою опцією у ABAQUS, та метод відносних зміщень на поверхнях тріщини, який запрограмований у середовищі Matlab® окремою програмою, використовуються для обчислення цих параметрів руйнування. Оцінюється вплив різних співвідношень згинальних моментів на напружений стан в околі вершини тріщини, швидкості вивільнення енергії руйнування і фазовий кут

Functionally Distinct Subsets of Lineage-Biased Multipotent Progenitors Control Blood Production in Normal and Regenerative Conditions.

Despite great advances in understanding the mechanisms underlying blood production, lineage specification at the level of multipotent progenitors (MPPs) remains poorly understood. Here, we show that MPP2 and MPP3 are distinct myeloid-biased MPP subsets that work together with lymphoid-primed MPP4 cells to control blood production. We find that all MPPs are produced in parallel by hematopoietic stem cells (HSCs), but with different kinetics and at variable levels depending on hematopoietic demands. We also show that the normally rare myeloid-biased MPPs are transiently overproduced by HSCs in regenerating conditions, hence supporting myeloid amplification to rebuild the hematopoietic system. This shift is accompanied by a reduction in self-renewal activity in regenerating HSCs and reprogramming of MPP4 fate toward the myeloid lineage. Our results support a dynamic model of blood development in which HSCs convey lineage specification through independent production of distinct lineage-biased MPP subsets that, in turn, support lineage expansion and differentiation.This work was supported by NIH awards F32HL106989 and K01DK098315 to E.M.P, grants from Leukaemia and Lymphoma Research, Cancer Research UK and core support by the Wellcome Trust to B.G.; and NIH grant R01HL092471, Rita Allen Scholar Award and Leukemia Lymphoma Society Scholar Award to E.P.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Elsevier/Cell Press

Improving clinical cognitive testing: Report of the AAN Behavioral Neurology Section Workgroup

OBJECTIVE: To evaluate the evidence basis of single-domain cognitive tests frequently used by behavioral neurologists in an effort to improve the quality of clinical cognitive assessment. METHODS: Behavioral Neurology Section members of the American Academy of Neurology were surveyed about how they conduct clinical cognitive testing, with a particular focus on the Neurobehavioral Status Exam (NBSE). In contrast to general screening cognitive tests, an NBSE consists of tests of individual cognitive domains (e.g., memory or language) that provide a more comprehensive diagnostic assessment. Workgroups for each of 5 cognitive domains (attention, executive function, memory, language, and spatial cognition) conducted evidence-based reviews of frequently used tests. Reviews focused on suitability for office-based clinical practice, including test administration time, accessibility of normative data, disease populations studied, and availability in the public domain. RESULTS: Demographic and clinical practice data were obtained from 200 respondents who reported using a wide range of cognitive tests. Based on survey data and ancillary information, between 5 and 15 tests in each cognitive domain were reviewed. Within each domain, several tests are highlighted as being well-suited for an NBSE. CONCLUSIONS: We identified frequently used single-domain cognitive tests that are suitable for an NBSE to help make informed choices about clinical cognitive assessment. Some frequently used tests have limited normative data or have not been well-studied in common neurologic disorders. Utilizing standardized cognitive tests, particularly those with normative data based on the individual's age and educational level, can enhance the rigor and utility of clinical cognitive assessment

Fibroblast heterogeneity in the cancer wound

Fibroblasts regulate the structure and function of healthy tissues, participate transiently in tissue repair after acute inflammation, and assume an aberrant stimulatory role during chronic inflammatory states including cancer. Such cancer-associated fibroblasts (CAFs) modulate the tumor microenvironment and influence the behavior of neoplastic cells in either a tumor-promoting or tumor-inhibiting manner. These pleiotropic functions highlight the inherent plasticity of fibroblasts and may provide new avenues to understand and therapeutically intervene in malignancies. We discuss the emerging themes of CAF biology in the context of tumorigenesis and therapy

Intracellular Trafficking Considerations in the Development of Natural Ligand-Drug Molecular Conjugates for Cancer

Overexpressed receptors, characteristic of many cancers, have been targeted by various researchers to achieve a more specific treatment for cancer. A common approach is to use the natural ligand for the overexpressed receptor as a cancer-targeting agent which can deliver a chemically or genetically conjugated toxic molecule. However, it has been found that the therapeutic efficacy of such ligand-drug molecular conjugates can be limited, since they naturally follow the intracellular trafficking pathways of the endogenous ligands. Therefore, a thorough understanding of the intracellular trafficking properties of these ligands can lead to novel design criteria for engineering ligands to be more effective drug carriers. This review presents a few commonly used ligand/receptor systems where intracellular trafficking considerations can potentially improve the therapeutic efficacy of the ligand-drug molecular conjugates

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference