In the past three decades invasive mycoses have globally emerged as a persistent source of healthcare-associated infections. The cell wall surrounding the fungal cell opposes the turgor pressure that ...otherwise could produce cell lysis. Thus, the cell wall is essential for maintaining fungal cell shape and integrity. Given that this structure is absent in host mammalian cells, it stands as an important target when developing selective compounds for the treatment of fungal infections. Consequently, treatment with echinocandins, a family of antifungal agents that specifically inhibits the biosynthesis of cell wall (1-3)β-D-glucan, has been established as an alternative and effective antifungal therapy. However, the existence of many pathogenic fungi resistant to single or multiple antifungal families, together with the limited arsenal of available antifungal compounds, critically affects the effectiveness of treatments against these life-threatening infections. Thus, new antifungal therapies are required. Here we review the fungal cell wall and its relevance in biotechnology as a target for the development of new antifungal compounds, disclosing the most promising cell wall inhibitors that are currently in experimental or clinical development for the treatment of some invasive mycoses.
While mentorship has been shown to be critical in helping graduate students persist and complete their studies, and enter upon and succeed in their academic careers, the under-representation of ...faculty of color and women in higher education greatly reduces the opportunities for graduate students from these selfsame groups to find mentors of their race, ethnicity or gender.Recognizing that mentoring across gender, race and ethnicity inserts levels of complexity to this important process, this book both fills a major gap in the literature and provides an in-depth look at successful mentorships between senior white and under-represented scholars and emerging women scholars and scholars of color. Following a comprehensive review of the literature, this book presents chapters written by scholars who share in-depth descriptions of their cross-gender and/or cross-race/ethnicity mentoring relationships. Each article is co-authored by mentors who are established senior scholars and their former protégés with whom they have continuing collegial relationships. Their descriptions provide rich insights into the importance of these relationships, and for developing the academic pipeline for women scholars and scholars of color. Drawing on a comparative analysis of the literature and of the narrative chapters, the editors conclude by identifying the key characteristics and pathways for developing successful mentoring relationships across race, ethnicity or gender, and by offering recommendations for institutional policy and individual mentoring practice. For administrators and faculty concerned about diversity in graduate programs and academic departments, they offer clear models of how to nurture the productive scholars and teachers needed for tomorrow's demographic of students; for under-represented students, they offer compelling narratives about the rewards and challenges of good mentorship to inform their expectations and the relationships they will develop as protégés.
The organization and characteristics of early and ancient states have become the focus of a renewed interest from archaeologists, ancient historians and anthropologists in recent years. On the one ...hand, neo-evolutionary schemas of political transformation find it difficult to define some of their most basic concepts, such as 'chiefdom', 'complex chiefdom' and 'state', not to mention the transition between them. On the other hand, teleological interpretations based on linear dynamics, from less to increasingly more complex political structures, in successive steps, impose biased and too rigid views on the available evidence. In fact, recent research stresses the existence of other forms of socio-political organization, less vertically integrated and more heterarchical, that proved highly successful and resilient in the long term in tying together social groups. What is more, such forms quite often represented the basic blocks on which states were built and that managed to survive once states collapsed. Finally, nomadic, maritime and mountain populations provide fascinating examples of societies that experienced alternative forms of political organization, sometimes on a seasonal basis. In other cases, their consideration as 'marginal' populations that cultivated specialized skills ensured them a certain degree of autonomy when living either within or at the borders of states.This book explores such small-scale socio-political organizations, their potential and the historical trajectories they stimulated. A selection of historical case studies from different regions of the world may help rethink current concepts and views about the emergence and organization of political complexity and the mechanisms that prevented, occasionally, the emergence of solid polities. They may also cast some light over trajectories of historical transformation, still poorly understood as are the limits of effective state power. This book explores the importance of comparative research and long-term historical perspectives to avoid simplistic interpretations, based on the characteristics of modern Western states abusively used retrospectively.
Molecular electronics Cuevas, Juan Carlos; Scheer, Elke
2010., 2010, 2010-06-23
eBook
This book provides a comprehensive overview of the rapidly developing field of molecular electronics. It focuses on our present understanding of the electrical conduction in single-molecule circuits ...and provides a thorough introduction to the experimental techniques and theoretical concepts. It will also constitute as the first textbook-like introduction to both the experiment and theory of electronic transport through single atoms and molecules. In this sense, this publication will prove invaluable to both researchers and students interested in the field of nanoelectronics and nanoscience in general.
Pluripotent stem-cell lines can be obtained through the reprogramming of somatic cells from different tissues and species by ectopic expression of defined factors. In theory, these cells--known as ...induced pluripotent stem cells (iPSCs)--are suitable for various purposes, including disease modelling, autologous cell therapy, drug or toxicity screening and basic research. Recent methodological improvements are increasing the ease and efficiency of reprogramming, and reducing the genomic modifications required to complete the process. However, depending on the downstream applications, certain technologies have advantages over others. Here, we provide a comprehensive overview of the existing reprogramming approaches with the aim of providing readers with a better understanding of the reprogramming process and a basis for selecting the most suitable method for basic or clinical applications.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
It is widely accepted in eukaryotes that the cleavage furrow only initiates after mitosis completion. In fission yeast, cytokinesis requires the synthesis of a septum tightly coupled to cleavage ...furrow ingression. The current cytokinesis model establishes that simultaneous septation and furrow ingression only initiate after spindle breakage and mitosis exit. Thus, this model considers that although Cdk1 is inactivated at early-anaphase, septation onset requires the long elapsed time until mitosis completion and full activation of the Hippo-like SIN pathway. Here, we studied the precise timing of septation onset regarding mitosis by exploiting both the septum-specific detection with the fluorochrome calcofluor and the high-resolution electron microscopy during anaphase and telophase. Contrarily to the existing model, we found that both septum and cleavage furrow start to ingress at early anaphase B, long before spindle breakage, with a slow ingression rate during anaphase B, and greatly increasing after telophase onset. This shows that mitosis and cleavage furrow ingression are not concatenated but simultaneous events in fission yeast. We found that the timing of septation during early anaphase correlates with the cell size and is regulated by the corresponding levels of SIN Etd1 and Rho1. Cdk1 inactivation was directly required for timely septation in early anaphase. Strikingly the reduced SIN activity present after Cdk1 loss was enough to trigger septation by immediately inducing the medial recruitment of the SIN kinase complex Sid2-Mob1. On the other hand, septation onset did not depend on the SIN asymmetry establishment, which is considered a hallmark for SIN activation. These results recalibrate the timing of key cytokinetic events in fission yeast; and unveil a size-dependent control mechanism that synchronizes simultaneous nuclei separation with septum and cleavage furrow ingression to safeguard the proper chromosome segregation during cell division.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This paper estimates the incidence of state corporate taxes on the welfare of workers, landowners, and firm owners using variation in state corporate tax rates and apportionment rules. We develop a ...spatial equilibrium model with imperfectly mobile firms and workers. Firm owners may earn profits and be inframarginal in their location choices due to differences in location-specific productivities. We use the reduced-form effects of tax changes to identify and estimate incidence as well as the structural parameters governing these impacts. In contrast to standard open economy models, firm owners bear roughly 40 percent of the incidence, while workers and landowners bear 30-35 percent and 25-30 percent, respectively.
Although mammalian hearts show almost no ability to regenerate, there is a growing initiative to determine whether existing cardiomyocytes or progenitor cells can be coaxed into eliciting a ...regenerative response. In contrast to mammals, several non-mammalian vertebrate species are able to regenerate their hearts, including the zebrafish, which can fully regenerate its heart after amputation of up to 20% of the ventricle. To address directly the source of newly formed cardiomyocytes during zebrafish heart regeneration, we first established a genetic strategy to trace the lineage of cardiomyocytes in the adult fish, on the basis of the Cre/lox system widely used in the mouse. Here we use this system to show that regenerated heart muscle cells are derived from the proliferation of differentiated cardiomyocytes. Furthermore, we show that proliferating cardiomyocytes undergo limited dedifferentiation characterized by the disassembly of their sarcomeric structure, detachment from one another and the expression of regulators of cell-cycle progression. Specifically, we show that the gene product of polo-like kinase 1 (plk1) is an essential component of cardiomyocyte proliferation during heart regeneration. Our data provide the first direct evidence for the source of proliferating cardiomyocytes during zebrafish heart regeneration and indicate that stem or progenitor cells are not significantly involved in this process.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The acid pretreatment process is the most employed technique used to disrupt the lignocellulosic matrix. Thus, this paper provides an overview of the acid pretreatment considering important aspects ...related to the operation conditions, yields, future improvements and the potential use to upgrade lignocellulosic biomass in energy vectors. Moreover, this paper is focused on technical and economic aspects of the use of the acid pretreatment in bioethanol production using olive tree biomass as a case study. This review will provide the framework of the acid pretreatment based on reported applications, experimental and theoretical data. The most well-studied applications of the acid pretreatment are in bioethanol and biogas production. Furthermore, this pretreatment has been improved using solid catalysts and by increasing the solids loading. These options have advantages compared to the traditional way. Even so, improvements in the technical and energy aspects must be performed to make the implementation of this process viable from an economic and environmental perspective. Instead, the kinetic modelling and statistical analysis of the acid pretreatment can be postulated as strong tools to predict the behaviour of different feedstocks under acidic conditions. Moreover, new alternatives to increase the mass and heat transfer in this process related to reactor design conform a new research field. Regarding the case study, the acid pretreatment is one of the most energy-consuming stages of bioethanol production. Low solids loadings are recommended to obtain production costs that are comparable with those reported on the industrial level. In contrast, a high solids loading allows the environmental impact of the process to be reduced in terms of liquid waste generation and carbon dioxide emissions. Finally, the acid pretreatment should be included as an effective method for the biotechnological conversion of lignocellulosic biomass to produce energy vectors once the technical, economic and environmental drawbacks have been overcome.
•Energy vectors production can be improved using optimal acid pretreatment operating conditions.•Operation conditions and kinetic modelling are shown as key information of the acid pretreatment.•Solid catalyst and dry acid pretreatment can serve as alternative methods for biomass upgrading.•The impact of solids loading on the bioethanol production process is demonstrated and discussed.•Low solids loading in acid pretreatment increases the feasibility of bioethanol production.
We study a Chinese policy that awards substantial tax cuts to firms with R&D investment over a threshold or “notch.” Quasi-experimental variation and administrative tax data show a significant ...increase in reported R&D that is partly driven by firms relabeling expenses as R&D. Structural estimates show relabeling accounts for 24.2 percent of reported R&D and that doubling R&D would increase productivity by 9 percent. Policy simulations show that firm selection and relabeling determine the cost-effectiveness of stimulating R&D, that notch-based policies are more effective than tax credits when relabeling is prevalent, and that modest spillovers justify the program from a welfare perspective.
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