The Devil Is in the Definitions

Problem: Traditional American zoning separates land uses, yet many urbanists and contemporary planners argue that bringing mixed use back to the American city is the key to restoring its vibrancy.

Purpose: This article compares the American and the German approaches to regulating land use.

Methods: I derive my conclusions from a review of German federal and local regulatory documents, and interviews I conducted in the German city of Stuttgart.

Results and conclusions: The U.S. zoning approach assumes that each land use district is suitable for only a single type of human activity, such as residential, commercial, or industrial use; whereas in Germany the prevailing principle is that each land use district is suitable for multiple types of activity, and most districts end up in mixed uses. Thus, despite some nominal similarities in the land use categories employed in both countries, the zoning methods are in fact starkly different.

Takeaway for practice: The German zoning system, which commonly mixes the land uses, challenges deeply engrained assumptions that underlie standard U.S. zoning, and it may offer useful alternatives for zoning reform.     

Molecular Pathogenesis of Glioblastoma in Adults and Future Perspectives: A Systematic Review

Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed the WHO classification approach, but also created the need for developing novel and personalised therapies. This systematic review aims to highlight recent advancements in understanding the molecular pathogenesis of the GBM and discuss related novel treatment targets. A systematic search of the literature in the PubMed library was performed following the PRISMA guidelines for molecular pathogenesis and therapeutic advances. Original and meta-analyses studies from the last ten years were reviewed using pre-determined search terms. The results included articles relevant to GBM development focusing on the aberrancy in cell signaling pathways and intracellular events. Theragnostic targets and vaccination to treat GBM were also explored. The molecular pathophysiology of GBM is complex. Our systematic review suggests targeting therapy at the stemness, p53 mediated pathways and immune modulation. Exciting novel immune therapy involving dendritic cell vaccines, B-cell vaccines and viral vectors may be the future of treating GBM.     

Biological Effects of Cyclin-Dependent Kinase Inhibitors Ribociclib,Palbociclib and Abemaciclib on Breast Cancer Bone Microenvironment

The CDK4/6 inhibitors (CDKi) palbociclib, ribociclib, and abemaciclib are currently approved in combination with anti-estrogen therapy for the treatment of advanced and/or metastatic hormone receptor-positive/HER2-neu-negative breast cancer patients. Given the high incidence of bone metastases in this population, we investigated and compared the potential effects of palbociclib, ribociclib, and abemaciclib on the breast cancer bone microenvironment. Primary osteoclasts (OCs) and osteoblasts (OBs) were obtained from human monocyte and mesenchymal stem cells, respectively. OC function was evaluated by tartrate-resistant acid phosphatase assay and real-time PCR; OB activity was assessed by an alizarin red assay. OB/breast cancer co-culture models were generated via the seeding of MCF-7 cells on a layer of OBs, and tumor cell proliferation was analyzed using flow cytometry. Here, we showed that ribociclib, palbociclib, and abemaciclib exerted similar inhibitory effects on the OC differentiation and expression of bone resorption markers without affecting OC viability. On the other hand, the three CDKi did not affect the ability of OB to produce bone matrix, even if the higher doses of palbociclib and abemaciclib reduced the OB viability. In OB/MCF-7 co-culture models, palbociclib demonstrated a lower anti-tumor effect than ribociclib and abemaciclib. Overall, our results revealed the direct effects of CDKi on the tumor bone microenvironment, highlighting differences potentially relevant for clinical practice.     

Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth

Connexin37 (Cx37) and Cx40 form intercellular channels between endothelial cells (EC), which contribute to the regulation of the functions of vessels. We previously documented the participation of both Cx in developmental angiogenesis and have further shown that loss of Cx40 decreases the growth of different tumors. Here, we report that loss of Cx37 reduces (1) the in vitro proliferation of primary human EC; (2) the vascularization of subcutaneously implanted matrigel plugs in Cx37−/− mice or in WT using matrigel plugs supplemented with a peptide targeting Cx37 channels; (3) tumor angiogenesis; and (4) the growth of TC-1 and B16 tumors, resulting in a longer mice survival. We further document that Cx37 and Cx40 function in a collaborative manner to promote tumor growth, inasmuch as the injection of a peptide targeting Cx40 into Cx37−/− mice decreased the growth of TC-1 tumors to a larger extent than after loss of Cx37. This loss did not alter vessel perfusion, mural cells coverage and tumor hypoxia compared to tumors grown in WT mice. The data show that Cx37 is relevant for the control of EC proliferation and growth in different tumor models, suggesting that it may be a target, alone or in combination with Cx40, in the development of anti-tumoral treatments.     

Identification of Human Adenovirus in Respiratory Samples with Luminex Respiratory Virus Panel Fast V2 Assay and Real-Time Polymerase Chain Reaction

In order to compare the last version of the Respiratory Virus Panel (RVP) Fast assay for human Adenovirus (hAdv) detection with a specific real-time polymerase chain reaction (qPCR), which is considered the gold standard for hAdv detection, nasopharyngeal samples collected from 309 children (age range, four months to eight years) with respiratory tract infection were tested using the RVP Fast v2 assay (Luminex Molecular Diagnostics, Inc., Toronto, ON, Canada) and a specific TaqMan qPCR to identify hAdv DNA. The RVP Fast v2 assay detected 30/61 (49.2%) hAdv infections that had been identified by real-time qPCR, demonstrating a significantly lower detection rate (p < 0.001). The sensitivity of the RVP Fast v2 assay in comparison to qPCR was lower in younger children (42.9% vs. 57.7%; Cohen’s kappa coefficient, 0.53); in samples with co-infections (40.0% vs. 56.7%; Cohen’s kappa coefficient, 0.52); and in samples with hAdv type C (45.9% vs. 57.1%; Cohen’s kappa coefficient, 0.60). Samples with lower viral loads were associated with a significantly lower sensitivity of the RVP Fast v2 assay (35.1% vs. 68.2%, p = 0.01; Cohen’s kappa coefficients, 0.49). The RVP Fast v2 assay has important limitations for the detection of hAdv and cannot be used to evaluate whether hAdvs are the main etiologic agent responsible for an outbreak or when epidemiological studies are performed.     

Effect of Laser Processing Parameters on the Formation of Intermetallic Compounds in Fe-Al Dissimilar Welding

Fusion welding of steel to aluminum is difficult due to formation of different types of Fe-Al intermetallics (IMs). In this work, 2 mm-thick steel was joined to 6 mm aluminum in overlap configuration using a 8 kW CW fiber laser. A defocused laser beam was used to control the energy input and allow melting of the aluminum alone and form the bond by wetting of the steel substrate. Experimentally, the process energy was varied by changing the power density (PD) and interaction time separately to understand the influence of each of these parameters on the IM formation. It was observed that the IM formation is a complex function of PD and interaction time. It was also found that the mechanical strength of such joint could not be simply correlated to the IM layer thickness but also depends on the area of wetting of the steel substrate by molten aluminum. In order to form a viable joint, PD needs to be over a threshold value where although IM growth will increase, the strength will be better due to increased wetting. Any increase in interaction time, with PD over the threshold, will have negative effect on the bond strength.     

Belgrade, Serbia

Few cities in Europe have a history as dramatic and tumultuous as that of the Serbian capital of Belgrade. The gracious “White City,” which rises spectacularly along the banks of the Danube and the Sava River, has been the site of wars, conquests and rapidly changing fortunes for much of its thousands-years long history. Belgrade suffered heavy destruction under both World Wars, and it has the unfortunate distinction of being the only European capital to be bombed at the end of the 20th century. Its modern history is marked by abrupt shifts in political status: from a capital of a relatively small nation-state, to a center of a larger and prosperous multi-national federation, to a capital of a nation-state once again. These shifts parallel the changing geopolitical position of Serbia/Yugoslavia in Europe. In this City Profile, I present the evolution of the built environment of Belgrade in five historic stages: ancient/medieval/Ottoman, early modern, communist, transitional, and contemporary. I show how each period left a distinct spatial imprint on Belgrade’s fabric. Finally, I discuss some contemporary challenges and opportunities in planning Belgrade’s future.     

Yardstick competition: which neighbours matter?

This paper aims at testing the existence of yardstick competition by estimating a fully specified vote-function on a panel data set of 104 French local governments from 1989 to 2001. When comparing the performance of their incumbent to the one of their “neighbours”, voters might consider their close geographical neighbours but also the nearby cities that are similar according to some socio-economic characteristics such as population size. The estimation results show that voters sanction their incumbent if their own local housing tax is high. Moreover, we find that voters reward their incumbent when neighbouring cities that are similar in terms of demographic characteristics have high local taxes.     

Collaborative and Cognitive Network Platforms: Vision and Research Challenges

In this paper, we present a visionary concept referred to as Collaborative and Cognitive Network Platforms (CCNPs) as a future-proof solution for creating a dependable, self-organizing and self-managing communication substrate for effective ICT solutions to societal problems. CCNP creates a cooperative communication platform to support critical services across a range of business sectors. CCNP is based on the personal network (PN) technology which is an inherently cooperative environment prototyped in the Dutch Freeband PNP2008 and the European Union IST MAGNET projects. In CCNP, the cognitive control plane strives to exploit the resources to better satisfy the requirements of networked applications. CCNP facilitates collaboration inherently. Through cognition in the cognitive control plane, CCNP becomes a self-managed substrate. The self-managed substrate, in this paper, is defined as cognitive and collaborative middleware on which future applications run without user intervention. Endemic sensor networks may be incorporated into the CCNP concept to feed its cognitive control plane. In this paper, we present the CCNP concept and discuss the research challenges related to collaboration and cognition.     

A new input indicator for the assessment of science &; technology research?

Traditional input indicators of research performance, such as research funding, number of active scientists, and international collaborations, have been widely used to assess countries’ publication output. However, while publication in today’s English-only research world requires sound research in readable English, English proficiency may be a problem for the productivity of non-native English-speaking (NNES) countries. Data provided by the Brazilian National Research Council (CNPq) containing the academic profile of 51,223 Brazilian researchers show a correlation between English proficiency and publication output. According to our results, traditional input indicators may fall short of providing an accurate representation of the research performance of NNES developing countries.