Focused Design of Novel Cyclic Peptides Endowed with GABARAP-Inhibiting Activity

(1) Background: Disfunctions in autophagy machinery have been identified in various conditions, including neurodegenerative diseases, cancer, and inflammation. Among mammalian autophagy proteins, the Atg8 family member GABARAP has been shown to be greatly involved in the autophagy process of prostate cancer cells, supporting the idea that GABARAP inhibitors could be valuable tools to fight the progression of tumors. (2) Methods: In this paper, starting from the X-ray crystal structure of GABARAP in a complex with an AnkirinB-LIR domain, we identify two new peptides by applying in silico drug design techniques. The two ligands are synthesized, biophysically assayed, and biologically evaluated to ascertain their potential anticancer profile. (3) Results: Two cyclic peptides (WC8 and WC10) displayed promising biological activity, high conformational stability (due to the presence of disulfide bridges), and K_d values in the low micromolar range. The anticancer assays, performed on PC-3 cells, proved that both peptides exhibit antiproliferative effects comparable to those of peptide K1, a known GABARAP inhibitor. (4) Conclusions: WC8 and WC10 can be considered new GABARAP inhibitors to be employed as pharmacological tools or even templates for the rational design of new small molecules.     

Mapping average equivalized income using robust small area methods

Measures of economic well‐being are often needed for geographically small areas, as economic indicators may be distributed unevenly among the subsets of relatively small regions. We consider small area estimation of average equivalized income. Disposable household income data are usually available only for a sample of households, typically too small to provide reliable estimates for small regions. We consider a small area estimation technique that is robust to outliers, produces results consistent with design weighted estimates obtained for larger areas and yield maps with approximately no shrinkage. The proposed methodology is applied to the Local Labour Systems in Tuscany (Italy).     

Coqoon

International Journal on Software Tools for Technology Transfer - User interfaces for interactive proof assistants have always lagged behind those for mainstream programming languages. Whereas...     

Formal Metatheory of Programming Languages in the Matita Interactive Theorem Prover

This paper is a report about the use of Matita, an interactive theorem prover under development at the University of Bologna, for the solution of the POPLmark Challenge, part 1a. We provide three different formalizations, including two direct solutions using pure de Bruijn and locally nameless encodings of bound variables, and a formalization using named variables, obtained by means of a sound translation to the locally nameless encoding. According to this experience, we also discuss some of the proof principles used in our solutions, which have led to the development of a generalized inversion tactic for Matita.     

Classification of drivers for industrial energy efficiency and their effect on the barriers affecting the investment decision-making process

Industrial energy efficiency represents a priority for European industrial competitiveness. Many studies offer contributions providing evidence of the existence of driving forces supporting the adoption of energy efficiency measures, but a structured approach to drivers for industrial energy efficiency is still lacking. Therefore, in the present study, we propose a definition of drivers, making emphasis on the industrial decision-maker perspective, that is needed for their classification here proposed. Focus is given to point out the difference between internal and external drivers, highlighting the major stakeholders responsible for their promotion. Drivers are further categorized into: regulatory, economic, informative, and vocational training. Moreover, we propose a framework describing the effect of drivers on barriers in the decision-making process, as well as a preliminary identification of the major stakeholders to promote drivers. The study opens several opportunities for further research in the area of industrial energy efficiency.     

Data Work: How Energy Advisors and Clients Make IoT Data Accountable

We present fieldwork findings from the deployment of an interactive sensing system that supports the work of energy advisors who give face-to-face advice to low-income households in the UK. We focus on how the system and the data it produced are articulated in the interactions between professional energy advisors and their clients, and how they collaboratively anticipate, rehearse, and perform data work. In addition to documenting how the system was appropriated in advisory work, we elaborate the ‘overhead cost’ of building collaborative action into connected devices and sensing systems, and the commensurate need to support discrete workflows and accountability systems to enable the methodical incorporation of the IoT into collaborative action. We contribute an elaboration of the social, collaborative methods of data work relevant to those who seek to design and study collaborative IoT systems.     

3D floor plan recovery from overlapping spherical images

Computational Visual Media - We present a novel approach to automatically recover, from a small set of partially overlapping spherical images, an indoor structure representation in terms of a 3D...