A heuristic approach for packing identical rectangles in convex regions

In this paper we propose a heuristic approach for the problem of packing equal rectangles within a convex region. The approach is based on an Iterated Local Search scheme, in which the key step is the perturbation move. Different perturbation moves, both combinatorial and continuous ones, are proposed and compared through extensive computational experiments on a set of test instances. The overall results are quite encouraging.     

Counting clicks and beeps: Exploring numerosity based haptic and audio PIN entry

Haptic and audio cues now appear commonly in computer interfaces, partially due to inherent advantages such as their support for eyes-free interaction. Their invisible, unobservable nature also makes them ideal candidates for security interfaces in which users have to enter secret information such as passwords. In particular, researchers have explored this idea through the design of PIN entry authentication systems based on multi-modal combinations of visual and non-visual content or on the recognition of small sets of unimodal haptic or audio stimuli. This paper highlights the benefits and performance limitations of these approaches and introduces an alternative based on unimodal audio or haptic temporal numerosity – the ability to accurately and rapidly determine the number of cues presented in rapid temporal succession. In essence, in a numerosity interface, rather than recognizing distinct cues, users must count the number of times that a single cue occurs. In an iterative process of design and evaluation, three prototypes implementing this concept are presented and studies of their use reported. The results show the fastest PIN entry times and lowest error rates to be 8 s and 2%, figures that improve substantially on previous research. These results are attained while maintaining low levels of workload and substantial resistance to observation attack (as determined via camera attack security studies). In sum, this paper argues that unimodal audio and haptic numerosity is a valuable and relatively unexplored metaphor for non-visual input and demonstrates the validity of this claim in the demanding task of unobservable authentication systems.     

Inverse Analysis of Impact Test Data: Experimental Study on Polymeric Materials Displaying Brittle Behaviour

This paper deals with the influence of the testing equipment on impact load measurements. A previously developed method of analysis and processing of the experimental data based on a refined analogical model of the impact event and inverse problem techniques is used. This method makes it possible to obtain the mechanical response of the material, notwithstanding the disturbance of the dynamic effects associated to the test. Results from tests carried out both on falling weight and swing pendulum instrumented testing machines are compared. It is shown that this method can give an accurate estimation of the actual bending force in impact testing independent of the testing equipment.     

Proteomics and Extracellular Vesicles as Novel Biomarker Sources in Peritoneal Dialysis in Children

Peritoneal dialysis (PD) represents the dialysis modality of choice for pediatric patients with end-stage kidney disease. Indeed, compared with hemodialysis (HD), it offers many advantages, including more flexibility, reduction of the risk of hospital-acquired infections, preservation of residual kidney function, and a better quality of life. However, despite these positive aspects, PD may be associated with several long-term complications that may impair both patient’s general health and PD adequacy. In this view, chronic inflammation, caused by different factors, has a detrimental impact on the structure and function of the peritoneal membrane, leading to sclerosis and consequent PD failure both in adults and children. Although several studies investigated the complex pathogenic pathways underlying peritoneal membrane alterations, these processes remain still to explore. Understanding these mechanisms may provide novel approaches to improve the clinical outcome of pediatric PD patients through the identification of subjects at high risk of complications and the implementation of personalized interventions. In this review, we discuss the main experimental and clinical experiences exploring the potentiality of the proteomic analysis of peritoneal fluids and extracellular vesicles as a source of novel biomarkers in pediatric peritoneal dialysis.     

From Reparative Surgery to Regenerative Surgery: State of the Art of Porous Hydroxyapatite in Cranioplasty

Decompressive craniectomy is one of the most common neurosurgical procedures, usually performed after neuropathological disorders, such as traumatic brain injury (TBI), but also vascular accidents (strokes), erosive tumours, infections and other congenital abnormalities. This procedure is usually followed by the reconstruction of the cranial vault, which is also known as cranioplasty (CP). The gold-standard material for the reconstruction process is the autologous bone of the patient. However, this is not always a feasible option for all patients. Several heterologous materials have been created in the last decades to overcome such limitation. One of the most prominent materials that started to be used in CP is porous hydroxyapatite. PHA is a bioceramic material from the calcium phosphate family. It is already widely used in other medical specialties and only recently in neurosurgery. In this narrative review of the literature, we summarize the evidence on the use of PHA for cranial reconstruction, highlighting the clinical properties and limitations. We also explain how this material contributed to changing the concept of cranial reconstruction from reparative to regenerative surgery.     

Insights into the Pharmacokinetics and In Vitro Cell-Based Studies of the Imidazoline I2 Receptor Ligand B06

The impact of neurodegenerative diseases (ND) is becoming unbearable for humankind due to their vast prevalence and the lack of efficacious treatments. In this scenario, we focused on imidazoline I₂ receptors (I₂-IR) that are widely distributed in the brain and are altered in patients with brain disorders. We took the challenge of modulating I₂-IR by developing structurally new molecules, in particular, a family of bicyclic α-iminophosphonates, endowed with high affinity and selectivity to these receptors. Treatment of two murine models, one for age-related cognitive decline and the other for Alzheimer’s disease (AD), with representative compound B06 ameliorated their cognitive impairment and improved their behavioural condition. Furthermore, B06 revealed beneficial in vitro ADME-Tox properties. The pharmacokinetics (PK) and metabolic profile are reported to de-risk B06 for progressing in the preclinical development. To further characterize the pharmacological properties of B06, we assessed its neuroprotective properties and beneficial effect in an in vitro model of Parkinson’s disease (PD). B06 rescued the human dopaminergic cell line SH-SY5Y from death after treatment with 6-hydroxydopamine (6-OHDA) and showed a crucial anti-inflammatory effect in a cellular model of neuroinflammation. This research reveals B06 as a putative candidate for advancing in the difficult path of drug discovery and supports the modulation of I₂-IR as a fresh approach for the therapy of ND.     

First Report on Genome Editing via Ribonucleoprotein (RNP) in Castanea sativa Mill.

Castanea sativa is an important tree nut species worldwide, highly appreciated for its multifunctional role, in particular for timber and nut production. Nowadays, new strategies are needed to achieve plant resilience to diseases, climate change, higher yields, and nutritional quality. Among the new plant breeding techniques (NPBTs), the CRISPR/Cas9 system represents a powerful tool to improve plant breeding in a short time and inexpensive way. In addition, the CRISPR/Cas9 construct can be delivered into the cells in the form of ribonucleoproteins (RNPs), avoiding the integration of exogenous DNA (GMO-free) through protoplast technology that represents an interesting material for gene editing thanks to the highly permeable membrane to DNA. In the present study, we developed the first protoplast isolation protocol starting from European chestnut somatic embryos. The enzyme solution optimized for cell wall digestion contained 1% cellulase Onozuka R-10 and 0.5% macerozyme R-10. After incubation for 4 h at 25 °C in dark conditions, a yield of 4,500,000 protoplasts/mL was obtained (91% viable). The transfection capacity was evaluated using the GFP marker gene, and the percentage of transfected protoplasts was 51%, 72 h after the transfection event. The direct delivery of the purified RNP was then performed targeting the phytoene desaturase gene. Results revealed the expected target modification by the CRISPR/Cas9 RNP and the efficient protoplast editing.