A Novel Human Neutralizing mAb Recognizes Delta,Gamma and Omicron Variants of SARS-CoV-2 and Can Be Used in Combination with Sotrovimab

The dramatic experience with SARS-CoV-2 has alerted the scientific community to be ready to face new epidemics/pandemics caused by new variants. Among the therapies against the pandemic SARS-CoV-2 virus, monoclonal Antibodies (mAbs) targeting the Spike glycoprotein have represented good drugs to interfere in the Spike/ Angiotensin Converting Enzyme-2 (ACE-2) interaction, preventing virus cell entry and subsequent infection, especially in patients with a defective immune system. We obtained, by an innovative phage display selection strategy, specific binders recognizing different epitopes of Spike. The novel human antibodies specifically bind to Spike-Receptor Binding Domain (RBD) in a nanomolar range and interfere in the interaction of Spike with the ACE-2 receptor. We report here that one of these mAbs, named D3, shows neutralizing activity for virus infection in cell cultures by different SARS-CoV-2 variants and retains the ability to recognize the Omicron-derived recombinant RBD differently from the antibodies Casirivimab or Imdevimab. Since anti-Spike mAbs, used individually, might be unable to block the virus cell entry especially in the case of resistant variants, we investigated the possibility to combine D3 with the antibody in clinical use Sotrovimab, and we found that they recognize distinct epitopes and show additive inhibitory effects on the interaction of Omicron-RBD with ACE-2 receptor. Thus, we propose to exploit these mAbs in combinatorial treatments to enhance their potential for both diagnostic and therapeutic applications in the current and future pandemic waves of coronavirus.     

Efficient breadth first search on multi-GPU systems

Simple algorithms for the execution of a Breadth First Search on large graphs lead, running on clusters of GPUs, to a situation of load unbalance among threads and un-coalesced memory accesses, resulting in pretty low performances. To obtain a significant improvement on a single GPU and to scale by using multiple GPUs, we resort to a suitable combination of operations to rearrange data before processing them. We propose a novel technique for mapping threads to data that achieves a perfect load balance by leveraging prefix-sum and binary search operations. To reduce the communication overhead, we perform a pruning operation on the set of edges that needs to be exchanged at each BFS level. The result is an algorithm that exploits at its best the parallelism available on a single GPU and minimizes communication among GPUs. We show that a cluster of GPUs can efficiently perform a distributed BFS on graphs with billions of nodes.     

Light Triggers the Antiproliferative Activity of Naphthalimide-Conjugated (η6-arene)ruthenium(II) Complexes

We report the synthesis and characterization of three half-sandwich Ru(II) arene complexes [(η⁶-arene)Ru(N,N′)L][PF₆]₂ containing arene = p-cymene, N,N′ = bipyridine, and L = pyridine meta- with methylenenaphthalimide (C1), methylene(nitro)naphthalimide (C2), or methylene(piperidinyl)naphthalimide (C3). The naphthalimide acts as an antenna for photoactivation. After 3 h of irradiation with blue light, the monodentate pyridyl ligand had almost completely dissociated from complex C3, which contains an electron donor on the naphthalimide ring, whereas only 50% dissociation was observed for C1 and C2. This correlates with the lower wavelength and strong absorption of C3 in this region of the spectrum (λ_max = 418 nm) compared with C1 and C2 (λ_max = 324 and 323 nm, respectively). All the complexes were relatively non-toxic towards A549 human lung cancer cells in the dark, but only complex C3 exhibited good photocytoxicity towards these cancer cells upon irradiation with blue light (IC₅₀ = 10.55 ± 0.30 μM). Complex C3 has the potential for use in photoactivated chemotherapy (PACT).     

Cultural ‘demons’ as future builders

Usually, the shape of the future is seen as the result of a cultural flow that, according to some privileged cultural variable, like technology, goes undisturbed towards its own outcome. This is a quite naive attitude that has been very rarely successful. Both conventional technology and technology of the artificial show that, within culture, ‘demons’ are always active trying to exploit or even bypass standards in order to give birth to unexpected novelties. This is true within the pure technology area and even more in its artistic extensions. Therefore, no deterministic process is going on but, rather, a permanent remixing of chances that makes any prophecy impossible.     

Deployment of RSS-Based Indoor Positioning Systems

Location estimation based on Received Signal Strength (RSS) is the prevalent method in indoor positioning. For such positioning systems, a massive collection of training samples is needed for their calibration. The accuracy of these methods is directly related to the placement of the reference points and the radio map used to compute the device location. Traditionally, deploying the reference points and building the radio map require human intervention and are extremely time-consuming. In this paper we present an approach to reduce the manual calibration efforts needed to deploy an RSS-based localization system, both when using only one RF technology or when using a combination of RF technologies. It is an automatic approach both to build a radio map in a given workspace by means of a signal propagation model, and to assess the system calibration that best fits the required accuracy by using a multi-objective genetic algorithm.     

1923 Gleno Dam Break: Case Study and Numerical Modeling

On the morning of December 1, 1923, the Gleno Dam (located in the Central Italian Alps) suddenly collapsed a few days after the first complete reservoir filling. Nearly 4.5×106??m3 of water was released. The consequent inundation caused significant destruction along the downstream valley and a death toll of at least 356 lives. This failure is the only historical case of dam break caused by structural deficiencies that has occurred in Italy. As a result, it has deeply influenced the evolution of Italian regulations regarding dam design and hydraulic risk evaluation. However, in spite of its relevance, this event has never been characterized from a hydraulic standpoint. This paper reports the main information obtained from the analysis of a vast amount of historical documents regarding the Gleno Dam break to set up a case study useful for validating dam-break models in mountain settings. Moreover, it presents the main results of one-dimensional (1D) modeling of the dam break wave propagation accomplished with a first-order finite volume numerical scheme recently proposed in the literature for field applications. The overall effectiveness and reliability of the model are evaluated for this case characterized by very irregular topography. Finally, the practical relevance of several choices that the numerical reconstruction of this kind of event demands is tested.     

Er doped waveguide amplifiers written with femtosecond laser in germanate glasses

The authors report the fabrication and characterization of active waveguides in GeO₂–PbO–Ga₂O₃ glass samples doped with Er³⁺, written with a femtosecond laser delivering pulses of 150 fs duration at 1 kHz repetition rate. Permanent refractive index change was obtained and waveguides were formed under different laser pulse energies and scan velocities. The passive and active optical properties of the waveguides were investigated. The minimum value of propagation loss was of 4.8 dB/cm. Optical amplification at 1.5 μm under 980 nm excitation was observed showing a maximal internal gain of 2.7 dB/cm.     

FC2Q: exploiting fuzzy control in server consolidation for cloud applications with SLA constraints

Modern cloud data centers rely on server consolidation (the allocation of several virtual machines on the same physical host) to minimize their costs. Choosing the right consolidation level (how many and which virtual machines are assigned to a physical server) is a challenging problem, because contemporary multitier cloud applications must meet service level agreements in face of highly dynamic, nonstationary, and bursty workloads. In this paper, we deal with the problem of achieving the best consolidation level that can be attained without violating application service level agreements. We tackle this problem by devising fuzzy controller for consolidation and QoS (FC2Q), a resource management framework exploiting feedback fuzzy logic control, that is able to dynamically adapt the physical CPU capacity allocated to the tiers of an application in order to precisely match the needs induced by the intensity of its current workload. We implement FC2Q on a real testbed and use this implementation to demonstrate its ability of meeting the aforementioned goals by means of a thorough experimental evaluation, carried out with real‐world cloud applications and workloads. Furthermore, we compare the performance achieved by FC2Q against those attained by existing state‐of‐the‐art alternative solutions, and we show that FC2Q works better than them in all the considered experimental scenarios. Copyright © 2014 John Wiley & Sons, Ltd.