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Developing drug delivery systems to target cytotoxic drugs directly into tumor cells is still a compelling need with regard to reducing side effects and improving the efficacy of cancer chemotherapy. In this work, silk fibroin nanoparticles (SFNs) have been designed to load a previously described cytotoxic compound (NDI-1) that disrupts the cell cycle by specifically interacting with non-canonical secondary structures of DNA. SFNs were then functionalized on their surface with cyclic pentapeptides incorporating the Arg-Gly-Asp sequence (cRGDs) to provide active targeting toward glioma cell lines that abundantly express ανβ3 and ανβ5 integrin receptors. Cytotoxicity and selective targeting were assessed by in vitro tests on human glioma cell lines U373 (highly-expressing integrin subunits) and D384 cell lines (low-expressing integrin subunits in comparison to U373). SFNs were of nanometric size (d50 less than 100 nm), round shaped with a smooth surface, and with a negative surface charge; overall, these characteristics made them very likely to be taken up by cells. The active NDI-1 was loaded into SFNs with high encapsulation efficiency and was not released before the internalization and degradation by cells. Functionalization with cRGDs provided selectivity in cell uptake and thus cytotoxicity, with a significantly higher cytotoxic effect of NDI-1 delivered by cRGD-SFNs on U373 cells than on D384 cells. This manuscript provides an in vitro proof-of-concept of cRGD-silk fibroin nanoparticles’ active site-specific targeting of tumors, paving the way for further in vivo efficacy tests.

Active spiral-wave active localization is a technique for determining location of acoustic targets [after Dzikowicz et al., JASA 146, 4821–4830 (2019)], which relies on measuring the phase difference between a reference and spiral wavefronts. This research presents a monostatic model of spiral detection and tracking for multiple targets in sparse noise limited environments. Simulation and experimental results from an acoustic spiral wave beacon in a small underwater test tank will be presented. Results show good agreement to resolve targets in horizontal and vertical dimensions with a compact aperture. [Work supported by ONR 321MS.]

Background: Italy has one of the world’s oldest populations, and suffered one the highest death tolls from Coronavirus disease 2019 (COVID-19) worldwide. Older people with cardiovascular diseases (CVDs), and in particular hypertension, are at higher risk of hospitalization and death for COVID-19. Whether hypertensionmedicationsmay increase the risk for death in older COVID 19 inpatients at the highest risk for the disease is currently unknown. Methods: Data from 5,625 COVID-19 inpatients were manually extracted from medical charts from 61 hospitals across Italy. From the initial 5,625 patients, 3,179 were included in the study as they were either discharged or deceased at the time of the data analysis. Primary outcome was inpatient death or recovery. Mixed effects logistic regression models were adjusted for sex, age, and number of comorbidities, with a random effect for site. Results: A large proportion of participating inpatients were ≥65 years old (58%), male (68%), non-smokers (93%) with comorbidities (66%). Each additional comorbidity increased the risk of death by 35% [adjOR = 1.35 (1.2, 1.5) p < 0.001]. Use of ACE inhibitors, ARBs, beta-blockers or Ca-antagonists was not associated with significantly increased risk of death. There was a marginal negative association between ARB use and death, and a marginal positive association between diuretic use and death. Conclusions: This Italian nationwide observational study of COVID-19 inpatients, the majority of which ≥65 years old, indicates that there is a linear direct relationship between the number of comorbidities and the risk of death. Among CVDs, hypertension and pre-existing cardiomyopathy were significantly associated with risk of death. The use of hypertension medications reported to be safe in younger cohorts, do not contribute significantly to increased COVID-19 related deaths in an older population that suffered one of the highest death tolls worldwide.

Arg-Gly-Asp (RGD)-based cyclopentapeptides (cRGDs) have a high affinity towards integrin αvβ3 and αvβ5, which are overexpressed by many tumor cells. Here, curcumin-loaded silk fibroin nanoparticles (SFNs) have been functionalized on the surface with cRGD to provide active targeting towards tumor cells, a “click reaction” between the RGD-based cyclopentapeptide carrying an azide group and triple-bond-functionalized nanoparticles has been exploited. Both naked and functionalized SFNs were less than 200 nm in diameter and showed a round-shaped morphology but, after functionalization, SFNs increased in size and protein molecular weight. The functionalization of SFNs’ surfaces with cRGD provided active internalization by cells overexpressing integrin receptors. At the lowest concentration tested (0.01 mg/mL), functionalized SFNs showed more effective uptake with respect to the naked by tumor cells that overexpress integrin receptors (but not for non-overexpressing ones). In contrast, at higher concentrations, the non-specific cell membrane protein–particle interactions are promoted and coupled to specific and target mediated uptake. Visual observations by fluorescence microscopy suggested that SFNs bind to integrin receptors on the cell surface and are then internalized by endocytosis. Overall, SFN functionalization provided in vitro active targeting for site-specific delivery of anticancer drugs, boosting activity and sparing healthy organs.

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p

Broadband multimode piezoelectric spherical shell transducers are investigated for underwater sound by exciting the zeroth and/or first order (0 + 1) extensional modes of vibration with and without acoustical baffles of different types. Measurements of the frequency response (transmit pressure per volt or TVR), radiation patterns and electromechanical impedance reveal useful tradeoffs and design guidance for many practical applications. Measurements are in good agreement with theoretical closed form analytical results.

Jamming, whether intentional or not, threatens stable wireless communications by impeding a transmitted signal. New jamming technologies are regularly developed and deployed for use, which behave differently from their predecessors in order to bypass defense mechanisms. This makes existing jammer classifiers difficult to implement in fast changing dynamic environments, since human intervention is needed every time a new jamming technology is introduced. Improper maintenance will result in misclassification of the technology or allow jammers to pass through defenses. These scenarios will greatly reduce the performance of wireless networks and increase the response time for recovering from these attacks. As 5G continues to become more widespread, and other faster networks are released, wireless data rates will continue to grow. This furthers the need for a faster and more reliable jammer classifier, as shorter interruptions in service will cause even more data loss to occur. Incremental learning (IL) is a technique in machine learning that allows the introduction of new information to a previously trained network. Using IL, it is possible to create classifiers that can grow in number of classes without the need to retrain a new network from nothing. This allows remote devices to learn to adapt in dynamic environments with far lower memory cost. In this paper, we developed an IL-based jammer classifier using software defined radio (SDR) to detect when a jammer is present and classify the type and learn to classify new technologies when the type has not been encountered before.

In the 1480s, da Vinci invented the first hygrometer using cellulose fibres to attract moisture from the atmosphere. Five hundred years later, Williams and Blanc showed that the depressed vapour pressure of a hygroscopic sessile droplet can inhibit condensation within an annular dry zone on the surface. What remains unresolved to this day is whether these regions of suppressed condensation around hygroscopic agents are due to inhibited nucleation versus inhibited growth of the condensate. We elucidate the competition between these two mechanisms by generating steady-state dry zones about frozen water droplets. The choice of ice as the hygroscopic material was motivated by its unique ability to remain undiluted as it attracts moisture from the air. Experiments, scaling models, and simulations where the ice droplet size, ambient humidity and surface temperature are systematically varied reveal that over the vast majority of the parameter space, the inhibited growth dry zone wins the duel over the nucleation dry zone.

We show that condensation growing on wheat leaves infected with the leaf rust fungus, Puccinia triticina , is capable of spontaneously launching urediniospores off the plant. This surprising liberation mechanism is enabled by the superhydrophobicity of wheat leaves, which promotes a jumping-droplet mode of condensation powered by the surface energy released from coalescence events. We found that urediniospores often adhere to the self-propelled condensate, resulting in liberation rates of approximately 10 cm −2 h −1 for leaves infected with rust. Urediniospores were catapulted up to 5 mm from the leaf’s surface, a distance sufficient to clear the laminar boundary layer for subsequent dispersal even in gentle winds.

We show that condensation growing on wheat leaves infected with the leaf rust fungus, Puccinia triticina is capable of spontaneously launching urediniospores off the plant. This surprising liberation mechanism is enabled by the superhydrophobicity of wheat leaves, which promotes a jumping-droplet mode of condensation powered by the surface energy released from coalescence events. We found that urediniospores often adhere to the self-propelled condensate, resulting in liberation rates of approximately 10 cm−2 h−1 for leaves infected with rust. Urediniospores were catapulted up to 5 mm from the leaf’s surface, a distance sufficient to clear the laminar boundary layer for subsequent dispersal even in gentle winds.

We report about three unliked cases of meningococcal meningitis caused by the ST-11/ET-37 strain of Neisseria meningitidis serogroup W. Two of the three cases, detected in Sicily on June and July 2014, were migrants from Mali and Eritrea. The third case was a fatal meningitis occurred on November 2014 in a 37 years old man, working in an immigrant center in Calabria. This report suggests that tetravalent conjugate vaccines (ACYW) should be actively offered to the staff of migrants’ reception centers.

We report about three unliked cases of meningococcal meningitis caused by the ST-11/ET-37 strain of Neisseria meningitidis serogroup W. Two of the three cases, detected in Sicily on June and July 2014, were migrants from Mali and Eritrea. The third case was a fatal meningitis occurred on November 2014 in a 37 years old man, working in an immigrant center in Calabria. This report suggests that tetravalent conjugate vaccines (ACYW) should be actively offered to the staff of migrants' reception centers.

New rigid-flexible copolymers based on poly( p -benzamide) (PBA) and poly[2-phenylene (5-benzimidazole)] (PABI) were synthesized, varying the molecular weight of the flexible block. Ternary solutions in dimethylacetamide—3% LiCl show the peculiar behaviour expected theoretically for this kind of system. In particular, it was demonstrated that more copolymer enters the anisotropic phase as the PABI chain length becomes shorter. Comparison with homopolymer mixtures shows the usefulness of the copolymer in improving the amount of flexible chains inside the mesophase.

The ternary diagram involving a rigid polymer [poly(p-benzamide) (PBA)], a flexible polymer [poly(2-phenylene(5-benzimidazole)isophthalamide) b) (PABI)] and a diluent composed of dimethylacetamide plus 3 wt.-% LiCl (DMAc/3LiCl) was investigated. Addition of PABI to PBA solutions increases the critical volume fraction value at which a nematic phase is observed. The line connecting these values at different PBA/PABI ratios divides a region of isotropic solutions from a biphasic area. No case of a single anisotropic phase was observed. A peculiarity of the diagram is that the composition of the anisotropic phase in the biphasic region lies on the PBA-diluent axis when the molecular weight of PABI is relatively high, whereas it shows a small content of PABI when its molecular weight is low. This result has recently been theoretically predicted by considering the existence of anisotropic interactions in the mesophase. The agreement between theoretical and experimental phase diagrams is fairly good.

High-dose Melphalan (HDM) is the most commonly used conditioning regimen for autologous stem cell transplantation (ASCT) in newly diagnosed transplant-eligible Multiple Myeloma (MM) patients. Recent evidence suggests that the depth of response after induction therapy influences progression free survival (PFS) and, in most studies, overall survival (OS). Actually the effect of the inclusion of new drugs in the conditioning regimen for ASCT is still unknown. Phase I-II clinical study showed that the addition of Bortezomib (Bor) to HDM is safe and a promising conditioning regimen. Thus, in this study we analyzed a single center experience on the use of Bor in combination with HDM (Bor-HDM) as conditioning regimen before ASCT as frontline treatment in MM patients in order to evaluate the safety and the response rates of this combination regimen. We analyzed a total cohort of 48 newly diagnosed MM patients (25 females and 23 males; median age 60 years, range 42-70) admitted consecutively to our Bone Marrow Transplantation Center from 2008 to 2014. Regarding prognostic stratification, 25% of patients were classified as stage III according to International Staging System (ISS), and 12% exhibited high-risk cytogenetic features (defined by presence of del(17p) and/or t(4;14) and/or t(14;16)). All patients with the exception of three underwent to 3-drugs Bor-based induction therapy including Bor (median cumulative dose: 28.9 mg/m2), Thalidomide and Dexamethasone (VTD). After induction therapy and stem cell collection 28 out of 48 patients were treated with Bor-HDM, whereas 20 patients with HDM alone as conditioning regimen before ASCT. HDM was administered on day -2 (median dose: 200 mg/m2), and a single-dose Bortezomib at the dosage of 1.3 mg/m2 was administered on day -1 in the Bor-HDM group. Stem cells were reinfused on day 0 (median number of CD34+ infused: 3.3x106/Kg, range 1.86-6x106/Kg). Responses were evaluated at day 100 after ASCT, and definitions of response were used according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for MM. Quantitative variables were compared by non-parametric Kruskal-Wallis and Mann-Whitney tests as appropriate and categorical variables were analyzed by Chi-square and Fisher's exact test. pvalue of Any significant difference was not observed between Bor-HDM group vs HDM group, regarding age at diagnosis (p=0.77), sex (p=0.24), cumulative induction dose of Bortezomib (p=0.42), dose of Melphalan used for conditioning (p=0.16) and the median number of CD34+ cells infused (p=0.12). Distribution of ISS stage was similar in the two groups (p=0.14), as well as that of high-risk cytogenetic (p=0.14). Moreover the response rates after the induction therapy was not statistically different in the two groups of patients analyzed (sCR + CR: 19% in Bor-HDM group vs 26% in HDM group; VGPR: 33% vs 48%; PR: 48% vs 26%, p=0.22). Any significant difference on hematopoietic recovery rates was not observed in Bor-HDM as compared to HDM alone with a mean time to neutrophil recovery of 12 days (range 9-18) and to platelet recovery of 12 days (range 9-21) in both groups. Bor-HDM conditioning was well tolerated, without increase of neuropathy occurrence. Then we analyzed the response rate after ASCT, showing that the overall response rate (ORR) was significantly higher in Bor-HDM group as compared to HDM (sCR+CR: 56% in Bor-HDM vs 17% in HDM; VGPR 30% vs 28%; PR: 15% vs 56%, p=0.0072) with a higher number of "good quality" response (sCR + CR + VGPR: 86% vs 45%; p=0.0075). The number of sCR was also significantly higher in Bor-HDM as compared to HDM alone (23% vs 0%, p=0.067). Moreover an improvement of the response rate after ABMT was seen more frequently in the Bor-HDM group as compared to the HDM group (p=0.0063). We then observed that the number of patients that underwent tandem ASCT was higher in the HDM group (66% vs 41%), even not reaching a statistical significance. In conclusion, this retrospective analysis suggests that BOR-HDM is safe as conditioning regimen with a higher response rate after ASCT as compared to the standard HDM regimen giving the rational design for randomized studies needed to assess whether this conditioning regimen is superior to HDM alone. Disclosures Giuliani: Celgene: Research Funding; Janssen: Research Funding.

Two different synthetic routes have been used to synthesize poly[2-phenylene-(5-benzimidazole)] isophthalamide (PABI), an aromatic polyamide that shows good compatibility with rigid chain polymers such as poly(p-benzamide). The influence of the conditions of synthesis in determining the molecular weight of PABI has been investigated in order to use this polymer for rigid—flexible copolymers with specific characteristics. Values of [η] and Mw have been determined in 96% H2SO4 and dimethylacetamide, and conformational properties have been investigated by viscometry and molecular dynamics simulations.