Study of new polar intermetallic compounds: synthesis, structural relations and real space chemical bonding analysis

The syntheses, structural characterizations and theoretical DFT-based investigations for different R\u2013M\u2013Ge (R = rare earth metal; M = another metal) germanides are reported. The R2PdGe6 and R2LiGe6 series, together with La2CuGe6 and La2AgGe6 compounds, were structurally characterized by single crystal X-ray diffraction, indicating the oS72-Ce2(Ga0.1Ge0.9)7 modification as the correct one. The alternative In-flux method, once optimized, produced three good quality R2PdGe6 single crystals: Pr2PdGe6 and the metastable La2PdGe6, which turned out to be mS36-La2AlGe6-type non-merohedrally twinned crystals, and the Yb2PdGe6 of oS72-Ce2(Ga0.1Ge0.9)7-type. These results were extended for a comprehensive study on the R2MGe6 (M = Li, Mg, Al, Cu, Zn, Pd, Ag, Pt, Au) family of compounds, employing symmetry-based structural rationalization and total energy calculations, revealing that the highest energy is always associated to the more reported oS18-Ce2CuGe6 structure. The knowledge of the correct structural models allowed a comparative chemical bonding analysis for La2MGe6 (M = Li, Mg, Al, Zn, Cu, Ag, Pd) and Y2PdGe6 germanides. State of the art position-space techniques (QTAIM, ELI-D and their basin intersection) were employed together with the proposal of new approaches developed during this work; i.e. the penultimate shell correction (PSC0) method and the ELI-D fine structure based on its relative Laplacian. The former was crucial to balance Ge\u2013La polar-covalent interactions against the Ge\u2013M ones, whereas the latter allows to reveal polyatomic bonding features. With these new tools at hand, it was possible to go beyond the Zintl picture (formally fulfilled only with M = Mg2+ and Zn2+) revealing Ge\u2013La and Ge\u2013M (M 60 Li, Mg) polar-covalent interactions. For M = Li, Mg a formulation as germanolanthanate M[La2Ge6] is appropriate. In addition, a consistent picture of La/Y\u2013M polar interactions was also described. A systematic study on the existence of R2Pd3Ge5 (R = La-Nd, Sm, Gd-Lu) was conducted and the desired phase was revealed to exist with R = La-Nd, Sm, Yb crystallizing with the oI40-U2Co3Si5 structure. A B\ue4rnighausen tree was constructed in order to rationalize the related crystal structures of the RPd2Ge2, RPdGe3 and R2Pd3Ge5 ternary compounds, enriching the large family of the BaAl4 derivatives. After magnetization and susceptibility measurements Yb2Pd3Ge5 was described as a paramagnet with \u3bceff close to 0.8 \u3bcB/Yb-atom, suggesting a nearly divalent Yb state. The new Lu5Pd4Ge8 and Lu3Pd4Ge4 intermetallics were synthesized. The former crystallizes with non-merohedral monoclinic twinned crystals (P21/m, mP34) and the latter is orthorhombic (Immm, oI22). COHP- and preliminary ELI-D-based chemical bonding analysis revealed the expected Ge-covalent fragments and in addition Ge\u2013Lu, Ge\u2013Pd and Pd-Lu polar-covalent interactions. These findings, together with the aforementioned results for La2MGe6 compounds, indicate the importance of these interactions within ternary rare-earth germanides. Finally, the existence of R4MgGe10-x and R4LiGe10-x phases along the R series was investigated. X-ray single crystal diffraction experiments show that all the phases, obtained with R = La-Nd, Sm, Gd-Dy, are non-merohedrally twinned with mS60-La4MgGe10-x structure. The presented results constitute a step forward in the comprehension of composition-structure-properties relationships and a good playground for further studies on analogous systems

A Fragment-Based Approach for the Development of G-Quadruplex Ligands: Role of the Amidoxime Moiety

G-quadruplex (G4) nucleic acid structures have been reported to be involved in several human pathologies, including cancer, neurodegenerative disorders and infectious diseases; however, G4 targeting compounds still need implementation in terms of drug-like properties and selectivity in order to reach the clinical use. So far, G4 ligands have been mainly identified through high-throughput screening methods or design of molecules with pre-set features. Here, we describe the development of new heterocyclic ligands through a fragment-based drug discovery (FBDD) approach. The ligands were designed against the major G4 present in the long terminal repeat (LTR) promoter region of the human immunodeficiency virus-1 (HIV-1), the stabilization of which has been shown to suppress viral gene expression and replication. Our method is based on the generation of molecular fragment small libraries, screened against the target to further elaborate them into lead compounds. We screened 150 small molecules, composed by structurally and chemically different fragments, selected from commercially available and in-house compounds; synthetic elaboration yielded several G4 ligands and two final G4 binders, both embedding an amidoxime moiety; one of these two compounds showed preferential binding for the HIV-1 LTR G4. This work presents the discovery of a novel potential pharmacophore and highlights the possibility to apply a fragment-based approach to develop G4 ligands with unexpected chemical features

Marble Trade in Antiquity: Looking at Labraunda

Introduction What is the provenance of the marble used at Labraunda? According to tradition, marble was supplied by quarries at Sodradağ at the feet of which Mylasa, the ancient capital of Karia, was laid out. Strabo reports that Mylasa was known for its many buildings of white marble, and he suggests that such marble might have been used at Labraunda too. Antique quarries identified at the southern slopes of Mount Sodra contribute to the proposition that Sodra provided marble for Labraunda. ..

Development of a pressure-measuring device to optimize compression treatment of lymphedema and evaluation of change in garment pressure with simulated wear and tear.

The use of compression garments in treating lymphedema following treatment of genital (penis, testes, uterus, cervical) and breast cancer treatment is a well-established practice. Although compression garments are classified in compression classes, little is known about the actual subgarment pressure exerted along the extremity. The aims of this study were to establish an in vitro method for measuring subgarment pressure along the extremity and to analyze initial and over time subgarment pressure of compression garments from three manufacturers. The measurements were performed with I-scan(®) (Tekscan Inc.) pressure measuring equipment once a week during a period of 4 weeks. Wear and tear was simulated by washing and putting on the garments on plastic legs every day. There was a statistically significant difference between the garments of some of manufacturers. There was no difference between garments from the same manufacturer. No significant decrease of subgarment pressure was observed during the trial period. The study demonstrated that Tekscan pressure-measuring equipment could measure subgarment pressure in vitro. The results may indicate that there was a difference in subgarment pressure exerted by garments from different manufacturers and that there was no clear decrease in subgarment pressure during the first four weeks of usage

Effects of Transport and Feeding Strategies Before Transportation on Redox Homeostasis and Gastric Ulceration in Horses

Transportation may lead to oxidative stress (OS) and gastric ulceration in horses, and optimal feed man-agement before, or during, transportation is unclear. This study aimed to evaluate the effects of trans-portation after three different feeding strategies on OS and to explore possible associations between OS and equine gastric ulcer syndrome (EGUS). Twenty-six mares were transported by truck for 12 hours without food or water. Horses were randomly divided into 3 groups; (1) fed 1 hour before departure (BD), (2) fed 6 hours BD, (3) fed 12 hours BD. Clinical examinations and blood collections were per-formed at approximately 4 hours BD (T0), at unloading (T1), 8 hours (T2) and 60 hours (T3) after un-loading. Gastroscopy was conducted prior to departure, and at T1 and T3. Although OS parameters re-mained in the normal range, transportation was associated with increased reactive oxygen metabolites (ROMS) at unloading (P = 0.004), with differences between horses fed 1 hour and 12 hours BD ( P < .05). The level of total antioxidant (PTAS) was affected by both transportation and feeding strategy ( P = 0.019), with horses fed 1 hour BD demonstrating greater PTAS at T = 0, and a different response in comparison with the other groups and the literature. Nine horses demonstrated clinically significant ulceration of the squamous mucosa at T1 but, although weak correlations were evident between OS parameters and ulcer scores, univariate logistic regression showed no associations. This study suggests that feed management prior to a long journey (12 hours) may affect oxidative balance. Further studies are needed to understand the nexus between feed management before and during transport, transport-related OS and EGUS.(c) 2023 Elsevier Inc. All rights reserved

Synthesis, Binding and Antiviral Properties of Potent Core-Extended Naphthalene Diimides Targeting the HIV-1 Long Terminal Repeat Promoter G-Quadruplexes

We have previously reported that stabilization of the G-quadruplex structures in the HIV-1 long terminal repeat (LTR) promoter suppresses viral transcription. Here we sought to develop new G-quadruplex ligands to be exploited as antiviral compounds by enhancing binding toward the viral G-quadruplex structures. We synthesized naphthalene diimide derivatives with a lateral expansion of the aromatic core. The new compounds were able to bind/stabilize the G-quadruplex to a high extent, and some of them displayed clear-cut selectivity toward the viral G-quadruplexes with respect to the human telomeric G-quadruplexes. This feature translated into low nanomolar anti-HIV-1 activity toward two viral strains and encouraging selectivity indexes. The selectivity depended on specific recognition of LTR loop residues; the mechanism of action was ascribed to inhibition of LTR promoter activity in cells. This is the first example of G-quadruplex ligands that show increased selectivity toward the viral G-quadruplexes and display remarkable antiviral activity

Dromedary Camel Health Care Practices Reported by Caretakers Working at a Permanent Market

Traditional health care practices and ethnoveterinary medicine are still common in camels. This study aimed at describing camel health issues reported by caretakers including their management and treatment practices. Associations between the health issues and caretakers’ background, management practices, and facilities were also investigated. Camel caretakers (n=49) at a permanent market in Qatar were interviewed and data related to the camel pens (e.g. presence of shelters, water, and feeding points) collected. During the interview, questions sought to elicit the following information; i) caretaker’s background (age, level of education, experience, and how they identify when a camel is sick), ii) caretaker’s management practices (feeding, watering, and health care practices), iii) caretaker’s description of the last health problem (camel details, recalled diagnosis/clinical signs, possible cause, treatment, and outcome). The majority of the caretakers were middle-aged (31-50 years old) and they used to identify a sick camel mainly observing its behavioural modifications (p < 0.001). Treatment for endo- and ectoparasites were usually administered by caretakers, health checks routinely performed by veterinarians, while vaccinations were not conducted in most of the pens (p < 0.001). A total of 38 health problems were described and the high environmental temperature was the most reported possible cause (43.2%; p < 0.001). Among the recalled health problems, sunstrokes were the most common (11/38; p = 0.046), followed by fever (9/38). Sunstroke was more likely to affect males (OR: 5.04; CI95%: 1.87-23.38; p = 0.039), while fever younger animals (OR: 0.68, CI95%: 0.47-1.00; p = 0.050). Sunstrokes were more likely managed by non-veterinarians (OR: 4.75; CI95%: 1.05-21.34; p = 0.042). The majority of the cases were early identified and had a full recovery, but 11/38 camels died. Interestingly, drugs were the most common treatment (73.7%, p < 0.001), but often bought and administered directly by caretakers. Duty of care, infectious disease prevention, early and appropriate treatments could be recommended to guarantee the principle of good health and consequently animal welfare. Education on how to identify a sick camel and how to manage it should be also promoted