The influence of preparation conditions on the electro-acoustic properties of the PZT-type piezoceramic sensors

The possibilities of the application of the microstructure analysis, X-ray powder diffraction, and Raman scattering methods for the fast and reliable control of the quality of piezoelectric ceramic sensors at every stage of preparation are shown

The influence of preparation conditions on the electro-acoustic properties of the PZT-type piezoceramic sensors

The possibilities of the application of the microstructure analysis, X-ray powder diffraction, and Raman scattering methods for the fast and reliable control of the quality of piezoelectric ceramic sensors at every stage of preparation are shown

Photoluminescence and electrical properties in Pr-modified (Ba1-xCax)TiO3 multifunctional ceramics

Mechanoluminescence materials, characterized with non-thermal light emission in response to mechanical stimuli, can have many applications in direct conversion of mechanical energy into light energy. The aim of this study was to develop wet chemistry approaches for the synthesis of the finest ceramic powders of barium calcium titanate for the use in the production of a mechanoluminescent detector. Wet chemistry route allows the control of the particle size of ceramic materials up to several nanometers. For the first time luminescence was recorded in Ba0.9Ca0.1TiO3 ceramics despite reports that light emission in BCT is possibly only over 23% of calcium content. The resulting ceramics showed high relative density, reasonable ferro and dielectric properties, and red light emission can be observed with the naked eye

Design, 3D printing and validation of a novel low-cost high-capacity sitting-drop bridge for protein crystallization

Sitting drop protein crystallization is not used as commonly as the hanging drop method for crystal optimization due to the limitations of commercially available sitting drop bridges, particularly when they are used in conjunction with 24-well crystallization plates. The commercially available sitting drop bridge, containing space for only a single drop, restricts their wider use. Proteins that preferentially crystallize under sitting-drop conditions therefore require more work, time and resources for their optimization. As a result of these limitations and using 3D-printing, we designed and developed a new sitting drop bridge where five crystallization drops can be placed simultaneously in each well of a 24-well crystallization plate. This significantly simplifies and increases the potential of sitting drops in crystal optimization, reducing costs and hence overcomes existing limitations of current approaches

Identification of fragments binding to SARS-CoV-2 nsp10 reveals ligand-binding sites in conserved interfaces between nsp10 and nsp14/nsp16

Since the emergence of SARS-CoV-2 in 2019, Covid-19 has developed into a serious threat to our health, social and economic systems. Although vaccines have been developed in a tour-de-force and are now increasingly available, repurposing of existing drugs has been less successful. There is a clear need to develop new drugs against SARS-CoV-2 that can also be used against future coronavirus infections. Non-structural protein 10 (nsp10) is a conserved stimulator of two enzymes crucial for viral replication, nsp14 and nsp16, exhibiting exoribonuclease and methyltransferase activities. Interfering with RNA proofreading or RNA cap formation represents intervention strategies to inhibit replication. We applied fragment-based screening using nano differential scanning fluorometry and X-ray crystallography to identify ligands targeting SARS-CoV-2 nsp10. We identified four fragments located in two distinct sites: one can be modelled to where it would be located in the nsp14–nsp10 complex interface and the other in the nsp16–nsp10 complex interface. Microscale thermophoresis (MST) experiments were used to quantify fragment affinities for nsp10. Additionally, we showed by MST that the interaction by nsp14 and 10 is weak and thereby that complex formation could be disrupted by small molecules. The fragments will serve as starting points for the development of more potent analogues using fragment growing techniques and structure-based drug design

Photocrosslinked Bioreducible Polymeric Nanoparticles for Enhanced Systemic siRNA Delivery as Cancer Therapy

Clinical translation of polymer‐based nanocarriers for systemic delivery of RNA has been limited due to poor colloidal stability in the blood stream and intracellular delivery of the RNA to the cytosol. To address these limitations, this study reports a new strategy incorporating photocrosslinking of bioreducible nanoparticles for improved stability extracellularly and rapid release of RNA intracellularly. In this design, the polymeric nanocarriers contain ester bonds for hydrolytic degradation and disulfide bonds for environmentally triggered small interfering RNA (siRNA) release in the cytosol. These photocrosslinked bioreducible nanoparticles (XbNPs) have a shielded surface charge, reduced adsorption of serum proteins, and enable superior siRNA‐mediated knockdown in both glioma and melanoma cells in high‐serum conditions compared to non‐crosslinked formulations. Mechanistically, XbNPs promote cellular uptake and the presence of secondary and tertiary amines enables efficient endosomal escape. Following systemic administration, XbNPs facilitate targeting of cancer cells and tissue‐mediated siRNA delivery beyond the liver, unlike conventional nanoparticle‐based delivery. These attributes of XbNPs facilitate robust siRNA‐mediated knockdown in vivo in melanoma tumors colonized in the lungs following systemic administration. Thus, biodegradable polymeric nanoparticles, via photocrosslinking, demonstrate extended colloidal stability and efficient delivery of RNA therapeutics under physiological conditions, and thereby potentially advance systemic delivery technologies for nucleic acid‐based therapeutics

Integrated care for patients with advanced chronic obstructive pulmonary disease

Przewlekła obturacyjna choroba płuc (POChP) jest trzecią przyczyną zgonów i trzecią przyczyną niesprawności (mierzonej za pomocą wskaźnika DALY) u osób powyżej 60. roku życia. Ciężką lub bardzo ciężką postać POChP (wskaźnik FEV1, odpowiednio, poniżej 50% i 30% należnej wartości) rozpoznaje się u mniej więcej jednej piątej ogółu chorych. Chorzy na zaawansowaną POChP z reguły cierpią z powodu fizycznej i umysłowej niepełnosprawności, w wielu przypadkach źle radzą sobie z problemami wynikającymi z choroby i współistniejących schorzeń. To z kolei stwarza duże ryzyko zaostrzeń POChP, które prowadzą do pogorszenia przebiegu choroby, istotnego zwiększenia kosztów medycznej opieki oraz zwiększenia ryzyka zgonu. Obecna organizacja medycznej opieki dla tej grupy chorych nie zapewnia odpowiednich warunków zdrowotnych i socjalnych. Wydaje się jednak, że zastosowanie modelu zintegrowanej opieki, zalecanego przez Światową Organizację Zdrowia stworzyłoby możliwość poprawy sytuacji chorych na zaawansowane POChP. W Polsce ta forma opieki jest realizowana od kilkunastu lat w zakładach medycyny paliatywnej i hospicjach w odniesieniu do chorych na zaawansowane nowotwory. Wykorzystanie tych doświadczeń powinno pomóc w integracji działań wokół lekarzy rodzinnych i wyspecjalizowanej pielęgniarki, z jednoczesnym zapewnieniem dostępu do specjalistów w zależności od indywidualnych potrzeb chorego. Powinno także umożliwić szersze wykorzystanie pracowników pomocniczych, jak: pracownicy socjalni, pomocnicy medyczni oraz wolontariusze, a także psycholodzy i duchowni (zwłaszcza w końcowej fazie choroby). Pneumonol. Alergol. Pol. 2010; 78, 2: 126-132Chronic obstructive pulmonary disease (COPD) is the third cause of mortality and disability (assed by DALY) among patients above 60 year old. Severe and very severe COPD (FEV1 = equal or less than 50% and 30% of expected value, respectively) is estimated at 20% of all COPD patients. Advanced COPD usually leads to physical and mental deterioration, the patients often manage with the problems caused by the disease and other comorbidities poorly. This leads to increased risk of COPD exacerbations and further deterioration of the patient’s status, increased costs of medical care and eventually increased risk of death. Current organization of medical care for those patients does not provide adequate health and social support for them. However, it seems that introducing an integrated approach proposed by World Health Organization, could improve the situation of advanced COPD patients. In Poland, this kind of care has been provided in advanced cancer patients throughout stationary palliative care units and hospices during the last several years. This experience should be helpful in integrating actions of general practitioners and specialized nurses, as well as providing access for the specialists’ consultations according to the individual needs of the patients. It should also allow for broad cooperation with auxiliary staff, such as social workers, medical assistants and volunteers, as well as psychologists and clergymen (especially in the terminal phase of the disease). Pneumonol. Alergol. Pol. 2010; 78, 2: 126-13

Determination of composition and structure of spongy bone tissue in human head of femur by Raman spectral mapping

Biomechanical properties of bone depend on the composition and organization of collagen fibers. In this study, Raman microspectroscopy was employed to determine the content of mineral and organic constituents and orientation of collagen fibers in spongy bone in the human head of femur at the microstructural level. Changes in composition and structure of trabecula were illustrated using Raman spectral mapping. The polarized Raman spectra permit separate analysis of local variations in orientation and composition. The ratios of ν2PO43−/Amide III, ν4PO43−/Amide III and ν1CO32−/ν2PO43− are used to describe relative amounts of spongy bone components. The ν1PO43−/Amide I ratio is quite susceptible to orientation effect and brings information on collagen fibers orientation. The results presented illustrate the versatility of the Raman method in the study of bone tissue. The study permits better understanding of bone physiology and evaluation of the biomechanical properties of bone

Neck-motor interactions trigger rotation of the kinesin stalk

Rotation of the coiled-coil stalk of the kinesin-14 motors is thought to drive displacements or steps by the motor along microtubules, but the structural changes that trigger stalk rotation and the nucleotide state in which it occurs are not certain. Here we report a kinesin-14 neck mutant that releases ADP more slowly than wild type and shows weaker microtubule affinity, consistent with defective stalk rotation. Unexpectedly, crystal structures show the stalk fully rotated – neck-motor interactions destabilize the stalk, causing it to rotate and ADP to be released, and alter motor affinity for microtubules. A new structural pathway accounts for the coupling of stalk rotation – the force-producing stroke – to changes in motor affinity for nucleotide and microtubules. Sequential disruption of salt bridges that stabilize the unrotated stalk could cause the stalk to initiate and complete rotation in different nucleotide states