Search

Fever is a typical symptom of most infectious diseases. While prolonged fever may be clinically undesirable, mild reversible fever (39℃, 312 K) can potentiate the immune responses against pathogens. Here, using molecular dynamics and free energy calculations, we investigated the effect of febrile temperatures (38℃ to 40℃, 311 K to 313 K) on the immune complexes formed by the SARS-CoV-2 spike protein with two neutralizing monoclonal antibodies. In analyzing the conformational dynamics of the interactions between the antibodies and the spike protein under different thermal conditions, we found that, at mild fever temperatures (311-312 K), the binding affinities of the two antibodies improve when compared to the physiological body temperature (37℃, 310 K). Furthermore, only at 312 K, antibodies exert distinct mechanical effects on the receptor binding domains of the spike protein that may hinder SARS-CoV-2 infectivity. Enhanced antibody binding affinity may thus be obtained using appropriate temperature conditions.

BackgroundHER2 receptor is overexpressed in different aggressive and recurrent tumors, and the modulation of its conformational changes has been achieved using immunotherapy or chemotherapy.ObjectiveTo assess the role of fever temperatures on the dynamics of HER2 in the absence of a binding partner.MethodsMolecular dynamics simulations of apo-HER2 were performed at 37□-40□, in order to gauge its intramolecular dynamics.ResultsHER2 assumes an inactive and “bent” conformation at 40□, while it maintains its extended, active conformation that can dimerize with other HER partners, in the 37□-39□ range.ConclusionThese novel results indicate the role of fever temperatures on modulating conformational changes in an essential tumor target. Cancer treatment can leverage the use of thermal therapy at particular fever points, in order to complement existing radio or chemotherapy options.

Background Systemic amyloidoses represent a heterogeneous group of diseases resulting from the deposition of misfolded proteins as amyloid fibrils into the extracellular matrix of different organs. Based on this precursor protein, cardiac amyloidosis (CA) can be most frequently classified as: light chain (AL) and transthyretin (ATTR) amyloidosis, with different management and prognosis. Purpose The purpose of this study is to establish a differential diagnosis algorithm targeted towards these two most frequent subtypes of CA. Although confirmation through invasive or non-invasive diagnostic algorithms is still mandatory for a final diagnosis, a series of clinical, paraclinical and imaging differences could possibly guide the choice for more complex diagnostic steps. Methods We prospectively included all consecutive patients with ATTR and AL evaluated between 2018 and 2022 in our center. All patients had a complete clinical, paraclinical and imaging evaluation including myocardial deformation study, and confirmation of the final diagnosis, according to the current international recommendations. Results The study population included 81 patients divided into 2 groups: ATTR (group 1, n=32: 30 variant and 2 wild type) and AL (group 2, n=49). ATTR patients were younger (50.7±13.9 vs. 60.2±7.3 years, p=0.0001), had predominantly more neurological symptoms, milder cardiac symptoms and lower values of cardiac biomarkers than AL: NT-proBNP (3095±4433 vs. 10382±9008 ng/ml, p=0.001) and high sensitive troponin I (0.0129±0.01 vs 0.177±0.2 ng/ml, p=0.0002), with better renal function (mean GFR 84.74±26.9 vs. 64.5±29.45 mL/min, p=0.003). We found no significant differences in terms of ECG changes. Moreover, at similar left ventricular (LV) wall thickness and ejection fraction, ATTR group had less pericardial effusions (53.6 vs. 86.8%, p=0.0027), better LV global longitudinal strain (−12.0±3.7 vs. −9.7±4.6%, p=0.03), RV strain (RVFW strain −19.7±6.2 vs. −14.5±11.0%, p=0.03) and also better reservoir and contractile function of the LA (LASr 17.2±12.3 vs. 11.2±7.4%, p=0.02). Based on this multiparametric comparison we proposed a prediction algorithm to differentiate between the 2 forms of CA. A score of equal or more than 4 from a maximum of 9 points, has been able to differentiate between AL and ATTR with a sensitivity and specificity of 78 and 80%, respectively; AUC= 0.82. Conclusions CA is a complex entity and requires extensive testing through serum biomarkers, imaging, and invasive confirmation of amyloid infiltration in some cases. This study highlighted a series of non-invasive checkpoints, which can be useful in guiding the decision making process towards a more accurate and rapid differential diagnosis, in cases where a final diagnosis is crucial to be immediately established. Funding Acknowledgement Type of funding sources: None.

Drug hypersensitivity reactions are an unavoidable clinical consequence of the presence of new therapeutic agents. These adverse reactions concern patients afflicted with infectious diseases (e.g., hypersensitivity to antibiotics), and with non-infectious chronic diseases, such as in cancers, diabetes or cystic fibrosis treatments, and may occur at the first drug administration or after repeated exposures. Here we revise recent key studies on the mechanisms underlying the desensitization protocols, and propose an additional temporal regulation layer that is based on the circadian control of the signaling pathway involved and on the modulation of the memory effects established by the desensitization procedures.

Silicon (Si) is one of the most promising anode candidates to further push the energy density of lithium ion batteries. However, its practical usage is still hindered by parasitic side reactions including electrolyte decomposition and continuous breakage and (re-)formation of the solid electrolyte interphase (SEI), leading to consumption of active lithium. Pre-lithiation is considered a highly appealing technique to compensate for active lithium losses. A critical parameter for a successful pre-lithiation strategy by means of Li metal is to achieve lithiation of the active material/composite anode at the most uniform lateral and in-depth distribution possible. Despite extensive exploration of various pre-lithiation techniques, controlling the lithium amount precisely while keeping a homogeneous lithium distribution remains challenging. Here, the thermal evaporation of Li metal as a novel pre-lithiation technique for pure Si anodes that allows both, that is, precise control of the degree of pre-lithiation and a homogeneous Li deposition at the surface is reported. Li nucleation, mechanical cracking, and the ongoing phase changes are thoroughly evaluated. The terms dry-state and wet-state pre-lithiation (without/with electrolyte) are revisited. Finally, a series of electrochemical methods are performed to allow a direct correlation of pre-SEI formation with the electrochemical performance of pre-lithiated Si.

Hemolysis modulates susceptibility to bacterial infections and predicts poor sepsis outcome. Hemolytic bacteria use hemolysins to induce erythrocyte lysis and obtain the heme that is essential for bacterial growth. Hemolysins are however potent immunogens and infections with hemolytic bacteria may cause a reversible fever response from the host that will aid in pathogen clearance. We hypothesized that fever temperatures impact the growth and infectivity of two hemolytic bacteria that are known to evoke fever in patients. To that end, we used high-sensitivity microcalorimetry to measure the evolution of heat production in fever-inducing strains of

According to the literature, a relatively simple models have been developed, capable of simulating the front compartment (FC) integrity during a frontal impact (FI) of a vehicle. These models, known as the Lumped Mass-Spring (LMS), approximates the main subassemblies of the vehicle using a simplified mass-spring system. The paper shows a analytical model for study of the FI behavior of the vehicle with a fixed non-deformable barrier. The principal subassemblies of the FC are approximate with concentrated mass points. These concentrated masses are connected by elastic elements. The generalized coordinates of the displacements of the centers of gravity of the bodies in the longitudinal direction are set. The equations of motion will be obtained based on Lagrange’s generalized equations. Initial conditions are required for the model. Solving the system of differential equations is done using the modeling and simulation environment provided by the Matlab Simulink program. Finally, the evolution of the system’s deformation, speed and deceleration over time is graphically represented.

Magnetic fluids based on single-domain magnetic spinel ferrite nanoparticles dispersed in various liquid media are of particular practical and scientific interest. This paper presents a muon spectroscopy study of a ferrofluid based on magnetic nanoparticles of CoFe2O4 molecules dispersed in water (H2O) with a nanoparticle concentration of 3%. In this study, it was determined that the structure and magnitude of the magnetization of a ferrofluid depend on the viscosity of the liquid itself. It was shown that, at room temperature (290 K) and under an external magnetic field of 527 G, the observed additional magnetization was ~20 G. In a small fraction of the sample under study (~20%), negative magnetization (diamagnetism) was observed. At low temperatures (~30 K), the sample acted as a paramagnet in a magnetic field. For the first time, the magnetic field inside and in the immediate vicinity of a CoFe2O4 nanoparticle has been measured experimentally using the μSR method: the value was 1.96 ± 0.44 kG, thus, direct measurement of the magnetization of a nanoscale object was performed.

The High Voltage Engineering Europa B.V. (HVEE) 1 MV spectrometer at NIPNE-Bucharest was extended to allow highly sensitive Accelerator Mass Spectrometry (AMS) measurements of tritium (3H). The new established analyzing procedure and a complete AMS experiment with tritium are described in detail.

Summary Regulated transcriptional readthrough during stress maintains genome structure and ensures access to genes that are necessary for cellular recovery. A broad number of genes, including of the bacterial sensor Toll-like receptor 4 (TLR-4), are markedly transcribed on initiating the systemic inflammatory response. Here we study the transcriptional patterns of tlr4 and of its modulator grp78 during human sepsis, and establish their correlations with the outcome of patients. We measured the daily tlr4 and grp78 RNA expression levels in peripheral blood of septic patients, immediately after admission to intensive care, and modeled these RNA values with a sine damping function. We obtained negative correlations between the transcription of tlr4 and grp78 RNA in the survivor group. In contrast, such relation is lost in the deceased patients. Loss of transcriptional homeostasis predicted by our model within the initial 4 days of hospitalization was confirmed by death of those patients up to 28 days later.

Decommissioning of nuclear reactors requires determination of all remnant long-lived isotopes that were produced during their long functioning time of the respective facilities. Radiocarbon (14C) is such an isotope (T1/2 = 5730 yr), widely produced by neutron reactions in a thermal column of a nuclear reactor. Accelerator mass spectrometry (AMS) uses 14C for precise dating of up to 50,000 years old archaeological artifacts. This study presents a premier AMS measurement of high concentrated 14C samples that are strictly forbidden in laboratories dedicated to perform 14C dating. The determined 14C activities range from the natural level (isotopic ratio 14C/12C = 1.2 × 10–12) up to values of 10,000 times higher. 14C bulk and depth profile concentrations were measured in the thermal column disks of a decommissioned nuclear reactor. Results have shown that the 14C concentration in the thermal column, close the reactor core is about 75 kBq/g and decreases to 0.7 Bq/g and the end of the column. Such AMS measurements are applicable for decommissioning and waste management of nuclear reactors.

The ongoing public concern about the Fukushima nuclear accident’s real consequences determined us to start a new Accelerator Mass Spectrometry study of 129I concentrations in the North Pacific Ocean. Our results show that currently, the radioiodine 129 concentrations from coastal Japanese sea water samples are in the range of (0.9–1.6) × 108 atoms L−1. Higher 129I concentrations of 6.4 × 108 atoms L−1 have been found in the Tadami River, located close to the damaged nuclear reactors. For the North Pacific and all the way into the western shore line we found to have now much lower concentrations, with an average of 2.5 × 107 atoms L−1. Therefore, Fukushima and its vicinities remain an isolated area of nuclear pollution.

Hemolysis modulates susceptibility to bacterial infections and predicts poor sepsis outcome. Hemolytic bacteria induce upon infection a reversible fever response from the host that may aid in pathogen clearance. To delineate the role of fever temperatures on the growth and infectivity of two hemolytic bacteria that are known to evoke fever in patients via hemotoxins, we used high-sensitivity microcalorimetry to measure the evolution of heat production by fever-inducing strains of Escherichia coli and Staphylococcus aureus under fever conditions. We determined specific aggregation profiles at temperatures equal to or exceeding 38.5□. We confirmed these results through bacterial incubation at relevant temperatures revealing the presence or absence of hemolysis. We thus reveal an additional positive role of febrile temperatures in directly contributing to the immune response, through the abolishment of hemolysis.

Impact of mutations on the evolution of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) are needed for ongoing global efforts to track and trace the current pandemic, in order to enact effective prevention and treatment options. SARS-Co-V-2 viral genomes were detected and sequenced from 18 Romanian patients suffering from coronavirus disease-2019. Viral Spike S glycoprotein sequences were used to generate model structures and assess the role of mutations on protein stability. We integrated the phylogenetic tree within the available European SARS-Co-V-2 genomic sequences. We further provide an epidemiological overview of the pre-existing conditions that are lethal in relevant Romanian patients. Non-synonymous mutations in the viral Spike glycoprotein relating to infectivity are constructed in models of protein structures. Continuing search to limit and treat SARS-CoV-2 benefit from our contribution in delineating the viral Spike glycoprotein mutations, as well as from assessment of their role on protein stability or complex formation with human receptor angiotensin-converting enzyme 2. Our results help implement and extend worldwide genomic surveillance of coronavirus disease-2019.

Summary B cells orchestrate pro-survival and pro-apoptotic inputs during unfolded protein response (UPR) to translate, fold, sort, secrete and recycle immunoglobulins. In common variable immunodeficiency (CVID) patients, activated B cells are predisposed to an overload of abnormally processed, misfolded immunoglobulins. Using highly accurate transcript measurements, we show that expression of UPR genes and immunoglobulin chains differs qualitatively and quantitatively during the first 4 h of chemically induced UPR in B cells from CVID patients and a healthy subject. We tested thapsigargin or tunicamycin as stressors and 4-phenylbutyrate, dimethyl sulfoxide and tauroursodeoxycholic acid as chemical chaperones. We found an early and robust decrease of the UPR upon endoplasmic reticulum (ER) stress in CVID patient cells compared to the healthy control consistent with the disease phenotype. The chemical chaperones increased the UPR in the CVID patient cells in response to the stressors, suggesting that misfolded immunoglobulins were stabilized. We suggest that the AMP-dependent transcription factor alpha branch of the UPR is disturbed in CVID patients, underlying the observed expression behavior.

The passive safety of the vehicle is ensured by designing optimized restraint systems to protect the occupants during the accident. The safety-belts have the role of restraining the occupants of the car on the seat during an impact or in the event of a rollover. Their retention prevents or minimizes the impact between the occupants and the interior components of the passenger compartment. Two simplified models of seat structures are proposed to determine the strength of the safety-belts anchorages. The test of the anchorage for safety-belts of the two seat models is performed in accordance with Regulation no. 14 UNECE. For the two seat models, a three-dimensional resistance structure was made. The 3D models of the seats were inserted in the FEA software. The analysis of the models is done by the finite element method with the Static Structural module of the FEA software. A tensile force is applied during the test on the safety-belts anchorages. The traction force shall be applied in the direction corresponding to the seating position, at an angle of 10°±5° above the horizontal, in a plane parallel to the median longitudinal plane of the vehicle. During the tests the safety-belt anchorages shall withstand the entire period of application of the traction force and the upper safety-belt anchorage shall not be displaced during the test forward of a transverse plane passing through the R point of the seat.

This study aimed to investigate the component structural behaviour and response under overturned truck crash that subsequently collides with road-side pole or tree. The safety of the truck occupants in an accident is very important and should be considered in the process of cabin design. Specific focus will be on the structural integrity of the truck cabin in response to a collision with a cylindrical pendulum. In the past, dynamic analysis was done by real world testing. Nowadays crash simulation is proven to be much more efficient by being a virtual representation of destructive crash impact and providing opportunities to reduce the number of physical prototypes consumed for design verification, thus reducing development time. According to cab strength tests (ECE R29), the cabin body of the truck shall be attached to the chassis in such a way that in the event of impact it ensures a sufficient survival space and eliminates the risk of injury. This paper investigates the FE (finite element) simulation of a frontal impact on the cabin structure to validate the cabin according to the ECE regulation 29 tests. The study also includes the assessment of the energy absorption capabilities of the cabin during the pendulum impact. The pendulum impact was carried out using Ansys LS-Dyna explicit solver to evaluate the cabin strength under the loads.

Experimental tests on the type-approval of motor vehicles with regard to safety belt anchorages, ISOFIX anchorages and ISOFIX top anchorages have been carried out in accordance with Regulation No. 14 UNECE [1]. From the design stage, the safety belt anchorages must comply with the requirements for the installation of a safety belt and reduce slipping and damage to the belt while wearing it. These can be components of the seat structure or of the body’s resistance structure, which have the role of fastening the seat belts. The position of the anchor points is determined by the R point. The R point is defined as the seat reference point on the seat. This point is set by the vehicle manufacturer for each seat in the vehicle. In this paper, two models of chairs were tested. Both seat models are equipped with seat belts anchored at three anchor points. Seat belt anchorages were tested simultaneously using parallel force devices. These traction devices are placed on the seat cushion and are pressed into the seat back. The pulling device has a vertical pulling arm, which has the role of anchoring the steel wire cables. Two test forces are applied simultaneously to the anchor points during the test.

Currently, several locations of the North Atlantic Ocean have the 129 I concentration levels 10 4 –10 5 times higher than those of the pre-nuclear era. As a consequence, the southeastern part of Europe, with its rivers and seawaters, should be influenced by the outspread through the atmospheric and hydrospheric transport of iodine-129. This is a long lived fission isotope and a “low beta emitter”. It can be used as long-term tracer for nuclear pollution if the concentration of 129 I is known in the investigated geographical region. This AMS study has determined the 129 I concentrations in the southeast part of Europe, from the Lower Danube River, the Danube Delta and the Black Sea. The 129 I concentrations measured in the Black Sea were in the range of (1–1.4) × 10 8 atoms/L, which equals the range values of the North Atlantic Ocean at latitudes (31°–50°N) of (0.4–1.3) × 10 8 atoms/L. For the Danube Delta, the measured concentration values were very close to those of the Black Sea, due to the small inflow from the sea. For the region of the Lower Danube, 129 I concentrations were (4.1–7.4) × 10 7 atoms/L. The averaged results of 129 I measurements provided the actual baseline of (1.2 ± 0.1) × 10 8 atoms/L valid for the Danube Delta and the Black Sea region and of (6.4 ± 0.1) × 10 7 atoms/L for the Lower Danube.

Chronic suppurated otomastoiditis is a chronic inflammatory damage of the middle ear and mastoid process that exceeds 12 weeks and which leads to the permanent perforation of the eardrum’s membrane. There is local damage such as osteitis, osteonecrosis and cholesteatoma, while a general view reveals an asymptomatic evolution, with a good general state, otorrhea being the only local symptom. This paper brings to light a case resulting from the thorough analysis of case studies run by the ENT Clinic of the Emergency County Hospital "Sf. Apostol Andrei” of Galaţi, through the fact that otomastoiditis progresses given the presence of a congenital hemangioma located on the left half of the cephalic extremity, at a cervical, thoracic and abdominal level. The patient, aged 41, has been suffering from this disease since childhood and has undergone numerous surgeries up to this moment, but none has proven to be adequate for the extent of the lesion due to the malformation and the difficulty in providing general anesthesia with orotracheal intubation, the hemangioma being present in the oropharynx, hypopharynx and larynx. Given the overlapping of the two disorders, the surgical-medical approach to the ear damage has proven insufficient in time due to the risk of massive bleeding, taking into account the fact that the hemangioma was extended to the left ear duct, pharynx and larynx. For this reason, the disease has progressed, leading to extended erosive cholesteatoma with left otomastoiditis. The particularities of the therapeutic approach are presented along with anesthesiologic and surgical problems involved by the hemangioma. Although the risk of hemorrhaging was great, approaching the condition by choosing to provide general anesthesia and making the incisions only with the help of an electric scalpel, the case was eventually solved successfully from a surgical point of view.

Accelerator Mass Spectrometry (AMS) and the Full Combustion (FC) method followed by isotope separation and liquid scintillation counting (LSC) have been applied for measuring the produced and accumulated 14C in the thermal column of the decommissioned VVR-S reactor in NIPNE Bucharest. The FC method has also been used to measure the tritium (3H) deposition in the reactor column. The two employed methods are complementary and during this study they were the subjects of a cross comparison exercise.

To correctly understand the requirements of a system, we must first study its schematics. In the case of energy systems, they require a detailed diagram of energy performance. Heat losses can be classified into high-temperature losses, medium-temperature and low-temperature losses. On board ships with low-speed propulsion engines, heat recovery systems operate in the range of 100-400 °C. Many residual energy recovery systems from internal combustion engines are under development: for example the MAN WHR development program for Tier III technologies. In this paper, I will treat both theoretical calculation elements and real elements of the operation of the turbocharging system, for the main reference engine. I chose to treat this system because it is a main subassembly for the engine, in terms of operation and thus its efficiency. In the theoretical calculation, I will start from the initial calculation data and I will expose the geometric and functional parameters of the turbocharger. The exhaust gases up to a temperature of 650 °C passes continuously through the turbine and heat its components, without its system of contraction cooling. In particular, the shaft bearing must withstand high operating temperatures without ever breaking the lubrication device. On the compressor side, the air is heated to over 200 °C. High temperatures lead to extreme thermal loads of the material in many locations. Speeds are extremely high: METxxSE turbochargers, as in figure 1, run at speeds between 10000 and 35000 rpm, depending on size. In this respect, the tangential speeds of 560 m / s and even more are reached at the compressor turbine, which rises to 1.7 times the speed of sound or 2000 km / h. The efficiency of the operation of the turbocharger system related to the main propulsion engine depends on the internal processes that take place in its operation, and also on the environmental conditions. In this way, the direction of processing on the installation is dictated by the engine load, taking into account the extreme situations, corresponding to the operation of the ship in special conditions (overload, tropical temperature, arctic temperature etc.).

A ship needs fuel for both travel and on-board operations. In the most general case, the fuel is converted on board the ship into energy in the form required for its end use: mechanical power for propulsion, electrical power for auxiliary board systems and thermal power for thermal needs. In this paper, I propose to deal with both elements of theoretical calculation and real elements of the operation of the freshwater generation system from the main engine of the ship. I chose to treat this system because it is the main subassembly of the residual heat recovery system from the main engine through cooling water. In the theoretical calculation, The results of the paper will be focus on calculation of the geometric and functional parameters of the fresh water generator. In the final part of the chapter, I will refer to the real parameters of the freshwater generation system where I will draw operation diagrams to highlight as concretely as possible the operation of this system on board the ship.

C’etait ingenieux mais deraisonnable. Il ne faut jamais rompre avec la tradition.Charles De Coster, La Legende d’Ulenspiegel En 1878, annee de la creation de ses deux chefs-d’œuvre Pornocrates et La Tentation de saint Antoine, Felicien Rops est deja l’un des illustrateurs litteraires les mieux payes de Paris. Il aura deja deploye « la plus fertile, la plus plaisante et la plus artiste invention libertine qu’il se peut imaginer »dans une trentaine d’ouvrages publies par le fameux editeur des p...

Protein-folding stress is characteristic of specialized secretory cells and plays a dominant role in a multitude of diseases. The unfolded protein response (UPR) thus triggered is a proteostatic signaling network that adapts the protein-folding capacity of the endoplasmic reticulum to the cellular demands. We have measured the binding affinities between human GRP78, an essential chaperone located in ER, and two transmembrane UPR sensors (human PERK and Ire1α), with or without the addition of an unfolded protein client. We reveal distinct binding affinities between the binary and ternary complexes thus formed, that suggest a preference for the PERK signaling branch under stress, and a predilection for the GRP78-UPR sensor complex formation upon stressor removal. These results imply a gated UPR mechanism that tunes the overall cellular behavior to the accumulation of unfolded proteins.

The ability to memorize changes in the environment is present at all biological levels, from social groups and individuals, down to single cells. Trans-generational memory is embedded subcellularly through genetic and epigenetic mechanisms. Evidence that cells process and remember features of the immediate environment using protein sensors is reviewed. It is argued that this mnemonic ability is encapsulated within the protein conformational space and lasts throughout its lifetime, which can overlap with the lifespan of the organism. Means to determine diachronic changes in protein activity are presented.