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Environmental changes have had an enormous impact on prehistoric hunter-gatherers as they affect the biotic landscape and availability of resources such as freshwater, edible plants, game and fish. To assess whether various innovations that took place in hunter-gatherer communities during the Boreal may be attributed to changes in the vegetation, a high-resolution pollen and macrofossil analysis of a well-AMS-dated Early Holocene peat record from the Grote Nete valley in the Belgian Campine was carried out. Shifts in the pollen assemblages indicate a change from a birch-pine woodland in the late Preboreal to pine-dominated forests in the Boreal. After the initial expansion of hazel, followed by oak and elm from the early Boreal onward, a prominent and abrupt reduction of the pollen concentration, by up to 95% over several spectra, is observed during the second half of the Boreal. This sharp decline affects all taxa and coincides with a decrease in pollen percentages of thermophilous trees and an increase of the cold-tolerant pine. This shift in pollen concentration and vegetation composition likely reflects a climatic cooling at 9.3 ka which is evident in the stable oxygen isotopic record of the Greenland ice cores. On the one hand, the vegetation dynamics are discussed in the light of the Boreal vegetation history in general and this temporary cooling more specifically. On the other hand, we discuss how these changes may have affected past hunter-gatherer communities.

The distribution of filler particles within a polymer matrix nanocomposite has a profound influence on the properties and processability of the material. While filler aggregation and percolation can significantly enhance particular functionalities such as thermal and electrical conductivity, the formation of larger filler clusters and networks can also impair mechanical properties like strength and toughness and can also increase the difficulty of processing. Here, a strategy is presented for the preparation of functional composites that enhance thermal conductivity over polymer alone, without negatively affecting mechanical performance or processability. Thermal cross-linking of self-suspended polymer grafted nanoparticles is used to prepare highly filled (50 vol %) macroscopic nanocomposites with homogeneously dispersed, non-percolating alumina particles in an organic matrix. The initial composites use low glass transition temperature polymer grafts and thus are flexible and easily shaped by thermoforming methods. However, after thermal aging, the resulting materials display high stiffness (10 GPa) and enhanced thermal conductivity (100% increase) and also possess mechanical strength similar to commodity plastics. Moreover, the covalent bonding between matrix and filler allows for the significant elevation of thermal conductivity despite the extensive interfacial area in the nanocomposite. The thermal aging of polymer grafted nanoparticles is therefore a promising method for producing easily processable, mechanically sturdy, and macroscopic nanocomposites with improved thermal conductivity.

In this article we present a case of a 35-year-old patient with a massive 43 × 35 × 34 mm cavernous venous malformation of the left orbit. The orbital lesion was initially observed in 2008 and remained untreated to 2021 due to the patient’s refusal to consent to the surgical procedure; which caused the tumor to grow to monstrous dimensions.

Stool specimens are frequently used to detect gastrointestinal tract colonization with antimicrobial-resistant enteric bacteria, but they cannot be rapidly collected. Perianal swab specimens can be collected more quickly and efficiently, but data evaluating their suitability as a specimen type for this purpose are sparse. We performed selective culture for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) and fluoroquinolone-resistant Enterobacterales (FQRE) using paired perianal swab and stool specimens that were collected within 1 day of each other from hematopoietic cell transplant recipients and patients with acute leukemia. Nineteen (7.6%) of 251 stool specimens yielded ESBL-E and 64 (26%) of 246 stool specimens yielded FQRE. The positive percent agreement of perianal swab specimens compared to stool specimens was 95% (18/19; 95% confidence interval [CI], 74% to 100%) for detecting ESBL-E and 95% (61/64; 95% CI, 87% to 99%) for detecting FQRE. The concordance between specimen types was 98% (95% CI, 97% to 100%). Perianal swabs are a reliable specimen type for surveillance of the gastrointestinal tract for ESBL-E and FQRE.

The self-assembly of colloidal nanoparticles into ordered superlattices typically uses dynamic interactions to govern particle crystallization, as these non-permanent bonds prevent the formation of kinetically trapped, disordered aggregates. However, while the use of reversible bonding is critical in the formation of highly ordered particle arrangements, dynamic interactions also inherently make the structures more prone to disassembly or disruption when subjected to different environmental stimuli. Thus, there is typically a trade-off between the ability to initially form an ordered colloidal material and the ability of that material to retain its order under different conditions. Here, we present a method for embedding colloidal nanoparticle superlattices into a polymer gel matrix. This encapsulation strategy physically prevents the nanoparticles from dissociating upon heating, drying, or the introduction of chemicals that would normally disrupt the lattice. However, the use of a gel as the embedding medium still permits further modification of the colloidal nanoparticle lattice by introducing stimuli that deform the gel network (as this deformation in turn alters the nanoparticle lattice structure in a predictable manner). Moreover, encapsulation of the lattice within a gel permits further stabilization into fully solid materials by removing the solvent from the gel or by replacing the solvent with a liquid monomer that can be photopolymerized. This embedding method therefore makes it possible to incorporate ordered colloidal arrays into a polymer matrix as either dynamic or static structures, expanding their potential for use in responsive materials.

Objective This study investigated if individual preferences with respect to the trade-off between a good signal-to-noise ratio and a distortion-free speech target were stable across different masking conditions and if simple adjustment methods could be used to identify subjects as either ""noise haters"" or ""distortions haters"". Design In each masking condition, subjects could adjust the target speech level according to their preferences by employing (i) linear gain or gain at the cost of (ii) clipping distortions or (iii) compression distortions. The comparison of these processing conditions allowed investigating the preferred trade-off between distortions and noise disturbance. Study sample Thirty subjects differing widely in hearing status (normal-hearing to moderately impaired) and age (23-85 years). Results High test-retest stability of individual preferences was found for all modification schemes. The preference adjustments suggested that subjects could be consistently categorised along a scale from ""noise haters"" to ""distortion haters"", and this preference trait remained stable through all maskers, spatial conditions, and types of distortions. Conclusions Employing quick self-adjustment to collect listening preferences in complex listening conditions revealed a stable preference trait along the ""noise vs. distortions"" tolerance dimension. This could potentially help in fitting modern hearing aid algorithms to the individual user.

Nanocomposite tectons (NCTs) are a recently developed building block for polymer-nanoparticle composite synthesis, consisting of nanoparticle cores functionalized with dense monolayers of polymer chains that terminate in supramolecular recognition groups capable of linking NCTs into hierarchical structures. In principle, the use of molecular binding to guide particle assembly allows NCTs to be highly modular in design, with independent control over the composition of the particle core and polymer brush. However, a major challenge to realize an array of compositionally and structurally varied NCT-based materials is the development of different supramolecular bonding interactions to control NCT assembly, as well as an understanding of how the organization of multiple supramolecular groups around a nanoparticle scaffold affects their collective binding interactions. Here, we present a suite of rationally designed NCT systems, where multiple types of supramolecular interactions (hydrogen bonding, metal complexation, and dynamic covalent bond formation) are used to tune NCT assembly as a function of multiple external stimuli including temperature, small molecules, pH, and light. Furthermore, the incorporation of multiple orthogonal supramolecular chemistries in a single NCT system makes it possible to dictate the morphologies of the assembled NCTs in a pathway-dependent fashion. Finally, multistimuli responsive NCTs enable the modification of composite properties by postassembly functionalization, where NCTs linked by covalent bonds with significantly enhanced stability are obtained in a fast and efficient manner. The designs presented here therefore provide major advancement for the field of composite synthesis by establishing a framework for synthesizing hierarchically ordered composites capable of complicated assembly behaviors. Copyright ©2019 American Chemical Society., U.S. Army Research Office (W911NF-18-1-0197), NSF CAREER Grant (CHE-1653289), NSF (DMR 14-19807), NSF Graduate Research Fellowship Program Grant (1122374)

Several species from the Clostridium genus show promise as industrial solvent producers and cancer therapeutic delivery vehicles. Previous development of shuttle plasmids and genome editing tools has aided the study of these species and enabled their exploitation in industrial and medical applications. Nevertheless, the precise control of gene expression is still hindered by the limited range of characterized promoters. To address this, libraries of promoters (native and synthetic), 5' UTRs, and alternative start codons were constructed. These constructs were tested in Escherichia coli K-12, Clostridium sporogenes NCIMB 10696, and Clostridium butyricum DSM 10702, using β-glucuronidase (gusA) as a gene reporter. Promoter activity was corroborated using a second gene reporter, nitroreductase (nmeNTR) from Neisseria meningitides. A strong correlation was observed between the two reporters. In C. sporogenes and C. butyricum, respectively, changes in GusA activity between the weakest and strongest expressing levels were 129-fold and 78-fold. Similar results were obtained with the nmeNTR. Using the GusA reporter, translation initiation from six alternative (non-AUG) start codons was measured in E. coli, C. sporogenes, and C. butyricum. Clearly, species-specific differences between clostridia and E. coli in translation initiation were observed, and the performance of the start codons was influenced by the upstream 5' UTR sequence. These results highlight a new opportunity for gene control in recombinant clostridia. To demonstrate the value of these results, expression of the sacB gene from Bacillus subtilis was optimized for use as a novel negative selection marker in C. butyricum. In summary, these results indicate improvements in the understanding of heterologous gene regulation in Clostridium species and E. coli cloning strains. This new knowledge can be utilized for rationally designed gene regulation in Clostridium-mediated industrial and medical applications, as well as fundamental research into the biology of Clostridium species.

Currently, kidney transplantation is widely accepted as the renal replacement therapy allowing for the best quality of life and longest survival of patients developing end-stage renal disease. However, chronic transplant rejection, recurrence of previous kidney disease or newly acquired conditions, or immunosuppressive drug toxicity often lead to a deterioration of kidney allograft function over time. Complement components play an important role in the pathogenesis of kidney allograft impairment. Most studies on the role of complement in kidney graft function focus on humoral rejection; however, complement has also been associated with cell mediated rejection, post-transplant thrombotic microangiopathy, the recurrence of several glomerulopathies in the transplanted kidney, and transplant tolerance. Better understanding of the complement involvement in the transplanted kidney damage has led to the development of novel therapies that inhibit complement components and improve graft survival. The analysis of functional complotypes, based on the genotype of both graft recipient and donor, may become a valuable tool for assessing the risk of acute transplant rejection. The review summarizes current knowledge on the pathomechanisms of complement activation following kidney transplantation and the resulting diagnostic and therapeutic possibilities.

DNA is a powerful tool for programming the three-dimensional organization of nanomaterials, where the specificity of nucleotide base-pairing can enable precise, complex, and dynamically addressable structures like colloidal crystals. However, because these DNA-programmed materials are often only stable in solution, their organization can be easily disrupted by changes to its local environment. Methods to stabilize these materials have been developed, but often come at the expense of altering or permanently fixing the materials' structures, removing many of the benefits of using DNA interactions to program assembly. Thus, these methods limit the application of DNA-assembled structures as dynamic and programmable material components. Here, a method is presented to resolve these drawbacks for DNA-grafted nanoparticles, also known as Programmable Atom Equivalents (PAEs), by embedding assembled lattices within a hydrogel matrix. The preformed lattices are exposed to polymerizable residues that electrostatically bind to the charged backbone of the DNA ligands and form a continuous, permeating gel network that stabilizes the colloidal crystals upon introduction of a radical initiator. After embedding PAEs in a hydrogel, deformation of the macroscopic matrix results in concomitant deformation of the PAE lattices, allowing superlattice structural changes to be induced by chemical methods (such as changing solute concentration to alter swelling pressure) or by application of mechanical strain. Changes to the structure of the PAE lattices are reversible and repeatable over multiple cycles and can be either isotropic (such as by swelling) or anisotropic (such as by mechanical deformation). This method of embedding nanoparticle crystals inside of a flexible and environmentally responsive hydrogel is therefore a useful tool in extending the utility of PAEs and other micro- and nanostructures assembled with DNA.

To study how severity and progression of coronavirus disease (COVID-19) affect cytokine profiles in pregnant women.69 third-trimester, pregnant women were tested for COVID-19 infection and SARS-CoV-2 specific IgM and IgG antibodies. Patients were stratified according to SARS-CoV-2 Reverse Transcriptase-PCR (RT-PCR) status and serology (IgM and IgG) status. Cytokines G-CSF, HGF, IL-18, IL-1Ra, IL-2Ra, IL-8, and IP-10 were measured via ELISA. Retrospective chart review for COVID-19 symptoms and patient vitals was conducted, and cytokine levels were compared between SARS-CoV-2 positive and negative cohorts, by seronegative and seropositive infection, by time course since onset of infection, and according to NIH defined clinical severity.IL-18, IL-1Ra, and IP-10 increased in the 44 RT-PCR positive pregnant women compared to the 25 RT-PCR negative pregnant controls. Elevated cytokine levels were found in early infections, defined by positive RT-PCR and seronegative status, and higher cytokine levels were also associated with more severe disease. By IgM seroconversion, IL-8 and IP-10 returned to levels seen in uninfected patients, while IL-18 levels remained significantly elevated.Cytokine profiles of third-trimester pregnant women vary with the time course of infection and are correlated with clinical severity.

This study examined how well individual speech recognition thresholds in complex listening scenarios could be predicted by a current binaural speech intelligibility model. Model predictions were compared with experimental data measured for seven normal-hearing and 23 hearing-impaired listeners who differed widely in their degree of hearing loss, age, as well as performance in clinical speech tests. The experimental conditions included two masker types (multi-talker or two-talker maskers), and two spatial conditions (maskers co-located with the frontal target or symmetrically separated from the target). The results showed that interindividual variability could not be well predicted by a model including only individual audiograms. Predictions improved when an additional individual ""proficiency factor"" was derived from one of the experimental conditions or a standard speech test. Overall, the current model can predict individual performance relatively well (except in conditions high in informational masking), but the inclusion of age-related factors may lead to even further improvements.

The paper concerns the numerical analysis of the influence for three different of welding heat source inclinations on the weld pool shape and mechanical properties of the resulting joint. Numerical analysis is based on the experimental tests of single-side welding of two sheets made of X5CrNi18-10 stainless steel. The joint is made using a laser welding heat source. Experimental test was performed for one heating source inclination. As a part of the work metallographic tests are performed on which the quality of obtained joints are determined. Numerical calculations are executed in Abaqus FEA. The same geometrical model is assumed as in the experiment. Material model takes into account changing with temperature thermophysical properties of austenitic steel. Modeling of the motion of heating source is performed in additional subroutine. The welding source parameters are assumed in accordance with the welding process parameters. Numerical calculations were performed for three different inclinations of the source. One inclination is consistent with experimental studies. The performed numerical calculations allowed to determine the temperature field, shape of welding pool as well as deformations and stress state in welded joint. The obtained results are compared to results of the experiment.

The paper presents displacement and strain fields measured at various stages of tension of flat samples in order to compare the effect of different technological parameters on mechanical properties of welded joints. Results of measurements are also compared with the results of tensile test of the base material to determine the impact of welding process on changes of mechanical properties of tested steel. The measurement of displacements and strains in tensed flat specimens made of S355 steel, hybrid welded using electric arc and laser beam is in the scope of this work. Welding process is performed using Yb:YAG laser and electric arc in GMAW method. D70 Trumpf laser head with maximum power up to 12 kW is used in welding tests with a spot diameter of the laser beam d=0.8 mm. Welded joints are made for different technological parameters of the process with laser beam heat source leading in the tandem. Tension tests of flat samples are performed in accordance with norm PN-EN ISO 6892-1. Dantec Q-400 ISTRA multi-camera 3D correlation system is used for strain and displacement measurements. The method of measurement is based on the correlation of digital images recorded by the three cameras. Surface of tested samples is covered with a layer of white and black paint. The measurement took place by tracking movements of spots covering the surface of the sample, loaded by longitudinal force. Рассмотрен характер смещения и поля деформации, которые были измерены на различных стадиях растяжения плоских образцов с целью сравнения влияния различных технологических параметров на механические свойства сварных соединений. Результаты измерений также сравниваются с результатами испытания на растяжение основного материала, позволяющие оценить влияние процесса сварки на изменения механических свойств испытанной стали. Представлены данные смещений и деформаций в плоских сварных образцах из стали S355, выполненных гибридной сваркой с использованием электрической дуги и лазерного пучка. Процесс сварки выполняся Yb:YAG лазером и электрической дугой при дуговой сварке металлическим электродом в защитном газе. В сварочных испытаниях использовалась лазерная головка D70 Trumpfc максимальной мощностью до 12 кВт и диаметром пятна лазерного пучка d = 0,8 м. Сварные соединения были выполнены для различных технологических параметров процесса. Испытания на растяжение плоских образцов выполняли в соответствии с нормами PN-EN ISO 6891-1. Многокамерная корреляционная 3D система Dantec Q-400 ISTRA использована для измерения деформаций и смещений. Метод измерения основывается на корреляции цифровых изображений, записанных при помощи трех камер. Поверхность испытанных образцов покрывали слоем белой и черной краски. Измерение проводили посредством следящего перемещения за точками, которые покрывают поверхность образца, нагруженного продольным усилием. Розглянуто характер зміщення і поля деформації, які були виміряні на різних стадіях розтягування пласких зразків з метою порівняння впливу різних технологічних параметрів на механічні властивості зварних з’єднань. Результати вимірювань також порівнюються з результатами випробування на розтягнення основного матеріалу, що дозволяють оцінити вплив процесу зварювання на зміни механічних властивостей випробуваної сталі. Представлені дані зсувів і деформацій в пласких зварних зразках зі сталі S355, виконаних гібридним зварюванням з використанням електричної дуги і лазерного пучка. Процес зварювання виконувався Yb:YAG лазером і електричною дугою при дуговому зварюванні металевим електродом в захисному газі. У зварювальних випробуваннях було розроблено лазерну голівку D70 Trumpfc максимальною потужністю до 12 кВт і діаметром плями лазерного пучка d = = 0,8 мм. Зварні з’єднання були виконані для різних технологічних параметрів процесу. Випробування на розтяг пласких зразків виконували відповідно до норм PN-EN ISO 6891-1. Багатокамерна кореляційний 3D система Dantec Q-400 ISTRA використана для вимірювання деформацій і зсувів. Метод вимірювання грунтується на кореляції цифрових зображень, записаних за допомогою трьох камер. Поверхні випробуваних зразків покривали шаром білої і чорної фарби. Вимірювання проводили за допомогою стеження за переміщенням точок, які покривають поверхню зразка, навантаженого поздовжнім зусиллям.

The RecA/LexA axis of the bacterial DNA damage (SOS) response is a promising, yet non-traditional drug target. The SOS response is initiated upon genotoxic stress, when RecA, a DNA damage sensor, induces LexA, the SOS repressor, to undergo autoproteolysis, thereby de-repressing downstream genes that can mediate DNA repair and accelerate mutagenesis. As genetic inhibition of the SOS response sensitizes bacteria to DNA damaging antibiotics and decreases acquired resistance, inhibitors of the RecA/LexA axis could potentiate our current antibiotic arsenal. Compounds targeting RecA, which has many mammalian homologs, have been reported; however, small-molecules targeting LexA autoproteolysis, a reaction unique to the prokaryotic SOS response, have remained elusive. Here, we describe the logistics and accomplishments of an academic-industry partnership formed to pursue inhibitors against the RecA/LexA axis. A novel fluorescence polarization assay reporting on RecA-induced self-cleavage of LexA enabled the screening of 1.8 million compounds. Follow-up studies on select leads show distinct activity patterns in orthogonal assays, including several with activity in cell-based assays reporting on SOS activation. Mechanistic assays demonstrate that we have identified first-in-class small molecules that specifically target the LexA autoproteolysis step in SOS activation. Our efforts establish a realistic example for navigating academic-industry partnerships in pursuit of anti-infective drugs, and offer starting points for dedicated lead optimization of SOS inhibitors that could act as adjuvants for current antibiotics.

Hybrid particle brushes and star polymers with a core-shell architecture were prepared via atom transfer radical polymerization (ATRP) and incorporated into bulk poly(methyl methacrylate) (PMMA) in order to improve the toughness and ductility of glassy, transparent PMMA. Mechanical and optical characterization demonstrated an improvement in both the strength and the toughness of the reinforced materials without significantly compromising the optical transparency.

We thank Cao et al. for their interest in our study.1 We acknowledge the importance of delayed scan time in DWI sensitivity and have previously highlighted this issue.2,3 Accordingly, there was a declining prevalence of DWI positivity with time, although 65% of our patients were scanned within 5 days.

Introduction. The data assessing the impact of beta blocker (BB) medication on survival in patients after heart transplantation (HTx) are scarce and unequivocal; therefore, we investigated this population. Methods. We retrospectively analyzed the HTx Zabrze Registry of 380 consecutive patients who survived the 30-day postoperative period. Results. The percentage of patients from the entire cohort taking BBs was as follows: atenolol 24 (17%), bisoprolol 67 (49%), carvedilol 11 (8%), metoprolol 28 (20%), and nebivolol 8 (6%). The patients receiving BBs were older (56.94 ± 14.68 years vs. 52.70 ± 15.35 years, p=0.008) and experienced an onset of HTx earlier in years (11.65 ± 7.04 vs. 7.24 ± 5.78 p≤0.001). They also had higher hematocrit (0.40 ± 0.05 vs. 0.39 ± 0.05, p=0.022) and red blood cells (4.63 (106/μl) ± 0.71 vs. 4.45 (106/μl) ± 0.68, p=0.015). Survival according to BB medication did not differ among the groups (p=0.655) (log-rank test). Univariate Cox proportional hazard regression analysis revealed that the following parameters were associated with unfavorable diagnosis: serum concentration of albumin (g/l) HR: 0.87, 95% CI (0.81–0.94), p=0.0004; fibrinogen (mg/dl) HR: 1.006, 95% CI (1.002–1.008), p=0.0017; and C-reactive protein (mg/l) HR: 1.014, 95% CI (1.004–1.023), p=0.0044. Conclusions. The use of BBs in our cohort of patients after HTx was not associated with survival benefits.

1. The increase in microbial resistance, and in particular multiple drug resistance (MDR), is an increasing threat to public health. The uncontrolled use of antibiotics and antibacterial chemotherapeutics in the poultry industry, especially in concentrations too low to cause inhibition, and the occurrence of residues in feed and in the environment play a significant role in the development of resistance among zoonotic food-borne microorganisms.2. Determining the presence and transmission methods of resistance in bacteria is crucial for tracking and preventing antibiotic resistance. Horizontal transfer of genetic elements responsible for drug resistance is considered to be the main mechanism for the spread of antibiotic resistance.3. Of the many well-known genetic elements responsible for horizontal gene transfer, integrons are among the most important factors contributing to multiple drug resistance. The mechanism of bacterial drug resistance acquisition through integrons is one of the essential elements of MDR prevention in animal production.

Introduction The incidence of stroke in young patients is increasing and is associated with significant morbidity, mortality and socioeconomic cost. Identifying potential underlying causes is central to their overall management to reduce recurrence and improve long-term outcomes. A proportion of these patients are found to have an underlying cardiac cause including atrial fibrillation (AF), patent foramen ovale (PFO) or an intracardiac source of embolus. This area has recently gained greater interest with evidence demonstrating a significant reduction in recurrent ischaemic events following PFO closure. The identification of these patients however, requires extensive investigation and has implications relating to cardiology resources. Outside of clinical trials the true incidence of these patients in a “real-world” population is poorly defined. Purpose The aim of this study was to determine the proportion of strokes attributable to cardiac causes in young patients presenting with ischaemic stroke. Methods The Sentinel Stroke National Audit Programme (SSNAP) database of a large UK stroke service was used to identify patients ≤55 years old presenting with stroke between 1/1/15 and 31/12/17. Clinical letters, imaging reports and laboratory reports were reviewed. Patients were then categorised by cause of stroke using the Trial of Acute Stroke Treatment (TOAST) criteria. Cardiac causes of stroke were defined as: AF, PFO and intracardiac source of embolus. Patients presenting with a haemorrhagic stroke or where an alternate diagnosis to stroke was more likely were excluded. Results During the study period, 206 patients were identified as having suffered a stroke. 35 patients were excluded resulting in a final study population of 171 patients (Figure). 24% (41/171) were identified as having a cardiac cause of stroke including 9.4% (16/171) PFO, 8.8% (15/171) intracardiac source of embolus and 5.8% (10/171) atrial fibrillation. 50.3% (86/171) were thought to have other causes: 24.6% (42/171) small vessel disease; 9.4% (16/171) large artery atherosclerosis; and 16.4% (28/171) other determined aetiology including 5.1% (8.8/171) with arterial dissection. 25.7% (44/171) presented with a stroke but with no clear underlying cause found. Causes of stroke in young patients Conclusion A high proportion (24%) of strokes in young patients were found to be likely secondary to a cardiac cause. With the significant benefit of intervention (medical or procedural) in this patient group, the resource provision allocated to this population does appear to be warranted and further demonstrates the importance of close interdisciplinary links between cardiologists and stroke physicians.

Currently, many therapies fail due to an insufficient drug dose reaching the target site and high systemic toxicity. Protein-based drug delivery systems that allow an increase in drug concentration at a specific location in the body or predominantly target malignant cells are promising technologies. Due to the high need for iron in many disorders including various types of cancer, iron-binding proteins: transferrin, ferritin and hemoglobin, are a promising tool as drug carriers. In this review we summarize the characteristics of human iron-binding proteins and present their use in targeted drug delivery strategies.

This chapter presents a complete synopsis of all clostridial genetic engineering activities that have been pursued to date in the context of cancer as well as an insight into the relevant genetic tools underpinning the efforts. Tumor-selective bacterial colonization is guaranteed, given that the hypoxic and necrotic areas uniquely found in solid tumors are the only places in which spores can germinate and grow. The chapter discusses opportunities that could be pursued in the future, highlighting the great promise that clostridial delivery systems hold as a treatment for cancer. Improvement of the colonization efficiency and elimination of the outer rim have been the focus of ongoing efforts in the development of clostridial cancer therapy. Genetic engineering of clostridial strains in an effort to further enhance, fine-tune, and optimize their oncolytic properties seemed a reasonable step in the direction of clinically advancing the genus for cancer therapy.

Numerical modeling of thermal phenomena with the motion of fusion zone in the welding pool taken into account is performed in this study for hybrid welding process using Yb:YAG laser with electric arc in GMAW method. New hybrid heat source model is developed on the basis of classical Goldak model for the electric arc and interpolation model for the laser beam with the experimental data of Yb:YAG laser beam distribution taken into account. Temperature field and melted material velocity field are calculated on the basis of numerical solution into mass, momentum and energy conservation equations in finite volume method with Chorin's projection method. Computer simulations of temperature field and melted material velocity field are performed in the welding pool for different distances between heat sources. The comparison of numerically estimated geometry of characteristic zones of joints with macroscopic pictures of cross sections of welds is made in order to evaluate the suitability of developed numerical model in industrial applications.

This work concerns experimental research on the determination of deformation during uniaxial tension test of samples made of laser-arc hybrid welded joints. Steel sheet made of S355 steel with thickness 5 mm is butt-welded without gap using hybrid welding technique involving GMAW method with Yb:YAG laser beam. Samples used to the tension test are made from welded joints and base material. Universal strength machine Zwick&Roel Z100 is used with extensometer Multisens in all performed tension tests. The machine works with Dantec Q-400 Istra multi-camera 3D correlation system. System of three cameras mounted on a beam line is used for accurate measurement of the spatial deformations. Presented results of the research include strain fields measured for the entire tension cycle at the frequency 40 Hz.

This work concerns issues of mathematical modelling of phase transformations in steels during a high-speed high-power heat source welding processes. The analysis of the influence of thermal cycle parameters such as: heating rate, cooling rate and the maximal heating temperature on the kinetics of phase transformations during heating and cooling is performed. The verification of classical mathematical and numerical models of phase transformations is presented in relation to advanced welding methods using a high-speed high-power heat source on the basis of data found in the literature and experimental research.

The mathematical model and numerical simulations of the mechanical phenomena in the gantry crane are presented in this paper. The design of modern mechanical constructions is a complex task that requires use of appropriate tools. Such a modern tool, that gives a broad opportunity to analyze strength parameters of designed structures, is numerical simulation which uses the various numerical methods. Here the problem was solved by the finite element method. The analysis of the stresses and strains of the structure of gantry crane was made using the advanced software with highly efficient possibilities of modeling. Motion of the crane trolley along the beam was also taken into account in the study. The research performed, allows the evaluation of the stress state, pointing out the critical areas and values which are made in order to increase the strength of the structure of the gantry crane. The results of numerical simulation are presented in the form of the fields of Huber-Misses stress for the selected location of the crane trolley.

Prediction of fusion zone and heat affected zone geometry in laser welding process.Estimation of structural composition of the laser welded joint.Considering austenitization temperatures changing with heating rates.Determining the impact of latent heats on the temperature field.Comparison of predicted characteristic zones of joints with experimental results. This paper concerns computational modelling of thermal phenomena and phase transformations in solid state in laser welding process. The analysis is performed on the basis of numerical solution into continuum mechanics governing equations as well as classic Johnson-Mehl-Avrami (JMA) and Koistinen-Marburger (KM) kinetics models with continuous heating transformation (CHT) and continuous cooling transformation (CCT) diagrams of S460 steel. The influence of latent heats on temperature distributions is analysed. Obtained results include temperature field, melted material velocity field in the fusion zone and structure composition of welded joint. Calculations are partially verified by experimental data.

This paper describes liver lobe torsion in a white-lipped tamarin (Saguinus labiatus) and an Alaotran gentle lemur (Hapalemur alaotrensis). Both animals had a history of acute collapse, and diagnosis was made post-mortem. To the authors' knowledge, these are the first reported cases of this pathology in non-human primates.

Laser beam processing of steel has increasing application in many industries, mainly due to high process speed and good quality of the product as well as a small zone of thermal influence on the material. The concentration of a laser heat energy leads to the generation of high cooling rates in heat affected zone (HAZ). As a result phase transformations in solid state are present, which leads to the formation of various structures in HAZ with differing mechanical properties. This work concerns numerical modelling and computer simulations of temperature field and phase transformations during Yb:YAG laser heating of sheets made of S355 steel. The distribution of Yb:YAG laser power emitted by Trumpf laser head D70 is used in the analysis. The heat source is modelled on the basis of interpolation algorithms using geostatistical kriging method. Coupled heat transfer and fluid flow in the fusion zone are described respectively by transient heat transfer equation with convective term and Navier-Stokes equation. The kinetics of phase transformations and volumetric fractions of arising phases are obtained on the basis of Johnson-Mehl-Avrami (JMA) and Koistinen-Marburger (KM) models. Continuous Heating Transformation (CHT) diagram is used for heating process and Continuous Cooling Transformation (CCT) diagram is used for heated steel with the decomposition of final volume fractions of phases transformed form austenite dependant on cooling rates. Examples of computer simulations are presented including temperature field, velocity field of liquid material in the fusion zone and estimated structure composition of elements made of S355 steel, heated by Yb:YAG laser.

This study concerns numerical modelling and computer simulation of thermal phenomena in spiral laser heating of shaft made of S355 steel. 3D numerical analysis is developed for the prediction of heat affected zone in Abaqus/FEA software. Power distribution of spirally moving heat source is implemented into additional DFLUX subroutine, written in Fortran programming language. Changing with temperature thermophysical properties are assumed in the analysis. The model of heat source motion takes into account the size of heat affected zone. Results of numerical analysis include temperature field, predicted heat affected zone and cooling rates. These results are a start point for the analysis of thermomechanical phenomena with the consideration of phase transformations in solid state.

Background Psoriatic arthritis (PsA) is affecting up to 40% of the patients with psoriasis. The pathogenesis of PsA in not completely understood. One of the hypothesis suggest that repeated micro injuries and trauma and lack of proper inhibition of inflammation lead to chronic inflammation spreading to surrounding tissue and other joints and ligaments. One of the mediators which lead to inhibition of inflammation in healthy conditions are derivatives of arachidonic acid – lipoxins. Objectives The aim of the study was to assess if the influence of lipoxin A4 on inhibition of synthesis of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMNCs) of patients with psoriatic arthritis. Methods The study group consisted of 10 patients with psoriatic arthritis and 5 healthy controls. The peripheral blood mononuclear cells from patients with PsA and healthy controls were isolated and were stimulated with lipopolisacharide (LPS) with or without 200 nM of lipoxin A4 for 24 hours. The supernatants were collected after 24 hour stimulation. The levels of IL-1b, IFN-gamma, TNF alfa, MCP-1, IL-6, IL-8 and IL-33 were assessed by cytometric bead array system. Results Incubation of cells with LPS, increased production of all cytokines assessed either in patients with psoriatic arthritis or in healthy controls. In PBMCs from healthy controls incubation of cells with lipoxine A4 decrease production of proinflammatory cytokines (IL-1b, MCP-1, IL-8, IL-6, IL-33 and TNF-alfa; p Conclusions Our study demonstrated that modulation of Inflammation by lipid mediatiors in patients with psoriatic arthritis is dysregulated. Disclosure of Interest None declared

This work concerns mathematical and numerical modelling of temperature field during hybrid welding process using Yb:YAG laser and electric arc in GMAW method. Numerical analysis is performed taking into account the motion of liquid steel in the fusion zone. Yb:YAG laser power distribution is determined on the basis of experimental research made on TruDisk 12002 laser. Geostatistical Kriging method is used in the interpolation of Yb:YAG laser power intensity distribution. Temperature field and melted material velocity field in the fusion zone of hybrid welded sheets made of S355 steel are obtained on the basis of numerical solution of continuum mechanics equations in Chorin's projection method and finite volume method. Experimental research of laser beam profile is performed in order to verify the correctness of developed heat source model. Fusion zone and heat affected zone geometry is predicted on the basis of calculated temperature field in the cross section of hybrid welded joint.

Numerical analysis of thermal treatment processes is an important issue to be considered by contemporary laboratories dealing with industrial designing in general. Phenomena associated with heat treatment are complex and not yet adequately explained. Improvement in this field of numerical solutions is particularly forced by industry which, striving for deployment of state of the art technologies and reduction of costs, is demanding continuous enhancement of tool thermal treatment. Phase transformations, in particular in cooling processes, involve considerable changes in kinetics that are not always associated with external thermal impact. Analyses of experimental data allowed developing many mathematical models to measure volume fractions of phase transformations in solid state. The Johnson-Mehl Avrami equation and generalised Kolmogorov equation are the two primary models applied in almost all tests evaluating transformation of austenite into ferrite, bainite and martensite. In order to calculate the martensitic phase volume fraction, usually the Koistinen-Marburger equation, or any of its modified formulas, are used.