Role of Somatostatin Signalling in Neuroendocrine Tumours

Somatostatin (SST) is a small peptide that exerts inhibitory effects on a wide range of neuroendocrine cells. Due to the fact that somatostatin regulates cell growth and hormone secretion, somatostatin receptors (SSTRs) have become valuable targets for the treatment of different types of neuroendocrine tumours (NETs). NETs are a heterogeneous group of tumours that can develop in various parts of the body, including the digestive system, lungs, and pituitary. NETs are usually slow growing, but they are often diagnosed in advanced stages and can display aggressive behaviour. The mortality rate of NETs is not outstandingly increased compared to other malignant tumours, even in the metastatic setting. One of the intrinsic properties of NETs is the expression of SSTRs that serve as drug targets for SST analogues (SSAs), which can delay tumour progression and downregulate hormone overproduction. Additionally, in many NETs, it has been demonstrated that the SSTR expression level provides a prognostic value in predicting a therapeutic response. Furthermore, higher a SSTR expression correlates with a better survival rate in NET patients. In recent studies, other epigenetic regulators affecting SST signalling or SSA–mTOR inhibitor combination therapy in NETs have been considered as novel strategies for tumour control. In conclusion, SST signalling is a relevant regulator of NET functionality. Alongside classical SSA treatment regimens, future advanced therapies and treatment modalities are expected to improve the disease outcomes and overall health of NET patients.     

The Adhesion‐Enhanced Contact Electrification and Efficiency of Triboelectric Nanogenerators

In the present work, the contact electrification of polymers that differ in adhesion strength is studied. Electrical current is measured along with adhesion in macroscale contacting‐separation experiments. Additionally, local adhesion and roughness are studied with atomic force microscopy to get deeper insight into relations between surface properties and electrification. Measurements reveal that higher surface charge is formed on more adhesive surfaces, thus confirming covalent bond cleavage as a mechanism for contact electrification of polymers. Investigated materials possess enhanced contact electrification making them attractive candidates for the conversion of mechanical energy to electrical in triboelectric nanogenerator devices.     

N-Terminal Modification of Gly-His-Tagged Proteins with Azidogluconolactone

Site-specific protein modifications are vital for biopharmaceutical drug development. Gluconoylation is a non-enzymatic, post-translational modification of N-terminal HisTags. We report high-yield, site-selective in vitro α-aminoacylation of peptides, glycoproteins, antibodies, and virus-like particles (VLPs) with azidogluconolactone at pH 7.5 in 1 h. Conjugates slowly hydrolyse, but diol-masking with borate esters inhibits reversibility. In an example, we multimerise azidogluconoylated SARS-CoV-2 receptor-binding domain (RBD) onto VLPs via click-chemistry, to give a COVID-19 vaccine. Compared to yeast antigen, HEK-derived RBD was immunologically superior, likely due to observed differences in glycosylation. We show the benefits of ordered over randomly oriented multimeric antigen display, by demonstrating single-shot seroconversion and best virus-neutralizing antibodies. Azidogluconoylation is simple, fast and robust chemistry, and should accelerate research and development.     

Gelation of semiflexible polyelectrolytes by multivalent counterions

Filamentous polyelectrolytes in aqueous solution aggregate into bundles by interactions with multivalent counterions. These effects are well documented by experiment and theory. Theories also predict a gel phase in isotropic rodlike polyelectrolyte solutions caused by multivalent counterion concentrations much lower than those required for filament bundling. We report here the gelation of Pf1 virus, a model semiflexible polyelectrolyte, by the counterions Mg(2+), Mn(2+) and spermine(4+). Gelation can occur at 0.04% Pf1 volume fraction, which is far below the isotropic-nematic transition of 0.7% for Pf1 in monovalent salt. Unlike strongly crosslinked gels of semiflexible polymers, which stiffen at large strains, Pf1 gels reversibly soften at high strain. The onset strain for softening depends on the strength of interaction between counterions and the polyelectrolyte. Simulations show that the elasticity of counterion crosslinked gels is consistent with a model of semiflexible filaments held by weak crosslinks that reversibly rupture at a critical force.     

Nonlinear Viscoelastic,Viscoplastic Characterization of Unidirectional GF/EP Composite

Viscoplastic strains of unidirectional continuous fiber composite (HEXCEL GF/EPprepreg system) are studied experimentally and theoretically. Creep and strainrecovery tests are used. Schapery's nonlinear viscoelastic viscoplasticconstitutive equations are used and generalized to describe inelastic behavior ofunidirectional composite under isothermal creep and strain recovery conditions. Themethodology to quantify the viscoplastic strains with respect to applied stress isproposed. Viscoplastic strains of composite are described by plastic shear strain inmaterial symmetry axis. Assumptions has been used and validated that the functiondescribing the stress and time dependence of viscoplastic strain can be presented asa product of two, time and correspondingly stress dependent, master curves.     

A boosted-trees method for name disambiguation

This paper proposes a method for classifying true papers of a set of focal scientists and false papers of homonymous authors in bibliometric research processes. It directly addresses the issue of identifying papers that are not associated (??false??) with a given author. The proposed method has four steps: name and affiliation filtering, similarity score construction, author screening, and boosted trees classification. In this methodological paper we calculate error rates for our technique. Therefore, we needed to ascertain the correct attribution of each paper. To do this we constructed a small dataset of 4,253 papers allegedly belonging to a random sample of 100 authors. We apply the boosted trees algorithm to classify papers of authors with total false rate no higher than 30% (i.e. 3,862 papers of 91 authors). A one-run experiment achieves a testing misclassification error 0.55%, testing recall 99.84%, and testing precision 99.60%. A 50-run experiment shows that the median of testing classification error is 0.78% and mean 0.75%. Among the 90 authors in the testing set (one author only appeared in the training set), the algorithm successfully reduces the false rate to zero for 86 authors and misclassifies just one or two papers for each of the remaining four authors.     

Methyl 2-Halo-4-Substituted-5-Sulfamoyl-Benzoates as High Affinity and Selective Inhibitors of Carbonic Anhydrase IX

Among the twelve catalytically active carbonic anhydrase isozymes present in the human body, the CAIX is highly overexpressed in various solid tumors. The enzyme acidifies the tumor microenvironment enabling invasion and metastatic processes. Therefore, many attempts have been made to design chemical compounds that would exhibit high affinity and selective binding to CAIX over the remaining eleven catalytically active CA isozymes to limit undesired side effects. It has been postulated that such drugs may have anticancer properties and could be used in tumor treatment. Here we have designed a series of compounds, methyl 5-sulfamoyl-benzoates, which bear a primary sulfonamide group, a well-known marker of CA inhibitors, and determined their affinities for all twelve CA isozymes. Variations of substituents on the benzenesulfonamide ring led to compound 4b, which exhibited an extremely high observed binding affinity to CAIX; the K_d was 0.12 nM. The intrinsic dissociation constant, where the binding-linked protonation reactions have been subtracted, reached 0.08 pM. The compound also exhibited more than 100-fold selectivity over the remaining CA isozymes. The X-ray crystallographic structure of compound 3b bound to CAIX showed the structural position, while several structures of compounds bound to other CA isozymes showed structural reasons for compound selectivity towards CAIX. Since this series of compounds possess physicochemical properties suitable for drugs, they may be developed for anticancer therapeutic purposes.     

High occurrence of Campylobacter spp. in Latvian broiler chicken production

Campylobacteriosis in humans is caused by thermotolerant Campylobacter spp., most commonly by C. jejuni and C. coli. However, no official data for human campylobacteriosis in Latvia is available or cases are heavily under-reported. In accordance with Commission Decision 2007/516/EC the Campylobacter spp. baseline study was performed in 2008 in Latvia but there was no continuous monitoring for the Campylobacter at broiler chicken production level in 2009. The aim of the present study was to determine the occurrence of Campylobacter spp. in broiler chicken production at slaughterhouse and retail level in Latvia. Poultry samples originated from the two biggest Latvian broiler slaughterhouses. Altogether, 240 fresh broiler chicken neck skins, 2400 intact broiler chicken intestines and 240 fresh broiler chicken carcasses were collected during the year 2010. A total of 92.5% of the pooled intestine samples; 60.8% of the neck skin samples and 56.3% of carcasses were positive for Campylobacter spp. There was seasonal variation in proportions of Campylobacter positive samples with seasonal peak on summer months.     

Effect of chitosan and chitooligosaccharide lactate on free lipids and reducing sugars content and on wheat bread firming

The amount of free lipids and reducing sugars as well as crumb color for wheat bread samples containing different amounts of chitosan and chitooligosaccharide lactate have been determined. Firmness of bread containing various contents of low molecular weight chitosan and chitooligosaccharide lactate was studied as a function of storage time. Possible mechanisms of redistribution of free and bound lipids during bread making are discussed. Addition of chitooligosaccharide lactate in wheat bread results in reduction in lipid binding to starch and gluten. Free lipid content increases from 0.11 to 0.35% in the presence of 1% chitooligosaccharide lactate. The total color changes in bread crumb containing chitosan are higher compared with the color changes in bread crumb containing chitooligosaccharide lactate. So it can be supposed that Maillard reactions proceed more intensively in the presence of chitosan than in the presence of chitooligosaccharide lactate.     

Measuring Piezoelectric Output—Fact or Friction?

Piezoelectric polymers are emerging as exceptionally promising materials for energy harvesting. While the theoretical figures of merit for piezoelectric polymers are comparable to ceramics, the measurement techniques need to be retrofitted to account for the different mechanical properties of the softer polymeric materials. Here, how contact electrification, including friction and contact separation, is often mistaken for piezoelectric charge is examined, and a perspective for how to separate these effects is provided. The state of the literature is assessed, and recommendations are made for clear and simple guidelines in reporting, for both sample geometry and testing methods, to enable accurate determination of piezoelectric figures of merit in polymers. Such improvements will allow an understanding of what types of material manipulation are required in order to enhance the piezoelectric output from polymers and enable the next generation of polymer energy harvester design.