Chiral recognition without π-π-interactions: Highly efficient chiral strong cation exchangers lacking an aromatic unit in the molecular structure.

Current state-of-the-art chiral stationary phases (CSPs) enable chiral resolution of almost any racemic mixture of choice. The exceptions represent ionizable and ionized substances that fail at any attempts to resolve on commercially available CSPs. These compounds, however, can be efficiently separated on chiral ion exchangers. Commercially available Cinchona alkaloids-based chiral weak ion-exchangers are typically used for chiral resolution of organic acids, while zwitterion ion-exchangers are efficient in the resolution of acids, bases, and zwitterions. The latter possess in their structure a cation exchange unit, which alone can serve as a cornerstone of chiral strong cation exchangers facilitating chiral separation of various basic racemic mixtures. Although chiral strong cation exchangers (cSCX) are efficient CSPs, their structural variations have not been thoroughly studied so far. It was assumed that the mechanism of chiral recognition of basic compounds by cSCX is based predominantly on π-π-interactions, hydrogen bonding and steric interactions (CSP I). To verify this assumption, we aimed in our study on the design and synthesis of cSCX first lacking lateral polar substituents on the aromatic unit in the selector's structure (CSP II), and second, to replace the aromatic unit by a cyclohexane ring (CSP III and IV), thereby to omit completely the π-π-interactions. We hypothesized that this structural change should lead to a partial or complete loss of enantiorecognition power of the selectors. Surprisingly, the non-aromatic cSCXs have shown chiral recognition capability comparable to that of previously described chiral cation exchange-type CSPs: from 16 analytes screened, 11 analytes were baseline resolved and 5 partially resolved on CSP I, while non-aromatic CSP III resolved 10 analytes baseline and 6 partially. We discuss the structural motifs of the known cSCX and the novel non-aromatic selectors in a relationship with their chromatographic performance using a set of basic analytes. Moreover, we present a theory of an effective chiral recognition mechanism by two novel non-aromatic cSCXs based on the chromatographic results and quantum mechanical calculations.

Chiral zwitterionic stationary phases based on Cinchona alkaloids and dipeptides - design, synthesis and application in chiral separation.

Chiral resolution of polar organic compounds such as amino acids and peptides represents an important chromatographic task due to increasing significance of natural species, which play important signaling and regulatory roles in the living organisms. Despite the number of available chiral stationary phases, this task remains challenging, since not many of the commercially available systems are capable to resolve non-derivatized zwitterionic species. In this study, we present a target-oriented design of a new class of chiral selectors. Pursuing the goal to separate amino acids, and especially short peptides, we have combined Cinchona alkaloids - quinine and quinidine - with three different biogenic dipeptides. We have synthesized six different chiral stationary phases, with selector loading of ∼200 µmol g-1, and tested their chiral recognition capabilities for acidic, basic and zwitterionic analytes using various mobile phases. We have observed that all chiral stationary phases retain the chiral anion exchange capability known for commercially available Cinchona-based columns leading to baseline or partial resolution of six out of ten analytes. The performance in chiral resolution of basic analytes is not optimum due to the weak cation exchange character of the peptidic residue. However, we report on encouraging results in the chiral resolution of short peptides, for which, depending on their structure, we see the chiral resolution of up to three stereoisomers (from four possible) in a preliminary screening.

Condition and Honey Productivity of Honeybee Colonies Depending on Type of Supplemental Feed for Overwintering.

Harvested honey is usually replaced by an alternative sugar to overwinter honeybee colonies. Supplementation of winter stores with beet or cane sucrose is safe for colonies and does not cause winter mortality. Despite this, there are hypotheses that supplementation of inverted sugars has the potential to give better results in overwintering, spring growth, and honey production of the colonies, because bees are consuming already cleaved feed. Therefore, we compared the condition parameters and honey production in 70 colonies at four apiaries overwintered with stores from sucrose or inverted sugars. No statistically significant differences in dependence on the type of the supplemental feed were found. Inverted sugar was more expensive than sucrose for feeding colonies. Economic efficiency, physiological consequences, and other disadvantages of using invert syrups are discussed.

The Optimization of Mechanical Alloying Conditions of Powder for the Preparation of a Fe-10Al-4Cr-4Y2O3 ODS Nanocomposite.

Mechanical alloying (MA) of powders represents the first processing step in the production of oxide dispersion-strengthened (ODS) alloys. MA is a time and energy-consuming process also in the production of Fe-10Al-4Cr-4Y2O3 creep and oxidation-resistant ODS nanocomposite, denoted as the FeAlOY, and it deserves to be optimized. MA is performed at two different temperatures at different times. The powder after MA, as well as the microstructure and high-temperature strength of the final FeAlOY, are characterized and the optimal MA conditions are evaluated. The obtained results show that the size distribution of the powder particles, as well as the dissolution and homogenization of the Y2O3, becomes saturated quite soon, while the homogenization of the metallic components, such as Al and Cr, takes significantly more time. The high-temperature tensile tests and grain microstructures of the secondary recrystallized FeAlOY, however, indicate that the homogenization of the metallic components during MA does not influence the quality of the FeAlOY, as the matrix of the FeAlOY is sufficiently homogenized during recrystallization. Thus, the conditions of MA correspond to sufficient dissolution and homogenization of Y2O3 and can be considered the optimal ones.

Polarized x-rays constrain the disk-jet geometry in the black hole x-ray binary Cygnus X-1.

A black hole x-ray binary (XRB) system forms when gas is stripped from a normal star and accretes onto a black hole, which heats the gas sufficiently to emit x-rays. We report a polarimetric observation of the XRB Cygnus X-1 using the Imaging X-ray Polarimetry Explorer. The electric field position angle aligns with the outflowing jet, indicating that the jet is launched from the inner x-ray-emitting region. The polarization degree is 4.01 ± 0.20% at 2 to 8 kiloelectronvolts, implying that the accretion disk is viewed closer to edge-on than the binary orbit. These observations reveal that hot x-ray-emitting plasma is spatially extended in a plane perpendicular to, not parallel to, the jet axis.

Substantial Improvement of High Temperature Strength of New-Generation Nano-Oxide-Strengthened Alloys by Addition of Metallic Yttrium.

Oxide-dispersion-strengthened (ODS) Fe-Al-Y2O3-based alloys (denoted as FeAlOY) containing 5 vol. % of nano-oxides have a potential to become top oxidation and creep-resistant alloys for applications at temperatures of 1100-1300 °C. Oxide dispersoids cause nearly perfect strengthening of grains; thus, grain boundaries with limited cohesive strength become the weak link in FeAlOY in this temperature range. One of the possibilities for significantly improving the strength of FeAlOY is alloying with appropriate elements and increasing the cohesive strength of grain boundaries. Nearly 20 metallic elements have been tested with the aim to increase cohesive strength in the frame of preliminary tests. A positive influence is revealed for Al, Cr, and Y, whereby the influence of Y is enormous (addition of 1% of metallic Y increases strength by a factor of 2), as it is presented in this paper.

Development of Machine Learning Models to Evaluate the Toughness of OPH Alloys.

Oxide Precipitation-Hardened (OPH) alloys are a new generation of Oxide Dispersion-Strengthened (ODS) alloys recently developed by the authors. The mechanical properties of this group of alloys are significantly influenced by the chemical composition and appropriate heat treatment (HT). The main steps in producing OPH alloys consist of mechanical alloying (MA) and consolidation, followed by hot rolling. Toughness was obtained from standard tensile test results for different variants of OPH alloy to understand their mechanical properties. Three machine learning techniques were developed using experimental data to simulate different outcomes. The effectivity of the impact of each parameter on the toughness of OPH alloys is discussed. By using the experimental results performed by the authors, the composition of OPH alloys (Al, Mo, Fe, Cr, Ta, Y, and O), HT conditions, and mechanical alloying (MA) were used to train the models as inputs and toughness was set as the output. The results demonstrated that all three models are suitable for predicting the toughness of OPH alloys, and the models fulfilled all the desired requirements. However, several criteria validated the fact that the adaptive neuro-fuzzy inference systems (ANFIS) model results in better conditions and has a better ability to simulate. The mean square error (MSE) for artificial neural networks (ANN), ANFIS, and support vector regression (SVR) models was 459.22, 0.0418, and 651.68 respectively. After performing the sensitivity analysis (SA) an optimized ANFIS model was achieved with a MSE value of 0.003 and demonstrated that HT temperature is the most significant of these parameters, and this acts as a critical rule in training the data sets.

The evolution and changing ecology of the African hominid oral microbiome.

The oral microbiome plays key roles in human biology, health, and disease, but little is known about the global diversity, variation, or evolution of this microbial community. To better understand the evolution and changing ecology of the human oral microbiome, we analyzed 124 dental biofilm metagenomes from humans, including Neanderthals and Late Pleistocene to present-day modern humans, chimpanzees, and gorillas, as well as New World howler monkeys for comparison. We find that a core microbiome of primarily biofilm structural taxa has been maintained throughout African hominid evolution, and these microbial groups are also shared with howler monkeys, suggesting that they have been important oral members since before the catarrhine-platyrrhine split ca. 40 Mya. However, community structure and individual microbial phylogenies do not closely reflect host relationships, and the dental biofilms of Homo and chimpanzees are distinguished by major taxonomic and functional differences. Reconstructing oral metagenomes from up to 100 thousand years ago, we show that the microbial profiles of both Neanderthals and modern humans are highly similar, sharing functional adaptations in nutrient metabolism. These include an apparent Homo-specific acquisition of salivary amylase-binding capability by oral streptococci, suggesting microbial coadaptation with host diet. We additionally find evidence of shared genetic diversity in the oral bacteria of Neanderthal and Upper Paleolithic modern humans that is not observed in later modern human populations. Differences in the oral microbiomes of African hominids provide insights into human evolution, the ancestral state of the human microbiome, and a temporal framework for understanding microbial health and disease.

The Effect of Heat Treatment on the Tribological Properties and Room Temperature Corrosion Behavior of Fe-Cr-Al-Based OPH Alloy.

The microstructure, mechanical, tribological, and corrosion properties of Fe-Cr-Al-Y-based oxide-precipitation-hardened (OPH) alloy at room temperature are presented. Two OPH alloys with a composition of 0.72Fe-0.15Cr-0.06Al-0.03Mo-0.01Ta-0.02Y2O3 and 0.03Y2O3 (wt.%) were prepared by mechanical alloying with different milling times. After consolidation by hot rolling, the alloys presented a very fine microstructure with a grain size of approximately 180 nm. Such a structure is relatively brittle, and its mechanical properties are enhanced by heat treatment. Annealing was performed at three temperatures (1000 °C, 1100 °C, and 1200 °C), with a holding time from 1 to 20 h. Tensile testing, wear testing, and corrosion testing were performed to evaluate the effect of heat treatment on the behavior and microstructural properties. The grain size increased almost 10 times by heat treatment, which influenced the mechanical properties. The ultimate tensile strength increased up to 300% more compared to the initial state. On the other hand, heat treatment has a negative effect on corrosion and wear resistance.

Influence of Hot Consolidation Conditions and Cr-Alloying on Microstructure and Creep in New-Generation ODS Alloy at 1100 °C.

The coarse-grained new-generation Fe-Al-Y2O3-based oxide dispersion strengthened (ODS) alloys contain 5 vol.% homogeneously dispersed yttria nano-precipitates and exhibit very promising creep and oxidation resistance above 1000 °C. The alloy is prepared by the consolidation of mechanically alloyed powders via hot rolling followed by secondary recrystallization. The paper presents a systematic study of influence of rolling temperature on final microstructure and creep at 1100 °C for two grades (Fe-10Al-4Y2O3 and Fe-9Al-14Cr-4Y2O3 in wt%) of new-generation ODS alloys. The hot rolling temperatures exhibit a rather wide processing window and the influence of Cr-alloying on creep properties is evaluated as only slightly positive.

Fundamental Improvement of Creep Resistance of New-Generation Nano-Oxide Strengthened Alloys via Hot Rotary Swaging Consolidation.

New-generation oxide dispersion-strengthened (ODS) alloys with a high volume fraction of nano-oxides of 5% are intended to become the leading creep- and oxidation-resistant alloys for applications at 1100-1300 °C. Hot consolidation of mechanically alloyed powders by intensive plastic deformation followed by heat treatment of the alloys are the key aspects for achieving top creep properties, typically ensured by a coarse-grained microstructure strengthened with homogeneously dispersed, very stable yttrium nano-oxides. The rotary swaging method proves to be favourable for hot consolidation of the new-generation ODS alloy presented. Compared to specimens consolidated by hot rolling, consolidation by hot rotary swaging predetermines the formation of coarse grains with a very high aspect ratio during subsequent secondary recrystallization. Such a grain morphology increases the creep strength of the new-generation ODS alloy considerably.

A wolf from Gravettian site Pavlov I, Czech Republic: Approach to skull pathology.

OBJECTIVE: Describe pathological features on internal and external aspects of the skull of an ancient grey wolf. MATERIALS: Wolf remains that were found at the southwestern settlement Area A of Gravettian site Pavlov I. METHODS: Visual observation and description; microcomputed tomography; porosity and fragmentation indices for internal and external skull features; histological section of the fourth upper premolar tooth. RESULTS: Dorsally, the sagittal crest revealed bone healing and remodeling. The sagittal lesion differential diagnosis was blunt trauma with or without fracture. Ventrally, otic region pathology included severe proliferation and lysis (osteomyelitis). The pathology was not resolvable among differential (microbial) causes of osteomyelitis, although other potential etiologies were ruled out. CONCLUSIONS: Probable first report of otic region osteomyelitis in an ancient grey wolf. SIGNIFICANCE: The proximity of the wolf remains to human-related findings, and presence of red ochre and shells, suggest human involvement in the burial. LIMITATIONS: This is a single specimen with differential diagnoses that were not resolvable to a single definitive diagnosis. SUGGESTIONS FOR FURTHER RESEARCH: Further investigation of the possible anthropological significance of the burial circumstances.

A chronology of landsliding based on archaeological and documentary data: Pavlovské vrchy Hills, Western Carpathian Flysch Belt.

Pavlovské vrchy Hills represent a distinctive elevation near the Czech-Austrian border where the active, dormant and relict landslides cover 12% of the area. Here we focused on the chronology of landsliding in this area using geological, archaeological and historical evidence. The earliest records of landsliding were determined in locations underlying the dated archaeological settlements. The Upper Paleolithic settlement complex dated between 37-24 ka cal BP, was originally deposited over these landslides. It was consequently destroyed in certain places by additional landslides preceding the last (Upper Pleniglacial) loess deposition (22 ka cal BP). These landslides took place before and after the Upper Paleolithic occupation of this area. This Pleistocene landslide event ranks among the oldest (albeit indirectly) dated landslide within the Czech part of the Western Carpathian Flysch Belt. The chronology of later, historical, landsliding was determined using written records (chronicles, official reports, archival evidence, etc.). Continuous records of landsliding were available as of the middle of the seventeenth century. The major concentration of landslides occurred at the beginning of the twentieth century (1910-1915). The 1663 landslide is currently the oldest landslide, in the Czech part of the Western Carpathian Flysch Belt, which was dated on the basis of documentary data.

Experimental evaluation of the potential for crayfish plague transmission through the digestive system of warm-blooded predators.

The crayfish plague pathogen (Aphanomyces astaci) can be transmitted through the digestive system of fish, but its dispersal through mammalian and bird digestive tracts has been considered unlikely, and direct experimental evidence remains scarce. We present a small-scale transmission experiment with European otter and American mink fed with infected crayfish, and experiments testing survival of cultures of five A. astaci strains at temperatures corresponding to those inside mammal and bird bodies. The pathogen was neither isolated from predator excrements nor transmitted to susceptible crayfish exposed to excrements. In agar-based artificial media, it occasionally survived for 15 min at 40.5°C and for 45 min at 37.5°C, but not so when incubated at those temperatures for 45 min and 75 min, respectively. The five tested strains differed in resistance to high temperatures, two (of genotype groups E and D) being more susceptible than other three (of groups A, B and D). Their survival to some extent varied when exposed to the same temperature after several weeks or months, suggesting that some yet-unknown factors may influence A. astaci resistance to temperature stress. Overall, we support the notion that passage through the digestive tract of warm-blooded predators makes A. astaci transmission unlikely.

Bent-core dimers with top-to-bottom linkage between central units.

A structurally new type of core-to-core dimer with a top-to-bottom linkage between the central cores of bent molecules is presented. The structure of the bent-core molecules was modified by changing the length of the spacer between the central cores and terminal chains, by changing the type of linkage groups in the bent-core arms and by variation of the terminal chain polarity - introducing polyfluoroalkyl and oligosiloxane units. Additionally, the outer phenyl ring was substituted with three alkyl chains to mimic a polycatenar system. For all compounds the mesophase behaviour and structural parameters were established to gain information about the molecular structure-mesomorphic property relationship.

Benefits of Islet Transplantation as an Alternative to Pancreas Transplantation: Retrospective Study of More Than 10 Ten Years of Experience in a Single Center.

BACKGROUND: Pancreas transplantation (PTx) represents the method of choice in type 1 diabetic patients with conservatively intractable hypoglycemia unawareness syndrome. In 2005, the Institute for Clinical and Experimental Medicine (IKEM) launched a program to investigate the safety potential of islet transplantation (ITx) in comparison to PTx. AIM: This study aims to compare the results of PTx and ITx regarding severe hypoglycemia elimination, metabolic control, and complication rate. METHODS: We analyzed the results of 30 patients undergoing ITx and 49 patients treated with PTx. All patients were C-peptide-negative and suffered from hypoglycemia unawareness syndrome. Patients in the ITx group received a mean number of 12,349 (6,387-15,331) IEQ/kg/person administered percutaneously into the portal vein under local anesthesia and radiological control. The islet number was reached by 1-3 applications, as needed. In both groups, we evaluated glycated hemoglobin, insulin dose, fasting and stimulated C-peptide, frequency of severe hypoglycemia, and complications. We used the Mann Whitney test, Wilcoxon signed-rank test, and paired t-test for analysis. We also individually assessed the ITx outcomes for each patient according to recently suggested criteria established at the EPITA meeting in Igls. RESULTS: Most of the recipients showed a significant improvement in metabolic control one and two years after ITx, with a significant decrease in HbA1c, significant elevation of fasting and stimulated C-peptide, and a markedly significant reduction in insulin dose and the frequency of severe hypoglycemia. Seventeen percent of ITx recipients were temporarily insulin-independent. The results in the PTx group were comparable to those in the ITx group, with 73% graft survival and insulin independence in year 1, 68% 2 years and 55% 5 years after transplantation. There was a higher rate of complications related to the procedure in the PTx group. Severe hypoglycemia was eliminated in the majority of both ITx and PTx recipients. CONCLUSION: This report proves the successful initiation of pancreatic islet transplantation in a center with a well-established PTx program. ITx has been shown to be the method of choice for hypoglycemia unawareness syndrome, and may be considered for application in clinical practice if conservative options are exhausted.

[Islet transplantation as a treatment for hypoglycemia unawareness syndrome. Evaluation of the pilot program and comparison with pancreas transplantation]. / Transplantace Langerhansových ostruvku v lécbe syndromu poruseného vnímání hypoglykemie. Vyhodnocení pilotního programu a porovnání s transplantací pankreatu.

Islet transplantation (ITx) started in 2005 in IKEM as a potentially safer alternative to pancreas transplantation (PTx), which so far had represented the method of choice in type-1 diabetic patients with conservatively intractable hypoglycemia unawareness syndrome. The aim of the study was to compare these two methods with regard to severe hypoglycemia elimination and to frequency of complications.Up to November 2015 a total number of 48 patients underwent ITx. The results from 22 patients with hypoglycemia unawareness were statistically analyzed. The mean number of transplanted islet equivalents was 12,096 (6,93316,705) IEQ/kg administered percutaneously in local anesthesia under radiological control to the portal vein. 44 patients underwent PTx from 1996. We evaluated glycated hemoglobin(HbA1c), insulin dose, fasting and stimulated C-peptide, frequency of severe hypoglycemia and complications. Medians (interquartile range) were analyzed using the Wilcoxon signed-rank test.One and two years after ITx, HbA1c decreased, C-peptide became significantly positive, insulin dose and frequency of severe hypoglycemia decreased and 18 % of ITx recipients were temporarily insulin-independent. Bleeding was present in 41 % of patients. One year after PTx, 73 % of patients were insulin and hypoglycemia-free, after two years 68 % of patients were insulin and hypoglycemia-free; graftectomy occurred in 20 % of recipients.Both methods led to restoration of insulin secretion and severe hypoglycemia elimination. PTx made more recipients insulin-independent at the cost of serious complications.

A Molecular Approach to the Sexing of the Triple Burial at the Upper Paleolithic Site of Dolní Vestonice.

In the past decades ancient DNA research has brought numerous insights to archaeological research where traditional approaches were limited. The determination of sex in human skeletal remains is often challenging for physical anthropologists when dealing with incomplete, juvenile or pathological specimens. Molecular approaches allow sexing on the basis of sex-specific markers or by calculating the ratio of DNA derived from different chromosomes. Here we propose a novel approach that relies on the ratio of X chromosome-derived shotgun sequencing data to the autosomal coverage, thus establishing the probability of an XX or XY karyotype. Applying this approach to the individuals of the Upper Paleolithic triple burial of Dolní Vestonice reveals that all three skeletons, including the individual DV 15, whose sex has long been debated due to a pathological condition, were male.

Pleistocene Mitochondrial Genomes Suggest a Single Major Dispersal of Non-Africans and a Late Glacial Population Turnover in Europe.

How modern humans dispersed into Eurasia and Australasia, including the number of separate expansions and their timings, is highly debated [1, 2]. Two categories of models are proposed for the dispersal of non-Africans: (1) single dispersal, i.e., a single major diffusion of modern humans across Eurasia and Australasia [3-5]; and (2) multiple dispersal, i.e., additional earlier population expansions that may have contributed to the genetic diversity of some present-day humans outside of Africa [6-9]. Many variants of these models focus largely on Asia and Australasia, neglecting human dispersal into Europe, thus explaining only a subset of the entire colonization process outside of Africa [3-5, 8, 9]. The genetic diversity of the first modern humans who spread into Europe during the Late Pleistocene and the impact of subsequent climatic events on their demography are largely unknown. Here we analyze 55 complete human mitochondrial genomes (mtDNAs) of hunter-gatherers spanning ∼35,000 years of European prehistory. We unexpectedly find mtDNA lineage M in individuals prior to the Last Glacial Maximum (LGM). This lineage is absent in contemporary Europeans, although it is found at high frequency in modern Asians, Australasians, and Native Americans. Dating the most recent common ancestor of each of the modern non-African mtDNA clades reveals their single, late, and rapid dispersal less than 55,000 years ago. Demographic modeling not only indicates an LGM genetic bottleneck, but also provides surprising evidence of a major population turnover in Europe around 14,500 years ago during the Late Glacial, a period of climatic instability at the end of the Pleistocene.

Effect of experimental exposure to differently virulent Aphanomyces astaci strains on the immune response of the noble crayfish Astacus astacus.

European crayfish are sensitive to the crayfish plague pathogen, Aphanomyces astaci, carried by North American crayfish species due to their less effective immune defence mechanisms against this disease. During a controlled infection experiment with a susceptible crayfish species Astacus astacus using three A. astaci strains (representing genotype groups A, B, and E), we investigated variation in their virulence and in crayfish immune defence indicators (haemocyte density, phenoloxidase activity, and production of reactive oxygen species). Experimental crayfish were exposed to two dosages of A. astaci spores (1 and 10 spores mL(-1)). The intensity and timing of the immune response differed between the strains as well as between the spore concentrations. Stronger and faster change in each immune parameter was observed in crayfish infected with two more virulent strains, indicating a relationship between crayfish immune response and A. astaci virulence. Similarly, the immune response was stronger and was observed earlier for the higher spore concentration. For the first time, the virulence of a strain of the genotype group E (isolated from Orconectes limosus) was experimentally tested. Total mortality was reached after 10 days for the two higher spore dosages (10 and 100 spores mL(-1)), and after 16 days for the lowest (1 spore mL(-1)), revealing equally high and rapid mortality as caused by the genotype group B (from Pacifastacus leniusculus). No mortality occurred after infection with genotype group A during 60 days of the experimental trial.