THE PREHISTORY OF MONTREAL LAKE, CENTRAL SASKATCHEWAN

The purpose of this thesis is to present an outline of the culture history of Montreal Lake in central Saskatchewan. This reconstruction is based on material culture remains recovered by a survey and excavation program carried out in the region during the summer field seasons of 1972 and 1973. The culture history of the Montreal Lake region consisted of a number of occupations which occurred sporadically and which varied in distribution and duration. Most of the occupational prehistory was represented by northern Plains related complexes and traditions. The earliest identified occupations included Oxbow, McKean, Duncan and Hanna complexes of the early Meso-Indian period, possibly dating to 2000 B.C. in this region. Succeeding complexes, including Pelican Lake and Besant materials, were also Plains affiliated although some unidentified cultural materials could have been derived from other areas. Around A.D. 1500, occupations indicative of a boreal forest cultural tradition, the Clearwater Lake complex, appeared and persisted until the contact period. The sites located in the Montreal Lake region constituted a settlement pattern which clustered around the entrance to the Montreal River. The sites in this locality were slightly larger than sites located around the lake, and also evidenced a greater density and temporal range of cultural materials. The analysis of faunal remains from one site in this locality permitted inferences to be drawn concerning subsistence resources and seasonality of occupation

Fragility of the Dirac Cone Splitting in Topological Crystalline Insulator Heterostructures

The 'double Dirac cone' 2D topological interface states found on the (001) faces of topological crystalline insulators such as Pb$_{1-x}$Sn$_{x}$Se feature degeneracies located away from time reversal invariant momenta, and are a manifestation of both mirror symmetry protection and valley interactions. Similar shifted degeneracies in 1D interface states have been highlighted as a potential basis for a topological transistor, but realizing such a device will require a detailed understanding of the intervalley physics involved. In addition, the operation of this or similar devices outside of ultra-high vacuum will require encapsulation, and the consequences of this for the topological interface state must be understood. Here we address both topics for the case of 2D surface states using angle-resolved photoemission spectroscopy. We examine bulk Pb$_{1-x}$Sn$_{x}$Se(001) crystals overgrown with PbSe, realizing trivial/topological heterostructures. We demonstrate that the valley interaction that splits the two Dirac cones at each $\bar{X}$ is extremely sensitive to atomic-scale details of the surface, exhibiting non-monotonic changes as PbSe deposition proceeds. This includes an apparent total collapse of the splitting for sub-monolayer coverage, eliminating the Lifshitz transition. For a large overlayer thickness we observe quantized PbSe states, possibly reflecting a symmetry confinement mechanism at the buried topological interface

Does incremental and radical innovation performance depend on different types of knowledge accumulation capabilities and organizational size?

While prior studies recognize the importance of knowledge accumulation capabilities in innovation performance, current research has still failed to empirically identify its role with regard to different types of innovation performance. The objective of this paper is to address this knowledge gap and to explore the relationships between internal knowledge creation and absorptive capabilities, and incremental and radical innovation performance. The study also contributes to analyzing the complex effect that organizational size has in the whole innovation process, influencing its antecedents (internal knowledge creation capability and absorptive capability) as well as its outputs (incremental and radical innovation performance), as the literature has produced inconsistent results and the issue is subject to continuing debate. This study demonstrates that incremental innovation performance is positively affected by both knowledge accumulation capabilities and size. However, results show that only absorptive capability has a positive direct effect on radical innovation performance, whereas size has a negative non-significant effect on it. The effect of size on knowledge accumulation capabilities also turns out to be mixed. It appears to increase internal knowledge creation capability, but it does not affect the absorption of new external knowledge.The authors gratefully acknowledge financial support from the National Plan for R&D of Spanish Ministry of Economy and Competitiveness (ref. ECO2009-12522)

Structural insights into the effect of active-site mutation on the catalytic mechanism of carbonic anhydrase

Enzymes are catalysts of biological processes. Significant insight into their catalytic mechanisms has been obtained by relating site-directed mutagenesis studies to kinetic activity assays. However, revealing the detailed relationship between structural modifications and functional changes remains challenging owing to the lack of information on reaction intermediates and of a systematic way of connecting them to the measured kinetic parameters. Here, a systematic approach to investigate the effect of an active-site-residue mutation on a model enzyme, human carbonic anhydrase II (CA II), is described. Firstly, structural analysis is performed on the crystallographic intermediate states of native CA II and its V143I variant. The structural comparison shows that the binding affinities and configurations of the substrate (CO2) and product (HCO3-) are altered in the V143I variant and the water network in the water-replenishment pathway is restructured, while the proton-transfer pathway remains mostly unaffected. This structural information is then used to estimate the modifications of the reaction rate constants and the corresponding free-energy profiles of CA II catalysis. Finally, the obtained results are used to reveal the effect of the V143I mutation on the measured kinetic parameters (k(cat) and k(cat)/K-m) at the atomic level. It is believed that the systematic approach outlined in this study may be used as a template to unravel the structure-function relationships of many other biologically important enzymes

Climate shapes the spatiotemporal variation in color morph diversity and composition across the distribution range of Chrysomela lapponica leaf beetle

Color polymorphism offers rich opportunities for studying the eco-evolutionary mechanisms that drive the adaptations of local populations to heterogeneous and changing environments. We explored the color morph diversity and composition in a Chrysomela lapponica leaf beetle across its entire distribution range to test the hypothesis that environmental and climatic variables shape spatiotemporal variation in the phenotypic structure of a polymorphic species. We obtained information on 13 617 specimens of this beetle from museums, private collections, and websites. These specimens (collected from 1830-2020) originated from 959 localities spanning 33 degrees latitude, 178 degrees longitude, and 4200 m altitude. We classified the beetles into five color morphs and searched for environmental factors that could explain the variation in the level of polymorphism (quantified by the Shannon diversity index) and in the relative frequencies of individual color morphs. The highest level of polymorphism was found at high latitudes and altitudes. The color morphs differed in their climatic requirements; composition of colour morphs was independent of the geographic distance that separated populations but changed with collection year, longitude, mean July temperature and between-year temperature fluctuations. The proportion of melanic beetles, in line with the thermal melanism hypothesis, increased with increasing latitude and altitude and decreased with increasing climate seasonality. Melanic morph frequencies also declined during the past century, but only at high latitudes and altitudes where recent climate warming was especially strong. The observed patterns suggest that color polymorphism is especially advantageous for populations inhabiting unpredictable environments, presumably due to the different climatic requirements of coexisting color morphs

Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study

<p>Abstract</p> <p>Background</p> <p>Normal tension glaucoma is a major subtype of glaucoma, associated with intraocular pressures that are within the statistically normal range of the population. Monogenic forms following classical inheritance patterns are rare in this glaucoma subtype. Instead, multigenic inheritance is proposed for the majority of cases. The present study tested common sequence variants in candidate genes for association with normal tension glaucoma in the German population.</p> <p>Methods</p> <p>Ninety-eight SNPs were selected to tag the common genetic variation in nine genes, namely OPTN (optineurin), RDX (radixin), SNX16 (sorting nexin 16), OPA1 (optic atrophy 1), MFN1 (mitofusin 1), MFN2 (mitofusin 2), PARL (presenilin associated, rhomboid-like), SOD2 (superoxide dismutase 2, mitochondrial) and CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1). These SNPs were genotyped in 285 cases and 282 fully evaluated matched controls. Statistical analyses comprised single polymorphism association as well as haplogroup based association testing.</p> <p>Results</p> <p>Results suggested that genetic variation in five of the candidate genes (RDX, SNX16, OPA1, SOD2 and CYP1B1) is unlikely to confer major risk to develop normal tension glaucoma in the German population. In contrast, we observed a trend towards association of single SNPs in OPTN, MFN1, MFN2 and PARL. The SNPs of OPTN, MFN2 and PARL were further analysed by multimarker haplotype-based association testing. We identified a risk haplotype being more frequent in patients and a vice versa situation for the complementary protective haplotype in each of the three genes.</p> <p>Conclusion</p> <p>Common variants of OPTN, PARL, MFN1 and MFN2 should be analysed in other cohorts to confirm their involvement in normal tension glaucoma.</p

Climate shapes the spatiotemporal variation in color morph diversity and composition across the distribution range of Chrysomela lapponica leaf beetle

Color polymorphism offers rich opportunities for studying the eco-evolutionary mechanisms that drive the adaptations of local populations to heterogeneous and changing environments. We explored the color morph diversity and composition in a Chrysomela lapponica leaf beetle across its entire distribution range to test the hypothesis that environmental and climatic variables shape spatiotemporal variation in the phenotypic structure of a polymorphic species. We obtained information on 13 617 specimens of this beetle from museums, private collections, and websites. These specimens (collected from 1830-2020) originated from 959 localities spanning 33 degrees latitude, 178 degrees longitude, and 4200 m altitude. We classified the beetles into five color morphs and searched for environmental factors that could explain the variation in the level of polymorphism (quantified by the Shannon diversity index) and in the relative frequencies of individual color morphs. The highest level of polymorphism was found at high latitudes and altitudes. The color morphs differed in their climatic requirements; composition of colour morphs was independent of the geographic distance that separated populations but changed with collection year, longitude, mean July temperature and between-year temperature fluctuations. The proportion of melanic beetles, in line with the thermal melanism hypothesis, increased with increasing latitude and altitude and decreased with increasing climate seasonality. Melanic morph frequencies also declined during the past century, but only at high latitudes and altitudes where recent climate warming was especially strong. The observed patterns suggest that color polymorphism is especially advantageous for populations inhabiting unpredictable environments, presumably due to the different climatic requirements of coexisting color morphs

Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1

To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols

Data S3: Morphometric data of the collected adder specimens

As the most widely distributed snake in Eurasia, the adder (Vipera berus) has been extensively investigated in Europe but poorly understood in Asia. The Southern Altay Mountains represent the adder’s southern distribution limit in Central Asia, whereas its population status has never been assessed. We conducted, for the first time, field surveys for the adder at two areas of Southern Altay Mountains using a combination of line transects and random searches. We also described the morphological characteristics of the collected specimens and conducted analyses of external morphology and molecular phylogeny. The results showed that the adder distributed in both survey sites and we recorded a total of 34 sightings. In Kanas river valley, the estimated encounter rate over a total of 137 km transects was 0.15 ± 0.05 sightings/km. The occurrence of melanism was only 17%. The small size was typical for the adders in Southern Altay Mountains in contrast to other geographic populations of the nominate subspecies. A phylogenetic tree obtained by Bayesian Inference based on DNA sequences of the mitochondrial cytochrome b (1,023 bp) grouped them within the Northern clade of the species but failed to separate them from the subspecies V. b. sachalinensis. Our discovery extends the distribution range of V. berus and provides a basis for further researches. We discuss the hypothesis that the adder expands its distribution border to the southwest along the mountains’ elevation gradient, but the population abundance declines gradually due to a drying climate

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion