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Canada's national parks system originated in western Canada. On 25 November 1885, a week after authorities executed Louis Riel for his role in the North-West Resistance, and about two weeks [...]

The timing of Tiwanaku's collapse remains contested. Here we present a generational-scale chronology of Tiwanaku using Bayesian models of 102 radiocarbon dates, including 45 unpublished dates. This chronology tracks four community practices: residing short- vs. long-term, constructing monuments, discarding decorated ceramics, and leaving human burials. Tiwanaku was founded around AD 100 and around AD 600, it became the region's principal destination for migrants. It grew into one of the Andes' first cities and became famous for its decorated ceramics, carved monoliths, and large monuments. Our Bayesian models show that monument building ended ~AD 720 (the median of the ending boundary). Around ~AD 910, burials in tombs ceased as violent deaths began, which we document for the first time in this paper. Ritualized murders are limited to the century leading up to ~AD 1020. Our clearest proxy for social networks breaking down is a precise estimate for the end of permanent residence, ~AD 1010 (970-1050, 95%). This major inflection point was followed by visitors who used the same ceramics until ~AD 1040. Temporary camps lasted until roughly ~AD 1050. These four events suggest a rapid, city-wide collapse at ~AD 1010-1050, lasting just ~20 years (0-70 years, 95%). These results suggest a cascading breakdown of community practices and social networks that were physically anchored at Tiwanaku, though visitors continued to leave informal burials for centuries. This generation-scale chronology suggests that collapse 1) took place well before reduced precipitation, hence this was not a drought-induced societal change and 2) a few resilient communities sustained some traditions at other sites, hence the chronology for the site of Tiwanaku cannot be transposed to all sites with similar material culture.

Major histocompatibility class II molecule-peptide-T-cell receptor (MHCII-p-TCR) complex-mediated antigen presentation for a minimal subunit-based, multi-epitope, multistage, chemically-synthesised antimalarial vaccine is essential for inducing an appropriate immune response. Deep understanding of this MHCII-p-TCR complex’s stereo-electronic characteristics is fundamental for vaccine development. This review encapsulates the main principles for achieving such epitopes’ perfect fit into MHC-II human (HLADRβ̞1*) or Aotus (Aona DR) molecules. The enormous relevance of several amino acids’ physico-chemical characteristics is analysed in-depth, as is data regarding a 26.5 ± 2.5Å distance between the farthest atoms fitting into HLA-DRβ1* structures’ Pockets 1 to 9, the role of polyproline II-like (PPIIL) structures having their O and N backbone atoms orientated for establishing H-bonds with specific HLA-DRβ1*-peptide binding region (PBR) residues. The importance of residues having specific charge and orientation towards the TCR for inducing appropriate immune activation, amino acids’ role and that of structures interfering with PPIIL formation and other principles are demonstrated which have to be taken into account when designing immune, protection-inducing peptide structures (IMPIPS) against diseases scourging humankind, malaria being one of them.

Fifty ~20–amino acid (aa)–long peptides were selected from functionally relevant SARS-CoV-2 S, M, and E proteins for trial B-21 and another 53 common ones, plus some new ones derived from the virus’ main genetic variants for complementary trial C-21. Peptide selection was based on tremendous SARS-CoV-2 genetic variability for analysing them concerning vast human immunogenetic polymorphism for developing the first supramutational, Colombian SARS-protection (SM-COLSARSPROT), peptide mixture. Specific physicochemical rules were followed, i.e., aa predilection for polyproline type II left-handed (PPIIL) formation, replacing β-branched, aromatic aa, short-chain backbone H-bond-forming residues, π-π interactions (n→π* and π-CH), aa interaction with π systems, and molecular fragments able to interact with them, disrupting PPIIL propensity formation. All these modified structures had PPIIL formation propensity to enable target peptide interaction with human leukocyte antigen-DRβ1* (HLA-DRβ1*) molecules to mediate antigen presentation and induce an appropriate immune response. Such modified peptides were designed for human use; however, they induced high antibody titres against S, M, and E parental mutant peptides and neutralising antibodies when suitably modified and chemically synthesised for immunising 61 major histocompatibility complex class II (MHCII) DNA genotyped Aotus monkeys (matched with their corresponding HLA-DRβ1* molecules), predicted to cover 77.5% to 83.1% of the world’s population. Such chemically synthesised peptide mixture represents an extremely pure, stable, reliable, and cheap vaccine for COVID-19 pandemic control, providing a new approach for a logical, rational, and soundly established methodology for other vaccine development.

Abstract The ruins of Tiwanaku (A.D. 500–950), in the modern republic of Bolivia, present an archaeological challenge owing to intense looting during the colonial period that effectively demolished the site. One building in particular, known as the Pumapunku, was described by Spanish conquistadors and travelers of the sixteenth and seventeenth centuries, as a wondrous, though unfinished, building with gateways and windows carved from single blocks. Unparalleled in the pre-Colombian New World, the craftsmanship of this masonry has long been considered the architectural apogee of Andean pre-Colombian lithic technology. Unfortunately, during the last 500 years, treasure hunters have ransacked this building to the point that none of approximately shattered remains of 150 blocks of the standing architecture are to be found in their original place. Over the last century and a half, several different scholars have carefully measured the shattered architecture and even managed to join several fragments to form complete pieces. This research revisited these historic field notes with a view to transforming this century and a half of documentation into solid 3D form. These measurements were entered by hand into an architectural modeling program; the virtual form was subsequently printed in 3D form at 4% reduced scale. Unlike large architectural pieces — or notes or models on a computer screen — 3D-printed pieces can be manipulated quickly and intuitively, allowing researchers to try combinations and seek connections rapidly, turning over pieces and testing possible fits. This tactile engagement, along with the ability to quickly try out combinations of the 3D-printed pieces, led to fresh and often unexpected insights. Once refined and simplified, this methodology, was demonstrated to the indigenous site managers who were provided with a full copy of the printed architectural fragments with a view to continuing research and to present the work to visitors, stakeholders and other scholars.

The timing of Tiwanaku's collapse remains contested. Here we present a generational-scale chronology of Tiwanaku using Bayesian models of 102 radiocarbon dates, including 45 unpublished dates. This chronology tracks four community practices: residing short- vs. long-term, constructing monuments, discarding decorated ceramics, and leaving human burials. Tiwanaku was founded around AD 100 and around AD 600, it became the region's principal destination for migrants. It grew into one of the Andes' first cities and became famous for its decorated ceramics, carved monoliths, and large monuments. Our Bayesian models show that monument building ended ~AD 720 (the median of the ending boundary). Around ~AD 910, burials in tombs ceased as violent deaths began, which we document for the first time in this paper. Ritualized murders are limited to the century leading up to ~AD 1020. Our clearest proxy for social networks breaking down is a precise estimate for the end of permanent residence, ~AD 1010 (970–1050, 95%). This major inflection point was followed by visitors who used the same ceramics until ~AD 1040. Temporary camps lasted until roughly ~AD 1050. These four events suggest a rapid, city-wide collapse at ~AD 1010–1050, lasting just ~20 years (0–70 years, 95%). These results suggest a cascading breakdown of community practices and social networks that were physically anchored at Tiwanaku, though visitors continued to leave informal burials for centuries. This generation-scale chronology suggests that collapse 1) took place well before reduced precipitation, hence this was not a drought-induced societal change and 2) a few resilient communities sustained some traditions at other sites, hence the chronology for the site of Tiwanaku cannot be transposed to all sites with similar material culture. [ABSTRACT FROM AUTHOR]

Determining immune protection-inducing protein structures (IMPIPS) involves defining the stereo-electron and topochemical characteristics which are essential in MHC-p-TCR complex formation. Modified high activity binding peptides (mHABP) were thus synthesised to produce a large panel of IMPIPS measuring 26.5 ±3.5Å between the farthest atoms fitting into Pockets 1 to 9 of HLA-DRβ1* structures. They displayed a polyproline II-like (PPIIL) structure with their backbone O and N atoms orientated to establish H-bonds with specific residues from HLA-DRβ1*-peptide binding regions (PBR). Residues having specific charge and gauche+ orientation regarding p3χ1, p5χ2, and p7χ1 angles determined appropriate rotamer orientation for perfectly fitting into the TCR to induce an appropriate immune response. Immunological assays in Aotus monkeys involving IMPIPS mixtures led to promising results; taken together with the aforementioned physicochemical principles, non-interfering, long-lasting, protection-inducing, multi-epitope, multistage, minimal subunit-based chemically-synthesised peptides can be designed against diseases scourging humankind.

Major histocompatibility class II molecule-peptide-T-cell receptor (MHCII-p-TCR) complex-mediated antigen presentation for a minimal subunit-based, multi-epitope, multistage, chemically-synthesised antimalarial vaccine is essential for inducing an appropriate immune response. Deep understanding of this MHCII-p-TCR complex's stereo-electronic characteristics is fundamental for vaccine development. This review encapsulates the main principles for achieving such epitopes' perfect fit into MHC-II human (HLADRβ̞1*) or Aotus (Aona DR) molecules. The enormous relevance of several amino acids' physico-chemical characteristics is analysed in-depth, as is data regarding a 26.5 ± 2.5Å distance between the farthest atoms fitting into HLA-DRβ1* structures' Pockets 1 to 9, the role of polyproline II-like (PPIIL) structures having their O and N backbone atoms orientated for establishing H-bonds with specific HLA-DRβ1*-peptide binding region (PBR) residues. The importance of residues having specific charge and orientation towards the TCR for inducing appropriate immune activation, amino acids' role and that of structures interfering with PPIIL formation and other principles are demonstrated which have to be taken into account when designing immune, protection-inducing peptide structures (IMPIPS) against diseases scourging humankind, malaria being one of them. [ABSTRACT FROM AUTHOR]

A study on creation and renovation of Pumapunku temple complex, a ritual space, at Tiwanaku, Bolivia is presented.

The journey of Thor Heyedahl's from Peru to Polynesia made him see the archaeologists experimenting with ancient technologies and the adventurers inventing more and more improbable ways to get from one place to another. Expeditioners seems to have spotted everything from popsicle sticks to wine corks including reed boat, and spent almost three months assembling 2 million reeds of Tetera bundled into a huge boat 13,000ft above sea level on the edge of lake Titicaca.

Analysis of our Plasmodium falciparum malaria parasite peptides' 1 H-NMR database in the search for H-bonds and π-interactions led us to correlate their presence or absence with a peptide's particular immunological behavior. It was concluded that a 26.5 ± 1.5 Å between positions 1 to 9 of the HLA-DRβ1* interacting region was necessary for proper docking of 20mer-long peptides and these MHC Class II molecules for full-protective immunity. Presence of intramolecular H-bonds or π-interactions leading to righ-handed α-helix or β-turn conformation in this peptide's region induces different immune responses or none. PPII L conformation and the absence of any intramolecular interaction thus became the first feature characterising our immune protection-inducing structures as malaria vaccine candidates. [ABSTRACT FROM AUTHOR]