Crowdsourced morphometrics data

This zip file contains geometric morphometric landmark data collected by Mechanical Turk workers, as well as BAMM input and output files

Supplementary Information: BAMM Assessment

Supplementary Information: BAMM Assessmen

Burin_et_al_suppmat

Burin_et_al_suppma

rate-smoothed mega-phylogeny of actinopterygiians

Phylogeny based upon RAXML analysis of 13 gene concatenated data set assembled using phlawd pipeline and rate-smoothed using treePL. See methods and supplemental methods for details of tree construction

The legacy of ICTY and its impact upon the Statue and the practice of the ICC

Legacy of ICTY and its Impact on Statute and Case Law of ICC Establishing of International Criminal Court is a significant moment in evolution of international criminal law. It is the first permanent institution of international justice with personal jurisdiction and it was founded for one purpose only - to finally end the era of impunity for war criminals all over the world. But ICC didn't appear from nowhere. There was a long road towards its establishment and who knows if it would ever happen without influence of so called ad hoc tribunals, International Criminal Tribunal for the former Yugoslavia and International Criminal Tribunal for Rwanda. It is a sad truth that international criminal law made its biggest evolution as a reflection of the world's most horrible conflicts. The purpose of this thesis is to analyze a legacy of one of these tribunals, International Criminal Tribunal for the former Yugoslavia, and to explore its influence not only on the Statute of International Criminal Court, but also on its case law. International Criminal Court is not operating for long, but we can still notice many references on ICTY case law in its judgments. The reason for this research is my particular relation towards Balkan region as well as my interest in international justice in general. The thesis is composed..

A Chemically Induced Vaccine Strategy for Prostate Cancer

Here we report the design and evaluation of a bifunctional, small molecule switch that induces a targeted immune response against tumors <i>in vivo</i>. A high affinity ligand for prostate specific membrane antigen (PSMA) was conjugated to a hapten that binds dinitrophenyl (DNP)-specific antibodies. When introduced into hu-PBL-NOD/SCID mice previously immunized with a KLH-DNP immunogen, this conjugate induced a targeted antibody-dependent cellular cytotoxicity (ADCC) response to PSMA-expressing tumor cells in a mouse xenograft model. The ability to create a small molecule inducible antibody response against self-antigens using endogenous non-autoreactive antibodies may provide advantages over the autologous immune response generated by conventional vaccines in certain therapeutic settings

Imidazolopiperazines: Lead Optimization of the Second-Generation Antimalarial Agents

On the basis of the initial success of optimization of a novel series of imidazolopiperazines, a second generation of compounds involving changes in the core piperazine ring was synthesized to improve antimalarial properties. These changes were carried out to further improve the potency and metabolic stability of the compounds by leveraging the outcome of a set of in vitro metabolic identification studies. The optimized 8,8-dimethyl imidazolopiperazine analogues exhibited improved potency, in vitro metabolic stability profile and, as a result, enhanced oral exposure in vivo in mice. The optimized compounds were found to be more efficacious than the current antimalarials in a malaria mouse model. They exhibit moderate oral exposure in rat pharmacokinetic studies to achieve sufficient multiples of the oral exposure at the efficacious dose in toxicology studies

Lead Optimization of Imidazopyrazines: A New Class of Antimalarial with Activity on <i>Plasmodium</i> Liver Stages

Imidazopyridine <b>1</b> was identified from a phenotypic screen against <i>P. falciparum</i> (Pf) blood stages and subsequently optimized for activity on liver-stage schizonts of the rodent parasite <i>P. yoelii</i> (Py) as well as hypnozoites of the simian parasite <i>P. cynomolgi</i> (Pc). We applied these various assays to the cell-based lead optimization of the imidazopyrazines, exemplified by <b>3</b> (KAI407), and show that optimized compounds within the series with improved pharmacokinetic properties achieve causal prophylactic activity <i>in vivo</i> and may have the potential to target the dormant stages of <i>P. vivax</i> malaria

Synthesis, Structure–Activity Relationships, and in Vivo Efficacy of the Novel Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor 5‑Chloro‑<i>N</i>2‑(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)‑<i>N</i>4‑(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) Currently in Phase 1 and Phase 2 Clinical Trials

The synthesis, preclinical profile, and in vivo efficacy in rat xenograft models of the novel and selective anaplastic lymphoma kinase inhibitor <b>15b</b> (LDK378) are described. In this initial report, preliminary structure–activity relationships (SARs) are described as well as the rational design strategy employed to overcome the development deficiencies of the first generation ALK inhibitor <b>4</b> (TAE684). Compound <b>15b</b> is currently in phase 1 and phase 2 clinical trials with substantial antitumor activity being observed in ALK-positive cancer patients