California Institute of Technology

About: California Institute of Technology is a education organization based out in Pasadena, California, United States. It is known for research contribution in the topics: Galaxy & Population. The organization has 57649 authors who have published 146691 publications receiving 8620287 citations. The organization is also known as: Caltech & Cal Tech.

SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies.

Abstract: The coronavirus disease 2019 (COVID-19) pandemic presents an urgent health crisis. Human neutralizing antibodies that target the host ACE2 receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein1–5 show promise therapeutically and are being evaluated clinically6–8. Here, to identify the structural correlates of SARS-CoV-2 neutralization, we solved eight new structures of distinct COVID-19 human neutralizing antibodies5 in complex with the SARS-CoV-2 spike trimer or RBD. Structural comparisons allowed us to classify the antibodies into categories: (1) neutralizing antibodies encoded by the VH3-53 gene segment with short CDRH3 loops that block ACE2 and bind only to ‘up’ RBDs; (2) ACE2-blocking neutralizing antibodies that bind both up and ‘down’ RBDs and can contact adjacent RBDs; (3) neutralizing antibodies that bind outside the ACE2 site and recognize both up and down RBDs; and (4) previously described antibodies that do not block ACE2 and bind only to up RBDs9. Class 2 contained four neutralizing antibodies with epitopes that bridged RBDs, including a VH3-53 antibody that used a long CDRH3 with a hydrophobic tip to bridge between adjacent down RBDs, thereby locking the spike into a closed conformation. Epitope and paratope mapping revealed few interactions with host-derived N-glycans and minor contributions of antibody somatic hypermutations to epitope contacts. Affinity measurements and mapping of naturally occurring and in vitro-selected spike mutants in 3D provided insight into the potential for SARS-CoV-2 to escape from antibodies elicited during infection or delivered therapeutically. These classifications and structural analyses provide rules for assigning current and future human RBD-targeting antibodies into classes, evaluating avidity effects and suggesting combinations for clinical use, and provide insight into immune responses against SARS-CoV-2. Eight structures of human neutralizing antibodies that target the SARS-CoV-2 spike receptor-binding domain are reported and classified into four categories, suggesting combinations for clinical use.

Evolution of binary black-hole spacetimes.

Abstract: We describe early success in the evolution of binary black-hole spacetimes with a numerical code based on a generalization of harmonic coordinates. Indications are that with sufficient resolution this scheme is capable of evolving binary systems for enough time to extract information about the orbit, merger, and gravitational waves emitted during the event. As an example we show results from the evolution of a binary composed of two equal mass, nonspinning black holes, through a single plunge orbit, merger, and ringdown. The resultant black hole is estimated to be a Kerr black hole with angular momentum parameter a[approximate]0.70. At present, lack of resolution far from the binary prevents an accurate estimate of the energy emitted, though a rough calculation suggests on the order of 5% of the initial rest mass of the system is radiated as gravitational waves during the final orbit and ringdown.

Ultrafine jagged platinum nanowires enable ultrahigh mass activity for the oxygen reduction reaction

Abstract: Improving the platinum (Pt) mass activity for the oxygen reduction reaction (ORR) requires optimization of both the specific activity and the electrochemically active surface area (ECSA). We found that solution-synthesized Pt/NiO core/shell nanowires can be converted into PtNi alloy nanowires through a thermal annealing process and then transformed into jagged Pt nanowires via electrochemical dealloying. The jagged nanowires exhibit an ECSA of 118 square meters per gram of Pt and a specific activity of 11.5 milliamperes per square centimeter for ORR (at 0.9 volts versus reversible hydrogen electrode), yielding a mass activity of 13.6 amperes per milligram of Pt, nearly double previously reported best values. Reactive molecular dynamics simulations suggest that highly stressed, undercoordinated rhombus-rich surface configurations of the jagged nanowires enhance ORR activity versus more relaxed surfaces.

Dynamic Analysis of Structural Systems Using Component Modes

Abstract: A method is developed for analyzing complex structural systems that can be divided into interconnected components. Displacements of the separate components are expressed in generalized coordinates that are defined by displacement modes. These are generated in three categories: rigid-body, "constraint," and "normal" modes. Rigid-body modes are convenient where displacements are denned in inertial space for dynamic analysis. "Constraint" modes are included to treat redundancies in the interconnection system. "Normal" modes define displacements relative to the connections. Generalized mass, stiffness, and damping matrices are determined for each component, as are generalized forces. The requirement of system continuity gives rise to equations of displacement compatibility at the connections. These serve as equations of constraint among the component coordinates and are used to construct a transformation relating component coordinates to system coordinates. This transformation is used to derive system properties and forces from component properties and forces. System equations of motion are formulated and solved to determine system response. Component responses are found using the transformation. Connection forces are computed from the component equations. Each component can then be isolated and treated separately.