Machine Learning With Tree Tensor Networks, CP Rank Constraints, and Tensor Dropout.

Tensor networks developed in the context of condensed matter physics try to approximate order- N tensors with a reduced number of degrees of freedom that is only polynomial in N and arranged as a network of partially contracted smaller tensors. As we have recently demonstrated in the context of quantum many-body physics, computation costs can be further substantially reduced by imposing constraints on the canonical polyadic (CP) rank of the tensors in such networks. Here, we demonstrate how tree tensor networks (TTN) with CP rank constraints and tensor dropout can be used in machine learning.

Targeting the Main Protease (M, nsp5) by Growth of Fragment Scaffolds Exploiting Structure-Based Methodologies.

The main protease M, nsp5, of SARS-CoV-2 (SCoV2) is one of its most attractive drug targets. Here, we report primary screening data using nuclear magnetic resonance spectroscopy (NMR) of four different libraries and detailed follow-up synthesis on the promising uracil-containing fragment Z604 derived from these libraries. Z604 shows time-dependent binding.

Large-Scale Crystallographic Fragment Screening Expedites Compound Optimization and Identifies Putative Protein-Protein Interaction Sites.

The identification of starting points for compound development is one of the key steps in early-stage drug discovery. Information-rich techniques such as crystallographic fragment screening can potentially increase the efficiency of this step by providing the structural information of the binding mode of the ligands in addition to the mere binding information. Here, we present the crystallographic screening of our 1000-plus-compound F2X-Universal Library against the complex of the yeast spliceosomal Prp8 RNaseH-like domain and the snRNP assembly factor Aar2.

Criticality and Phase Classification for Quadratic Open Quantum Many-Body Systems.

We study the steady states of translation-invariant open quantum many-body systems governed by Lindblad master equations, where the Hamiltonian is quadratic in the ladder operators, and the Lindblad operators are either linear or quadratic and Hermitian. These systems are called quasifree and quadratic, respectively. We find that steady states of one-dimensional systems with finite-range interactions necessarily have exponentially decaying Green's functions.

The 3-triangle method preserves the posterior tibial slope during high tibial valgus osteotomy: first preliminary data using a mathematical model.

Purpose: Despite much improved preoperative planning techniques accurate intraoperative assessment of the high tibial valgus osteotomy (HTO) remains challenging and often results in coronal over- and under-corrections as well as unintended changes of the posterior tibial slope. Noyes et al. reported a novel method for accurate intraoperative coronal and sagittal alignment correction based on a three-dimensional mathematical model.

Sweeping-beam technique with electrons for large treatment areas as total skin irradiation : Dosimetric and technical aspects of a modified Stanford technique.

Purpose: Total skin electron beam therapy (TSEBT) is still a technical and therapeutic challenge today. Thus, we developed TSEBT using a sweeping-beam technique.

Methods: For treatment delivery, a linear accelerator Versa HD (ELEKTA, Stockholm, Sweden) with high-dose-rate electrons (HDRE) was used with a dose rate of 9000 MU/min.

DYW domain structures imply an unusual regulation principle in plant organellar RNA editing catalysis.

RNA editosomes selectively deaminate cytidines to uridines in plant organellar transcripts-mostly to restore protein functionality and consequently facilitate mitochondrial and chloroplast function. The RNA editosomal pentatricopeptide repeat proteins serve target RNA recognition, whereas the intensively studied DYW domain elicits catalysis. Here we present structures and functional data of a DYW domain in an inactive ground state and activated.

Frag4Lead: growing crystallographic fragment hits by catalog using fragment-guided template docking.

In recent years, crystallographic fragment screening has matured into an almost routine experiment at several modern synchrotron sites. The hits of the screening experiment, i.e.

Focal cartilage defects of the lateral compartment do influence the outcome after high tibial valgus osteotomy.

Introduction: High tibial medial open-wedge valgus osteotomy (HTO) is a well-established procedure for unicompartimental medial osteoarthritis of the young and active patient. However, the influence of cartilage defects of the lateral compartment on the total outcome remains obscure.

Methods: From 2005 to 2012, a total of 63 patients underwent HTO for medial osteoarthritis of the knee at a single university orthopaedic center.

Eigenstate Entanglement: Crossover from the Ground State to Volume Laws.

For the typical quantum many-body systems that obey the eigenstate thermalization hypothesis (ETH), we argue that the entanglement entropy of (almost) all energy eigenstates is described by a single crossover function. The ETH implies that the crossover functions can be deduced from subsystem entropies of thermal ensembles and have universal properties. These functions capture the full crossover from the ground-state entanglement regime at low energies and small subsystem size (area or log-area law) to the extensive volume-law regime at high energies or large subsystem size.

Large-scale ratcheting in a bacterial DEAH/RHA-type RNA helicase that modulates antibiotics susceptibility.

Many bacteria harbor RNA-dependent nucleoside-triphosphatases of the DEAH/RHA family, whose molecular mechanisms and cellular functions are poorly understood. Here, we show that the DEAH/RHA protein, HrpA, is an ATP-dependent 3 to 5' RNA helicase and that the RNA helicase activity of HrpA influences bacterial survival under antibiotics treatment. Limited proteolysis, crystal structure analysis, and functional assays showed that HrpA contains an N-terminal DEAH/RHA helicase cassette preceded by a unique N-terminal domain and followed by a large C-terminal region that modulates the helicase activity.

FragMAXapp: crystallographic fragment-screening data-analysis and project-management system.

Crystallographic fragment screening (CFS) has become one of the major techniques for screening compounds in the early stages of drug-discovery projects. Following the advances in automation and throughput at modern macromolecular crystallography beamlines, the bottleneck for CFS has shifted from collecting data to organizing and handling the analysis of such projects. The complexity that emerges from the use of multiple methods for processing and refinement and to search for ligands requires an equally sophisticated solution to summarize the output, allowing researchers to focus on the scientific questions instead of on software technicalities.

Students' perceptions of training and experiences with interpreters in a pro bono physical therapy setting.

Professional interpreters are an essential part of the healthcare team in providing high-quality care to all patients. However, interprofessional skills for working with professional interpreters are often not developed until after entering the workforce. Little is known about the educational impact of working with interpreters in a pro bono setting during graduate education.

Facilitated crystal handling using a simple device for evaporation reduction in microtiter plates.

In the past two decades, most of the steps in a macromolecular crystallography experiment have undergone tremendous development with respect to speed, feasibility and increase of throughput. The part of the experimental workflow that is still a bottleneck, despite significant efforts, involves the manipulation and harvesting of the crystals for the diffraction experiment. Here, a novel low-cost device is presented that functions as a cover for 96-well crystallization plates.

USE OF INTRACARPAL INTERLEUKIN RECEPTOR ANTAGONIST PROTEIN (IRAP) AND HYALURONIC ACID IN A MULTIMODAL THERAPEUTIC REGIME FOR OSTEOARTHRITIS IN AN ASIAN ELEPHANT ().

An approximately 41-yr-old female Asian elephant ( experiencing forelimb stiffness and decreased range of motion was diagnosed with bilateral carpal osteoarthritis (OA). Standing sedation combined with local anesthesia was used to deliver ultrasound-guided carpal articular injections of an autologous conditioned serum product, interleukin receptor antagonist protein, combined with hyaluronic acid. Within 2 mo of completing therapy, improved range and speed of motion were evident.

Workflow and Tools for Crystallographic Fragment Screening at the Helmholtz-Zentrum Berlin.

Fragment screening is a technique that helps to identify promising starting points for ligand design. Given that crystals of the target protein are available and display reproducibly high-resolution X-ray diffraction properties, crystallography is among the most preferred methods for fragment screening because of its sensitivity. Additionally, it is the only method providing detailed 3D information of the binding mode of the fragment, which is vital for subsequent rational compound evolution.

Why compromise the patella? Five-year follow-up results of medial patellofemoral ligament reconstruction with soft tissue patellar fixation.

Purpose: This study investigates the redislocation rate and functional outcome at a minimum follow-up of five years after medial patellofemoral ligament (MPFL) reconstruction with soft tissue patellar fixation for patella instability.

Methods: Patients were retrospectively identified and knees were evaluated for trochlea dysplasia according to Dejour, for presence of patella alta and for presence of cartilage lesion at surgery. At a minimum follow-up of five years, information about an incident of redislocation was obtained.

Effects of Lupron and surgical castration on fecal androgen metabolite concentrations and intermale aggression in capybaras (Hydrochoerus hydrochaeris).

To curb agonistic interactions in a bachelor group of three male capybaras (Hydrochoerus hydrochaeris), a single dose of leuprolide acetate (Lupron®) was used in an attempt to chemically sterilize the males. Concurrently, fecal androgen metabolite (FAM) concentrations were quantified via enzyme immunoassay to monitor changes in testosterone production after injection of the gonadotropin-releasing hormone agonist. When Lupron proved ineffective in suppressing intraspecific aggression, surgical castration was performed on two males, with continued noninvasive endocrine monitoring.

Utilizing Camera Traps, Closed Circuit Cameras and Behavior Observation Software to Monitor Activity Budgets, Habitat Use, and Social Interactions of Zoo-Housed Asian Elephants ().

Accredited zoos and aquariums value superior animal husbandry and strive to ensure that the physical, psychological, and social needs of animals are met. In North America, the Association of Zoos and Aquariums (AZA) relies on species-specific standards to ensure facilities provide the best care for collection animals. The AZA also makes explicit recommendations for long-term monitoring of welfare.

F2X-Universal and F2X-Entry: Structurally Diverse Compound Libraries for Crystallographic Fragment Screening.

Crystallographic fragment screening (CFS) provides excellent starting points for projects concerned with drug discovery or biochemical tool compound development. One of the fundamental prerequisites for effective CFS is the availability of a versatile fragment library. Here, we report on the assembly of the 1,103-compound F2X-Universal Library and its 96-compound sub-selection, the F2X-Entry Screen.

Is debridement beneficial for focal cartilage defects of the knee: data from the German Cartilage Registry (KnorpelRegister DGOU).

Introduction: Focal cartilage defects of the knee are often treated with arthroscopic debridement. Existing literature discussing the benefit of debridement for small articular cartilage lesions is scarce, especially if the debridement was not part of a combined operative cartilage procedure including meniscal and ligament repair. The purpose of this study was to examine the patients´ benefit after arthroscopic debridement for the treatment of isolated focal chondral defects with or without partial meniscus resection.

[Indications and techniques of arthroscopic anterior and lateral acromioplasty].

Objective: Arthroscopic anterior acromioplasty (AAAP) for treatment of symptomatic subacromial spur. Arthroscopic lateral acromioplasty (ALAP) to reduce a pathological critical shoulder angle (CSA) and prevent rotator cuff re-tear after reconstruction.

Indications: AAAP is indicated for acromial impingement due to an anterolateral acromial spur with or without bursa-sided rotator cuff lesion.