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.

[Autonomy and Participation As Common Goals of Nursing, Therapy and Social Medicine: Proposal for an Organizational Configuration Model on the Basis of Service Blueprinting].

Background: Every person who is in the need of long-term care (according to German Social Code SGB XI §14) fulfills the requirements of disability according to German Social Code SGB IX, § 2. The right of participation and autonomy must be specially protected and realized for persons with long-term care needs because these persons have a limited capacity to advance their interests. The rights of people in the need of long-term care or assistance are protected not only by the national constitution but also by the UN Disability Rights Convention.

Knee implant kinematics are task-dependent.

Although total knee arthroplasty (TKA) has become a standard surgical procedure for relieving pain, knowledge of the in vivo knee joint kinematics throughout common functional activities of daily living is still missing. The goal of this study was to analyse knee joint motion throughout complete cycles of daily activities in TKA subjects to establish whether a significant difference in joint kinematics occurs between different activities. Using dynamic videofluoroscopy, we assessed tibio-femoral kinematics in six subjects throughout complete cycles of walking, stair descent, sit-to-stand and stand-to-sit.

A comprehensive assessment of the musculoskeletal system: The CAMS-Knee data set.

Combined knowledge of the functional kinematics and kinetics of the human body is critical for understanding a wide range of biomechanical processes including musculoskeletal adaptation, injury mechanics, and orthopaedic treatment outcome, but also for validation of musculoskeletal models. Until now, however, no datasets that include internal loading conditions (kinetics), synchronized with advanced kinematic analyses in multiple subjects have been available. Our goal was to provide such datasets and thereby foster a new understanding of how in vivo knee joint movement and contact forces are interlinked - and thereby impact biomechanical interpretation of any new knee replacement design.

A moving fluoroscope to capture tibiofemoral kinematics during complete cycles of free level and downhill walking as well as stair descent.

Videofluoroscopy has been shown to provide essential information in the evaluation of the functionality of total knee arthroplasties. However, due to the limitation in the field of view, most systems can only assess knee kinematics during highly restricted movements. To avoid the limitations of a static image intensifier, a moving fluoroscope has been presented as a standalone system that allows tracking of the knee during multiple complete cycles of level- and downhill-walking, as well as stair descent, in combination with the synchronous assessment of ground reaction forces and whole body skin marker measurements.

[Social Medicine and Interfaces in Sectoral Health Care Provision].

In addition to the consideration of individual medicine, social medicine focuses on the social references of health and sickness. In this context, it reflects the structures of the entire health care system, its functions and its functional deficits. It deals with the specific interaction between medicine and society and functions such as a link to the classical social sciences (1).

Site Selection: a Case Study in the Identification of Optimal Cysteine Engineered Antibody Drug Conjugates.

As the antibody drug conjugate (ADC) community continues to shift towards site-specific conjugation technology, there is a growing need to understand how the site of conjugation impacts the biophysical and biological properties of an ADC. In order to address this need, we prepared a carefully selected series of engineered cysteine ADCs and proceeded to systematically evaluate their potency, stability, and PK exposure. The site of conjugation did not have a significant influence on the thermal stability and in vitro cytotoxicity of the ADCs.

A PTK7-targeted antibody-drug conjugate reduces tumor-initiating cells and induces sustained tumor regressions.

Disease relapse after treatment is common in triple-negative breast cancer (TNBC), ovarian cancer (OVCA), and non-small cell lung cancer (NSCLC). Therapies that target tumor-initiating cells (TICs) should improve patient survival by eliminating the cells that can drive tumor recurrence and metastasis. We demonstrate that protein tyrosine kinase 7 (PTK7), a highly conserved but catalytically inactive receptor tyrosine kinase in the Wnt signaling pathway, is enriched on TICs in low-passage TNBC, OVCA, and NSCLC patient-derived xenografts (PDXs).

Natural Product Splicing Inhibitors: A New Class of Antibody-Drug Conjugate (ADC) Payloads.

There is a considerable ongoing work to identify new cytotoxic payloads that are appropriate for antibody-based delivery, acting via mechanisms beyond DNA damage and microtubule disruption, highlighting their importance to the field of cancer therapeutics. New modes of action will allow a more diverse set of tumor types to be targeted and will allow for possible mechanisms to evade the drug resistance that will invariably develop to existing payloads. Spliceosome inhibitors are known to be potent antiproliferative agents capable of targeting both actively dividing and quiescent cells.

[Participation as Target of Social Medicine and Nursing Care: - Legal Definition of Long-Term Care Dependency - Strategies to Prevent Long-Term Care Dependency].

By the "Second Bill to Strengthen Long-Term Care", a new concept of long-term care dependency will be introduced, valid from 2017. Long-term care dependency according to Social Code XI will be defined covering more aspects than today. Therefore, the working group "Nursing Care" of the division "Social Medicine in Practice and Rehabilitation" in the German Society for Social Medicine and Prevention presents their results after working on the social medicine perspective of the definition and prevention of long-term care dependency.

Reliability of Phase Velocity Measurements of Flexural Acoustic Waves in the Human Tibia In-Vivo.

Purpose: Axial-transmission acoustics have shown to be a promising technique to measure individual bone properties and detect bone pathologies. With the ultimate goal being the in-vivo application of such systems, quantification of the key aspects governing the reliability is crucial to bring this method towards clinical use.

Materials And Methods: This work presents a systematic reliability study quantifying the sources of variability and their magnitudes of in-vivo measurements using axial-transmission acoustics.

Three-dimensional kinematics of an unconstrained ankle arthroplasty: a preliminary in vivo videofluoroscopic feasibility study.

Background: Understanding the functionality of total ankle arthroplasties (TAA) requires thorough knowledge of the kinematics during activities of daily life. Videofluoroscopy enables the in vivo measurement of the 3D kinematics of implant components more accurately than by means of skin marker tracking. The aim of the present preliminary study was to quantify the 3D kinematics of a TAA during the stance phase of level and slope walking using single plane videofluoroscopy.

Comparison of the angles and corresponding moments in the knee and hip during restricted and unrestricted squats.

The aim of this study was to compare the angles and corresponding moments in the knee and hip during squats. Twenty subjects performed restricted and unrestricted squats with barbell loads that were 0, ¼, and ½ their body weight. The experimental setup consisted of a motion capture system and 2 force plates.

Characterizing the mechanical parameters of forward and backward falls as experienced in snowboarding.

Wrist injuries are frequently observed after falls in snowboarding. In this study, laboratory experiments mimicking forward and backward falls were analysed. In six different falling scenarios, participants self-initiated falls from a static initial position.

Evolution of the 3-dimensional video system for facial motion analysis: ten years' experiences and recent developments.

Since the implementation of the computer-aided system for assessing facial palsy in 1999 by Frey et al (Plast Reconstr Surg. 1999;104:2032-2039), no similar system that can make an objective, three-dimensional, quantitative analysis of facial movements has been marketed. This system has been in routine use since its launch, and it has proven to be reliable, clinically applicable, and therapeutically accurate.

Medial support by fibula bone graft in angular stable plate fixation of proximal humeral fractures: an in vitro study with synthetic bone.

Background: Failure to achieve stable fixation with medial support in proximal humeral fractures can result in varus malalignment and cut-through of the proximal screws. The purpose of this study was to investigate the influence of an intramedullary fibula bone graft on the biomechanical properties of proximal humeral fractures stabilized by angular stable plate fixation in a bone model under cyclic loading.

Methods: Two fixation techniques were tested in 20 composite analog humeri models.

Validity and test-retest reliability of manual goniometers for measuring passive hip range of motion in femoroacetabular impingement patients.

Background: The aims of this study were to evaluate the construct validity (known group), concurrent validity (criterion based) and test-retest (intra-rater) reliability of manual goniometers to measure passive hip range of motion (ROM) in femoroacetabular impingement patients and healthy controls.

Methods: Passive hip flexion, abduction, adduction, internal and external rotation ROMs were simultaneously measured with a conventional goniometer and an electromagnetic tracking system (ETS) on two different testing sessions. A total of 15 patients and 15 sex- and age-matched healthy controls participated in the study.

Ultrasound tissue Doppler imaging reveals no delay in abdominal muscle feed-forward activity during rapid arm movements in patients with chronic low back pain.

Study Design: Cross-sectional study.

Objective: Comparison of the timing of onset of lateral abdominal muscle activity during rapid arm movements in patients with nonspecific chronic low back pain (cLBP) and back-pain-free controls.

Summary Of Background Data: Rapid movements of the arm are normally associated with prior activation of trunk-stabilizing muscles in readiness for the impending postural perturbation.

Biomechanical testing of a polymer-based biomaterial for the restoration of spinal stability after nucleotomy.

Background: Surgery for disc herniations can be complicated by two major problems: painful degeneration of the spinal segment and re-herniation. Therefore, we examined an absorbable poly-glycolic acid (PGA) biomaterial, which was lyophilized with hyaluronic acid (HA), for its utility to (a) re-establish spinal stability and to (b) seal annulus fibrosus defects. The biomechanical properties range of motion (ROM), neutral zone (NZ) and a potential annulus sealing capacity were investigated.

The combination of muscle transpositions and static procedures for reconstruction in the paralyzed face of the patient with limited life expectancy or who is not a candidate for free muscle transfer.

Background: In long-standing complete and irreversible facial palsy where reconstruction by nerve grafting alone is no longer sufficient, reconstruction by dynamic procedures such as muscle transplantation or muscle transposition is required. The authors present the results obtained by regional muscle transposition for reconstruction of eye closure and smile in patients with irreversible facial palsy.

Methods: Twenty-nine patients treated by temporalis transposition for the eye and eight patients treated by masseter transposition for the mouth are presented.

Three-dimensional video analysis of the paralyzed face reanimated by cross-face nerve grafting and free gracilis muscle transplantation: quantification of the functional outcome.

Background: Surgeons have found it difficult to quantify facial paralysis and its improvement by reconstructive surgery. This article presents the results achieved by free functional muscle transplantation for reconstruction of the paralyzed face, registered by three-dimensional video analysis of facial movements.

Methods: Of patients treated consecutively between 1997 and 2006, two groups were constituted: group 1 comprised 22 patients with reinnervation completed after a single cross-face nerve graft and a free gracilis muscle graft for reconstruction of the smile; group 2 comprised nine patients treated with two cross-face nerve grafts followed by a territorially differentiated gracilis muscle transplant for reconstruction of the smile and eye closure.

Workplace observation of work stressors, catecholamines and musculoskeletal pain among male employees.

Objectives: Prolonged activation of the sympathetic-adrenal medullary system during work and the lack of recovery after work may indicate a risk for musculoskeletal pain (ie, neck, shoulder, or low-back pain). This field study tested whether a high level of work stressors are associated with musculoskeletal pain and higher urinary norepinephrine excretion rates at work, after work, and on Sundays.

Methods: Altogether 32 male employees working in adult education took part in a three-phase repeated-measures field study including workplace observation, self-report of musculoskeletal pain, and measurement of urinary catecholamine at work, in the evening after work, and at corresponding times on Sundays.

Muscle thickness changes during abdominal hollowing: an assessment of between-day measurement error in controls and patients with chronic low back pain.

Spine stabilization exercises, in which patients are taught to perform isolated contractions of the transverses abdominus (TrA) during "abdominal hollowing", are a popular physiotherapeutic treatment for low back pain (LBP). Successful performance is typically judged by the relative increase in TrA thickness compared with that of the internal (OI) and external (OE) oblique muscles, measured using ultrasound. The day-to-day measurement error (imprecision) associated with these indices of preferential activation has not been assessed but is important to know since it influences the interpretation of changes after treatment.

Stratified prokaryote network in the oxic-anoxic transition of a deep-sea halocline.

The chemical composition of the Bannock basin has been studied in some detail. We recently showed that unusual microbial populations, including a new division of Archaea (MSBL1), inhabit the NaCl-rich hypersaline brine. High salinities tend to reduce biodiversity, but when brines come into contact with fresher water the natural haloclines formed frequently contain gradients of other chemicals, including permutations of electron donors and acceptors, that may enhance microbial diversity, activity and biogeochemical cycling.

Three-dimensional kinematics and kinetics of total knee arthroplasty during level walking using single plane video-fluoroscopy and force plates: a pilot study.

The goal of the study was to simultaneously obtain accurate kinematic and kinetic data from a total knee arthroplasty (TKA) during level walking, by coupling force plate data with the kinematics of TKA measured by a movable video-fluoroscopic system. Kinematic and kinetic information of a TKA is crucial for the improvement of implant designs and for the increased longevity of the implant components. Instrumented gait analysis, with skin mounted marker tracking and force plates, is a well-established method for the acquisition of kinematic and kinetic data of TKA in vivo and for non-invasive estimation of joint function.