Equilibrium states for potentials with \sup\phi - \inf\phi < \htop(f)

In the context of smooth interval maps, we study an inducing scheme approach to prove existence and uniqueness of equilibrium states for potentials $\phi$ with he `bounded range' condition \sup \phi - \inf \phi < \htop, first used by Hofbauer and Keller. We compare our results to Hofbauer and Keller's use of Perron-Frobenius operators. We demonstrate that this `bounded range' condition on the potential is important even if the potential is H\"older continuous. We also prove analyticity of the pressure in this context.Comment: Added Lemma 6 to deal with the disparity between leading eigenvalues and operator norms. Added extra references and corrected some typo

Evidence for local inflammation in complex regional pain syndrome type 1.

BACKGROUND: The pathophysiology of complex regional pain syndrome type 1 (CRPS 1) is still a matter of debate. Peripheral afferent, efferent and central mechanisms are supposed. Based on clinical signs and symptoms (e.g. oedema, local temperature changes and chronic pain) local inflammation is suspected. AIM: To determine the involvement of neuropetides, cytokines and eicosanoids as locally formed mediators of inflammation. METHODS: In this study, nine patients with proven CRPS 1 were included. Disease activity and impairment was determined by means of a Visual Analogue Scale, the McGill Pain Questionnaire, the difference in volume and temperature between involved and uninvolved extremities, and the reduction in active range of motion of the involved extremity. Venous blood was sampled from and suction blisters made on the involved and uninvolved extremities for measurement of cytokines interleukin (IL)-6, II-1beta and tumour necrosis factor-alpha (TNF-alpha), the neuropetides NPY and CRGP, and prostaglandin E2RESULTS: The patients included in this study did have a moderate to serious disease activity and impairment. In plasma, no changes of mediators of inflammation were observed. In blister fluid, however, significantly higher levels of IL-6 and TNF-alpha in the involved extremity were observed in comparison with the uninvolved extremity. CONCLUSIONS: This is the first time that involvement of mediators of inflammation in CRPS 1 has been so clearly and directly demonstrated. This observation opens new approaches for the succesful use and development of immunosuppressives in CRPS 1

Do I-Pass for FAIR?:A self-assessment tool to measure the FAIR-ness of an organization

The 15 FAIR data principles are intended to be applied to a dataset, but the acronym FAIR is also used as an adjective for other (digital) matters, such as FAIR data stewardship, FAIR data infrastructure and FAIR data services. Moreover, in the context of Open Science and scientific integrity, more and more Dutch universities and research organizations discuss a FAIR organization as an important goal, thus implementing RDM practices and support with the FAIR principles as a main driver. Triggered by this use of the acronym FAIR for organizations, an LCRDM (National Coordination Point Research Data Management) task group explored the definition, characteristics and principles of a so-called ‘FAIR enabling organization’. The task group delivered two products: (1) a definition for a FAIR enabling organization and (2) a self-assessment tool to evaluate the FAIR-ness of a research organization (research institute, university or university of applied sciences). This self-assessment tool is a simple instrument, presented in an editable PDF form. By answering the questions and evaluating the level (beginner, intermediate, or advanced) at which you assess the performance of your organization, you will be able to define the actual FAIR-ness. In addition you can define a Road Map to become a FAIR Enabling Research Organization using the information in de more advances level(s)

Versatile Coordination of Cyclopentadienyl-Arene Ligands and Its Role in Titanium-Catalyzed Ethylene Trimerization

Cationic titanium(IV) complexes with ansa-(η5-cyclopentadienyl,η6-arene) ligands were synthesized and characterized by X-ray crystallography. The strength of the metal-arene interaction in these systems was studied by variable-temperature NMR spectroscopy. Complexes with a C1 bridge between the cyclopentadienyl and arene moieties feature hemilabile coordination behavior of the ligand and consequently are active ethylene trimerization catalysts. Reaction of the titanium(IV) dimethyl cations with CO results in conversion to the analogous cationic titanium(II) dicarbonyl species. Metal-to-ligand backdonation in these formally low-valent complexes gives rise to a strongly bonded, partially reduced arene moiety. In contrast to the η6-arene coordination mode observed for titanium, the more electron-rich vanadium(V) cations [cyclopentadienyl-arene]V(NiPr2)(NC6H4-4-Me)+ feature η1-arene binding, as determined by a crystallographic study. The three different metal-arene coordination modes that we experimentally observed model intermediates in the cycle for titanium-catalyzed ethylene trimerization. The nature of the metal-arene interaction in these systems was studied by DFT calculations.

Mitochondrial dysfunction increases pro-inflammatory cytokine production and impairs repair and corticosteroid responsiveness in lung epithelium

COPD is characterized by chronic lung inflammation and irreversible lung tissue damage. Inhaled noxious gases, including cigarette smoke, are the major risk factor for COPD. Inhaled smoke first encounters the epithelial lining of the lungs, causing oxidative stress and mitochondrial dysfunction. We investigated whether a mitochondrial defect may contribute to increased lung epithelial pro-inflammatory responses, impaired epithelial repair and reduced corticosteroid sensitivity as observed in COPD. We used wild-type alveolar epithelial cells A549 and mitochondrial DNA-depleted A549 cells (A549 Rho-0) and studied pro-inflammatory responses using (multiplex) ELISA as well as epithelial barrier function and repair (real-time impedance measurements), in the presence and absence of the inhaled corticosteroid budesonide. We observed that A549 Rho-0 cells secrete higher levels of pro-inflammatory cytokines than wild-type A549 cells and display impaired repair upon wounding. Budesonide strongly suppressed the production of neutrophil attractant CXCL8, and promoted epithelial integrity in A549 wild-type cells, while A549 Rho-0 cells displayed reduced corticosteroid sensitivity compared to wild-type cells. The reduced corticosteroid responsiveness may be mediated by glycolytic reprogramming, specifically glycolysis-associated PI3K signaling, as PI3K inhibitor LY294002 restored the sensitivity of CXCL8 secretion to corticosteroids in A549 Rho-0 cells. In conclusion, mitochondrial defects may lead to increased lung epithelial pro-inflammatory responses, reduced epithelial repair and reduced corticosteroid responsiveness in lung epithelium, thus potentially contributing to the pathogenesis of COPD

Utilization of multiparametric prostate magnetic resonance imaging in clinical practice and focal therapy: report from a Delphi consensus project

To codify the use of multiparametric magnetic resonance imaging (mpMRI) for the interrogation of prostate neoplasia (PCa) in clinical practice and focal therapy (FT). An international collaborative consensus project was undertaken using the Delphi method among experts in the field of PCa. An online questionnaire was presented in three consecutive rounds and modified each round based on the comments provided by the experts. Subsequently, a face-to-face meeting was held to discuss and finalize the consensus results. mpMRI should be performed in patients with prior negative biopsies if clinical suspicion remains, but not instead of the PSA test, nor as a stand-alone diagnostic tool or mpMRI-targeted biopsies only. It is not recommended to use a 1.5 Tesla MRI scanner without an endorectal or pelvic phased-array coil. mpMRI should be performed following standard biopsy-based PCa diagnosis in both the planning and follow-up of FT. If a lesion is seen, MRI-TRUS fusion biopsies should be performed for FT planning. Systematic biopsies are still required for FT planning in biopsy-naïve patients and for patients with residual PCa after FT. Standard repeat biopsies should be taken during the follow-up of FT. The final decision to perform FT should be based on histopathology. However, these consensus statements may differ for expert centers versus non-expert centers. The mpMRI is an important tool for characterizing and targeting PCa in clinical practice and FT. Standardization of acquisition and reading should be the main priority to guarantee consistent mpMRI quality throughout the urological communit

PROMISE:effect of protein supplementation on fat-free mass preservation after bariatric surgery, a randomized double-blind placebo-controlled trial

Introduction: Protein malnutrition after bariatric surgery is a severe complication and leads to significant morbidity. Previous studies have shown that protein intake and physical activity are the most important factors in the preservation of fat-free mass during weight loss. Low protein intake is very common in patients undergoing bariatric surgery despite dietary counseling. Protein powder supplements might help patients to achieve the protein intake recommendations after bariatric surgery and could therefore contribute to preserve fat-free mass. This double-blind randomized placebo-controlled intervention study aims to assess the effect of a daily consumed clear protein powder shake during the first 6 months after bariatric surgery on fat-free mass loss in the first 12 months after laparoscopic Roux-en-Y gastric bypass (LRYGB). Methods and analysis:Inclusion will take place at the outpatient clinic of the bariatric expertise center for obesity of the Maasstad Hospital. Patients will be randomly assigned to either the intervention or control group before surgery. The intervention group will receive a clear protein powder shake of 200 ml containing 20 g of whey protein dissolved in water which should be taken daily during the first 6 months after LRYGB on top of their normal postoperative diet. The control group will receive an isocaloric, clear, placebo shake containing maltodextrine. Postoperative rehabilitation and physiotherapeutical guidance will be standardized and similar in both groups. Also, both groups will receive the same dietary advice from specialized dieticians. The main study parameter is the percentage of fat-free mass loss 6 months after surgery, assessed by multi-frequency bioelectrical impedance analysis (MF-BIA). Ethics and dissemination: The protocol, version 2 (February 20, 2022) has been approved by the Medical Research Ethics Committees United (MEC-U) (NL 80414.100.22). The results of this study will be submitted to peer-reviewed journals. Trial registration: ClinicalTrials.gov NCT05570474. Registered on October 5, 2022.</p

Гарантоздатність як фундаментальний узагальнюючий та інтегруючий підхід

Представлені головні принципи та умови становлення і етапи розвитку фундаментальної теорії і практики узагальнюючих та інтегруючих концепцій гарантоздатності, починаючи з першої об’єднаної конференції двох наукових шкіл Дж. фон Неймана і Н. Вінера. Приведені основні положення розвитку теоретичних засад і результатів прикладних досліджень інтеграційних процесів безвідмовності (надійності), відмовостійкості та гарантоздатності інформаційно-управляючих комп’ютерних систем (ІУКС).Представлены главные принципы, условия становления и этапы развития фундаментальной теории и практики обобщающих и интегрирующих концепций гарантоспособности, начиная с первой объединённой конференции двух научных школ Дж. фон Неймана и Н. Винера. Приведены основные положения развития теоретических основ и результатов прикладных исследований интеграционных процессов безотказности (надёжности), отказоустойчивости и гарантоспособности информационно-управляющих компьютерных систем (ИУКС).The main principles and conditions of formation and stages of development of the fundamental theory and practice of the generalizing and integrating concepts of dependability were presented after the leadthrough the first joint conference of two scientific schools of J. von Neumann and N. Wiener. The basic aspects of development of theoretical principles and results of applied researches of integration processes of reliability (fail-safety)

Active growth signaling promotes senescence and cancer cell sensitivity to CDK7 inhibition

Tumor growth is driven by continued cellular growth and proliferation. Cyclin-dependent kinase 7’s (CDK7) role in activating mitotic CDKs and global gene expression makes it therefore an attractive target for cancer therapies. However, what makes cancer cells particularly sensitive to CDK7 inhibition (CDK7i) remains unclear. Here, we address this question. We show that CDK7i, by samuraciclib, induces a permanent cell-cycle exit, known as senescence, without promoting DNA damage signaling or cell death. A chemogenetic genome-wide CRISPR knockout screen identified that active mTOR (mammalian target of rapamycin) signaling promotes samuraciclib-induced senescence. mTOR inhibition decreases samuraciclib sensitivity, and increased mTOR-dependent growth signaling correlates with sensitivity in cancer cell lines. Reverting a growth-promoting mutation in PIK3CA to wild type decreases sensitivity to CDK7i. Our work establishes that enhanced growth alone promotes CDK7i sensitivity, providing an explanation for why some cancers are more sensitive to CDK inhibition than normally growing cells