Numerical modeling in timber engineering – moisture transport and quasi-brittle failure

With the rising popularity of timber structures and the increasing complexity of timber engineering projects, the need for numerical simulation tools specific to this building material is gaining rapidly in importance. in particular, moisture transport processes and the quasi-brittle failure behavior, both difficult to describe, present major challenges and are of great relevance in practical construction. For these reasons, this article presents numerical modeling concepts for predicting moisture gradients, estimating effective stiffness and strength, and numerically identifying potential cracking mechanisms in wooden components. These concepts are validated through experimental test programs, and the associated challenges are addressed. selected results ultimately demonstrate the capabilities and relevance of such methods for timber engineering

HPK1 Associates with SKAP-HOM to Negatively Regulate Rap1-Mediated B-Lymphocyte Adhesion

BACKGROUND: Hematopoietic progenitor kinase 1 (HPK1) is a Ste20-related serine/threonine kinase activated by a range of environmental stimuli including genotoxic stress, growth factors, inflammatory cytokines and antigen receptor triggering. Being inducibly recruited to membrane-proximal signalling scaffolds to regulate NFAT, AP-1 and NFkappaB-mediated gene transcription in T-cells, the function of HPK1 in B-cells to date remains rather ill-defined. METHODOLOGY/PRINCIPAL FINDINGS: By using two loss of function models, we show that HPK1 displays a novel function in regulating B-cell integrin activity. Wehi 231 lymphoma cells lacking HPK1 after shRNA mediated knockdown exhibit increased basic activation levels of Ras-related protein 1 (Rap1), accompanied by a severe lymphocyte function-associated antigen-1 (LFA-1) dependent homotypic aggregation and increased adhesion to intercellular adhesion molecule 1 (ICAM-1). The observed phenotype of enhanced integrin activity is caused downstream of Src, by a signalling module independent of PI3K and PLC, involving HPK1, SKAP55 homologue (SKAP-HOM) and Rap1-GTP-interacting adaptor molecule (RIAM). This alters actin dynamics and renders focal adhesion kinase (FAK) constitutively phosphorylated. Bone marrow and splenic B-cell development of HPK1(-/-) mice are largely unaffected, except age-related tendencies for increased splenic cellularity and BCR downregulation. In addition, naïve splenic knockout B-cells appear hyperresponsive to a range of stimuli applied ex vivo as recently demonstrated by others for T-cells. CONCLUSIONS/SIGNIFICANCE: We therefore conclude that HPK1 exhibits a dual function in B-cells by negatively regulating integrin activity and controlling cellular activation, which makes it an interesting candidate to study in pathological settings like autoimmunity and cancer

The significance of calcium metabolism in uric acid stone formers

Introduction: Uric acid urolithiasis, a prevalent type of urinary stone disease, poses significant healthcare challenges. Effective treatment requires an understanding of factors contributing to stone formation and recurrence. We conducted a single-center observational study to explore these factors. Objectives: Our study aimed to investigate the relationship between specific demographic and clinical variables and the recurrence of uric acid urolithiasis. We hypothesized that factors related to calcium metabolism would play a significant role in the pathophysiologic processes of uric acid stone recurrence. Patients and methods: We analysed various variables from a database of uric acid stone formers, including age, gender, serum potassium, calcium-related variables and more. 381 urolithiasis patients were analyzed for a correlation with stone episodes, and an ordinal logistic regression model was employed to identify predictors of stone recurrence. Results: The study revealed a male predominance among uric acid stone formers (76.9%). Age and gender correlated negatively with stone episodes (P = 0.019 and P = 0.030, respectively), while serum potassium correlated positively (P = 0.010), as well as urine calcium (P = 0.049), and urine creatinine (P = 0.038). Our regression analysis revealed a potential protective effect of older age on stone episodes (P = 0.010) and suggested that elevated serum potassium levels could be a predictor of recurrence (P = 0.015) Conclusion: Our results proposed a potential role of urine calcium in uric acid stone recurrence, although it did not maintain significance in the regression model. Age and serum potassium were identified as significant predictors of recurrence.Uvod: Kamenci podrijetlom iz mokraćne kiseline vrlo su učestali predstavljaju značajan izazov za zdravstveni sustav. Učinkovito liječenje zahtijeva razumijevanje faktora koji doprinose stvaranju i ponovnom javljanju kamenaca. Proveli smo monocentričnu opservacijsku studiju kako bismo istražili ove faktore. Ciljevi: Naša studija imala je za cilj istražiti odnos između određenih demografskih i kliničkih varijabli te ponovnog javljanja uratnih kamenaca. Pretpostavili smo da će faktori povezani s metabolizmom kalcija odigravati značajnu ulogu u patofiziološkim procesima ponovnog javljanja uratnih kamenaca. Bolesnici i metode: Analizirali smo različite varijable iz baze podataka bolesnika s uratnim kamencima, uključujući dob, spol, razinu serumskog kalija, varijable povezane s kalcijem i druge. Analizirano je ukupno 381 bolesnik s urolitijazom kako bi se utvrdila povezanost s brojem epizoda kamenaca, te je korištena ordinalna logistička regresijska analiza kako bi se identificirali prediktori ponovnog javljanja kamenaca. Rezultati: Studija je otkrila premoć muškaraca među bolesnicima s uratnim kamenjem (76.9%). Dob i spol su negativno korelirali s brojem epizoda kamenaca (P = 0.019, odnosno P = 0.030), dok je serumski kalij pokazao pozitivnu korelaciju (P = 0.010), kao i razina urinarnog kalcija (P = 0.049), i kreatinina (P = 0.038). Regresijska analiza otkrila je potencijalno zaštitno djelovanje starije dobi u odnosu na broj epizoda kamenaca (P = 0.010), te je sugerirala da povišene razine serumskog kalija mogu biti prediktor ponovnog javljanja (P = 0.015). Zaključak: Naši rezultati sugeriraju potencijalnu ulogu urinarnog kalcija u ponovnom javljanju uratnih kamenaca, iako taj faktor nije održao značajnost u regresijskom modelu. Dob i serumski kalij identificirani su kao značajni prediktori ponovnog javljanja

The significance of calcium metabolism in uric acid stone formers

Introduction: Uric acid urolithiasis, a prevalent type of urinary stone disease, poses significant healthcare challenges. Effective treatment requires an understanding of factors contributing to stone formation and recurrence. We conducted a single-center observational study to explore these factors. Objectives: Our study aimed to investigate the relationship between specific demographic and clinical variables and the recurrence of uric acid urolithiasis. We hypothesized that factors related to calcium metabolism would play a significant role in the pathophysiologic processes of uric acid stone recurrence. Patients and methods: We analysed various variables from a database of uric acid stone formers, including age, gender, serum potassium, calcium-related variables and more. 381 urolithiasis patients were analyzed for a correlation with stone episodes, and an ordinal logistic regression model was employed to identify predictors of stone recurrence. Results: The study revealed a male predominance among uric acid stone formers (76.9%). Age and gender correlated negatively with stone episodes (P = 0.019 and P = 0.030, respectively), while serum potassium correlated positively (P = 0.010), as well as urine calcium (P = 0.049), and urine creatinine (P = 0.038). Our regression analysis revealed a potential protective effect of older age on stone episodes (P = 0.010) and suggested that elevated serum potassium levels could be a predictor of recurrence (P = 0.015) Conclusion: Our results proposed a potential role of urine calcium in uric acid stone recurrence, although it did not maintain significance in the regression model. Age and serum potassium were identified as significant predictors of recurrence.Uvod: Kamenci podrijetlom iz mokraćne kiseline vrlo su učestali predstavljaju značajan izazov za zdravstveni sustav. Učinkovito liječenje zahtijeva razumijevanje faktora koji doprinose stvaranju i ponovnom javljanju kamenaca. Proveli smo monocentričnu opservacijsku studiju kako bismo istražili ove faktore. Ciljevi: Naša studija imala je za cilj istražiti odnos između određenih demografskih i kliničkih varijabli te ponovnog javljanja uratnih kamenaca. Pretpostavili smo da će faktori povezani s metabolizmom kalcija odigravati značajnu ulogu u patofiziološkim procesima ponovnog javljanja uratnih kamenaca. Bolesnici i metode: Analizirali smo različite varijable iz baze podataka bolesnika s uratnim kamencima, uključujući dob, spol, razinu serumskog kalija, varijable povezane s kalcijem i druge. Analizirano je ukupno 381 bolesnik s urolitijazom kako bi se utvrdila povezanost s brojem epizoda kamenaca, te je korištena ordinalna logistička regresijska analiza kako bi se identificirali prediktori ponovnog javljanja kamenaca. Rezultati: Studija je otkrila premoć muškaraca među bolesnicima s uratnim kamenjem (76.9%). Dob i spol su negativno korelirali s brojem epizoda kamenaca (P = 0.019, odnosno P = 0.030), dok je serumski kalij pokazao pozitivnu korelaciju (P = 0.010), kao i razina urinarnog kalcija (P = 0.049), i kreatinina (P = 0.038). Regresijska analiza otkrila je potencijalno zaštitno djelovanje starije dobi u odnosu na broj epizoda kamenaca (P = 0.010), te je sugerirala da povišene razine serumskog kalija mogu biti prediktor ponovnog javljanja (P = 0.015). Zaključak: Naši rezultati sugeriraju potencijalnu ulogu urinarnog kalcija u ponovnom javljanju uratnih kamenaca, iako taj faktor nije održao značajnost u regresijskom modelu. Dob i serumski kalij identificirani su kao značajni prediktori ponovnog javljanja

The significance of calcium metabolism in uric acid stone formers

Introduction: Uric acid urolithiasis, a prevalent type of urinary stone disease, poses significant healthcare challenges. Effective treatment requires an understanding of factors contributing to stone formation and recurrence. We conducted a single-center observational study to explore these factors. Objectives: Our study aimed to investigate the relationship between specific demographic and clinical variables and the recurrence of uric acid urolithiasis. We hypothesized that factors related to calcium metabolism would play a significant role in the pathophysiologic processes of uric acid stone recurrence. Patients and methods: We analysed various variables from a database of uric acid stone formers, including age, gender, serum potassium, calcium-related variables and more. 381 urolithiasis patients were analyzed for a correlation with stone episodes, and an ordinal logistic regression model was employed to identify predictors of stone recurrence. Results: The study revealed a male predominance among uric acid stone formers (76.9%). Age and gender correlated negatively with stone episodes (P = 0.019 and P = 0.030, respectively), while serum potassium correlated positively (P = 0.010), as well as urine calcium (P = 0.049), and urine creatinine (P = 0.038). Our regression analysis revealed a potential protective effect of older age on stone episodes (P = 0.010) and suggested that elevated serum potassium levels could be a predictor of recurrence (P = 0.015) Conclusion: Our results proposed a potential role of urine calcium in uric acid stone recurrence, although it did not maintain significance in the regression model. Age and serum potassium were identified as significant predictors of recurrence.Uvod: Kamenci podrijetlom iz mokraćne kiseline vrlo su učestali predstavljaju značajan izazov za zdravstveni sustav. Učinkovito liječenje zahtijeva razumijevanje faktora koji doprinose stvaranju i ponovnom javljanju kamenaca. Proveli smo monocentričnu opservacijsku studiju kako bismo istražili ove faktore. Ciljevi: Naša studija imala je za cilj istražiti odnos između određenih demografskih i kliničkih varijabli te ponovnog javljanja uratnih kamenaca. Pretpostavili smo da će faktori povezani s metabolizmom kalcija odigravati značajnu ulogu u patofiziološkim procesima ponovnog javljanja uratnih kamenaca. Bolesnici i metode: Analizirali smo različite varijable iz baze podataka bolesnika s uratnim kamencima, uključujući dob, spol, razinu serumskog kalija, varijable povezane s kalcijem i druge. Analizirano je ukupno 381 bolesnik s urolitijazom kako bi se utvrdila povezanost s brojem epizoda kamenaca, te je korištena ordinalna logistička regresijska analiza kako bi se identificirali prediktori ponovnog javljanja kamenaca. Rezultati: Studija je otkrila premoć muškaraca među bolesnicima s uratnim kamenjem (76.9%). Dob i spol su negativno korelirali s brojem epizoda kamenaca (P = 0.019, odnosno P = 0.030), dok je serumski kalij pokazao pozitivnu korelaciju (P = 0.010), kao i razina urinarnog kalcija (P = 0.049), i kreatinina (P = 0.038). Regresijska analiza otkrila je potencijalno zaštitno djelovanje starije dobi u odnosu na broj epizoda kamenaca (P = 0.010), te je sugerirala da povišene razine serumskog kalija mogu biti prediktor ponovnog javljanja (P = 0.015). Zaključak: Naši rezultati sugeriraju potencijalnu ulogu urinarnog kalcija u ponovnom javljanju uratnih kamenaca, iako taj faktor nije održao značajnost u regresijskom modelu. Dob i serumski kalij identificirani su kao značajni prediktori ponovnog javljanja