Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
440
result(s) for
"Mayer, Benjamin"
Sort by:
Autonomous assembly : designing for a new era of collective construction
\"We are now on the brink of a new era in construction - that of autonomous assembly. For some time, the widespread adoption of robotic and digital fabrication technologies has made it possible for architects and academic researchers to design non-standard, highly customised structures. These technologies have largely been limited by scalability, focusing mainly on top-down, bespoke fabrication projects, such as experimental pavilions and structures. Autonomous assembly and bottom-up construction techniques hold the promise of greater scalability, adaptability and potentially evolved design possibilities. By capitalising on the advances made in swarm robotics, the collective construction of the animal/insect kingdom, and advances in physical computational, programmable materials or self-assembly, architects and designers are now able to build from the bottom up. This issue presents future scenarios of autonomous assembly by highlighting the viability of decentralised, collective assembly systems, demonstrating the potential to deliver reconfigurable and adaptive solutions.\"--Back cover.
Book
Epigallocatechin Gallate Inhibits Cell Growth and Hedgehog Signalling in Human Rhabdomyosarcoma Cell Lines
Epigallocatechin gallate (EGCG), a major polyphenol of green tea, has been shown to inhibit cancer cell proliferation. In this study the effect of EGCG on cell metabolism and the human hedgehog signalling pathway (HH) in human rhabdomyosarcoma (RMS) cells was investigated.
Two human RMS cell lines (RD and RH30) were incubated with EGCG. To evaluate the effects of EGCG on RMS cells, cell viability, colony formation, cell migration, and alteration of genes related to the HH signalling pathway were investigated.
EGCG showed cytostatic effects on RMS cells in a dose-dependent manner. Incubation with 25 μM EGCG resulted in a significant reduction of cell migration by 70% and downregulation of the HH pathway transcription factor GLI1.
EGCG inhibits RMS cells in vitro by reducing cell proliferation and downregulating the HH signalling pathway. It may therefore be a promising agent in chemoresistant or advanced RMS in children.
Journal Article
Substitution matrix based color schemes for sequence alignment visualization
Background
Visualization of multiple sequence alignments often includes colored symbols, usually characters encoding amino acids, according to some (physical) properties, such as hydrophobicity or charge. Typically, color schemes are created manually, so that equal or similar colors are assigned to amino acids that share similar properties. However, this assessment is subjective and may not represent the similarity of symbols very well.
Results
In this article we propose a different approach for color scheme creation: We leverage the similarity information of a substitution matrix to derive an appropriate color scheme. Similar colors are assigned to high scoring pairs of symbols, distant colors are assigned to low scoring pairs. In order to find these optimal points in color space a simulated annealing algorithm is employed.
Conclusions
Using the substitution matrix as basis for a color scheme is consistent with the alignment, which itself is based on the very substitution matrix. This approach allows fully automatic generation of new color schemes, even for special purposes which have not been covered, yet, including schemes for structural alphabets or schemes that are adapted for people with color vision deficiency.
Journal Article
Comparison of Conventional Methods for Bowel Length Measurement in Laparoscopic Surgery to a Novel Computer-Assisted 3D Measurement System
PurposeAccurate laparoscopic bowel length measurement (LBLM), which is used primarily in metabolic surgery, remains a challenge. This study aims to three conventional methods for LBLM, namely using visual judgment (VJ), instrument markings (IM), or premeasured tape (PT) to a novel computer-assisted 3D measurement system (BMS).Materials and MethodsLBLM methods were compared using a 3D laparoscope on bowel phantoms regarding accuracy (relative error in percent, %), time in seconds (s), and number of bowel grasps. Seventy centimeters were measured seven times. As a control, the first, third, fifth, and seventh measurements were performed with VJ. The interventions IM, PT, and BMS were performed following a randomized order as the second, fourth, and sixth measurements.ResultsIn total, 63 people participated. BMS showed better accuracy (2.1±3.7%) compared to VJ (8.7±13.7%, p=0.001), PT (4.3±6.8%, p=0.002), and IM (11±15.3%, p<0.001). Participants performed LBLM in a similar amount of time with BMS (175.7±59.7s) and PT (166.5±63.6s, p=0.35), but VJ (64.0±24.0s, p<0.001) and IM (144.9±55.4s, p=0.002) were faster. Number of bowel grasps as a measure for the risk of bowel lesions was similar for BMS (15.8±3.0) and PT (15.9±4.6, p=0.861), whereas VJ required less (14.1±3.4, p=0.004) and IM required more than BMS (22.2±6.9, p<0.001).ConclusionsPT had higher accuracy than VJ and IM, and lower number of bowel grasps than IM. BMS shows great potential for more reliable LBLM. Until BMS is available in clinical routine, PT should be preferred for LBLM.
Journal Article
Machine learning analysis predicts a person’s sex based on mechanical but not thermal pain thresholds
Sex differences in pain perception have been extensively studied, but precision medicine applications such as sex-specific pain pharmacology have barely progressed beyond proof-of-concept. A data set of pain thresholds to mechanical (blunt and punctate pressure) and thermal (heat and cold) stimuli applied to non-sensitized and sensitized (capsaicin, menthol) forearm skin of 69 male and 56 female healthy volunteers was analyzed for data structures contingent with the prior sex structure using unsupervised and supervised approaches. A working hypothesis that the relevance of sex differences could be approached via reversibility of the association, i.e., sex should be identifiable from pain thresholds, was verified with trained machine learning algorithms that could infer a person's sex in a 20% validation sample not seen to the algorithms during training, with balanced accuracy of up to 79%. This was only possible with thresholds for mechanical stimuli, but not for thermal stimuli or sensitization responses, which were not sufficient to train an algorithm that could assign sex better than by guessing or when trained with nonsense (permuted) information. This enabled the translation to the molecular level of nociceptive targets that convert mechanical but not thermal information into signals interpreted as pain, which could eventually be used for pharmacological precision medicine approaches to pain. By exploiting a key feature of machine learning, which allows for the recognition of data structures and the reduction of information to the minimum relevant, experimental human pain data could be characterized in a way that incorporates \"non\" logic that could be translated directly to the molecular pharmacological level, pointing toward sex-specific precision medicine for pain.
Journal Article
Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis
ObjectiveTo determine the diagnostic and prognostic performance of serum neurofilament light chain (NFL) in amyotrophic lateral sclerosis (ALS).MethodsThis single-centre, prospective, longitudinal study included the following patients: 124 patients with ALS; 50 patients without neurodegenerative diseases; 44 patients with conditions included in the differential diagnosis of ALS (disease controls); 65 patients with other neurodegenerative diseases (20 with frontotemporal dementia, 20 with Alzheimer’s disease, 19 with Parkinson’s disease, 6 with Creutzfeldt-Jakob disease (CJD)). Serum NFL levels were measured using the ultrasensitive single molecule array (Simoa) technology.ResultsSerum NFL levels were higher in ALS in comparison to all other categories except for CJD. A cut-off level of 62 pg/mL discriminated between ALS and all other conditions with 85.5% sensitivity (95% CI 78% to 91.2%) and 81.8% specificity (95% CI 74.9% to 87.4%). Among patients with ALS, serum NFL correlated positively with disease progression rate (rs=0.336, 95% CI 0.14 to 0.506, p=0.0008), and higher levels were associated with shorter survival (p=0.0054). Serum NFL did not differ among patients in different ALS pathological stages as evaluated by diffusion-tensor imaging, and in single patients NFL levels were stable over time.ConclusionsSerum NFL is increased in ALS in comparison to other conditions and can serve as diagnostic and prognostic biomarker. We established a cut-off level for the diagnosis of ALS.
Journal Article
Comparison of CSF and serum neurofilament light and heavy chain as differential diagnostic biomarkers for ALS
ObjectiveElevated levels of neurofilament light (NfL) and heavy (NfH) chain in amyotrophic lateral sclerosis (ALS) cerebrospinal fluid (CSF) and serum reflect neuro-axonal degeneration and are used as diagnostic biomarkers. However, studies comparing the differential diagnostic potential for ALS of all four parameters are missing. Here, we measured serum NfL/NfH and CSF NfL/NfH in a large cohort of ALS and other neurological disorders and analysed the differential diagnostic potential.MethodsIn total CSF and serum of 294 patients were analysed. The diagnostic groups comprised: ALS (n=75), frontotemporal lobar degeneration (FTLD) (n=33), Alzheimer’s disease (n=20), Parkinson’s disease (dementia) (n=18), Creutzfeldt-Jakob disease (n=11), non-neurodegenerative controls (n=77) (Con) and 60 patients who were seen under the direct differential diagnosis of a patient with ALS (Con.DD).ResultsCSF and serum NfL and NfH showed significantly increased levels in ALS (p<0.0001) compared with Con and Con.DD. The difference between ALS and FTLD was markedly stronger for NfH than for NfL. CSF and serum NfL demonstrated a stronger correlation (r=0.84 (95% CI 0.80 to 0.87), p<0.001) than CSF and serum NfH (r=0.68 (95% CI 0.61 to 0.75), p<0.0001). Comparing ALS and Con.DD, receiver operating characteristic analysis revealed the best area under the curve (AUC) value for CSF NfL (AUC=0.94, 95% CI 0.91 to 0.98), followed by CSF NfH (0.93, 95% CI 0.88 to 0.98), serum NfL (0.93, 95% CI 0.89 to 0.97) and serum NfH (0.88, 95% CI 0.82 to 0.94).ConclusionOur results demonstrate that CSF NfL and NfH as well as serum NfL are equally suited for the differential diagnosis of ALS, whereas serum NfH appears to be slightly less potent.
Journal Article
Protein sociology of ProA, Mip and other secreted virulence factors at the Legionella pneumophila surface
The pathogenicity of L. pneumophila , the causative agent of Legionnaires’ disease, depends on an arsenal of interacting proteins. Here we describe how surface-associated and secreted virulence factors of this pathogen interact with each other or target extra- and intracellular host proteins resulting in host cell manipulation and tissue colonization. Since progress of computational methods like AlphaFold, molecular dynamics simulation, and docking allows to predict, analyze and evaluate experimental proteomic and interactomic data, we describe how the combination of these approaches generated new insights into the multifaceted “protein sociology” of the zinc metalloprotease ProA and the peptidyl-prolyl cis/trans isomerase Mip (macrophage infectivity potentiator). Both virulence factors of L. pneumophila interact with numerous proteins including bacterial flagellin (FlaA) and host collagen, and play important roles in virulence regulation, host tissue degradation and immune evasion. The recent progress in protein-ligand analyses of virulence factors suggests that machine learning will also have a beneficial impact in early stages of drug discovery.
Journal Article
Linking Gene Fusions to Bone Marrow Failure and Malignant Transformation in Dyskeratosis Congenita
Dyskeratosis Congenita (DC) is a multisystem disorder intrinsically associated with telomere dysfunction, leading to bone marrow failure (BMF). Although the pathology of DC is largely driven by mutations in telomere-associated genes, the implications of gene fusions, which emerge due to telomere-induced genomic instability, remain unexplored. We meticulously analyzed gene fusions in RNA-Seq data from DC patients to provide deeper insights into DC’s progression. The most significant DC-specific gene fusions were subsequently put through in silico assessments to ascertain biophysical and structural attributes, including charge patterning, inherent disorder, and propensity for self-association. Selected candidates were then analyzed using deep learning-powered structural predictions and molecular dynamics simulations to gauge their potential for forming higher-order oligomers. Our exploration revealed that genes participating in fusion events play crucial roles in upholding genomic stability, facilitating hematopoiesis, and suppressing tumors. Notably, our analysis spotlighted a particularly disordered polyampholyte fusion protein that exhibits robust higher-order oligomerization dynamics. To conclude, this research underscores the potential significance of several high-confidence gene fusions in the progression of BMF in DC, particularly through the dysregulation of genomic stability, hematopoiesis, and tumor suppression. Additionally, we propose that these fusion proteins might hold a detrimental role, specifically in inducing proteotoxicity-driven hematopoietic disruptions.
Journal Article
Renal Autotransplantation for Resection of Bilateral Nephroblastoma and High-Risk Neuroblastoma in Children
Background/Objectives: In bilateral nephroblastoma and high-risk neuroblastoma in children with extensive tumor involvement of the renal vessels or pedicle, complete tumor resection with preservation of healthy renal tissue is not feasible with in situ nephron-sparing surgery or vascular replacement. The aim of this study was to present our experience with ante situ tumor resection and renal autotransplantation (RATX) in these children. Methods: A retrospective study of children with bilateral nephroblastoma and high-risk neuroblastoma who underwent tumor resection and RATX at an international referral center for pediatric surgical oncology between 2006 and 2024 was performed. RATX was performed by transection of renal vessels, ante situ mobilization, and perfusion of the kidney with Bretschneider’s solution. Tumor resection was performed on a bloodless kidney under hypothermia. Results: Ante situ tumor resection and RATX were performed at a median age of 36 months (range 13–62) in 4 children with bilateral nephroblastoma and 4 children with high-risk neuroblastoma. Complete tumor resection was achieved in all patients. One patient with neuroblastoma died of sepsis after 14 days. The 7 surviving patients showed no evidence of disease and normal to slightly decreased glomerulofiltration rates at a median follow-up of 20 months (range 3–155). Limitations include the retrospective design, small sample size, and heterogeneity of the study population due to very rare indication. Conclusions: Ante situ tumor resection and RATX is a feasible surgical approach for children with multifocal bilateral nephroblastoma or high-risk neuroblastoma who are ineligible for in situ nephron-sparing surgery or vascular reconstruction.
Journal Article