The theory of critical distances Taylor, D.
Engineering fracture mechanics,
05/2008, Letnik:
75, Številka:
7
Journal Article, Conference Proceeding
Recenzirano
The aim of this review article is to introduce the theory of critical distances, to which this special issue of the journal is devoted. The theory of critical distances (TCD) is the name which I have ...given to a group of theories used for predicting the effects of notches and other stress concentration features. The basic methodology is described, along with a number of variants which have developed over the years. After a brief history of the TCD, the predictive power of this group of theories is demonstrated, showing that they are capable of predicting experimental data on fracture and fatigue in a wide variety of circumstances. After some discussion regarding the fundamental scientific basis of the TCD, areas for future work in this field are suggested.
Mucin-degrading microbes are known to harbor glycosyl hydrolases (GHs) which cleave specific glycan linkages. Although several microbial species have been identified as mucin degraders, there are ...likely many other members of the healthy gut community with the capacity to degrade mucins. The aim of the present study was to systematically examine the CAZyme mucin-degrading profiles of the human gut microbiota. Within the Verrucomicrobia phylum, all Akkermansia glycaniphila and muciniphila genomes harbored multiple gene copies of mucin-degrading GHs. The only representative of the Lentisphaerae phylum, Victivallales, harbored a GH profile that closely mirrored Akkermansia. In the Actinobacteria phylum, we found several Actinomadura, Actinomyces, Bifidobacterium, Streptacidiphilus and Streptomyces species with mucin-degrading GHs. Within the Bacteroidetes phylum, Alistipes, Alloprevotella, Bacteroides, Fermenitomonas Parabacteroides, Prevotella and Phocaeicola species had mucin degrading GHs. Firmicutes contained Abiotrophia, Blautia, Enterococcus, Paenibacillus, Ruminococcus, Streptococcus, and Viridibacillus species with mucin-degrading GHs. Interestingly, far fewer mucin-degrading GHs were observed in the Proteobacteria phylum and were found in Klebsiella, Mixta, Serratia and Enterobacter species. We confirmed the mucin-degrading capability of 23 representative gut microbes using a chemically defined media lacking glucose supplemented with porcine intestinal mucus. These data greatly expand our knowledge of microbial-mediated mucin degradation within the human gut microbiota.
In the limit of dilute alloyingthe so-called “single-atom alloy” (SAA) regimecertain bimetallic systems exhibit weak mixing between constituent metal wave functions, resulting in sharp, ...single-atom-like electronic states localized on the dilute component of the alloy. This work shows that when these sharp states are appropriately positioned relative to given molecular orbitals, selective hybridization is enhanced, in accordance with intuitive principles of molecular orbital theory. We demonstrate the phenomenon for activation pathways of crotonaldehyde, a model α,β-unsaturated aldehyde relevant to a wide range of chemical manufacturing. This analysis suggests new possible strategies for selectivity control in heterogeneous catalysis.
Lightweight, flexible, and electrically conductive thin films with high electromagnetic interference (EMI) shielding effectiveness are highly desirable for next‐generation portable and wearable ...electronic devices. Here, spin spray layer‐by‐layer (SSLbL) to rapidly assemble Ti3C2Tx MXene‐carbon nanotube (CNT) composite films is shown and their potential for EMI shielding is demonstrated. The SSLbL technique allows strategic combinations of nanostructured materials and polymers providing a rich platform for developing hierarchical architectures with desirable cross‐functionalities including controllable transparency, thickness, and conductivity, as well as high stability and flexibility. These semi‐transparent LbL MXene‐CNT composite films show high conductivities up to 130 S cm−1 and high specific shielding effectiveness up to 58 187 dB cm2 g−1, which is attributed to both the excellent electrical conductivity of the conductive fillers (i.e., MXene and CNT) and the enhanced absorption with the LbL architecture of the films. Remarkably, these values are among the highest reported values for flexible and semi‐transparent composite thin films. This work could offer new solutions for next‐generation EMI shielding challenges.
Lightweight, flexible, and electrically conductive thin films with high electromagnetic interference shielding effectiveness are highly desirable for next‐generation portable and wearable electronic devices. Here, spin spray layer‐by‐layer is demonstrated to rapidly assemble Ti3C2Tx MXene‐carbon nanotube composite films with desirable cross‐functionalities including controllable transparency, thickness, and conductivity, as well as high stability and flexibility.
Recent advances in metallic glass nanostructures (MGNs) are reported, covering a wide array of synthesis strategies, computational discovery, and design solutions that provide insight into distinct ...electrocatalytic applications. A brief introduction to the development and unique features of MGNs with an overview of top‐down and bottom‐up synthesis strategies is presented. Specifically, the morphology and structural analysis of several examples applying MGNs as electrodes are highlighted. Subsequently, a comprehensive discussion of commonly employed kinetic parameters and their connection with the unique material structures of MGNs on individual electrocatalytic reactions is made, including the hydrogen evolution reaction, oxygen reduction reaction, and alcohol (methanol or ethanol) oxidation reaction. Finally, a summary of the challenges and perspective on the future research and development relevant to MGNs as electrocatalysts is provided.
The most recent advances of metallic glass nanostructures are discussed, including a wide array of synthesis strategies, computational discovery, and design solutions that provide insight into distinct electrocatalytic applications, along with a summary of the challenges and perspectives on the future research and development relevant to electrocatalysis.
Medulloblastoma is the most common pediatric malignant brain tumor. Advances in molecular profiling have uncovered significant heterogeneity among medulloblastomas and led to the identification of ...four distinct subgroups (wingless WNT, sonic hedgehog SHH, group 3, and group 4) that represent distinct disease entities in both underlying biology and clinical characteristics. The rapidly expanding repertoire of tools to study developmental and cancer biology is providing a wealth of knowledge about these embryonal tumors and is continuously refining the understanding of this complex cancer. In this review, the history of discovery in medulloblastoma is discussed, setting a foundation to outline the current state of understanding of the molecular underpinnings of this disease, with a focus on genomic events that define the aforementioned subgroups and evolving areas of focus, such as the cell of origin of medulloblastoma and medulloblastoma subtypes. With these recent discoveries in mind, the current state of medulloblastoma treatment and clinical trials is reviewed, including a novel risk stratification system that accounts for the molecular biomarkers of patients with a high risk for refractory disease. Lastly, critical areas of focus for future basic science and clinical research on this disease are discussed, such as the complexities of medulloblastoma metastases and recurrence as well as the priorities and strategies to implement in future clinical trials.
In perovskite solar cells, doped organic semiconductors are often used as chargeextraction interlayers situated between the photoactive layer and the electrodes. The n-conjugated small molecule ...2,2',7,7'-tetrakisA,A-di(4-methoxyphenyl)amino9,9-spirobifluorene (spiro-OMeTAD) is the most frequently used semiconductor in the hole-conducting layer1-6, and its electrical properties considerably affect the charge collection efficiencies of the solar cell7. To enhance the electrical conductivity of spiro-OMeTAD, lithium bis(trifluoromethane)sulfonimide (LiTFSI) is typically used in a doping process, which is conventionally initiated by exposing spiroOMeTAD:LiTFSI blend films to air and light for several hours. This process, in which oxygen acts as the p-type dopant8-11, is time-intensive and largely depends on ambient conditions, and thus hinders the commercialization of perovskite solar cells. Here we report a fast and reproducible doping method that involves bubbling a spiro-OMeTAD:LiTFSI solution with CO2 under ultraviolet light. CO2 obtains electrons from photoexcited spiro-OMeTAD, rapidly promoting its p-type doping and resulting in the precipitation of carbonates. The CO2-treated interlayer exhibits approximately 100 times higher conductivity than a pristine film while realizing stable, high-efficiency perovskite solar cells without any post-treatments. We also show that this method can be used to dope n-conjugated polymers.
In this study, we present a facile and scalable approach to fabricate omniphobic nanofiber membranes by constructing multilevel re-entrant structures with low surface energy. We first prepared ...positively charged nanofiber mats by electrospinning a blend polymer–surfactant solution of poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and cationic surfactant (benzyltriethylammonium). Negatively charged silica nanoparticles (SiNPs) were grafted on the positively charged electrospun nanofibers via dip-coating to achieve multilevel re-entrant structures. Grafted SiNPs were then coated with fluoroalkylsilane to lower the surface energy of the membrane. The fabricated membrane showed excellent omniphobicity, as demonstrated by its wetting resistance to various low surface tension liquids, including ethanol with a surface tension of 22.1 mN/m. As a promising application, the prepared omniphobic membrane was tested in direct contact membrane distillation to extract water from highly saline feed solutions containing low surface tension substances, mimicking emerging industrial wastewaters (e.g., from shale gas production). While a control hydrophobic PVDF-HFP nanofiber membrane failed in the desalination/separation process due to low wetting resistance, our fabricated omniphobic membrane exhibited a stable desalination performance for 8 h of operation, successfully demonstrating clean water production from the low surface tension feedwater.
Medulloblastoma: From Myth to Molecular Ramaswamy, Vijay; Taylor, Michael D
Journal of clinical oncology,
2017-Jul-20, Letnik:
35, Številka:
21
Journal Article
Recenzirano
Current therapies for medulloblastoma were introduced primarily in the 1980s and consist of predominantly cytotoxic, nontargeted approaches. Mortality from medulloblastoma remains significant. In ...addition, many survivors suffer from severe treatment-related effects of radiation and cytotoxic chemotherapy. Further intensification of nonspecific therapy is unlikely to offer additional benefits, because survival rates have reached a plateau. Recent publications in medulloblastoma have revolved largely around the recognition that medulloblastoma per se does not exist, but rather, that there are a group of histologically similar but clinically and molecularly distinct entities that have been grouped under that rubric. Distinguishing the four molecular subgroups of medulloblastoma-wingless (WNT), sonic hedgehog (SHH), group 3, and group 4-in the daily treatment of patients, as well in the setting of clinical trials, is an important challenge in the near term for the pediatric neuro-oncology community. The preponderance of morbidity in treating patients with medulloblastoma is secondary to the treatment or prophylaxis of leptomeningeal metastases, and the cause of most deaths is leptomeningeal metastases. Recurrence of medulloblastoma is a nearly universally fatal event, with no significant salvage rate. The extent of spatial and temporal intratumoral heterogeneity as medulloblastoma metastasizes to leptomeninges and as it evolves in the face of radiation and cytotoxic chemotherapy is just beginning to be understood as a major barrier to therapeutic success. Pediatric neuro-oncology clinicians and scientists must now determine how best to incorporate rapid changes in our biologic understanding of medulloblastoma into the next generation of upfront clinical trials, with the goal of both improving survival for the highest-risk patients and improving quality of life for survivors.
We present a comprehensive analysis of all ring systems (both heterocyclic and nonheterocyclic) in clinical trial compounds and FDA-approved drugs. We show 67% of small molecules in clinical trials ...comprise only ring systems found in marketed drugs, which mirrors previously published findings for newly approved drugs. We also show there are approximately 450 000 unique ring systems derived from 2.24 billion molecules currently available in synthesized chemical space, and molecules in clinical trials utilize only 0.1% of this available pool. Moreover, there are fewer ring systems in drugs compared with those in clinical trials, but this is balanced by the drug ring systems being reused more often. Furthermore, systematic changes of up to two atoms on existing drug and clinical trial ring systems give a set of 3902 future clinical trial ring systems, which are predicted to cover approximately 50% of the novel ring systems entering clinical trials.