Small Data Can Play a Big Role in Chemical Discovery

The chemistry community is currently witnessing a surge of scientific discoveries in organic chemistry supported by machine learning (ML) techniques. Whereas many of these techniques were developed for big data applications, the nature of experimental organic chemistry often confines practitioners to small datasets. Herein, we touch upon the limitations associated with small data in ML and emphasize the impact of bias and variance on constructing reliable predictive models. We aim to raise awareness to these possible pitfalls, and thus, provide an introductory guideline for good practice. Ultimately, we stress the great value associated with statistical analysis of small data, which can be further boosted by adopting a holistic data-centric approach in chemistry.     

0.18μm铜金属双重镶嵌工艺中空间成像套刻精度分析

由于空间成像套刻(Overlay)技术的预算随集成电路(IC)设计规范的紧缩而吃紧,因此,Overlay测量技术准确度的重要意义也随之提高。通过对后开发(AfterDevelopDI)阶段和后蚀刻(AfterEtchFI)阶段的Overlay测量结果进行比较,研究了0.18μm设计规范下的铜金属双重镶嵌工艺过程中的Overlay准确度。在确保对同一个晶圆进行后开发(DI)阶段和后蚀刻(FI)阶段测试的条件下,我们对成品晶圆的5个工艺层进行了比较。此外,还利用CD-SEM(线宽-扫描电子显微镜)测量了某个工艺层(PolyGate)上的芯片内Overlay,并与采用分割线方法的光学Overlay测量结果进行了比较。发现对芯片内overlay的校准存在着严重的局限性,即在应用CD-SEM时缺乏合适的结构进行Overlay测量。我们还将继续为大家提供定量的比较结果,同时也会向大家推荐组合的CD-SEM测量结构,使其能够被应用到今后的光刻设计中。     

Sensitivity of Staphylococcus aureus strains to broadband visible light

The phototoxic effect of illumination with broadband visible light on the viability of two Staphylococcus aureus strains was examined in the present study. A difference in the light sensitivity of the two strains was found. Illumination of the tested strains with a fluence rate of 180 J cm⁻² caused a reduction of up to 99.8% in the colony count of one of the strains (the "sensitive" strain). Illumination of the other strain (the "resistant" strain) resulted in a 55.5% reduction in viability. Proliferation of both strains was observed at low fluence rates of light. The phototoxic effect was found to be dependent on oxy radical production. The light-sensitive strain produced higher amounts of hydroxyl and superoxide radicals than the "resistant" strain. Adaptation to oxidative stress was exhibited only by the "resistant" strain. The "sensitive" strain produced ten times more endogenous porphyrins and secreted almost nine times more porphyrins than the resistant strain. Furthermore, the "resistant" strain produced twice as many carotenoids that protect the strain from illumination than the "sensitive" strain. These results indicate that high intensities of visible light cause bacterial photoeradication, a reaction which may assist wound healing by killing the infecting bacteria. On the other hand, low intensities of white light were found to enhance bacterial proliferation and thus prolong wound infection.     

Cognitive‐Performance Recovery of Alzheimer's Disease Model Mice by Modulation of Early Soluble Amyloidal Assemblies

A rationally designed oligomerization inhibitor interacts with early intermediate assemblies of amyloid‐β polypeptide (Aβ) through the aromatic elements and inhibits their assembly into the toxic oligomers that cause Alzheimer's disease by a unique C^α‐methylation β‐breakage strategy. The electrostatic potential of the low‐energy conformation of the dipeptide inhibitor bound to Aβ is shown.

     

Application of spherical harmonics derived space rotation invariant indices to the analysis of multiple sclerosis lesions' geometry by MRI

In the longitudinal study of multiple sclerosis (MS) lesions, varying position of the patient inside the MRI scanner is one of the major sources of assessment errors. We propose to use analytical indices that are invariant to spatial orientation to describe the lesions, rather than focus on patient repositioning or image realignment. Studies were made on simulated lesions systematically rotated, from in vitro MS lesions scanned on different days, and from in vivo MS lesions from a patient that was scanned five times the same day with short intervals of time between scans. Each of the lesions' 3D surfaces was approximated using spherical harmonics, from which indices that are invariant to space rotation were derived. From these indices, an accurate and highly reproducible volume estimate can be derived, which is superior to the common approach of 2D slice stacking. The results indicate that the suggested approach is useful in reducing part of the errors that affect the analysis of changes of MS lesions during follow-up studies. In conclusion, our proposed method circumvents the need for precise patient repositioning and can be advantageous in MRI longitudinal studies of MS patients.     

Expression and Structure/Function Relationships of Human Defensin 5

The innate immunity utilizes a battery of broad-spectrum antibacterial cationic polypeptides (3–5 kDa), among them defensins. In humans, defensins are the first line of defense against pathogens and their expression has been implicated in several diseases. The antibacterial activity of defensins is generally ascribed to their overall positive charge, which enables them to disrupt bacterial membrane integrity and function, but their active surface has not been fully elucidated. To perform structural and functional assays, an efficient, high-yield, easy-to-use expression and purification system must be established. Up to now, most efforts to obtain larger quantities of active recombinant defensins have been only moderately successful. Herein, we report the establishment of an efficient, high-yield expression and purification system for human defensin 5 (HD-5). Using site-directed mutagenesis, we pinpoint several arginine residues and Y27 as important for HD-5 antibacterial activity. Our expression and purification system can be harnessed for structure/activity relationship studies of defensins in particular and small polypeptides in general.     

The role of multiple solution tasks in developing knowledge and creativity in geometry

This paper describes changes in students’ geometrical knowledge and their creativity associated with implementation of Multiple Solution Tasks (MSTs) in school geometry courses. Three hundred and three students from 14 geometry classes participated in the study, of whom 229 students from 11 classes learned in an experimental environment that employed MSTs while the rest learned without any special intervention in the course of one school year. This longitudinal study compares the development of knowledge and creativity between the experimental and control groups as reflected in students’ written tests. Geometry knowledge was measured by the correctness and connectedness of the solutions presented. The criteria for creativity were: fluency, flexibility, and originality. The findings show that students’ connectedness as well as their fluency and flexibility benefited from implementation of MSTs. The study supports the idea that originality is a more internal characteristic than fluency and flexibility, and therefore more related with creativity and less dynamic. Nevertheless, the MSTs approach provides greater opportunity for potentially creative students to present their creative products than conventional learning environment. Cluster analysis of the experimental group identified three clusters that correspond to three levels of student performance, according to the five measured criteria in pre- and post-tests, and showed that, with the exception of originality, performance in all three clusters generally improved on the various criteria.     

An Organoid for Woven Bone

Bone formation (osteogenesis) is a complex process in which cellular differentiation and the generation of a mineralized organic matrix are synchronized to produce a hybrid hierarchical architecture. To study the mechanisms of osteogenesis in health and disease, there is a great need for functional model systems that capture in parallel, both cellular and matrix formation processes. Stem cell-based organoids are promising as functional, self-organizing 3D in vitro models for studying the physiology and pathology of various tissues. However, for human bone, no such functional model system is yet available. This study reports the in vitro differentiation of human bone marrow stromal cells into a functional 3D self-organizing co-culture of osteoblasts and osteocytes, creating an organoid for early stage bone (woven bone) formation. It demonstrates the formation of an organoid where osteocytes are embedded within the collagen matrix that is produced by the osteoblasts and mineralized under biological control. Alike in in vivo osteocytes, the embedded osteocytes show network formation and communication via expression of sclerostin. The current system forms the most complete 3D living in vitro model system to investigate osteogenesis, both in physiological and pathological situations, as well as under the influence of external triggers (mechanical stimulation, drug administration).