Estimating long-term time-resolved indoor PM2.5 of outdoor and indoor origin using easily obtainable inputs

To evaluate the separate impacts on human health and establish effective control strategies, it is crucial to estimate the contribution of outdoor infiltration and indoor emission to indoor PM_2.5 in buildings. This study used an algorithm to automatically estimate the long-term time-resolved indoor PM_2.5 of outdoor and indoor origin in real apartments with natural ventilation. The inputs for the algorithm were only the time-resolved indoor/outdoor PM_2.5 concentrations and occupants’ window actions, which were easily obtained from the low-cost sensors. This study first applied the algorithm in an apartment in Tianjin, China. The indoor/outdoor contribution to the gross indoor exposure and time-resolved infiltration factor were automatically estimated using the algorithm. The influence of outdoor PM_2.5 data source and algorithm parameters on the estimated results was analyzed. The algorithm was then applied in four other apartments located in Chongqing, Shenyang, Xi'an, and Urumqi to further demonstrate its feasibility. The results provided indirect evidence, such as the plausible explanations for seasonal and spatial variation, to partially support the success of the algorithm used in real apartments. Through the analysis, this study also identified several further development directions to facilitate the practical applications of the algorithm, such as robust long-term outdoor PM_2.5 monitoring using low-cost light-scattering sensors.     

A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.     

河南省灵宝市董家埝银矿原生晕特征及地质意义

董家埝银矿是豫西小秦岭矿集区南成矿带目前发现的唯一大型矿床。为了矿床深部勘查工作的顺利进行,了解有用元素在垂向上的变化规律,选用原生晕地球化学方法,通过典型矿床剖面的原生晕特征研究,实现对深部矿体变化趋势的判断。经计算,确定As、Sb、Ag、Au、Cu、Pb、Zn、Co和Mo等9种元素可作为指示元素,其中As和Sb为前缘晕指示元素,Ag、Au、Cu、Pb和Zn为近矿晕指示元素,Co和Mo为尾晕指示元素。分带指数和浓集指数2种方法计算得出的元素在分带序列上的位置总体趋势一致。用分带指数法确定的主矿体自上而下的原生晕轴向分带序列为Co-Mo-Cu-Au-Sb-Zn-Pb-Ag-As,出现"反分带"现象。结合原生晕地球化学参数变化特征、矿体剥蚀程度研究和理想模型,预测M1-I主矿体向深部仍有较大的延伸。研究成果可以为区域同类型矿化地质体深部的趋势判断和决策提供参考。     

Accelerated multi-contrast high isotropic resolution 3D intracranial vessel wall MRI using a tailored k-space undersampling and partially parallel reconstruction strategy

Objective

To develop a 3D multi-contrast IVW protocol with 0.5-mm isotropic resolution and a scan time of 5 min per sequence.

Materials and methods

Pre-contrast T1w VISTA, DANTE prepared PDw VISTA, SNAP, and post-contrast T1w VISTA were accelerated using cartesian undersampling with target ordering method (CUSTOM) and self-supporting tailored k-space estimation for parallel imaging reconstruction (STEP). CUSTOM + STEP IVW was compared to full-sample IVW, SENSE-accelerated IVW, and CUSTOM + zero-filled Fourier reconstruction in normal volunteers and subjects with intracranial atherosclerotic disease (ICAD). Image quality, vessel delineation, CSF suppression, and blood suppression were compared.

Results

CUSTOM + STEP vessel wall delineation was comparable to full-sample IVW and better than SENSE IVW for vessel wall delineation on T1w VISTA and luminal contrast on SNAP. Average image quality and wall depiction were significantly improved using STEP reconstruction compared with zero-filled Fourier reconstruction, with no significant difference in CSF or blood suppression.

Conclusions

CUSTOM + STEP allowed multi-contrast 3D 0.5-mm isotropic IVW within 30 min. Although some quantitative and qualitative scores for CUSTOM − STEP were lower than fully sampled IVW, CUSTOM + STEP provided comparable vessel wall delineation as full-sample IVW and was superior to SENSE. CUSTOM + STEP IVW was well tolerated by patients and showed good delineation of ICAD plaque.

     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.