An Integrated System Dynamics and Discrete Event Supply Chain Simulation Framework for Supply Chain Resilience with Non-Stationary Pandemic Demand

COVID-19 resulted in some of the largest supply chain disruptions in recent history. To mitigate the impact of future disruptions, we propose an integrated hybrid simulation framework to couple nonstationary demand signals from an event like COVID-19 with a model of an end-to-end supply chain. We first create a system dynamics susceptible-infected-recovered (SIR) model, augmenting a classic epidemiological model to create a realistic portrayal of demand patterns for oxygen concentrators (OC). Informed by this granular demand signal, we then create a supply chain discrete event simulation model of OC sourcing, manufacturing, and distribution to test production augmentation policies to satisfy this increased demand. This model utilizes publicly available data, engineering teardowns of OCs, and a supply chain illumination to identify suppliers. Our findings indicate that this coupled approach can use realistic demand during a disruptive event to enable rapid recommendations of policies for increased supply chain resilience with controlled cost

Identification of Biomarkers Associated With Pathological Stage and Prognosis of Clear Cell Renal Cell Carcinoma by Co-expression Network Analysis

Clear cell renal cell carcinoma (ccRCC) is the most common subtype among renal cancer whose prognostic is affected by the tumor progression associated with complex gene interactions. However, there is currently no available molecular markers associated with ccRCC progression and used or clinical application. In our study, microarray data of 101 ccRCC samples and 95 normal kidney samples were analyzed and 2,425 differentially expressed genes (DEGs) were screened. Weighted gene co-expression network analysis (WGCNA) was then conducted and 11 co-expressed gene modules were identified. Module preservation analysis revealed that two modules (red and black) were found to be most stable. In addition, Pearson's correlation analysis identified the module most relevant to pathological stage(patho-module) (r = 0.44, p = 3e-07). Functional enrichment analysis showed that biological processes of the patho-module focused on cell cycle and cell division related biological process and pathway. In addition, 29 network hub genes highly related to ccRCC progression were identified from the stage module. These 29 hub genes were subsequently validated using 2 other independent datasets including GSE53757 (n = 72) and TCGA (n = 530), and the results indicated that all hub genes were significantly positive correlated with the 4 stages of ccRCC progression. Kaplan-Meier survival curve showed that patients with higher expression of each hub gene had significantly lower overall survival rate and disease-free survival rate, indicating that all hub genes could act as prognosis and recurrence/progression biomarkers of ccRCC. In summary, we identified 29 molecular markers correlated with different pathological stages of ccRCC. They may have important clinical implications for improving risk stratification, therapeutic decision and prognosis prediction in ccRCC patients

Janus monolayers of transition metal dichalcogenides.

Structural symmetry-breaking plays a crucial role in determining the electronic band structures of two-dimensional materials. Tremendous efforts have been devoted to breaking the in-plane symmetry of graphene with electric fields on AB-stacked bilayers or stacked van der Waals heterostructures. In contrast, transition metal dichalcogenide monolayers are semiconductors with intrinsic in-plane asymmetry, leading to direct electronic bandgaps, distinctive optical properties and great potential in optoelectronics. Apart from their in-plane inversion asymmetry, an additional degree of freedom allowing spin manipulation can be induced by breaking the out-of-plane mirror symmetry with external electric fields or, as theoretically proposed, with an asymmetric out-of-plane structural configuration. Here, we report a synthetic strategy to grow Janus monolayers of transition metal dichalcogenides breaking the out-of-plane structural symmetry. In particular, based on a MoS2 monolayer, we fully replace the top-layer S with Se atoms. We confirm the Janus structure of MoSSe directly by means of scanning transmission electron microscopy and energy-dependent X-ray photoelectron spectroscopy, and prove the existence of vertical dipoles by second harmonic generation and piezoresponse force microscopy measurements

The breast cancer somatic 'muta-ome': tackling the complexity

Acquired somatic mutations are responsible for approximately 90% of breast tumours. However, only one somatic aberration, amplification of the HER2 locus, is currently used to define a clinical subtype, one that accounts for approximately 10% to 15% of breast tumours. In recent years, a number of mutational profiling studies have attempted to further identify clinically relevant mutations. While these studies have confirmed the oncogenic or tumour suppressor role of many known suspects, they have exposed complexity as a main feature of the breast cancer mutational landscape (the 'muta-ome'). The two defining features of this complexity are (a) a surprising richness of low-frequency mutants contrasting with the relative rarity of high-frequency events and (b) the relatively large number of somatic genomic aberrations (approximately 20 to 50) driving an average tumour. Structural features of this complex landscape have begun to emerge from follow-up studies that have tackled the complexity by integrating the spectrum of genomic mutations with a variety of complementary biological knowledge databases. Among these structural features are the growing links between somatic gene disruptions and those conferring breast cancer risk, mutually exclusive coexistence and synergistic mutational patterns, and a clearly non-random distribution of mutations implicating specific molecular pathways in breast tumour initiation and progression. Recognising that a shift from a gene-centric to a pathway-centric approach is necessary, we envisage that further progress in identifying clinically relevant genomic aberration patterns and associated breast cancer subtypes will require not only multi-dimensional integrative analyses that combine mutational and functional profiles, but also larger profiling studies that use second- and third-generation sequencing technologies in order to fill out the important gaps in the current mutational landscape

SDSS-IV MaNGA : spatial evolution of star formation triggered by galaxy interactions

Galaxy interaction is considered a key driver of galaxy evolution and star formation (SF) history. In this paper, we present an empirical picture of the radial extent of interaction-triggered SF along the merger sequence. The samples under study are drawn from the integral field spectroscopy survey SDSS-IV MaNGA, including 205 star-forming galaxies in pairs/mergers and ~1350 control galaxies. For each galaxy in pairs, the merger stage is identified according to its morphological signatures: incoming phase, at first pericenter passage, at apocenter, in merging phase, and in final coalescence. The effect of interactions is quantified by the global and spatially resolved SF rate (SFR) relative to the SFR of a control sample selected for each individual galaxy (Δlog SFR and Δlog sSFR(r), respectively). Analysis of the radial Δlog sSFR(r) distributions shows that galaxy interactions have no significant impact on Δlog sSFR(r) during the incoming phase. Right after the first pericenter passage, the radial Δlog sSFR(r) profile decreases steeply from enhanced to suppressed activity for increasing galactocentric radius. Later on, SF is enhanced on a broad spatial scale out to the maximum radius we explore (~6.7 kpc) and the enhancement is in general centrally peaked. The extended SF enhancement is also observed for systems at their apocenters and in the coalescence phase, suggesting that interaction-triggered SF is not restricted to the central region of a galaxy. Further explorations of a wide range in parameter space of merger configurations (e.g., mass ratio) are required to constrain the whole picture of interaction-triggered S

Antitumor Agents. 250. † Design and Synthesis of New Curcumin Analogues as Potential Anti-Prostate Cancer Agents

In a continuing study of curcumin analogs as potential drug candidates to treat prostate cancer at both androgen-dependent and androgen-refractory stages, we designed and synthesized over 40 new analogs classified into four series: monophenyl analogs (series A), heterocycle-containing analogs (series B), analogs bearing various substituents on the phenyl rings (series C) and analogs with various linkers (series D). These new compounds were tested for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Antiandrogenic activity was also evaluated in LNCaP cells and PC-3 cells transfected with wild-type androgen receptor. Ten compounds possessed potent cytotoxicity against both LNCaP and PC-3 cells; seven only against LNCaP; and one solely against PC-3. This study established an advanced structure-activity relationship (SAR), and these correlations will guide the further design of new curcumin analogs with better anti-prostate cancer activity

Planck Galactic Cold Clumps at High Galactic Latitude-a Study with CO Lines

Gas at high Galactic latitude is a relatively little noticed component of the interstellar medium. In an effort to address this, 41 Planck Galactic Cold Clumps at high Galactic latitude (HGal; divide b divide > 25 degrees) were observed in (CO)-C-12, (CO)-C-13, and (CO)-O-18 J = 1-0 lines, using the Purple Mountain Observatory 13.7 m telescope. (CO)-C-12 (1-0) and (CO)-C-13 (1-0) emission was detected in all clumps, while (CO)-O-18 (1-0) emission was only seen in 16 clumps. The highest and average latitudes are 71.degrees 4 and 37.degrees 8, respectively. Fifty-one velocity components were obtained, and then each was identified as a single clump. Thirty-three clumps were further mapped at 1 ' resolution, and 54 dense cores were extracted. Among dense cores, the average excitation temperature T (ex) of (CO)-C-12 is 10.3 K. The average line widths of thermal and nonthermal velocity dispersions are 0.19 and 0.46 km s(-1), respectively, suggesting that these cores are dominated by turbulence. Distances of the HGal clumps given by Gaia dust reddening are about 120-360 pc. The ratio of X (13)/X (18) is significantly higher than that in the solar neighborhood, implying that HGal gas has a different star formation history compared to the gas in the Galactic disk. HGal cores with sizes from 0.01 to 0.1 pc show no notable Larson's relation, and the turbulence remains supersonic down to a scale of slightly below 0.1 pc. None of the HGal cores that bear masses from 0.01 to 1 M (circle dot) are gravitationally bound, and all appear to be confined by outer pressure.Peer reviewe

Identification and Localization of Proteins Associated with Biomineralization in the Iron Deposition Vesicles of Honeybees (Apis mellifera)

Honeybees (Apis mellifera) form superparamagnetic magnetite to act as a magnetoreceptor for magnetoreception. Biomineralization of superparamagnetic magnetite occurs in the iron deposition vesicles of trophocytes. Even though magnetite has been demonstrated, the mechanism of magnetite biomineralization is unknown. In this study, proteins in the iron granules and iron deposition vesicles of trophocytes were purified and identified by mass spectrometry. Antibodies against such proteins were produced. The major proteins include actin, myosin, ferritin 2, and ATP synthase. Immunolabeling and co-immunoprecipitation studies suggest that iron is stored in ferritin 2 for the purpose of forming 7.5-nm diameter iron particles and that actin-myosin-ferritin 2 may serve as a transporter system. This system, along with calcium and ATP, conveys the iron particles (ferritin) to the center of iron deposition vesicles for iron granules formation. These proteins and reactants are included in iron deposition vesicles during the formation of iron deposition vesicles from the fusion of smooth endoplasmic reticulum. A hypothetical model for magnetite biomineralization in iron deposition vesicles is proposed for honeybees