A differential autophagic response to hyperglycemia in the developing murine embryo

Autophagy is critical to the process of development because mouse models have shown that lack of autophagy leads to developmental arrest during the pre-implantation stage of embryogenesis. The process of autophagy is regulated through signaling pathways, which respond to the cellular environment. Therefore, any alteration in the environment may lead to the dysregulation of the autophagic process potentially resulting in cell death. Using both in vitro and in vivo models to study autophagy in the pre-implantation murine embryo, we observed that the cells respond to environmental stressors (i.e. hyperglycemic environment) by increasing activation of autophagy in a differential pattern within the embryo. This upregulation is accompanied by an increase in apoptosis, which appears to plateau at high concentrations of glucose. The activation of the autophagic pathway was further confirmed by an increase in GAPDH activity in both in vivo and in vitro hyperglycemic models, which has been linked to autophagy through the activation of the Atg12 gene. Furthermore, this increase in autophagy in response to a hyperglycemic environment was observed as early as the oocyte stage. In conclusion, in this study, we provided evidence for a differential response of elevated activation of autophagy in embryos and oocytes exposed to a hyperglycemic environment.     

Nanocube Superlattices of Cesium Lead Bromide Perovskites and Pressure‐Induced Phase Transformations at Atomic and Mesoscale Levels

Lead halide perovskites are promising materials for a range of applications owing to their unique crystal structure and optoelectronic properties. Understanding the relationship between the atomic/mesostructures and the associated properties of perovskite materials is crucial to their application performances. Herein, the detailed pressure processing of CsPbBr₃ perovskite nanocube superlattices (NC‐SLs) is reported for the first time. By using in situ synchrotron‐based small/wide angle X‐ray scattering and photoluminescence (PL) probes, the NC‐SL structural transformations are correlated at both atomic and mesoscale levels with the band‐gap evolution through a pressure cycle of 0 ? 17.5 GPa. After the pressurization, the individual CsPbBr₃ NCs fuse into 2D nanoplatelets (NPLs) with a uniform thickness. The pressure‐synthesized perovskite NPLs exhibit a single cubic crystal structure, a 1.6‐fold enhanced photoluminescence quantum yield, and a longer emission lifetime than the starting NCs. This study demonstrates that pressure processing can serve as a novel approach for the rapid conversion of lead halide perovskites into structures with enhanced properties.     

Correlation of fine needle aspiration biopsy and fluoride-18 fluorodeoxyglucose positron emission tomography in the assessment of locally recurrent and metastatic head and neck neoplasia

OBJECTIVE: Patients with primary head and neck neoplasia can present during follow-up with suspected recurrence, and both fine needle aspiration biopsy (FNAB) and fluoride-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan are available methodologies for evaluating these patients. Our objective was to retrospectively correlate patients who underwent both FNAB and FDG-PET scan in order to assess the possibility of recurrent neoplasia. STUDY DESIGN: The cytopathology files at Saint Louis University Health Sciences Center were retrospectively searched for patients with known primary head and neck malignancies beginning in 1995. Suspected recurrence and local metastases evaluated by both FNAB and FDG-PET scan were correlated. RESULTS: Twenty-eight patients received a combined total of 37 FNABs with concurrent FDG-PET scans. The majority of patients had primary oropharyngeal squamous cell carcinoma with intermixed, single cases of other primary head and neck neoplasms. Thirty of the 32 aspirates with recurrent or locally metastatic disease had combined positive findings by both FNAB and FDG-PET scan, yielding a sensitivity of 94%. One nonspecific and one negative FDG-PET scan came from a patient who had disease confirmed by FNAB. Five patients had negative findings by both methods that were supported by the subsequent clinical course. CONCLUSION: FNAB can provide confirmatory evidence of disease in a clinically suspicious abnormality with nonspecific FDG-PET results. FNAB and FDG-PET are highly sensitive for tumors in cases of clinically suspected recurrence and locally metastatic disease.     

Multiple myeloma with monoclonal surface immunoglobulin expression: a case report

BACKGROUND: Plasma cells from patients with multiple myeloma have been found to express the immunophenotype of normal plasma cells without surface immunoglobulin expression. CASE: A case occurred of multiple myeloma with monoclonal surface immunoglobulin expression, defined by morphology and flow cytometric immunophenotyping of a fine needle aspiration biopsy of an osteolytic rib lesion and a bone marrow aspirate as well as urine and serum protein electrophoresis with immunofixation. CONCLUSION: The clinical significance of monoclonal surface immunoglobulin expression in rare cases of multiple myeloma is uncertain, and other parameters with clinical significance (CD10 positivity, multiple myeloid antigen expression) will continue to be more useful until additional cases accrue.     

Xe-p9, a Xenopus Suc1/Cks protein, is essential for the Cdc2-dependent phosphorylation of the anaphase- promoting complex at mitosis

Degradation of mitotic cyclins on exit from M phase occurs by ubiquitin-mediated proteolysis. The ubiquitination of mitotic cyclins is regulated by the anaphase-promoting complex (APC) or cyclosome. Xe-p9, the Xenopus homolog of the Suc1/Cks protein, is required for some step in mitotic cyclin destruction in Xenopus egg extracts. Specifically, if p9 is removed from interphase egg extracts, these p9-depleted extracts are unable to carry out the proteolysis of cyclin B after entry into mitosis and thus remain arrested in M phase. To explore the molecular basis of this defect, we depleted p9 from extracts that had already entered M phase and thus contained an active APC. We found that ubiquitin-mediated proteolysis of cyclin B was not compromised under these circumstances, suggesting that p9 is not directly required for ubiquitination or proteolysis. Further analysis of extracts from which p9 had been removed during interphase showed that, at the beginning of mitosis, these extracts are unable to carry out the hyperphosphorylation of the Cdc27 component of the APC, which coincides with the initial activation of the APC. p9 can be found in a complex with a small fraction of the Cdc27 protein during M phase but not interphase. The phosphorylation of the Cdc27 protein (either associated with the APC or in an isolated, bacterially expressed form) by recombinant Cdc2/cyclin B is strongly enhanced by p9. Our results indicate that p9 directly regulates the phosphorylation of the APC by Cdc2/cyclin B. These studies indicate that the Suc1/Cks protein modulates substrate recognition by a cyclin-dependent kinase.     

Extensive Ozonation of C60: Degradation or Polymerization?

The impact of the oxidizing agent ozone (O₃) on the structure of the most common spherical allotrope of carbon, buckminsterfullerene (C₆₀) is studied. Past studies measured ozonation of C₆₀ over short periods of time. In this study, we establish that C₆₀ is completely degraded, not polymerized, during ozonation. The techniques, laser desorption time-of-flight mass spectrometry, UV/Vis absorbance spectroscopy, and FT-Raman are used to study the molecular degradation of the spherical allotrope C₆₀ by O₃.     

Legal Case-based Reasoning as Practical Reasoning

In this paper we apply a general account of practical reasoning to arguing about legal cases. In particular, we provide a reconstruction of the reasoning of the majority and dissenting opinions for a particular well-known case from property law. This is done through the use of Belief-Desire-Intention (BDI) agents to replicate the contrasting views involved in the actual decision. This reconstruction suggests that the reasoning involved can be separated into three distinct levels: factual and normative levels and a level connecting the two, with conclusions at one level forming premises at the next. We begin by summarising our general approach, which uses instantiations of an argumentation scheme to provide presumptive justifications for actions, and critical questions to identify arguments which attack these justifications. These arguments and attacks are organised into argumentation frameworks to identify the status of individual arguments. We then discuss the levels of reasoning that occur in this reconstruction and the properties and significance of each of these levels. We illustrate the different levels with short examples and also include a discussion of the role of precedents within these levels of reasoning.     

Statistical analysis of baseline load models for non-residential buildings

Policymakers are encouraging the development of standardized and consistent methods to quantify the electric load impacts of demand response programs. For load impacts, an essential part of the analysis is the estimation of the baseline load profile. In this paper, we present a statistical evaluation of the performance of several different models used to calculate baselines for commercial buildings participating in a demand response program in California. In our approach, we use the model to estimate baseline loads for a large set of proxy event days for which the actual load data are also available. Measures of the accuracy and bias of different models, the importance of weather effects, and the effect of applying morning adjustment factors (which use data from the day of the event to adjust the estimated baseline) are presented. Our results suggest that (1) the accuracy of baseline load models can be improved substantially by applying a morning adjustment, (2) the characterization of building loads by variability and weather sensitivity is a useful indicator of which types of baseline models will perform well, and (3) models that incorporate temperature either improve the accuracy of the model fit or do not change it.