Climatic Signals in Wood Property Variables of Picea Crassifolia

Little attention has been given to climatic signals in wood properties. In this study, ring width(RW), annual average microfibril angle (MFA), annual average tracheid radial diameter (TRD), andannual average density (DEN), as the annual and intra-annual wood property variables, were measured at high resolution by SilviScan-3 on dated Picea crassifolia trees. Dendroclimatological methods were used to analyze climatic signals registered in wood property variables. RW, MFA, and TRD negatively correlated with temperature and positively correlated with precipitation in the growing season, whereas the reverse was true for DEN. Climatic signals recorded in the earlywood were similar to those measured for the full width of the annual rings. Climatic signals recorded in latewood were very weak except for latewood MFA. This study showed that wood property variables could be extensive resources for learning more about the influences of climate on tree growth and how trees adapt to ongoing climate change

The VHL/HIF Axis in the Development and Treatment of Pheochromocytoma/Paraganglioma

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors originating from chromaffin cells in the adrenal medulla (PCCs) or extra-adrenal sympathetic or parasympathetic paraganglia (PGLs). About 40% of PPGLs result from germline mutations and therefore they are highly inheritable. Although dysfunction of any one of a panel of more than 20 genes can lead to PPGLs, mutations in genes involved in the VHL/HIF axis includin

>Quality-time-complexity universal intelligence measurement

Purpose - With development of machine learning techniques, the artificial intelligence systems such as crowd networks are becoming more and more autonomous and smart. Therefore, there is a growing demand to develop a universal intelligence measurement so that the intelligence of artificial intelligence systems can be evaluated. This paper aims to propose a more formalized and accurate machine intelligence measurement method. Design/methodology/approach - This paper proposes a quality–time–complexity universal intelligence measurement method to measure the intelligence of agents. Findings - By observing the interaction process between the agent and the environment, we abstract three major factors for intelligence measure as quality, time and complexity of environment. Practical implications - In a crowd network, a number of intelligent agents are able to collaborate with each other to finish a certain kind of sophisticated tasks. The proposed approach can be used to allocate the tasks to the agents within a crowd network in an optimized manner. Originality/value - This paper proposes a calculable universal intelligent measure method through considering more than two factors and the correlations between factors which are involved in an intelligent measurement

Genotype-phenotype correlation in patients with 21-hydroxylase deficiency.

INTRODUCTION: 21-hydroxylase deficiency (21OHD) is the most common cause of congenital adrenal hyperplasia (CAH). However, patients with 21OHD manifest various phenotypes due to a wide-spectrum residual enzyme activity of different CYP21A2 mutations. METHODS: A total of 15 individuals from three unrelated families were included in this study. Target Capture-Based Deep Sequencing and Restriction Fragment Length Polymorphism was conducted on peripheral blood DNA of the three probands to identify potential mutations/deletions in CYP21A2; Sanger sequencing was conducted with the DNA from the family members of the probands. RESULTS: Dramatically different phenotypes were seen in the three probands of CAH with different compound heterozygous mutations in CYP21A2. Proband 1 manifested simple virilizing with mutations of 30-kb deletion/c.[188A\u3eT;518T\u3eA], the latter is a novel double mutants classified as SV associated mutation. Although both probands carry the same compound mutations [293-13C\u3eG]:[518T\u3eA], gonadal dysfunction and giant bilateral adrenal myelolipoma were diagnosed for proband 2 and proband 3, respectively. CONCLUSION: Both gender and mutations contribute to the phenotypes, and patients with the same compound mutations and gender could present with different phenotypes. Genetic analysis could help the etiologic diagnosis, especially for atypical 21OHD patients

Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) patient with ARMC5 mutations.

BACKGROUND: Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a highly heterogeneous disease with divergent manifestations ranging from asymptomatic subclinical Cushing syndrome (CS) to overt Cushing syndrome with severe complications. ARMC5 mutations occur in 20 to 55% PBMAH patients usually with more severe phenotypes. Different ARMC5 mutations might be associated with diverse phenotypes of PBMAH. CASE PRESENTATION: A 39-year-old man was admitted to our hospital with progressive weight gain and severe hypertension. He presented typical CS and its classical metabolic and bone complications like hypertension and osteoporosis. The laboratory results showed high levels of cortisol and low levels of ACTH. Low- and high-dosed dexamethasone suppression tests were negative. Contrast-enhanced computed tomography (CT) revealed multiple bilateral irregular macronodular adrenal masses. Adrenal venous sampling (AVS) confirmed that the right adrenal gland with larger nodules secreted more hormone that the left side did. Right adrenalectomy and subsequent contralateral subtotal resection were conducted. His blood pressure and CS symptoms as well as comorbidities including backache and muscle weakness improved. Whole exome sequencing identified one ARMC5 germline mutation (c.1855C \u3e T, p. R619*), five ARMC5 somatic mutations (four novel mutations) in his right and left adrenal nodules. CONCLUSIONS: This PBMAH patient was identified with one ARMC5 germline mutation and five different somatic ARMC5 mutations (four novel mutations) in the different nodules of the bilateral adrenal masses. AVS combined with CT imagine could be helpful to determine the dominant side for adrenalectomy. Genetic testing is important for the diagnosis and management of the patient with PBMAH

A Renal Cell Carcinoma with Biallelic Somatic TSC2 Mutation: Clinical Study and Literature Review.

OBJECTIVES: To elucidate the effect of the biallelic somatic TSC2 mutations, identified in one adolescent patient, in renal cell carcinoma (RCC). METHODS: Mutation analyses, immunohistochemistry and real-time polymerase chain reaction (PCR) were conducted. RESULTS: Two novel somatic mutations of TSC2 in unilateral and solitary RCC samples from a 14-year-old female were identified. The pathological features suggest the tumor as a clear-cell renal cell carcinoma. In addition, immunohistochemistry revealed elevated levels of phosphorylated S6K1. Results from in vitro cellular experiments suggest that the mutant TSC2 proteins were quickly degraded and they failed to repress the phosphorylation of S6K1 and STAT3, which leads to constitutive activation of mTORC1 pathway and ultimately cause the development of RCC. CONCLUSIONS: Detecting TSC2 mutation in patients with early RCC onset would be beneficial and mTOR inhibitor could be a therapeutic option for TSC2 mutation-induced RCC

LSD1 Promotes Bladder Cancer Progression by Upregulating LEF1 and Enhancing EMT.

Epithelial-to-mesenchymal transition (EMT) is one of the important underlying molecular mechanisms for most types of cancers including bladder cancer. The precise underlying molecular mechanism in EMT-mediated bladder cancer progression is far from completed. LSD1, a histone lysine-specific demethylase, is known to promote cancer cell proliferation, metastasis, and chemoresistance. We found in this study that LSD1 is highly upregulated in bladder cancer specimens, especially those underwent chemotherapy, and the elevated levels of LSD1 are highly associated with bladder cancer grades, metastasis status, and prognosis. Inhibiting or knockdown LSD1 repressed not only EMT process but also cancer progression. Mechanistically, LSD1 complexes with β-catenin to transcriptionally upregulate LEF1 and subsequently enhances EMT-mediated cancer progression. More importantly, LSD1 specific inhibitor GSK2879552 is capable of repressing tumor progression in patient-derived tumor xenograft. These findings altogether suggest that LSD1 can serve as not only a prognostic biomarker but also a promising therapeutic target in bladder cancer treatment

First-in-Human Trial of EphA2-Redirected CAR T-Cells in Patients With Recurrent Glioblastoma: A Preliminary Report of Three Cases at the Starting Dose

Glioblastoma is the most common primary brain malignancy with limited treatment options. EphA2 is a tumor-associated-antigen overexpressed in glioblastoma. Pre-clinical studies have demonstrated the promise of EphA2-redirected CAR T-cells against glioblastoma. We conduct the first-in-human trial of EphA2-redirected CAR T-cells in patients with EphA2-positive recurrent glioblastoma and report the results of three patients enrolled as the first cohort receiving the starting dosage (1×106 cells/kg). A single infusion of EphA2-redirected CAR T-cells was administrated intravenously, with the lymphodepletion regimen consisting of fludarabine and Cyclophosphamide. In two patients, there was grade 2 cytokine release syndrome accompanied by pulmonary edema, which resolved completely with dexamethasone medication. Except that, there was no other organ toxicity including neurotoxicity. In both the peripheral blood and cerebral-spinal-fluid, we observed the expansion of CAR T-cells which persisted for more than four weeks. In one patient, there was a transit diminishment of the tumor. Among these three patients, one patient reported SD and two patients reported PD, with overall survival ranging from 86 to 181 days. At the tested dose level (1×106 cells/kg), intravenously infusion of EphA2-rediretected CAR T-cells were preliminary tolerable with transient clinical efficacy. Future study with adjusted dose and infusion frequency of CAR T-cells is warranted.Trial Registration NumbersNCT 0342399