The Forkhead box transcription factor FOXM1 is required for the maintenance of cell proliferation and protection against oxidative stress in human embryonic stem cells

published_or_final_versio

Evaluation of bone-tendon junction healing using water jet ultrasound indentation method

2009-2010 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

The Newsvendor Problem: Review and Directions for Future Research

In this paper, we review the contributions to date for analyzing the newsvendor problem. Our focus is on examining the specific extensions for analyzing this problem in the context of modeling customer demand, supplier costs, and the buyer risk profile. More specifically, we analyze the impact of market price, marketing effort, and stocking quantity on customer demand; how supplier prices can serve as a coordination mechanism in a supply chain setting; integrating alternative supplier pricing policies within the newsvendor framework; and how the buyer’s risk profile moderates the newsvendor order quantity decision. For each of these areas,we summarize the current literature and develop extensions. Finally, we also propose directions for future research

Noncontact evaluation of articular cartilage degeneration using a novel ultrasound water jet indentation system

Author name used in this publication: Y. P. ZhengAuthor name used in this publication: A. MakAuthor name used in this publication: Q.-H. HuangAuthor name used in this publication: M.-H. Lu2008-2009 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

Radial Growth of Qilian Juniper on the Northeast Tibetan Plateau and Potential Climate Associations

There is controversy regarding the limiting climatic factor for tree radial growth at the alpine treeline on the northeastern Tibetan Plateau. In this study, we collected 594 increment cores from 331 trees, grouped within four altitude belts spanning the range 3550 to 4020 m.a.s.l. on a single hillside. We have developed four equivalent ring-width chronologies and shown that there are no significant differences in their growth-climate responses during 1956 to 2011 or in their longer-term growth patterns during the period AD 1110–2011. The main climate influence on radial growth is shown to be precipitation variability. Missing ring analysis shows that tree radial growth at the uppermost treeline location is more sensitive to climate variation than that at other elevations, and poor tree radial growth is particularly linked to the occurrence of serious drought events. Hence water limitation, rather than temperature stress, plays the pivotal role in controlling the radial growth of Sabina przewalskii Kom. at the treeline in this region. This finding contradicts any generalisation that tree-ring chronologies from high-elevation treeline environments are mostly indicators of temperature changes

DLX1 acts as a crucial target of FOXM1 to promote ovarian cancer aggressiveness by enhancing TGF-β/SMAD4 signaling

Recent evidence from a comprehensive genome analysis and functional studies have revealed that FOXM1 is a crucial metastatic regulator that drives cancer progression. However, the regulatory mechanism by which FOXM1 exerts its metastatic functions in cancer cells remains obscure. Here, we report that DLX1 acts as a FOXM1 downstream target, exerting pro-metastatic function in ovarian cancers. Both FOXM1 isoforms (FOXM1B or FOXM1C) could transcriptionally upregulate DLX1 through two conserved binding sites, located at +61 to +69bp downstream (TFBS1) and -675 to -667bp upstream (TFBS2) of the DLX1 promoter, respectively. This regulation was further accentuated by the significant correlation between the nuclear expression of FOXM1 and DLX1 in high-grade serous ovarian cancers. Functionally, the ectopic expression of DLX1 promoted ovarian cancer cell growth, cell migration/invasion and intraperitoneal dissemination of ovarian cancer in mice, whereas small interfering RNA-mediated DLX1 knockdown in FOXM1-overexpressing ovarian cancer cells abrogated these oncogenic capacities. In contrast, depletion of FOXM1 by shRNAi only partially attenuated tumor growth and exerted almost no effect on cell migration/invasion and the intraperitoneal dissemination of DLX1-overexpressing ovarian cancer cells. Furthermore, the mechanistic studies showed that DLX1 positively modulates TGF- signaling by upregulating PAI-1 and JUNB through direct interaction with SMAD4 in the nucleus upon TGF-1 induction. Taken together, these data strongly suggest that DLX1 plays a pivotal role in FOXM1 signaling to promote cancer aggressiveness through intensifying TGF-/SMAD4 signaling in high-grade serous ovarian cancer cells.published_or_final_versio

Extending colonic mucosal microbiome analysis - Assessment of colonic lavage as a proxy for endoscopic colonic biopsies

This study was supported through GI Research funds and MRC Grant Ref: MR/M00533X/1 to GH.Peer reviewedPublisher PD

An Enhanced Tilted-Angle Acoustofluidic Chip for Cancer Cell Manipulation

In recent years, surface acoustic wave (SAW) devices have demonstrated great potentials and increasing applications in the manipulation of nano- and micro-particles including biological cells with the advantages of label-free, high sensitivity and accuracy. In this letter, we introduce a novel tilted-angle SAW devices to optimise the acoustic pressure inside a microchannel for cancer-cell manipulation. The SAW generation and acoustic radiation force are improved by seamlessly patterning electrodes in the space surrounding the microchannel. Comparisons between this novel SAW device and a conventional device show a 32% enhanced separation efficiency while the input power, manufacturing cost and fabrication effort remain the same. Effective separation of HeLa cancer cells from peripheral blood mononuclear cells is demonstrated. This novel SAW device has the advantages in minimizing device power consumption, lowering component footprint and increasing device density.This work was supported by the Natural Science Basic Research Program of Shaanxi Province (2020JQ-233); Fundamental Scientific Research of Central Universities (grant number 3102017OQD116); the Engineering and Physical Sciences Research Council (EPSRC) (EP/P002803/1 and EP/P018998/1); and the Royal Society (IEC/NSFC/170142, IE161019)

An Enhanced Tilted-Angle Acoustofluidic Chip for Cancer Cell Manipulation

In recent years, surface acoustic wave (SAW) devices have demonstrated great potentials and increasing applications in the manipulation of nano- and micro-particles including biological cells with the advantages of label-free, high sensitivity and accuracy. In this letter, we introduce a novel tilted-angle SAW devices to optimise the acoustic pressure inside a microchannel for cancer-cell manipulation. The SAW generation and acoustic radiation force are improved by seamlessly patterning electrodes in the space surrounding the microchannel. Comparisons between this novel SAW device and a conventional device show a 32% enhanced separation efficiency while the input power, manufacturing cost and fabrication effort remain the same. Effective separation of HeLa cancer cells from peripheral blood mononuclear cells is demonstrated. This novel SAW device has the advantages in minimizing device power consumption, lowering component footprint and increasing device density.This work was supported by the Natural Science Basic Research Program of Shaanxi Province (2020JQ-233); Fundamental Scientific Research of Central Universities (grant number 3102017OQD116); the Engineering and Physical Sciences Research Council (EPSRC) (EP/P002803/1 and EP/P018998/1); and the Royal Society (IEC/NSFC/170142, IE161019)

In-Vitro Helix Opening of M. tuberculosis oriC by DnaA Occurs at Precise Location and Is Inhibited by IciA Like Protein

BACKGROUND: Mycobacterium tuberculosis (M.tb), the pathogen that causes tuberculosis, is capable of staying asymptomatically in a latent form, persisting for years in very low replicating state, before getting reactivated to cause active infection. It is therefore important to study M.tb chromosome replication, specifically its initiation and regulation. While the region between dnaA and dnaN gene is capable of autonomous replication, little is known about the interaction between DnaA initiator protein, oriC origin of replication sequences and their negative effectors of replication. METHODOLOGY/PRINCIPAL FINDINGS: By KMnO(4) mapping assays the sequences involved in open complex formation within oriC, mediated by M.tb DnaA protein, were mapped to position -500 to -518 with respect to the dnaN gene. Contrary to E. coli, the M.tb DnaA in the presence of non-hydrolysable analogue of ATP (ATPgammaS) was unable to participate in helix opening thereby pointing to the importance of ATP hydrolysis. Interestingly, ATPase activity in the presence of supercoiled template was higher than that observed for DnaA box alone. M.tb rRv1985c, a homologue of E.coli IciA (Inhibitor of chromosomal initiation) protein, could inhibit DnaA-mediated in-vitro helix opening by specifically binding to A+T rich region of oriC, provided the open complex formation had not initiated. rIciA could also inhibit in-vitro replication of plasmid carrying the M.tb origin of replication. CONCLUSIONS/SIGNIFICANCE: These results have a bearing on the functional role of the important regulator of M.tb chromosomal replication belonging to the LysR family of bacterial regulatory proteins in the context of latency