STUDY OF MAMMALIAN CELL SIZE REGULATION AND DIVISION PLANE DETERMINATION WITH MICRO-CHANNEL

Ph.DDOCTOR OF PHILOSOPHY (FOS

Probing Mammalian Cell Size Homeostasis by Channel-Assisted Cell Reshaping

Cell size homeostasis can be achieved by size checkpoints that couple cell size to cell-cycle progression or by alternative mechanisms such as constant extension. In mammalian cells, the existence of strict size checkpoints remains controversial due to the technical limitations in determining cell size directly and accurately. We developed a microfabricated channel system that linearizes mammalian cell growth and facilitates cell size measurements. By tracking cell length, while directly visualizing cell-cycle progression in rat basophilic leukemia cells and RAW 264.7 macrophages, we examined the mechanisms of size homeostasis and the existence of a size checkpoint at the G1/S transition. Our analysis revealed a two-tier size homeostasis mechanism where a G1 “sizer” or “adder” could operate, depending on the birth size of the cells

New Chimeric Antigen Receptor Design for Solid Tumors

In recent years, chimeric antigen receptor (CAR) T-cell therapy has become popular in immunotherapy, particularly after its tremendous success in the treatment of lineage-restricted hematologic cancers. However, the application of CAR T-cell therapy for solid tumors has not reached its full potential because of the lack of specific tumor antigens and inhibitory factors in suppressive tumor microenvironment (TME) (e.g., programmed death ligand-1, myeloid-derived suppressor cells, and transforming growth factor-β). In this review, we include some limitations in CAR design, such as tumor heterogeneity, indefinite spatial distance between CAR T-cell and its target cell, and suppressive TME. We also summarize some new approaches to overcome these hurdles, including targeting neoantigens and/or multiple antigens at once and depleting some inhibitory factors

Event-related potential P3 elicited by a single tone in personality disorders

Background: A cerebral P3 potential (passive P3) in response to a single tone shares similar morphology to the classical P3 elicited in the active "oddball" paradigm, but reflects passive attention. As the patients with schizotypal, antisocial and borderline personality disorders showed reduced amplitude and prolonged latency of classical P3, it is reasonable to expect that these patients might show an abnormal passive P3. In order to test this hypothesis, we tried the single tone elicited event-related potentials (ERPs) in patients with several sorts of personality disorders. Methods: We tested the passive ERPs in 205 patients with personality disorders (22 patients with the paranoid type, 11 schizoid, 14 schizotypal, 18 antisocial, 18 borderline, 16 histrionic, 20 narcissistic, 27 avoidant, 30 dependent and 29 obsessive-compulsive) and in 30 healthy volunteers. Their Axis I symptoms of depression and anxiety were measured by Zung's Self-rating Depression Scale and Self-rating Anxiety Scale. Results: Both schizoid and paranoid groups showed significantly reduced P3 amplitude. In addition, the schizoid group showed significantly shorted N1 latency and enhanced N2 amplitude. Most patient groups except schizoids scored higher on the Depression or Anxiety scales, or both, but the ERP findings were not correlated with the Axis I symptoms in any given group alone. Conclusions: The abnom1al negative components implied a higher vigilance or cortical arousal level in the schizoid patients, while the reduced P3 amplitude indicated a poorer passive attention in both schizoid and paranoid patients.14 page(s

Relationship between personality disorder functioning styles and the emotional states in bipolar I and II disorders.

BACKGROUND:Bipolar disorder types I (BD I) and II (BD II) behave differently in clinical manifestations, normal personality traits, responses to pharmacotherapies, biochemical backgrounds and neuroimaging activations. How the varied emotional states of BD I and II are related to the comorbid personality disorders remains to be settled. METHODS:We therefore administered the Plutchick - van Praag Depression Inventory (PVP), the Mood Disorder Questionnaire (MDQ), the Hypomanic Checklist-32 (HCL-32), and the Parker Personality Measure (PERM) in 37 patients with BD I, 34 BD II, and in 76 healthy volunteers. RESULTS:Compared to the healthy volunteers, patients with BD I and II scored higher on some PERM styles, PVP, MDQ and HCL-32 scales. In BD I, the PERM Borderline style predicted the PVP scale; and Antisocial predicted HCL-32. In BD II, Borderline, Dependent, Paranoid (-) and Schizoid (-) predicted PVP; Borderline predicted MDQ; Passive-Aggressive and Schizoid (-) predicted HCL-32. In controls, Borderline and Narcissistic (-) predicted PVP; Borderline and Dependent (-) predicted MDQ. CONCLUSION:Besides confirming the different predictability of the 11 functioning styles of personality disorder to BD I and II, we found that the prediction was more common in BD II, which might underlie its higher risk of suicide and poorer treatment outcome

Imipramine Protects against Bone Loss by Inhibition of Osteoblast-Derived Microvesicles

The maintenance of bone homeostasis is largely dependent upon cellular communication between osteoclasts and osteoblasts. Microvesicles (MVs) represent a novel mechanism for osteoblasts and osteoclasts communication, as has been demonstrated in our previous study. Sphingomyelinases catalyze the hydrolysis of sphingomyelin, which leads to increased membrane fluidity and facilitates MV generation. This effect can be inhibited by imipramine, an inhibitor of acid sphingomyelinase (ASM), which is also known as a member of tricyclic antidepressants (TCAs). A recent study has reported that in vitro treatment of imipramine blocked MVs release from glial cells. However, whether imipramine has this effect on osteoblast-derived MVs and whether it is involved in MV generation in vivo is unclear. Here, our investigations found that imipramine slightly reduced the expression of osteoblast differentiation of related genes, but did not impact parathyroid hormone (PTH) regulation for these genes and also did not affect receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclast formation; however, imipramine treatment blocked MVs released from osteoblasts and inhibited MV-induced osteoclast formation. In vivo, mice administrated with imipramine were protected from ovariectomy-induced bone loss as evaluated by various bone structural parameters and serum levels of biochemical markers. Our results suggest that inhibiting the production of MVs containing RANKL in vivo is very important for preventing bone loss

Effects of Flow Spillage Strategies on the Aerodynamic Characteristics of Diverterless Hypersonic Inlets

This paper compares the aerodynamic characteristics of a central-spillage diverterless hypersonic inlet (i.e., bump inlet, Form 1) with a side-spillage inlet (Form 2) under on/off design conditions when faced with non-uniform inflow. Both forms are designed for a flight Mach number of 6.0 and a cruise altitude of 24.0 km. Numerical methods are introduced and validated. Integrated design results indicate that based on identical contraction ratios, Form 2 is 27.8% lower in height, 28.3% shorter in length, and 34.4% smaller in the windward projection area than Form 1. This provides the evidence that the side-spillage strategy will suppress the external drag less. Then, the aerodynamic performance is investigated under various upstream/downstream boundary conditions (inflow speed range: Mach 2.0~6.0; backpressure fluctuation range: 1~110.0 times the freestream static pressure). The evaluation methods for non-uniform flow fields are first introduced in this paper. Form 2 has a relatively stronger shock system, which allows it to suppress 4.52% more of the pressure fluctuation from the downstream combustion chamber than Form 1. The inlet start margin is widened by approximately 250% due to the self-adaptive flow spillage ability established by the side-spillage strategy. Furthermore, the compression efficiency, internal shock system, spillage ability, etc., are analyzed in detail. In summary, the side-spillage flow organization strategy has better potential for designing wide-ranging air-breathing flight vehicles

Effects of Flow Spillage Strategies on the Aerodynamic Characteristics of Diverterless Hypersonic Inlets

This paper compares the aerodynamic characteristics of a central-spillage diverterless hypersonic inlet (i.e., bump inlet, Form 1) with a side-spillage inlet (Form 2) under on/off design conditions when faced with non-uniform inflow. Both forms are designed for a flight Mach number of 6.0 and a cruise altitude of 24.0 km. Numerical methods are introduced and validated. Integrated design results indicate that based on identical contraction ratios, Form 2 is 27.8% lower in height, 28.3% shorter in length, and 34.4% smaller in the windward projection area than Form 1. This provides the evidence that the side-spillage strategy will suppress the external drag less. Then, the aerodynamic performance is investigated under various upstream/downstream boundary conditions (inflow speed range: Mach 2.0~6.0; backpressure fluctuation range: 1~110.0 times the freestream static pressure). The evaluation methods for non-uniform flow fields are first introduced in this paper. Form 2 has a relatively stronger shock system, which allows it to suppress 4.52% more of the pressure fluctuation from the downstream combustion chamber than Form 1. The inlet start margin is widened by approximately 250% due to the self-adaptive flow spillage ability established by the side-spillage strategy. Furthermore, the compression efficiency, internal shock system, spillage ability, etc., are analyzed in detail. In summary, the side-spillage flow organization strategy has better potential for designing wide-ranging air-breathing flight vehicles