The Role of CD4 T Cell Help in Effective CD8 T Cell Responses during Mycobacterium Tuberculosis Infection

Tuberculosis (TB), a transmissible disease caused by Mycobacterium tuberculosis (Mtb), is a global health threat. To design an effective vaccine, we need to better understand how different elements of our immune system collaborate to fight against Mtb. CD4 T cells are crucial in protective immunity to Mtb because they produce cytokines including interferon-γ. In contrast, CD8 T cells are thought to play a modest role. Whether CD4 T cells act as “helper” cells to promote optimal CD8 T cell responses during TB is unknown. We argue CD8 T cells’ role are likely underestimated because CD8 T cell functions are compromised without CD4 T cells. Here, using two independent models, I show that CD4 T cell help promotes CD8 T cell effector functions and prevents CD8 T cell exhaustion. I demonstrate CD4 and CD8 T cells synergistically enhance the survival of infected mice. Purified helped, but not helpless, CD8 T cells effectively restrict intracellular Mtb growth. Thus, CD4 T cell help is indispensable for generating protective CD8 T cell responses. In addition, I investigate the mechanisms of CD4 T cell help. Signals from CD4 T cells, and signals relayed by antigen presenting cells collectively shape CD8 T cell responses. We infer that vaccines aimed for eliciting both CD4 and CD8 T cells, in which CD8 T cells are properly helped by CD4 T cells, are more likely to be successful

Lack of Association Between Total Serum Homocysteine and Extracranial Cerebral Flow

Background/PurposeHigh homocysteine (Hcy) concentration is associated with slow coronary flow. This study examined the association between Hcy and hemodynamic status in the extracranial cerebral arteries in healthy individuals.MethodsA total of 535 healthy adults underwent physical examination and duplex ultrasonography of the extracranial carotid and vertebral arteries, and blood laboratory tests, including biochemistry and serum total Hcy. Flow hemodynamic parameters including velocity, resistance, and volume of the carotid and vertebral arteries were measured. Multiple regression analysis was performed to examine the association between Hcy and the flow parameters.ResultsParticipants with higher Hcy were more likely to have a lower systolic velocity of the internal carotid artery (p = 0.01) and vertebral artery (p < 0.001), and lower resistance of the vertebral artery (p = 0.004). However, the multiple-adjusted means of the flow velocity, resistance, and flow volume of the carotid or vertebral artery were not significantly different across quartiles of Hcy. When Hcy was treated as a continuous variable, there was still no significant relationship between Hcy levels and the aforementioned hemodynamic status.ConclusionOur results did not support the hypothesis that the levels of Hcy are associated with the flow velocity, resistance, and volume of the extracranial cerebral artery in healthy individuals

FACTORS AFFECTING THE TRANSFER OF INTER-ORGANIZATIONAL SYSTEMS TO CHINA: A CASE STUDY OF HIGH-TECH ENTERPRISES

Due to the huge market potentiality, profuse production resource such as workforce and land, and low production costs in China, many international high-tech enterprises are moving their production line to China. Accompanying production offshoring is the transfer of Information Technology (IT) to ensure that the production processes remain efficient and effective at home and abroad. Many enterprises however encounter problems in transferring their IT to China, especially when the IT is an inter-organizational system (IOS), which is across organizational boundaries and involves the management of relationships among participants. In order to understand how to successfully transfer IOS to China, we aim to find out key relational factors of IOS performance in China through an observation of a binary relationship built upon an e-procurement system between a Taiwanese PC ODM (Original Design Manufacturer) and its Chinese suppliers. Based on the relational view of the firm, four relational factors are proposed and examined. The results show that IOS specific investments and effective IOS governance most strongly affects the result of IOS transfer to China, whereas complementary resource endowment has least influence

MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway.

The Hippo pathway plays a central role in tissue homoeostasis, and its dysregulation contributes to tumorigenesis. Core components of the Hippo pathway include a kinase cascade of MST1/2 and LATS1/2 and the transcription co-activators YAP/TAZ. In response to stimulation, LATS1/2 phosphorylate and inhibit YAP/TAZ, the main effectors of the Hippo pathway. Accumulating evidence suggests that MST1/2 are not required for the regulation of YAP/TAZ. Here we show that deletion of LATS1/2 but not MST1/2 abolishes YAP/TAZ phosphorylation. We have identified MAP4K family members--Drosophila Happyhour homologues MAP4K1/2/3 and Misshapen homologues MAP4K4/6/7-as direct LATS1/2-activating kinases. Combined deletion of MAP4Ks and MST1/2, but neither alone, suppresses phosphorylation of LATS1/2 and YAP/TAZ in response to a wide range of signals. Our results demonstrate that MAP4Ks act in parallel to and are partially redundant with MST1/2 in the regulation of LATS1/2 and YAP/TAZ, and establish MAP4Ks as components of the expanded Hippo pathway

Social-Loc: Improving indoor localization with social sensing

Location-based services, such as targeted advertisement, geo-social networking and emergency services, are becoming in-creasingly popular for mobile applications. While GPS pro-vides accurate outdoor locations, accurate indoor localiza-tion schemes still require either additional infrastructure support (e.g., ranging devices) or extensive training before system deployment (e.g., WiFi signal fingerprinting). In or-der to help existing localization systems to overcome their limitations or to further improve their accuracy, we propose Social-Loc, a middleware that takes the potential locations for individual users, which is estimated by any underlying indoor localization system as input and exploits both so-cial encounter and non-encounter events to cooperatively calibrate the estimation errors. We have fully implemented Social-Loc on the Android platform and demonstrated its performance on two underlying indoor localization systems: Dead-reckoning and WiFi fingerprint. Experiment results show that Social-Loc improves user’s localization accuracy of WiFi fingerprint and dead-reckoning by at least 22 % and 37%, respectively. Large-scale simulation results indicate Social-Loc is scalable, provides good accuracy for a long du-ration of time, and is robust against measurement errors

CD4 T cell help prevents CD8 T cell exhaustion and promotes control of Mycobacterium tuberculosis infection [preprint]

CD4 T cells are essential for immunity to tuberculosis because they produce cytokines including interferon-γ. Whether CD4 T cells act as “helper” cells to promote optimal CD8 T cell responses during Mycobacterium tuberculosis is unknown. Using two independent models, we show that CD4 T cell help enhances CD8 effector functions and prevents CD8 T cell exhaustion. We demonstrate synergy between CD4 and CD8 T cells in promoting the survival of infected mice. Purified helped, but not helpless, CD8 T cells efficiently restrict intracellular bacterial growth in vitro. Thus, CD4 T cell help plays an essential role in generating protective CD8 T cell responses against M. tuberculosis infection in vitro and in vivo. We infer vaccines that elicit both CD4 and CD8 T cells are more likely to be successful than vaccines that elicit only CD4 or CD8 T cells

Room-temperature organic-based spin polarizer

We report a magnetic tunnel junction operating at room-temperature with organic magnetic semiconductor V[TCNE](x) (x similar to 2, TCNE: tetracyanoethylene) and Fe as the spin polarizer and analyzer while 10 mu rubrene layer serves as the tunnel barrier between them. At room-temperature, the magnetoresistance (MR) presents 16.7% of its peak value at 100K. We observed sign inversion of MR with increasing temperature, while the sign of the MR is independent of the polarity of the bias voltages. Our results suggest that V[TCNE](x) is a promising material for room-temperature spintronic applications.open5

Monitoring Apnea in the Elderly by an Electromechanical System with a Carbon Nanotube-based Sensor

SummaryBackgroundBreathing, a part of respiration, is one of the vital functions. Breathing disorders are common in the elderly. An effective breathing sensor for real-time detection of apnea is important in clinical critical care. We aimed to construct a real-time warning platform with a combination of carbon nanotubes (CNTs) and related nano-electromechanical system (NEMS) for elderly care.MethodsThrough a specific acid-treated procedure, multiwalled carbon nanotubes (MWCNTs) were immobilized on a thin silicon dioxide (SiO2) film, coated on a heated silicon wafer. Techniques of photolithography and sputtering with chromium and gold were then implemented on the MWCNT film to develop micro-interdigitated electrodes as a base for the breathing sensor. The sensor was equipped with a programmed microchip processor to become a warning detector for abnormal human breathing, namely less than six breaths per minute. Elderly volunteers were enrolled for examining the effective sensitivity of this novel electromechanical device.ResultsThere were 15 elderly volunteers (9 males and 6 females) tested in this experiment. The dynamic analyses of the MWCNT sensor to exhaled breath showed that it had characteristics of rapid response, high aspect ratio, small tip ratio, and high electrical conductivity. Responses of the MWCNT sensor to exhaled breath was recorded according to different performance parameters, i.e., strength, frequency, flow rate, and breath components. In this study, variable pattern-simulated tests showed that a MWCNT sensor combined with a processor could accurately evoke warning signals (100% of sensitivity rate), indicating its effectiveness and usefulness for detecting abnormal breathing rates, especially apnea.ConclusionOur results showed that a new device composed of an NEMS by combining an MWCNT sensor and complementary metal-oxide semiconductor (CMOS) circuits could be integrated to effectively detect apnea in the elderly. This novel device may improve the pattern of safe respiratory care for the elderly in the future

Effects of ranibizumab on human corneal endothelial cells

AbstractPurposeThis study aims to evaluate corneal endothelial changes occurring over a 3-month period after intravitreal injections of ranibizumab in patients with wet age-related macular degeneration.MethodsThis is a prospective case series. A total of 29 patients (29 eyes) received a 0.5-mg intravitreal injection of ranibizumab. Specular microscopy, including measurement of central corneal thickness and endothelial cell count, was performed on each patient prior to and after completing three intravitreal injections.ResultsAll patients received three intravitreal injections and were followed up for a mean of 3 months. There was no significant change in corneal thickness (p = 0.32) or endothelial cell density (p = 0.38) after ranibizumab injections.ConclusionIntravitreal ranibizumab injections (0.5 mg) have no harmful effects on corneal endothelial cells