The Neurotrophic Receptor Ntrk2 Directs Lymphoid Tissue Neovascularization during Leishmania donovani Infection

The neurotrophic tyrosine kinase receptor type 2 (Ntrk2, also known as TrkB) and its ligands brain derived neurotrophic factor (Bdnf), neurotrophin-4 (NT-4/5), and neurotrophin-3 (NT-3) are known primarily for their multiple effects on neuronal differentiation and survival. Here, we provide evidence that Ntrk2 plays a role in the pathologic remodeling of the spleen that accompanies chronic infection. We show that in Leishmania donovani-infected mice, Ntrk2 is aberrantly expressed on splenic endothelial cells and that new maturing blood vessels within the white pulp are intimately associated with F4/80hiCD11bloCD11c+ macrophages that express Bdnf and NT-4/5 and have pro-angiogenic potential in vitro. Furthermore, administration of the small molecule Ntrk2 antagonist ANA-12 to infected mice significantly inhibited white pulp neovascularization but had no effect on red pulp vascular remodeling. We believe this to be the first evidence of the Ntrk2/neurotrophin pathway driving pathogen-induced vascular remodeling in lymphoid tissue. These studies highlight the therapeutic potential of modulating this pathway to inhibit pathological angiogenesis

An improved inverter-based readout scheme for low-power ISFET sensing array

Digital read-out scheme in ISFET sensing array is more advantageous when compared to the analog counterpart because of its lower power consumption, less area and less susceptible to environmental noise and parasitic. This work proposes an improved readout scheme in which each ISFET is stacked with a CMOS inverter to form a pH-to-time converter. pH level of the solution regulates the strength of the ISFET, which in turn modulates the delay of the stacked inverter and hence the pulse-width of the output signal. Simulation results using 0.18 μm/2.5V CMOS process show that the modulated pulse width changes linearly over a wide range of pH. Our design achieves 5 orders of magnitude smaller leakage, 40% lower dynamic power consumption while requires only 50% of silicon area when compared to the conventional design. It is therefore more suitable for large ISFET array implemented in nanoscale CMOS technologies.Accepted versio

Transmission of disorder and etiological information: Effects on health knowledge recollection and health-related cognition

Biased transmission of health knowledge has far-reaching effects on information reproduction and health-related cognitions. We examined whether transmissions of different types of disorder and etiological information influence recollections of health knowledge and evaluations of patients, by simulating the digital transmission of information. Transmission chains of four non-interacting persons (i.e., four generations) were formed. The first generation read three vignettes describing fictitious patients with one of three disorders (physiological, psychological, culture-bound) uniquely paired with one of three etiologies (genetic, environmental, unknown etiology). Next, they evaluated patients' well-being, rated desired social distance, and recalled the vignettes. These written recollections replaced the original vignettes for a second-generation of participants, whose recollections were used for the third generation and so on. The framing of disorders affected recollections of etiology, in which culture-bound framings resulted in the poorest recall of etiologies. Participants also perceived the culture-bound disorder as the least serious but desired the most social distance from patients diagnosed with it, when compared to other disorders. The study showed that health information is selectively attended to and reproduced, possibly affected by perceived self-relevance. Faulty recollections and framing of disorders affect health cognitions, potentially instigating biased transmission of disorder- and patient-related narratives

Integrated circuits design for neural recording sensor interface

Neural signal recording is attracting more and more attention, as it provides an necessary approach to read brain activities, understand the brain operation and restore the lost motor function of the body. One of the most important modules in the neural recording system is the sensor interface IC, which captures, amplifies, filters, and digitizes the weak neural signal. In order to preserve free movement of the subject under testing and minimize the risk of infection, the sensor interface IC is usually implanted under the skin or skull with wireless transmission. The nature of the neural signal and its recording scenarios impose rigid design specifications to the sensor interface IC, such as low noise, low power, low cut-off frequency and minimum chip size. Many designs have been reported recently to tackle these challenges in neural recording system. In this paper, design techniques for neural recording sensor interface IC will be introduced, including the design of system architecture and neural amplifier. Methods to realize low power, low noise and low cut-off frequency are investigated. In addition, the methods to achieve system power and area optimization are also discussed.Accepted versio

Low power implantable neural recording front-end

Low power smart electronic designs for neural recording applications have recently become a major research topic in circuits and system society. Challenged by the complicated nature of the biology-electronic interface, implantable neural recording circuits must offer high quality signal acquisition while consuming as little power as possible. Furthermore, many applications demand on-chip smart features to maximize energy efficiency as well as to assist the subsequent software-based digital signal processing. This paper reviews the recent advancements in the field, followed by a proposed ultra low-power recording front-end. The proposed design consists of an adjustable gain and bandwidth low-noise amplifier, a bandpass filter, a unity gain buffer and a 9-bit ADC. When simulated using a 0.18 μm/1 V CMOS process, the whole channel consumes only 2.76 μW

A 9.87 nW 1 kS/s 8.7 ENOB SAR ADC for implantable epileptic seizure detection microsystems

This paper presents an ultra low-power SAR ADC in 0.18 μm CMOS technology for epileptic seizure detection applications. The ADC is powered by a single supply voltage of both analog and digital circuits to avoid using the level-shifters. A latched comparator is used to quickly generate the comparison results while consuming no DC current. Split-cap architecture with an attenuation cap is used to minimize area and to further reduce the power consumption. A smaller-than-unit capacitor is used at the end of the least significant bit array to mitigate the negative impact of the parasitic components on the linearity of the capacitors array. As a result, both DNL/INL and SNDR of the ADC is improved. Our post-layout simulation shows that at 1 V supply, 1 kS/s the proposed SAR archives 8.7 ENOB while consuming only 9.87 nW. This yields an FOM of 23.7 fJ/conversion-step. Its leakage power consumption is 1.46 nW

A 160 nW 25 kS/s 9-bit SAR ADC for neural signal recording applications

This paper presents a 9-bit 25 kS/s SAR ADC in 0.18 μm CMOS technology for neural signal recording applications. The ADC is powered by a single supply voltage of 1V to comply with other digital processing units on the same chip. The proposed ADC has one common-mode DC input of 0.5V thus offering a full-range sampling with only one pair of PMOS input transistors in the latched comparator. A versatile digital interface block is implemented to translate external control signals to internally useful Sample-and-Hold (S/H) commands, allowing a flexible S/H duration to match with the driving strength of the input buffer. To realize an ultra low-power performance, all digital blocks and the comparator are carefully optimized. At the same time, split-cap architecture with an attenuation cap is used to minimize area and to further reduce the power consumption. Our simulation shows that the proposed SAR archives 8.5 ENOB while consuming only 160 nW

Conditional Knockout of Hypoxia-Inducible Factor 1-Alpha in Tumor-Infiltrating Neutrophils Protects against Pancreatic Ductal Adenocarcinoma

Large numbers of neutrophils infiltrate tumors and comprise a notable component of the inflammatory tumor microenvironment. While it is established that tumor cells exhibit the Warburg effect for energy production, the contribution of the neutrophil metabolic state to tumorigenesis is unknown. Here, we investigated whether neutrophil infiltration and metabolic status promotes tumor progression in an orthotopic mouse model of pancreatic ductal adenocarcinoma (PDAC). We observed a large increase in the proportion of neutrophils in the blood and tumor upon orthotopic transplantation. Intriguingly, these tumor-infiltrating neutrophils up-regulated glycolytic factors and hypoxia-inducible factor 1-alpha (HIF-1α) expression compared to neutrophils from the bone marrow and blood of the same mouse. This enhanced glycolytic signature was also observed in human PDAC tissue samples. Strikingly, neutrophil-specific deletion of HIF-1α (HIF-1αΔNφ) significantly reduced tumor burden and improved overall survival in orthotopic transplanted mice, by converting the pro-tumorigenic neutrophil phenotype to an anti-tumorigenic phenotype. This outcome was associated with elevated reactive oxygen species production and activated natural killer cells and CD8+ cytotoxic T cells compared to littermate control mice. These data suggest a role for HIF-1α in neutrophil metabolism, which could be exploited as a target for metabolic modulation in cancer