Quantitative multiplex immunohistochemistry reveals inter-patient lymphovascular and immune heterogeneity in primary cutaneous melanoma

IntroductionQuantitative, multiplexed imaging is revealing complex spatial relationships between phenotypically diverse tumor infiltrating leukocyte populations and their prognostic implications. The underlying mechanisms and tissue structures that determine leukocyte distribution within and around tumor nests, however, remain poorly understood. While presumed players in metastatic dissemination, new preclinical data demonstrates that blood and lymphatic vessels (lymphovasculature) also dictate leukocyte trafficking within tumor microenvironments and thereby impact anti-tumor immunity. Here we interrogate these relationships in primary human cutaneous melanoma. MethodsWe established a quantitative, multiplexed imaging platform to simultaneously detect immune infiltrates and tumor-associated vessels in formalin-fixed paraffin embedded patient samples. We performed a discovery, retrospective analysis of 28 treatment-naïve, primary cutaneous melanomas. ResultsHere we find that the lymphvasculature and immune infiltrate is heterogenous across patients in treatment naïve, primary melanoma. We categorized five lymphovascular subtypes that differ by functionality and morphology and mapped their localization in and around primary tumors. Interestingly, the localization of specific vessel subtypes, but not overall vessel density, significantly associated with the presence of lymphoid aggregates, regional progression, and intratumoral T cell infiltrates. DiscussionWe describe a quantitative platform to enable simultaneous lymphovascular and immune infiltrate analysis and map their spatial relationships in primary melanoma. Our data indicate that tumor-associated vessels exist in different states and that their localization may determine potential for metastasis or immune infiltration. This platform will support future efforts to map tumor-associated lymphovascular evolution across stage, assess its prognostic value, and stratify patients for adjuvant therapy

Simultaneous gas density and fuel concentration measurements in a supersonic combustor using laser induced breakdown

Laser-induced breakdown is used for quantitative gas property measurements (gas density and ethylene fuel concentration) in a cavity flameholder in a supersonic crossflow. A plasma is produced by a focused laser beam (Nd:YAG, 532 nm) in the cavity to measure gas properties at the location of the plasma and to ignite cavity flames. Plasma energy (PE), defined by the laser pulse energy absorbed/scattered in the plasma, and plasma emission spectra are recorded for estimating gas density and species concentration, respectively. To obtain correlations of PE vs. gas density and emission spectra vs. fuel concentration, calibration experiments are conducted using a variable-pressure (0–900 mbar)/temperature (300–900 K) chamber and a Hencken burner installed in a variable-pressure (50–900 mbar) combustion chamber. Total measurement time is sufficiently short, ~80 ns after laser arrival at the plasma region, to capture the high intensity portion of the emission and to minimize effects of plasma displacement (in the high-speed flow). Specifically, the laser pulse energy incident and transmitted (through the plasma) are measured, and the plasma emission spectra are captured during a 50-ns gate, after an approximate 30-ns time delay (relative to onset of emission from the plasma volume) to avoid strong background emission from the plasma

A 64 Gb/s 2.09 pJ/b PAM-4 VCSEL Transmitter with Bandwidth Extension Techniques in 40 nm CMOS

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Combustion and Flame 153 (2008) 603-615 Optimal discharge placement in plasma-assisted combustion of a methane jet in cross flow

Abstract Repetitively pulsed, nonequilibrium plasma discharges are studied for their ability to ignite and stabilize methane jet flames in cross flow air. The placement of the discharge is surveyed to optimize the flame duty cycle (stability). We find that flame ignition is not achieved when the discharge is located in the potential core region of the fuel jet or on the windward side of the most upstream part of the near field of the jet. A low (but nonzero) duty cycle is seen when the discharge is placed on the leeward side of the upstream near-field region. A high duty cycle (up to unity) is seen for discharge placement on both the leeward and windward sides of the downstream part of the near field. These results confirm that the effectiveness of the nonequilibrium discharge in stabilizing this flame depends on its placement in the complex scalar and velocity field. The mixture fraction at the discharge placement is characterized by plasma-induced breakdown spectroscopy (PIBS). The ratio of emission intensity of the CN band at 388 nm to the N 2 band at 337 nm is used to map the local equivalence ratio in the flow. We find that the methane mixture fraction at optimal discharge placements is lower than that where the flame resides in non-discharge-stabilized diffusion flames and is equal to that found in plasma-assisted methane jets in coflow air. Planar laser-induced fluorescence (PLIF) imaging of CH radicals is carried out to qualitatively understand the structure of the ignition flame kernel. The plasma discharge and flame base are spatially separated, suggesting that the discharge is a steady supplier of reactive species but not an instantaneous flame ignition source

4-Channel Push-Pull VCSEL Drivers for HDMI Active Optical Cable in 0.18-mu m CMOS

The price and power consumption of standard HDMI cables exponentially rise when the data rate increases or cable runs longer. HDMI active optical cable (AOC) can potentially solve price and power issues since fibers are tolerant to loss. However, additional optical components such as vertical-cavity surface-emitting laser (VCSEL) and photodiode (PD) are required. Therefore, drivers and transimpedance amplifiers should be designed carefully for normal operations. In this paper, two types of 4-channel VCSEL drivers for HDMI AOC are presented. The first type of the driver passes data and bias separately. It uses off-chip capacitors for AC coupling. On the other hand, the second type of the driver passes data including DC value without using off-chip capacitors. Structures of the both drivers are based on push-pull current-mode logic (CML) to achieve better power efficiency. Drivers fabricated in 0.18-mu m CMOS process consume 36.5 mW/channel at 6 Gb/s and 24.7 mW/channel at 12 Gb/s, respectively.N

A 64Gb/s 2.29pJ/b PAM-4 VCSEL Transmitter With 3-Tap Asymmetric FFE in 65nm CMOS

This paper presents a 64Gb/s, 2.29pJ/b PAM-4 optical transmitter (TX) utilizing a VCSEL. To improve the power efficiency, the TX adopts a quarter-rate architecture consisting of a quadrature clock generator and a 4:1 MUX. By employing an asymmetric push-pull FFE, high-speed PAM-4 signaling based on a VCSEL can be achieved. It is fabricated in a 65nm CMOS technology, occupying an active area of 0.278mm(2).N