Indigenous Philosophy in the Valley of Mexico

This study has been undertaken in the hope of helping to open new avenues of research in both philosophy and anthropology, avenues that have heretofore been largely overlooked. It has used as an example the pre-Conquest culture-complex of the Valley of Mexico. It is not intended to be an exhaustive exposition of every aspect of that complex, for that would take it out of the realm of philosophy and too far into that of anthropology. It is rather an examination of the salient features of Aztec culture in a philosophical light. It begins with a discussion of primitive philosophy in general based on the thesis that philosophy is a universal activity of man\u27s mind rather than a given product of it. The remainder of the study is largely an attempt to show that the indigenous peoples of the Valley of Mexico were all well beyond the primitive not only in their material culture but in philosophical thought as well

LAPAS: A SiGe Front End Prototype for the Upgraded ATLAS LAr Calorimeter

We have designed and fabricated a very low noise preamplifier and shaper to replace the existing ATLAS Liquid Argon readout for use at the Large Hadron Collider upgrade (sLHC). IBM’s 8WL 130nm SiGe process was chosen for it’s radiation tolerance, low noise bipolar NPN devices, wide voltage rand and potential use in other sLHC detector subsystems. Although the requirements for the final design can not be set at this time, the prototype was designed to accommodate a 16 bit dynamic range. This was accomplished by using a single stage, low noise, wide dynamic range preamp followed by a dual range shaper. The low noise of the preamp is made possible by the low base spreading resistance of the Silicon Germanium NPN bipolar transistors. The relatively high voltage rating of the NPN transistors is exploited to allow a gain of 650V/A in the preamplifier which eases the input voltage noise requirement on the shaper. Each shaper stage is designed as a cascaded differential operational amplifier doublet with a common mode operating point regulated by an internal feedback loop. Measurement of the fabricated circuits indicates their performance is consistent with the desig

A 64-pixel Positron-Sensitive Surgical Probe

We report on the continued development of a 64-pixel positron-sensitive surgical probe with a dual-layer detector and multi-anode PMT. An 8 x 8 array of this plastic scintillators in teh first layer detects positrons and a matched GSO crystal array in the second layer detects annihilation 511 keV gammas, which are required to be in coincidence with the detected positrons. Also, the 64 PMT anode signals are differentiated and an overshoot threshold is applied to separate the fast decay plastic anode signals from the slower GSO signals. Finally, an energy threshold is applied to the summed anode signal to distinguish 511 keV gammas from the 140 keV gammas commonly used in sentinel lymph node (SLN) surgery. Previously we reported on how these signal selection criteria were individually tested and optimized based on 9 channels of prototype electronics [1-2]. Currently the electronics shave been upgraded to Xilinx® programmable components, allowing on-the-fly alteration of signal selection criteria, and all 64 channels are operational. Initial measurements of the complete 64-pixel probe were conducted using 18F-FDG positron sources and 18F-FDG and 99mTcphantoms (background 511 keV and 140 keV gammas), simulating lesions in the SLN surgery environment. The average positron sensitivity is measured to be 3.0-7.0 kcps/µCi at different signal selection criteria. The lower bound on sensitivity corresponds to settings optimized for high image resolution and high background rejection ability. The upper bound on sensitivity corresponds to settings optimized for high sensitivity at the cost of lower image resolution and lower background rejection ability. The measured true-to-background contrast in the presence of clinically observed levels of 511 keV and 140 keV background gammas is ~3:1 for a tumor-to-background uptake ratio of 5:1. Performance measurements of the complete 64-pixel probe including sensitivity, true-to-background ratio, and the pixel separation ability are presented

Noise Spectral Density Measurements of a Radiation Hardened CMOS Process in the Weak and Moderate Inversion

We have measured the noise of MOS transistors of the United Technology Microelectronics Center (UTMC) 1.2 µm radiation hardened CMOS P-well process from the weak to moderate inversion region. The noise power spectral densities of both NMOS and PMOS devices were measured from 1 KHz to 50 MHz. The bandwidth was chosen such that the important components of the spectral densities such as the white thermal noise and the l/f noise could be easily resolved and analyzed in detail. The effects of different device terminal DC biases and channel geometries on the noise are described

Performance of the ABCN-25 readout chip for the ATLAS Inner Detector Upgrade

We present the test results of the ABCN-25 front end chip implemented in CMOS 0.25 μm technology and optimised for the short, 2.5 cm, silicon strips intended to be used in the upgrade of the ATLAS Inner Detector. We have obtained the full functionality of the readout part, the expected performance of the analogue front-end and the operation of the power control circuits. The performance is evaluated in view of the minimization of the power consumption, as the upgrade detector may contain up to 70 million of channels. System tests with different power distribution schemes proposed for the future tracker detectors are possible with this chip. The ABCN-25 ASIC is now serving as the prototype readout chip in the developments of the modules and staves for the upgrade of the ATLAS Inner Detector

LAPAS: A SiGe Front End Prototype for the Upgraded ATLAS LAr

We have designed and fabricated a very low noise preamplifier and shaper with a (RC)2 – CR response to replace the existing ATLAS Liquid Argon readout for use at SLHC. IBM’s 8WL 130nm SiGe process was chosen for its radiation tolerance wide voltage range and potential for use in other LHC detector subsystems. The required dynamic range of 15 bits is accomplished by utilization of a single stage, low noise, wide dynamic range preamp connected to a dual range shaper. The low noise of the preamp (~.01nA / √Hz) is achieved by utilizing the process Silicon Germanium bipolar transistors. The relatively high voltage rating of the npn transistors is exploited to allow a gain of 650V/A. With this gain the equivalent input voltage noise requirement on the shaper to about 2.2nV/ √Hz. Each shaper stage is designed as a cascaded differential op amp doublet with a common mode operating point regulated by an internal feedback loop. The shaper outputs are designed to be compatible with the 130nm CMOS ADC being developed in parallel with this effort. Preliminary measurement of the fabricated circuits indicates their performance is consistent with the design specifications

Cytotoxic sigma-2 ligands trigger cancer cell death via cholesterol-induced-ER-stress

Sigma-2-ligands (S2L) are characterized by high binding affinities to their cognate sigma-2 receptor, overexpressed in rapidly proliferating tumor cells. As such, S2L were developed as imaging probes (ISO1) or as cancer therapeutics, alone (SV119 [C6], SW43 [C10]) and as delivery vehicles for cytotoxic drug cargoes (C6-Erastin, C10-SMAC). However, the exact mechanism of S2L-induced cytotoxicity remains to be fully elucidated. A series of high-affinity S2L were evaluated regarding their cytotoxicity profiles across cancer cell lines. While C6 and C10 displayed distinct cytotoxicities, C0 and ISO1 were essentially non-toxic. Confocal microscopy and lipidomics analysis in cellular and mouse models revealed that C10 induced increases in intralysosomal free cholesterol and in cholesterol esters, suggestive of unaltered intracellular cholesterol trafficking. Cytotoxicity was caused by cholesterol excess, a phenomenon that contrasts the effects of NPC1 inhibition. RNA-sequencing revealed gene clusters involved in cholesterol homeostasis and ER stress response exclusively by cytotoxic S2L. ER stress markers were confirmed by qPCR and their targeted modulation inhibited or enhanced cytotoxicity of C10 in a predicted manner. Moreover, C10 increased sterol regulatory element-binding protein 2 (SREBP2) and low-density lipoprotein receptor (LDLR), both found to be pro-survival factors activated by ER stress. Furthermore, inhibition of downstream processes of the adaptive response to S2L with simvastatin resulted in synergistic treatment outcomes in combination with C10. Of note, the S2L conjugates retained the ER stress response of the parental ligands, indicative of cholesterol homeostasis being involved in the overall cytotoxicity of the drug conjugates. Based on these findings, we conclude that S2L-mediated cell death is due to free cholesterol accumulation that leads to ER stress. Consequently, the cytotoxic profiles of S2L drug conjugates are proposed to be enhanced via concurrent ER stress inducers or simvastatin, strategies that could be instrumental on the path toward tumor eradication