The Role of the Corn Products Doctrine in Foreign Exchange Transactions

Exchange rate gain or loss may result from fluctuations of exchange rates or from formal governmental action such as revaluation and devaluation. In evaluating the significance of foreign exchange transactions and their tax consequences, the types of transactions that produce exchange rate gain or loss must be distinguished. The first type of transaction is currency speculation in which exchange rate gain or loss is the only profit or loss realized. The second type of transaction involves the purchase and sale of inventory in which the exchange rate gain or loss is ancillary to the monetary gain or loss realized on the underlying commercial transaction. The last type is credit transactions involving the borrowing and repayment of foreign currency, which may produce exchange rate gain or loss on the closing of the transaction with currency purchased at a higher or lower exchange rate than at the time the transaction originated. The significant question raised by these foreign exchange transactions is the type of tax treatment to be accorded to the gains and losses realized. Do the gains or losses qualify for ordinary income or loss status or do they qualify for long or short term capital treatment? The answer to this question depends upon several factors including the type of foreign exchange transaction involved, the party\u27s intent, and the status of the individual or corporation undertaking the transaction. The objective of this paper is to examine the tax consequences of foreign exchange transactions and the role played by the Corn Products doctrine in limiting long term capital gains treatment for such transactions

Niche Markets

Is evolutionary theory is incomplete and are we failing to understand phenomena as disparate as ecosystem development and the interplay of genes and culture in shaping human evolution

Simplified and Highly-Reliable Automated Production of [8F]FSPG for Clinical Studies

Background: (S)-4-(3-18F-Fluoropropyl)-L-Glutamic Acid ([18F]FSPG) is a positron emission tomography (PET) tracer that specifically targets the cystine/glutamate antiporter (xc-), which is frequently overexpressed in cancer and several neurological disorders. Pilot studies examining the dosimetry and biodistribution of [18F]FSPG in healthy volunteers and tumor detection in patients with non-small cell lung cancer, hepatocellular carcinoma, and brain tumors showed promising results. In particular, low background uptake in the brain, lung, liver, and bowel was observed that further leads to excellent imaging contrasts of [18F]FSPG PET. However, reliable production-scale cGMP-compliant automated procedures for [18F]FSPG production are still lacking to further increase the utility and clinical adoption of this radiotracer. Herein, we report the optimized automated approaches to produce [18F]FSPG through two commercially available radiosynthesizers capable of supporting centralized and large-scale production for clinical use. Results: Starting with activity levels of 60-85 GBq, the fully-automated process to produce [18F]FSPG took less than 45 min with average radiochemical yields of 22.56 ± 0.97% and 30.82 ± 1.60% (non-decay corrected) using TRACERlab™ FXFN and FASTlab™, respectively. The radiochemical purities were \u3e 95% and the formulated [18F]FSPG solution was determined to be sterile and colorless with the pH of 6.5-7.5. No radiolysis of the product was observed up to 8 h after final batch formulation. Conclusions: In summary, cGMP-compliant radiosyntheses and quality control of [18F]FSPG have been established on two commercially available synthesizers leveraging high activity concentration and radiochemical purity. While the clinical trials using [18F]FSPG PET are currently underway, the automated approaches reported herein will accelerate the clinical adoption of this radiotracer and warrant centralized and large-scale production of [18F]FSPG

evoText: A new tool for analyzing the biological sciences

We introduce here evoText, a new tool for automated analysis of the literature in the biological sciences. evoText contains a database of hundreds of thousands of journal articles and an array of analysis tools for generating quantitative data on the nature and history of life science, especially ecology and evolutionary biology. This article describes the features of evoText, presents a variety of examples of the kinds of analyses that evoText can run, and offers a brief tutorial describing how to use it

cGMP Compliant One-Step, One-Pot Automated [18F]FBnTP Production for Clinical Imaging of Mitochondrial Activity

Background 4-[18F]fluorobenzyl-triphenylphosphonium ([18F]FBnTP) is a lipophilic cation PET tracer. The cellular uptake of [18F]FBnTP is correlated with oxidative phosphorylation by mitochondria, which has been associated with multiple critical diseases. To date, [18F]FBnTP has been successfully applied for imaging myocardial perfusion, assessment of severity of coronary artery stenosis, delineation of the ischemic area after transient coronary occlusion, and detection/quantification of apoptosis in various animal models. Recent preclinical and clinical studies have also expanded the possibilities of using [18F]FBnTP in oncological diagnosis and therapeutic monitoring. However, [18F]FBnTP is typically prepared through a tediously lengthy four-step, three-pot reaction and required multiple synthesizer modules; Thus, such an approach remains a challenge for this promising radiopharmaceutical to be implemented for routine clinical studies. Herein, we report an optimized one-step, one-pot automated approach to produce [18F]FBnTP through a single standard commercially-available radiosynthesizer that enables centralized production for clinical use. Results The fully automated production of [18F]FBnTP took less than 55 min with radiochemical yields ranging from 28.33 ± 13.92% (non-decay corrected), apparent molar activity of 69.23 ± 45.62 GBq/µmol, and radiochemical purities of 99.79 ± 0.41%. The formulated [18F]FBnTP solution was determined to be sterile and colorless with a pH of 4.0–6.0. Our data has indicated no observable radiolysis after 8 h from the time of final product formulation and maximum assay of 7.88 GBq. Conclusions A simplified and cGMP-compliant radiosynthesis of [18F]FBnTP has been established on the commercially available synthesizer in high activity concentration and radiochemical purity. While the preclinical and clinical studies using [18F]FBnTP PET are currently underway, the automated approaches reported herein facilitate clinical adoption of this radiotracer and warrant centralized production of [18F]FBnTP for imaging multiple patients

Assessment of Mucin 13 (MUC13) as an Imaging Target for Guiding Colorectal Cancer Treatment: A Pathway Towards Theranostic Development

Background: A theranostic strategy combining diagnostic imaging and targeted therapy in a single regimen is proposed for improved management and treatment of colorectal cancer (CRC). Increased specificity in detection by the noninvasive imaging technique positron emission tomography (PET) can be achieved by radiolabeling antibodies (Abs) designed to target tumor-associated antigens with increased expression post-translational modifications present in cancer cells. In this study, an Ab designed to target the transmembrane glycoprotein mucin 13 (MUC13) was radiolabeled with the positron-emitting radionuclide zirconium-89 (89Zr) for PET imaging of a xenograft mouse model of CRC. Specified uptake of this radioimmunoconjugate was observed in the presence of increased MUC13 expression was observed through imaging along with in vitro and ex vivo analyses. Methods: Radiochemistry: The MUC13-targeting Ab C14 conjugated with desferrioxamine (DFO) was radiolabeled with 89Zr alongside isotype control Ab MOPC-21 (IgG) at a 59 kBq/µg (1.6 µCi/µg) ratio, producing [89Zr]Zr-DFO-C14 and [89Zr]Zr-DFO-IgG. Radiochemical purity (RCP) was determined using radio-iTLC and radio-SEC. Radiochemical yield (RCY) was determined with a well-type dose calibrator. Cellular Binding and Internalization: Cultured human CRC cell lines T84 (MUC13+) and SW480 (MUC13-) were incubated with either [89Zr]Zr-DFO-C14 or [89Zr]Zr-DFO-IgG. At 2 and 24h, cell membranes were separated and radioactivity measured to compare membrane-bound and cell-internalized activity. To determine binding specificity of radiolabeled C14, cells were co-incubated with excess unmodified Ab. µPET/CT Imaging: T84 and SW480 cells were introduced subcutaneously in athymic nude mice. Once palpable tumors were detected, mice were placed in the following treatment groups for 1.9 MBq (50 µCi) injection: T84+[89Zr]Zr-DFO-C14 (n=5), T84+[89Zr]Zr-DFO-C14 with 350 µg C14 (n=2), SW480+[89Zr]Zr-DFO-C14 (n=5), and T84+[89Zr]Zr-DFO-IgG (n=4). PET imaging was performed 24, 48, and 120h post-injection (p.i.) alongside computational tomography (CT) imaging to provide anatomical context. After 120h, mice were euthanized and blood, organs, and tissues were collected to measure radioactivity biodistribution and radioimmunoconjugate distribution in tumor tissue. Results: Radiolabeled C14 and IgG were successfully produced with RCY\u3e83% (n.d.c.) and RCP\u3e95%. Reflecting rapid internalization observed in vitro (57.9±13% [89Zr]Zr-DFO-C14 uptake in T84 at 2h compared to 6.57±0.6% uptake in SW480 (p89Zr]Zr-DFO-IgG uptake (p89Zr]Zr-DFO-C14 at 24h p.i. through 120h p.i. compared to that measured in SW480 xenografts (5.5±0.7% ID/cc vs. 2.8±0.5% ID/cc at 24h p.i., p89Zr]Zr-DFO-IgG (1.9±0.2% ID/cc at 24h p.i., p89Zr]Zr-DFO-C14 within the tumor. Furthermore, co-injection with excess C14 resulted in reduced PET signal (2.7±0.1% ID/cc, p=0.0002), supporting the targeting specificity of [89Zr]Zr-DFO-C14. Ex vivo biodistribution comparison confirmed high, persistent [89Zr]Zr-DFO-C14 uptake in T84-derived tumor (18.5% ID/g at 120h p.i.). Conclusion: MUC13 expression was clearly represented by PET/CT imaging in a xenograft mouse model of CRC using a 89Zr-labeled MUC13-targeting Ab, which also demonstrated target specificity both in vitro and ex vivo. These promising results justify further exploration into developing a theranostic platform for CRC treatment. Future work will test the therapeutic efficacy of the MUC13-targeting Ab radiolabeled with a beta particle-emitting radionuclide

Feasibility of [18F]FSPG PET for Early Response Assessment to Combined Blockade of EGFR and Glutamine Metabolism in Wild-Type KRAS Colorectal Cancer

Early response assessment is critical for personalizing cancer therapy. Emerging therapeutic regimens with encouraging results in the wild-type (WT) KRAS colorectal cancer (CRC) setting include inhibitors of epidermal growth factor receptor (EGFR) and glutaminolysis. Towards predicting clinical outcome, this preclinical study evaluated non-invasive positron emission tomography (PET) with (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) in treatment-sensitive and treatment-resistant WT KRAS CRC patient-derived xenografts (PDXs). Tumor-bearing mice were imaged with [18F]FSPG PET before and one week following the initiation of treatment with either EGFR-targeted monoclonal antibody (mAb) therapy, glutaminase inhibitor therapy, or the combination. Imaging was correlated with tumor volume and histology. In PDX that responded to therapy, [18F]FSPG PET was significantly decreased from baseline at 1-week post-therapy, prior to changes in tumor volume. In contrast, [18F]FSPG PET was not decreased in non-responding PDX. These data suggest that [18F]FSPG PET may serve as an early metric of response to EGFR and glutaminase inhibition in the WT KRAS CRC setting

Binding of NIR-conPK and NIR-6T to Astrocytomas and Microglial Cells: Evidence for a Protein Related to TSPO

PK 11195 and DAA1106 bind with high-affinity to the translocator protein (TSPO, formerly known as the peripheral benzodiazepine receptor). TSPO expression in glial cells increases in response to cytokines and pathological stimuli. Accordingly, [11C]-PK 11195 and [11C]-DAA1106 are recognized molecular imaging (MI) agents capable of monitoring changes in TSPO expression occurring in vivo and in response to various neuropathologies

Isotopes of nitrogen on Mars: Atmospheric measurements by Curiosity's mass spectrometer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102173/1/wong_readme.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102173/2/wong2013_SM_v4b.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102173/3/grl51166.pd

Primordial argon isotope fractionation in the atmosphere of Mars measured by the SAM instrument on Curiosity and implications for atmospheric loss

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102170/1/grl51048.pd