Thermodynamic and Transport Property Correlation Formulas for Equilibrium Air from 1,000 Degrees Kelvin to 15,000 Degrees Kelvin

The thermodynamic properties, density and temperature, as well as transport property parameters involving viscosity, Prandtl number (including diffusion effects), and gaseous radiation absorption coefficients have been correlated as a function of enthalpy at four pressure levels (10 (sup -1), 10 (sup 0), 10, and 10 (sup 2) atmospheres). The correlation formulas are written in a generalized form for which coefficients for a particular property and pressure level are tabulated. The correlation formulas are useful in digital computer programs for non-adiabatic viscous flow problems

Isoprenoid biosynthesis inhibition disrupts Rab5 localization and food vacuolar integrity in Plasmodium falciparum

The antimalarial agent fosmidomycin is a validated inhibitor of the nonmevalonate isoprenoid biosynthesis (methylerythritol 4-phosphate [MEP]) pathway in the malaria parasite, Plasmodium falciparum. Since multiple classes of prenyltransferase inhibitors kill P. falciparum, we hypothesized that protein prenylation was one of the essential functions of this pathway. We found that MEP pathway inhibition with fosmidomycin reduces protein prenylation, confirming that de novo isoprenoid biosynthesis produces the isoprenyl substrates for protein prenylation. One important group of prenylated proteins is small GTPases, such as Rab family members, which mediate cellular vesicular trafficking. We have found that Rab5 proteins dramatically mislocalize upon fosmidomycin treatment, consistent with a loss of protein prenylation. Fosmidomycin treatment caused marked defects in food vacuolar morphology and integrity, consistent with a defect in Rab-mediated vesicular trafficking. These results provide insights to the biological functions of isoprenoids in malaria parasites and may assist the rational selection of secondary agents that will be useful in combination therapy with new isoprenoid biosynthesis inhibitors

Healing Through History: a qualitative evaluation of a social medicine consultation curriculum for internal medicine residents

Background: Social context guides care; stories sustain meaning; neither is routinely prioritized in residency training. Healing Through History (HTH) is a social medicine consultation curriculum integrating social determinants of health narrative into clinical care for medically and socially complex patients. The curriculum is part of an internal medicine (IM) residency outpatient clinical rotation at a Veterans Health Administration hospital. Our aim was to explore how in-depth social medicine consultations may impact resident clinical practice and foster meaning in work. Methods: From 2017 to 2019, 49 categorical and preliminary residents in their first year of IM training were given two half-day sessions to identify and interview a patient; develop a co-produced social medicine narrative; review it with patient and faculty; and share it in the electronic health record (EHR). Medical anthropologists conducted separate 90-min focus groups of first- and second-year IM residents in 2019, 1–15 months from the experience. Results: 46 (94%) completed HTH consultations, of which 40 (87%) were approved by patients and published in the EHR. 12 (46%) categorical IM residents participated in focus groups; 6 PGY1, and 6 PGY2. Qualitative analysis yielded 3 themes: patient connection, insight, and clinical impact; clinical skill development; and structural barriers to the practice of social medicine. Conclusions: HTH offers a model for teaching co-production through social and narrative medicine consultation in complex clinical care, while fostering meaning in work. Integration throughout training may further enhance impact

The Large-scale J=3-2 and J=2-1 CO Emission from M17 and its Implications for Extragalactic CO Observations

We observed a 10x20 pc region of the molecular cloud M17 in the 12CO and 13CO J=3-2 and J=2-1 transitions to determine their global behavior and to assess the reliability of using ratios of CO line intensities integrated over an entire cloud to determine the physical conditions within the cloud. Both the 12CO/13CO J=2-1 and J=3-2 line ratios correlate with the 13CO integrated intensity, with smaller line ratios observed at locations with large integrated intensities. This correlation is likely due to variations in the column density from one position to another within M17. The 12CO and 13CO (J=3-2/J=2-1) line ratios show no significant variation from place to place within M17, even on the peak of the photon-dominated region. A Large Velocity Gradient analysis of globally averaged line ratios gives results in reasonable agreement with the results obtained for individual lines-of-sight through the cloud, which suggests that the typical physical conditions in a molecular cloud can be determined using CO line ratios integrated over the entire cloud. There appears to be a clear trend of increasing 12CO/13CO J=2-1 and J=3-2 line ratios as one moves from Galactic molecular cloud cores to entire Galactic molecular clouds to normal galaxies. The most likely explanation of the high line ratios for normal galaxies is a significant contribution to the CO emission by low column density material, such as diffuse molecular clouds or the outer envelopes of giant molecular clouds.Comment: 26 pages, 6 figures, 2 tables. Accepted for publication in Ap

Successful use of axonal transport for drug delivery by synthetic molecular vehicles

We report the use of axonal transport to achieve intraneural drug delivery. We constructed a novel tripartite complex of an axonal transport facilitator conjugated to a linker molecule bearing up to a hundred reversibly attached drug molecules. The complex efficiently enters nerve terminals after intramuscular or intradermal administration and travels within axonal processes to neuron cell bodies. The tripartite agent provided 100-fold amplification of saturable neural uptake events, delivering multiple drug molecules per complex. _In vivo_, analgesic drug delivery to systemic and to non-targeted neural tissues was greatly reduced compared to existing routes of administration, thus exemplifying the possibility of specific nerve root targeting and effectively increasing the potency of the candidate drug gabapentin 300-fold relative to oral administration

Ex-vivo HRMAS of adult brain tumours: metabolite quantification and assignment of tumour biomarkers

Background: High-resolution magic angle spinning (HRMAS) NMR spectroscopy allows detailed metabolic analysis of whole biopsy samples for investigating tumour biology and tumour classification. Accurate biochemical assignment of small molecule metabolites that are “NMR visible” will improve our interpretation of HRMAS data and the translation of NMR tumour biomarkers to in-vivo studies. Results: 1D and 2D 1H HRMAS NMR was used to determine that 29 small molecule metabolites, along with 8 macromolecule signals, account for the majority of the HRMAS spectrum of the main types of brain tumour(astrocytoma grade II, grade III gliomas, glioblastomas, metastases, meningiomas and also lymphomas). Differences in concentration of 20 of these metabolites were statistically significant between these brain tumour types. During the course of an extended 2D data acquisition the HRMAS technique itself affects sample analysis: glycine, glutathione and glycerophosphocholine all showed small concentration changes; analysis of the sample after HRMAS indicated structural damage that may affect subsequent histopathological analysis. Conclusions: A number of small molecule metabolites have been identified as potential biomarkers of tumour type that may enable development of more selective in-vivo 1H NMR acquisition methods for diagnosis and prognosis of brain tumours

There is no association between the omega-3 index and depressive symptoms in patients with heart disease who are low fish consumers

Background: Long chain Omega-3 polyunsaturated fatty acids (LCn3PUFAs) may improve cardiovascular health and depression. This study investigated the relationships between erythrocyte membrane LCn3PUFA status, depression and angina symptoms in patients with heart disease.  Methods: We recruited 91 patients (65 males and 26 females, mean age 59.2 ± 10.3 years) with heart disease and depressive symptoms (Center for Epidemiological Studies Depression Scale, CES-D ≥ 16) and low fish/fish oil intakes. The Omega-3 Index (EPA+DHA) of erythrocyte membranes (as a percentage of total fatty acids) was assessed by gas chromatography. Depression status was measured by both self-report and clinician-report scales; CES-D and the Hamilton depression scale (HAM-D). Angina symptoms were measured using the Seattle Angina Questionnaire and the Canadian Cardiovascular Society Classification for Angina Pectoris.  Results: The mean Omega-3 Index was 4.8 ± 1.0% (±SD). Depression scores measured by CES-D and HAM-D were 29.2 ± 8.8 (moderate to severe) and 11.0 ± 5.7 (mild) (arbitrary units) respectively reflecting a different perception of depressive symptoms between patients and clinicians. Angina status was inversely associated with depression scores (r > -0.26, P < 0.03). There were no significant relationships between individual LCn3PUFA or the Omega-3 Index and either the depression scores or the angina symptoms.  Conclusion: Worse angina status was associated with worse depression, but the Omega-3 Index was not associated with symptoms of depression or angina in patients with heart disease

Book Reviews

Reviews of the following books: Mainers in the Civil War by Harry Gratwick; The 22nd Maine Volunteer Infantry in the Civil War: A History and Roster by Ned Smith; Write Quick: War and a Woman\u27s Life in Letters 1835-1867 Edited by Ann Fox Chandonnet and Robert Gibson Pevear; Civil War Senator: William Pitt Fessenden and the Fight to Save the American Republic by Robert J. Cook; Lincoln\u27s Friend: Leonard Swett by Robert S. Eckley; We Are in His Hands Whether We Live or Die: The Letters of Brevet Brigadier General Charles Henry Howard edited by David K. Thomson; Fanny & Joshua: The Enigmatic Lives of Frances Caroline Adams and Joshua Lawrence Chamberlain by Diane Monroe Smith; This Birth Place of Souls:The Civil War Nursing Diary of Harriet Eaton edited with an Introduction by Jane E. Schultz; Army at Home: Women and the Civil War on the Northern Home Front by Judith Giesberg; A Visitation of God: Northern Civilians Interpret the Civil War by Sean A. Scott; Freedom National: The Destruction of Slavery in the United States, 1861-1865 by James Oakes; War Upon the Land: Military Strategy and the Transformation of Southern Landscapes during the American Civil War by Lisa M. Brady; Remembering the Civil War: Reunion and the Limits of Reconciliation by Caroline E. Janne

Classification of brain tumours from MR spectra: the INTERPRET collaboration and its outcomes.

The INTERPRET project was a multicentre European collaboration, carried out from 2000 to 2002, which developed a decision-support system (DSS) for helping neuroradiologists with no experience of MRS to utilize spectroscopic data for the diagnosis and grading of human brain tumours. INTERPRET gathered a large collection of MR spectra of brain tumours and pseudo-tumoural lesions from seven centres. Consensus acquisition protocols, a standard processing pipeline and strict methods for quality control of the aquired data were put in place. Particular emphasis was placed on ensuring the diagnostic certainty of each case, for which all cases were evaluated by a clinical data validation committee. One outcome of the project is a database of 304 fully validated spectra from brain tumours, pseudotumoural lesions and normal brains, along with their associated images and clinical data, which remains available to the scientific and medical community. The second is the INTERPRET DSS, which has continued to be developed and clinically evaluated since the project ended. We also review here the results of the post-INTERPRET period. We evaluate the results of the studies with the INTERPRET database by other consortia or research groups. A summary of the clinical evaluations that have been performed on the post-INTERPRET DSS versions is also presented. Several have shown that diagnostic certainty can be improved for certain tumour types when the INTERPRET DSS is used in conjunction with conventional radiological image interpretation. About 30 papers concerned with the INTERPRET single-voxel dataset have so far been published. We discuss stengths and weaknesses of the DSS and the lessons learned. Finally we speculate on how the INTERPRET concept might be carried into the future.Funding from project MARESCAN (SAF2011-23870) from Ministerio de Economia y Competitividad in Spain. This work was also partially funded by CIBER-BBN, which is an initiative of the VI National R&D&i Plan 2008-2011, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. JRG acknowledges support from Cancer Research UK, the University of Cambridge and Hutchison Whampoa Ltd.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/nbm.343

Pea3 Transcription Factors and Wnt1-Induced Mouse Mammary Neoplasia

The role of the PEA3 subfamily of Ets transcription factors in breast neoplasia is controversial. Although overexpression of PEA3 (E1AF/ETV4), and of the related factors ERM (ETV5) and ER81 (ETV1), have been observed in human and mouse breast tumors, PEA3 factors have also been ascribed a tumor suppressor function. Here, we utilized the MMTV/Wnt1 mouse strain to further interrogate the role of PEA3 transcription factors in mammary tumorigenesis based on our previous observation that Pea3 is highly expressed in MMTV/Wnt1 mammary tumors. Pea3 expression in mouse mammary tissues was visualized using a Pea3NLSlacZ reporter strain. In normal mammary glands, Pea3 expression is predominantly confined to myoepithelial cells. Wnt1 transgene expression induced marked amplification of this cell compartment in nontumorous mammary glands, accompanied by an apparent increase in Pea3 expression. The pattern of Pea3 expression in MMTV/Wnt1 mammary glands recapitulated the cellular profile of activated β-catenin/TCF signaling, which was visualized using both β-catenin immunohistochemistry and the β-catenin/TCF-responsive reporter Axin2NLSlacZ. To test the requirement for PEA3 factors in Wnt1-induced tumorigenesis, we employed a mammary-targeted dominant negative PEA3 transgene, ΔNPEA3En. Expression of ΔNPEA3En delayed early-onset tumor formation in MMTV/Wnt1 virgin females (P = 0.03), suggesting a requirement for PEA3 factor function for Wnt1-driven tumor formation. Consistent with this observation, expression of the ΔNPEA3En transgene was profoundly reduced in mammary tumors compared to nontumorous mammary glands from bigenic MMTV/Wnt1, MMTV/ΔNPEA3En mice (P = 0.01). Our data provide the first description of Wnt1-mediated expansion of the Pea3-expressing myoepithelial compartment in nontumorous mammary glands. Consistent with this observation, mammary myoepithelium was selectively responsive to Wnt1. Together these data suggest the MMTV/Wnt1 strain as a potential model of basal breast cancer. Furthermore, this study provides evidence for a protumorigenic role of PEA3 factors in breast neoplasia, and supports targeting the PEA3 transcription factor family in breast cancer