cssi/SciSciGPT-SciSciNet huggingface dataset:
Peripubertal estrogen levels and physical activity affect femur geometry in young adult women

Summary The growing skeleton is particularly responsive to exercise around the time of puberty, suggesting a possible role for estrogen in mechanical adaptation in young women. We assessed femoral neck strength index at age 17 in young women with varying adolescent physical activity levels and E2 levels in the first 3 years after menarche. The results indicate that both E2 levels in the first year after menarche and adolescent physical activity are positively associated with bone strength in young adulthood, such that hormone levels may modify human osteogenic responses to exercise. Introduction It is well established that physical activity contributes to bone strength in young females, but less is known about how peripubertal estrogen affects skeletal responses to exercise. Methods We used data from 84 participants in the Penn State Young Women's Health Study to test the prediction that young women who (1) had higher E2 levels during the first year after menarche or (2) were more physically active in adolescence will have greater bone strength at the end of adolescence. Subjects were divided into tertiles of physical activity and of E2 level in the first, second, and third postmenarchal years, and femoral strength was calculated from dual-energy X-ray absorptiometry scans of the proximal femur using hip structure analysis. Results At age 17, subjects with the highest E2 levels in year1 after menarche had 5-14% greater strength in the narrow neck and intertrochanteric region, and the most active subjects had 10-11% greater strength in the femoral narrow neck vs. less active girls. Conclusions This study suggests that both physical activity and peripubertal estrogen have important influences on young adult bone strength and that hormone levels may be mediators of human osteogenic responses to exercise.
A study of mitochondrial membranes in relation to elementary particles.

Elementary particles that commonly have been seen by electron microscopy to be attached by stalks to mitochondrial cristae in negatively stained preparations, were not apparent in similarly stained mitochondria from exponentially growing wild-type Neurospora crassa when these were isolated in sucrose solution containing 1 x 10^-3 M EDTA. However, elementary particles were easily demonstrable in electron micrographs if the mitochondria were isolated without EDTA in the sucrose solution. A biochemical study indicated that both kinds of mitochondrial preparations, isolated in the presence or absence of EDTA, had about the same capacity for oxidative phosphorylation. Observations on rat-liver mitochondria also suggested that the stalked elementary particles were more easily demonstrated if the preparation was made in the absence of EDTA. It was difficult to demonstrate elementary particles in wild-type Neurospora mitochondria isolated with or without EDTA and subsequently prepared for electron microscopy by spreading on the surface of an aqueous solution of potassium phosphotungstate. Elementary particles could be demonstrated in poky Neurospora mitochondria isolated with EDTA if the mitochondria were spread on the surface of an aqueous solution of phosphotungstate. It was concluded that biochemical functions associated with elementary particles are independent of structural configuration as seen by electron microscopy.
Computer-Guided Orbital Reconstruction to Improve Outcomes

Objectives (1) To describe repair of complex orbital fractures using computer planning with preoperative virtual reconstruction, mirror image overlay, endoscopy, and surgical navigation. (2) To tes...
Mapping multi-dimensional signals into hierarchical memory organizations

The storage requirements of the array-dominated and loop-organized algorithmic specifications running on embedded systems can be significant. Employing a data memory space much larger than needed has negative consequences on the energy consumption, latency, and chip area. Finding an optimized storage of the usually large arrays from these algorithmic specifications is an important step during memory allocation. This paper proposes an efficient algorithm for mapping multi-dimensional arrays to the data memory. Similarly presented in R. Toncon et al., 2002, it computes bounding windows for live elements in the index space of arrays, but this algorithm is several times faster. Moreover, since this algorithm works not only for entire arrays, but also parts of arrays-like, for instance, array references or, more general, sets of array elements represented by lattices (Schrijver, 1986), this signal-to-memory mapping technique can be also applied in multi-layer memory hierarchies
Updates from the Neuro-Oncology Section of the 2015 American Neurological Association Annual Meeting

American Neurological Association Annual Meeting, Chicago, IL, USA, 27–29 September 2015 The American Neurological Association (ANA) held its annual meeting in Chicago, IL, USA on 27–29 September 2015. The Scientific Programming Advisory Committee was chaired by Dr S Pleasure from the University of California-San Francisco (CA, USA). The Neuro-Oncology session, chaired by Dr A Pruitt from the University of Pennsylvania (PA, USA) and cochaired by Dr J Laterra from Johns Hopkins University (MD, USA), was held on 27 September 2015. Speakers included Dr D Wainwright (Northwestern University, IL, USA), Dr N Kolb (University of Utah, UT, USA), Dr A Nath (NINDS/NIH, MD, USA), Dr D Franz (Cincinnati Children's Hospital, OH, USA) and Dr R Lukas (University of Chicago, IL, USA). A summary of key presentations from the Neuro-Oncology section of the 2015 American Neurological Association annual meeting is reported. Preclinical and clinical advances in the use of immunotherapies for the treatment of primary and metast...
Democracy, Disillusion, and Thresholding

I have presented some symptoms of the unraveling of our age. Positively construed, they herald a growing attempt on the part of individuals to rely more on themselves, a strengthening, thus, of self-reliance. But these symptoms leave many unresolved questions regarding the optimal conditions for and the true nature of self-reliance. They also move us further into the coming Age of Thresholding, for individuality, self-reliance, and thresholding are significantly interconnected, and, at a minimum, this interconnection is undoing coercive formations.
Molecular Dynamics Simulation of Water Mobility in Magnesium-Smectite Hydrates

Water diffusion and interlayer structure in Mg-smectite hydrates was investigated by molecular dynamics and Monte Carlo computer simulation. Smectites with only tetrahedral layer charge (Mg-beidellite) were examined at 300 and 400 K, each with two layers of adsorbed water. Previous quasielastic neutron-scattering experiments have indicated that nonsolvating water molecules in Mg-smectites exhibit faster diffusional motion within a “cage” formed by the solvated Mg(H2O)62+ counterions than they do via inter-cage motion. Our 500−1175 ps MD simulations suggested that the dimension of this “cage” region is approximately 5.5 A, but two-phase diffusional behavior was observed only for water in Mg-beidellite at 300 K. The counterions in Mg-beidellite formed outer-sphere surface complexes with the clay mineral siloxane surface, but nonsolvating water molecules showed a significant tendency to occupy ditrigonal cavities in the surface. This behavior could be responsible for the small equilibrium layer spacing in Mg...
The Economic Family Doesn't Live Here Anymore: Self-Insurance Alternatives for Tax-Exempt Organizations and New Issues

Elizabeth M. Mills, McDermott, Will & Emery, Chicago, in "The Economic Family Doesn't Live Here Anymore: Self-Insurance Alternatives for Tax-Exempt Organizations and New Issues," analyzes the tax and non-tax considerations that nonprofits should take into account when exploring alternatives to the commercial insurance market in financing and managing risk. The article explores the background of nonprofit activity in the insurance market, the mechanisms and theories under which exempt organizations have obtained access to insurance, and the tax treatment of alternative risk management structures.
Comparison of prostate cancer detection at 3-T MRI with and without an endorectal coil: A prospective, paired-patient study.

Abstract Objectives To compare the sensitivity of 2 different non–endorectal coil strategies vs. endorectal coil (ERC) magnetic resonance imaging (MRI) for detection of prostate cancer (PCa). Methods In this prospective, single-center, paired-patient, paired-reader study, 49 men with a clinical indication for MRI underwent non-ERC (phased-array coil only) T2-weighted imaging and diffusion-weighted imaging followed by the same sequences using both ERC and phased-array coils (ERC Protocol). Patients were randomized into 1 of 2 arms: standard non-ERC protocol and augmented non-ERC protocol. Lesions with Likert score≥3 were defined as suspicious for cancer. Radical prostatectomy specimen or combined systematic plus targeted biopsies served as the standard of reference. Cancers were stratified into risk groups according to the National Comprehensive Cancer Network guidelines. Generalized estimating equations with Bonferroni correction were used for comparisons. The level of reader confidence was inferred by the Likert scores assigned to index lesions. Results The ERC protocol provided sensitivity (78%) superior to MRI without ERC for PCa detection, both with a standard (43%) ( P P P = 0.02) and augmented non-ERC MRI (25%), although the latter did not reach significance ( P = 0.09). The ERC improved radiologist confidence for the detection of PCa (average Likert score = 4.2±1.4) compared to standard (2.3±2.3) and augmented (2.9±2.1) non-ERC ( P = 0.001). Conclusions The use of combined ERC and pelvic phased-array coil for T2-weighted imaging and diffusion-weighted imaging provides superior sensitivity for the detection of PCa compared to an examination performed without the ERC.
Assessing girls’ HIV vulnerability: evidence from Botswana, Malawi and Mozambique

Past research documents multiple factors associated with girls' susceptibility to human immunodeficiency virus transmission; yet a literature review found no systematic approach to measure vulnerability. This study characterized, developed and tested a set of indicators to measure girls' vulnerability, resulting in the vulnerable girls index (VGI). A quasi- experimental, separate-sample pre-/post-test design was used to test the index. Adolescent girls were randomly drawn for the pre-test (2277 respondents) and post-test (1418 respondents) from 16 purposively selected communities in Botswana, Malawi and Mozambique. The higher the VGI score-or the more vulnerable the girl-the more likely she was to report premarital sexual experience across the three countries and the more likely she was to report low agency to insist upon condom use in Botswana and Mozambique. The VGI can be used to assess girls' vulnerability levels across time and space for policy and programme planning purposes, and as part of programme evaluations.
Who Says What About Black Women

This chapter serves not only as a review of academic literature but reviews several discourses – including images (see Figure 1) – that have been instrumental in the construction of knowledge regarding Black women’s bodies, psyches, and everyday lives. This review follows a historical trajectory, which begins with “Scientific Discourse” and its role in shaping “Government Discourse”.
Interactivity and the Dimensionality of Data Displays

Using mathematical models of data and displays, we illustrate the importance of distinguishing between independent and dependent variables when counting the dimensions of data sets and displays. The number of independent variables occurring as dimensions of a display model is the most important factor determining its information carrying capacity. Independent variables in a display model also require interactive techniques for their implementation, as illustrated by our VIS-AD system and Beshers’ and Feiner’s worlds within worlds technique. Thus interactivity is critical for visually communicating large amounts of information, and the perceptual properties of interaction techniques are an important topic for visualization research.
The Transnational Excavation of Ancient Egypt and Palestine

Sir Robert Mond’s intellectual and philanthropic interest in archeology predated his extensive support for the Infants’ Hospital. When Mond in the late 1890s spent the winter in Egypt, his interest in Egyptian history was born. From 1902 to his death, Sir Robert Mond figured as one of the most prominent supporters of British Egyptology. But he wanted to be more than just a financier who watched excavations. He desired to be part of it and to engage in archaeological field work. The Egyptologist Percy Newberry wrote in his obituary of Sir Robert Mond: “Ever ready to help in financing explorations in the field, he himself took the keenest pleasure in the actual work of excavating and enjoyed nothing better than being at the bottom of a tomb-shaft, sifting the sand with his own hands in the hope of finding some hidden treasure.”1 His archaeological interest grew with age and extended beyond Egypt. From 1902 to 1938, Sir Robert Mond funded and participated in many archeological excavations in Egypt, Palestine, and France (Fig. 6.1).
Identification of buried lunar impact craters from GRAIL data and implications for the nearside maria

Gravity observations from the dual Gravity Recovery and Interior Laboratory (GRAIL) spacecraft have revealed more than 100 quasi-circular mass anomalies, 26–300 km in diameter, on the lunar nearside. These anomalies are interpreted to be impact craters filled primarily by mare deposits, and their characteristics are consistent with those of impact structures that formed prior to, and during, intervals of flooding of feldspathic terrane by mare basalt lavas. We determine that mare deposits have an average density contrast of 850−200+300 kg m−3 relative to the surrounding crust. The presence of a large population of volcanically buried craters with minimal topographic expression and diameters up to 300 km requires an average nearside mare thickness of at least 1.5 km and local lenses of mare basalt as thick as ~7 km.
Thyrotropin Stimulates Differentiation Not Proliferation of Normal Human Thyrocytes in Culture.

Although TSH has been suggested to be a proliferative agent of thyrocytes, the effect of TSH on human thyroid cells remains controversial. In particular, most of the reported studies relied primarily on changes in DNA synthesis but have not included measurement of the number of cells. We argue that only a direct count of cell number, demonstrating classical exponential expansion, serves as a valid measurement of proliferation. Thus, although some data support TSH as a proliferative agent, most do not provide conclusive evidence. To generate conclusive evidence with regard to a proliferative effect of TSH in human thyrocytes, we performed various experiments using primary cultures of human thyrocytes. In contrast to previous reports, TSH (+IGF-1) did not induce proliferation of thyrocytes under a variety of different conditions. However, TSH/IGF-1 cotreatment did upregulate thyroid-specific gene expression including thyroglobulin (TG) and TSHR in a manner consistent with cellular differentiation. Evidence for a proliferative effect of TSH has been used to inform the American Thyroid Association’s guidelines for the management of thyroid cancer patients, which include TSH suppression. While these recommendations are admittedly based on low to moderate quality evidence, TSH suppression is still widely used. We present data that questions the consensus view that TSH promotes proliferation of human thyrocytes (upon which the American Thyroid Association’s guidelines are based) and suggest that additional studies, including randomized controlled trials, are warranted to address this important clinical question.
Statins Reduce Disease Activity (SLAM-R) and Organ Damage Accrual (SLICC Damage Index, SDI) Scores in SLE Patients From A Multi-Center, Multi-Ethnic, US Cohort.

Abstract Abstract 5066 Purpose Statins, in addition to lower cholesterol levels, have anti-thrombotic, anti-inflammatory and cardiovascular protective effects. Cardiovascular morbidity and accelerated atherosclerosis are important SLE features, but It is unclear whether statins have beneficial effects in these patients. Objectives To assess longitudinally the impact of statins on levels of biomarkers (cytokines/chemokines), SLAM-R and SDI. Methods Sera from 21 SLE patients (ACR criteria) from a multi-ethnic, multi-center cohort were assessed at baseline and at a subsequent visit after statin treatment started. Patients on >10 mg prednisone/day, or on other immunosuppressant were excluded (age range: 16-67; mean age: 44.6 yrs); 38% African American, 9% Caucasians and 4% Puerto Rican Hispanics; 86% female. Serum levels of IL1b, IL6, IL8, IFN- α, IP-10, MCP-1. VEGF, sCD40L and TNF- α, were measured using a Millipore Millliplex™ Multiplex Assay and titers of soluble (s) E-selectin (E-sel), intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), were detected by ELISA. High sensitive C reactive protein (hsCRP) was measured by nephelometry. Changes in the levels of biomarkers were tested using a signed rank test. Changes in levels of biomarkers and those in SLAM-R or SDI scores were examined with Spearman correlations. Results SLAM-R and SDI scores were significantly decreased by statins (p=0.0199 and 0.039, respectively). IL1b, IL6, IL8, TNF-α, VEGF, IP-10, sCD40L and sVCAM-1 levels were reduced after treatment with statins in 28%, 28%, 52%. 43%, 57%, 42%, 52% and 62% of the subjects that had detectable levels of the biomarkers at baseline, respectively, but the overall reduction was not statistically significant (see Table ). hsCRP was increased in 50% of the subjects at baseline (over the cut-off point) and reduced by 37% after treatment with statins. Importantly, the changes in IL-6 after treatment with statins correlated with changes in SLICC scores (p=0.036 Biomarker Median(before treatment) (pg/ml) Median (after treatment) pg/ml IL-1b 0 0 IL-6 7.81 23.9 IL8 32.1 50.7 MCP-1 535.3 602.8 IP-10 209.4 282.5 IFN-α 0 1.92 TNF-α 5.5 7.4 sCD40L 1089.6 583.7 sE-sel 6.3 6.5 sICAM-1 9.6 11.4 sVCAM-1 48.4 39.7 Conclusions Significant number of SLE patients' samples showed a decrease in levels of some cytokines and chemokines and of hsCRP after statin treatment. Importantly, SLAM-R and SDI scores were significantly reduced by statins and the changes in IL-6 correlated with a significant decrease in organ damage accrual (SLICC). Disclosures No relevant conflicts of interest to declare.
Ultrasound during mid-gestation: Agreement with physical foetal and placental measurements and use in predicting gestational age in sheep.

To determine the effects of poor maternal nutrition and litter size on foetal growth during mid-gestation, pregnant ewes (n = 82) were fed 100%, 60% or 140% of NRC TDN beginning at day 30.2 ± 0.2 of gestation. Transabdominal ultrasound was performed weekly between day 46.0 ± 0.4 and 86.0 ± 0.7 to monitor foetal heart width (HW), umbilical diameter (UMB), rib width (RW) and placentome outer (OD) and inner diameter (ID). Data were analysed with repeated-measures using the mixed procedure for effects of maternal diet, litter size and gestation, and equations predictive of gestational age were generated using the regression procedure. To determine the agreement of ultrasound measurement and actual size, ewes (n = 20-21) were euthanized at day 45 or 90 to obtain corresponding postmortem measurements for Bland-Altman analysis. The HW, UMB and placentome OD and ID increased with gestation (p < .0001) but were unaffected by maternal diet or litter size (p ≥ .12). Ultrasound underestimated postmortem measurements of HW (14.8%), UMB (7.3%), placentome OD (4.5%) and ID (37.3%) at day 90 of gestation. Ultrasound underestimated RW at day 45 (7.7%) but overestimated RW (23.8%) at day 90, indicating inconsistent bias when reporting RW by ultrasound. Combining the HW, UMB, RW and placentome OD generated the strongest equation predictive of gestational age (R2 = .91). These findings indicate that during mid-gestation, maternal diet or litter size did not affect HW, UMB or placentome diameters and these factors can be used to estimate gestational age.
Visual Response Properties in the Three Layer Turtle Visual Cortex

Turtle dorsal cortex provides us with unique insights into cortical processing. It is known to share many features with the mammalian hippocampus and olfactory cortex as well as geniculo-cortical areas in stem amniotes from which mammals evolved. To this end, we have used data from extracellular recordings from microelectrode arrays to study spatial and temporal patterns of responses to visual stimuli as seen in both local field potential and action potentials. We discovered surprisingly large receptive fields, responsiveness to a broad range of stimuli, and high correlation between distant neural ensembles across recording array. Moreover, we found significant response variability regarding latency and strength in the presence of adaptation to both ongoing and visually evoked activity.
Evolution in the Treatment of Esophageal Disease at a Single Academic Institution: 2004–2013

Abstract Introduction: Management of benign and malignant esophageal disease has changed rapidly over the past decade. The aim of this study was to analyze evolution in surgical management of esophageal disease at a single academic medical center during this period. Materials and Methods: We reviewed a retrospective cohort of patients who underwent esophagectomy between 2004 and 2013. Patient, institutional, treatment, and outcomes variables were reviewed. Results: 317 patients were analyzed. Median age was 63.5 years; 80% were male. Average inhospital mortality rate was 3.8%. Operative indications changed significantly from 2004 to 2013, with more operations performed for invasive malignancy (77% vs. 95%) and fewer for high-grade dysplasia (12% vs. 3%, P = .008). In 2004, Ivor Lewis esophagectomy was the most common surgical technique, but the three-field technique was the operation of choice in 2013. A minimally invasive approach was used in 19% of cases in 2004 and 100% of cases in 2013 (P < .001). Ana...
Creation of a Composite Score to Predict Adnexal Torsion in Children and Adolescents

Abstract Study Objective To create a composite score to predict adnexal torsion in children and adolescents. Design A prospective cross-sectional study. Setting Emergency department of a tertiary care children's hospital. Participants Three hundred twenty-four female participants aged 6-21 years who presented to the emergency department with lower abdominal pain and underwent ultrasound or computed tomography imaging. Interventions Collection of possible clinical and radiologic predictors of torsion. Main Outcome Measures The primary outcome was a composite score to predict adnexal torsion. We used χ 2 analyses to identify possible risk factors. The classification and regression tree decision method was used to identify risk factor cutoff points. Independent risk factors were combined into a composite score. Receiver operating characteristic curve analyses were used to assessed score performance. Results Of 324 participants with abdominal pain, 241 underwent imaging, and 6.6% (16 of 241) had torsion. Duration of pain, intermittent pain, nausea, and absence of arterial or venous flow were not associated with torsion. Vomiting ( P = .05 in premenarchal subjects; P P = .008 in premenarchal subjects; P P = .04 in premenarchal subjects; P Conclusion Independent predictors of torsion can reliably be combined into a composite score to identify children and adolescents at risk for adnexal torsion. This score might aid in improving triage and management of these challenging patients.
Digital Beam Switch For Agile Beam Lasar Radar

Experimental results achieved with a multiple-position random access switch for 10.6 μm radiation are described. A set of cascaded Fabry-Perot interferometers produces a two-dimensional array of beam positions with a wide field-of-view.© (1980) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Actinides and Heavy Fermions

The actinide series of elements begins with f-shell electrons forming energy bands, contributing to the bonding, and possessing no magnetic moments. At americium the series switches over to localized f electrons with magnetic moments, as in most of the lanthanide elements. In metallic compounds this crossover of behavior can be modified and studied. In this continuum of behavior a few compounds on the very edge of localized f-electron behavior exhibit enormous electronic heat capacities at low temperatures. This is associated with an enhanced thermal mass of the conduction electrons, which is well over a hundred times the free electron mass, and is what led to the label heavy fermion for such compounds. A few of these become superconducting at even lower temperatures. The excitement in this field comes from attempting to understand how this heaviness arises and from the liklihood that the superconductivity is different from that of previously known superconductors. We have continued to study the effects of thorium impurities in UBe13 as a representative system for studying the nature of the superconductivity.
Insertion, protonolysis and photolysis reactivity of a thorium monoalkyl amidinate complex.

The reactivity of the thorium monoalkyl complex Th(CH2SiMe3)(BIMA)3 [1, BIMA = MeC(NiPr)2] with various small molecules is described. While steric congestion prohibits the insertion of N,N′-diisopropylcarbodiimide into the Th–C bond in 1, the first thorium tetrakis(amidinate) complex, Th(BIMA)4 (2), is synthesized via an alternative salt metathesis route. Insertion of p-tolyl azide leads to the triazenido complex Th[(p-tolyl)NNN(CH2SiMe3)-κ2N1,2](BIMA)3 (3), which then undergoes thermal decomposition to the amido species Th[(p-tolyl)N(SiMe3)](BIMA)3 (4). The reaction of 1 with 2,6-dimethylphenylisocyanide results in the thorium iminoacyl complex Th[η2-(CN)-2,6-Me2-C6H3(CH2SiMe3)](BIMA)3 (5), while the reaction with isoelectronic CO leads to the products Th[OC(CH2)SiMe3](BIMA)3 (6) and Th[OC(NiPr)C(CH2SiMe3)(C(Me)N(iPr))O-κ2O,O′](BIMA)2 (7), the latter being the result of CO coupling and insertion into an amidinate ligand. Protonolysis is achieved with several substrates, producing amido (9), aryloxide (10), phosphido (11a,b), acetylide (12), and cationic (13) complexes. Ligand exchange with 9-borabicyclo[3.3.1]nonane (9-BBN) results in formation of the thorium borohydride complex (BIMA)3Th(μ-H)2[B(C8H14)] (14). Complex 1 also reacts under photolytic conditions to eliminate SiMe4 and produce Th(BIMA)2(BIMA*) [15, BIMA* = (iPr)NC(CH2)N(iPr)], featuring a rare example of a dianionic amidinate ligand. Complexes 2, 3, 5, 6, 11a, and 12–15 were characterized by 1H and 13C{1H} NMR spectroscopy, FTIR, EA, melting point and X-ray crystallography. All other complexes were identified by one or more of these spectroscopic techniques.
Pluralising the Narrative: Reconfiguring ‘Vernacular Modernism’ in Assamese Literary Culture

The term ‘vernacular modernism’ came into being amidst proliferating conceptual frameworks to explain the diverse paradigms of modernity as a global process. More specifically, ‘vernacular modernis...
Discussion: The Axiomatization of Classical Mechanics

The purpose of this note is to examine a recent axiomatization of classical particle mechanics, and its relation to an alternative axiomatization I had earlier proposed.1 A comparison of the two proposals casts some interesting light on the problems of operationalism in classical celestial mechanics.
Induction of Physical Dependence on Alcohol in Rodents

The understanding of human diseases and their treatment in terms of molecular mechanisms owes much to animal experimentation. Specifically, the induction of diseases in animals by the same pathogenetic factors that induce the disease in man has been of great value, particularly if the experimental conditions closely simulate those of the human diseases. Typical examples are infectious diseases, hypertension secondary to renal disease, coronary artery disease secondary to hyperlipemias, diabetes mellitus secondary to insulin deficiency and many others. The development of drugs for the treatment of diseases in man has often been developed empirically in animal models and the molecular mechanisms have been studied almost as an afterthought. With the rapid development of molecular pharmacology, the order of events is increasingly reversed. A classical example is the development of the cancer drug 5-fluorouracil by Heidelberger (1) based purely on predictions made from theoretical molecular pharmacology.
Nanotechnology in Cancer

Cancer nanotechnology, defined as nanotechnology applicable for diagnosis, prognosis, and therapy of cancer, offers exciting possibilities but also challenges. Although nanotechnology became fruitful in the field of diagnostics, to date the desire of improving current cancer treatments through nanotechnology has surpassed the research or development stage only in a handful of cases. However, efforts to clinically translate more of these treatments remain highly focused. Drug-bearing nanoparticles, which are usually injected directly into the bloodstream, are sent on a journey full of obstacles to overcome such as bypassing RES organs and crossing endothelial cells, as well as various membranes of cellular and extracellular compartments, before finally encountering tumor tissue. Therefore, a cornucopia of different nanoparticle designs varying in size, architecture, and surface properties has been designed to be deployed to tumor sites within the human body either passively or promoting the association with a particular cell or tissue type through targeting. Early clinical results with nanomedicines were indeed able to show reduced toxicity, improving patients’ quality of life, but are still in need of stronger coupling with superior clinical efficacy to help justify the often high costs associated with this new class of therapeutics and their complexity. Nanotechnology aiming for the development of novel cancer therapeutics must focus in on potential, unforeseen toxicities and also consider the emerging role of epigenetics. The following chapter introduces most of the basic nanoconstructs developed to date, which inevitably will continue to evolve and eventually find an important place in health care, though to become the cancer medicines of tomorrow, nanotechnology’s future success and translation must early on be connected to diagnostic and therapeutic potential for clinical applications. To be equally aware of potential benefits, risks and costs will be necessary to stimulate future research with emphases on how to improve therapeutic outcomes such as the extension of life in patients with cancer in times burdened with unsustainable healthcare costs.
“New” Coagulation Inhibitors

Blood coagulation proceeds through a series of reactions in which plasma zymogens of serine proteases are sequentially activated by limited proteolytic cleavage. Studies concerning the regulation of this process have focused on protease inhibitors that, with the exception of α2-macroglobulin, belong to the SERPIN family of protease inhibitors — for example antithrombin III, heparin cofactor II, α1-antitrypsin, Cl esterase inhibitor and plasminogen activator inhibitor 1. Recently, two “new” protease inhibitors that may regulate coagulation have been identified, and both belong to the Kunitz family of protease inhibitors. One is referred to as the lipoprotein-associated coagulation inhibitor (LACI) (Broze et al., 1987a), or extrinsic pathway inhibitor (EPI) (Rao and Rapaport, 1987). This inhibitor inactivates factor Xa directly, and in a factor Xa dependent manner also inhibits the factor VIIa/tissue factor (VIIa/TF) catalytic complex. The other inhibitor appears to represent a form of the Alzheimer β-amyloid precursor protein, is released by stimulated platelets, and inhibits factor XIa.
In vivo Hippocampal Serotonin Dynamics in Male and Female Mice: Determining Effects of Acute Escitalopram Using Fast Scan Cyclic Voltammetry

Depression is a highly prevalent psychiatric disorder, impacting females at a rate roughly twice that of males. This disparity has become the focus of many studies which are working to determine if there are environmental or biological underpinnings to depression pathology. The biology of depression is not well understood, but experts agree that a key neurotransmitter of interest is serotonin. Most research on basic serotonin neurochemistry, by us and others, has predominantly focused on male models. Thus, it is now critical to include female models to decipher possible fundamental differences between the sexes that may underlie this disorder. In this paper, we seek to determine any such differences using fast-scan cyclic voltammetry (FSCV) and fast-scan controlled adsorption voltammetry. These techniques allow us to probe the serotonergic system via measurement of evoked and ambient serotonin at carbon fiber microelectrodes (CFMs). Our data reveal no statistical differences, in the hippocampus, in female serotonin chemistry during the different stages of the estrous cycle compared to the mean female response. Furthermore, no difference was observed in evoked serotonin release and reuptake, nor ambient extracellular serotonin levels between male and female mice. We applied a previously developed mathematical model that fits our serotonin signals as a function of several synaptic processes that control the extracellular levels of this transmitter. We used the model to study potential system differences between males and females. One hypothesis brought fourth, that female mice exhibit tighter autoreceptor control of serotonin, is validated via literature and methiothepin challenge. We postulate that this tight regulation may act as a control mechanism against changes in the serotonin signal mediated by estrogen spikes. Importantly, this safety mechanism has no consequence for acutely administered escitalopram's (ESCIT's) ability to increase extracellular serotonin between the sexes. This work demonstrates little fundamental differences in in vivo hippocampal serotonin between the sexes, bar control mechanisms in female mice that can be observed under extraneous circumstances. We thus highlight the importance of considering sex as a biological factor in determining pharmacodynamics for personalized medical treatments that involve targeting serotonin receptors.
Low temperature formation of CH3NH3PbI3 perovskite films in supercritical carbon dioxide

Abstract A new method for the production of high-quality CH3NH3PbI3 perovskite films at low temperature is reported. It is shown that CO2 above the critical point (31 ℃ , 7.38 MPa (1071 psi)) acts as an anti-solvent to perovskite precursors and significantly enhances the solid-state film crystallization rate at low temperatures and also assists in the removal of residual solvent from within the film. Post deposition treatment in supercritical carbon dioxide (scCO2) resulted in complete conversion of perovskite compared to incomplete conversion at the same temperatures using thermal annealing alone. Complete crystallization and an average crystal grain size of 408 nm at 45 ℃ was observed using scCO2 treatment compared to incomplete crystal formation with average grain size of 175 nm at 45 ℃ with thermal annealing alone.
The Lattice-Continuum Correspondence in the Ising Model

Starting from the operator algebra of the (1+1)D Ising model on a spatial lattice, this paper explicitly constructs a subalgebra of smooth operators that are natural candidates for continuum fields in the scaling limit. At the critical value of the transverse field, these smooth operators are analytically shown to reproduce the operator product expansions found in the Ising conformal field theory.
Esmolol in the management of pre-hospital refractory ventricular fibrillation: A systematic review and meta-analysis.

Abstract Background Esmolol has been proposed as a viable adjunctive therapy for pre-hospital refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT). Objectives We performed a systematic review and meta-analysis to assess the effectiveness of esmolol on pre-hospital refractory VF/pVT, compared with standard of care. Methods MEDLINE, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for eligible studies. Two investigators independently extracted relevant data and assessed the methodological quality of each included study using the ROBINS-I tool. The quality of evidence for summary estimates was assessed according to GRADE guidelines. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) for each outcome of interest were calculated. Results The search yielded 3253 unique records, of which two studies were found to be in accordance with the research purpose, totaling 66 patients, of whom 33.3% (n = 22) received esmolol. Additional evidence was provided in the paper but was not relevant to the analysis and was therefore not included. Esmolol was likely associated with an increased rate of survival to discharge (RR 2.82, 95% CI 1.01–7.93, p = 0.05) (GRADE: Very low) and survival with favorable neurological outcome (RR 3.44, 95% CI 1.11–10.67, p = 0.03) (GRADE: Very low). Similar results were found for return of spontaneous circulation (ROSC) (RR 2.63, 95% CI 1.37–5.07, p = 0.004) (GRADE: Very low) and survival to intensive care unit (ICU)/hospital admission (RR 2.63, 95% CI 1.37–5.07, p = 0.004) (GRADE: Very low). Conclusion The effectiveness of esmolol for refractory VF/pVT remains unclear. Trial sequential analysis (TSA) indicates that the evidence is inconclusive and that further trials are required in order to reach a conclusion. Therefore, it is imperative to continue to accumulate evidence in order to obtain a higher level of scientific evidence.
Magnetization of UBe 13 to 60 T

We have measured the isothermal magnetization of ${\mathrm{UBe}}_{13}$ to 60 T in a pulsed magnetic field. The measurements were made over a temperature range of 0.5 to 4 K. The data are well fit by both a $J=1/2$ Brillouin function model and a simple band model. Both fits extrapolate to a saturation moment of $1.9\ifmmode\pm\else\textpm\fi{}0.2{\ensuremath{\mu}}_{B}/\mathrm{U}$ atom. Our results suggest that a metamagnetic transition in ${\mathrm{UBe}}_{13}$ is unlikely.
SERS spectroscopy for the therapeutic drug monitoring of the anticancer drug 6-Mercaptopurine: Molecular and kinetic studies

Abstract Gold colloidal solutions were investigated as SERS platforms for the detection and the quantitative analysis of the anticancer drug 6-Mercaptopurine. The study was aimed at verifying the feasibility of a SERS-based assaying method for Therapeutic Drug Monitoring. The interaction mechanism and the adsorbate structure were investigated by a QM vibrational analysis of the title molecule. Furthermore, a kinetic analysis of the adsorption/aggregation processes made by time- resolved SERS experiments and DLS analysis provided relevant information on the complex behaviour of the system. It was found that the adsorption process is fast and produces significant SERS signalling in the 5–20 μM range. At 15 and 20 μM composition, the kinetic analysis evidenced the formation of long-lived metastable aggregates; at 50 μM the colloidal solution collapsed immediately. A range of high linearity was identified between 5 and 20 μM, wherein a reliable quantitative analysis could be performed, with an estimated limiting sensitivity (LOD) of 1.0 μM.
Möbius disjointness for analytic skew products

We show that the Mobius function is disjoint to every analytic skew product dynamical system on \(\mathbb {T}^2\) over a rotation of the circle.
Neuromolecular and behavioral effects of ethanol deprivation in Drosophila

Abstract Alcohol use disorder (AUD) is characterized by loss of control in limiting alcohol intake. This may involve intermittent periods of abstinence followed by alcohol seeking and, consequently, relapse. However, little is understood of the molecular mechanisms underlying the impact of alcohol deprivation on behavior. Using a new Drosophila melanogaster repeated intermittent alcohol exposure model, we sought to identify how ethanol deprivation alters spontaneous behavior, determine the associated neural structures, and reveal correlated changes in brain gene expression. We found that repeated intermittent ethanol exposures followed by ethanol-deprivation dynamically induces behaviors associated with a negative affect state. Although behavioral states broadly mapped to many brain regions, persistent changes in social behaviors mapped to the mushroom body and surrounding neuropil. This occurred concurrently with changes in expression of genes associated with sensory responses, neural plasticity, and immunity. Like social behaviors, immune response genes were upregulated following three-day repeated intermittent ethanol-exposures and persisted with one or two days of ethanol-deprivation, suggesting an enduring change in molecular function. Our study provides a framework for identifying how ethanol deprivation alters behavior with correlated underlying circuit and molecular changes.
Influence of supply chain technology responsiveness on supply chain and market performance

Innovation adoption is linked to firm competitiveness, yet guidance about adopting a proactive stance across a portfolio of technologies is circumspect. We examine relationships between firm techno...
AI-enabled dynamic finish machining optimization for sustained surface integrity

Abstract While machining processes are typically leveraged to establish geometric features, many functional characteristics of advanced materials are directly determined by their machining-induced quality, i.e. surface integrity. Current modeling approaches struggle to predict surface integrity, and typically neglect the effects of progressive tool-wear, resulting in inefficient ‘static’ process parameters. We present a novel integrated approach based on model-informed artificial intelligence (AI), which quickly and efficiently optimizes ‘dynamic’ process parameters. By maximizing the useful life of a cutting tool over which required quality parameters can be maintained, our paradigm will enable significantly more efficient processing of next-generation materials and components.
Tissue engineered skeletal muscle model of rheumatoid arthritis using human primary skeletal muscle cells.

Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily targeting the joints. Autoreactive immune cells involved in RA affect other tissues, including skeletal muscle. Patients with RA experience diminished physical function, limited mobility, reduced muscle function, chronic pain, and increased mortality. To explore the impact of RA on skeletal muscle, we engineered electrically responsive, contractile human skeletal muscle constructs (myobundles) using primary skeletal muscle cells isolated from the vastus lateralis muscle of 11 RA patients (aged 57-74) and 10 aged healthy donors (aged 55-76), as well as from the hamstring muscle of six young healthy donors (less than 18 years of age) as a benchmark. Since all patients were receiving treatment for the disease, RA disease activity was mild. In 2D culture, RA myoblast purity, growth rate, and senescence were not statistically different than aged controls; however, RA myoblast purity showed greater variance compared to controls. Surprisingly, in 3D culture, contractile force production by RA myobundles was greater compared to aged controls. In support of this finding, assessment of RA myofiber maturation showed increased area of sarcomeric α-actinin (SAA) expression over time compared to aged controls. Furthermore, a linear regression test indicated a positive correlation between SAA protein levels and tetanus force production in RA and controls. Our findings suggest that medications prescribed to RA patients may maintain-or even enhance-muscle function, and this effect is retained and observed in in vitro culture. Future studies regarding the effects of RA therapeutics on RA skeletal muscle, in vivo and in vitro, are warranted.
Gene expression of serotonergic neurons in the central nervous system: molecular and developmental analysis.

Publisher Summary Serotonin (5-HT) is an indoleamine neurotransmitter implicated in the neurochemical, physiological, and behavioral changes occurring in major psychiatric syndromes, such as obsessive–compulsive disorders and depression. This chapter presents a molecular and developmental analysis of the gene expression of serotonergic neurons in the central nervous system. Serotonin is synthesized from tryptophan by sequential enzymatic reactions catalyzed by tryptophan hydroxylase (TPH) and aromatic L-amino acid decarboxylase (AADC). Functional analysis of the TPH gene and TPH gene expression and regulation are essential to the understanding of 5-HT activity in behavioral abnormalities and psychiatric disorders. The chapter describes the (1) recent findings for abnormal central serotonergic inversion of a neurodevelopmental mutant mouse, anorexia; (2) functional analysis of the TPH gene; and (3) cell-type specific expression of the TPH gene in transgenic mice. Six independent transgenic mouse lines carrying pWH6.l LacZ showed the transgene expression in both pineal gland and the raphe nuclei or in pineal gland alone as demonstrated by X-gal staining, β-galactosidase enzyme assay, or immunohistochemistry. Non-serotonergic cell bodies of the substantia nigra compacta, the locus ceruleus, thalamus, corpus striatum, septum, and other brain regions did not exhibit detectable β-galactosidase expression. These data strongly suggest that the 6.1 kb of 5´ flanking sequence may contain sufficient DNA element to direct targeted expression of the transgene in the serotonergic pineal gland and brain tissues.
What Is the Optimal Transplant for Older Patients With Idiopathic Pulmonary Fibrosis

Background There is controversy regarding the optimal type of lung transplant—single orthotopic lung transplantation (SOLT) versus bilateral orthotopic lung transplantation (BOLT)—for patients with idiopathic pulmonary fibrosis. We performed this study to determine which type of transplant is more appropriate for older patients with this condition. Methods We conducted a review of the United Network for Organ Sharing database from 2005 to 2013 for patients aged 65 years or more with idiopathic pulmonary fibrosis. A 1:1 nearest-neighbor propensity match was utilized to determine differences in survival by transplant procedure type (SOLT versus BOLT). Logistic regression modeling taking into account interaction terms between prespecified variables and the type of transplant was utilized to determine variables that altered the survival outcomes associated with SOLT versus BOLT. Results Of 1,564 patients who met study criteria, 521 (33.3%) received BOLT. After propensity matching 498 BOLT recipients to 498 SOLT recipients, BOLT was associated with a significantly improved 5-year survival (48.7% versus 35.2%, p Conclusions Bilateral orthotopic lung transplantation is associated with significantly improved survival over SOLT for older patients with idiopathic pulmonary fibrosis, driven by a late survival benefit from bilateral transplantation. However, patients with a reduced preoperative functional status do not appear to derive a similar benefit from bilateral transplantation.