cssi/SciSciGPT-SciSciNet huggingface dataset:
Gene therapy of genetic diseases and cancer.

: The scope of gene transfer applications in human therapy has expanded enormously over the last 15 years to include not only several types of genetic diseases but also a variety of genetic approaches to the treatment of cancer. Hematopoietic stem cells have been considered excellent targets for therapeutic gene transfer because of their capacity for self-renewal and for differentiation into multiple cellular lineages. Retrovirus-mediated gene transfer has been tested for treatment of diseases that specifically affect the hematopoietic system, such as adenosine deaminase deficiency and chronic granulomatous disease. Storage disorders such as Gaucher disease, Hurler syndrome and Hunter syndrome, genetic deficiencies that affect a broad range of tissue types, may also be amenable to treatment by gene transfer into hematopoietic cells, owing to the release of enzyme expressed in transduced cells with subsequent uptake by untransduced cells (“metabolic cross-correction”). Hematopoietic stem cells may also be targeted for introduction of drug-resistance genes for the purpose of protecting normal tissues from the toxic side-effects of cancer chemotherapeutic agents, thus allowing more effective antitumor chemotherapy. The danger of introducing drug-resistance function into tumor cells may be dealt with by including sequences specifically designed to reduce expression of oncogenes or to restore expression of tumor suppressor genes. Current limitations on the efficiency of gene transfer into hematopoietic stem cells may be alleviated by the development of new vector systems such as adeno-associated virus or lentivirus vectors, or by advances in cell processing that render hematopoietic cells more susceptible to transduction. Drug-resistance genes may also be applied for in vivo selection to expand the representation of a small proportion of transduced hematopoietic cells. These approaches toward increasing the frequency of hematopoietic cell transduction contribute to the anticipated feasibility of gene therapy for genetic diseases and cancer.
Islet-like cell clusters: viability, cell types, and subretinal transplantation in pancreatectomized cats

We investigated a method for isolating sufficient feline islets of Langerhans to restore normoglycaemia following transplantation into the subretinal space of pancreatectomized cats. Collagenase digestate of feline pancreas was maintained in serum-free tissue culture medium for 1-9 days. Viability of islet-like cell clusters (ICC) was assessed with ethidium bromide and fluorescein diacetate staining; cell types were identified immunohistochemically. After nine days, the ICC were transplanted. We estimated viable ICC in tissue culture at nine days as 3800 +/- 2000 (mean +/- SD) per pancreas. While numbers of beta cells decreased over time in culture, ductal cells increased. Bromodeoxyuridine labelling showed no proliferation of beta cells but extensive proliferation of ductal cells. Subretinal transplants of cultured ICC in the diabetic cats maintained normoglycaemia for up to 12 days, while they provoked massive lymphocyte infiltration indicating rejection. Islet transplantation into the feline subretinal space temporarily restored normoglycaemia. Our current method of culture achieved sufficient reduction of acinar cells but an insufficient yield of insulin-producing cells.
Embryo/fetal toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in rats and rabbits.

BACKGROUND: The purpose of this study was to evaluate the effects of lasofoxifene, a selective estrogen receptor modulator (SERM), on rat and rabbit fetal development. METHODS: Lasofoxifene was administered orally to rats (1, 10, 100 mg/kg) between gestation days (GD) 6–17, and in rabbits (0.1, 1, 3 mg/kg) between GD 6–18. Maternal body weight and food consumption were monitored throughout pregnancy. Fetuses were delivered by Cesarean section on GD 21 in rats, and GD 28 in rabbits, to evaluate fetal viability, weight, and morphology. Drug concentrations in maternal plasma were measured in a separate cohort of animals at several time points commencing on GD 17 (rats) and 18 (rabbits). On GD 18 (rat) and GD 19 (rabbit) drug concentrations were measured in maternal plasma and in fetal tissue 2 hr post dosing to determine the fetal to maternal drug ratio. RESULTS: In rats, there were dose-related declines in maternal weight gain and food consumption. Post implantation loss was significantly increased at dosages of 10 and 100 mg/kg, and the number of viable fetuses was decreased at 100 mg/kg. The placental weights increased, whereas fetal weights decreased in a dose-dependent manner. Lasofoxifene-related teratologic findings were noted at 10 and 100 mg/kg and included imperforate anus with hypoplastic tails, dilatation of the ureters and renal pelvis, misaligned sternebrae, hypoflexion of hindpaw, wavy ribs, and absent ossification of sternebrae. In rabbits, neither maternal weight gain nor food consumption were affected during treatment. Between GD 26–28, there was a dose-dependent increased incidence of red discharge beneath the cages. At 1 and 3 mg/kg, resorptions and post-implantation loss increased. There were no significant external or visceral effects, but 3 mg/kg there was an increased incidence of supernumerary ribs. Although the maternal plasma Cmax and AUC(0–24) were dose-dependent, the exposures in the rat were many orders of magnitude greater than in the rabbit even for the same 1 mg/kg dose. The single time point fetal/maternal drug ratio was higher in the rat (1.3–0.78) than in the rabbit (0.21–0.16). CONCLUSION: In general, both maternal and fetal effects of lasofoxifene were similar to those reported with other SERMs. Although the incidence or severity of these effects was, in some instances, greater in the rat than in the rabbit, the doses and the resultant maternal and fetal exposures were many orders of magnitude higher in the rat, suggesting the rabbit to be more sensitive to the toxicological effects of lasofoxifene. Birth Defects Res B 71:161–170, 2004. © 2004 Wiley-Liss, Inc.
Motor system’s role in grounding, receptive field development, and shape recognition

Vision is basically a sensory modality, so it is no surprise that the investigation into the brainpsilas visual functions has been focused on its sensory aspect. Thus, questions like (1) how can external geometric properties represented in internal states of the visual system be grounded, (2) how do the visual cortical receptive fields (RFs) form, and (3) how can visual shapes be recognized have all been addressed within the framework of sensory information processing. However, this view is being challenged on multiple fronts, with an increasing emphasis on the motor aspect of visual function. In this paper, we will review works that implicate the important role of motor function in vision, and discuss our latest results touching upon the issues of grounding, RF development, and shape recognition. Our main findings are that (1) motor primitives play a fundamental role in grounding, (2) RF learning can be biased and enhanced by the motor system, and (3) shape recognition is easier with motor-based representations than with sensor-based representations. The insights we gained here will help us better understand visual cortical function. Also, we expect the motor-oriented view of visual cortical function to be generalizable to other sensory cortices such as somatosensory and auditory cortices.
AUTOMATIC SEGMENTATION OF CORONARY ARTERIES USING BAYESIAN DRIVEN IMPLICIT SURFACES

In this paper, we propose a hybrid approach for the automatic three-dimensional segmentation of coronary arteries using multi-scale vessel filtering and a Bayesian probabilistic approach in a level set image segmentation framework. The initial surface of the coronaries is obtained from the multiscale vessel filter response, and the surface then evolves to capture the exact boundary of the coronaries according to an improved evolution model of implicit surfaces. In our model, the image force and the propagation terms are re-defined using posterior probabilities obtained via Bayes' rule in order for the surface to approach to the boundaries faster and stop at the boundaries more accurately. The proposed method is tested on seven CT angiography (CTA) data-sets of left and right coronary arteries, and the quantitative comparison of our result against manually delineated contours on two of the data-sets yields a mean error of 0.37 mm
The lipid composition of the blood of marine mammals—III. The fatty acid composition of plasma and erythrocytes of Atlantic bottlenose dolphin, Tursiops truncatus

Abstract 1. 1. The fatty acid composition of the whole plasma and erythrocytes was determined in four Atlantic bottlenosed dolphins. 2. 2. The plasma contained 27% saturated, 46% monounsaturated and 27% polyunsaturated fatty acids. 3. 3. The red cells contained 33% saturated, 33% monounsaturated and 33% polyunsaturated fatty acids. 4. 4. Arachidonic acid was a major polyunsaturated fatty acid in the erythrocytes (13·3%) but a less important component of plasma (2·5%). 5. 5. The iso, anteiso and multibranched chain fatty acids were minor but significant components of the fatty acid profile of plasma but were present at markedly lower levels, or not detected at all, in the red cell. 6. 6. The plasma fatty acids, which in general reflect the dietary fat intake of the dolphin, exhibited a typical marine fatty acid profile. 7. 7. The erythrocyte fatty acids, being mainly synthesized endogenously, are similar in composition to those of terrestrial mammals except for lesser amounts of 18-carbon unsaturated fatty acids.
Focal Mechanism Determination Using High Frequency Waveform Matching and Its Application to Small Magnitude Induced Earthquakes

S U M M A R Y We present a new method using high-frequency full waveform information to determine the focal mechanisms of small, local earthquakes monitored by a sparse surface network. During the waveform inversion, we maximize both the phase and amplitude matching between the observed andmodelled waveforms. In addition, we use the polarities of the firstP-wave arrivals and the average S/P amplitude ratios to better constrain the matching. An objective function is constructed to include all four criteria. An optimized grid search method is used to search over all possible ranges of source parameters (strike, dip and rake). To speed up the algorithm, a library of Green’s functions is pre-calculated for each of the moment tensor components and possible earthquake locations. Optimizations in filtering and cross correlation are performed to further speed the grid search algorithm. The new method is tested on a five-station surface network used for monitoring induced seismicity at a petroleum field. The synthetic test showed that our method is robust and efficient to determine the focal mechanism when using only the vertical component of seismograms in the frequency range of 3–9 Hz. The application to dozens of induced seismic events showed satisfactory waveform matching between modelled and observed seismograms. The majority of the events have a strike direction parallel with the major NE–SW faults in the region. The normal faulting mechanism is dominant, which suggests the vertical stress is larger than the horizontal stress.
Intercomparison and coupling of magnesium-induced co-precipitation and long-path liquid-waveguide capillary cell techniques for trace analysis of phosphate in seawater

Currently, two common techniques for nanomolar-level phosphate measurements in seawater are magnesium-induced co-precipitation (MAGIC) and long-path liquid-waveguide capillary cell (LWCC) spectrophotometry. These techniques have been applied in the open ocean, and our understanding of phosphate distributions in oligotrophic subtropical gyres is based on those data. However, intercomparison of these methods has not previously been performed at nanomolar levels. Here, we report experimental results directly comparing the MAGIC and LWCC techniques. We also evaluated the impact of various commonly employed filters on phosphate determinations, as well as interferences from dissolved organic phosphorus (DOP) and arsenate. Our results find agreement between these methods at phosphate concentrations <100 nM. We found that filter selection is important for accurate determinations of phosphate, and that DOP hydrolysis affects both techniques similarly. Finally, we demonstrate the advantage of combining MAGIC preconcentration and LWCC spectrophotometry for analysis of very low nanomolar concentrations.
“Orientation induced memory effect” in polyamides and the relationship to hydrogen bonding

The influence of molecular orientation on the “memory effect” of polyamides was investigated by differential scanning calorimetry. Melt crystallization of undrawn and drawn polyamide 6 (N6) and polyamide 66 (N66) fibers showed no difference either in the rate of crystallization or crystallization temperature. We demonstrated that hydrogen bonding does not play a major role in melt crystallization kinetics of polyamides (N6 and N66), and the “memory effect” is only retained for polymers, including N6 and N66, because of insufficient time spent above the melting temperature. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 772–775, 2003
Simulation of Membrane Sculpting by EFC F-BAR Domain Lattices

Cells, during cellular morphogenesis, are dynamically sculpted into different compartments by membranes with the help of proteins. The BAR domain is one of the conserved protein domains that is involved in shaping cellular membranes in vivo, and is observed to induce tubule formation from liposomes in vitro. Previous simulations showed that certain lattice arrangements of N-BAR domains shape membranes into tubules (Yin, Arkhipov, and Schulten, 2009). Here we show, by means of several microsecond coarse-grained simulations of F-BAR domains in different lattice configurations on POPC/POPS membranes, that extended-FCH (EFC) F-BAR domains shape membrane in a fashion similar to what has been seen in N-BAR simulations. The membrane bending property of several F-BAR domain lattice arrangements is characterized, showing that different lattice configurations induce a range of membrane curvatures. A highly detailed view of the dynamic membrane sculpting process by F-BAR domain lattices on a microsecond timescale is obtained.Yin, Y., Arkhipov, A., and Schulten, K. (2009). Simulations of membrane tubulation by lattices of amphiphysin N-BAR domains. Structure17(6), 882-92.
Frequency domain identification with fixed zeros: first generation seismic-AMD benchmark

Frequency domain linear multi-variable system identification has been extensively studied. Many of the existing algorithms assume no prior knowledge of the underlying system structure, e.g. zero and pole locations that are pre-determined (or fixed). However such information, if available, helps to reduce the error in the interesting frequency range and the number of the model parameters to be estimated. In the paper, an algorithm that explicitly includes the fixed zeros is developed using the polynomial matrix curve-fitting technique. A simple and effective method is introduced to constrain the identified model to be stable. An application study is presented to demonstrate the effectiveness of the identification algorithm.
Mitford vs. Hemans: Resisting the “Omnipotence of Words” in Dramatic Romance and Romantic Drama

Romance poetry, drama, and theatrical productions shared common elements in the early nineteenth century, reflecting a hybridization of genres characteristic of Romanticism. In both published and performed work, the verse romances, dramatic poems, and staged historical tragedies of Mary Russell Mitford and Felicia Hemans bear comparison in featuring silence and withdrawal in the parts of lead characters. Mitford's and Hemans's use of antitype characters to represent large-scale national crises reflects their mutual grounding in German theater and drama, particularly that of Friedrich Schiller. Each poet has been associated with liberal idealism in representing corruptions of language as a sign of tyranny, and each poet develops characters who resist and evade the dictums of authority through silence. Nevertheless, Mitford's approach differs from Hemans's in the deployment of silent resistance to test problems with liberal idealism. Hemans emphasizes futility to alter a patriarchal script of destiny so that her resisting characters can only connect with audiences in a future time and cannot affect their own moment, while Mitford brings alternate possibilities within reach of her resisting characters in their time, leaving them to face a tentative future yet to be defined.
The kidney and hypertension.

in 1898, the year the American Journal of Physiology first went to press, Tigerstedt and Bergman ([36][1]) published experiments suggesting the existence of a humoral substance of renal origin that induces hypertension (see also Ref. [27][2]). Initially, not much attention was paid to these
Quantum Kibble-Zurek Mechanism in a Spin-1 Bose-Einstein Condensate

The dynamics of a quantum phase transition are explored using slow quenches from the polar to the broken-axisymmetry phases in a small spin-1 ferromagnetic Bose-Einstein condensate. Measurements of the evolution of the spin populations reveal a power-law scaling of the temporal onset of excitations versus quench speed as predicted from quantum extensions of the Kibble-Zurek mechanism. The satisfactory agreement of the measured scaling exponent with the analytical theory and numerical simulations provides experimental confirmation of the quantum Kibble-Zurek model.
Reactive Al-O-Al sites in a natural zeolite; triple-quantum oxygen-17 nuclear magnetic resonance

In framework aluminosilicate materials (e.g., feldspars, zeolites and many others), it is generally assumed that AlO 4 tetrahedra do not share corners, i.e., that Al-O-Al oxygen sites are avoided when stoichiometry permits. This assumption plays a key role in models of thermodynamic properties and of reaction kinetics. We present a new approach to directly test this assumption, based on 17 O triple-quantum magic-angle spinning nuclear magnetic resonance (3QMAS NMR). We show that thermodynamically significant concentrations of Al-O-Al sites can be observed in a naturally occurring zeolite (stilbite), and that these sites react faster with H 2 O vapor than do Si-O-Si and Si-O-Al sites.
Therapeutic Orphans, Pediatric Victims? The Best Pharmaceuticals for Children Act and Existing Pediatric Human Subject Protection

In 2002 the President signed into law the Best Pharmaceuticals for Children Act, which gives incentives for research on a group that has previously been considered therapeutic orphans when it comes to drug safety and dosage testing: Children. The Act offers an extra 6 months of market exclusivity for a drug if the manufacturer conducts drug trials in pediatric populations meeting FDA's requirements. While the intent of Congress with this act was to make drugs safer for children, it is an open question whether this is being achieved at the expense of pediatric research subjects, and the threat of a race to the bottom in research ethics looms large.This Article describes the Act, its origins, and existing federal regulations protecting children as research subjects, while reviewing the history of pediatric research and the bioethical dilemmas it poses. The Article then discusses shortcomings in the existing scheme and describes necessary changes to better protect the welfare of children in the research setting.
Equipment Procurement and Rate of Return

The procurement of large and expensive equipment presents the contractor with some very difficult decisions concerning how such acquisitions should be financed. An important consideration in this regard is the after-tax rate of return that the contractor can expect to receive on his equipment investment. Using discounted cash-flow methods, the rates of return are computed for several procurement alternatives including a true-lease, full-equity purchase, and several instances of financed purchase. Based upon after-tax rates of return, the lease and financed purchase with minimal down payment are shown to be the most desirable procurement alternatives for the acquisition example analyzed. However, other practical considerations are involved and their effect upon the total decision process is discussed.
Case Report: Fatal Overdose with Sustained-Release Verapamil

Verapamil is generally a safe and effective drug in the treatment of many vascular disorders. During the past 10 years, a number of serious poisonings have been attributed to verapamil overdose. A relatively new problem is toxicity with the sustained-release form of verapamil. Complications of verapamil overdose can be understood as simply an extension of its pharmacologic activity. Consistently effective therapy remains elusive. Specific calcium channel blocker antidotes are under investigation, but supportive therapy remains the mainstay for serious verapamil overdose.
Watch your back: A randomized efficacy study of a theory-guided website to promote melanoma knowledge and skin self-examination among young adults

Melanoma is the most deadly form of skin cancer, and incidence rates have been rising steadily for decades. Early detection improves prognosis, but even though most melanomas are visible to the naked eye, skin self-examination (SSE) rates are low, especially among young adults. These low SSE rates are troubling since melanoma is one of the most commonly diagnosed cancers among people ages 18–29 years. We developed a theory-guided website to promote melanoma knowledge and SSE among young adults and tested its efficacy in a randomized controlled study with 190 university students. Intervention group participants scored higher on average than control group participants on all outcome measures including melanoma knowledge (P < 0.001), perceived severity of melanoma (P < 0.001), perceived susceptibility for developing melanoma (P < 0.01), self-efficacy for performing SSE correctly (P < 0.001), response efficacy of SSE for helping people identify melanoma in its earlier most treatable stages (P < 0.001), and in...
Importance of repeat angiography in the diagnosis of iatrogenic anterior cerebral artery territory pseudoaneurysm following endoscopic sinus surgery.

Iatrogenic intracranial pseudoaneurysm formation and rupture are rare complications following endoscopic sinus surgery. Given the propensity for devastating neurologic injury after a relatively routine procedure, swift diagnosis and treatment is essential. The authors present a patient who experienced bifrontal intracranial hemorrhage and subarachnoid hemorrhage due to a ruptured iatrogenic frontopolar artery pseudoaneurysm caused during routine endoscopic sinus surgery. The pseudoaneurysm was not present on initial angiograms but became apparent radiographically 19 days after the endoscopic procedure. Endovascular treatment consisted of coil and Onyx embolization for sacrifice of the parent vessel proximal to the lesion. Early recognition of iatrogenic intracranial vascular injury is important to allow for rapid treatment. Initial radiographic studies may be unreliable in excluding the presence of a pseudoaneurysm so delayed repeat angiographic assessment is necessary, particularly in the presence of a high index of clinical suspicion. Endovascular techniques may provide an effective and safe option for the treatment of iatrogenic anterior cerebral artery distribution pseudoaneurysms.
Survival and Development of Heliothis zea (Lepidoptera: Noctuidae) Larvae on Selected Soybean Growth Stages

Corn earworm, Heliothis zea (Boddie), larval survival and development on determinate cultivar soybeans, Glycine max (L.) Merrill, at plant growth stages from prebloom to bean maturation stage were tested. Larvae confined to plants established on all stages tested, although fewer established on plants at more mature stages. Mortality of later instars was low in all treatments. Larvae feeding on prebloom stage plants weighed more after 12 d than those feeding on bloom or podfill stage plants. However, larvae from podfill stages had higher pupal weights. Development rates of larvae were not significantly different for the cultivars of soybean and plant stages tested from field-grown plants, except for one ‘Forrest’ prebloom growth stage.
Aflatoxin Effects in White Leghorn Chickens Selected for Response to Sheep Erythrocyte Antigen.1. Body Weight, Feed Conversion, and Temperature Responses

Chickens from lines selectively bred for high and low antibody response to sheep red blood cell antigen and reciprocal crosses between them were fed diets containing 0, 1, 2, 3, and 6 micrograms of total aflatoxin/g diet from 2 to 42 days of age. Low-line birds, although larger, did not differ from the high-line birds in feed consumption, feed conversion, surface, or cloacal temperatures. Differences between crosses and parental lines varied according to the particular trait. Responses to dietary aflatoxin were similar regardless of population. Aflatoxin depressed body weight, feed consumption, and feed conversion at 14 days and subsequent ages with the effect on body weight and feed consumption occurring at lower levels than that noted for feed conversion. Although aflatoxin did not alter cloacal temperatures, there were progressive decreases in surface temperatures at 2 micrograms/g and higher.
Effect of the Anion Activity on the Stability of Li Metal Anodes in Lithium-Sulfur Batteries

With the significant progress made in the development of cathodes in lithium-sulfur (Li-S) batteries, the stability of Li metal anodes becomes a more urgent challenge in these batteries. Here the systematic investigation of the stability of the anode/electrolyte interface in Li-S batteries with concentrated electrolytes containing various lithium salts is reported. It is found that Li-S batteries using LiTFSI-based electrolytes are more stable than those using LiFSI-based electrolytes. The decreased stability is because the N–S bond in the FSI− anion is fairly weak and the scission of this bond leads to the formation of lithium sulfate (LiSOx) in the presence of polysulfide species. In contrast, in the LiTFSI-based electrolyte, the lithium metal anode tends to react with polysulfide to form lithium sulfide (LiSx), which is more reversible than LiSOx formed in the LiFSI-based electrolyte. This fundamental difference in the bond strength of the salt anions in the presence of polysulfide species leads to a large difference in the stability of the anode-electrolyte interface and performance of the Li-S batteries with electrolytes composed of these salts. Therefore, anion selection is one of the key parameters in the search for new electrolytes for stable operation of Li-S batteries.
The Politics of Crisis in Europe

The Politics of Crisis in Europe explores the resilience of the European Union in the face of repeated crises perceived to threaten its very existence. While it is often observed after the fact that these crises serve as opportunities for integration, this is the first critical analysis to suggest that we cannot fully understand the nature and severity of these crises without recognising the role of societal reaction to events and the nature of social narratives about crisis, especially those advanced by the media. Through a close examination of the 2003 Iraq crisis, the 2005 constitutional crisis, and the 2010–12 Eurozone crisis, this book identifies a pattern across these episodes, demonstrating how narratives about crises provide the means to openly air underlying societal tensions that would otherwise remain under the surface, impeding further integration.
Human–Wildlife Interactions and Environmental Dynamics in the Okavango Delta, Botswana

ABSTRACTThe Okavango Delta in Botswana hosts abundant wildlife and a human population with diverse livelihoods. Representing a heterogeneous landscape nuanced by spatial and temporal variability, the region has recently seen an expansion of floodwaters with social impacts ranging from livelihood disruption to human displacement. This article reports on in-depth interviews conducted in 2012 regarding these transitions in Mababe, a community in the eastern Okavango Delta, to evaluate how dynamic environmental processes alter perceptions and livelihood responses. We focus on community members’ variable interactions with wildlife in spaces of human–wildlife overlap also experiencing change. While human–wildlife interactions can have negative effects, we find that perpetuating the common narrative of human–wildlife conflict overlooks how disruptions can usher in new relationships between people and animals. In order to move beyond the conflict narrative, we conclude that spatial and temporal context is essenti...
A Hormone Therapy Model for Breast Cancer Using Linear Cancer Networks

Hormone therapy is a viable technique used to treat endocrine receptor positive cancers. Using the recently developed theory of cancer networks, we create a mathematical model describing the growth of an estrogen-receptive cancer governed by a linear cancer network. We then present hormone therapy as a drug that blocks the estrogen receptors of different cells in the network. Depending on the effectiveness of the drug, the model predicts coexistence of healthy and cancerous cells as well as a cure state. In the case of coexistence, the carrying capacities of all cancerous cells are reduced by hormone therapy, increasing effectiveness of other treatments such as surgery. keywords: cancer stem cells, breast cancer, hormone therapy, tamoxifen Acknowledgements: A special thanks to my research mentor Dr. Zachary Abernathy, program director Dr. Joseph Rusinko, and the 2013 NREUP at Winthrop University funded by NSA grant H98230-13-1-0270 and NSF grant DMS-1156582. Page 144 RHIT Undergrad. Math. J., Vol. 15, No. 1
Crimean-Congo Hemorrhagic Fever in Spain - New Arrival or Silent Resident?

Why has CCHFV hit Spain now? It has probably been there for a while, supported by sufficient populations of two competent tick vectors that don’t generally coexist, but the specific ecologic contributors to the recent cases remain unclear.
Molecular Alterations Associated with DNA Repair in Pancreatic Adenocarcinoma Are Associated with Sites of Recurrence

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies with a rising incidence. Mutational analysis of PDAC has provided valuable information but has not yet dramatically changed the therapeutic landscape due to the number of variations detected in any one individual. The pattern of molecular alterations—gene mutations, variations in copy number, and changes in gene expression—has been described in the literature. The purpose of this study is to further investigate the molecular alterations in recurrent or metastatic PDAC based on the site of disease. Molecular alterations in patients with recurrent or metastatic PDAC from 2007 to 2015 were analyzed. The most common molecular alterations found in PDAC tumors from the pancreas were compared to metastatic PDAC specimens from the liver, lung, peritoneum, and other locations. Means were compared with a two-tailed Student’s t test or ANOVA as appropriate. Rates of molecular alterations among the different groups were compared with Pearson’s χ2. Two thousand five hundred fifty-two patients with PDAC were identified in a retrospective database, and the 15 most common molecular alterations were utilized for analysis. The most common alterations among all patients were mutations in KRAS and PTEN (59 and 62%, respectively), with differences in prevalence by site of metastasis (p = 0.042 and p = 0.037, respectively). KRAS mutations were more commonly found in metastasis in the lung (72%) than in other sites (59%, p = 0.042). Low expression of ERCC1 was found in 49% of lung metastases from PDAC but only 15% in PDAC in the pancreas (p < 0.001). Five of the 8 molecular alterations significantly associated with site of metastatic disease were involved in DNA maintenance, repair, replication, or transcription (each p < 0.001). Aberrant expression or mutation in genes involved in DNA maintenance is found in association with specific sites of metastatic PDAC. Personalizing therapy for metastatic PDAC based on site of disease and their associated molecular alterations warrants further investigation.
Contraction frequency after administration of misoprostol in obese versus nonobese women.

Objective: To examine impact of obesity on contraction frequency following misoprostol. Our hypothesis is that an increased volume of distribution reduces the bioavailability of misoprostol and may...
Myocardial Performance and Adrenergic Modulation of Cyclic AMP Following Endotoxin Administration

Myocardial contractility may change in response to altered circulatory demands imposed by physiological stimuli. Many studies have explored the behavior of cardiac contraction during shock of various etiologies. In the final phase of circulatory shock, clinical signs of circulatory insufficiency are indicated by low peripheral perfusion, low mean arterial blood pressure, high heart rate, and central venous congestion. A point is reached in the progression of the syndrome where fatal cardiovascular collapse occurs.
3-(4-Chlorophenyl)-2-(4-diethylaminoethoxyphenyl)-a-pentenonitrile monohydrogen citrate and related analogs: Reversible, competitive, first half-reaction squalene synthetase inhibitors

Abstract Squalene synthetase (SQS) catalyzes the head-to-head condensation of two molecules of farnesyl pyrophosphate (FPP) to form squalene. The reaction is unique when compared with those of other FPP-utilizing enzymes, and proceeds in two distinct steps, both of which involve carbocationic reaction intermediates. In this report, we describe the mechanism of action of, and structure-activity relationships within, a series of substituted diethylaminoethoxystilbenes that mimic these reaction intermediates, through characterization of the biochemical properties of 3-(4-chlorophenyl)-2-(4-diethylaminoethoxyphenyl)-A-pentenonitrile monohydrogen citrate (P-3622) and related analogs. As a representative member of this series, P-3622 inhibited SQS reversibly and competitively with respect to FPP (Ki = 0.7 μM), inhibited the enzymatic first half-reaction to the same extent as the overall reaction, exhibited a 300-fold specificity for SQS inhibition relative to protein farnesyltransferase inhibition, inhibited cholesterol synthesis in rat primary hepatocytes (IC50 = 0.8 μM), in cultured human cells (Hep-G2, CaCo-2, and IM-9; IC50 = 0.2, 1.2, and 1.0 μM), and in chow-fed hamsters (62% at 100 mg/kg) without accumulation of post-squalene sterol precursors, and reduced plasma cholesterol in experimental animals. Structure-activity relationships among 72 related analogs suggest that the phenyl residues and central trans-olefin of the stilbene moiety serve as mimics of the three isoprene units of the donor FPP, that substitutions across the central olefin and para-substitutions on the terminal phenyl residue mimic the branching methyl groups of the donor FPP, and that the diethylaminoethoxy moiety of these molecules mimics the various carbocations that develop in the C1–C3 region of the acceptor FPP during reaction. Members of this series of reversible, competitive, first half-reaction SQS inhibitors that show a high degree of specificity for SQS inhibition relative to inhibition of other FPP-utilizing enzymes and other cholesterol synthesis pathway enzymes may serve as useful tools for probing the unique catalytic mechanisms of this important enzyme.
Uncertainty, Risk Aversion, and the Demand for Insurance

The discussion in Chapter 4 of workers’ choices was made without any risk in the outcomes of the injuries: i.e., the disabilities discussed in Chapter 4 took place at the beginning of the first period. The workers knew at the beginning of their lifecycle that the disabilities had occurred, exactly how long they would last, and what the consequences would be for their wage rates. This is a somewhat unrealistic assumption for workplace injuries in general. The demand for insurance is derived from risky outcomes: both the timing and severity of injury are generally unknown to the worker1. In this first section of the chapter, we focus on a special, but universally used and empirically relevant case where leisure is held constant and the worker faces a risk in the level of lifetime income.
Abstract B69: The effects of patient-physician relationships on perceptions of breast cancer treatment in African American women

According to Indiana.gov, 4,400 new cases of breast cancer are diagnosed in Indiana annually. “During 2008 to 2012, the mortality rates of African American breast cancer patients were almost 40% higher than Caucasian Americans” (Cancer.org), which sheds light on the health disparities African Americans face in the United States. Disparities among cancer patients have not only led to African American women (AAW) being diagnosed in later stages of this disease than their counterparts and thus raising their mortality rates, but AAW tend to be diagnosed with more aggressive forms of cancer such as triple-negative breast cancer, which occurs in 10% to 20% of patients. AAW face many barriers today: limited access to screening services, lack of quality screening equipment, limited access to treatment services, and an unspoken distrust of health care providers. Research indicates that during their breast cancer treatment trajectory, AAW experience delay in initiating chemotherapy after surgery, less satisfaction with treatment, increased symptoms, and lower participation in clinical trials (Mcarthy). Despite this, there is no study that has followed and assessed AAW during the treatment sessions to examine challenges in their lives and their impact. Studies of AAW who have survived breast cancer suggest the need to look not only at factors within the medical care system, but well beyond it into the everyday lives of these women and the resources available to them through social networks and other means to overcome challenges. This project explores themes in the baseline and exit interviews of 38 participants. In their initial interview, we asked questions related to support system, their views of treatment going into the process, and the quality of care that they feel they have received. At the end of treatments, we ask about patient-physician relationships and how the women perceived their care. Women in the study reported the need to readdress concerns with physicians. Patient-physician relationships among AAW diagnosed with breast cancer have been strained and have had a negative impact on patient satisfaction with care. Note: This abstract was not presented at the conference. Citation Format: Alexandria N. Lauray, Silvia Bigatti. The effects of patient-physician relationships on perceptions of breast cancer treatment in African American women [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr B69.
A multiscale dislocation pattern dynamics: Towards an atomistic-informed crystal plasticity theory

Abstract Dislocations in a deformed crystal tend to aggregate into various dense formations separated by relatively dislocation free regions. These dense formations are called dislocation patterns that underlie most important crystal plasticity features such as work hardening and strain localization. In this work, we put forth a novel concept of the geometrically compatible dislocation pattern (GCDP), and we further show that the previously developed multiscale crystal defect dynamics (MCDD) method (Li et al. (2015) Philosophical Magazine, 94,1414-1450. and Lyu and Li, (2017) Journal of Mechanics and Physics of Solids, 107, 379-410.) is actually a discrete dislocation pattern dynamics that can describe evolutions of geometrically compatible dislocation patterns, which may be the dominant dislocation patterns at early stage. The main developments of present work are: (1) We demonstrated that the geometrically compatible dislocation pattern is related to the original crystal lattice microstructure as part of material genome; (2) Using a hierarchical strain gradient formulation, we justified that the multiscale crystal defect dynamics is indeed a multiscale dislocation pattern dynamics, and (3) We showed that the multiscale dislocation pattern dynamics may lead to an atomistic-informed crystal plasticity theory. In doing so, we have developed a MCDD based crystal plasticity finite element method (CPFEM) to simulate crystal slip and shear band formation in single crystals at sub micron scale. The work is highlighted by the use of the MCDD method capturing different types of dislocation patterns, and early cyclic plastic responses of FCC crystals.
Entangled with Numbers: Quantified Self and Others in a Team-Based Online Game

Quantification is a process that produces and communicates numbers, imbued with the expectation of generating knowledge and optimizing human behavior and social process. In this paper, we explore how quantification mediates virtual teamwork through an ethnographic study of quantification in League of Legends, a popular team-based online game with a highly competitive culture. In the game, rich statistics about each individual player's gaming history and performance are publicly available, analyzed and displayed on numerous third-party sites. We describe how players were entangled with numbers. They derived knowledge from numbers but struggled with proper ways of interpretation. They utilized numbers to quantify teammates and opponents, but in-game tensions and conflicts easily ensued. They noticed how quantification became burdensome and stressed the importance of proper use. We discuss how this case of quantified self and others manifests complex relationships between self-knowledge, numerical authority, and virtual teamwork.
Cervical length, cervical dilation, and gestational age at cerclage placement and the risk of preterm birth in women undergoing ultrasound or exam indicated Shirodkar cerclage

Background: Preterm birth is a major cause of neonatal morbidity and mortality in the USA. In many patients at risk for preterm birth, cervical length (CL) screening is used to guide decisions rega...
Proceedings of the International Conference on Software and Systems Process

Welcome to the International Conference on Software and Systems Process (ICSSP) 2016 held in Austin, USA, from 14 to 15 May 2016. The ICSSP conference, continuing the success of Software Process Workshop and International Conference on Software Process (ICSP) conference series, has become an established premier event in the field of software and systems engineering process and is incooperation with ACM/SIGSOFT. It provides a leading forum for the exchange of research outcomes and industrial best-practices in process development from software and systems disciplines. The International Conference on Software and Systems Process (ICSSP) 2016 publishes papers in the many exciting areas of research going on in the domain of Software and Systems process. At the same time, the theme of this year's conference is focused on studying Process(es) in Action and recognizing that the AS-Planned and AS-Practiced processes can be quite different. ICSSP believes there is a strong need to bring practitioners and scientists together to discuss the role of the software process in current and future development of complex systems and in rapidly changing markets. To encourage these discussions and collaborative research, ICSSP provides a proven forum for the exchange of research outcomes and industrial best practices in process development.
Chapter 5 Determination of absolute configuration by CD. Applications of the Octant Rule and the Exciton Chirality Rule

Publisher Summary The origins of two chirality rules—the Octant Rule for ketones and the Exciton Chirality Rule—are described in this chapter. The chapter highlights the way the rules can be applied to the determination of molecular absolute configuration. In applications of the Octant Rule, when the absolute configuration of a ketone is known, the rule may be used to determine its conformation. The applications of the Exciton Chirality Rule to determine the absolute configuration of diols follows from the derivatization with strongly UV–visible absorbing chromophores. Although chiral molecules may exhibit optical activity as detected by circular dichroism (CD), the focus of understanding is typically the light absorbing unit (chromophore) in the molecule. A chromophore is said to be optically active if it exhibits CD in the region of its UV–visible absorption bands. Any chromophore in a chiral molecule can be expected to exhibit Cotton effects. The Octant Rule has been one of the first, and probably the most successful, of many different chirality sector rule relating Cotton effects (CE's) to organic stereochemistry.
Efficacy of a first-grade mathematics intervention on measurement and data analysis

Well-designed mathematics instruction focused on concepts and problem-solving skills associated with measurement and data analysis can build a foundational understanding for more advanced mathemati...
A Distraction Score for Watermarks.

In this work we propose a novel technique to quantify how distracting watermarks are on an image. We begin with watermark detection using a two-tower CNN model composed of a binary classification task and a semantic segmentation prediction. With this model, we demonstrate significant improvement in image precision while maintaining per-pixel accuracy, especially for our real-world dataset with sparse positive examples. We fit a nonlinear function to represent detected watermarks by a single score correlated with human perception based on their size, location, and visual obstructiveness. Finally, we validate our method in an image ranking setup, which is the main application of our watermark scoring algorithm.
Solid Organ Transplant Is Associated With Increased Morbidity and Mortality in Patients Undergoing One or Two-level Anterior Cervical Decompression and Fusion.

STUDY DESIGN Retrospective database review OBJECTIVE.: The aim of this study was to analyze the implications of solid organ transplant (SOT) on postoperative outcomes following elective one or two-level anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA Although SOTs have been associated with increased morbidity, postoperative outcomes in SOT recipients undergoing cervical spinal surgery are not well studied. METHODS A retrospective database review of Medicare patients younger than 85 years who underwent an elective one to two-level ACDF from 2006-2013 was conducted. Following our exclusion criteria, patients were then divided into the following groups: those with a prior history of kidney, liver, heart or lung transplant (SOT group) and non-SOT patients. Both groups were compared for hospital length of stay, 90-day major medical complications, 90-day hospital readmission, 1-year surgical site infection (SSI), 1-year revision ACDF, and 1-year mortality. RESULTS A total of 992 (0.5%) SOT recipients (1,144 organs) were identified out of 199,288 ACDF patients. SOT recipients had a significantly longer length of stay (2.32 vs. 5.22 days, p<0.001), higher rate of major medical complications (8.2% vs. 4.5%; OR 1.85, 95% CI 1.45-2.33, p<0.001) and hospital readmission (19.5% vs. 7.5%, OR 2.05, 95% CI 1.74-2.41, p<0.001). In addition, SOT patients had increased mortality within one year of surgery (5.8% vs. 1.3%; OR 3.01, 95% CI 2.26-3.94, p<0.001) compared to non-SOT patients. SOT was not independently associated with SSI (OR 1.25, 95% CI 0.85-1.75, p=0.230), and there was no significant difference in revision rate (0.9% vs. 0.5%; OR 1.54, 95% CI 0.73-2.82, p=0.202) between both groups. CONCLUSION SOT is independently associated with longer hospital stay, increased rate of major medical complications, hospital readmission and mortality. Spine surgeons should be aware of the higher rates of morbidity and mortality in these patients and take it into consideration when developing patient-specific treatment plans. LEVEL OF EVIDENCE 3.