cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 2034: Personalized chemotherapy regimen selection for breast cancer

Despite the rapid progress in personalized cancer therapy (PCT) for breast cancer, no previous studies have used genomic predictors to choose among multiple chemotherapy regimens. It is unclear that given the current regimens how much PCT can improve the response rate for patients who will receive chemotherapy. In this study, we reanalyzed data from published studies of 1111 breast cancer patients who were treated with neoadjuvant chemotherapies. Those patients were divided into three regimen groups: an anthracycline alone, anthracycline plus paclitaxel, and anthracycline plus docetaxel. We developed a new strategy called PRES (Personalized REgimen Selection) to reassign the optimal regimen to each of the patients. First, a variable selection scheme was developed to identify significant genetic predictors for chemotherapy response. The selected genetic variables were then combined with clinical variables to build random forest models to predict the response of a patient to each regimen using pCR (pathological complete response) as the measure of response. The models were used to assign an optimal regimen to each patient to maximize the chance of pCR. We found that the expected rate of pCR was improved from 21.2% to 39.6% (95% CI: 34.6% - 43.0%). We also found that 31.1% of the patients may have been overtreated and 8.2% patients undertreated. A validation study on 21 cell lines showed that our prediction agrees with their paclitaxel-sensitivity profiles. We performed additional analysis on the Cancer Genome Atlas (TCGA) data and found that 18 of the 19 genes identified are significantly differentially expressed between normal and tumor tissues, and 2 of them, TAF6L and METRN (meteorin), are associated with overall survival. In conclusion, PRES could substantially increase response rates for breast cancer patients who will receive one of the widely-accepted chemotherapy regimens at present. Citation Format: Jinfeng Zhang, Kaixian Yu, Qingxiang Amy Sang, Winston Tan, Mayassa B. Dargham, Jun S. Liu, Ty Lively, Cedric Sheffield. Personalized chemotherapy regimen selection for breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2034.
Photoreceptor Cells Influence Retinal Vascular Degeneration in Mouse Models of Retinal Degeneration and Diabetes.

Purpose Loss of photoreceptor cells is associated with retinal vascular degeneration in retinitis pigmentosa, whereas the presence of photoreceptor cells is implicated in vascular degeneration in diabetic retinopathy. To investigate how both the absence and presence of photoreceptors could damage the retinal vasculature, we compared two mouse models of photoreceptor degeneration (opsin−/− and RhoP23H/P23H ) and control C57Bl/5J mice, each with and without diabetes.
Renin–angiotensin II–aldosterone system blockers and time to renal replacement therapy in children with CKD

Clinical care decisions to treat chronic kidney disease (CKD) in a growing child must often be made without the benefit of evidence from clinical trials. We used observational data from the Chronic Kidney Disease in Children cohort to estimate the effectiveness of renin–angiotensin II–aldosterone system blockade (RAAS) to delay renal replacement therapy (RRT) in children with CKD. A total of 851 participants (median age: 11 years, median glomerular filtration rate [GFR]: 52 ml/min/1.73 m2, median urine protein to creatinine ratio: 0.35 mg/mg) were included. RAAS use was reported at annual study visits. Both Cox proportional hazards models with time-varying RAAS exposure and Cox marginal structural models (MSM) were used to evaluate the effect of RAAS use on time to RRT. Analyses were adjusted or weighted to control for age, male sex, glomerular diagnosis, GFR, nephrotic range proteinuria, anemia, elevated blood pressure, acidosis, elevated phosphate and elevated potassium. There were 217 RRT events over a 4.1-year median follow-up. At baseline, 472 children (55 %) were prevalent RAAS users, who were more likely to be older, have a glomerular etiology, have higher urine protein, be anemic, have elevated serum phosphate and potassium, take more medications, but less likely to have elevated blood pressure, compared with non-users. RAAS use was found to reduce the risk of RRT by 21 % (hazard ratio: 0.79) to 37 % (hazard ratio: 0.63) from standard regression adjustment and MSM models, respectively. These results support inferences from adult studies of a substantial benefit of RAAS use in pediatric CKD patients.
Effects of an integrated collision warning system on teenage driver behavior.

Abstract Introduction Crash warning systems have been shown to provide safety benefits, but no studies have examined how teenagers respond. This study sought to find out whether young, inexperienced drivers change behavior in response to warnings. Methods Forty 16–17 year-olds drove an instrumented vehicle equipped with a system that warned for lane departures and potential rear-end and lane change/merge crashes. Participants were randomly assigned to experimental or control groups, and their driving was monitored for 14 weeks during 2011–12. For the experimental group, this included a treatment period, when crash alerts were received by drivers, and baseline and post-treatment periods, when warnings were recorded but not received. The control group never received warnings. Data were analyzed to determine whether warnings were associated with changes in driving behavior. Results A total of 15,039 trips were analyzed. Lane drifts accounted for 73% of warnings. Forward collision warning rates doubled for all drivers during the treatment period and continued at an increased rate post-treatment. This was likely a result of the fact that, as time went on, all drivers spent more time following vehicles at close distances. Receiving alerts was associated with effects on following and lane-changing behavior, including more time spent following at close distances (17%), fewer lateral drifts (37%) and fewer unsignaled lane changes (80%). Receiving warnings wasn't associated with an increased likelihood of engaging in secondary tasks. Conclusions Warning systems may result in improved lane-keeping and turn-signal behaviors by novice drivers, but there is some indication they may result in more close-following behaviors. Practical applications There is some evidence that lane departure warning may improve turn-signal use for young drivers. While there is no evidence of safety benefits from the other types of warnings, there is some evidence of an increase in close-following behavior but no increase in secondary tasks due to the presence of those capabilities.
OR33: CLINICALLY USEFUL TOOL FOR COMPARING THEORETICAL AND EVIDENCE BASED HLA EPITOPES

Aim Theoretical HLA epitopes (THEps) were defined structurally by three-dimensional molecular modeling and amino acid sequence differences whereas evidence based HLA epitopes (EBHEps) considers the ability of a putative HLA epitope (HEps) to induce antibody. Such HEps are clinically relevant if the antibody is produced in humans on exposure to alloantigen. The aim of this study is to provide a cross reference tool for comparison of structurally defined HEps and EBHEps that may be of use to laboratories interested in defining patient sera by epitope reactivity. Method A comparative analysis of THEps from the International Registry of Antibody-Defined HLA Epitopes ( http://epregistry.com.br ), and evidence based Class I and Class II HLA epitopes from publications. The analysis was arranged in a cross referenced tabular format. Results We found 67 EBHEps that corresponded to theoretical Class I HEps epitope. Of the 67 theoretical Class I HEps, 7 were reactive with mouse monoclonal antibodies only and 60/67 epitopes were reactive with human allosera. Interestingly, 6 of the 60 human allosera - reactive epitopes were present on HLA-A and B, 2/60 were present on HLA-A, B and C, and 3/60 human reactive epitopes were present on HLA-B and C. We also found 55 EBHEps that corresponded to theoretical DR epitopes and16 evidence based DQ epitopes that corresponded to theoretical epitopes. Based on this data, tables were created to cross reference each of the THEps with the EBHEps thereby facilitating analysis of the patient’s antibody data. Conclusion The nomenclature of the theoretical epitopes ( http://epregistry.com.br ) is based on the position of the polymorphic amino acid residue in numerical order in the polypeptide chain followed by the single letter amino acid code (in alphabetical order). Evidence based epitopes had been published as a list in consecutive numerical order unrelated to the polymorphic amino acid position. One of the major goals of the HLA epitope registry is to identify clinically relevant HLA epitopes that have been verified experimentally with human allosera. The charts developed in our study allow for the convenient cross correlation between evidence based epitopes and theoretical epitopes that will be updated according to new evidence of human allosera reactivity. A.J. Norin: Speaker’s Bureau; Company/Organization; Immuncor - Lifecodes. Scientific/Medical Advisor; Company/Organization; ICON CL.
The design and implementation of a new magnetic field stimulation device

We have developed a new type of magnetic field generation and stimulation device based on the principle of electromagnetic induction for the needs of the research on biological signals base on some magnetic field stimulation in our laboratory,. The design can output a single or continuous low frequency pulse magnetic signals, the maximum magnetic induction intensity in the magnetic stimulation coil center can reach more than 10T. The biological cells produce real-time response with the stimulating of themag+netic induced curren.
Eogenetic diagenesis of Chinle sandstones, Petrified Forest National Park (Arizona, USA): A record of Late Triassic climate change

Fluvially derived tuffaceous Chinle sandstones from Petrified Forest National Park provide a well-preserved Late Triassic archive of climate information. Petrographic analysis of 38 Chinle sandstones provides new insight into the depositional history and evolution of palaeoclimate during Chinle deposition. This study focuses on the relationship between climate and meteoric diagenesis as a guide for constraining climate change in western equatorial Pangea during the Late Triassic. Petrographic analysis of Chinle sandstones reveals their wide range of textural attributes, as well as pedogenic and shallow burial diagenetic features that occurred during the Late Triassic. These diverse petrological characteristics are indicative of the evolving Late Triassic climate, when placed into a well-constrained stratigraphic and geochronological framework. The stratigraphic succession is characterized by variations in the abundance of framework grains, detrital matrix, weathering intensity of feldspar and volcanic rock fragments, and the mineralogy of clay cements. Climate records from Chinle palaeosol geochemistry indicate a progression from wet to dry conditions. This trend is also reflected in the meteoric diagenetic features of Chinle sandstones. During deposition of the lower Chinle, elevated rainfall promoted the weathering of labile volcanic detritus to kaolinite, whereas feldspars (especially plagioclase) were partially or completely dissolved. In the upper Chinle, a trend towards drier conditions favoured the formation of smectite and less feldspar dissolution resulting in a higher abundance of well-preserved plagioclase grains. Shallow burial meteoric weathering reactions in Chinle sandstones reflect the evolving climate during the Late Triassic.
Cape Fear’s Forgotten Fleet: The Eagles Island Ship Graveyard, Wilmington, North Carolina

Settlers established Wilmington, North Carolina, on the east bank of the Cape Fear River in 1731. The town grew rapidly as a result of the lucrative naval stores industry supported by the abundant pine forests of the surrounding the area. From the early nineteenth century through the turn of the twentieth century, Wilmington grew to be the most populous city in North Carolina and the only significant port. Wilmington continued to grow and decline with changing local and global economic and cultural conditions, but its maritime industry always remained at the forefront of the development of the port city.
Survival in patients with Parkinson's disease after deep brain stimulation or medical management.

Objective: Deep brain stimulation has been shown to have a significant long-term beneficial effect on motor function. However, whether it affects survival is not clear. In this study, we compared survival rates for Parkinson's disease (PD) patients who underwent deep brain stimulation (DBS) with those who were medically managed. Methods: A retrospective analysis of Veterans Affairs and Medicare administrative data of veterans with PD who received DBS and were propensity score matched to a cohort of veterans with PD who did not receive DBS between 2007-2013. Results: Veterans with PD who received DBS had a longer survival measured in days than a matched group of veterans who did not undergo DBS (mean = 2291.1 [standard error = 46.4] days [6.3 years] vs 2063.8 [standard error = 47.7] days [5.7 years]; P = .006; hazard ratio = 0.69 [95% confidence interval 0.56-0.85]). Mean age at death was similar for both groups (76.5 [standard deviation = 7.2] vs 75.9 [standard deviation = 8.4] years, P = .67), respectively, and the most common cause of death was PD. Conclusions: DBS is associated with a modest survival advantage when compared with a matched group of patients who did not undergo DBS. Whether the survival advantage reflects a moderating influence of DBS on PD or on comorbidities that might shorten life or whether differences may be a result of unmeasured differences between groups is not known. © 2017 International Parkinson and Movement Disorder Society
Management of venous thromboembolism with non-vitamin K oral anticoagulants: A review for nurse practitioners and pharmacists.

ABSTRACTBackground and purpose:Venous thromboembolism (VTE), comprising deep-vein thrombosis and pulmonary embolism, is associated with significant morbidity and mortality. Non–vitamin K oral anticoagulants (NOACs), including apixaban, betrixaban, dabigatran, edoxaban, and rivaroxaban, are as effect
Some Conformational Effects of Chelate Rings

The basis for stereospecific or stereoselective processes is now understood from the classic paper by Corey and Bailar.1 Their approach and predictions have been well substantiated; the paper is one of the most often cited references in the field of coordination chemistry. It provides the basis for interpreting pmr studies and for detailed stereochemical studies of metal chelates, including conformational effects of chelate rings.
Nonlinear Modeling and Vibrations of Sandwiches and Laminated Composites

In the preceding chapter, a method of developing nonlinear dynamical models has been applied to homogeneous beams, plates, and shallow shells through the use of a pseudo-variational equation of motion in nonlinear elasticity. The famous Timoshenko beam equations, von Karman plate equations, and Marguerre shallow shell equations have been rederived and extended. In this chapter, the method is further applied to layered plates, including sandwiches and laminated composites. The equations derived are next applied to the analysis of nonlinear vibrations.
Abdominal Cysts and Duplications

Many intra-abdominal cystic masses are being detected by prenatal imaging. They are often asymptomatic but those that cause symptoms usually do so in the first year or two of life. Symptoms are usually the result of compression or obstruction due to enlargement of the cyst as it gradually fills with fluid, or bleeding and ulceration due to gastric or pancreatic lining of the cyst. Cysts can arise from solid or hollow organs and various imaging modalities can help to distinguish the specific site of origin. Enteric duplication cysts are sometimes associated with intestinal atresias whereas tubular colonic or rectal duplications are commonly associated with genitourinary malformations. Optimal treatment usually involves complete resection of the cyst; but in some situations asymptomatic cysts detected prenatally can be observed clinically and radiographically.
Chairmen’s Overview on Enzyme Markers

When looking for suitable biological markers of cell alteration as a response to the action of carcinogens, enzymes are obvious candidates for several reasons. Firstly, the enzyme complement of an adult, differentiated tissue is unique to that tissue, being optimal for its functioning. Thus, although many enzymes are ubiquitous, since they are essential for general cell metabolism, the activities in different tissues generally differ. Secondly, a specific adult differentiated tissue has some enzymes which are unique to that tissue, or which occur in much higher concentration in that tissue than in other tissues. Thirdly, many enzymes exist in multiple forms, or isozymes; again, the isozyme pattern may distinguish a particular adult differentiated tissue from other differentiated adult tissues. Fourthly, because most enzymes are highly specific towards their substrates, it is possible to assay an enzyme and its isozymes in a crude homogenate containing many other proteins. Tumors frequently have a different enzyme and isozyme profile to the tissue of origin, since their metabolic requirements are so different. A potential carcinogen might thus be expected to perturb the metabolic profile of an adult differentiated tissue, as reflected in the enzyme and isozyme complement, and this can easily be detected by suitable assay procedures.
Epigenetic Programming by Maternal Behavior in the Human Infant.

OBJECTIVES: We sought to determine if variations in maternal care alter DNA methylation in term, healthy, 5-month-old infants. This work was based on landmark studies in animal models demonstrating that nurturing care by dams would alter their newborns’ stress responses through epigenetic mechanisms. We used breastfeeding as a proxy for animal maternal behavior. We hypothesized alterations in DNA methylation of the glucocorticoid receptor gene and less hypothalamic stress response in infants of mothers who breastfed their infants versus infants of mothers who did not breastfeed. METHODS: A cohort study of term, healthy infants and their mothers who did (n = 21) or did not (n = 21) breastfeed for the first 5 months was used in this analysis. Cortisol stress reactivity was measured in infant saliva by using a mother-infant interaction procedure and DNA methylation of an important regulatory region of the glucocorticoid receptor gene. Changes in DNA methylation of this gene in humans were compared to homologous regions of the rat gene. DNA samples were prepared from cheek swabs and subjected to quantitative analysis of the extent of methylation by using sensitive sequencing techniques. RESULTS: Breastfeeding was associated with decreased DNA methylation of the glucocorticoid receptor promoter and decreased cortisol reactivity in 5-month-old infants. Decreased DNA methylation occurred in the promoter region involved in regulation of the hypothalamic-pituitary-adrenal and immune system responses. CONCLUSIONS: Maternal care in humans may impact the hypothalamic-pituitary-adrenal stress response through behavioral programming and manifest as offspring epigenetic change. These results explain, in part, some of the positive effects observed in children who are breastfed.
Pretreatment and fermentation of salt-water grown algal biomass as a feedstock for biofuels and high-value biochemicals

Abstract Utilization of halotolerant algal strains and saline water resources is necessary to increase the areas available for algal cultivation and to mitigate fresh water use issues. However, the added salt content from salt-water algae cultivation may impact downstream biomass pretreatment and conversion processes especially when combined with the salt that is generated as part of our Combined Algal Processing (CAP) scheme which includes pretreatment with sulfuric acid for cell disruption and carbohydrate hydrolysis. Here we compared the pretreatment, fermentation, and lipid extraction processes on salt-water versus fresh-water grown algal biomass. Response surface pretreatment plots showed that a broader range of conditions for the salt-water grown algae species yield >90% sugar yield compared to a narrower range for fresh-water species. Despite this, we anticipated that high salt content would inhibit fermentation of algal sugars, a key element the CAP scheme and sought to reduce the formation of additional salt from pretreatment and neutralization by substituting oxalic acid for sulfuric acid. The sugar release response surface for oxalic acid was of a different shape than that of sulfuric acid but achieved >90% sugar release at 2% acid. Fermentation results showed that for Saccharomyces cerevisiae, the added salts had minimal impact on sugar utilization rates or ethanol production. For Actinobacillus succinogenes however, a significant delay was observed due to the additional salts and fermentation was further delayed or inhibited by pretreatment with oxalic acid. This was remedied by removal of the oxalic acid either by the addition of CaCO3 or trioctylamine whereupon fermentation rates recovered. Differences in lipid extraction yields were observed from the fermentation broth between the salt-water grown and fresh-water grown algal biomass and was species dependent.
The extrinsic risk and its association with neural alterations in spasmodic dysphonia

Abstract Introduction Spasmodic dysphonia (SD) is an isolated focal dystonia characterized by laryngeal spasms during voluntary voice production. Environmental factors have been assumed to play a role in SD pathophysiology; however, the exact extrinsic risk factors and their association with neural alterations remain unknown. Methods A total of 186 SD patients and 85 healthy controls completed a structured 177-question survey, consisting of questions on general biographical information, medical history, symptomatology of dystonia. Data were imputed in a stepwise regression model to identify extrinsic risk factors for SD. In addition, functional MRI data from a subset of this cohort were analyzed to determine brain activation abnormalities associated with the SD extrinsic risk. Results We found that (1) recurrent upper respiratory infections, gastroesophageal reflux, and neck trauma, all of which influence sensory feedback from the larynx, represent extrinsic risk factors, likely triggering the manifestation of SD symptoms, and (2) neural alterations in the regions necessary for sensorimotor preparation and integration are influenced by an extrinsic risk in susceptible individuals. Conclusions These findings provide evidence for the extrinsic risk in SD development and demonstrate the link with alterations in the sensorimotor preparatory network that collectively contribute to the multifactorial pathophysiology of SD.
Mapping Charge Percolation in Flowable Electrodes Used in Capacitive Deionization

Electrical percolation in flow electrode capacitive deionization is critical to mitigate electronic resistance and maximize ion electrosorption. It is experimentally challenging to characterize mas...
Avoiding Beach's Boojum Effect: Enhancing bench to bedside translation with field to laboratory considerations in optimal animal models.

Abstract Pioneering comparative neuroendocrinologist Frank Beach cautioned researchers of the dangers of investing too much research energy in a single species (i.e., the laboratory rat) in the pursuit of limited behavioral investigations (e.g., learning) in his 1950 article entitled The snark was a boojum. Over a half-century later, behavioral neuroscientists continue to focus disproportionately on rodent models and, although exciting cutting-edge neuroscience techniques are currently utilized, the sophistication of behavioral approaches often lag behind these neurobiological methodological tools. The predictable, sterile laboratory environments, referred to as niceties by Beach, also present challenges to the investigation of relevant, species-specific responses to unpredictable natural environments. As more attention is directed to these methodological issues, fundamental information about nervous systems, as well as the translational value of studies utilizing various animal models, will be enhanced.
Urban Political Ecology in the Anthropo-obscene: Interruptions and Possibilities

Thirteen years since the publication of In the Nature of Cities: Urban Political Ecology and the Politics of Urban Metabolism (Heynen, Kaika, and Swyngedouw 2006) set the agenda for urban political...
Future development of amifostine as a radioprotectant

Animal data and clinical trials document the efficacy of amifostine (WR-2721, Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) in decreasing the effects of radiation on normal tissues without decreasing the cytotoxic effects on malignant tumors. The selection of the optimal dose may depend on the intensity of the regimen to be administered as well as on the normal tissues to be protected. Also of important consideration is the question of how to sequence amifostine infusion. The optimal amifostine schedule during the course of the combined-modality treatment may require shortening the duration of chemotherapy infusion or giving amifostine in two split doses (before and after chemotherapy). Wide application of amifostine in once-daily/multiple-daily fractionated radiotherapy regimens may be facilitated by the availability of other, nonintravenous delivery routes, which are being explored. Although efforts are currently directed at amifostine-mediated modification of acute or late mucosal reactions associated with radiation therapy, there are many other radiation-induced toxicities. Further randomized studies are necessary to document the effects of amifostine on nonmucosal damage. Amifostine has the potential to protect a broad range of normal tissues from the toxicities of radiation and from certain forms of chemotherapy.
Montesquieu and History

I am very pleased to have a chance to participate in a discussion of these two fine books. They are both very clear and tightly argued, full of attention to detail without losing sight of the broad...
Translation and Loss-Aversion

This paper is about the inflation of loss talk in a certain discourse on translation and how translation is often presented as a disaster or even an emblem of what is always missing. My guiding questions will be: Why has the notion of loss become such a dominant concept when talking about translation? Where does this rhetoric of loss—in translators’ reflections, in translation reviews as well as in scholarly material of theoreticians—come from? What are some of the assumptions that underlie this loss discourse on translation products? Can we go beyond a descriptive perspective of the phenomenon and try to come up with a few explanations for this loss talk on translation? I shall furthermore explore the concept of loss-aversion from economics and decision theory (Kahneman, 2011), and argue that loss-aversion may help us to better understand how the notion of loss, and more generally the gain-loss equation, operate in the field of translation. Finally looking at translation discourse through the losing-glass, I will briefly discuss a few “unlosables” from the field of biblical Hebrew translation.
Virtual Laparoscopic Skills Training Guide for FLS (Fundamentals of Laparoscopic Surgery)

Study Objective The objective of this video is to provide an example of how to teach laparoscopic skills, specifically FLS (fundamentals of Laparoscopic Surgery) virtually and remotely. Design This is an educational video. Institutional review board approval was not required for this video article as the video does not describe a clinical case but rather laparoscopic simulation. Setting Academic teaching hospital. Patients or Participants Gynecologic surgery trainees. Interventions The video demonstrates how to set up a portable laparoscopic trainer box for mobile devices and provides tips and tricks to optimize a virtual platform for teaching FLS (Fundamentals of Laparoscopic Surgery). Measurements and Main Results The key elements for successful implementation of virtual laparoscopic skills training include accessibility to low-cost portable laparoscopic trainers, a mobile device and a virtual platform. Conclusion Tele-simulation for laparoscopic skills training is feasible and cost-effective.
2.5D Metastructures; Design, Optimization, and Experimental Demonstration

We present the design, fabrication, and characterization of multifunctional 2.5D metastructures using adjoint optimization. Our technique considers complex interactions among meta-atoms and offers significantly improved performance compared to conventional unit-cell-based techniques.
Danuglipron (PF-06882961) in type 2 diabetes: a randomized, placebo-controlled, multiple ascending-dose phase 1 trial.

Agonism of the glucagon-like peptide-1 receptor (GLP-1R) results in glycemic lowering and body weight loss and is a therapeutic strategy to treat type 2 diabetes (T2D) and obesity. We developed danuglipron (PF-06882961), an oral small-molecule GLP-1R agonist and found it had comparable efficacy to injectable peptidic GLP-1R agonists in a humanized mouse model. We then completed a placebo-controlled, randomized, double-blind, multiple ascending-dose phase 1 study ( NCT03538743 ), in which we enrolled 98 patients with T2D on background metformin and randomized them to receive multiple ascending doses of danuglipron or placebo for 28 d, across eight cohorts. The primary outcomes were assessment of adverse events (AEs), safety laboratory tests, vital signs and 12-lead electrocardiograms. Most AEs were mild, with nausea, dyspepsia and vomiting most commonly reported. There were no clinically meaningful AEs in laboratory values across groups. Heart rate generally increased with danuglipron treatment at day 28, but no heart-rate AEs were reported. Systolic blood pressure was slightly decreased and changes in diastolic blood pressure were similar with danuglipron treatment at day 28, compared with placebo. There were no clinically meaningful electrocardiogram findings. In this study in T2D, danuglipron was generally well tolerated, with a safety profile consistent with the mechanism of action of GLP-1R agonism. Results from a phase 1 study testing a new oral GLP-1 receptor agonist, danuglipron, in patients with type 2 diabetes demonstrate acceptable safety, tolerability and pharmacokinetic profiles of the drug, with exploratory analyses suggesting potential beneficial effects on glycemic control.
Ultrasound-induced structural modification and thermal properties of oat protein

Abstract The objective of this study was to characterize the solubility, structural, thermal, and aggregation properties of oat protein under high-intensity ultrasound (HIU) treatment. Suspensions of oat protein isolate (OPI) at pH 2.0–8.0 were subjected to HIU for 5 min at 70% amplitude; solubility, particle size, surface attributes, UV–Vis absorption, intrinsic fluorescence, polypeptide profiles, calorimetric properties, and thermal aggregation were determined. The HIU treatment significantly reduced particle size (up to 37%) and increased surface charge of OPI leading to solubility increases (up to 48%, P
Recent Developments in Privacy-preserving Mining of Clinical Data

With the dramatic improvements in both the capability to collect personal data and the capability to analyze large amounts of data, increasingly sophisticated and personal insights are being drawn....
Confined projection on selected sub-surface using a robust binary-coded pattern for pico-projectors

Traditional projection environments typically comprise projectors and custom-built projection screens in a static setting. However, with the availability of embedded and standalone pico-projectors, the representative use-case of such hand-held projectors is shifting from static to mobile. Users are increasingly using such devices to project content in random indoor environments that are cluttered and hence not completely suitable for projection. This paper proposes a robust binary-coded pattern that enables the reliable selection of a clutter-free sub-surface from within the projected area and thus allows the confinement of projection to the selected sub-region. Experiments confirm that the proposed pattern provides better resilience to the detection errors as compared to the state-of-the-art binary-coded patterns for the case of mobile-grade low-resolution pico-projectors.
Hume on presentation and philosophy

Most philosophers agree that an argument's presentation is relevant to its philosophical merit. This paper explains why David Hume considered presentation philosophically important. On Hume's epistemology, presentation is closely connected with two principal aims of philosophical arguments: persuasion and epistemic justification. Hume's views imply that presentation is a factor determining an argument's persuasiveness and that, by philosophical standards of justification, presentation is also a factor determining the extent to which an argument's conclusion is justified.
Analysis of Time-Periodic Nonlinear Dynamical Systems Undergoing Bifurcations

In this study a new procedure for analysis of nonlinear dynamical systems with periodically varying parameters under critical conditions is presented through an application of the Liapunov-Floquet (L-F) transformation. The L-F transformation is obtained by computing the state transition matrix associated with the linear part of the problem. The elements of the state transition matrix are expressed in terms of Chebyshev polynomials in time t which is suitable for algebraic manipulations. Application of Floquet theory and the eigen-analysis of the state transition matrix at the end of one principal period provides the L-F transformation matrix in terms of the Chebyshev polynomials. Since this is a periodic matrix, the L-F transformation matrix has a Fourier representation. It is well known that such a transformation converts a linear periodic system into a linear time-invariant one. When applied to quasi-linear equations with periodic coefficients, a dynamically similar system is obtained whose linear part is time-invariant and the nonlinear part consists of coefficients which are periodic. Due to this property of the L-F transformation, a periodic orbit in original coordinates will have a fixed point representation in the transformed coordinates. In this study, the bifurcation analysis of the transformed equations, obtained after the application of the L-F transformation, is conducted by employing time-dependent center manifold reduction and time-dependent normal form theory. The above procedures are analogous to existing methods that are employed in the study of bifurcations of autonomous systems. For the two physical examples considered, the three generic codimension one bifurcations namely, Hopf, flip and fold bifurcations are analyzed. In the first example, the primary bifurcations of a parametrically excited single degree of freedom pendulum is studied. As a second example, a double inverted pendulum subjected to a periodic loading which undergoes Hopf or flip bifurcation is analyzed. The methodology is semi-analytic in nature and provides quantitative measure of stability when compared to point mappings method. Furthermore, the technique is applicable also to those systems where the periodic term of the linear part does not contain a small parameter which is certainly not the case with perturbation or averaging methods. The conclusions of the study are substantiated by numerical simulations. It is believed that analysis of this nature has been reported for the first time for this class of systems.
Spatial Memory Processing: Enhancement during Hypnosis

Hypnosis is a state in which responsive individuals commonly report that their imagery is more vivid, spontaneous, and effortless than during the waking state. The loss of a generalized reality orientation (Shor, 1970), so that the distinction between imagination and reality is decreased or nonexistent with a concomitant increase in imagery and possibly primary process thinking, is seen to be an important reason why hypnosis is an effective therapeutic technique. Additionally, some highly hypnotizable subjects report during hypnosis that their cognitive processing becomes more holistic and visual in nature. Such phenomenological descriptions suggest that there may be a shift in emphasis from a more verbal, detailoriented coding system during the normal state to a more visual, imageoriented coding system during hypnosis. This paper will present research which is concerned with whether or not information is processed differently during hypnosis, and, if it is indeed differently processed, what is different about it.
Analysis of Sulfoglycolipids by Mass Spectrometry

Glycosphingolipid (GSL) expression in developing tissues is spatially and temporally regulated. Post-synthetic glycan modifications such as sulfation, phosphorylation, and O-acetylation are associated with specific cell types within complex tissues and with specific developmental stages. Sulfated GSLs (sulfo-GSLs) have been shown to bind a variety of cell surface and extracellular matrix proteins and to also play an important role as adhesion molecules, acting as ligands for Pand L-selectin. In addition, sulfo-GSL expression correlates with cancer progression and facilitates the phagocytic clearance of cancer cells by macrophages. In general, glycoconjugate sulfation impacts a wide variety of intercellular interactions and signaling pathways. Glycomic approaches for analyzing GSLs in biological samples frequently utilize enzymatic release of oligosaccharide chains from their ceramide lipid moieties. Ceramides are structurally heterogeneous, composed of one of several sphingosine bases in M. Tiemeyer • K. Aoki (*) Department of Biochemistry and Molecular Biology, Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA e-mail: mtiemeyer@ccrc.uga.edu; kaoki@ccrc.uga.edu # Springer Japan 2015 N. Taniguchi et al. (eds.), Glycoscience: Biology and Medicine, DOI 10.1007/978-4-431-54841-6_13 155 amide linkage to a variety of fatty acids. Thus, enzymatic release of the GSL glycan has the useful property of simplifying the complexity of the sample. Unfortunately, this approach suffers from the limited specificity of the enzyme most commonly used for glycan release, an endoglycosylceramidase, EGCase. EGCase releases the glycans of GSLs with complex modifications, such as sulfation, sialylation, or unique monosaccharide sequences, with decreased efficiency. Therefore, in order to explore the full complements of GSLs including glycan and ceramide moieties, a sensitive, robust, and selective methodology for glycolipidomics is required. This chapter describes a procedure for comprehensive glycolipidomics that is also applicable to the characterization of sulfoglycoconjugates.
Structure-function of muscarinic receptor coupling to G proteins. Random saturation mutagenesis identifies a critical determinant of receptor affinity for G proteins.

Abstract To derive structure-function relationships for receptor-G protein coupling, libraries were created of human m5 muscarinic acetylcholine receptors (m5) randomly mutated in the C-terminal region of the third intracellular loop. Functional receptors were identified based on their ability to amplify NIH 3T3 cells in a ligand-dependent manner. These receptors either had wild-type phenotypes (Group 1) or were functionally impaired (Group 2). No “activated receptors” were identified. Tolerated substitutions in Group 2 receptors were randomly distributed and frequently included prolines and glycines. In contrast, tolerated substitutions in Group 1 receptors exhibited a periodicity proximal to transmembrane domain 6 where proline and glycine substitutions were not observed. These observations are consistent with a short α-helical extension of the C-terminal region of the third intracellular loop from transmembrane domain 6. Mutations at Ala-441 were most commonly associated with impaired function of Group 2 receptors. Twelve point mutations at Ala-441 were tested, and all caused marked increases in EC values with little effect on maximal response or agonist binding affinity. These results indicate that Ala-441 is a key determinant of m5 receptor affinity for G proteins and exists within the structural context of a short α-helix.
Droning on: Explaining the Proliferation of Unmanned Aerial Vehicles

Unmanned Aerial Vehicles (UAVs), more popularly known as "drones," have become emblematic of 21st century military technologies. Yet scholars have yet to convincingly explain the drivers of UAV proliferation. This article makes sense of the intensifying global interest in UAV technology. We develop and present initial evidence on four theoretical arguments for why countries pursue UAVs, utilizing a new comprehensive dataset on UAV proliferation. Our data underscore the vital importance of understanding drone proliferation: 87 countries have some UAV capability, 23 possess more sophisticated drones, and 30 have armed UAV programs. Our analysis reveals some important findings. First, countries that experience security threats – including territorial disputes and terrorism – are more likely to seek UAVs. Second, prestige-seeking countries are especially likely to obtain tactical UAVs, but prestige is less relevant for acquiring more sophisticated drones. Third, we find a "U-shaped" relationship between a state's regime and the spread of armed UAV programs, suggesting that autocracies and democracies have their own unique incentives to acquire this technology. Fourth, supply-side factors play a major role in the UAV proliferation process. A state's level of technological sophistication and its alliance relationships with major suppliers are strong predictors of unarmed drone proliferation. The theories and evidence presented in this article challenge emerging wisdoms about UAV proliferation, and shed useful light on how and why drones spread.
Cellular Localization of Huntingtin in Striatal and Cortical Neurons in Rats: Lack of Correlation with Neuronal Vulnerability in Huntington’s Disease

Immunohistochemistry and single-cell RT-PCR were used to characterize the localization of huntingtin and/or its mRNA in the major types of striatal neurons and in corticostriatal projection neurons in rats. Single-label immunohistochemical studies revealed that striatum contains scattered large neurons rich in huntingtin and more numerous medium-sized neurons moderate in huntingtin. Double-label immunohistochemical studies showed that the large huntingtin-rich striatal neurons include nearly all cholinergic interneurons and some parvalbuminergic interneurons. Somatostatinergic striatal interneurons, which are medium in size, rarely contained huntingtin. Calbindin immunolabeling showed that the vast majority of the medium-sized striatal neurons that contain huntingtin are projection neurons, but only ∼65% of calbindin-labeled projection neurons (localized to the matrix compartment of striatum) were labeled for huntingtin. Calbindin-containing projection neurons of the matrix compartment and calbindin-negative projection neurons of the striatal patch compartment contained huntingtin with comparable frequency. Single-cell RT-PCR confirmed that striatal cholinergic interneurons contain huntingtin, but only ∼65% of projection neurons contained detectable huntingtin message. The finding that huntingtin is not consistently found in striatal projection neurons [which die in Huntington’s disease (HD)] but is abundant in striatal cholinergic interneurons (which survive in Huntington’s disease) suggests that the mutation in huntingtin that causes HD may not directly kill neurons. In contrast to the heterogeneous expression of huntingtin in the different striatal neuron types, we found all corticostriatal neurons to be rich in huntingtin protein and mRNA. One possibility raised by our findings is that the HD mutation may render corticostriatal neurons destructive rather than render striatal neurons vulnerable.
The effect of rotenone on the regulation of fatty acid synthesis in heart mitochondria.

Acetate-1-14C incorporation into long chain fatty acids by rabbit heart mitochondria was increased up to 20-fold by citrate, isocitrate, malate, or succinate in the presence of rotenone and ATP. Rotenone blocked NADH oxidation and enabled the maintenance of a high NADH:NAD+ ratio. The rate of fatty acid synthesis was linearly related to the resulting endogenous mitochondrial NADH:NAD+ ratio. By inhibiting reversed electron flow, rotenone inhibited the early high rate of acetate incorporation observed with succinate oxidation. In this situation, succinate supplied reducing equivalents for fatty acid synthesis via malate dehydrogenase. Rotenone also blocked the ADP- or dinitrophenol-induced cleavage of newly incorporated acetate-1-14C from mitochondrial fatty acids by preventing a decrease in the NADH:NAD+ ratio. The NAD oxidation-reduction state is concluded to be the regulator of the rate and direction of the heart mitochondrial fatty acid synthetic-oxidation system.
An investigation of stack based algorithms for voice-packet transmission in microcellular wireless environments

We present the results of a simulation study that explores the performance of four stack based reservation random access (RRA) protocols for transmitting voice packets over a common radio broadcast channel in a microcellular radio environment. These algorithms provide a mechanism that enables all of the terminals within a microcell to differentiate between available voice and available data time slots; therefore, voice-data integration can be achieved by eliminating competition between voice and data terminals for available slots. We consider voice transmissions over an ideal channel, over a channel subject to memoryless errors, and over a channel with capture. Our results show that by varying the size of the stack (2 cell or 3 cell) and/or the feedback (binary versus ternary) we can make a trade off between voice and data traffic performance.
MAPPING REPLICATIONAL SITES IN THE EUCARYOTIC CELL NUCLEUS

We have used fluorescent microscopy to map DNA replication sites in the interphase cell nucleus after incorporation of biotinylated dUTP into permeabilized PtK-1 kangaroo kidney or 3T3 mouse fibroblast cells. Discrete replication granules were found distributed throughout the nuclear interior and along the periphery. Three distinct patterns of replication sites in relationship to chromatin domains in the cell nucleus and the period of S phase were detected and termed type I (early to mid S), type II (mid to late S) and type III (late S). Similar patterns were seen with in vivo replicated DNA using antibodies to 5-bromodeoxyuridine. Extraction of the permeabilized cells with DNase I and 0.2 M ammonium sulfate revealed a striking maintenance of these replication granules and their distinct intranuclear arrangements with the remaining nuclear matrix structures despite the removal of greater than 90% of the total nuclear DNA. The in situ prepared nuclear matrix structures also incorporated biotinylated dUTP into replication granules that were indistinguishable from those detected within the intact nucleus.