cssi/SciSciGPT-SciSciNet huggingface dataset:
Refinement of the crystal structure of wheat germ agglutinin isolectin 2 at 1.8 A resolution.

Abstract The crystal structure of wheat germ agglutinin isolectin 2 has been refined by the restrained least-squares method of Hendrickson & Konnert (1980). The asymmetric unit of the C 2 crystals contains two chemically identical protomers related by a non-crystallographic 2-fold screw operation. A total of 2290 protein atoms and 186 ordered water sites refined to a final R -factor of 0.179 and an average B -value of 21.6A 2 , using 54% (15,601) of the total possible number of reflections in the resolution range 8 to 1.8Awith F o > 3σ(F o ). The final model conforms to stereochemically correct bond distances and angles with root-mean-square (r.m.s.) values of 0.018Aand 3.3 °, respectively. Accuracy of this model is estimated to be 0.20Aon the basis of a Luzzati plot. Main-chain atomic positions in the two independent promoters, designated I and II, agree with an r.m.s. deviation of 0.30A(0.58Afor all atoms), indicating identical backbone conformation. The largest discrepancies are seen at flexible surface residues. One error was detected in the amino acid sequence at position 41 (Ser), which refined satisfactorily as a Trp. Loss of electron density for residue A171 during the course of refinement suggests either disorder or absence of this C-terminal residue. residue domains (A, B, C and D), was analyzed in terms of dihedral angles, backbone hydrogen bond lengths and CA-atom positions. The four domains were found to be very similar according to all these criteria and superposition of their CA-atoms yielded r.m.s. distances ranging from 0.36 to 0.72Afor the six possible comparisons. Large deviations (> 1.0A) are only seen in the five-residue segments that link adjacent domains and at the N and C termini. Refinement has also allowed critical examination of each of the two unique sugar binding sites, referred to as “primary” and “secondary” sites, in different lattice environments. While the essential tyrosyl side-chain in each of these sites (Y73, Y159) assumes precise orientation for optimum hydrophobic contact with the N -acetyl methyl group of the sugar ligand, side-chains involved in hydrogen bonds (S62, E115; and S148, D29) were found to be relatively flexible and able to adapt their conformation to changes in environment. Ordered water structure present in these binding sites is not completely analogous in the different environments. In addition, intermolecular interactions as well as protein-solvent association, important for dimerization and stabilization of the crystal lattice, have been examined and compared in the independent environments.
Visual Motion Retards Alternations between Conflicting Perceptual Interpretations

When the visual system is faced with conflicting or ambiguous stimulus information, visual perception fluctuates over time. We found that perceptual alternations are slowed when inducing stimuli move within the visual field, constantly engaging fresh, unadapted neural tissue. During binocular rivalry, dominance durations were longer when rival figures moved compared to when they were stationary, yielding lower alternation rates. Rate was not reduced, however, when observers tracked the moving targets, keeping the images on approximately the same retinal area. Alternations were reliably triggered when rival targets passed through a local region of the visual field preadapted to one of the rival targets. During viewing of a kinetic globe whose direction of rotation was ambiguous, observers experienced fewer alternations in perceived direction when the globe moved around the visual field or when the globe's axis of rotation changed continuously. Evidently, local neural adaptation is a key ingredient in the instability of perception.
Dimension reduction with gene expression data using targeted variable importance measurement

When a large number of candidate variables are present, a dimension reduction procedure is usually conducted to reduce the variable space before the subsequent analysis is carried out. The goal of dimension reduction is to find a list of candidate genes with a more operable length ideally including all the relevant genes. Leaving many uninformative genes in the analysis can lead to biased estimates and reduced power. Therefore, dimension reduction is often considered a necessary predecessor of the analysis because it can not only reduce the cost of handling numerous variables, but also has the potential to improve the performance of the downstream analysis algorithms. We propose a TMLE-VIM dimension reduction procedure based on the variable importance measurement (VIM) in the frame work of targeted maximum likelihood estimation (TMLE). TMLE is an extension of maximum likelihood estimation targeting the parameter of interest. TMLE-VIM is a two-stage procedure. The first stage resorts to a machine learning algorithm, and the second step improves the first stage estimation with respect to the parameter of interest. We demonstrate with simulations and data analyses that our approach not only enjoys the prediction power of machine learning algorithms, but also accounts for the correlation structures among variables and therefore produces better variable rankings. When utilized in dimension reduction, TMLE-VIM can help to obtain the shortest possible list with the most truly associated variables.
Activation of purified prothrombin.

SummaryPurified prothrombin can be activated by dissolving it in a 25 per cent solution of sodium citrate, but the yield of thrombin is usually low. By adding a small amount of 3-chloro-4, 4'-diaminodiphenyl sulfone to the activation mixture the yield of thrombin is increased to the maximum. Several other diphenyl sulfones also increase the yield. In contrast, 3, 4, 4'-triaminodiphenyl sulfone and 2-hydroxy-4, 4'-diaminodiphenyl sulfone act as inhibitors of the activation process.
Abstract C31: Vemurafenib selectively radiosensitizes BRAF V600E mutant papillary and anaplastic thyroid carcinoma cells in vitro

Background: BRAF mutations are oncogenic drivers which occur in about 60% of papillary thyroid cancer (PTC) as well as a significant proportion of anaplastic thyroid cancer (ATC). BRAF mutations drive MAPK signaling and treatment resistance in thyroid cancer. BRAFV600E is the most common of these mutations in PTC, and can be selectively inhibited by vemurafenib. Methods: We used a panel of PTC and ATC cell lines to assess how the presence/absence of BRAFV600E impacts radiation sensitivity. We used radiation clonogenics, comet assays, nuclear foci formation, and western blots to determine the effect of vemurafenib on PTC and ATC cell lines. Results: Analysis of radiation clonogenics revealed relative radioresistance in cell lines containing the BRAFV600E mutation versus wild-type. Vemurafenib inhibited MAPK signaling in V600E mutants, but showed no effect on BRAF wild-type cell lines. Vemurafenib pretreatment selectively radiosensitized BRAFV600E mutants, as assessed by radiation clonogenic assays. Neutral comet assays also showed that vemurafenib impairs DNA repair in BRAFV600E lines. Furthermore, γ-H2A.x westerns and nuclear foci staining indicated that vemurafenib pretreatment decreases the ability of cells to repair double-strand DNA breaks in cell lines containing the BRAFV600E mutation. Vemurafenib also appeared to alter the kinetics of nuclear foci formation and resolution of 53BP1 as well as Rad51 in these cell lines. Conclusions: From our initial results, BRAF mutations appear to be associated with radioresistance in PTC and ATC cell lines. Vemurafenib selectively radiosensitizes both PTC and ATC cells through inhibition of DNA repair mechanisms. Together, these data suggest that combining vemurafenib and radiation may improve therapeutic control for BRAFV600E mutant thyroid cancers. Citation Format: Ryan N. Robb, Linlin Yang, Moumita Chatterjee, Moto Saji, Matt Ringel, Arnab Chakravarti, Terence Williams. Vemurafenib selectively radiosensitizes BRAF V600E mutant papillary and anaplastic thyroid carcinoma cells in vitro. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C31.
Establishment and preliminary application of indirect ELISA for anti-Saculin antibody

The study aimed to establish an indirect ELISA method for anti-Saculin antibody detection and apply for clinical immunology test.Saculin was used to generate the antiserum in rabbits,and the specificity of the antibody was identified by Western blot.We screened different results to optimize the best working conditions in indirect ELISA.The indirect ELISA results showed the titer of the rabbit antiserum was up to 1∶6 553 600.We detected the levels of antibodies in serum of 55 clinical subjects(36 were in Saculin group and 19 were in placebo group) after 3 weeks,which all got negative results.All the results support that this indirect ELISA method is stable and sensitive,whcih could be used in clinical serum detection.
Discussion on coupling mode of carrier communication on distribution network

Coupling device is very important for carrier signal transmission in distribution network.A safe,effective and economical coupling mode is the key to realize power line communication.Because the framework of distribution network and characteristic of communication channel are different from the high-voltage transmission line,the traditional high-voltage power line carrier communication coupling technology and modes are not applicable in the distribution power line communication network.This paper introduces the framework and the channel characteristics of distribution network in brief,analyzes both the capacitance and inductance coupling mode deeply.It also compares and analyzes different application environments and actual effect under these two coupling modes on distribution network.
Response of the In Vitro Whole Bladder (Rabbit) Preparation to Autonomic Agonists

Abstract Using an in vitro whole bladder preparation (rabbit), we studied both the volume-pressure relationship and the response of the bladder to specific autonomic agonists. We determined the response in: 1) an isovolumetric system in which the intravesical pressure was monitored in the absence of volume changes; 2) a system in which volume alterations were monitored in the presence of increasing pressure; and 3) a system in which the bladder emptied in the presence of a constant pressure. The results of these studies demonstrated: 1) volume-pressure studies generated a typical cystometric curve; 2) bethanechol produced a dose-dependent increase in intravesical pressure (decrease in bladder volume); 3) the whole bladder responded very poorly to isoproterenol; and 4) methoxamine and ATP both produced a modest increase in intravesical pressure. One advantage of the “whole bladder” in vitro preparation is that it can objectively measure a functional response of the bladder to pharmacological agents.
Fluorescence resonance energy transfer as a method for dissecting in vivo mechanisms of transcriptional activation.

The first step in transcriptional activation of protein-coding genes involves the assembly on the promoter of a large PIC (pre-initiation complex) comprising RNA polymerase II and a suite of general transcription factors. Transcription is greatly enhanced by the action of promoter-specific activator proteins (activators) that function, at least in part, by increasing PIC formation. Activator-mediated stimulation of PIC assembly is thought to result from a direct interaction between the activator and one or more components of the transcription machinery, termed the ‘target’. The unambiguous identification of direct, physiologically relevant in vivo targets of activators has been a considerable challenge in the transcription field. The major obstacle has been the lack appropriate experimental methods to measure direct interactions with activators in vivo . The development of spectral variants of green fluorescent protein has made it possible to perform FRET (fluorescence resonance energy transfer) analysis in living cells, thereby allowing the detection of direct protein–protein interactions in vivo . Here we discuss how FRET can be used to identify activator targets and to dissect in vivo mechanisms of transcriptional activation.
From electronics to anyonics

Textbooks on quantum mechanics traditionally divide elementary particles into two types: fermions and bosons. Fermions such as electrons have antisymmetric wavefunctions, which means that a minus sign (i.e. a phase of ?) is introduced into a system when two fer-mions in that system are interchanged. Bosons such as photons, on the other hand, have symmetric wave-functions that do not change when two bosons are exchanged. Fermions and bosons also have different intrinsic angular momentum or spin: fermions have half-integer spins in quantum units, while bosons have integer spins.
Mechanism of exercise-induced ocular hypotension.

PURPOSE. Although acute dynamic exercise reduces intraocular pressure (IOP), the factors that provoke this response remain ill-defined. To determine whether changes in colloid osmotic pressure (COP) cause the IOP changes during exercise, standardized exercise was performed after dehydration and hydration with isosmotic fluid. METHODS. Progressive cycle ergometer exercise to volitional exhaustion was performed after 4 hours dehydration, and after hydration with 946 ml isosmotic liquid (345 mOsM). In each experiment, venous blood taken before and immediately after exercise was analyzed for hematocrit, plasma protein concentration, total plasma osmolality, and plasma COP. RESULTS. Exercise in both experiments significantly reduced IOP and elevated COP (each P < 0.01). Dehydration, compared with hydration, also significantly reduced IOP and elevated COP hen measured before and after exercise (P < 0.05). The correlation of mean IOP with mean COP, over the entire range created by varying exercise and hydration statuses, was statistically significant (r = -0.99; P < 0.001). In contrast, other indexes of hydration status, including hematocrit, total plasma osmolality, and plasma protein concentration, failed to change as IOP changed and failed to correlate with IOP, on either a group or individual basis, in conditions of varying levels of exercise and hydration. CONCLUSIONS. Acute dynamic exercise and isosmotic fluid ingestion each seem to change IOP through changes in COP.
The Influence of Leadership and Strategic Emphasis on Social Media Use of Regional Nonprofit Organizations

Prior work has established the prevalence of social media as an information dissemination tool for large, national nonprofit organizations. This project adds to that literature by examining the impact of an organization's leadership executive director background and board influence and strategic emphasis customer orientation and financial allocations to social media on the use of social media for information transmission by regional nonprofit organizations. Insights are gained from leadership at 121 nonprofits and through analysis of 377 days of Facebook data for seven nonprofit organizations. The results suggest that organizations with executive directors who have more experience in the corporate sector and board members who exert greater influence are more likely to utilize social media for information transmission. Greater financial investments in social media actually result in less strategic use of social media, suggesting more investment does not always equate to more effective strategy.
PACAP Modulates Distinct Neuronal Components to Induce Cell-Specific Plasticity at Central and Autonomic Synapses

Despite its widespread expression and diverse functional roles, PACAP is well suited to mediate and modulate synaptic transmission since it is often localized in presynaptic neuron terminals, with cognate receptors present on postsynaptic neurons. Here, we review select cases where PACAP signals via its associated receptors and intracellular pathways to induce acute or persistent changes in cellular components involved in synaptic transmission, thereby supporting its role as a neurotransmitter and/or neuromodulator. Two themes that emerge are that PACAP can rapidly induce synaptic plasticity by altering the function of presynaptic and postsynaptic components, or change general membrane excitability by altering the balance of voltage-dependent Ca2+ and K+ channel contributions to action potential firing. We discuss the need to determine how these two themes are related, to extend studies to endogenous PACAP, and to determine how the synaptic modifications induced by PACAP contribute to its postulated roles in widespread behaviors and stress disorders such as PTSD.
Acute Myeloid Leukemia Is Characterized by Wnt Pathway Inhibitor Promoter Methylation.

The Wnt pathway contributes to a stem-cell like phenotype in a variety of cancer subtypes. Nuclear localization of non-phosphorylated, active β-catenin is a surrogate marker for Wnt pathway activation and has been associated with adverse outcome in patients with acute myeloid leukemia (AML). Wnt pathway inhibitors including APC , DKK1 , DKK3 , LKB1/STK11 , RASSF1A , RUNX3 , SFRP1 , SFRP2 , SFRP4 , SFRP5 , SOX17 , and WIF1 contain extensive promoter region CpG islands. Wnt pathway inhibitors are silenced by promoter methylation in many malignancies including lung cancer, colon cancer and acute lymphoid leukemias. To determine if methylation of these Wnt pathway inhibitors is present in AML, we evaluated leukemia cell lines (i.e., K562, HNT34, KG1, KG1A, U937, and HL60) for evidence of promoter methylation. Additionally, 188 AML patient (median age 61 years) samples from the Johns Hopkins Hospital leukemia tumor bank were assessed for the presence of Wnt pathway inhibitor methylation. All samples were bisulfite treated and evaluated for promoter methylation using methylation specific PCR. Diagnostic samples from a subgroup of patients with normal cytogenetics (n=73) who received high dose induction therapy were evaluated for potential associations between methylation of individual Wnt pathway inhibitor genes or total number of methylated genes and event free or overall survival. RESULTS: Extensive promoter methylation of the Wnt pathway inhibitor genes was observed in leukemia cell lines. Of the primary leukemia samples, 85% had at least one methylated gene. Promoter methylation of Wnt inhibitors was common in these samples with the following frequencies: DKK1 (16%;30/188), DKK3 (8%;15/188), RUNX3 (27%;50/188), SFRP1 (34%;63/188), SFRP2 (66%;124/188), SFRP4 (9%;16/188), SFRP5 (54%;102/188), SOX17 (29%;54/188), and WIF1 (32%;61/188). This is among the first comprehensive evaluations of Wnt pathway inhibitor methylation in primary samples from AML patients. The frequency of methylation seen here is comparable to that observed in established tumor suppressor genes in patients with AML, including p15 INK4B , SOCS1 and CDH1 . In marked contrast with epithelial tumors, methylation of APC (2%;2/108) and RASSF1A (0%;0/188) was rare. LKB1/STK11 methylation was also uncommon (2%;2/108). Previous reports have associated Wnt pathway activation with poor prognosis. In our treated patients with normal cytogenetics, no correlation was observed between methylation of Wnt pathway inhibitors and event free or overall survival. In conclusion, in patients with AML (a) there is a high frequency of Wnt pathway inhibitor methylation; (b) Wnt pathway inhibitor methylation is distinct from that observed in epithelial malignancies; and (c) methylation of Wnt pathway genes does not correlate with adverse clinical outcome.
Abstract 4599: Somatic mutation profile differences of “driver” mutations in 26 oncogenic lung cancer genes between African American and European American non-small cell lung cancer patients

African-Americans (AAs) are disproportionately affected by Lung Cancer (LC), having a higher incidence and a lower 5-year survival rate than any ethnic group ((European-Americans (EA) have 2nd highest incidence)). While tobacco use accounts for 90% of lung cancer cases, excess risk of LC in AAs is unlikely due to differences in cigarette smoking, since AAs and EAs smoke at comparable rates (∼20%) and even among smokers, AAs smoke fewer cigarettes. While social and environmental factors contribute to ethnic disparities in LC, it is likely that ethnic differences in genetic susceptibility play a role. A major barrier to this field of research has been historically low enrollment rates of AA LC patients for clinical studies. The University of Maryland is uniquely poised to address these research questions with a large database of ∼1000 Non-Small Cell Lung Cancer (NSCLC) (90% of LC cases) that includes a biobank of tissue samples with extensive clinical information. Not only is this database enriched for AA patients (40%), but it includes both tumor and non-tumor tissue allowing for examination of heritable (germline) and acquired (somatic) mutation. To address ethnic disparities, we are assessing somatic variability in the exons of 26 oncogenic lung cancer genes with the Ion Ampliseq™ Comprehensive Cancer Panel (CCP) and characterizing mutational profile differences in tumor samples between AA and EA NSCLC patients. We hypothesize that AA NSCLC patients will carry an excess of known recurrent driver mutations, and a differing mutational profile of somatic lung cancer driver mutations as compared to EA patients. Of the 10 patients (6 AA, 4 EA) sequenced to date, we detected oncogenic driver mutations in 18 of the 26 LC genes examined. Of the 6 AAs, all had multiple driver mutations and as a group, mutations were detected in 17 of the 26 LC genes. For the 4 EA patients, 3 were found to have 1 driver mutation each and in separate LC genes (AKT1, EGFR, STK11). Although results should be considered cautiously due to sample size, we observe that AA NSCLC patients have more driver mutations overall and per individual as compared to EA NSCLC patients. Citation Format: Sarah H. Stephens, Patrice J. Fleming, Braxton D. Mitchell, Nicholas Ambulos, Joan E. Bailey-Wilson, Christy Chang, Josephine L. Feliciano, Edward A. Sausville, Martin J. Edelman. Somatic mutation profile differences of “driver” mutations in 26 oncogenic lung cancer genes between African American and European American non-small cell lung cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4599. doi:10.1158/1538-7445.AM2015-4599
The nonarrival of black freedom (c. 12.6.84)

This article seeks to mark the twentieth anniversary of the publication of Saidiya V. Hartman’s Scenes of Subjection: Terror, Slavery, and Self-Making in Nineteenth-Century America through a series...
Preclinical Evaluation of Safety of Fucoidan Extracts From Undaria pinnatifida and Fucus vesiculosus for Use in Cancer Treatment

Objectives: To evaluate potential hepatic metabolism-mediated drug interactions with fucoidan from Undaria pinnatifida (UPF) or Fucus vesiculosus (FVF) and potential growth inhibition activity with...
The case definition of chronic fatigue syndrome

The 1994 case definition of chronic fatigue syndrome is widely used not only for diagnosis but also for clinical and laboratory-based observations of this clinical entity. The criteria for the 1994 case definition are based primarily on symptoms and not on physical signs or chemical or immunological tests. This situation has resulted in conflicting clinical and laboratory observations that in all likelihood is due to different populations of patients being studied in different centers. Based on some of the recent publications, there appears to be an emerging picture of this disease entity that we propose could be used to subgroup chronic fatigue syndrome into four different subclasses. These subclasses would consist of chronic fatigue with primarily nervous system disorders such as impaired memory or concentration and headache, chronic fatigue with primarily endocrine system disorders such as unrefreshing sleep and postexertional malaise, chronic fatigue with musculoskeletal system disorders such as muscle pain and joint pain, and chronic fatigue with immune system/infectious disorders such as sore throat and tender lymph nodes. It is suggested that if clinical and laboratory-based studies on chronic fatigue syndrome were conducted on more homogeneous subgroups of patients, the data from one center to the other might not be as conflicting and more insights can be shed on the nature of this clinical condition.
Existential Ennui: Examining the Reciprocal Relationship Between Self-Alienation and Academic Amotivation

Two studies (N = 649) examined the association between self-alienation (SA; i.e., feelings of detachment from one’s true self) and academic amotivation (AA; i.e., lack of motivation in the academic...
Mindfulness, burnout, and effects on performance evaluations in internal medicine residents

PURPOSE Burnout has been documented at high levels in medical residents with negative effects on performance. Some dispositional qualities, like mindfulness, may protect against burnout. The purpose of the present study was to assess burnout prevalence among internal medicine residents at a single institution, examine the relationship between mindfulness and burnout, and provide preliminary findings on the relation between burnout and performance evaluations in internal medicine residents. METHODS Residents (n = 38) completed validated measures of burnout at three time points separated by 2 months and a validated measure of dispositional mindfulness at baseline. Program director end-of-year performance evaluations were also obtained on 22 milestones used to evaluate internal medicine resident performance; notably, these milestones have not yet been validated for research purposes; therefore, the investigation here is exploratory. RESULTS Overall, 71.1% (n = 27) of the residents met criteria for burnout during the study. Lower scores on the "acting with awareness" facet of dispositional mindfulness significantly predicted meeting burnout criteria χ2(5) = 11.88, p = 0.04. Lastly, meeting burnout criteria significantly predicted performance on three of the performance milestones, with positive effects on milestones from the "system-based practices" and "professionalism" domains and negative effects on a milestone from the "patient care" domain. CONCLUSION Burnout rates were high in this sample of internal medicine residents and rates were consistent with other reports of burnout during medical residency. Dispositional mindfulness was supported as a protective factor against burnout. Importantly, results from the exploratory investigation of the relationship between burnout and resident evaluations suggested that burnout may improve performance on some domains of resident evaluations while compromising performance on other domains. Implications and directions for future research are discussed.
Drug Interactions and Obstetric Anesthesia

Often, parturients may receive antibiotics for various disease processes. This is particularly observed in high risk management labor and delivery units. Most of the antibiotics will prolong the effect of nondepolarizing muscle relaxants, but prolongation of depolarizing muscle relaxants has also been observed (Table 4-1).1,2 The table cites the example of d-tubocurarine; however, the duration of action of presently used muscle relaxants including vecuronium and rocuronium are also prolonged by antibiotics.3–5 The mechanism of this phenomenon is unknown. Antagonism of this action by neostigmine and pyridostigmine is found to be unpredictable; however, neuromuscular blockade from antibiotics could be reversed predictably by 4-aminopyridine.2 An interesting observation made in rats that may have clinical bearing is that the neuromuscular block produced by a combination of neuromuscular-blocking drugs and antibiotics could be prolonged in the presence of local anesthetic lidocaine.6
High serum IGF-1 levels are associated with pregnancy loss following frozen-thawed euploid embryo transfer cycles.

Abstract An elevated level of insulin growth factor (IGF-1) in rat uterine fluid has been shown to exert detrimental effects of embryo development possibly leading to an increase in pregnancy loss. Interestingly, the administration of somatostatin to rats undergoing superovulation reduced IGF-1 levels in uterine luminal fluid and thus reversed its deleterious effects on embryo development and increased the number of normal embryos. Therefore, we investigated whether serum levels of IGF-1 correlate with the incidence of pregnancy loss following IVF. To account for aneuploidy and the effect of hormonal supplementation on serum IGF levels, we only included natural frozen-thawed euploid embryo transfer (N-FET) cycles. Sera collected in the follicular phase (cycle day 10) were tested for levels of IGF-1, IGF-2, and IGF-binding protein 1 (IGFBP-1) using quantitative ELISA. A total of 156 N-FET cycles were included: 120 resulted in a live birth whereas 36 led to a first trimester pregnancy loss. Women with a pregnancy loss had significantly higher serum IGF-1 levels compared to those who achieved a live birth (18.0 ± 1.1 vs. 14.6 ± 0.7 ng/mL, respectively). The two groups had comparable serum IGF-2 and IGFBP-1 levels. There was no significant difference in maternal age, body mass index, gravidity, parity, number of prior miscarriages, peak endometrial thickness, or infertility diagnosis between the two groups. In conclusion, women undergoing euploid blastocyst transfer with elevated serum IGF-1 concentrations may be at increased risk of pregnancy loss. This may constitute a novel molecular explanation of pregnancy loss of euploid conceptus.
Fitness, Exercise, and Coronary Calcification.

Article, see p 1888 Both higher coronary artery calcification (CAC) scores and reduced cardiorespiratory fitness (CRF) are independently strong predictors of future cardiovascular events. CAC is a direct measure of coronary atherosclerosis, the cause of most cardiovascular events. CRF, often measured by exercise treadmill time, is an estimate of maximal oxygen uptake and a surrogate measure of cardiac stroke volume. Rearranging the Fick equation demonstrates that maximal oxygen uptake is the product of cardiac output (heart rate × stroke volume) and the arterial-venous O2 difference. Because heart rate is largely age-determined and the arterial-venous O2 difference varies little among healthy individuals, maximal oxygen uptake, and therefore CRF, are proxies for stroke volume and cardiac performance. Consequently, it is not surprising that Radford and colleagues1 in this issue of Circulation demonstrate that higher levels of CRF are associated with decreased cardiovascular events across the spectrum of CAC scores. These authors followed 8425 men without cardiovascular disease, who had CRF and CAC scores determined at baseline and followed for an average of 8.4 years. Both total cardiovascular events (cardiovascular death, myocardial infarction, stroke, and coronary revascularization) as well as “hard” cardiovascular events (death, myocardial infarction, and stroke) were analyzed. This is an important issue in CAC studies because high CAC scores could prompt testing and revascularization procedures. Subjects were divided into 4 groups based on CAC Agatston unit scores of 0, 1 to 99, 100 to 399, and ≥400. Only the results for men were analyzed because too few cardiovascular events occurred in women. CRF was measured in metabolic …
The new cholinesterase inhibitors for Alzheimer's disease, Part 2: illustrating their mechanisms of action.

Issue: Three new pharmacologic agents for the treatment of Alzheimer's disease all inhibit the enzyme acetylcholinesterase. These include donepezil (Aricept), rivastigmine (Exelon), and soon galantamine (Reminyl). Rivastigmine also inhibits the enzyme butyrylcholinesterase. Galantamine is also a selective booster of nicotinic action by allosterically modulating nicotinic receptors. These distinct pharmacologic profiles are potentially important to clinicians who must decide when to treat Alzheimer 's disease and which cholinesterase inhibitors to use.
Comparison of all-electric secondary power systems for civil subsonic transports

Three separate studies have shown operational, weight, and cost advantages for commercial subsonic transport aircraft using an all-electric secondary power system. The first study in 1982 showed that all-electric secondary power systems produced the second largest benefit compared to four other technology upgrades. The second study in 1985 showed a 10 percent weight and fuel savings using an all-electric high frequency (20 kHz) secondary power system. The last study in 1991 showed a 2 percent weight savings using today's technology (400 Hz) in an all-electric secondary power system. This paper will compare the 20 kHz and 400 Hz studies, analyze the 2 to 10 percent difference in weight savings and comment on the common benefits of the all-electric secondary power system.
Law, Liberty and Reason

Do laws always restrict the liberty of the people who live under them? Or, if some laws are thought to be non-coercive—for example, laws that make voting possible— is this at least true of coercive laws? Does the coercion involved in threatening to impose penalties mean that the subjects of the laws thereby suffer a loss of freedom? The answer that appears to have a nearly universal hold on the minds of legal theorists and philosophers today is that yes, coercive law does always reduce people’s freedom. The canonical text is from Jeremy Bentham.
Risk reduction strategies in ischaemic stroke : the role of antiplatelet therapy.

Stroke is a common and serious disorder, and is a leading cause of disability and death in adults. Transient ischaemic attacks are now recognised as being common precursors of stroke, with a high risk of subsequent vascular events. The majority of strokes are ischaemic in origin, and are typically due to atherothrombosis/microatheromatosis involving a large or small cerebral blood vessel or to an embolic event. Owing to the diffuse nature of atherothrombosis, these patients are at risk of ischaemic events in other vascular beds. Options for treating patients with acute ischaemic stroke are very limited; therefore prevention is a key strategy for reducing the risk of recurrent stroke and other vascular events. Treatment of risk factors such as hypertension, diabetes mellitus, smoking and obesity is an important approach for stroke prevention. Platelets are involved in the development of thrombi and emboli, making antiplatelet therapy an important preventive strategy. Antiplatelet agents are effective in preventing recurrent ischaemic stroke and other vascular ischaemic events, such as myocardial infarction and vascular death. In some cases, anticoagulants may be effective in preventing ischaemic stroke recurrence. Carotid endarterectomy can reduce stroke risk in patients with moderate- or high-grade carotid artery stenosis. Choosing the most appropriate therapy for the individual patient is key to optimising stroke prevention.
ThinPrep Pap Test: performance and biopsy follow-up in a university hospital.

BACKGROUND The ThinPrep® Pap Test™ (TP), a liquid-based cervical cytology preparation, was approved for use in the U.S. in 1996. The purpose of this study was to compare TP performance and biopsy follow-up studies with a similar population of high risk patients sampled by conventional Papanicolaou (Pap) smear (CS). METHODS Diagnostic and specimen adequacy interpretations for 2727 TP direct-to-vial Pap tests from a high risk university hospital practice were compared with 5000 CS preparations from the same physicians taken 1 year previously. Biopsy follow-up studies for the categories of squamous intraepithelial lesion (SIL), carcinoma, and atypical squamous cells of undetermined significance (ASCUS) for each time period and technique were contrasted. RESULTS The SIL/carcinoma detection rate increased from 7.7% to 10.5% (P < 0.01) and the ASCUS rate decreased from 12.5% to 6.9% (P < 0.01); the percentage of satisfactory but limited specimens decreased from 19.4% to 10.5% (P < 0.01). Low grade SIL cases increased by 57% (P < 0.01) whereas the 26% increase in high grade SIL cases was not statistically significant. Greater than 90% of ungraded SIL, high grade SIL, and carcinoma cases had abnormal biopsies by both the TP and CS methods. The number of biopsy-confirmed high grade dysplasias and carcinomas was similar in the two groups. A low grade SIL detected by TP was less likely to have an abnormal biopsy (70% vs. 85% for CS). Nevertheless, the 57% increase in low grade SIL diagnoses by TP resulted in more TP patients with dysplastic biopsy diagnoses. Follow-up studies for ASCUS cases diagnosed by either TP or CS were similar, and 21–24% of patients eventually were found to have dysplasia. CONCLUSIONS The TP technique appears to lead to the increased detection of low grade SIL lesions, decreased satisfactory but limited samples, and fewer equivocal specimens. No increase in biopsy-confirmed high grade dysplasias and carcinomas was found. Follow-up studies for the ASCUS category were nearly identical to those for CS. Cancer (Cancer Cytopathol) 1999;87:105–12. © 1999 American Cancer Society.
Applying a simplified energy-budget model to explore the effects of temperature and food availability on the life history of green sturgeon (Acipenser medirostris)

Abstract In highly regulated systems, like large dammed rivers, conservation legislation requires that systems are managed, in part, to avoid adverse impacts on endangered species. However, multiple endangered species can occur in the same system, and management actions that benefit one species may be detrimental to another species. The current water management strategies in the Sacramento River basin are an example of this conflict. Cold-water releases from Shasta Reservoir during the summer and fall months are aimed at protecting Sacramento River winter-run Chinook (SRWRC) salmon by providing suitable incubation temperatures for their eggs. However, the effects of these regulated water temperature releases on another threatened species, green sturgeon, are less well understood. In this study, we applied a simplified dynamic energy budget (DEB) model (aka DEBkiss) to explore the effect of food limitation and water temperature on the growth rates of green sturgeon. This model captures these effects and able to predict the growth of green sturgeon at different food levels and temperature conditions. We then linked the DEB model with a physically‐based water temperature model. We applied the DEB - water temperature linked model for green sturgeon along with a temperature-dependent egg to fry survival model for SRWRC salmon to quantify the consequences of managing water temperatures to improve salmon eggs survival on the growth rate of green sturgeon. We found that mean temperature-dependent egg-to-fry survival of salmon increased across a modeled environmental gradient from critically dry to wet water year types, while the fractional growth rate of juvenile green sturgeon showed the opposite trend, and decreased as water years transitioned from dry to wet conditions. We also found a non-linear negative correlation between temperature-dependent mean growth rate of green sturgeon and mean temperature-dependent egg-to-fry survival of salmon, which indicated there is a river temperature related trade-off between early growth rate of green sturgeon and embryonic stage survival of salmon. However, the relatively small gains in the growth rate of green sturgeon achieved in years when temperature criteria for SRWRC salmon eggs were not met came at the cost of large reduction in temperature-dependent egg-to-fry survival of salmon. Thus, we concluded the current Sacramento River water-temperature management for the eggs of the endangered SRWRC salmon eggs have a relatively small impact on the growth rate of green sturgeon.
Improved Harmonics in Metal Insulator Metal Capacitors Using Design Techniques

The measured harmonic distortion from a metal-insulator-metal (MIM) capacitor is reduced using series, anti-series and anti-parallel configurations. The anti-series and anti-parallel connections of matched capacitors can completely eliminate the 2ndharmonics originating from the device and the measured 2nd harmonics for those structures is mostly due to the substrate and hence high resistivity silicon-on-insulator (HR-SOI) substrates are preferred. 2-stack series and anti-series configurations can reduce the 3rd harmonics by almost 12 dBm which can be further decreased by increasing the number of capacitors in the stack. Anti-parallel connection can be designed for the same Q factor and footprint as that of a single device. To achieve the same Q of a single device the width has to be doubled for 2-stack series and anti-series configurations while the footprint increases four times.
On a Question of Zannier

We formulate and answer a question of Zannier about elliptic curves over varying prime fields. We then give some experimental findings. In a final section, we formulate some analogous questions for...
Validation of an Extensible Rod Model for Soft continuum Manipulators

Numerous soft and continuum robotic manipulators have demonstrated their potential for compliant operation in highly unstructured environments or near people. Despite their recent popularity, modeling of their smooth bending deformation remains a challenge. For soft continuum manipulators, the widespread, constant curvature approach to modeling is inadequate for modeling some deformations that occur in practice, such as combined bending and twisting deformations. In this paper, we extend the classical Cosserat rod approach to model a variable-length, pneumatic soft continuum arm. We model the deformation of a pneumatically driven soft continuum manipulator, and the model is then compared against experimental data collected from a three degree of freedom, pneumatically actuated, soft continuum manipulator. The model shows good agreement in capturing the overall behavior of the bending deformation, with mean Euclidean error at the tip of the robot of 2.48 cm for a 22 cm long robot. In addition, the model shows good numerical stability for simulating long duration computations.
Analysis of feedforward mechanisms of multiwhisker receptive field generation in a model of the rat barrel cortex

Abstract There is substantial anatomical segregation in the organization of the rodent barrel system – each whisker on the mystacial pad sends input to TC cells within a dedicated thalamic barreloid, which in turn innervates a corresponding cortical barrel, and RS cells within a barrel respond primarily to deflections of the corresponding whisker at the beginning of the dedicated transmission line (the principal whisker, PW). However, it is also well-established that barrel cells exhibit multiwhisker receptive fields (RFs), and display lower amplitude, longer latency responses to deflections of non-PWs (or adjacent whiskers, AWs). There is considerable controversy regarding the origin of such multiwhisker RFs; three possibilities include: (i) TC cells within a barreloid respond to multiple whiskers, and barrel RS cells simply inherit multiwhisker responses from their aligned barreloid; (ii) TC cells respond only to the PW, but individual barreloids innervate multiple barrels; (iii) multiwhisker responses of barrel cells arise from lateral corticocortical (barrel-to-barrel) synaptic transmission. Ablation studies attempting to pinpoint the source of RS cell AW responses are often contradictory (though experimental work tends to suggest possibilities (i) or (iii) to be most plausible), and hence it is important to carefully evaluate these hypotheses in terms of available physiological data on barreloid and barrel response dynamics. In this work, I employ a biologically detailed model of the rat barrel cortex to evaluate possibility (i) , and I show that, within the model, hypothesis (i) is capable of explaining a broad range of the available physiological data on responses to single (PW or AW) deflections and paired whisker deflections (AW deflection followed by PW deflection), as well as the dependence of such responses on the angular direction of whisker deflection. In particular, the model shows that barrel RS cells can exhibit AW direction tuning despite the fact that barreloid to barrel wiring has no systematic dependence on the AW direction preference of TC cells. Future modeling work will examine the other possibilities for the generation of multiwhisker RS cell RFs, and compare and contrast the different possible mechanisms within the context of available experimental data.
Abstract LB-083: Combination of an ERK1/2 inhibitor (LY3214996) with pan-RAF inhibitor enhances anti-tumor activity in KRAS mutant colorectal cancer (CRC) and non-small cell lung cancer (NSCLC)

Cancer patients with KRAS mutations have poor prognosis and represent an unmet medical need. Mutant KRAS driven MAPK activation is present in ~ 40% and ~ 30% of CRC and NSCLC patients, respectively. ERK1/2, a key downstream effector of KRAS mutations, is involved in the critical signaling network to drives cell proliferation, survival, metastasis and drug resistance. LY3214996, an ERK1/2 inhibitor which is in Phase I clinical trial (NCT02857270), has potent anti-tumor activities in KRAS mutant tumor cells in vitro and in vivo. However, some KRAS mutant cancer cells were less sensitive to LY3214996 single agent, suggesting that combination therapy is needed to maximize the benefit from ERK1/2 inhibition. The combined inhibition of RAS/RAF/MEK/ERK pathway components (such as the inhibition of both BRAF and MEK) has shown the promising anti-cancer activity in melanoma. Based on interaction between activated RAS with RAF which is responsible for cancer progression and resistance in KRAS mutant cancers, we hypothesized that inhibiting both ERK and RAF may augment efficacy of the single agents and delay the resistance. Therefore in this study we have investigated the combination effect of LY3214996 with a pan-RAF inhibitor LY3009120 in KRAS mutant CRC and NSCLC in vitro and in vivo. The combination of LY3214996 and LY3009120 showed synergistic or additive inhibition of cell proliferation in all KRAS mutant CRC (n=8) and NSCLC (n=8) cell lines tested. The LY3214996 and LY3009120 combination significantly decreased the phosphorylation levels of ERK, Rb, S6 and H3, and induced more complete cell death in NCI-H2122 (G-12C), A549 (G-12S), NCI-H441 (G-12V), HCT-116 (G-13D) and in LY3009120-resistant HCT-116 cells compared with either single agent. Subsequent combination efficacy was evaluated in the HCT-116 xenograft model. LY3214996 alone, LY3009120 alone and the combination of LY3214996 and LY3009120 resulted in 52%, 68% and 94% tumor growth inhibition, respectively; and the combination significantly augmented the efficacy (p Citation Format: Wenjuan Wu, Shripad Bhagwat, Lisa Kindler, William McMillen, Sajan Joseph, Sean Buchanan, Christoph Reinhard, Ramon V. Tiu, Sheng-Bin Peng. Combination of an ERK1/2 inhibitor (LY3214996) with pan-RAF inhibitor enhances anti-tumor activity in KRAS mutant colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-083.
A wearable electrofluidic actuation system

We report a wearable electrofluidic actuation system, which exploits the alternating current electrothermal (ACET) effects to engineer biofluid flow profiles on the body. The wearable ACET flow is induced with the aid of corrosion-resistant electrode configurations (fabricated on a flexible substrate) and custom-developed, wirelessly programmable high frequency (MHz) excitation circuitry. Various tunable flow profiles are demonstrated with the aid of the devised flexible ACET electrode configurations, where the induced profiles are in agreement with the ACET theory and simulation. The demonstrated capabilities rendered by the presented system create new degrees of freedom for implementing advanced bioanalytical operations for future lab-on-the-body platforms.