cssi/SciSciGPT-SciSciNet huggingface dataset:
Data strip mining for the virtual design of pharmaceuticals with neural networks

A novel neural network based technique, called "data strip mining" extracts predictive models from data sets which have a large number of potential inputs and comparatively few data points. This methodology uses neural network sensitivity analysis to determine which predictors are most significant in the problem. Neural network sensitivity analysis holds all but one input to a trained neural network constant while varying each input over its entire range to determine its effect on the output. Elimination of variables through neural network sensitivity analysis and predicting performance through model cross-validation allows the analyst to reduce the number of inputs and improve the model's predictive ability at the same time. This paper demonstrates its effectiveness on a pair of problems from combinatorial chemistry with over 400 potential inputs each. For these data sets, model selection by neural sensitivity analysis outperformed other variable selection methods including the forward selection and genetic algorithm.
Resistance to N -Benzyladriamycin-14-valerate in Mouse J774.2 Cells: P-Glycoprotein Expression without Reduced N -Benzyladriamycin-14-valerate Accumulation

Abstract N -Benzyladriamycin-14-valerate (AD 198) is a highly lipophilic analogue of Adriamycin with novel cytotoxic mechanisms, greater in vivo antitumor activity, and the ability to circumvent multidrug resistance due to P-glycoprotein-mediated drug efflux or decreased topoisomerase II activity. To identify the mechanism(s) which may confer AD 198 resistance, J774.2 mouse macrophage-like cells were selected for growth in cytotoxic levels of AD 198 (AD 198 R ). AD 198 R cell exhibited over-expression of the mdr1b (P-glycoprotein) gene, cross-resistance to Adriamycin and vinblastine, and potentiation of drug cytotoxicity by verapamil. However, net intracellular accumulation of AD 198 in AD 198 R cells was unchanged compared to parental cells, while Adriamycin and vinblastine accumulations were reduced 40% and 95%, respectively. AD 198 was localized in the perinuclear region of the cytoplasm in both parental and AD 198 R cells, with additional vesicular compartmentalization in AD 198 R cells. Verapamil-induced reversal of AD 198 resistance coincided with some drug redistribution from cytoplasmic vesicles, but without redistribution of AD 198 into the nucleus. These results suggest that AD 198 resistance was not conferred through a P-glycoprotein-mediated reduction in intracellular drug accumulation but through other cytoplasmic mechanisms, including, but not limited to, drug compartmentalization.
Angular signatures, and a space-borne measurement concept

The nature and value of angular signatures in remote sensing are reviewed with emphasis on the canopy hot-spot as a directionally localized angular signature and an important special case of a BRDF. A new concept is presented that allows hot spot measurements from space by using active (laser) illumination and bistatic detection. The detectors are proposed as imaging array sensors that are circulating the illumination source (or vice versa) and are connected with it through tethers in space which also provide the directional controls needed so that the entire system becomes pointable like a search light. Near infrared or IR operation in an atmospheric transmission window is envisioned with night-time data acquisition. Detailed feasibility and systems analyses have yet to be performed.
Spectral correlation in ultrasonic pulse echo signal processing

The effects of using spectral correlation in a maximum-likelihood estimator (MLE) for backscattered energy corresponding to coherent reflectors embedded in media of microstructure scatterers is considered. The spectral autocorrelation (SAC) function is analyzed for various scatterer configurations based on the regularity of the interspacing distance between scatterers. It is shown that increased regularity gives rise to significant spectral correlation, whereas uniform distribution of scatters throughout a resolution cell results in no significant correlation between spectral components. This implies that when a true uniform distribution for the effective scatterers exists, the power spectral density (PSD) is sufficient to characterize their echoes. However, as the microstructure scatterer distribution becomes more regular, SAC terms become more significant. MLE results for 15 A-scans from stainless steel specimens with three different grain sizes indicate an average 6-dB signal-to-noise ratio (SNR) improvement in the coherent scatterer (flat-bottom hole) echo intensities for estimators using the SAC characterization as opposed to the PSD characterization. >
Salting and Drying Fish. 3. Diffusion of Water

SUMMARY– Drying of salted fish was studied in the falling rate period. It was found that this period consisted of two distinct phases, each of which was characterized by a Fickian diffusion coefficient. The coefficient for the first phase was, in all cases, greater than that for the second phase. The effect, on both diffusion coefficients, of the following variables was studied: degree of salting, drying temperature, and degree of hydration of -the muscle (varied by addition of acid, base and sodium trypolyphosphate to the muscle). The first diffusion coefficient was found to increase, pass through a maximum, and then decrease with degree of salting. The second coefficient was found to decrease with degree of salting within the range for which it was determined. The first diffusion coefficient was found to be directly correlated with the degree of hydration of the muscle; a plot of the coefficient versus water content of the muscle (expressed as pounds of water per pound of bone-dry solids) yielded a straight line, the regression equation of which was found to be D = 0.16W + 0.09, where D is the diffusion coefficient in cm2/sec × 105 and W is the water content. Variations in the diffusion coefficient due to degree of salting and due to addition of acid, base, and phosphate could be explained by the hydration-dependence of the coefficient. The temperature variation of both coefficients was found not to be great.
Immunological reactions of the Coxsackie viruses. I. The neutralization test; technic and application.

The neutralization test is a reliable and useful procedure for following immunological reactions of the Coxsackie viruses (C virus). The standard procedure has been an incubation period of 1 hour at room temperature followed by subcutaneous inoculation into newborn mice. However, this time and temperature are not critical, for the virus in neutralized within 10 minutes of mixing with immune serum and remains neutralized for long periods. During the variable incubation periods used, the control virus remained active, even in dilute suspensions. The neutralization test is not affected by the presence or absence of complement. Neutralizing antibody is stable at 65°C. for 30 minutes, and immune serum has to be heated to 80°C. for 30 minutes before the antibody is no longer detectable. As the quantity of virus is increased, the quantity of serum required for neutralization likewise increases, but not in a regular or predictable fashion. Neutralized mixtures of the virus can be made infective again by simple dilution before inoculation. The neutralization test is a satisfactory means for typing Coxsackie viruses. At least seven antigenic types have been identified. Similar antigenic types have been found to be scattered over wide areas. Thus the Conn.-5 type was present in 1948 in Massachusetts, Connecticut, New York, and North Carolina. The Texas-1 type was present in 1943 in Connecticut and in 1948 in North Carolina and Texas. Further information on the specificity of the neutralizing antibody response has been obtained from a study of the occurrence and development of antibodies in 6 patients who contracted infections with one or another of the C viruses while working with them in the laboratory. From each patient a virus was isolated during the illness. No patient had detectable antibodies to his strain before his illness, but each soon thereafter developed antibodies to his own strain and to the prototype strain to which it was related. By means of the neutralization test, it has been shown that a family epidemic may include two different immunological types of virus. Neutralizing antibodies appear at the time of or soon after onset of illness, increase rapidly to titers of about 1:1000 which are maintained during the period of 1 to 3 months following infection, and are still present 2 years later, although at lower levels. Neutralizing antibodies are present in the normal population. In North Carolina, over 80 per cent of the children have antibodies at birth. The level falls rapidly to a minimum of 14 per cent at the age of 1, and then it quickly rises to reach the adult level at the age of 7. Gamma globulin collected in various parts of the United States between 1944 and 1949 and in Denmark in 1949 neutralizes at least four antigenically different Coxsackie viruses.
Discrete-Time Reduced-Complexity Youla Parameterization for Dual-Input Single-Output Systems

A controller design is presented for directly shaping the sensitivity function in the feedback control of dual-input single-output (DISO) systems. We provide special forms of discrete-time Youla-Kucera (YK) parameterization to obtain stabilizing controllers for DISO systems, and discuss concepts to achieve a reduced-complexity formulation. The proposed YK parameterization is based on an inverse of the loop transfer function, which gives benefits such as clearer design intuition and reduced complexity in construction. The algorithm is verified by simulations and experiments on hard disk drive systems, with application to wideband vibration and harmonic disturbance rejections.
Electrochemical Research on N-Type and P-Type Semiconductor Pyrite

Studies on cyclic voltammetry, Tafel polarization curve and DFT calculations on N type and P type semiconductor pyrite in or out of bacterial solution were carried out. Cyclic voltammetry showed that the effect of bacterial was not simply in enrich the Fe3+ in the EPS. Tafel polarization curve research showed that bacteria can enhance the oxidation reaction sharply, no matter in the Fe3+ solution and in the bacteria solution, the corrosion current of N type pyrite was much bigger than that of P type pyrite. The DFT calculation shows that containing one Ni or Co atom means a more stable property, containing one As atom meaning a less stable property. However, an energy band around 5eV occurred in N type pyrite (contained Cu or Ni) meaning that N type pyrite is easier to be oxidation than P type pyrite.
Seasonal and sex differences in responsiveness to adrenocorticotropic hormone contribute to stress response plasticity in red-sided garter snakes (Thamnophis sirtalis parietalis)

ABSTRACT As in many vertebrates, hormonal responses to stress vary seasonally in red-sided garter snakes ( Thamnophis sirtalis parietalis ). For example, males generally exhibit reduced glucocorticoid responses to a standard stressor during the spring mating season. We asked whether variation in adrenal sensitivity to adrenocorticotropic hormone (ACTH) explains why glucocorticoid responses to capture stress vary with sex, season and body condition in red-sided garter snakes. We measured glucocorticoids at 0, 1 and 4 h after injection with ACTH (0.1 IU g −1 body mass) or vehicle in males and females during the spring mating season and autumn pre-hibernation period. Because elevated glucocorticoids can influence sex steroids, we also examined androgen and estradiol responses to ACTH. ACTH treatment increased glucocorticoids in both sexes and seasons. Spring-collected males had a smaller integrated glucocorticoid response to ACTH than autumn-collected males. The integrated glucocorticoid response to ACTH differed with sex during the spring, with males having a smaller glucocorticoid response than females. Although integrated glucocorticoid responses to ACTH did not vary with body condition, we observed an interaction among season, sex and body condition. In males, ACTH treatment did not alter androgen levels in either season, but androgen levels decreased during the sampling period. Similar to previous studies, plasma estradiol was low or undetectable during the spring and autumn, and therefore any effect of ACTH treatment on estradiol could not be determined. These data provide support for a mechanism that partly explains how the hypothalamus–pituitary–adrenal (HPA) axis integrates information about season, sex and body condition: namely, variation in adrenal responsiveness to ACTH.
Bypass, Augment, or Integrate How Secondary Mathematics Teachers Address the Literacy Demands of Standards-Based Curriculum Materials

This 3-year qualitative study examined how 26 teachers in four U.S. secondary schools addressed the literacy demands of curriculum materials based on standards from the National Council of Teachers of Mathematics. It was grounded in sociocultural perspectives that encourage study of language in local contexts, including classrooms, communities, and disciplines. The research question asked, “How do secondary mathematics teachers in a teacher–researcher collaboration understand and address the literacy demands of standards-based curriculum materials?” An interdisciplinary team of literacy and mathematics education researchers and graduate students worked with teachers to examine required curriculum materials, plan lessons, and share resources, while collecting qualitative data to capture teachers’ understandings and actions. Findings indicated that teachers responded in three ways to the materials’ literacy demands: (a) they used the materials selectively to bypass or reduce the literacy demands, (b) they a...
Dynamic Study of Knitting Elements of Circular Machine

A study was carried out on a method of measurement of frictional force of moving meedles on the cylinder wall and the cam surface of a circular machine in its operation.The horizontal (tangential to the circumferenece of the cylinder) and the vertical to the vertical (parallel to the needle track) components of the force acting on a stitch cam were measured by a strain gauge bondend on a cantilever at the end of which the cam is supported.Comparison of the direction of the force acting on the cam with the cam angle gives the frictional coefficient between the needle and the cam, and the change of the coefficient.The general change of the magnitude and the direction of the force acting on the cam gives frictional coefficient between the needle and the cylinder wall.
Validation of Tank Self-Pressurization Models in Normal Gravity

In optimizing the design of cryogenic storage facilities for future in-orbit or on-surface applications the boil-off and the self-pressurization rates must be accurately predicted for different g-levels and for a variety of heat distributions and engineering design parameters. In this paper, a thermodynamic and a CFD model will be presented that describe the selfpressurization behavior of a flightweight partially filled LH2 experimental tank prototype in a normal gravity environment. Existing experimental data at different fill levels are used to assess the predictive capability of these models. Comparisons between the data and the model predictions indicate that the thermodynamic model can accurately predict the self-pressurization rate, but fails to capture the magnitude of the pressure rise. In contrast, the computational model captures both the self-pressurization rate and vapor pressure magnitude at lower fill levels. Slight deviations are observed for the higher fill level cases. Possible sources of this discrepancy are discussed.
A Retrospective Sero-epidemiological Investigation on Antibody Level against Epidemic Cerebrospinal Meningitis Serogroup C among Recruits

[Objective]To learn the distribution of epidemic cerebrospinal meningitis(serogroup C) antibody IgG among recruits,provide the scientific evidence for further prevention and control of the disease.[Methods]The seroepidemiology was applied,360 recruits who came from 7 provinces in the past four years in Beijing military area were colleted,the levels of antibody IgG against epidemic cerebrospinal meningitis(serogroup C) were tested by Enzyme-linked Immunosorbent Assay(ELISA),and the positive rate was analyzed statistically.[Results]The positive rate of antibody IgG against epidemic cerebrospinal meningitis(serogroup C) among recruits significantly increased year by year,which ranged from 41.33% to 70.07% with the average value of 55.56%.The content of antibody ranged from 0.173μg/ml to 77.655μg/ml with the average value of(4.766±8.396) μg/ml.There existed obvious regional difference,the positive rate of recruits from Henan(74.07%),Hubei(65.00%) and Shandong(60.00%) was high,and that of recruits from Beijing(41.33%) and Zhejiang(42.22%) was low.The main reason for the difference might be related to the vaccination rate,inapparent infection and vaccination time in different regions.There was no significant difference in positive rate between recruits who had a job and did not have a job before recruitment.[Conclusion]The positive rate of antibody IgG against epidemic cerebrospinal meningitis(serogroup C) among recruits ranged from 41.33% to 70.07%,and there existed obvious regional difference.The positive rate was significantly lower than the warning limits of 75%,which should draw great attention,in order to prevent the outbreak of epidemic cerebrospinal meningitis serogroup C in troops.The average content of antibody was(4.766±8.396) μg/ml,so the effective control measures which included vaccination and health education should be conducted among recruits.
Effect on Prevention and Treatment of Anemia Among Primary and Secondary School Students in Jiangmen for 10 Years

[Objective] To understand dynamic change of anemia status among primary and secondary school students over the past 10 years in Jiangmen and evaluate the effect of prevention and treatment of anemia.[Methods] Stratified cluster random sampling was applied to investigate anemia status,and integrated measures were conducted for students with anemia.Hemoglobin values were determined by cyanmethemoglobin method according to the WHO1972 diagnostic criteria for anemia.[Results] Incidence of anemia declined annually,from 18.91% in 1997 to 2.31% in 2007.Anemia constitutive ratio above moderate degree declined from 25.90% in 1997 to 1.00% in 2001.No case was detected during 2002—2007.Downtrend in prevalence of anemia among primary school students was better than that of secondary school students,boys better than girls;the average prevalence of anemia among primary school students were higher than secondary school students,girls higher than boys in secondary school.[Conclusion] The effect of prevention and treatment of anemia was significant.Anemia control focus groups were primary school students and secondary school girls.
The regulation of IgA B-cell differentiation.

SUMMARY IgA B-cell differentiation is affected by several kinds of events (Fig. 3). One key event, IgA B-cell switch differentiation, is a process that may be controlled by tissue-specific “switch” cells or an identifiable switching cytokine or lymphokine that operates in an IgA-specific fashion. Another event, or group of events is IgA B-cell terminal differentiation in B cells already switched to IgA. Such terminal differentiation may also be regulated in an IgA-specific fashion, at least insofar as class-nonspecific lymphokines can be presented to IgA B cells in a class-specific fashion by cells bearing IgA-Fc receptors. Emerging knowledge of the regulation of IgA B cells offers many opportunities to enhance or inhibit IgA B-cell development at several levels. In coming years this will prove important, not only in devising ways of protecting against mucosal pathogens, but also in modifying immunologic diseases that have their basis in mucosal immune system dysfunction.
Adenosine receptor-mediated calcium mobilization in cortical collecting tubule cells.

To investigate the cellular mechanisms underlying the epithelial actions of adenosine, we studied adenosine receptor-effector coupling in cultured rabbit cortical collecting tubule (RCCT) cells. We previously reported, in RCCT cells isolated by immunodissection, that a potent A2 adenosine analogue [59-N-ethylcarboxamideadenosine (NECA)] stimulates cAMP production [effective concentration 50% (EC50) = 1 microM], and potent A1 analogues [N6-cyclohexyladenosine (CHA) and R-N6-phenylisopropyladenosine (PIA)] inhibit basal and AVP-stimulated cAMP production (EC50 = 5 nM). The present study was undertaken to determine whether adenosine receptors in RCCT cells are also coupled to a signal transduction system leading to the mobilization of intracellular free calcium. RCCT cells were loaded with the fluorescent calcium indicator, fura-2, and were treated with the adenosine analogues NECA, CHA, and PIA. All three adenosine analogues produced dose-dependent (1 nM-0.1 mM), transient increases in intracellular calcium concentration with equal potency (EC50 = 0.5 microM). Chelation of extracellular calcium with ethyleneglycol-bis(beta-aminoethyl ether)N,N,N9,N9 tetraacetic acid (EGTA) did not abolish the increase in calcium. The adenosine receptor antagonists, 1,3-diethyl-8-propylxanthine and 8-cyclopentyl-1,3-dipropylxanthine, and pretreatment of RCCT cells with pertussis toxin blocked the increase in calcium. These results demonstrate that RCCT cells have, in addition to adenosine receptors associated with the stimulation and inhibition of cAMP, a pertussis-toxin sensitive receptor system that leads to the mobilization of intracellular calcium.
Aneurysma der Keilbeinhöhle, eine seltene Komplikation der endonasalen Nasennebenhöhlen-Chirurgie

Die Autoren berichten uber eine intraoperative Blutung bei einer endonasalen Siebbeinoperation. Ursache war ein gestieltes Aneurysma der linken Keilbeinhohle. Wahrend der Operation kam es zu einer akzidentellen Verletzung des Aneurysmas. Die Blutung konnte intraoperativ sofort durch Tamponade gestillt werden, spater wurde diesembolisiert. In einer zweiten Operation wurde die Keilbeinhohle durch eine autologe Muskelplombe okkludiert.
The physical basis of learning

This chapter discusses the techniques that help in exploration of the physical machinery that underlies overt behavior. The most widely used methods of studying the physical basis of learning include the lesion, electrical, and chemical techniques. In lesion techniques, specific parts of the brain are damaged, removed, or destroyed. The investigator then looks for specific, consistent behavior changes that are correlated with this damage. Some studies suggest that overt learning events can be reflected in consistent changes in electroencephalograph records. Hippocampal theta activity is the electrical brain activity displayed by the cat during learning. Theta waves are slow and of a high amplitude relative to waves occurring during non-training. Some experimenters feel that theta activity shows that the hippocampus is involved in encoding, storage, and retrieval, whereas others feel the hippocampus is involved in attention to the environment. In chemical technique, various chemicals or drugs are introduced into the brain and to observe concomitant behavior changes. Psychologists have been concerned with the effects of various drugs both within cells and between cells.
Boundary-condition analysis for physics-based modeling of ionic-polymer metal composite electroactive polymers

Ionic-polymer metal composites (IPMCs) are a subset of ionic electroactive polymers (EAPs). They produce an actuation response based on the electrically induced flux of mobile ions through a parent-polymer matrix. This response is a result of the accumulation of cations and anions on opposing sides of the matrix and is directly related to the size disparity between the two types of ions. These factors impose a differential expansion across the matrix, which generates the macroscopic bending that is observed. It is well known that the motion of these EAPs is highly nonlinear and time dependent, making for a process that is difficult to model. A simplistic approach to modeling the physics behind this phenomenon and correlating that to experimental results is outlined, herein. This new methodology enables a comprehensive analysis of the boundary conditions (BCs) needed to be considered in order to accurately characterize the IPMC actuation response. The subsequent series of equations developed, which depict the ionic motion under these BCs, is presented. Empirical data for model analysis was acquired from IPMCs created using poly(ethylene oxide) (PEO), a well-known, biodegradable, solid-polymer electrolyte infused with lithium perchlorate, as the ionic salt. Experimental results fitted with this new model returned a favorable average adjusted-R2, goodness-of-fit, of 0.987, 0.994, and 0.992 when PEO films were tested under varying conditions, including: ionic concentration, applied voltage, and testing temperature, respectively.
Child to Parent Kindey Transplant

A 62 year old obese business executive who developed end-stage renal failure after twenty-three years of non-insulin-dependent diabetes (type 2) has a “troubled” course on maintenance hemodialysis. Repeated infections of his vascular access site and several episodes of pulmonary edema after dietary indiscretion necessitated seven hospitalizations during the first year of dialytic therapy. Depressed over his failed rehabilitation and an anticipated delay of longer than one year for a cadaver donor kidney transplant, the patient proposes that his 22 year old daughter serve as a kidney donor. Recognizing that because both parents are diabetic, she faces a highly probable risk of becoming diabetic in later life, the daughter insists on donating her kidney to “save her father.” A consulting endocrinologist states that any child-to-parent organ transplant in a diabetic family is dangerous and unethical.
Variable aromatase inhibitor plasma concentrations do not correlate with circulating estrogen concentrations in post-menopausal breast cancer patients.

The aromatase inhibitors (AI) exemestane (EXE), letrozole (LET), and anastrozole suppress estrogen biosynthesis, and are effective treatments for estrogen receptor (ER)-positive breast cancer. Prior work suggests that anastrozole blood concentrations are associated with the magnitude of estrogen suppression. The objective of this study was to determine whether the magnitude of estrogen suppression, as determined by plasma estradiol (E2) concentrations, in EXE or LET treated patients is associated with plasma AI concentrations. Five hundred post-menopausal women with ER-positive breast cancer were enrolled in the prospective Exemestane and Letrozole Pharmacogenetic (ELPh) Study conducted by the COnsortium on BReast cancer phArmacogomics (COBRA) and randomly assigned to either drug. Estrogen concentrations were measured at baseline and after 3 months of AI treatment and drug concentrations were measured after 1 or 3 months. EXE or LET concentrations were compared with 3-month E2 concentration or the change from baseline to 3 months using several complementary statistical procedures. Four-hundred patients with on-treatment E2 and AI concentrations were evaluable (EXE n = 200, LET n = 200). Thirty (7.6%) patients (EXE n = 13, LET n = 17) had 3-month E2 concentrations above the lower limit of quantification (LLOQ) (median: 4.75; range: 1.42–63.8 pg/mL). EXE and LET concentrations were not associated with on-treatment E2 concentrations or changes in E2 concentrations from baseline (all p > 0.05). Steady-state plasma AI concentrations do not explain variability in E2 suppression in post-menopausal women receiving EXE or LET therapy, in contrast with prior evidence in anastrozole treated patients.
MALDI Mass Spectrometry and Infectious Diseases

MALDI mass spectrometry is an emerging technology that has revolutionized the field of diagnostic microbiology. MALDI mass spectrometry has the potential to significantly impact the field of infectious diseases as new technology emerges. In particular, the use of histology-directed MALDI-MS profiling of biofluids and tissues presents a way to potentially perform bacterial typing and monitor host response without an additional culture step to culture the microorganism. MALDI Imaging Mass Spectrometry is another attractive technology to study the pathogen-host interaction within infected tissues. This allows an unprecedented view of the molecular changes associated with infection. Pairing advanced Imaging Mass Spectrometry with emerging analyte identification strategies, the identity of these molecular changes can be determined. Utilizing such technologies could revolutionize the study of microbial pathogenesis and may reveal a number of novel targets for future antimicrobial intervention.
Temporomandibular Joint Disorders

Temporomandibular joint functional disorders are classified into derangements of the condyle-disc complex, structural incompatibility of the articular surfaces, and inflammatory joint disorders. Clinical signs and symptoms may range from non-painful signs of joint noises to acute and chronic pain and dysfunction. These conditions are prevalent; nevertheless, only some require treatment. Diagnostic criteria are described in the AAOP guidelines [1] and diagnostic criteria for TMD [2]. The clinician should always match the level of complexity of the management program with the complexity of the patient. In complex patients, the use of a pain clinic team to facilitate success is often needed. Employing clinical paradigms of self-care, education, and self-responsibility in the patient’s care will enhance long-term outcomes and maintain positive relationships between the patient and the clinician.
Copper homeostasis networks in the bacterium Pseudomonas aeruginosa

Bacterial copper (Cu+) homeostasis enables both precise metallation of diverse cuproproteins and control of variable metal levels. To this end, protein networks mobilize Cu+ to cellular targets with remarkable specificity. However, the understanding of these processes is rather fragmented. Here, we use genome-wide transcriptomic analysis by RNA-Seq to characterize the response of Pseudomonas aeruginosa to external 0.5 mm CuSO4, a condition that did not generate pleiotropic effects. Pre-steady-state (5-min) and steady-state (2-h) Cu+ fluxes resulted in distinct transcriptome landscapes. Cells quickly responded to Cu2+ stress by slowing down metabolism. This was restored once steady state was reached. Specific Cu+ homeostasis genes were strongly regulated in both conditions. Our system-wide analysis revealed induction of three Cu+ efflux systems (a P1B-ATPase, a porin, and a resistance-nodulation-division (RND) system) and of a putative Cu+-binding periplasmic chaperone and the unusual presence of two cytoplasmic CopZ proteins. Both CopZ chaperones could bind Cu+ with high affinity. Importantly, novel transmembrane transporters probably mediating Cu+ influx were among those largely repressed upon Cu+ stress. Compartmental Cu+ levels appear independently controlled; the cytoplasmic Cu+ sensor CueR controls cytoplasmic chaperones and plasma membrane transporters, whereas CopR/S responds to periplasmic Cu+. Analysis of ΔcopR and ΔcueR mutant strains revealed a CopR regulon composed of genes involved in periplasmic Cu+ homeostasis and its putative DNA recognition sequence. In conclusion, our study establishes a system-wide model of a network of sensors/regulators, soluble chaperones, and influx/efflux transporters that control the Cu+ levels in P. aeruginosa compartments.
Laser Forming for Complex 3D Folding

Laser heating to generate plastic strains for controlled bending, known as laser forming, is a promising technique for creating 3D structures based on origami-inspired principles. Here, for the first time, laser cutting and forming are used to go from flat unpatterned metal sheet to final folded part, including up and down folds, all without manual handling. Folding direction is controlled by adjusting laser travel speed to create either a lateral or a vertical thermal gradient in the workpiece. Numerical modeling followed by experimental verification is used to determine the transition point between bending toward and away from the laser, followed by demonstration of a variety of complex 3D folded parts. Using this approach, laser forming is then used to precisely align two components, demonstrating the positioning of an optical reflector to guide the laser and pattern a portion of the sheeting originally inaccessible on the underside. All work here is done with a commercially available 20 W marking laser without modification.
Impact of Course Policy Changes on Calculus I DFW Rates

This paper examines the impact of departmental policy changes on the trend in DFW proportions for introductory calculus at a large research university. We defined three distinct policy periods: Traditional (2002-2005), Active Learning (SCALE-UP) (2006-2013), and Return to Traditional (2014-2015). Regression analysis showed DFW proportions were increasing during the Traditional period, significantly decreased after the switch to SCALE-UP, remained fairly consistent during the SCALE-UP period, and then significantly increased during Return to Traditional. Individual trends for D, F, and W proportions were also analyzed. The two policy changes had the greatest influence on the trend in F and W proportions. Potential factors that could influence a student to withdraw from the course were examined. Students who withdrew had midterm averages similar to students who failed the course during the SCALE-UP period, but their averages were significantly lower than the F students during the Return to Traditional period.
Etiology of Global Corneal Blindness and Current Practices of Corneal Transplantation: A Focused Review.

Purpose The purpose of this focused review was to explore the etiologies of corneal blindness worldwide and compare them with the indications and type of keratoplasties (eg, full-thickness penetrating keratoplasty, anterior lamellar keratoplasty, or endothelial keratoplasty) performed. Methods A literature search of the articles published in the top 10 journals (based on the Altmetrics score) relevant to corneal transplantation within the past 20 years was performed to determine how the focus within corneal transplantation has changed over time. These data were compared with the prevalence and etiology of corneal blindness in each respective region worldwide. Results The leading etiologies of corneal blindness worldwide are primarily due to anterior corneal pathology with a normal endothelium, and the prevalence is highest in developing countries. In addition, the number and type of corneal transplantations performed globally indicate that current practices are disproportionately skewed in favor of endothelial keratoplasty, which is targeted for the pathology prevalent in developed countries. Despite the large number of individuals who would benefit from anterior lamellar keratoplasty, this technique seems to be infrequently performed. Conclusions Most corneal blindness worldwide is secondary to anterior corneal pathology because of infections and trauma. However, this does not align with the current trends and practices in the field of corneal transplantation. We discuss potential solutions to address the current leading causes of global corneal blindness, including increasing the number of anterior lamellar keratoplasties performed, using long-term preserved corneas by trained surgeons, and improving eye bank handling and distribution of procured tissues.
A PROBLEM OF RUSHING

Publisher Summary This chapter presents a problem of Rushing. It presents an assumption where α and β are tame arcs in three-space, R 3 . If α∩β is wild, it fails to be locally tame only at the point { P }= α∩β. Such arcs have been called mildly wild. The chapter presents theorem that states that if and β are tame arcs in three-space, R 3 and α∩β = { P } is an end-point of each of α ∩and β and α∩β is locally peripherally unknotted at P, then there is an arc γ such that α∩ γ and β ∩ γ meet only at P, an end-point of γ, and α∩ γ and β∩ γ are tame.
Hospital percutaneous coronary intervention volume and patient mortality, 1998 to 2000: does the evidence support current procedure volume minimums?

Abstract Objectives The aim of this study was to evaluate current American College of Cardiology/American Heart Association (ACC/AHA) hospital percutaneous coronary intervention (PCI) volume minimum recommendations. Background In order to reduce procedure-associated mortality, ACC/AHA guidelines recommend that hospitals offering PCIs perform at least 400 PCIs annually. It is unclear whether this volume standard applies to current practice. Methods We conducted a retrospective analysis of the Agency for Healthcare Research and Quality's Nationwide In-patient Sample hospital discharge database to evaluate in-hospital mortality among patients (n = 362,748) who underwent PCI between 1998 and 2000 at low (5 to 199 cases/year), medium (200 to 399 cases/year), high (400 to 999 cases/year), and very high (1,000 cases or more/year) PCI volume hospitals. Results Crude in-hospital mortality rates were 2.56% in low-volume hospitals, 1.83% in medium-volume hospitals, 1.64% in high-volume hospitals, and 1.36% in very high-volume hospitals (p Conclusions We found no evidence of higher in-hospital mortality in patients undergoing PCI at medium-volume hospitals compared with patients treated at hospitals with annual PCI volumes of 400 cases of more, suggesting current ACC/AHA PCI hospital volume minimums may merit reevaluation.
Measuring human capital: a systematic analysis of 195 countries and territories, 1990-2016.

Summary Background Human capital is recognised as the level of education and health in a population and is considered an important determinant of economic growth. The World Bank has called for measurement and annual reporting of human capital to track and motivate investments in health and education and enhance productivity. We aim to provide a new comprehensive measure of human capital across countries globally. Methods We generated a period measure of expected human capital, defined for each birth cohort as the expected years lived from age 20 to 64 years and adjusted for educational attainment, learning or education quality, and functional health status using rates specific to each time period, age, and sex for 195 countries from 1990 to 2016. We estimated educational attainment using 2522 censuses and household surveys; we based learning estimates on 1894 tests among school-aged children; and we based functional health status on the prevalence of seven health conditions, which were taken from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016). Mortality rates specific to location, age, and sex were also taken from GBD 2016. Findings In 2016, Finland had the highest level of expected human capital of 28·4 health, education, and learning-adjusted expected years lived between age 20 and 64 years (95% uncertainty interval 27·5–29·2); Niger had the lowest expected human capital of less than 1·6 years (0·98–2·6). In 2016, 44 countries had already achieved more than 20 years of expected human capital; 68 countries had expected human capital of less than 10 years. Of 195 countries, the ten most populous countries in 2016 for expected human capital were ranked: China at 44, India at 158, USA at 27, Indonesia at 131, Brazil at 71, Pakistan at 164, Nigeria at 171, Bangladesh at 161, Russia at 49, and Mexico at 104. Assessment of change in expected human capital from 1990 to 2016 shows marked variation from less than 2 years of progress in 18 countries to more than 5 years of progress in 35 countries. Larger improvements in expected human capital appear to be associated with faster economic growth. The top quartile of countries in terms of absolute change in human capital from 1990 to 2016 had a median annualised growth in gross domestic product of 2·60% (IQR 1·85–3·69) compared with 1·45% (0·18–2·19) for countries in the bottom quartile. Interpretation Countries vary widely in the rate of human capital formation. Monitoring the production of human capital can facilitate a mechanism to hold governments and donors accountable for investments in health and education. Funding Institute for Health Metrics and Evaluation.
Visualizing High Dimensional and Big Data

Abstract The amount of data created by people, machines and corporations around the world is growing every year. Thanks to innovations such as the Internet of Things, this trend will continue, giving rise to the creation of Big Data. Data visualization leverages principles of visual psychology to help stakeholders identify patterns, trends and correlations that might go undetected in text-based or spreadsheet data. The return on investment (ROI) of big data visualization is well-documented in numerous studies and use cases. However, to achieve ROI from analytics investments, key insights must be uncovered, understood and communicated. Synthesizing huge quantities of data into key insights grows more challenging as data volumes and varieties increase. To address visualization challenges posed by big and high-dimensional data, this paper explores algorithms and techniques that compress the amount of data and/or reduce the number of attributes to be analyzed and visualized. Specifically, this paper examines applying dimensionality reduction and data compression algorithms to reduce attributes, tuples and data points returned to the visualization. By reducing data returned to the visualization, trends, patterns and correlations are easier to view and visualization tool performance is optimized.
Analysis of >30,000 abstracts suggests higher false discovery rates for oncology journals, especially those with low impact factors

Background: Recently, there has been increasing concern about the replicability, or lack thereof, of published research. An especially high rate of false discoveries has been reported in some areas motivating the creation of resource-intensive collaborations to estimate the replication rate of published research by repeating a large number of studies. The substantial amount of resources required by these replication projects limits the number of studies that can be repeated and consequently the generalizability of the findings. Methods and findings: In 2013, Jager and Leek developed a method to estimate the empirical false discovery rate from journal abstracts and applied their method to five high profile journals. Here, we use the relative efficiency of Jager and Leek9s method to gather p-values from over 30,000 abstracts and to subsequently estimate the false discovery rate for 94 journals over a five-year time span. We model the empirical false discovery rate by journal subject area (cancer or general medicine), impact factor, and Open Access status. We find that the empirical false discovery rate is higher for cancer vs. general medicine journals (p = 5.14E-6). Within cancer journals, we find that this relationship is further modified by journal impact factor where a lower journal impact factor is associated with a higher empirical false discovery rates (p = 0.012, 95% CI: -0.010, -0.001). We find no significant differences, on average, in the false discovery rate for Open Access vs closed access journals (p = 0.256, 95% CI: -0.014, 0.051). Conclusions: We find evidence of a higher false discovery rate in cancer journals compared to general medicine journals, especially those with a lower journal impact factor. For cancer journals, a lower journal impact factor of one point is associated with a 0.006 increase in the empirical false discovery rate, on average. For a false discovery rate of 0.05, this would result in over a 10% increase to 0.056. Conversely, we find no significant evidence of a higher false discovery rate, on average, for Open Access vs. closed access journals from InCites. Our results identify areas of research that may need of additional scrutiny and support to facilitate replicable science. Given our publicly available R code and data, others can complete a broad assessment of the empirical false discovery rate across other subject areas and characteristics of published research.
Interaction of life-cycle phases in a probabilistic life-cycle framework for civil infrastructure system sustainability

Infrastructure system sustainability is dependent on contributions from different life-cycle phases like construction, operation, maintenance, failure and end-of-life demolition. While existing lif...
NAVIGATE: Explainable Visual Graph Exploration by Examples

We demonstrate NAVIGATE, an explai\underlineNA ble query engine for \underlineVI sual \underlineG r\underlineA ph explora\underlineT ion by \underlineE xamples. NAVIGATE interleavesquery rewriting and query answering to help users (1) search graphs \textslwithout writing complex queries, and (2) understand answers by providing intuitive explanations. Users can visually construct queries and specify missing or unwanted example entities to guide the exploration towards desired answers. NAVIGATE can rewrite queries with answers close to examples, by minimally altering their topological and semantic constraints. Another unique feature is its ability to explain query results by tracing the query manipulation operators that are responsible for transforming the original answers to desirable ones. In addition, NAVIGATE optimizes system response time by referring to dynamically cachedstar views to reduce both query evaluation and rewriting cost at run time. We also demonstrate its ease-of-use, efficiency, and explainable exploration in applications such as recommendation and knowledge base search.
Hydroxypropylation of Guar Splits: Kinetics and Rheology

Hydroxypropyl guar (HPG) is one of the most important derivatives of natural guar gum. In this paper, we describe the hydroxypropylation kinetics when these functional groups are added to guar splits, which are the form of guar gum typically modified in an industrial process. NMR spectroscopy was applied to quantify the amount of reacted propylene as a function of reaction time. A kinetic model was then established, enabling the derivation of a reaction rate law for the hydroxypropylation of guar. Finally, we investigated the rheological properties of aqueous-phase HPG and its cross-linked derivatives as a function of propylene content and cross-linker amount.
A study to evaluate the effect of investigator attendance on the efficiency of IRB review.

Institutional Review Boards (IRBs) are challenged to review increasing volumes of proposed research studies while meeting high ethical and regulatory standards.' A growing literature has documented concerns about the IRB review process, including administrative delays,z inadequate institutional support,3 and poor investigator-IRB relations.4 IRBs also carry significant operational costs,s creating a strong incentive for institutions to identify mechanisms to improve the efficiency of the review process. Some suggest that IRBs can become more efficient and decrease