cssi/SciSciGPT-SciSciNet huggingface dataset:
Assessing Effects of Aircraft and Fuel Technology Advancement on Select Aviation Environmental Impacts

The ability to simultaneously assess airline operations, economics, and emissions would help evaluate the progress toward reduction of aviation’s environmental impact as outlined in the NASA Enviro...
Community as Resistance: Reconceptualizing Historical Instances of Community within Latin@ Education

ABSTRACTThe term “community” is drawn upon within critical educational literature that seeks to address inequity experienced by students of color in schools, yet little explicit discussion of its meaning and history is presented. In this article, I offer one way of thinking about community. I propose that it has existed as resistance within the context of Latin@ education between the turn of the twentieth century through the latter part. Using a critical human geography lens, I argue that this history holds importance because spaces are (re)productions of past spaces. This offers possibilities for informing and inspiring present-day critical pedagogies.
Quantitative imaging biomarkers: Effect of sample size and bias on confidence interval coverage:

Introduction Quantitative imaging biomarkers (QIBs) are being increasingly used in medical practice and clinical trials. An essential first step in the adoption of a quantitative imaging biomarker is the characterization of its technical performance, i.e. precision and bias, through one or more performance studies. Then, given the technical performance, a confidence interval for a new patient's true biomarker value can be constructed. Estimating bias and precision can be problematic because rarely are both estimated in the same study, precision studies are usually quite small, and bias cannot be measured when there is no reference standard. Methods A Monte Carlo simulation study was conducted to assess factors affecting nominal coverage of confidence intervals for a new patient's quantitative imaging biomarker measurement and for change in the quantitative imaging biomarker over time. Factors considered include sample size for estimating bias and precision, effect of fixed and non-proportional bias, clustered data, and absence of a reference standard. Results Technical performance studies of a quantitative imaging biomarker should include at least 35 test-retest subjects to estimate precision and 65 cases to estimate bias. Confidence intervals for a new patient's quantitative imaging biomarker measurement constructed under the no-bias assumption provide nominal coverage as long as the fixed bias is <12%. For confidence intervals of the true change over time, linearity must hold and the slope of the regression of the measurements vs. true values should be between 0.95 and 1.05. The regression slope can be assessed adequately as long as fixed multiples of the measurand can be generated. Even small non-proportional bias greatly reduces confidence interval coverage. Multiple lesions in the same subject can be treated as independent when estimating precision. Conclusion Technical performance studies of quantitative imaging biomarkers require moderate sample sizes in order to provide robust estimates of bias and precision for constructing confidence intervals for new patients. Assumptions of linearity and non-proportional bias should be assessed thoroughly.
Microbial fuel cells: Running on gas

Methane is an abundant energy source that is used for power generation in thermal power plants via combustion, but direct conversion to electricity in fuel cells remains challenging. Now, a microbial fuel cell is demonstrated to efficiently convert methane directly to current by careful selection of a consortium of microorganisms.
Binding Selectivity of Methanobactin from Methylosinus trichosporium OB3b for Copper(I), Silver(I), Zinc(II), Nickel(II), Cobalt(II), Manganese(II), Lead(II), and Iron(II)

Methanobactin (Mb) from Methylosinus trichosporium OB3b is a member of a class of metal binding peptides identified in methanotrophic bacteria. Mb will selectively bind and reduce Cu(II) to Cu(I), and is thought to mediate the acquisition of the copper cofactor for the enzyme methane monooxygenase. These copper chelating properties of Mb make it potentially useful as a chelating agent for treatment of diseases where copper plays a role including Wilson's disease, cancers, and neurodegenerative diseases. Utilizing traveling wave ion mobility-mass spectrometry (TWIMS), the competition for the Mb copper binding site from Ag(I), Pb(II), Co(II), Fe(II), Mn(II), Ni(II), and Zn(II) has been determined by a series of metal ion titrations, pH titrations, and metal ion displacement titrations. The TWIMS analyses allowed for the explicit identification and quantification of all the individual Mb species present during the titrations and measured their collision cross-sections and collision-induced dissociation patterns. The results showed Ag(I) and Ni(II) could irreversibly bind to Mb and not be effectively displaced by Cu(I), whereas Ag(I) could also partially displace Cu(I) from the Mb complex. At pH ≈ 6.5, the Mb binding selectivity follows the order Ag(I)≈Cu(I)>Ni(II)≈Zn(II)>Co(II)>>Mn(II)≈Pb(II)>Fe(II), and at pH 7.5 to 10.4 the order is Ag(I)>Cu(I)>Ni(II)>Co(II)>Zn(II)>Mn(II)≈Pb(II)>Fe(II). Breakdown curves of the disulfide reduced Cu(I) and Ag(I) complexes showed a correlation existed between their relative stability and their compact folded structure indicated by their CCS. Fluorescence spectroscopy, which allowed the determination of the binding constant, compared well with the TWIMS analyses, with the exception of the Ni(II) complex. Graphical abstract ᅟ.
Joint mobilization and static stretching for individuals with chronic ankle instability – A pilot study

Abstract Objective To complete preliminary analysis regarding the effects joint mobilization timing during a 4-week calf stretching intervention on clinician-oriented and patient-oriented outcomes in individuals with chronic ankle instability (CAI). Additionally, a secondary objective was to examine the combined effect of joint mobilization and calf stretching. Design Randomized two-group pretest posttest design. Setting Laboratory. Participants Ten adults (age = 24.4 ± 4.7years; height = 172.1 ± 11.3 cm; weight = 76.2 ± 17.1 kg) with self-reported CAI participated. Interventions Participants completed outcome measures at three collection sessions (baseline, pre-intervention, and post-intervention). Participants were randomized into either into an early-mobilization or late-mobilization group in which they completed a joint mobilization intervention during the first or last 2 weeks of a 4-week calf stretching intervention. Main outcome measures Outcome measures included: dorsiflexion ROM, dynamic postural control, single-limb postural control, Disablement in the Physically Active Scale (DPA), Foot and Ankle Ability Measure (FAAM), and Fear-Avoidance Beliefs Questionnaire (FABQ). Wilcoxon Sign Rank Tests examined pre-intervention to post-intervention differences for each dependent variable. Mann-Whitney U tests examined differences between early-mobilization and late-mobilization groups. Alpha was set a priori at p Results No significant differences were identified between early-mobilization and late-mobilization groups at post intervention (p > .095). FAAM-Activities of Daily Living, DPA, FABQ-Physical Activity, and dorsiflexion ROM were significantly improved at post-intervention compared to pre-intervention (p .057). Conclusion Preliminarily results suggest the timing of joint mobilization when used in conjunction with calf stretching does not effect treatment efficacy. However, the combination of joint mobilization and calf stretching can improve dorsiflexion ROM and self-reported function in individuals with CAI. Improvements from the combined intervention are similar to previously reported effects of isolated joint mobilization or stretching.
Structural insights into the mechanisms of CNBD channel function.

Cyclic nucleotide-binding domain (CNBD) channels are a family of ion channels in the voltage-gated K+ channel superfamily that play crucial roles in many physiological processes. CNBD channels are structurally similar but functionally very diverse. This family includes three subfamilies: (1) the cyclic nucleotide-gated (CNG) channels, which are cation-nonselective, voltage-independent, and cyclic nucleotide-gated; (2) the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are weakly K+ selective, hyperpolarization-activated, and cyclic nucleotide-gated; and (3) the ether-a-go-go-type (KCNH) channels, which are strongly K+ selective, depolarization-activated, and cyclic nucleotide-independent. Recently, several high-resolution structures have been reported for intact CNBD channels, providing a structural framework to better understand their diverse function. In this review, we compare and contrast the recent structures and discuss how they inform our understanding of ion selectivity, voltage-dependent gating, and cyclic nucleotide–dependent gating within this channel family.
Relation generation and fast similarity testing for unsupervised learning

Unsupervised learning of concepts is essential for analogical thinking, which is considered a hallmark of human intelligence. We argue that signals in the brain constantly generate relations among their constituents. Unsupervised learning is then accomplished by fast similarity testing of the stored relation sets using resonance transients and time sequenced memory units. We discuss specific algorithms to achieve these functions.
Numerical characterization of the edge transport conditions and limiter fluxes of the HIDRA stellarator

The Hybrid Illinois Device for Research and Applications (HIDRA) is a new device for education and Plasma-Material Interaction research at the University of Illinois at Urbana-Champaign. In advance of its first operational campaign, EMC3-EIRENE simulations have been run on the device. EMC3-EIRENE has been modified to calculate a per-plasma-cell relaxed Bohm-like diffusivity simultaneously with the electron temperature at each iteration. In our characterization, the electron temperature, diffusivity, heat fluxes, and particle fluxes have been obtained for varying power levels on a HIDRA magnetic grid, and scaling laws have been extracted, using constraints from previous experimental data taken when the device was operated in Germany (WEGA facility). Peak electron temperatures and heat fluxes were seen to follow a power-law dependence on the deposited radiofrequency (RF) power of type f(PRF)∝aPRFb, with typical exponents in the range of b ∼0.55 to 0.60. Higher magnetic fields have the tendency to linearize ...
Tolerance of low oxygen stress in insecticide-resistant and susceptible populations of mosquitofish (Gambusia affinis).

Abstract The tolerance of low oxygen stress in insecticide-resistant and susceptible populations of mosquitofish ( Gambusia affinis ) was investigated. Dissolved oxygen was reduced chemically with formaldehyde and sodium sulfite treatment. Available oxygen was reduced physically through barriers, both by preventing oxygen exchange at the air-water interface and by preventing the fish from contacting the surface of the water. In all cases, the tolerance to low oxygen stress was reduced in the insecticide-resistant population compared to the susceptible population. The results indicate that although tolerance of pesticides in the resistant population has been dramatically increased by environmental selective pressures, tolerance to other stresses has not been concomitantly increased.
Potential Medical (Clinical) Applications of EPR: Overview & Perspectives

While there are ample reasons for the development and use of in vivo EPR techniques for strictly experimental applications in animals, there are also some very attractive potential clinical applications. The aim of this chapter is to provide an overview of the status of in vivo EPR applied to human subjects and, especially, the rationale and future prospects for clinical applications. The approaches based on dynamic nuclear polarization, described in chapter 20, are not covered here because of the very different instrumental approaches that are involved with that technique. The area with the most obvious immediate and effective clinical use appears to be oximetry, where EPR almost uniquely can make repeated accurate measures of pO2 which can provide clinicians with information that can impact directly on diagnosis and therapy, especially for oncology and peripheral vascular disease. A closely related area of potential widespread applications is the use of EPR to measure nitric oxide. Another area of potential extensive early applications in human subjects is in pharmacology where the unique capabilities of in vivo EPR to detect and characterize free radicals may be applied immediately to measure free radical intermediates from drugs and oxidative process. These unique capabilities, combined with the sensitivity of EPR spectra to the immediate environment (e.g. pH, motion, charge) has already resulted in some very productive applications in animals and these are likely to expand substantially in the near future. They should provide a continually developing base for establishing and extending clinical uses of in vivo EPR.
Comments on the Systematics and Classification of the Beavers (Rodentia, Castoridae)

The systematics of the beavers (Castoridae) are reviewed and definitions are presented for each subfamilial group. Four subfamilies are recognized: primitive Agnotocastorinae (divided into two tribes, Agnotocastorini and Anchitheriomyini); burrowing beavers, Palaeocastorinae; giant beavers, Castoroidinae (containing two tribes, Castoroidini and Trogontheriini); and the Castorinae. The agnotocastorines are viewed as the ancestral group for all later subfamilies. The Palaeocastorinae is viewed as a side-branch, not ancestral or closely related to any of the later subfamilies. The Castorinae and Castoroidinae may represent a distinct clade united by dental features.
Obesity at diagnosis and after treatment in breast cancer survivors and risk of neuropathy.

e22085Background: Guidelines recommend that breast cancer survivors maintain a healthy body weight as obesity (BMI≥30 kg/m2) predicts worse survival outcomes. We sought to identify patient characte...
Ultra-Rapid Reporting of GENomic Targets (URGENTseq): Clinical Next-Generation Sequencing Results within 48 Hours of Sample Collection

Next-generation sequencing (NGS)-based mutation panels profile multiple genes simultaneously, allowing the reporting of numerous genes while saving labor and resources. However, one drawback of using NGS is that the turnaround time is often longer than conventional single gene tests. This delay can be problematic if molecular results are required to guide therapy in patients with clinically aggressive diseases, such as acute myeloid leukemia. To overcome this limitation, we developed a novel custom platform designated as Ultra-rapid Reporting of GENomic Targets (URGENTseq), an integrated solution that includes workflow optimization and an innovative custom bioinformatics pipeline to provide targeted NGS results on fresh peripheral blood and bone marrow samples within an actionable time period. URGENTseq was validated for clinical use by determining mutant allelic frequency and minimum coverage in silico to achieve 100% concordance for all positive and negative calls between the URGENTseq and conventional sequencing approach. URGENTseq enables the reporting of selected genes useful for immediate diagnosis (CALR, CSF3R, JAK2, KRAS, MPL, NPM1, NRAS, SF3B1) and treatment decisions (IDH1, IDH2) in hematologic malignancies within 48 hours of specimen collection. In addition, we summarize the molecular findings of the first 272 clinical test results performed using the URGENTseq platform.
Will outpatients complete living wills? A comparison of two interventions.

Objective:To test the efficacy of two intervention methods that aimed to increase the percentage of adult clinic patients who completed living wills and placed them on file with their physicians within a four-month period.
Variability of millennial‐scale trends in the geomagnetic axial dipole

Author(s): Buffett, B; Davis, W; Avery, MS | Abstract: The historical trend in the axial dipole is sufficient to reverse the field in less than 2 kyr. Assessing the prospect of an imminent polarity reversal depends on the probability of sustaining the historical trend for long enough to produce a reversal. We use a stochastic model to predict the variability of trends for arbitrary time windows. Our predictions agree well with the trends computed from paleomagnetic models. Applying these predictions to the historical record shows that the current trend is likely due to natural variability. Furthermore, an extrapolation of the current trend for the next 1 to 2 kyr is highly unlikely. Instead, we compute the trend and time window needed to reverse the field with a specified probability. We find that the dipole could reverse in the next 20 kyr with a probability of 2%.
Teaching writing in Brazilian public high schools

Writing skills are crucial for high school students’ academic, social, and professional success in Brazil. Developing the ability to write, however, is a demanding process that requires considerable support from teachers. The purpose of this study was to survey the population of high school language arts teachers in two Brazilian states about their writing instructional practices, including the use of instructional practices supported by scientifically based research (evidence-based practices), perceptions of their preparation, and perceived self-efficacy in teaching writing. A second aim of this study was to examine whether teacher perceived preparation and self-efficacy predicted teachers’ use of evidence-based writing practices. Nine hundred fifty-three teachers completed the survey. The teachers’ responses point to some potential shortcomings in high school writing instruction, as the majority of teachers reported spending only 50 min per week teaching writing. Although teachers indicated that they were familiar with and used a variety of evidence-based writing practices in their classrooms, they used these practices infrequently. Further, teachers rated the preparation they personally undertook outside college or in-service higher than the preparation they received in college or in-service. The present study provides tentative support for the following recommendations for reforming high school writing instruction in Brazil: (a) increasing the amount of writing instruction and time students spend writing; (b) placing more emphasis on evidence-based writing practices; and (c) strengthening professional development for writing teachers in teacher education degree programs and for those already in the field.
Impact of Admission Calcium-phosphate Product on 1-year Mortality among Hospitalized Patients.

Background: Calcium-phosphate product is associated with mortality among patients with end-stage kidney disease on dialysis. However, clinical evidence among hospitalized patients is limited. The objective of this study was to investigate the relationship between admission calcium-phosphate product and 1-year mortality in hospitalized patients. Materials and Methods: All adult patients admitted to a tertiary referral hospital in 2009–2013 were studied. Patients who had both available serum calcium and phosphate measurement within 24 h of hospital admission were included. Admission calcium-phosphate product (calcium × phosphate) was stratified based on its distribution into six groups:
Accelerated Estimation of Long-Timescale Kinetics from Weighted Ensemble Simulation via Non-Markovian "Microbin" Analysis.

The weighted ensemble (WE) simulation strategy provides unbiased sampling of nonequilibrium processes, such as molecular folding or binding, but the extraction of rate constants relies on character...
Unique models and initiatives that states are working on to “close” the family care gap

Abstract Caregiving is physically and emotionally draining, and public awareness of the unique needs of family caregivers is on the rise. Implementation of support-based programs has been found to successfully decrease depression and levels of stress and have also highlighted the substantial benefits present in caregiving. Unique implementation initiatives include the New York University Caregiver Intervention, Resources for Enhancing Alzheimer's Caregiver Health, Caring for You, Caring for Me, and virtual support. The execution of these initiatives has been carried out across a number of states. This chapter will highlight the impact of these evidence-based and evidence-driven programs. Particular attention will be given to how these programs address care gaps. There is no doubt that more initiatives are on the horizon to support caregivers throughout the United States, and one of our most challenging tasks is helping caregivers discern the distinctions and potential benefits to extend and bolster the considerable help they provide to older adults in need.
Acetylcholine signaling genes are required for cocaine-stimulated egg laying in Caenorhabditis elegans

The toxicity and addictive liability associated with cocaine abuse are well known. However, its mode of action is not completely understood, and effective pharmacotherapeutic interventions remain elusive. The cholinergic effects of cocaine on acetylcholine receptors, synthetic enzymes, and degradative enzymes have been the focus of relatively little empirical investigation. Due to its genetic tractability and anatomical simplicity, the egg laying circuit of the hermaphroditic nematode, Caenorhabditis elegans, is a powerful model system to precisely examine the genetic and molecular targets of cocaine in vivo. Here, we report a novel cocaine-induced behavioral phenotype in Caenorhabditis elegans, cocaine-stimulated egg laying. In addition, we present the results of an in vivo candidate suppression screen of synthetic enzymes, receptors, degradative enzymes, and downstream components of the intracellular signaling cascades of the main neurotransmitter systems that control Caenorhabditis elegans egg laying. Our results show that cocaine-stimulated egg laying is dependent on acetylcholine synthesis and synaptic release, functional nicotinic acetylcholine receptors, and the Caenorhabditis elegans acetylcholinesterases.
Don't Judge a Letter by its Title: Linguistic Analysis of Letters of Recommendation by Author's Academic Rank.

OBJECTIVE This study analyzed the linguistic differences in letters of recommendation (LORs) for general surgery residency applicants written by authors of various academic ranks. Given that many general surgery residency programs require a LOR from the Chair of surgery, this study also examined whether LORs written by the Chair demonstrate linguistic differences to support this practice. DESIGN A single institution, retrospective review analyzed LORs from two application cycles of general surgery residency applicants who were selected for interview at a large academic institution. Word count (WC) and linguistic characteristics of LORs were analyzed with a previously developed institution-specific dictionary using the Linguistic Inquiry and Word Count software (LIWC2015; Pennebaker Conglomerates, Inc., Austin, Texas). WC and linguistic characteristics of LORs reported as frequencies of terms within twenty-four categories were examined based on the letter authors’ academic rank. Further examination compared LORs written by a Chair of surgery with those written by non-Chairs. SETTING A single large, Midwestern academic general surgery residency program PARTICIPANTS Four hundred and sixty–five letters of recommendation received during two interview cycles were included for analysis. RESULTS A total of 465 LORs written by assistant (n = 82), associate (n = 94), and full professors (n = 289) were included in the study. No statistically significant difference was noted in the WC of LORs based on the letter writers’ academic ranks (p = 0.95). Assistant professors utilized grindstone, communal, and technical skill terms with higher frequencies compared to associate professors and full professors. LORs written by assistant professors demonstrated the highest authentic variable score followed by associate professors then full professors (4.94, 3.92, 3.28, p CONCLUSIONS Linguistic analysis of LORs for general surgery residency applicants demonstrated minor yet statistically significant differences based on the author's academic rank. If applicants can obtain linguistically similar LORs from surgeons of any academic rank, but less authentic LORs from writers with higher academic ranks, these LORs may be less valuable for the residency programs when evaluating applicants. Based on the subgroup analysis, less than 40% of Chair LORs indicated that the Chair worked directly with the applicant, calling into question the utility of the Chair LORs as meaningful evaluation of applicants. Further study to compare LORs of applicants selected and not selected for interview may add additional insight into linguistic differences in LORs written by authors of different academic ranks.
The Effects of Education Savings Accounts (ESAs) on Teacher Pay in Texas

Given that public school districts employ roughly 90 percent of teachers in Texas, teachers have little negotiating power in today’s labor market. Budget reallocations at public school districts and private schools from ESAs could increase teacher salaries in the first year, with some increasing by as much as $28,000. More competitive teacher labor markets will gradually contribute to increases in teacher salaries beyond those facilitated by ESAs and improvements in working conditions.
Which households are energy insecure? An empirical analysis of race, housing conditions, and energy burdens in the United States

Abstract Energy insecurity refers to a household’s inability to meet its basic energy needs. Previous research has shown that this type of material hardship can lead to negative mental and physical health outcomes, especially for children and the elderly. This study analyzes a state-representative sample of low-income households to evaluate if households of color are more likely than white households to be energy insecure, and, if the reasons are either poor housing conditions or higher energy burdens. We find that energy insecurity is widespread. Over a year period, 30 percent of respondents were unable to pay at least one energy bill, 33 percent received at least one disconnection notice, and 13 percent were disconnected from their electric utility service. Regression analysis further suggests that Black and Hispanic households are more likely than white households to be energy insecure. Additionally, deficient housing conditions and higher energy burdens are both independent predictors of household energy insecurity. Through a mediating variables analysis, however, we find that housing conditions and energy burdens only explain a small proportion of the association between race and energy insecurity. These results indicate that there remains considerable uncertainty about the reasons that households of color experience energy insecurity at higher rates than white households and that future research is needed to uncover the mechanisms underlying these disparities.
Meaning and Context in Computer Programs

When you look at a function program's source code, how do you know what it means? Is the meaning found in the return values of the function, or is it located inside the function body? What about th...
Carboxymethylation of sperm whale myoglobin in the crystalline state.

Abstract Crystals of sperm whale ferrimyoglobin were treated with 0.2 m sodium bromoacetate in concentrated ammonium sulfate solution at pH 6.8 for 10 days. The product obtained after dissolving the crystals retained most of the physical properties of the unmodified protein, except for the development of a small number of electrophoretic components representing an increment of about six to eight net negative charges on the average, judged at pH 9.2. The most fully studied preparation contained 6.4, 2.7, 2.0, and 0.8 residue per molecule of histidine, 1,3-dicarboxymethylhistidine, 3-carboxymethylhistidine, and 1-carboxymethylhistidine, respectively. The amino-terminal valyl residue was largely alkylated. Between 1 and 2 residues of lysine were alkylated. No modification of methionine was detected. After removal of heme the modified protein was subjected to cleavage by trypsin and chymotrypsin and the peptides were isolated by chromatography on ion exchange resins and, as required, by paper chromatography or paper electrophoresis. The state of alkylation of 10 of the 12 histidyl residues was established by quantitative estimation of the yields of appropriate tryptic and chymotryptic peptides. The state of residue 12 was determined qualitatively, and that of residue 113 surmised by difference. The following residues were recovered as unmodified histidine: 24, 48, 82, 93, and 97. Residue 119 was recovered primarily in the unmodified form but partly as 1-carboxymethylhistidine. The following residues were recovered primarily or exclusively as 1,3-dicarboxymethylhistidine: 12, 81, 114, and 116. Residue 116 was recovered partly as 3-carboxymethylhistidine. Residue 36 was recovered in high yield exclusively as 3-carboxymethylhistidine. Without exception these results appear to conform to the implications of the crystalline structure reported by Kendrew and Watson when account is taken of the geometry of interactions between neighboring myoglobin molecules in the crystal lattice.
Managerial Rationality and Agency Problem in the IPO Market

When firms raise equity capital through initial public offerings (IPOs), do the managers act rationally? Recently Loughran and Ritter (2002) argued that some IPO issuers become "complacent" on receiving "good news", and that such issuers do not negotiate optimally. In this paper, I show that, upon observing good news, managers strategically select certain option quantities to their advantage. These options have a positive payoff only if the underlying IPO shares are underpriced. The evidence does not corroborate that managers become complacent upon observing good news. For the underpriced IPOs, potential payoff or recovery from the option is approximately 4 million dollars on average. Competition among underwriters reduces friction and improves the recovery rate while top ranked IPO underwriters with primarily institutional clients have the opposite impact. Finally, negotiated outcome for the option term is superior when interests of the directors and managers are aligned and less favorable when the directors have incentive but the managers do not. This may be construed as a weak evidence of effort based agency problem.
Anticancer drug FL118 is more than a survivin inhibitor: where is the Achilles’ heel of cancer?

Can a solution be found that overcomes all chemotherapy and/or radiation resistance resulting from different genetic and epigenetic alternations in various cancer types? The answer is likely NO. However, there are two ways that may be followed to approach this goal. One way is through the use of poly-therapies that target multiple mechanisms to kill cancer cells, which is the current state of the art. This approach raises issues of high costs and/or toxic limitations, since the toxicities of each agent are often additive. This poly-pharmacy approach has not proven to be a major success, although it has proven to be superior to most current mono-pharmacy approaches. The other way to approach the goal is to find a single anticancer drug that targets multiple different treatment resistant mechanisms. In this regard, a small chemical molecule (FL118) was recently discovered by serendipity during targeted discovery of anticancer drugs using the survivin gene as a target and biomarker. FL118 was found to not only inhibit multiple antiapoptotic proteins (survivin, XIAP, cIAP2) in the inhibitor of apoptosis (IAP) family, but to also inhibit the antiapoptotic protein Mcl-1 in the Bcl-2 family, while inducing the pro-apoptotic proteins Bax and Bim expression. Importantly, inhibition of these target genes and of tumor growth by FL118 is independent of p53 status (wild type, mutant or null), although mechanisms of action may be distinct among cells with different p53 status. Therefore, FL118 may effectively control cancer that loses functional p53, in which most DNA damage drugs (if not all) show a marked lack of efficiency. Recent studies further revealed that the superior anticancer activity of FL118 is highly dependent on its primary structure and steric configuration, suggesting that FL118 may be a promising drug platform for generating novel derivatives based on its core structure. Intriguingly, although FL118 has structural similarity to irinotecan and topotecan, two FDA-approved topoisomerase 1 (Top1) inhibitors for cancer treatment, cancer cells with Top1 mutations shows little contributions of treatment resistance to FL118 antitumor activity, while strikingly increasing irinotecan and topotecan resistance. Furthermore, both irinotecan and topotecan are the efflux pump ABCG2 substrates; cancer cells with high expression of ABCG2 showed strong irinotecan and topotecan resistance. In contrast, FL118 is not an ABCG2 substrate; ABCG2 overexpression in cancer cells does not show resistance to FL118 treatment. Current evidence suggests that future studies may unravel more unexpected mechanisms of action for this unique small molecule FL118.
The Unappreciated Intracellular Lifestyle of Blastomyces dermatitidis

Blastomyces dermatitidis, a dimorphic fungus and the causative agent of blastomycosis, is widely considered an extracellular pathogen, with little evidence for a facultative intracellular lifestyle. We infected mice with spores, that is, the infectious particle, via the pulmonary route and studied intracellular residence, transition to pathogenic yeast, and replication inside lung cells. Nearly 80% of spores were inside cells at 24 h postinfection with 10 4 spores. Most spores were located inside of alveolar macrophages, with smaller numbers in neutrophils and dendritic cells. Real-time imaging showed rapid uptake of spores into alveolar macrophages, conversion to yeast, and intracellular multiplication during in vitro coculture. The finding of multiple yeast in a macrophage was chiefly due to intracellular replication rather than multiple phagocytic events or fusion of macrophages. Depletion of alveolar macrophages curtailed infection in mice infected with spores and led to a 26-fold reduction in lung CFU by 6 d postinfection versus nondepleted mice. Phase transition of the spores to yeast was delayed in these depleted mice over a time frame that correlated with reduced lung CFU. Spores cultured in vitro converted to yeast faster in the presence of macrophages than in medium alone. Thus, although advanced B. dermatitidis infection may exhibit extracellular residence in tissue, early lung infection with infectious spores reveals its unappreciated facultative intracellular lifestyle.
In vitro phosphorylation of ciliary dyneins by protein kinases from Paramecium

Paramecium dyneins were tested as substrates for phosphorylation by cAMP-dependent protein kinase, cGMP-dependent protein kinase, and two Ca(2+)-dependent protein kinases that were partially purified from Paramecium extracts. Only cAMP-dependent protein kinase caused significant phosphorylation. The major phosphorylated species was a 29 kDa protein that was present in both 22 S and 12 S dyneins; its phosphate-accepting activity peaked with 22 S dynein. In vitro phosphorylation was maximal at five minutes, then decreased. This decrease in phosphorylation was inhibited by the addition of vanadate or NaF. The 29 kDa protein was not phosphorylated by a heterologous cAMP-dependent protein kinase, the bovine catalytic subunit. Phosphorylation of dynein did not change its ATPase activity. In sucrose gradient fractions from the last step of dynein purification, phosphorylation by an endogenous kinase occurred. This phosphorylation could not be attributed to the small amounts of cAMP- and cGMP-dependent protein kinases known to be present, nor was it Ca(2+)-dependent. This previously uncharacterized ciliary protein kinase used casein as an in vitro substrate.
Emergency medicine resident physicians' perceptions of electronic documentation and workflow: a mixed methods study.

Objective: To understand emergency department (ED) physicians’ use of electronic documentation in order to identify usability and workflow considerations for the design of future ED information system (EDIS) physician documentation modules. Methods: We invited emergency medicine resident physicians to participate in a mixed methods study using task analysis and qualitative interviews. Participants completed a simulated, standardized patient encounter in a medical simulation center while documenting in the test environment of a currently used EDIS. We recorded the time on task, type and sequence of tasks performed by the participants (including tasks performed in parallel). We then conducted semi-structured interviews with each participant. We analyzed these qualitative data using the constant comparative method to generate themes. Results: Eight resident physicians participated. The simulation session averaged 17 minutes and participants spent 11 minutes on average on tasks that included electronic documentation. Participants performed tasks in parallel, such as history taking and electronic documentation. Five of the 8 participants performed a similar workflow sequence during the first part of the session while the remaining three used different workflows. Three themes characterize electronic documentation: physicians report that location and timing of documentation varies based on patient acuity and workload, physicians report a need for features that support improved efficiency; and physicians like viewing available patient data but struggle with integration of the EDIS with other information sources. Conclusion: We confirmed that physicians spend much of their time on documentation (65%) during an ED patient visit. Further, we found that resident physicians did not all use the same workflow and approach even when presented with an identical standardized patient scenario. Future EHR design should consider these varied workflows while trying to optimize efficiency, such as improving integration of clinical data. These findings should be tested quantitatively in a larger, representative study.
Analysis and optimization of vertically oriented, through-wafer, laminated magnetic cores in silicon

This paper compares two fabrication methods for achieving through-wafer, laminated magnetic cores in silicon, intended for microfabricated magnetic devices where vertically oriented (normal to the wafer) magnetic laminations are required to reduce eddy current losses. Given certain fabrication constraints for each method, a theoretical framework is presented to permit the design of the optimal lamination scheme for a particular application. As an example, the analysis is applied to the optimization of laminations for a miniaturized synchronous permanent magnet motor/generator.
Computers in medicine.

Since previous Contempo reports on computers in medicine in 1989 and 1990, computing systems and devices have been incorporated into medical practice at an accelerating rate. The influence of computing can be seen in diagnostic imaging systems, radiation therapy, the intensive care unit, the clinical laboratory, and the business office. Planning for institution-wide advanced information management systems has become more sophisticated and widespread. 1 The American Medical Informatics Association has been formed as a forum for open scientific meetings and education in the field of medical informatics. Virtually every US academic medical center and many hospitals have on-line or CD-ROM systems that allow individual health professionals and students to search MEDLINE and other databases for themselves. A rapidly growing group of institutions and individuals use Internet connections to reach information sources and to transmit and receive the full text of documents. 2 Many physician "end-users" search databases from home or
Effects of speciation on serum proteins in the genus Macaca with special reference to the polymorphic state of transferrin.

THE effects of speciation on the serum proteins of macaque monkeys and other primates are being studied in our laboratory by a combination of starch-gel electrophoretic and immunological techniques1,2. In an initial survey of the sera from 19 cynomolgus monkeys (Macaca irus) and 17 rhesus monkeys (Macaca mulatta) we found that the cynomolgus sera contained a larger proportion of γ-globulin than the rhesus sera and also that all the cynomolgus sera showed only one transferrin whereas 10 of the 17 rhesus sera showed more than one transferrin. At the time, we observed that one of the ten rhesus sera showed three transferrin components and that in the other nine sera, each of which showed two components, the relative positions of the transferrins in starch-gel varied in some cases between the samples. In order further to define the polymorphic state of transferrin in the species Macaca mulatta and the apparent absence of this state in the species Macaca irus, the sera from 40 more rhesus monkeys, newly arrived from India, and from 40 more cynomolgus monkeys, newly arrived from the Philippines, were kindly provided for study by Parke, Davis and Co. The rhesus monkeys in this shipment were captured in an area the size of a township near the Nepal border. It was not possible to trace exactly where in the Philippines the cynomolgus monkeys were captured. We have now detected fourteen transferrin patterns in the rhesus monkeys and still only one pattern in the cynomolgus monkeys. Thirteen of the transferrin patterns were represented in the last shipment. Our work, then, not only independently confirms but also considerably extends the report by Blumberg3 of eight transferrin patterns in rhesus monkeys. Our results are particularly interesting in indicating that while the environment of one species selects for a polymorphic state, the environment of a closely related species selects against this state.
Circadian regulation of response to oxidative stress in Drosophila melanogaster.

Abstract Circadian rhythms are fundamental biological phenomena generated by molecular genetic mechanisms known as circadian clocks. There is increasing evidence that circadian synchronization of physiological and cellular processes contribute to the wellness of organisms, curbing pathologies such as cancer and premature aging. Therefore, there is a need to understand how circadian clocks orchestrate interactions between the organism’s internal processes and the environment. Here, we explore the nexus between the clock and oxidative stress susceptibility in Drosophila melanogaster. We exposed flies to acute oxidative stress induced by hydrogen peroxide (H2O2), and determined that mortality rates were dependent on time at which exposure occurred during the day/night cycle. The daily susceptibility rhythm was abolished in flies with a null mutation in the core clock gene period (per) abrogating clock function. Furthermore, lack of per increased susceptibility to H2O2 compared to wild-type flies, coinciding with enhanced generation of mitochondrial H2O2 and decreased catalase activity due to oxidative damage. Taken together, our data suggest that the circadian clock gene period is essential for maintaining a robust anti-oxidative defense.
A rationale for administering leukocyte endogenous mediator to protein malnourished, hospitalized patients

Abstract Leukocyte endogenous mediator is a low molecular-weight protein synthesized by circulating monocytes and fixed macrophages of the reticuloendothelial system. Exogenous administration of leukocyte endogenous mediator to a well-nourished animal stimulates both specific and nonspecific immune function and replicates the protein metabolic response to infection, characterized by fever and increased amino acid oxidation, skeletal protein degradation and synthesis of “acute-phase” proteins. Leukocyte endogenous mediator administration also affords protection against semilethal doses of bacteremia in the well-nourished animal. In the protein-depleted host, synthesis or release of leukocyte endogenous mediator in response to infection appears to be reduced and the attenuated metabolic response may be attributed, in part, to a deficit in its production. However, nutritional repletion of the malnourished patient results in restoration of the capacity to produce leukocyte endogenous mediator usually within three to seven days, if adequate dietary protein is provided. Since protein malnutrition is associated with increased incidence and severity of bacterial infections, we postulate that the reduced synthesis and/or release of leukocyte endogenous mediator in protein malnutrition is detrimental. In those critically-ill, malnourished patients who cannot endogenously synthesize leukocyte endogenous mediator, and for clinical reasons cannot be repleted rapidly or are already infected and/or undergoing operative stress, exogenous administration of leukocyte endogenous mediator should be considered along with nutritional support. Administration of this protein to a seriously-ill malnourished individual should produce a metabolic profile of fever, increased urinary nitrogen excretion and falls in serum albumin concentrations that are generally considered pathologic. However, administration of leukocyte endogenous mediator over short periods of time should also provide the anabolic impetus for the augmented synthesis of proteins beneficial to recovery. In most cases, these countervailing forces of anabolism and catabolism should be of benefit to the host if the response to infection and injury is viewed as a physiologic redistribution of endogenous nutrients to meet the more critical and immediate needs of the stressed patient.
Partitioned garbage collection of a large object store

We present new techniques for efficient garbage collection in a large persistent object store. The store is divided into partitions that are collected independently using information about inter-partition references. This information is maintained on disk so that it can be recovered after a crash. We use new techniques to organize and update this information while avoiding disk accesses. We also present a new global marking scheme to collect cyclic garbage across partitions. Global marking is piggybacked on partitioned collection; the result is an efficient scheme that preserves the localized nature of partitioned collection, yet is able to collect all garbage.We have implemented the part of garbage collection responsible for maintaining information about inter-partition references. We present a performance study to evaluate this work; the results show that our techniques result in substantial savings in the usage of disk and memory.
Tepa Sterilization and Its Effect upon Respiration of the Spotted Cucumber Beetle, Diabrotica undecimpunctata howardi,,

The effect of sterilization by tris-(1-aziridinyl) phosphinc oxide (tepa) upon oxygen consumption of the spotted cucumber beetle, Diabrotica undecimpunctata howardi Barber, has not been reported. The study reported here was designed to determine if tepa could be used as an effective male sterilant, and if so, the dosage required to effect sterilization and the effect of sterilization on oxygen consumption.