cssi/SciSciGPT-SciSciNet huggingface dataset:
A Novel Classification Method with Superior Prediction of Drug Arrhythmia Risk

Many drugs, both cardiac and non-cardiac, cause fatal arrhythmias. Current assays to evaluate arrhythmia risk based on block of the delayed rectifier K+ current (hERG) and QT interval prolongation are limited by poor specificity. We hypothesize that physiological, dynamical simulations of drug effects on heart cells will yield better algorithms to discriminate between arrhythmogenic and safe drugs. To test this, we model drug action in cardiomyocyte models based on drug interaction with 3 cardiac ion channels: hERG, the L-type Ca2+ channel, and the fast Na+ channel. For 67 distinct drugs, we measure 15 cellular physiological metrics under multiple pacing conditions and in the 3 ventricular cell types, each in 3 human ventricular cell models. Additionally, we evaluate the influences of gender and inter-individual variability on risk by conducting simulations in both female and male models, and in a simulated population of individuals, respectively. Principal component analysis of these drug effect metrics reveals distinct behaviors of arrhythmogenic drugs. This segregation of drugs in principal component space facilitates their classification into arrhythmogenic and safe categories. Our classification by this method is more sensitive and specific than the hERG block assay or, to our knowledge, any other published predictors, with an area under the receiver-operator characteristic of 0.9630. Furthermore, because it is based on cellular physiological metrics, our algorithm can predict the arrhythmogenicity of drugs with a range of cardiac molecular targets, beyond those of the drugs used to train the algorithm. In conclusion, we have developed a classification algorithm using dynamical heart cell models, suitable for cardiac safety assessments early in drug development, that outperforms current methods in the discrimination of arrhythmogenic and safe drugs.
Polyphilo, or, the Dark Forest Revisited: An Erotic Epiphany of Architecture

(1994). Polyphilo, or, the Dark Forest Revisited: An Erotic Epiphany of Architecture. Journal of Architectural Education: Vol. 47, No. 4, pp. 265-267.
An endogenous inhibitor protein of brain adenylate cyclase and cyclic nucleotide phosphodiesterase

Abstract Brain adenylate cyclase (EC 4.6.1.1) and cyclic nucleotide phosphodiesterase (EC 3.1.4.17) require an endogenous Ca2+-dependent activator protein for full activity (Cheung et al. (1975) Biochem. Biophys. Res. Commun. 66, 1055–1062). We now describe another brain factor which inhibited both brain adenylate cyclase and phosphodiesterase in vitro. The factor appeared to be a protein; it was inactivated by incubation with trypsin, but not with ribonuclease or deoxyribonuclease. Gel filtration with a calibrated column indicated a molecular weight of 80,000 and a Stokes' radius of 3.85 nm. In the presence of Ca2+, the inhibitor interacted with the activator protein to form an inhibitor activator complex. This makes the activator unavailable to adenylate cyclase or phosphodiesterase, resulting in a decrease of enzyme activity.
Embedded-ring migration on graphene zigzag edge

Abstract Reaction pathways are presented for hydrogen-mediated isomerization of a zigzag graphene edge containing a five-member carbon ring surrounded by six-member rings. A new reaction sequence in which this embedded five-member ring moves, or migrates, through the edge has been identified. The elementary steps of the pathways were analyzed using density functional theory (DFT). Rate coefficients were obtained by classical transition state theory utilizing the DFT energies, frequencies, and geometries. The results indicate that this new reaction sequence is competitive with the other important zigzag edge reactions allowing embedded five-member rings to move freely within a zigzag edge. The embedded rings have slight thermodynamic preference for the interior of the edge over the corner for large substrates.
Contributions to selected phenotypic characteristics of large species- and lineage-specific genomic regions in Listeria monocytogenes.

Abstract We hypothesized that genomic regions specific to Listeria monocytogenes or selected L. monocytogenes strains may contribute to virulence and phenotypic differences among the strains. A whole genome alignment of two completed L. monocytogenes genomes and the one completed Listeria innocua genome initially identified 28 genomic regions of difference (RD) > 4 kb that were found in one or both L. monocytogenes genomes, but absent from the non-pathogenic L. innocua . In silico analyses using an additional 18 draft L. monocytogenes genomes showed that (i) 15 RDs were found in all or most L. monocytogenes genomes; (ii) three RDs were found in all or most lineage I genomes, but absent from lineage II genomes; and (iii) four RDs were found in all lineage II genomes, but no lineage I genomes. Null mutants in two L. monocytogenes- specific RDs (RD16 and RD30; found in most L. monocytogenes ) and the lineage II-specific RD25 showed no evidence for impaired invasion or intracellular growth in selected tissue culture cells. Although, in pH 5.5 minimal media, the ΔRD30 null mutant showed reduced ability to compete with its parent strain, indicating that RD30 may have a role in L. monocytogenes growth under limited nutrient conditions at acidic pH.
Postmenopausal hormone replacement and obesity.

Abstract Objective: To compare the association of postmenopausal hormone replacement therapy and lipid and lipoprotein levels in obese and nonobese women. Methods: We studied 4,851 postmenopausal women participating in a population-based observational study. Using cross-sectional data, women were classified into four groups according to their hormone use: current users of estrogen only, current users of estrogen and progestin, never users of hormone replacement therapy, and former users of hormone replacement therapy. Body mass index was categorized as: normal (BMI 32.3 kg/m2). Results: Hormone use was associated with lower total cholesterol and low-density lipoprotein levels and higher triglyceride levels among all categories of body mass index. However, there was an interaction between hormone use and body mass index for the outcome variable high-density lipoprotein. Among users of estrogen and progestin, high-density lipoprotein levels decreased as body mass index increased. Obese users of combination therapy had a mean high-density lipoprotein level similar to that in obese never users and obese former users of hormone replacement therapy. Conclusion: Our results suggest that, in general, hormone replacement therapy is associated with a favorable lipid profile regardless of body mass index. However, among obese women on combination estrogen and progestin therapy, hormone use was not associated with higher high-density lipoprotein concentrations compared to nonusers. This observation needs further study.
Saccharin aversions in hamsters as a result of nicotine injections

Abstract Golden Syrian hamsters (males, N=70) showed dose-related conditioned taste aversion (CTA) when saccharin drinking was followed by delayed nicotine injections. Baseline consisted of measuring amounts consumed after 20 minutes of daily access to tap water. Measures were taken for five days. The hamsters were then conditioned by offering them saccharin solution (0.1%, w/v) for 20 minutes; afterwhich a 30 minute delay was imposed. Subsequent to the delay, groups of 10 animals were treated as follows: nicotine injection,(1.0, 3.0, or 9.0 mg/kg, IP), saline injection, lithium chloride injection (2% body weight of a 0.15 M solution), sham injection, or left in their cages as handling/stress controls. Following two recovery days with plain water available for 20 minutes, all animals were tested for CTA by offering them saccharin solution. Dose-related CTA was demonstrated in the nicotine animals as measured by a decrease in saccharin consumption compared to drinking measures obtained from animals injected with saline. Lithium chloride produced the same degree of CTA as 9 mg/kg of nicotine, and the aversions had extinguished in all groups by the third test day.
Spectrum of pulmonary diseases associated with the acquired immune deficiency syndrome

Abstract Over a four-year period, 130 patients with the acquired immune deficiency syndrome were studied to assess the incidence and spectrum of pulmonary disease associated with this illness. In 61 patients (47 percent), respiratory abnormalities were either present on admission or later developed. Multiple pathologic processes were present simultaneously in 24 patients and serial pulmonary problems developed in seven patients. Infection was the most common cause of pulmonary parenchymal disease and was due to Pneumocystis carinil (35 patients), cytomegalovirus (21 patients), Mycobacterium avium-intracellulare (13 patients), and bacteria (four patients). Noninfectious causes of parenchymal lung diseases were also frequently seen and included Kaposi's sarcoma (eight patients), nonspecific pneumonitis (seven patients), and adult respiratory distress syndrome (four patients). Significant pleural disease was present In six cases and was usually related to Kaposi's sarcoma. A bronchospastic disorder developed in four patients. Pulmonary function tests, in particular the diffusing capacity and the difference between rest and exercise alveolar-arterial oxygen tension, were helpful in screening for pulmonary diseases. Patterns of clinical features and radiographic abnormalities were recognized and suggested specific diagnoses. Overall mortality from respiratory causes identified during the study was 41 percent, but varied markedly with the etiologic agent. Respiratory failure, however, carried a 100 percent mortality despite the underlying cause.
Estimates of the incidence and prevalence of sexually transmitted diseases in the United States. American Social Health Association Panel.

Background:Accurate, updated estimates of the incidence and prevalence of sexually transmitted infections in the United States remain elusive. The most widely quoted number of new sexually transmitted disease (STD) cases each year is 12 million. However, this figure has not changed in more than a de
Developing Information Literacy Skills Early in an Undergraduate Curriculum.

Several core competencies related to information literacy have been identified by the Association of College and Research Libraries. Students must learn to gather relevant information and communicate their findings effectively. The collaborative activity described here, which could easily be adapted for other disciplines, introduces first-semester freshmen to the standards of professional scientific writing, the different forms of publication, search strategies to effectively find information using a relevant database, and plagiarism. Analysis of our pre- and post-activity assessment demonstrates that students gain both confidence and knowledge on several important skills as a result of this activity. Providing content-relevant information literacy experience lays the foundation for students to be successful consumers of information.
Growth and structural investigations of epitaxial hexagonal YMnO3 thin films deposited on wurtzite GaN(001) substrates

Abstract Epitaxial hexagonal YMnO3 (h-YMnO3) films having sharp (00l) X-ray diffraction peaks were grown above 700 °C in 5 mTorr O2 via pulsed laser deposition both on as-received wurtzite GaN/AlN/6H-SiC(001) (w-GaN) substrates as well as on w-GaN surfaces that were etched in 50% HF solution. High-resolution transmission electron microscopy revealed an interfacial layer between film and the unetched substrate; this layer was absent in those samples wherein an etched substrate was used. However, the substrate treatment did not affect the epitaxial arrangement between the h-YMnO3 film and w-GaN substrate. The epitaxial relationships of the h-YMnO3 films with the w-GaN(001) substrate was determined via X-ray diffraction to be (001)YMnO3 ‖ (001)GaN : [11¯0]YMnO3 ‖ [110]GaN; in other words, the basal planes of the film and the substrate are aligned parallel to one another, as are the most densely packed directions in planes of the film and the substrate. Interestingly, this arrangement has a larger lattice mismatch than if the principal axes of the unit cells were aligned.
What Exactly Do the Trends Mean

Although the adverse public health and economic consequences of obesity have been reported for some time, little success has been achieved in controlling the progressive increase in population prevalence and severity of obesity. The obesity epidemic in children is especially sobering. More than 17% of children are obese, and these rates have increased with each new survey. A consequence of childhood obesity has been the premature onset of diseases associated with obesity. The chronic disorders of hypertension, type 2 diabetes mellitus, and sleep apnea, which had been considered conditions of middle to late adulthood, now appear in childhood. When the cardiovascular morbidity associated with these conditions is considered, the health impact of childhood-onset hypertension or diabetes mellitus is likely to be enormous. Article p 1488 The extent to which childhood obesity could contribute to an increase in the prevalence of hypertension was studied in a report in this issue of Circulation . Din-Dzietham et al1 conducted a study in which they examined the secular trend in the prevalence of high blood pressure (BP) among children and adolescents to determine if the rise in childhood obesity contributes to an increase in the prevalence of high BP. Data were drawn from serial health surveys conducted by the National Center for Health Statistics between 1963 and 2002 on a representative sample of the noninstitutionalized civilian US population. Data on children between the ages of 8 to 17 years, which included measurement of BP, were the focus of their analysis. The investigators applied the current BP criteria for hypertension and prehypertension in childhood2 to the data from the participants in each of the 6 survey periods between 1963 and 2002 to determine the prevalence of high BP in each survey period. The representations of non-Hispanic white, non-Hispanic black, and Mexican-American children were …
GROUND AND AIRBORNE RESISTIVITY SURVEYS OF PERMAFROST NEAR FAIRBANKS, ALASKA

In permafrost regions investigations for such geotechnical endeavors as route selection for roads and pipelines and site investigations for buildings and dam construction often require that a careful assessment be made of the presence or absence of frozen ground, of the ice content of frozen ground, and of the depth of frozen ground. In the vicinity of Fairbanks, Alaska, where the permafrost is discontinuous, ground and airborne methods of mapping electrical resistivity using radiowaves were tested as means of delineating permafrost. When the resistivity maps are compared with surficial geological data, the following conclusions are reached: (1) In areas of fine‐grained sediments, where the near surface sediments are relatively uniform, VLF resistivity delineates permafrost. (2) In areas where surface sediments vary widely (flood plains), VLF resistivity shows little information on permafrost conditions but can provide other important geotechnical information, such as, depth to bedrock, surface soil type,...
Microsurgical anatomy of the carotid cave.

Background The carotid cave was first described more than 20 years ago, but its relationships to the dural rings defining the clinoid segment of the internal carotid artery (ICA), the carotid collar, and the adjacent osseous structures need further definition. Objective To further define the microanatomy of the carotid cave and its relationships to the adjacent structures. Methods : The cave and its relationships were examined in cadaveric specimens using 3 to 40× magnification. Results The cave is an intradural pouch, found in 19 of 20 paraclinoid areas, that extends below the level of the distal dural ring between the wall of the ICA and the dural collar surrounding the ICA. The distal dural ring is tightly adherent to the anterior and lateral walls of the ICA adjacent the anterior clinoid process and optic strut but not on the medial and posterior sides of the artery facing the upper part of the carotid sulcus where the carotid cave is located. The superior hypophyseal artery frequently arises in the cave. The depth and circumferential length of the cave averaged 2.4 mm (range, 1.5-5 mm) and 9.9 mm (range, 4.5-12 mm), respectively. Aneurysms arising at the level of the cave, although appearing on radiological studies to extend below the level of the upper edge of the anterior clinoid, may extend into and may be a source of subarachnoid space. Conclusion The surgical treatment of aneurysms arising in the cave requires an accurate understanding of the relationships of the cave to the ICA, dural rings, and carotid collar.
Fitting a model to categorical response data with application to species extrapolation of toxicity.

The evaluation of toxicity data for noncarcinogens is complicated by the multiplicity of possible end points, and variations in both severity of effect and response rate. Often the response rates are not reported, so that "dose-response" analysis involves the relation between dose and severity of effect. Severity is usually reported as a description of the nature of the effects; measured values are rare. One approach is to then assign severity descriptions to ordered categories and to model the dose-category relationship. The application presented here is to interspecies scaling, i.e., the estimation of parameters in the model used to convert animal doses into equally toxic human doses.
Interleukin‐24 and its receptors

Interleukin 24 (IL-24) is a new member of the IL-10 family of cytokines and it signals through two heterodimeric receptors: IL-20R1/IL-20R2 and IL-22R1/IL-20R2. Upon binding to its receptors, IL-24 induces rapid activation of Stat-1 and Stat-3 transcription factors, which appear to play a role in cell survival and proliferation. Under physiological conditions, the major sources of IL-24 are the activated monocytes and T helper 2 cells, whereas the major IL-24 target tissues, based on the receptor expression pattern, are non-haematopoietic in origin, and include skin, lung and reproductive tissues. Structurally and functionally, IL-24 is highly conserved across species. This review highlights our current knowledge of IL-24 as a cytokine, with much less emphasis placed on the non-receptor-mediated functions (a subject of several reviews) focused on in much of the earlier literature on IL-24. The potential roles of IL-24 as part of a complex cytokine network in wound healing, psoriasis and cancer are discussed.
Information Systems Satisfaction

Previous studies have examined the satisfaction of users with information services, but most measured attitudes after use of the system had begun. The focus in this paper is upon the design and test of an instrument suitable for the systems development stage. The traditional “user satisfaction” construct is examined in two parts; user satisfaction with the process and user satisfaction with the product.The research instrument was administered in an experimental environment that simulated a work situation. Participants were asked not only to do their “normal” tasks but also to cooperate in a systems development project. Some were placed into time‐constrained situations; others were not. Results indicate that the user satisfaction construct can be evaluated during development and should be separated from product satisfaction. Further, attitudes toward the process and about the product are correlated positively but they are not perfect substitutes.The experimental situation yielded some evidence that requiring people to participate on development teams without compensatory release time or other incentives is likely to make them feel negative about the process. Although this negativity is not fully transferred to attitudes toward the product, it does exist and needs to be managed effectively.
Disadvantaged by Diversity? The Effects of Diversity Goals on Competence Perceptions1

This research examined how efforts to ensure demographic diversity in a work group affected perceptions of the competence of individuals who are likely targets of such efforts. In three experiments, 262 undergraduates gave their impressions and performance expectations of members of a group assembled to work on a task. When a diversity rationale rather than a merit rationale was provided for how the work group was assembled, both women (Studies 1 and 2) and Black men (Study 3) were perceived as less competent and were expected to be less influential. This effect occurred regardless of the proportional representation of women or the degree of the groups' heterogeneity. The diversity rationale also produced more negative characterizations than did another non-merit-based rationale: scheduling convenience.
Kin Social Undermining, Adjustment and Family Relations Among Low-Income African American Mothers and Adolescents: Moderating Effects of Kin Social Support

Moderating effects of kin social support on the association of kin undermining with mothers’ and adolescents’ adjustment and mothers’ parenting were assessed among 200 African American mothers. Kinship social support was positively associated with mother’s optimism and negatively associated with their depressive symptoms. Kin support was negatively associated with mother’s report of adolescent’s externalizing problems. In the area of parenting, kin support was positively linked to mother’s emotional support and acceptance. In comparison, kin undermining was negatively associated with mother’s optimism and positively linked depressive symptoms. Kin undermining was also positively associated with mother’s report of adolescent’s internalizing and externalizing problems. Kin undermining was negatively associated with mother’s acceptance and positively associated with mother/adolescent communication problems. Moderating effects of kin social support revealed that the positive association of kin undermining with adolescent externalizing was less apparent as mothers reported higher compared to lower kin social support. Also, the positive association of kin undermining with mother/adolescent communication problems was less apparent as mothers reported higher compared to lower levels of kin support. The findings were discussed in terms of the need for more research on how families manage the beneficial and detrimental aspects of their social networks.
Special Section Guest Editorial: Nanophotonics and Plasmonics for Solar Energy Harvesting and Conversion

This PDF file contains the editorial “Special Section Guest Editorial: Nanophotonics and Plasmonics for Solar Energy Harvesting and Conversion” for JPE Vol. 5 Issue 01
Crosstalk between c‐Myc and ribosome in ribosomal biogenesis and cancer

Protein production is driven by protein translation and relies on ribosomal biogenesis, globally essential for cell growth, proliferation, and animal development. Deregulation of these sophisticated cellular processes leads to abnormal homeostasis and carcinogenesis. Thus, their tight regulation is vitally important for a cell to warrant normal growth and proliferation. One newly identified key regulator for ribosomal biogenesis and translation is the oncoprotein c-Myc, whose aberrantly excessive level and activity are highly associated with human cancers, too. Recently, we have shown that ribosomal protein L11 functions as a feedback regulator of c-Myc. Hence, in this review, we will provide some prospects on the interplay between c-Myc and ribosomal proteins during ribosomal biogenesis and discuss its implications in cancer.
Exact inversion of the fugacity-density relation for ideal quantum gases

The fugacities of ideal Fermi and Bose gases are calculated explicity as a function of density and temperature, using the analytic properties of the integral appearing in the fugacity-density equation. The Hilbert problem of the theory of analytic functions is encountered.
Impact Of NaV1.7-PEPD Missense Mutations That Slow The Rate Of Inactivation On Sensory Neuronal Resurgent Sodium Currents

Voltage-gated sodium (Nav1.1-9) channels are dynamic transmembrane proteins that, in response to changes in the potential across the lipophilic cell membrane, undergo specific conformational (gating) modifications, between ion-conducting (open) and non-conducting (closed and inactivated) states, to selectively conduct sodium ions through their aqueous pore. Importantly, changes in these voltage-dependent gating properties can impact action potential (AP) characteristics. TTX-sensitive sodium channels in cerebellar neurons can produce resurgent currents (Raman & Bean, 1997), intriguing currents that are re-activated during intermediate repolarizations following strong, but short, depolarizations. We observe resurgent currents in some DRG neurons and found that wild-type Nav1.6 but not wild-type Nav1.7 channels can generate resurgent currents in DRG neurons (Cummins et al., 2005). It has been demonstrated that, in cerebellar neurons from Nav1.6-null mice, slowing inactivation of the remaining Nav current can induce resurgent currents (Grieco & Raman, 2004). Interestingly, single-point missense mutations in the SCN9A gene that encode for Nav1.7, implicated in paroxysmal extreme pain disorder (PEPD), slow the rate of Nav1.7 inactivation (Jarecki et al., 2008). Therefore, we hypothesized that slowing of Nav1.7 by PEPD mutations might induce abnormal resurgent currents, thus altering AP properties. To explore this hypothesis, we transiently transfected adult rat DRG neurons with a TTX-resistant form of human Nav1.7-wild-type or PEPD mutant cDNA and rat Nav1.8-targeted shRNA. Voltage-dependent properties were observed using whole-cell voltage-clamp electrophysiology and AP generation was tested using current-clamp electrophysiology. Recordings were made in the presence and absence of extracellular TTX. These experiments should yield insight into (1) the mechanism of resurgent sodium current generation in DRG neurons, (2) a potential additive effect in channel dysfunction observed in PEPD, and (3) how these mutant channels contribute to alterations in AP characteristics.
Interactive sonification of neural activity

We discuss our ongoing research in sonification of neural activity as demonstrated in the "Fish and Chips" and "BrainWaves" projects. We argue that sonification can serve as an effective technique for the representation of complex spatial information such as neural activity due to the auditory system's ability to perceive stimuli at a wide spatial cover and its inclination to perceive spatial patterns in sonic input. The paper discusses aesthetic and functional aspects of sonification in this context and describes the evolution of our technique, artistic approach, and interaction design -- from the low-resolution graphical user interface in "Fish and Chips" to the high-resolution tangible interaction with newly developed controllers in "BrainWaves". We conclude with an evaluative discussion and a number of suggestions for future work.
TGI Monday?: Drug-dependent outpatients report lower stress and more happiness at work than elsewhere

In the general population, experience-sampling studies show that work is the aspect of daily life most associated with momentary unhappiness and a desire to be elsewhere. We assessed whether this holds true for urban outpatients in treatment for heroin and cocaine dependence. In a 25-week natural-history study, 79 employed methadone-maintained misusers of heroin and cocaine carried electronic diaries on which mood and behavior were assessed up to five times per day. Being at work was associated with lower stress, greater happiness, and lower drug craving. Work accounted for 14% of the variance in stress, 30% of the variance in happiness, and 50% of the variance in cocaine craving. Participants with skilled jobs reported more positive and less negative mood states (and lower cocaine craving) at all times compared to participants with semi/unskilled jobs, although the latter reported greater mood improvement at work. In all participants, mood improvements occurred specifically in the presence of coworkers (not other companions). Our seemingly unusual findings might be specific to substance-disorder patients (for whom work may be a respite from drug-using companions), but might also hold for other urban dwellers of similar socioeconomic backgrounds (for whom work may be a respite from environmental stressors).
Spatio-Temporal Modeling of Legislation and Votes

A model is presented for analysis of multivariate binary data with spatio-temporal dependencies, and applied to congressional roll call data from the United States House of Representatives and Senate. The model considers each legislator's constituency (location), the congressional session (time) of each vote, and the details (text) of each piece of legislation. The model can predict votes of new legislation from only text, while imposing smooth temporal evolution of legislator latent features, and correlation of legislators with adjacent constituencies. Additionally, the model estimates the number of latent dimensions required to represent the data. A Gibbs sampler is developed for posterior inference. The model is demonstrated as an exploratory tool of legislation and it performs well in quantitative comparisons to a traditional ideal-point model.
A note on non-negative singular infinity-harmonic functions in the half-space.

In this work we study non-negative singular infinity-harmonic functions in the half-space. We assume that solutions blow-up at the origin while vanishing at infinity and on a hyperplane. We show that blow-up rate is of the order .
A case study in change and conflict : The Dallas Independent School District

This research is a case study of change and racial/ethnic conflict in the Dallas, Texas, Independent School District (DISD). Data are drawn from observations of monthly meetings of the school board. The focus is on communication as cultural projection among African American and Mexican American delegations at meetings and on the reactions evoked in board decision making. No evidence was found of Black-Brown coalition building; however, findings suggest that different styles of communication influence the treatment African American and Mexican American groups receive and ultimately may affect their access to the scarce resources of public education.
A microfluidic method to synthesize transferrin-lipid nanoparticles loaded with siRNA LOR-1284 for therapy of acute myeloid leukemia

The siRNA LOR-1284 targets the R2 subunit of ribonucleotide reductase (RRM2) and has shown promise in cancer therapy. In this study, transferrin (Tf) conjugated lipid nanoparticles (Tf–NP–LOR-1284) were synthesized by microfluidic hydrodynamic focusing (MHF) and evaluated for the targeted delivery of LOR-1284 siRNA into acute myeloid leukemia (AML) cells. The in vitro study showed that Tf–NP–LOR-1284 can protect LOR-1284 from serum nuclease degradation. Selective uptake of Tf–NP–LOR-1284 was observed in MV4-11 cells. In addition, qRT-PCR and Western blot results revealed that Tf–NP–LOR-1284 was more effective than the free LOR-1284 in reducing the R2 mRNA and protein levels. The Tf–NP–LOR-1284 showed prolonged circulation time and increased AUC after i.v. administration relative to the free LOR-1284. Furthermore, Tf–NP–LOR-1284 facilitated increased accumulation at the tumor site along with the decreased R2 mRNA and protein expression in a murine xenograft model. These results suggest that Tf-conjugated NPs prepared by MHF provide a suitable platform for efficient and specific therapeutic delivery of LOR-1284 into AML cells.
Physiological Effects of Peroxynitrite Potential Products of the Environment

Peroxynitrite is a potent oxidant formed from the reaction between superoxide radicals and NO in a one-to-one stoichiometry. This reaction occurs at 6.7×109 mol/L−1 · s−1,1 and it is essentially irreversible because of its highly exothermic nature. Therefore, the reaction is diffusion-limited, and it out-competes the reaction of superoxide dismutase for superoxide radicals, which proceeds at a rate of 2×109 mol/L−1 · s−1. A key regulator of peroxynitrite production is the concentration of NO, and the reaction proceeds when the concentration of NO increases and can overcome dismutation by superoxide dismutase. This situation occurs when NO achieves micromolar concentrations as when there is a burst of NO production during ischemia/reperfusion and when NO is produced by cytokine-stimulated inducible NO synthase (iNOS) activity. The toxic effect of ONOO− and its protonated form, peroxynitrous acid, may stem from its oxidation of zinc fingers, protein thiols, membrane lipids, and iron and sulfur clusters of biological molecules. In addition, hydroxyl-like and nitrogen dioxide radicals are produced by homolytic cleavage, increasing the potential for oxidant-mediated tissue injury. Intermediates are also formed from the heterolytic cleavage of ONOO− to hydroxyl anion and nitronium ion (NO2+), catalyzed by the transition metal centers of superoxide dismutase and myeloperoxidase. The nitration of protein tyrosine residues gives rise to 3-nitrotyrosine, which is frequently used as an assay for ONOO− in tissues, blood, and perfusates. Like NO, peroxynitrite has been associated with both deleterious and beneficial effects. An advantage of the oxidant-mediated deleterious effects of peroxynitrite is that it has been suggested to contribute to the host-defense response to bacterial invasion. Both neutrophils and macrophages produce peroxynitrite by the rapid biradical reaction between NO and superoxide anions generated simultaneously from those cells.2 …
Layer-to-layer alignment for step and flash imprint lithography

The Step and Flash Imprint Lithography (SFIL) process is a low-cost, high-throughput patterning technique with a sub- 100 nm resolution capability. Investigation by this group and others indicates that the resolution of replication by imprint lithography is limited only by the size of the structures that can be created on the template. It has also been demonstrated that the SFIL process is capable of eliminating contaminants from the template (master) during a step and repeat imprinting process. The low pressure, room temperature nature of SFIL and the transparent imprint templates make it particularly attractive for high- resolution layer-to-layer alignment. Another aspect of SFIL that assists in the layer to layer alignment is the presence of a thin layer of low viscosity liquid between the template and wafer prior to UV curing. The liquid maintains a small gap (~0.2 micrometers ) and acts as lubrication and damping agents, which allows for accurate in situ error measurement and compensation. In this paper, we present results from overlay alignment experiments using the SFIL process. A Canon mask aligner was modified to implement a layer-to-layer alignment scheme for SFIL. The objective of this research was to achieve alignment accuracy of about 0.5 micrometers , which is the practical limit of the X-Y stage in the mask aligner. The overlay alignment error measurements and the corresponding corrections in X,Y and Theta were performed using the modified mask aligner. In its current state, the alignment resolution appears to be limited by the resolution of the mask aligner stage. It is expected that other high resolution alignment techniques have been developed for optical projection lithography and X-ray lithography processes can be adapted to the SFIL process to significantly improve the alignment resolution.
One‐dimensional anion vacancy diffusion in the calcium apatites

Correlated random walk statistics are used to derive an expression for the diffusion coefficient for vacancies in a linear chain containing impurities. The results are applied to the problem of anion mobility in the calcium apatites. For fluorapatite the analysis indicates energies of motion for fluorine and oxygen ions to be 0.77 and 2.0 eV, respectively. Le coefficient de diffusion des lacunes, dans une chaǐne lineaire contenant des impuretes, est obtenu a ľaide de statistique ďevenements aleatoires non independants. Le resultat est applique au probleme de la mobilitye des anions dans les apatites de calcium. Pour la fluorapatite, ľanalyse indique des energies de motion des ions fluor et oxygene de 0,77 et 2,0 eV, respectivement.
SPECTROCHEMICAL PROCEDURE IN CLAY ANALYSIS

Five types of electrodes and arcing techniques were compared. Complete qualitative analyses of four clays were run, and a quantitative method has been set up for trace elements, giving a short method for sample preparation. Two elements were determined quantitatively to show the described procedure.
Sleep in Patients with Respiratory Muscle Weakness

The physiologic effects of sleep on respiratory muscle activity and breathing are described. The evidence of disruption of sleep architecture, SDB and nocturnal oxygenation in patients with respiratory muscle weakness is reviewed. Finally, the more specific findings in various diseases, and the evaluation and management of these conditions, are described.
Intentional Changes: A Fresh Approach to Helping People Change

This article presents a review of the book “Intentional Changes: A Fresh Approach to Helping People Change,” by Allen Tough.
PBS: proven Boolean simplification

We describe PBS, a formally proven implementation of multi-level logic synthesis based on the weak division algorithm. We have proved that for all legal input circuits, PBS generates an output circuit that is functionally correct and has minimal size. PBS runs on large examples in reasonable time for a prototype system. PBS, was verified using the Nuprl proof development system. The proof of PBS, which required several months, was well worth the effort since the benefits are realized every time the program is run. When engineers use a verified synthesis tool, they get the increased confidence of applying formal methods to their designs without the cost of varying each design produced. >
Metagenomic identification, seasonal dynamics, and potential transmission mechanisms of a Daphnia-associated single-stranded DNA virus in two temperate lakes

We used a metagenomic approach to identify viruses that may be involved in the ecology of Daphnia spp. in Oneida and Cayuga lakes (upstate New York). We identified several highly represented, putative eukaryotic, circular, single-stranded deoxyribonucleic acid (DNA) viral genomes. Among these, we discovered a genotype similar in both sequence and genomic architecture to a virus previously reported from a hyperthermal lake that shares characteristics of both single-stranded ribonucleic acid (RNA) and single-stranded DNA viruses. We used quantitative polymerase chain reactions to study the prevalence and viral load of both positive-sense and negative-sense strands of the Daphnia mendotae–associated (Cladocera) hybrid virus (DMClaHV) over a summer season in Oneida and Cayuga lakes. DMClaHV had high prevalence within Daphnia populations, where viral load and the proportion of virus-positive individuals were higher preceding host population decline. DMClaHV viral load was different between two species of Daphnia (D. mendotae and D. retrocurva), and the dynamics between viruses and their hosts varied between the two lakes. We detected DMClaHV in eggs (ephippia) retrieved from Oneida Lake sediments with an estimated age of 30 yr. Using transmission electron microscopy, we observed small (20 nm diameter) virus-like particles in Daphnia that were well away from gut tissues and not associated with intracellular parasites. Because Daphnia plays a critical role in many lake ecosystems, DMClaHV may have important effects on herbivory and thus carbon flow through the lake ecosystem. More than two decades of investigation have highlighted the crucial importance of viruses to aquatic biogeochemistry and ecosystem function. Virus-like particles are highly abundant in plankton, and viruses of microorganisms cause considerable lysis, influencing elemental cycling, community diversity, and gene exchange among taxa (Fuhrman 1999; Weinbauer 2004; Suttle 2007). Despite the incorpo
Toward a Model for the Be Binary System Φ Per

Arguments are presented against the adoption of an early B-red giant combination for the Φ Persei system. Velocity curves of the primary and secondary components based on the measures of the He i lines on nearly two hundred plates are shown and discussed insofar as orbital parameters and system membership are concerned. Evidence from the He i lines, the emission edges, shell absorptions, and underlying wide absorptions of the hydrogen lines indicate that the system is made up of a B1 primary and a B3 secondary, both of which are emission-line stars.
Auditory Cortex Responsiveness During Talking and Listening: Early Illness Schizophrenia and Patients at Clinical High-Risk for Psychosis

Objective: The corollary discharge mechanism is theorized to dampen sensations resulting from our own actions and distinguish them from environmental events. Deficits in this mechanism in schizophrenia may contribute to misperceptions of self-generated sensations as originating from external stimuli. We previously found attenuated speech-related suppression of auditory cortex in chronic patients, consistent with such deficits. Whether this abnormality precedes psychosis onset, emerges early in the illness, and/or progressively worsens with illness chronicity, is unknown. Methods: Event-related potentials (ERPs) were recorded from schizophrenia patients (SZ; n = 75) and age-matched healthy controls (HC; n = 77). A subsample of early illness schizophrenia patients (ESZ; n = 39) was compared with patients at clinical high-risk for psychosis (CHR; n = 35) and to a subgroup of age-matched HC (n = 36) during a Talk-Listen paradigm. The N1 ERP component was elicited by vocalizations as subjects talked (Talk) and heard them played back (Listen). Results: As shown previously, SZ showed attenuated speech-related N1 suppression relative to HC. This was also observed in ESZ. N1 suppression values in CHR were intermediate to HC and ESZ and not statistically distinguishable from either comparison group. Age-corrected N1 Talk-Listen difference z scores were not correlated with illness duration in the full SZ sample. Conclusions: Putative dysfunction of the corollary discharge mechanism during speech is evident early in the illness and is stable over its course. The intermediate effects in CHR patients may reflect the heterogeneity of this group, requiring longitudinal follow-up data to address if speech-related N1 suppression abnormalities are a risk marker for conversion to psychosis.
Feasibility of exercising adults with asthma: a randomized pilot study

Aerobic exercise appears to have clinical benefits for many asthmatics, yet a complete understanding of the mechanisms underlying these benefits has not been elucidated at this time. The objective of this study was to determine feasibility for a larger, future study that will define the effect of aerobic exercise on cellular, molecular, and functional measures in adults with mild-moderate asthma. Recruited subjects were randomized into usual care (sedentary) or usual care with moderate intensity aerobic exercise treatment groups. Nineteen adults with mild-moderate asthma but without a recent history of exercise were recruited at the UAB Lung Health Center, Birmingham, AL. The exercise group underwent a 12 week walking program exercising at 60 – 75% of maximum heart rate (HRmax). Subjects self-monitored HRmax levels using heart rate monitors; exercise diaries and recreation center sign-in logs were also used. Functional measures, including lung function and asthma control scores, were evaluated for all subjects at pre- and post-study time-points; fitness measures were also assessed for subjects in the exercise group. Peripheral blood and nasal lavage fluid were collected from all subjects at pre- and post-study visits in order to evaluate cellular and molecular measures, including cell differentials and eosinophilic cationic protein (ECP). Sixteen subjects completed the prescribed protocol. Results show that subjects randomized to the exercise group adhered well (80%) to the exercise prescription and exhibited a trend toward improved fitness levels upon study completion. Both groups exhibited improvements in ACQ scores. No changes were observed in lung function (FEV1, FEV1/FVC), cell differentials, or ECP between groups. Results indicate that a moderate intensity aerobic exercise training program may improve asthma control and fitness levels without causing asthma deterioration in adult asthmatics. As such, these findings demonstrate the feasibility of the study protocol in preparation for a larger, clinical trial that will elucidate the functional consequences of aerobic exercise on asthmatic cellular and molecular responses.
Injectable Self-Assembling Peptide Nanofibers Create Intramyocardial Microenvironments for Endothelial Cells

Background— Promoting survival of transplanted cells or endogenous precursors is an important goal. We hypothesized that a novel approach to promote vascularization would be to create injectable microenvironments within the myocardium that recruit endothelial cells and promote their survival and organization. Methods and Results— In this study we demonstrate that self-assembling peptides can be injected and that the resulting nanofiber microenvironments are readily detectable within the myocardium. Furthermore, the self-assembling peptide nanofiber microenvironments recruit progenitor cells that express endothelial markers, as determined by staining with isolectin and for the endothelial-specific protein platelet–endothelial cell adhesion molecule-1. Vascular smooth muscle cells are recruited to the microenvironment and appear to form functional vascular structures. After the endothelial cell population, cells that express α-sarcomeric actin and the transcription factor Nkx2.5 infiltrate the peptide micro...
Age-dependent threshold and superthreshold behavior of ultrasound-induced lung hemorrhage in pigs

Age-dependent threshold and superthreshold behavior of ultrasound-induced lung hemorrhage was investigated with 116 4.9/spl plusmn/1.6-day-old neonate crossbred pigs, 103 39/spl plusmn/5-day-old crossbred pigs, and 104 58/spl plusmn/5-day-old crossbred pigs. Exposure conditions were: 3.1 MHz, 10-s exposure duration, 1-kHz PRF, and 1.4-/spl mu/s pulse duration. The in situ (at the pleural surface) peak rarefactional pressure ranged between 2.2 and 10.4 MPa with either 8 or 9 acoustic pressure groups for each of the three pig ages (12 pigs/exposure group) plus sham exposed pigs; there were no lesions in the shams. Pigs were exposed bilaterally with the order of exposure (left and right lung) and acoustic pressure both randomized. Logistic regression analysis was used to examine the dependence of the lesion incidence rates on in situ peak rarefactional pressure, left versus right lung, order of exposure (first versus second) and age in three categories. Likewise, lesion depth and root surface area were analyzed using Gaussian to bit regression analysis. A significant threshold effect on lesion occurrence was observed as a function of age; younger pigs were less susceptible to lung damage given equivalent in situ exposure.