cssi/SciSciGPT-SciSciNet huggingface dataset:
Protective effects of flavonoids in acute models of light-induced retinal degeneration

Degeneration of photoreceptors caused by excessive illumination, inherited mutations, or aging is the principal pathology of blinding diseases. Pharmacological compounds that stabilize the visual receptor rhodopsin and modulate the cellular pathways triggering death of photoreceptors could avert this pathology. Interestingly, flavonoids can modulate the cellular processes, such as oxidative stress, inflammatory responses, and apoptosis, that are activated during retinal degeneration. As we found previously, flavonoids also bind directly to unliganded rod opsin, enhancing its folding, stability, and regeneration. In addition, flavonoids stimulate rhodopsin gene expression. Thus, we evaluated the effect of two main dietary flavonoids, quercetin and myricetin, in ATP-binding cassette subfamily A member 4 -/- /retinol dehydrogenase 8 -/- and wild-type BALB/c mice susceptible to light-induced photoreceptor degeneration. Using in vivo imaging, such as optical coherence tomography, scanning laser ophthalmoscopy, and histologic assessment of retinal morphology, we found that treatment with these flavonoids prior to light insult remarkably protected retina from deterioration and preserved its function. Using high-performance liquid chromatography-mass spectrometry analysis, we detected these flavonoids in the eye upon their intraperitoneal administration. The molecular events associated with the protective effect of quercetin and myricetin were related to the elevated expression of photoreceptor-specific proteins, rhodopsin and cone opsins, decreased expression of the specific inflammatory markers, and the shift of the equilibrium between cell death regulators BCL2-associated X protein (BAX) and B-cell lymphoma 2 toward an antiapoptotic profile. These results were confirmed in photoreceptor-derived 661W cells treated with either H2O2 or all-trans-retinal stressors implicated in the mechanism of retinal degeneration. Altogether, flavonoids could have significant prophylactic value for retinal degenerative diseases. SIGNIFICANCE STATEMENT: Flavonoids commonly present in food exhibit advantageous effects in blinding diseases. They bind to and stabilize unliganded rod opsin, which in excess accelerates degenerative processes in the retina. Additionally, flavonoids enhance the expression of the visual receptors, rod and cone opsins; inhibit the inflammatory reactions; and induce the expression of antiapoptotic markers in the retina, preventing the degeneration in vivo. Thus, flavonoids could have a prophylactic value for retinal degenerative diseases.
Putting Theory into Practice

This essay introduces the Special Issue devoted to the impact that the Luce Foundatin’s LIASE initiative has had on liberal-arts campuses across the United States.
Characteristics of VCP mutation-associated cardiomyopathy

Abstract VCP associated inclusion body myopathy, Paget's disease of bone, and Frontotemporal Dementia (IBMPFD, VCP disease, or multisystem proteinopathy type 1 (MSP1)) is an autosomal dominant disease caused by missense mutations in the VCP gene, which plays a crucial role in ubiquitin-proteasome dependent degradation of cytosolic proteins. Those diagnosed with the disorder often suffer from cardiovascular complications in the advanced stages. We conducted an observational cross-section study to investigate echocardiographic features of asymptomatic carriers and those affected by the disease to determine the differences and potential early features of the VCP-associated cardiomyopathy. The study cohort constituted of 32 patients with VCP mutations including 23 affected individuals diagnosed with myopathy +/- Paget disease of bone, and 9 asymptomatic carriers. Among the affected individuals, 95.7% had myopathy, 43.5% had Paget's disease of bone, and none had frontotemporal dementia, and the carriers were asymptomatic. Not surprisingly the carriers were younger (mean age 38.4 ± 3.8 years), than the affected cohort (mean age 50.6 ± 9.1 years; p
Ultra Efficient Transfer Learning with Meta Update for Continuous EEG Classification Across Subjects

The pattern of Electroencephalogram(EEG) signal differs significantly across different subjects, and poses challenge for EEG classifiers in terms of 1) effectively adapting a learned classifier onto a new subject, 2) retaining knowledge of known subjects after the adaptation. We propose an efficient transfer learning method, named Meta UPdate Strategy (MUPS-EEG), for continuous EEG classification across different subjects. The model learns effective representations with meta update which accelerates adaptation on new subject and mitigate forgetting of knowledge on previous subjects at the same time. The proposed mechanism originates from meta learning and works to 1) find feature representation that is broadly suitable for different subjects, 2) maximizes sensitivity of loss function for fast adaptation on new subject. The method can be applied to all deep learning oriented models. Extensive experiments on two public datasets demonstrate the effectiveness of the proposed model, outperforming current state of the arts by a large margin in terms of both adapting on new subject and retain knowledge of learned subjects.
Reactive force fields for modeling oxidative degradation of organic matter in geological formations

In an attempt to better explore organic matter reaction and properties, at depth, to oxidative fluid additives, we have developed a new ReaxFF potential to model and describe the oxidative decompositions of aliphatic and aromatic hydrocarbons in the presence of the oxychlorine ClOn− oxidizers. By carefully adjusting the new H/C/O/Cl parameters, we show that the potential energies in both training and validation sets correlate well with calculated density functional theory (DFT) energies. Our parametrization yields a reliable empirical reactive force field with an RMS error of ∼1.57 eV, corresponding to a 1.70% average error. At this accuracy level, the reactive force field provides a reliable atomic-level picture of thermodynamically favorable reaction pathways governing oxidative degradation of H/C/O/Cl compounds. We demonstrate this capability by studying the structural degradation of small aromatic and aliphatic hydrocarbons in the presence of oxychlorine oxidizers in aqueous environments. We envision that such reactive force fields will be critical in understanding the oxidation processes of organic matter in geological reservoirs and the design of the next generation of reactive fluids for enhanced shale gas recovery and improved carbon dioxide adsorption and sequestration.
Centering race/ethnicity: Differences in traumatic brain injury inpatient rehabilitation outcomes.

Introduction Persons of color have a higher incidence of Traumatic Brain Injury (TBI) and experience disparities in the quality and quantity of interventions received, discharge disposition, functional outcomes, and mortality rate post TBI. Objective To examine racial/ethnic differences in rehabilitation outcomes for TBI patients. Design Multi-year (2005-2016) and retrospective cohort using secondary data analysis from Inpatient Rehabilitation Facilities (IRFs) across the Unites States. Setting eRehabData participating IRFs throughout the United States. Patients 41847 adults with a diagnosis of TBI, admitted to U.S. eRehabData participating IRFs. Interventions Not applicable. Main outcome measures Inpatient rehabilitation functional outcomes and discharge disposition. Results Participants were 41 847 non-Hispanic Whites (NHW), Hispanics, non-Hispanic Asians (NHA), and non-Hispanic Blacks (NHB) aged 18-107 years. NHW were used as the reference group. NHB had the longest length of stay (17.65 ± 14.96). At admission, NHB, Hispanic, and NHA race/ethnicities were significantly associated with 1-3 point lower motor, cognitive, and total Functional Independence Measure (FIM) scores. NHB race/ethnicity was significantly associated with less than 1-point lower cognitive, motor, and total efficiency FIMscores. At discharge, NHB race/ethnicity was significantly associated with 1-2 point lower motor, cognitive, and total FIM scores; Hispanics and NHA race/ethnicity were associated with less than 1-point lower cognitive FIM scores. Compared to NHWs, Hispanic race/ethnicity was associated with greater odds of a discharge to home (OR = 1.163, 95% CI = 1.06-1.27). Conclusion Contrary to established literature on functionality differences 1-year post TBI, the current study found racial/ethnic differences in functional outcomes during inpatient rehabilitation. These findings suggest a need for cultural competence/sensitivity in the care of racial/ethnic persons and centering potential contributing factors for racial/ethnic differences in TBI rehabilitation outcomes. This article is protected by copyright. All rights reserved.
Whole-genome copy number variation analysis in anophthalmia and microphthalmia

Anophthalmia/microphthalmia (A/M) represent severe developmental ocular malformations. Currently, mutations in known genes explain less than 40% of A/M cases. We performed whole-genome copy number variation analysis in 60 patients affected with isolated or syndromic A/M. Pathogenic deletions of 3q26 (SOX2) were identified in four independent patients with syndromic microphthalmia. Other variants of interest included regions with a known role in human disease (likely pathogenic) as well as novel rearrangements (uncertain significance). A 2.2-Mb duplication of 3q29 in a patient with non-syndromic anophthalmia and an 877-kb duplication of 11p13 (PAX6) and a 1.4-Mb deletion of 17q11.2 (NF1) in two independent probands with syndromic microphthalmia and other ocular defects were identified; while ocular anomalies have been previously associated with 3q29 duplications, PAX6 duplications, and NF1 mutations in some cases, the ocular phenotypes observed here are more severe than previously reported. Three novel regions of possible interest included a 2q14.2 duplication which cosegregated with microphthalmia/microcornea and congenital cataracts in one family, and 2q21 and 15q26 duplications in two additional cases; each of these regions contains genes that are active during vertebrate ocular development. Overall, this study identified causative copy number mutations and regions with a possible role in ocular disease in 17% of A/M cases.
Lung Defenses Against Infection: A Clinical Correlation

The current state of knowledge of lung defenses has been reviewed. First, mechanical factors such as aerodynamic filtration and mucociliary transport were considered. Then, in general terms, the contributions of alveolar macrophages, neutrophils, lymphocytes, and immunoglobulins, and the roles of complement, antiproteases, lysozyme, and fibronectin were examined. Interactions between these components may regulate their effect. Finally, the responses to five specific microorganisms were reviewed to illustrate different aspects of the lung's defenses. Streptococcus pneumoniae was selected as a representative extracellular bacterial pathogen, Mycobacterium tuberculosis as an intracellular bacterial pathogen, Mycoplasma pneumoniae because it elicits significant humoral and cell-mediated immunity, respiratory syncytial virus as an example of a local viral pathogen, and measles as a viral pathogen that causes generalized disease. It was shown that these responses may not always be beneficial for the host. For each of the five infections, recommendations for improving the outcome were made.
Examining the Endogenous Antioxidant Response Through Immunofluorescent Analysis of Nrf2 in Tissue

As organisms designed to depend upon oxygen to sustain life, humans are necessarily and continually exposed to damaging oxidizing agents. As a vital protective measure, oxygen-dependent organisms have developed a highly evolutionarily conserved mechanism for preventing oxidative stress. NF-E2 (nuclear factor (erythroid-derived 2))-related faetor-2 (Nrf2) is the primary regulator of this endogenous antioxidant response. Many diseases that plague human society, ranging from various cancers to neurodegenerative diseases, have oxidative stress as a component of their etiology, and thus, much disease research has focused on Nrf2, both as a potential point of biological failure and as a promising therapeutic target. As a transcription factor, Nrf2 is active only when it is nuclear, and is regulated largely by its subcellular distribution. Thus, Nrf2 protein levels and subcellular localization are both key pieces of information when studying the endogenous antioxidant response. Immunofluorescent analysis (IFA) of Nrf2 in human tissue is a particularly powerful tool in the study of Nrf2 in disease, because it allows examination of both of these regulatory mechanisms that modulate Nrf2 activity.
Polymeric and Composite Materials for Use in Systems Utilizing Hot, Flowing Geothermal Brine III

Further progress is reported on a continuing experimental program designed to select high-performance polymeric materials for use in geothermal power plants. In field tests 12 nozzles, 27 wear plates, and 2 types of polymer lined pipe were tested. Nozzles made of Teflons TFE and PFA, Tefzel, Ryton PPS and H-Resin/carbon cloth were little changed except for some scaling. The fluorocarbons scaled least rapidly. All blade type wear plates eroded, those based on Tefzel, PPQ, and PPS the least. Fluorocarbon lined pipes were little affected by exposure. In laboratory tests samples were heated at 250 and 300/sup 0/C in brine. Several materials including fluorocarbon and unhydrolyzable aromatic or cross-linked aliphatic, thermally stable polymers survived for periods up to 1300 h. In erosion tests, coatings based on epoxy resins and a fluorocarbon were most resistant; good adhesion was required.
Abstract 5213: RUNX2 modulates the angiogenic potential of human neuroblastoma cells

Neuroblastoma is the most common extracranial pediatric solid tumor with an undifferentiated status and characterized by heterogeneous clinical courses ranging from spontaneous regression to a very aggressive malignant progression. The RUNX gene family comprises RUNX1, RUNX2, and RUNX3 transcription factors and plays pivotal roles in development, differentiation and tumorigenesis. Hypoxia is known to be a significant physiological stress in the tumor microenvironment and is associated with tumor malignant phenotype. In this study, we examined the effects of hypoxia on the Runx2 expression in human neuroblastoma cells and the role of RUNX2 on angiogenic potential of neuroblastoma cells. Runx2 has two isoforms, Runx2-I and Runx2-II. Isoform I is controlled by the P2 proximal promoter whereas isoform II is transcribed from the P1 distal promoter. Increased expression of mRNAs of isoform I and II as well as intact isoform of RUNX2 was observed in NB1691 cells exposed to hypoxia. Furthermore, hypoxia enhanced the activity of a luciferase reporter containing Runx2 P1 promoter in NB1691 cells. Hypoxic exposure caused an increase in protein levels of RUNX2 as well as survivin, a RUNX2 downstream target gene in NB1691 cells. Hypoxia also stabilized RUNX2 protein levels in NB1691 cells without altering the stability of RUNX2 mRNA. Hypoxia enhanced angiogenic potential of NB1691 cells. Knockdown of Runx2 significantly decreased VEGF mRNA and protein in NB1691 cells exposed to hypoxia. A decrease in angiogenesis was observed in chorioallantoic membrane assay performed using conditioned medium collected from RUNX2 siRNA treated hypoxic NB1691 cells compared with control. Further, transcript levels were measured by PCR array of human angiogenesis pathway and the analysis showed down regulation of EDN1, FIGF, TEK and VEGF A mRNAs in hypoxic NB1691 cells treated with RUNX2 siRNA. In conclusion, our study suggests that hypoxia upregulates RUNX2 expression in NB1691 cells and knockdown of RUNX2 decreases the angiogenic potential of hypoxic NB1691 cells. Citation Format: Manu Gnanamony, Indra Mohanam, Sanjeeva Mohanam. RUNX2 modulates the angiogenic potential of human neuroblastoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5213. doi:10.1158/1538-7445.AM2015-5213
Synthesis of Molecular Brushes with Gradient in Grafting Density by Atom Transfer Polymerization

Macromolecular brushes with a gradient of side-chain spacing along the backbone have been synthesized by the “grafting from” approach using atom transfer radical polymerization. A macroinitiator was prepared in two steps, first by conducting a gradient copolymerization of MMA and HEMA-TMS followed by transformation of the resulting poly(MMA-grad-HEMA-TMS) to poly(MMA-grad-BPEM). The gradient composition of the macroinitiator was a forced gradient formed by continuous feeding of HEMA-TMS during MMA polymerization. The gradient structure was characterized by monitoring monomer conversion (GC) and molecular weight evolution (GPC) during copolymerization. AFM measurements demonstrated the characteristic anisotropy of the molecular structure by resolving individual brush molecules with a bulky head and a thin tail.
Alteration of the MT1 melatonin receptor gene and its expression in primary human breast tumors and breast cancer cell lines

The MT1 melatonin receptor is bound and activated by the pineal hormone melatonin. This G protein-coupled melatonin receptor is expressed in human breast tumor cell lines, and when activated, mediates the growth-suppressive and steroid hormone/nuclear receptor modulatory actions of melatonin on breast tumor cells. In the current studies, we have examined the expression of the MT1 receptor in breast cancer cell lines and primary human breast tumors and correlated MT1 receptor expression with the deletion, rearrangement and amplification of the MT1 gene and established markers of breast cancer such as tumor size, stage, estrogen receptor alpha (ERα) and progesterone receptor (PR) expression. Theses studies suggest amplification of the MT1 gene in some breast tumors and an inverse correlation with ERα, PR and MT1 protein expression. Furthermore, these approaches employing immunohistochemical and immunofluorescent/confocal microscopic studies demonstrate that the MT1 receptor is localized to the caveoli and that MT1 expression in MCF-7 breast cancer cells can be repressed by estradiol and melatonin.
Evaluation of Dosing Interval and Optimum Dose of Cibenzoline

Fifteen patients with ventricular premature complexes (VPCs) were included in this open study designed to assess the relative efficacy of bid (two times daily) and tid (three times daily) dosing regimens for cibenzoline as compared with qid (four times daily) administration. Patients started therapy with qid administration; this was followed in sequence by tid and bid administration at the maximum effective total daily dose determined during the qid administration. Of the nine patients evaluated for efficacy for suppression of VPCs, eight demonstrated a 75% or greater suppression of VPCs with cibenzoline administered qid (total daily dose of 130-325 mg). This effectiveness was maintained in four patients with a bid regimen and in three with a tid regimen. All four patients who had ventricular tachycardia (VT) had a decrease in the number of VT episodes while receiving cibenzoline (only one of these patients had satisfactory suppression of VPCs at the same dosage regimen). Twelve patients continued to receive extended therapy with cibenzoline for up to two years, as this was considered to be the optimum antiarrhythmic treatment for these patients. Two patients had to be removed from the study and two had the dosage lowered because of adverse reactions (dry mouth, blurred vision, dizziness, congestive heart failure) although in one instance, the congestive heart failure was subsequently considered to be unrelated to cibenzoline. One patient was able to complete the short-term phase of the trial, but was not given extended treatment because of persistent dry mouth. Two patients had treatment discontinued during the extended therapy phase because of adverse reactions (fever, nausea, vomiting, asthenia).(ABSTRACT TRUNCATED AT 250 WORDS)
Lunar gravity traverse experiment

Purpose: The purpose of the Traverse Gravity Experiment is to measure the value of lunar gravity (relative to the value at the landing site) at selected points along the lunar surface traverse. A secondary purpose is to make an Earth-Moon gravity tie.
Lumber-Boxed Concrete Structural System—Concept and Preliminary Analysis

Lumber has the advantages of being a lightweight construction material, easy to handle, and environmentally benign. However, large creep deflections and significant issues with sound transmission, particularly the footfall problem, generally limit lumber use to small spans and low-rise buildings. A concrete topping on lumber subfloors may mitigate some of these issues, but even with well-engineered wood systems, the spans are relatively short. In this study, a new structural system is analytically explored. Called a lumber-boxed concrete structural system, the dual system utilizes the positive attributes of both dimensional lumber and reinforced concrete; composite action is not a requirement of the system. A stress-block approach is developed to calculate strength and deformation behavior. An analytical stress-block-based moment-curvature analysis is performed on the lumber-boxed concrete structural elements. Results show that the structural lumber-boxed concrete members may have better strength and duct...
Eosinophilia and helminthic infections.

Among microbial agents, helminths are the most common cause of eosinophilia. An approach to the evaluation of a patient with eosinophilia is outlined, with particular emphasis on clues in the history, examination and routine laboratory data that can help with the diagnosis. Multiple helminthic infections have been associated with eosinophilia, and the characteristic modes of spread, clinical manifestations, diagnostic tests and therapeutic considerations of these infections are discussed.
Right to Inclusive Education for Students with Disabilities in Kenya

Abstract This article explores the current inclusive education system in Kenya, and how those practices relate to Article 24 of the United Nations' Convention on the Rights of Persons with Disabili...
Expression profile of G-protein βγ subunit gene transcripts in the mouse olfactory sensory epithelia.

Heterotrimeric G-proteins mediate a variety of cellular functions, including signal transduction in sensory neurons of the olfactory system. Whereas the Gα subunits in these neurons are well characterized, the gene transcript expression profile of Gβγ subunits is largely missing. Here we report our comprehensive expression analysis to identify Gβ and Gγ subunit gene transcripts in the mouse main olfactory epithelium (MOE) and the vomeronasal organ (VNO). Our reverse transcriptase PCR (RT-PCR) and realtime qPCR analyses of all known Gβ(β1,2,3,4,5) and Gγ(γ1,2,2t,3,4,5,7,8,10,11,12,13) subunits indicate presence of multiple Gβ and Gγ subunit gene transcripts in the MOE and the VNO at various expression levels. These results are supported by our RNA in situ hybridization (RISH) experiments, which reveal the expression patterns of two Gβ subunits and four Gγ subunits in the MOE as well as one Gβ and four Gγ subunits in the VNO. Using double-probe fluorescence RISH and line intensity scan analysis of the RISH signals of two dominant Gβγ subunits, we show that Gγ13 is expressed in mature olfactory sensory neurons (OSNs), while Gβ1 is present in both mature and immature OSNs. Interestingly, we also found Gβ1 to be the dominant Gβsubunit in the VNO and present throughout the sensory epithelium. In contrast, we found diverse expression of Gγ subunit gene transcripts with Gγ2, Gγ3 and Gγ13 in the Gαi2-expressing neuronal population, while Gγ8 is expressed in both layers. Further, we determined the expression of these Gβγ gene transcripts in three post-natal developmental stages (p0, 7 and 14) and found their cell-type specific expression remains largely unchanged, except the transient expression of Gγ2 in a single basal layer of cells in the MOE during P7 and P14. Taken together, our comprehensive expression analyses reveal cell-type specific gene expression of multiple Gβ and Gγ in sensory neurons of the olfactory system.
Dermatofibrosarcoma protuberans of the vulva: a rare tumor presenting during pregnancy in a teenager.

:Objectives. We report a case of a young patient with dermatofibrosarcoma protuberans of the vulva diagnosed during pregnancy. We also provide a review of the literature on this topic. Materials and Methods. This patient’s case was reviewed retrospectively. A current literature search was performed and findings were reported. Results. This rare malignancy was diagnosed during pregnancy in a teenager. Conclusions. Dermatofibrosarcoma protuberans of the vulva, a rare vulvar neoplasm mostly associated with older patients and never before reported during pregnancy, should be considered as part of the differential diagnosis for any vulvar mass and cannot be excluded on the basis of the patient’s age or pregnancy status.
STUDY OF THE EFFECT OF PRESSURE ON THE DNB IN A CROSSED ROD MATRIX WITH R- 113 COOLANT.

Abstract Earlier investigations of departure from nucleate boiling (DNB) in a crossed rod matrix show that such a geometry holds promise as a possible configuration for the fuel core in a highly compact and efficient nuclear reactor. This investigation is an extension of Coffield's work, further studying the effect of pressure. The fluid used was R - 113 (C Cl 2 FC Cl F 2 ). The coolant pressures for the test were 75, 100 and 125 psig. The subcooling was 40°, 60° and 80°F. Mass velocities ranged from 1.0 × 10 5 to 3.5 × 10 5 lb/hr-ft 2 . An increase in critical heat flux of the order of 10 000, 15 000 and 20 000 BTU/hr-ft 2 was obtained for a 25 psi increase for 40,60 and 80°F subcooling respectively. An empirical equation correlated the critical heat flux q ″ crit to within ± 25.0%.
Revisiting NO2 on Ag(1 1 1): a detailed TPD and RAIRS study

Abstract The interactions of NO 2 with Ag(1 1 1) at various temperatures were investigated by means of temperature programmed desorption and reflection–adsorption infrared spectroscopy and found to be sensitively coverage- and temperature-dependent. During dosing at 508 K, NO 2 decomposes into NO(g) and O(a). NO 2 decomposes at 215 K also, however, NO and O remain adsorbed. The NO(a) occupy threefold-bridged sites and atop sites in sequence. Orientations of the NO(a) axes are affected by neighboring O(a). A sharp and narrow desorption peak (γ-NO) arises for high NO 2 doses. During dosing at 90 K, decomposition occurs initially and is followed sequentially by accumulation of NO 2 (a), NO 3 (a), N 2 O 4 monolayer and N 2 O 4 multilayer. NO 2 (a) chemisorbs to form a Ag(1 1 1) μ -N, O-nitrito surface chelate with C s symmetry. Upon heating, the N 2 O 4 multilayer and monolayer desorb molecularly while most NO 2 (a) disproportionates into NO(g) or NO(a) and NO 3 (a) at 165 K. Surface NO 3 (a) decomposes below 320 K. All surface species except O(a) desorb below 500 K.
Magnetorheological fluid based automotive steer-by-wire systems

The idea of this paper is to design a Magnetorheological (MR) fluid based damper for steer-by-wire systems to provide sensory feedback to the driver. The advantages of using MR fluids in haptic devices stem from the increase in transparency gained from the lightweight semiactive system and controller implementation. The performance of MR fluid based steer-by wire system depends on MR fluid model and specifications, MR damper geometry, and the control algorithm. All of these factors are addressed in this study. The experimental results show the improvements in steer-by-wire by adding force feedback to the system.
Are the Duocarmycin and CC-1065 DNA Alkylation Reactions Acid-Catalyzed? Solvolysis pH-Rate Profiles Suggest They Are Not.

A study of the solvolysis pH−rate profiles for two key reactive CC-1065/duocarmycin alkylation subunit analogues is detailed. Unlike the authentic alkylation subunits and N-BOC-CBI (4) which are too stable to establish complete solvolysis pH−rate profiles, the analogues N-BOC-CBQ (5) and N-BOC-CNA (6) are reactive throughout the pH range of 2−12. Moreover, they possess progressively diminished vinylogous amide conjugation resulting in a corresponding progressively increasing reactivity adopting and reflecting conformations analogous to that proposed for DNA-bound CC-1065. For both, the acid-catalyzed reaction was observed only at the lower pH of 2−5, and the uncatalyzed solvolysis reaction rate dominated at pH ≥6, indicating that the CC-1065 and duocarmycin DNA alkylation reaction observed at pH 7.4 need not be an acid-catalyzed reaction. The studies provide further strong evidence that catalysis for the DNA alkylation reaction (pH 7.4) is derived from a DNA binding-induced conformational change in the ag...
Chronic cocaine exposure potentiates prolactin and head shake responses to 5-HT2 receptor stimulation in rats

The effect of repeated cocaine administration on serotonin2 (5-HT2) receptor function was examined in male rats. Rats were fitted with indwelling jugular catheters and subsequently received cocaine (15 mg/kg, i.p., b.i.d.) or saline for 7 days. Rats were challenged with the 5-HT2 agonist DOI (25, 100, 400 μg/kg, i.v.) or saline 42 hr and 8 days after cessation of chronic treatment. Serial blood samples were collected at various times after DOI challenge and analyzed for prolactin levels. DOI-induced head shakes and skin jerks were examined concurrently in the same subjects. After 42 hr of withdrawal, the stimulatory effects of DOI on prolactin release and shaking behavior were significantly enhanced in cocaine-treated rats. Conversely, the skin jerk response to DOI was not altered by prior cocaine exposure. After 8 days of withdrawal, the prolactin and head shake responses to DOI were still potentiated in cocaine-treated rats, but this effect was no longer statistically significant. The data indicate that chronic cocaine enhances the sensitivity of 5-HT2 receptor mechanisms. Our findings further suggest the possibility that altered 5-HT2 receptor function may be involved in the mood disturbances experienced by abstinent cocaine addicts.
High performance liquid chromatographic assay of amprolium and ethopabate in chicken feed using solid-phase extraction

A method for the assay of mixtures of amprolium and ethopabate in chicken feed was developed utilizing reversed-phase high-performance liquid chromatography (HPLC) after sample clean-up of a methanolic extract by solid-phase extraction using CN cartridges. HPLC was done with benzocaine as internal standard on a C-8 column with methanol-water 40:60, containing octanesulfonic acid, triethylamine and acetic acid, as mobile phase. Eluate was monitored at 274 nm. Baseline separation was achieved with retention times of approximately 7.5, 9.4, and 10.4 min, for amprolium, benzocaine, and ethopabate respectively. Feed constituents did not give peaks after 6.5 min. Peak area ratios were linear over 10-180 ng of amprolium, and 2-18 ng of ethopabate injected. Limits of quantitation at AUFS 0.05 were 0.5 and 0.3 ng respectively. Recovery studies from spiked feed (n = 9), covering +/- 30% of usual doses in feed, gave percent recoveries (+/- SD) of 99.4 +/- 1.4% for amprolium and 100.5 +/- 2.6% for ethopabate. Applying the method to two different batches of commercial feed gave results which were comparable to those obtained by the AOAC spectrofluorometric methods.
ATP-evoked calcium signal stimulates protein phosphorylation/dephosphorylation in astrocytes.

Abstract Extracellular adenosine 5′-triphosphate (ATP)-evoked increases in intracellular calcium and the consequent stimulation of calcium-mediated protein phosphorylation systems were investigated in primary cultures of rat cerebral cortical astrocytes. Measurement of calcium responses in fura-2-loaded astrocytes indicated that extracellular ATP stimulated a transient calcium peak followed by a sustained increase in intracellular calcium which declined to baseline when external calcium was removed, thereby indicating that ATP evokes mobilization of internal calcium as well as influx of external calcium. Protein phosphorylation studies revealed that application of extracellular ATP resulted in increased phosphorylation of 55 and 52 kDa proteins (4-fold and 2-fold, respectively) and decreased phosphorylation of 24 and 21 kDa proteins (approximately 50% for each protein). These effects were time- and dose-dependent. The changes in phosphate incorporation were (a) inhibited by lanthanum, (b) reduced when calcium was omitted from the bath and (c) mimicked by ionomycin, thus suggesting that the ATP-induced changes in protein phosphorylation were dependent on increased levels of intracellular calcium. Adenosine diphosphate (ADP) gave similar, but reduced, effects while adenosine and guanosine triphosphate (GTP) were ineffective, findings consistent with activation of P2 purinergic receptors. The 52 kDa protein co-migrated with glial fibrillary acidic protein. These results support the premise that calcium-dependent protein kinases and phosphatases are transducing elements for the calcium signal brought about by activation of P2 purinergic receptors in astrocytes. Since ATP is released from neurons and endothelial cells, this signal transduction mechanism may be an important component of neuronal- and endothelial-astrocytic communication.
Theory of the Magnetoresistive Effect in Semiconductors

Experiments show that the application of a magnetic field increases the resistivity of a semiconductor and produces a decrease in the magnitude of the Hall coefficient. Existing theoretical treatments predict much smaller effects than are actually observed in semiconductors. The present calculation has been carried out to see if theory is brought closer to experiment by considering (1) scattering of conduction electrons by impurity ions as well as by the lattice, and (2) conduction by both holes and electrons at high temperatures. The calculation shows that the presence of impurity scattering decreases the magnitude of the effects produced by a magnetic field and thus increases the gap between theoretical and experimental values. It is noted that the discrepancy decreases with falling temperatures and is no longer present for data measured on a Ge sample at 20\ifmmode^\circ\else\textdegree\fi{}K. The calculated magnetic field effects are very much greater for an intrinsic semiconductor than for an impurity semiconductor. The fractional changes in resistivity and Hall coefficient are given, for several different values of the electron-hole mobility ratio, as functions of a parameter containing magnetic field strength and temperature. The absence of experimental values of the magnetic field effects at high temperatures prevents comparison of theory and experiment for the intrinsic semiconductor.
Feasibility study of actuators and sensors using electroactive polymers reinforced with carbon nanotubes

Electro-active polymers reinforced with carbon nanotubes have attracted many researchers in the recent years. Recent activities in this area show that conducting polymers with carbon nanotubes in an electrolytic medium possess actuation and sensing properties due to the change in bond length in the carbon atoms. However, their applications are limited due to their operation in a wet medium. In this paper, we explore the feasibility of electro-active polymers with dispersed carbon nanotubes that can be used for actuation and sensing in a dry medium like air to make them viable. Different polymer composites are considered for mixing with single-walled and multi-walled carbon nanotubes manufactured by chemical vapor deposition technique. Various dispersing techniques for aligning the carbon nanotubes like smart blending and chaotic mixing are also explored. The feasibility of actuation and sensing of these composites are verified by experimentation on several macrosystems comprised of these functional nanostructures.
Overuse Syndromes Among Endoscopists

A survey of 400 gastroenterological endoscopists was carried out to determine what kinds of overuse syndromes they suffer from as a result of doing endoscopic procedures. The response rate was 72%. Thumb pain, hand pain, elbow pain, low back pain, and possibly shoulder pain all appear to be caused by endoscopy to at least some extent. Physicians who perform the most procedures tend to have the highest risk of developing such problems. Age, sex, practice setting, and hobbies did not seem to have an impact on the overuse conditions identified. These conditions are most likely due to the equipment and technique of endoscopy. Further study is needed to determine the anatomic lesions causing the various pain states, so that they can be treated or prevented.
Nonlinear photonic crystals: II. Interaction classification for quadratic nonlinearities

Abstract Weakly nonlinear interactions between wavepackets in lossless periodic dielectric media are studied based on the classical nonlinear Maxwell equations. We consider nonlinear processes such that: (i) the amplitude of the wave component due to the nonlinearity does not exceed the amplitude of its linear component; (ii) the spatial range of a probing wavepacket is much smaller than the dimension of the medium sample, and it is not too small compared with the dimension of the primitive cell. These nonlinear processes are naturally described in terms of the Bloch modes and the dispersion relations of the underlying linear periodic medium. It turns out that only a few triads of modes have significant nonlinear interactions. They are singled out by the frequency and phase matching conditions and, as we show, by an additional selection rule: the group velocity matching condition. The latter condition is the most important selection rule for the nonlinear regimes. We give a complete quantitative classific...
Endoscopic treatment of vesicoureteral reflux : Current status

Vesicoureteral reflux (VUR) affects around 1% of all children. It carries an increased risk of febrile urinary tract infections (UTIs) and is associated with impaired renal function. Endoscopic treatment with NASHA/Dx gel (dextranomer microspheres in a stabilized hyaluronic acid-based gel of nonanimal origin) is minimally invasive, well tolerated and provides cure rates approaching those of open surgery: approximately 90% in several studies. It has also been shown to be effective in a variety of 'complicated' cases. Endoscopic treatment is therefore considered preferable to open surgery and long-term antibiotic prophylaxis. Nontreatment of VUR is being discussed as an alternative option, whereby children are treated with antibiotics only when UTIs occur. Considering all the available evidence, however, active intervention with endoscopic treatment remains preferable. A new approach to managing VUR may nevertheless be considered, with treatment decisions based not only on the grade of reflux, but also factors such as age, sex, renal scarring, and bladder dysfunction. Open surgery would be reserved for use only in the ( approximately )10% of children not responding to endoscopic treatment, and patients with refluxing primary megaureter.
Stability of lyophilized siRNA nanosome formulations.

Abstract The goal of this study is to evaluate the stability of lyophilized siRNA formulations. The gene silencing efficiency of a stored lyophilized siRNA formulation (i.e. siRNA nanosomes) was evaluated in interferon-α (IFN-α) resistant hepatitis C virus (HCV) at different time points up to three months in an in vitro cell culture model and compared with freshly prepared siRNA formulations. Novel siRNA sequences were encapsulated within nanosize liposomes following condensation with protamine sulfate. The siRNA encapsulated nanosomes were lyophilized and stored at 4 °C for 3 months, along with liquid liposomes (L) and lyophilized liposome powder (P) which were subsequently used to prepare siRNA nanosomes (L) and siRNA nanosomes (P), respectively at different time points. Physiochemical and biological properties of all three formulations were compared at different time points up to 3 months. The particle size of the stored siRNA nanosomes (642 ± 25 nm) was considerably larger initially in comparison with the liquid liposomes (134 ± 5 nm) and lyophilized liposomes (118 ± 3). However, the particle size gradually became smaller over time (413 ± 128 nm by the third month). The zeta potential of all three formulations was initially very high (> +40 mV), followed by a gradual decrease over time. The amount of siRNA in the stored siRNA nanosomes decreased ∼18% during the 3 month storage period (1.16 ± 0.03 nmol initially on day 1 vs. 0.95 ± 0.04 nmol after 3 months). With respect to biological potency, all three formulations were significantly effective to knock-down HCV throughout the storage time. The cell viability was well-maintained throughout this period. Thus, this study indicates that the stored lyophilized siRNA formulation is as effective as the fresh preparation and that long-term storage could be a viable option to treat deadly diseases such as cancer and viral infection.
An Improved Goodness-of-Fit Statistic for Sparse Multinomials

Abstract A new goodness-of-fit statistic for sparse multinomials is proposed. It is assumed that the null distribution exhibits smoothness. The test statistic is based on the maximum posterior estimator probability estimates of Simonoff (1983). Computer simulations are used to estimate the null distribution, significance levels, and the power function of the test. It is shown that power of the test is a great improvement over that of the standard tests if the alternative distribution exhibits smoothness.
Research Budgeting and Project Selection

A summary is presented of a study of decision-making in the area of research budgeting and project selection. Data were obtained from three major chemical companies. The objective of the study was to determine if scientific analysis could be employed to derive objective and quantitative procedures in these areas, currently dominated by a mixture of intuition, judgment, and experience. A two-fold classification of R and D is used? ``product research'' and ``process research.'' A solution is presented for the general R and D budgeting problem, involving a budgeting model. A computational procedure for this general problem is illustrated. The special problem of allocation of the budget to specific projects is treated briefly in this paper.
Effect of Water Residence Time on Annual Export and Denitrification of Nitrogen in Estuaries: A Model Analysis

A simple model of annual average response of an estuary to mean nitrogen loading rate and freshwater residence time was developed and tested. It uses nitrogen inputs from land, deposition from the atmosphere, and first-order calculations of internal loss rate and net export to perform a steady-state analysis over a yearly cycle. The model calculates the fraction of total nitrogen input from land and the atmosphere that is exported and the fraction that is denitrified or lost to other processes within the estuary. The model was tested against data from the literature for 11 North American and European estuaries having a wide range of physical characteristics, nitrogen loading rates, and geographical and climatic settings. The model shows that the fraction of nitrogen entering an estuary that is exported or denitrified can be predicted from the freshwater residence time. The first-order rate constant for nitrogen loss within an estuary, as a fraction of total nitrogen in the water column, is 0.30 mo−1. Denitrification typically accounts for 69–75% of the total annual net nitrogen removal from the water column by processes within the estuary. The model makes explicit the dependence of nitrogen concentration in the water column on the loading rate of nitrogen, water residence time, estuary volume, and the rate constant for loss within the estuary.
Micromolar changes in lysophosphatidylcholine concentration cause minor effects on mitochondrial permeability but major alterations in function.

Abstract Mice deficient in group 1b phospholipase A 2 have decreased plasma lysophosphatidylcholine and increased hepatic oxidation that is inhibited by intraperitoneal lysophosphatidylcholine injection. This study sought to identify a mechanism for lysophosphatidylcholine-mediated inhibition of hepatic oxidative function. Results showed that in vitro incubation of isolated mitochondria with 40–200 μM lysophosphatidylcholine caused cyclosporine A-resistant swelling in a concentration-dependent manner. However, when mitochondria were challenged with 220 μM CaCl 2 , cyclosporine A protected against permeability transition induced by 40 μM, but not 80 μM lysophosphatidylcholine. Incubation with 40–120 μM lysophosphatidylcholine also increased mitochondrial permeability to 75 μM CaCl 2 in a concentration-dependent manner. Interestingly, despite incubation with 80 μM lysophosphatidylcholine, the mitochondrial membrane potential was steady in the presence of succinate, and oxidation rates and respiratory control indices were similar to controls in the presence of succinate, glutamate/malate, and palmitoyl-carnitine. However, mitochondrial oxidation rates were inhibited by 30–50% at 100 μM lysophosphatidylcholine. Finally, while 40 μM lysophosphatidylcholine has no effect on fatty acid oxidation and mitochondria remained impermeable in intact hepatocytes, 100 μM lysophosphatidylcholine inhibited fatty acid stimulated oxidation and caused intracellular mitochondrial permeability. Taken together, these present data demonstrated that LPC concentration dependently modulates mitochondrial microenvironment, with low micromolar concentrations of lysophosphatidylcholine sufficient to change hepatic oxidation rate whereas higher concentrations are required to disrupt mitochondrial integrity.
Ultrasensitive detection of scrapie prion protein using seeded conversion of recombinant prion protein.

The scrapie prion protein isoform, PrPSc, is a prion-associated marker that seeds the conformational conversion and polymerization of normal protease-sensitive prion protein (PrP-sen). This seeding activity allows ultrasensitive detection of PrPSc using cyclical sonicated amplification (PMCA) reactions and brain homogenate as a source of PrP-sen. Here we describe a much faster seeded polymerization method (rPrP-PMCA) which detects ≥50 ag of hamster PrPSc (≈0.003 lethal dose) within 2–3 d. This technique uses recombinant hamster PrP-sen, which, unlike brain-derived PrP-sen, can be easily concentrated, mutated and synthetically tagged. We generated protease-resistant recombinant PrP fibrils that differed from spontaneously initiated fibrils in their proteolytic susceptibility and by their infrared spectra. This assay could discriminate between scrapie-infected and uninfected hamsters using 2-μl aliquots of cerebral spinal fluid. This method should facilitate the development of rapid, ultrasensitive prion assays and diagnostic tests, in addition to aiding fundamental studies of structure and mechanism of PrPSc formation.