cssi/SciSciGPT-SciSciNet huggingface dataset:
Location of the heme in horse heart ferricytochrome c by x-ray diffraction.

Abstract A low resolution (4A) electron density map of horse heart cytochrome c crystals has been obtained by x-ray diffraction methods. The molecule is a prolate spheroid, approximately 25 x 25 x 37 A. It has a cleft or crevice along one side into which the heme is inserted, normal to the surface, with only one of the edges of the porphyrin ring exposed to solvent. The ligands occupying coordination positions 5 and 6 of the heme iron extend out from either side of the cleft. The thioether links binding the vinyl side chains of the heme to cysteinyl residues in positions 14 and 17 of the amino acid sequence are visible. One of the iron ligands can be identified from its shape and location as the imidazole side chain of the histidyl residue in position 18. The other is not an imidazole side chain and is probably located in the carboxyl-terminal half of the amino acid sequence. There is little or no α-helix present, the body of the molecule being an extended chain shell around a core of packed hydrophobic side chains.
Fragmentation of the silacyclohexane ring

Abstract The title reaction proceeds in dichloromethane with a pseudo-first-order rate constant of 1.19 x 10 − 3 sec − , 5000 times faster than the reaction of trityl fluoroborate with tetraethylsilane, yielding as products 4-pentenyldimethylfluorosilane, triphenylmethane, aand boron trifluoride. The enhanced reactivity of the title silane is attributable to σπ conjugation.
Effective Gain Measurements in Chromium-Doped Forsterite

Effective gain cross section in tetravalent chromium-doped forsterite laser crystal was measured over the 1180-1330 nm spectral range. The experiment was performed using two collinear laser beams in a pump-and-probe arrangement. The peak-gain cross section from this measurement is estimated to be 1.9 x 10 to the -19th sq cm at 1215 nm, which is comparable to the value of about 2 x 10 to the -19th sq cm predicted by fluorescence linewidth and lifetime measurements. These results indicate that excited-state absorption is not a major loss mechanism in tetravalent chromium-doped forsterite.
Beyond “A&OX3”: What Temporal and Spatial Orientation Questions Tell Clinicians about Cognitive Dysfunction in Alzheimer's Disease

Orientation to time and place is frequently assessed in conditions such as Alzheimer's disease (AD). Despite the ubiquitous nature of orientation screening in mental status examinations, relatively little is known about the psychometric properties of orientation subscales. This article seeks to provide detailed psychometric information about the orientation items on the Mini Mental State Examination (MMSE) in individuals with AD. Orientation responses from 1,238 patients with AD (mean age = 75.5 years, SD = 8.4, range = 39 to 94) were examined within an item response theory (IRT) framework. Responses revealed that orientation items on the MMSE functioned differently across the spectrum of cognitive ability, with spatial orientation items tapping the breadth of cognitive impairment better than temporal items, which tended to have overlapping properties. Key clinical implications such as choosing appropriate items for different clinical purposes are highlighted.
Knowledge-based direct 3-D texture segmentation system for confocal microscopic images

In this paper, we present a knowledge-based texture segmentation system for the identification of 3D structures in biomedical images. The segmentation is guided by in Iterative Octree Expansion and (leaf node) Linking control algorithm. The segmentation is performed directly in 3D space which is contrary to that done in common approaches where 3D structures are reconstructed from results of 2D segmentation of a sequence of consecutive, cross-sectional images. Test result of a prototype of this system on real data confocal scanning fluorescence microscopic images of a developing chick embryo heart is reported.© (1991) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Metabolism of 3H-l-dopa by the rat gut in vivo—evidence for glucuronide conjugation☆☆☆

Abstract The metabolism of intravenous 3 H- l -dopa by the rat gut in vivo has been studied. After a single i.v. bolus of a pharmacologic dose of l -dopa, the rat duodenum accumulated 3 H-noncatechol metabolites of dopa at a far greater rate than stomach, spleen or heart. 3 H-noncatechols were localized predominantly in the duodenal mucosa and not the muscularis. In the mucosa, 3 H-noncatechols accounted for 90 per cent of the total 3 H, most of which was in the amino acid noncatechol fraction after Chromatographic separation on Alumina and Dowex. Accumulation of noncatechol metabolites in duodenal mucosa was not dependent on the administration of a pharmacologic dose of dopa; after a tracer dose of 3 - l -dopa the per cent of 3 H-noncatechols in the amino acid fraction actually increased. The pattern of dopa metabolites in duodenal mucosa was substantially different from a variety of other tissues, but was similar to liver, jejunum and colon. Diversion of the bile by cannulation of the common bile duct prior to the administration of 3 H- l -dopa did not change the accumulation or pattern of metabolites in the duodenum. Analysis of the noncatechol amino acid fraction from duodenal mucosa by incubation with Glusulase and β-glucuronidase, thin-layer chromatography, and fluorescent assay revealed that the compounds accumulated by duodenal mucosa were largely glucuronide conjugates of catechols, particularly dopamine. It is concluded that circulating dopa is taken up by the rat intestinal mucosa, decarboxylated, conjugated and stored, largely in the form of glucuronide conjugates. The gut thus makes a major contribution to the over-all metabolism of circulating dopa. Dopa metabolites stored in the gut, moreover, are a potential reservoir of catechols for reutilization by the organism, and this may have important implications for the clinical pharmacology of l -dopa in man.
Regional ultrahigh-pressure coesite-bearing eclogitic terrane in central China: Evidence from country rocks, gneiss, marble, and metapelite

The Dabie Mountains represent a fault-bounded, coesite-bearing eclogite gneissic terrane within the collisional belt between the Sino-Korean and Yangtze cratons. The following geologic evidence indicates that this terrane has been subjected to regional ultrahigh-pressure metamorphism. (1) The country rocks have a metamorphic pressure-temperature evolution compatible with that of the eclogites, on the basis of the occurrence of quartz pseudomorphs after coesite, calcite pseudomorphs after aragonite, relict high-pressure assemblages in different rock types of the country rocks, and consistent, comparable compositional zonations of garnets in both country rocks and eclogites. (2) Peak metamorphic pressure-temperature conditions consistently decrease both from east to west in the collisional belt and from north to south in the Dabie Mountains, and clockwise pressure-temperature paths are common for eclogites over the region. (3) Layered eclogites interbedded with gneisses and amphibolites contain omphacite, kyanite, and garnet, indicating a minimum pressure of 20 kbar at 600 °C for formation of these rocks.
Contested Jurisdictions: Psychiatry, Psychoanalysis, and Clinical Psychology in the United States, 1940-2010

American psychiatry on the eve of Pearl Harbor was a small, stigmatised, and isolated specialty, for the most part confined as surely inside the high walls of its barrack-asylums as the patients over whom it exercised near-autocratic powers. The number of mentally ill patients incarcerated in state and county mental hospitals had grown sharply, from 150,000 at the turn of the century to 445,000 in 1940. The fiscal crisis of the states that accompanied the Great Depression had produced a steady deterioration of conditions in these institutions, a deterioration that would intensify as a result of the exigencies of total war. In the immediate aftermath of that prolonged conflict, conditions had degenerated to such a parlous state that a number of outside observers compared America’s asylums to Nazi death camps. 1 Yet the size of the psychiatric profession essentially doubled during the war years, from 2,295 to almost 5,000. More importantly, the intellectual centre of gravity of the profession shifted equally dramatically. Through the 1930s, the bulk of the profession had embraced biologically reductionist accounts of mental illness. Correspondingly, they had also engaged in an orgy of experimentation with somatic treatments for mental disorder: surgical evisceration in pursuit of hypothesised septic causes of mental illness; fever therapy, first for general paralysis of th ei nsane (or tertiary syphilis) and later for other forms of psychosis; efforts to put patients into prolonged comas, originally using barbiturates and subsequently using injections of insulin; convulsive therapies using metrazol or electricity; and direct surgical assaults on the frontal lobes of the brain. 2 Led by Brigadier-General William Menninger, who had
Increasing Understanding of Decision Making in Higher Education: the case of Taiwan

Abstract This paper seeks to explicate the processes of decision making in higher education in order to assist decision makers and stakeholders. The research examines the relationship between the locus of decision making and the mode of decision making in Taiwanese higher education and the relationship of decision making to specific policy areas. Based on a review of the literature and interviews with university presidents, other administrative officers, teaching staff, and Ministry of Education (MOE) officials, this study examined the extent to which both locus of decision making and mode of decision making are related to policy decisions relative to institutional mission, organisation, governance, admissions, finance, facilities and equipment, personnel, curriculum, and research. The data supported the conclusion that neither variable is sufficient explanation and that both the mode and the locus of decision making are linked to policy area.
Coping With an Embarrassment of Riches: How Stroke Centers May Participate in Multiple, Concurrent Clinical Stroke Trials

Background The recent remarkable proliferation of multicenter clinical trials investigating novel treatments for acute ischemic stroke has created a new dilemma for stroke investigators. Promising agents and trials are many, competent clinical centers few. May a single clinical center, without scientific bias, participate in multiple, concurrent clinical trials recruiting overlapping populations of subjects with acute stroke? Summary of Comment Many clinical stroke centers already participate in multiple overlapping trials. I delineate a variety of patient-allotment strategies that are presently used, although often not explicitly stated. Methods include assignment by time window, unique criteria, site, belief in agent efficacy, remuneration, and quota urgency. All have drawbacks, chiefly the introduction of bias into the selection of subjects for clinical trials, compromising the generalizability of trial findings to broader clinical populations. Several solutions are proposed that permit single centers ...
A circular dichroism study of human erythrocyte ghost proteins during exposure to 2450 MHz microwave radiation.

The effect of 2450 MHz microwave radiation on the proteins of human erythrocyte ghosts has been investigated using circular dichroism spectroscopy. A specially constructed waveguide inserted into the spectropolarimeter allowed the continuous recording of optical activity before, during and after microwave irradiation. The data indicate that high levels of microwave radiation (600 mW/g, specific absorption rate) induce decreases in α-helical conformation that may result from both thermal vibrations and increased strain on the intramolecular hydrogen bonds that maintain secondary structure. The latter effect may result from differential intramolecular interactions with the oscillating electric field. Spectrin (bands 1 and 2) isolated from the ghosts was more sensitive to microwave irradiation than intact ghosts, and spectrin-depleted vesicles were the least sensitive. The data, therefore, indicate that the α-helical conformation of spectrin is altered by high levels of microwave radiation.
The effect of sildenafil citrate on bladder outlet obstruction: a mouse model

OBJECTIVE To investigate if sildenafil citrate can inhibit the functional and structural changes of the detrusor in a murine model of bladder outlet obstruction (BOO). Phosphodiesterase type 5 (PDE-5) inhibitors have recently been used for treating urinary symptoms associated with prostatic obstruction, but it is unclear whether PDE-5 inhibition acts on the prostatic urethra or the bladder. MATERIALS AND METHODS In 18 male Balb/CAN mice, partial BOO was created and the mice allowed to survive for 6 weeks. Half of the mice (nine) were treated with oral sildenafil citrate daily (10 mg/kg) by oral lavage (BOO + V), and half (nine) were not (BOO). Six mice were used as sham-operated controls and received no sildenafil. The mice were assessed by urodynamics at baseline and after 6 weeks, with a measurement of volume at first uninhibited non-voiding contraction (VDO1), bladder capacity (BC), and detrusor pressure during void (Pdet). At 6 weeks, bladders were harvested, fixed and sectioned, and stained with haematoxylin and eosin (HE the results were compared with those from normal controls. RESULTS BOO mice had a significantly greater BC than control mice, with a mean (sd) of 153 (66) vs 58 (13) µL (P = 0.004). Treatment with sildenafil did not significantly alter BC. BOO caused an increase in Pdet compared to controls, with a mean (sd) of 25 (7) vs 12 (5) cm H2O. Pdet was not significantly different after treatment with sildenafil. The median VDO1 as a percentage of BC was significantly lower in BOO than in control mice (20% vs 53%, P > 0.03) and increased significantly after sildenafil treatment (20% vs 44%, P = 0.04). BOO was associated with a greater bladder weight than in control mice, with a mean (sd) of 89 (32) vs 27 (6) mg (P = 0.001), which was decreased with sildenafil treatment, to 40 (14) vs 89 (32) mg (P = 0.013). BOO caused an increase in detrusor muscular hypertrophy vs control mice, with a median H&E score of 3 vs 2 (P = 0.01) and an increase in fibrosis vs control mice, with a median trichrome score of 3 vs 2 (P = 0.01). BOO + V mice had reduced muscular hypertrophy and fibrosis, with a median H&E score of 3 vs 2 (P = 0.01) and a median trichrome score of 3 vs 1 (P = 0.01). CONCLUSIONS BOO mediates both functional and structural changes in the mouse bladder. Six weeks of obstruction caused an increase in BC, detrusor overactivity and voiding pressure, and mediated an increase in bladder weight, detrusor muscle hypertrophy and collagen deposition in the lamina propria and smooth muscle. Treatment with 6 weeks of oral sildenafil beginning at the time of BOO prevented the increase in detrusor overactivity without affecting voiding pressures, and prevented the increase in detrusor muscle hypertrophy and collagen deposition that otherwise occurred with BOO. It appears therefore that sildenafil citrate acts on the bladder rather than on the outlet.
The structures of free-base carbahemiporphyrazines

In this report we present an X-ray crystallographic study of two N-deficient hemiporphyrazines: dicarbahemiporphyrazine (1) and benziphthalocyanine (2). Both compounds can be isolated in multiple crystal forms, and five different solvated forms of macrocycle 1 are presented. Four of the five are non-planar, showing the high degree of flexibility and capacity for hydrogen bonding from solvent to N-H groups in the macrocycle. The remaining structure of 1 is a planar dicationic species that represents a tautomeric form of the macrocycle often seen in metal binding. Four structures of macrocycle 2 are also presented in this report. The structure of 2 is also planar due to the tautomerism of the internal protons, and structural elucidation of this macrocycle reveals the presence of three ionizable protons rather than the expected single proton postulated by Elvidge and Golden.
Morphological structures produced by mixing in chaotic flows

Fluid mixing is poorly understood. However, some of the main concepts can be captured by both computational and experimental studies of two-dimensional flows. The identification of coherent structures and how they change with variations of the governing parameters gives insight into the behaviour of chaotic systems and can serve as a model for a variety of problems found in nature.
Changes in regional ventilation after autologous blood clot pulmonary embolism.

BackgroundPrevious studies have suggested that pulmonary embolism (PE) and pulmonary artery occlusion result in a shift in alveolar ventilation away from unperfused regions. This study aimed to directly assess changes in regional specific ventilation (sVA) due to autologous blood clot PE using posi
Effect of guided resonance modes on emission from GaN core–shell nanorod arrays

We model the process of incoherent emission from $$\hbox {In}_{x}\hbox {Ga}_{1-x}\hbox {N/GaN}$$ quantum wells in GaN core–shell nanorod arrays using finite-difference time-domain simulations. We find that high-intensity features in the emitted field correspond to guided resonance modes near the $$\varGamma $$ -point of the photonic band structure. We identify one $$\varGamma $$ -point mode whose electric field intensity profile is ideal for core–shell nanorod array geometries. Using this mode, we are able to simultaneously enhance the radiative recombination rate and extraction efficiency relative to an in-filled slab. We determine the conditions on radiative and nonradiative recombination rates for which the nanorod array has a higher internal and external quantum efficiency than a reference slab. We present one nanorod array geometry where the external quantum efficiency is enhanced up to a factor of 25.
Hard turning of M50 steel with different microstructures in continuous and intermittent cutting

Abstract Different types of M50 steel (63 HRc) have been hard turned using cubic boron nitride (CBN) tools to experimentally investigate microstructual effects on both continuous and intermittent cutting. In continuous cutting, powder metallurgy (PM) M50 results in substantially lower tool wear and wear rate than conventional M50, presumably due to refined carbides that may delay delamination wear. In intermittent cutting, fine microstructures of PM steel also lead to reduced wear rate, however, not as drastically as in continuous cutting. In intermittent cutting, the bulk impact loading may be dominant in tool wear and attrition wear affected by carbide sizes becomes less significant. Nevertheless, fine carbides in PM steel seem to alleviate delamination wear on tool flank, which limits tool life at lower speed in intermittent cutting of conventional M50. Furthermore, low CBN content tools consistently outperform high CBN content tools in PM M50 intermittent cutting, contradictory to the results in intermittent cutting of conventional counterparts. This study provides guidelines on tool and work material selections in machining of hardened steel components. For continuous hard turning, PM steel may induce substantially lower tool wear, and thus, have much better machinability. In intermittent cutting, PM steel still offers reduced tool wear, however, less effectively.
Basal nitric oxide limits immune, nervous and cardiovascular excitation: human endothelia express a mu opiate receptor

Nitric oxide (NO) is a major signaling molecule in the immune, cardiovascular and nervous systems. The synthesizing enzyme, nitric oxide synthase (NOS) occurs in three forms: endothelial (e), neuronal (n) and inducible (i) NOS. The first two are constitutively expressed. We surmise that in many tissues there is a basal level of NO and that the actions of several signaling molecules initiate increases in cNOS-derived NO to enhance momentary basal levels that exerts inhibitory cellular actions, via cellular conformational changes. It is our contention that much of the literature concerning the actions of NO really deal with i-NOS-derived NO. We make the case that cNOS is responsible for a basal or 'tonal' level of NO; that this NO keeps particular types of cells in a state of inhibition and that activation of these cells occurs through disinhibition. Furthermore, naturally occurring signaling molecules such as morphine, anandamide, interleukin-10 and 17-beta-estradiol appear to exert, in part, their beneficial physiological actions, i.e., immune and endothelial down regulation by the stimulation of cNOS. In regard to opiates, we demonstrate the presence of a human endothelial mu opiate receptor by RT-PCR and sequence determination, further substantiating the role of opiates in vascular coupling to NO release. Taken together, cNOS derived NO enhances basal NO actions, i.e., cellular activation state, and these actions are further enhanced by iNOS derived NO.
The clinical development of MEK inhibitors

Aberrant activation of the RAS-RAF-MEK-ERK1/2 pathway occurs in more than 30% of human cancers. As part of this pathway, MEK1 and MEK2 have crucial roles in tumorigenesis, cell proliferation and inhibition of apoptosis and, therefore, MEK1/2 inhibition is an attractive therapeutic strategy in a number of cancers. Highly selective and potent non-ATP-competitive allosteric MEK1/2 inhibitors have been developed and assessed in numerous clinical studies over the past decade. These agents are not efficacious in a broad range of unselected cancers, although single-agent antitumour activity has been detected mainly in tumours that harbour mutations in genes encoding the members of the RAS and RAF protein families, such as certain melanomas. Combinations of MEK1/2 inhibitors and cytotoxic chemotherapy, and/or other targeted agents are being studied to expand the efficacy of this class of agents. Identifying predictive biomarkers, and delineating de novo and acquired resistance mechanisms are essential for the future clinical development of MEK inhibitors. We discuss the clinical experience with MEK inhibitors to date, and consider the novel approaches to MEK-inhibitor therapy that might improve outcomes and lead to the wider use of such treatments.
Gender Differences in Perception of Attractiveness of Men and Women in Bars

The idea that men and women appear more attractive as the closing time of a bar approaches is suggested by both popular folklore and social science research. In an empirical test of this hypothesis, male and female subjects at a college bar were asked to rate the attractiveness of same -and opposite-gender bar patrons at three times (9:00 PM., 10:30(PM., and 12:00 A.M.) throughout an evening and to record type and amount of alcohol consumed. In addition, subjects rated six opposite-gender photographs that had been previously determined to represent a broad range of facial attractiveness. Ratings of opposite-gender patrons increased over time for both men and women (although female patrons received higher attractiveness ratings than male patrons), but no support was found for the hypothesis that increased ratings were due to alcohol consumption. Further, men rated photographic images of attractive women to be even more attractive as the evening progressed, while scores for less attractive female photograph...
Hybrid Models Identified a 12-Gene Signature for Lung Cancer Prognosis and Chemoresponse Prediction

Background: Lung cancer remains the leading cause of cancer-related deaths worldwide. The recurrence rate ranges from 35-50% among early stage non-small cell lung cancer patients. To date, there is no fully-validated and clinically applied prognostic gene signature for personalized treatment. Methodology/Principal Findings: From genome-wide mRNA expression profiles generated on 256 lung adenocarcinoma patients, a 12-gene signature was identified using combinatorial gene selection methods, and a risk score algorithm was developed with Naive Bayes. The 12-gene model generates significant patient stratification in the training cohort HLM & UM (n = 256; log-rank P = 6.96e-7) and two independent validation sets, MSK (n = 104; log-rank P = 9.88e-4) and DFCI (n = 82; log- rank P = 2.57e-4), using Kaplan-Meier analyses. This gene signature also stratifies stage I and IB lung adenocarcinoma patients into two distinct survival groups (log-rank P,0.04). The 12-gene risk score is more significant (hazard ratio = 4.19, 95% CI: (2.08, 8.46)) than other commonly used clinical factors except tumor stage (III vs. I) in multivariate Cox analyses. The 12-gene model is more accurate than previously published lung cancer gene signatures on the same datasets. Furthermore, this signature accurately predicts chemoresistance/chemosensitivity to Cisplatin, Carboplatin, Paclitaxel, Etoposide, Erlotinib, and Gefitinib in NCI-60 cancer cell lines (P,0.017). The identified 12 genes exhibit curated interactions with major lung cancer signaling hallmarks in functional pathway analysis. The expression patterns of the signature genes have been confirmed in RT-PCR analyses of independent tumor samples. Conclusions/Significance: The results demonstrate the clinical utility of the identified gene signature in prognostic categorization. With this 12-gene risk score algorithm, early stage patients at high risk for tumor recurrence could be identified for adjuvant chemotherapy; whereas stage I and II patients at low risk could be spared the toxic side effects of chemotherapeutic drugs.
The accommodative lag of the young hyperopic patient.

Purpose. To determine the accommodative accuracy of infants and young children before they had had any form of clinical intervention or treatment, in an attempt to determine the difference between ‘normal’ and ‘abnormal’ visual experience for these individuals.
Stationary dual prices and depreciation

This paper models a machine replacement and capacity expansion problem as an infinite-horizon linear program. We establish a strong duality result and show that stationary dual prices are optimal, regardless of initial conditions. These prices measure the economic value of owning vintage machinery and thus define depreciation schedules. We present necessary and sufficient conditions for straight-line depreciation.
Neurokinin-1 Receptor Antagonist (Aprepitant) Inhibits Drug-Resistant HIV-1 Infection of Macrophages in vitro

Despite the success of antiretroviral therapy in controlling HIV replication, treatment failure may ultimately occur in more than 50% of the individuals on antiretroviral therapy. Cellular targets offer an attractive alternative, as it may be more difficult for HIV to develop resistance to alternative cellular inhibitory pathways. We have previously shown that CP-96,345, a neurokinin-1 receptor (NK-1R) antagonist, inhibits HIV-1 infection of macrophages in vitro by downregulating CCR5 expression (Lai JP, Ho WZ, Zhan GX, Yi Y, Collman RG, Douglas SD 2001). We have now investigated the effects of a Food and Drug Administration (FDA)-approved NK-1R antagonist, aprepitant (Emend®), on HIV infection of macrophages in an in vitro system. Aprepitant is in clinical use for the prevention of nausea and vomiting associated with cancer chemotherapy or following surgical procedures. Monocytes isolated from healthy donors were cultured for 7 days and then treated with or without aprepitant (10−6 M) for 2 h, followed by HIV infection with drug-resistant strains for 2 h. Untreated and HIV-infected macrophages were used as controls. Culture supernatants were harvested for p24 enzyme-linked immunosorbent assay (ELISA) or HIV reverse transcriptase (RT) activity at different time points after infection. R5X4 tropic and AZT-resistant strains (R5X4 tropic: A012 and A018) and RT inhibitor-resistant HIV strains (R5 tropic: TC60 and TC49) were used for infection. Aprepitant suppressed HIV Bal infection of macrophages. Treatment with aprepitant (10−6 M) inhibited infection of macrophages with the AZT-resistant viruses (A018, A012) by 0.7 log10. Aprepitant also suppressed infection of macrophages with RT inhibitor-resistant virus (TC 49 and TC 60) by 0.5 log10. Furthermore, aprepitant significantly enhanced the anti-HIV activity of antiretrovirals (AZT, Efavirenz, and Indinavir) in HIV Bal-infected macrophages, and aprepitant inhibited CCR5 expression on macrophages, ranging from 50.5 to 29.6%. Donor heterogeneity was observed in antiviral activity and CCR5 receptor expression. Aprepitant is active against HIV drug-resistant isolates and enhances the anti-HIV activity of the antiretrovirals. Aprepitant downregulates CCR5 expression on macrophages. NK-1R antagonists merit further investigation as potential HIV therapeutic and immunomodulatory agents.
Acridine-N peptide conjugates display enhanced affinity and specificity for boxB RNA targets.

Arginine-rich peptides and small-molecule intercalating agents utilize distinct molecular mechanisms for RNA recognition. Here, we combined these distinct binding modules in an effort to create conjugate ligands with enhanced affinity and specificity using the bacteriophage λ N peptide−boxB interaction as a model system. We first designed and synthesized a series of peptide−acridine conjugates using portions of the RNA-binding domain of N protein (11- and 22- residue peptide segments) and then compared the binding affinity, specificity, salt dependence, and structural properties of the RNA−peptide and RNA−peptide−acridine conjugate complexes using steady-state fluorescence, CD spectroscopy, NMR, and native gel mobility shift assays (GMSAs). These analyses revealed that the full-length peptide−acridine conjugate displayed substantially improved RNA binding affinity (~80-fold; K_d 15 pM) relative to that of the peptide alone (K_d ~ 1.2 nM). In accordance, we also observed specificity enhancement (~25-fold) as determined via comparison of the binding of the best conjugate to a cognate λ boxB RNA with that to a noncognate P22 RNA hairpin (80-fold vs 3.2-fold enhancement). Furthermore, the observed binding enhancement was unique to the full-length conjugate with a flexible linker, implying that the structural context of the acridine presentation was critical. Taken together, our observations support the idea that peptide- and intercalation-based binding can be combined to create a new class of high-affinity, high-specificity RNA-binding ligands.
Cerebral Abnormalities in Myotonic Dystrophy: Cerebral Blood Flow, Magnetic Resonance Imaging, and Neuropsychological Tests

• Objective. —To study cerebral abnormalities in myotonic dystrophy (MD) and determine the different patterns of cerebral function in patients with MD with maternal (mMD) vs paternal (pMD) inheritance. Design. —Patients with MD and normal controls were studied with neuropsychological testing, magnetic resonance imaging, and single photon emission computed tomography. Setting. —Studies were done at Harbor-UCLA Medical Center, Torrance, Calif. Patients and Other Participants. —Twenty-two consecutive patients with MD, 11 of whom had pMD and eight mMD, and 10 normal controls were studied. Diagnoses were made on the basis of family history, electromyography, and clinical examinations. Normal subjects in the same age distribution were studied for comparisons. Results. —We found significantly lower neuropsychological performance and cerebral blood flow in the patients with MD compared with the controls. Patients with mMD had statistically lower scores on IQ tests and more extensive cerebral hypoperfusion when compared with those with pMD. Changes in cerebral blood flow were most severe in the frontal and temporoparietal association cortex. Cerebral blood blow measures strongly correlated with IQ. Conclusions. —Patients with mMD had earlier onset of disease and lower IQs than the pMD group. The pattern of cerebral perfusion in the mMD group was consistent with a diffuse brain injury, while cerebral perfusion in pMD showed more minor changes. These findings emphasize the cognitive differences between mMD and pMD.
The solar system beyond Mars: An exobiological survey

Exobiological survey of solar system beyond Mars, considering asteroids, Jovian planets and moons, Pluto and comets
Neck flexion and extension in children with Down syndrome : a somatosensory study

The cervical spine in Down syndrome patients is often lax, at least at radiographic imaging, and the risk of spinal cord embarrassment is increased. This study was performed to obtain information that would help identify patients at risk for this problem and reduce the risk of endotracheal intubation and other surgical procedures in patients with Down syndrome. Somatosensory evoked potential studies were performed in 15 consecutive children who were undergoing elective otolaryngic surgery. None had neurologic symptoms or the physical examination finding of cervical spinal cord embarrassment, and their cervical spines were considered normal by plain radiographs obtained in the neutral, flexed, and extended positions. No significant change in latency (P = .16) or amplitude (P = .19) was found when the anesthetized children had their necks placed in either full flexion or full extension. With more than 90% certainty, the authors believe that children with Down syndrome who have "normal" plain cervical spine radiographs are exposed to no extra risks from neck flexion or extension during surgery.
Freud’s dream of the double

While the motif of the double serves a prominent role in Freud’s writings from early on, this essay is an examination of the determinative power of the double in two key texts, texts in which specific, new sets doubles emerge for the first time in Freud’s career. Totem and Taboo features a double that manifests itself primarily in the form of ambivalence. Beyond the Pleasure Principle features a double that manifests itself primarily in the form of a very peculiar conflict that also entails complicity.
NETWORK STRUCTURE AND INNOVATION AMBIGUITY EFFECTS ON DIFFUSION IN DYNAMIC ORGANIZATIONAL FIELDS

Computational modeling simulated innovation diffusion through six prototypical interregional network structures and two distributions of partnering tendencies in dynamic organizational fields. Comp...
Cost-effectiveness modeling for a decision support system in computer security

The increasing number of corporate computer failures and crimes has forced managers to tighten controls of their Electronic Data Processing systems. However, the costs of an exhaustive program of controls are often inordinately expensive, and the effectiveness of such an operation is not necessarily guaranteed. Assuming that managers have limited time and capital resources, a comprehensive and formalized methodology is considered essential to assess vulnerability of computer systems, determine acceptable levels of potential losses, and identify cost-effective control strategies. This paper presents a Cost-Effectiveness Model (CEM) that determines an optimal program for control of EDP systems. The Cost-Effectiveness Model has been implemented in Pascal as a microcomputer-based Decision Support System (DSS). The CEM-DSS is geared to help the EDP manager: (i) identify alternative sets of control activities, (ii) evaluate and choose the most preferred set, and (iii) monitor and upgrade the security of EDP systems frequently.
Effects of chronic total sleep deprivation on central noradrenergic receptors in rat brain

The effect of chronic total sleep deprivation (TSD) on the regulation of central noradrenergic receptors was evaluated. Rats were subjected to 10 days of TSD by the disk-over-water method. As in previous TSD studies, these rats showed greater increases in food intake and energy expenditure and greater eventual declines in waking body temperature than their yoked-control (TSC) rats. After sacrifice, alpha 1-, alpha 2-, and beta-adrenoceptors were determined in 11 brain regions using radioligand binding assays with [3H]prazosin, [3H]rauwolscine, and 125I-iodocyanopindolol, respectively. Adrenoceptor density and affinity values were significantly different among TSD, TSC, and normally caged control rat groups only for the cerebellum, which showed higher alpha 2-binding density concomitant with lower affinity and lower beta-binding density than cage control rats. Such changes are attributable to apparatus or stimulus effects common to TSD and TSC rats. Given the absence of firm evidence for a TSD-induced downregulation of central noradrenergic receptors, the present results offer no support for the hypothesis of Siegel and Rogawski that a major function of paradoxical sleep is to upregulate these receptors.
Larval Responses of Three Midwestern Anurans to Chronic, Low-Dose Exposures of Four Herbicides

Low levels of agricultural herbicides often contaminate surface water and might persist throughout the growing season, potentially acting as stressors on aquatic organisms. Although low-dose, chronic exposures to agrochemicals are likely common for many nontarget organisms, studies addressing these effects using end-use herbicide formulations are rare. We exposed three common species of tadpoles to conservative levels of atrazine, S-metolachlor, and glyphosate end-use herbicide formulations throughout the larval period to test for survival differences or life-history trait alterations. Exposure to the glyphosate product Roundup WeatherMax® at 572 ppb glyphosate acid equivalents (a.e.) resulted in 80% mortality of western chorus frog tadpoles, likely as a result of a unique surfactant formulation. Exposure to WeatherMax® or Roundup Original Max® at 572 ppb a.e. also lengthened the larval period for American toads. Chronic atrazine and S-metolachlor exposures induced no significant negative effects on survival, mass at metamorphosis, or larval period length at the levels tested. These results highlight the importance of explicitly tying chronic tests to the natural environment and considering contributions of surfactant/adjuvant components to end-use formulation toxicities, even between very similar products.
The Concept of Irreversibility in Heat Exchanger Design: Counterflow Heat Exchangers for Gas-to-Gas Applications

The thermal design of counterflow heat exchangers for gas-to-gas applications is based on the thermodynamic irreversibility rate or useful power no longer available as a result of heat exchanger frictional pressure drops and stream-to-stream temperature differences. The irreversibility (entropy production) concept establishes a direct relationship between the heat exchanger design parameters and the useful power wasted due to heat exchanger nonideality. The paper presents a heat exchanger design method for fixed or for minimum irreversibility (number of entropy generation units N/sub s/). In contrast with traditional design procedures, the amount of heat transferred between streams and the pumping power for each side become outputs of the N/sub s/ design approach. To illustrate the use of this method, the paper develops the design of regenerative heat exchangers with minimum heat transfer surface and with fixed irreversibility N/sub s/.
Isospectral deformations I: Riemannian structures on two‐step nilspaces

On montre comment construire des exemples de deformations isospectrales de metriques de Riemann sur des varietes sur lesquelles des recouvrements de certains groupes de Lie nilpotents agissent
In situ colorimetric and composite coloration efficiency measurements for electrochromic Prussian blue

An in situ colorimetric method, based on the CIE (Commission Internationale de l'Eclairage) system of colorimetry, has been successfully applied to the study of electrochromism in electrochemically deposited films of Prussian blue (iron(III) hexacyanoferrate(II), PB) on transmissive ITO/glass substrates for the first time. On electrochemical reduction of PB to Prussian white (iron(II) hexacyanoferrate(II), PW), sharp and reversible changes in the hue and saturation occur, as shown by the track of the CIE 1931 xy chromaticity coordinates. For PB, the CIELAB 1976 colour space coordinates were L* = 73, a* = −26 and b* = −33, with a dominant wavelength calculated as 488 nm. Concurrently, as the intensely absorbing PB mixed-valence chromophore is ‘bleached’ to the transparent PW, a large increase in the relative luminance of the electrochromic film is observed. On oxidation of PB, the CIELAB 1976 colour space coordinates show the transition through intermediate green to the Prussian yellow (iron(III) hexacyanoferrate(III), PY) state (L* = 94, a* = 2 and b* = 18), with a steady increase in relative luminance. To reliably compare the power requirement of PB films with other electrochromic systems, composite coloration efficiencies (CCE's) have been calculated, using a tandem chronoabsorptometry/chronocoulometry method, as previously developed for organic polymer systems. Using 95% of the total transmittance change at λmax as reference point, coloration efficiencies, η = ΔA(λmax)/Q, were calculated as 143 and 150 cm2 C−1 respectively for the PB/PW and PW/PB electrochromic transitions.
Truth, correspondence, and success

L'A. etudie l'argument du succes developpe par H. Field en faveur de la theorie de la verite-correspondance, contre ses opposants deflationnistes: il s'agit de demontrer que le role de la notion de verite dans l'explication des comportements de reussite ne peut se faire que dans le cadre d'une theorie de la correspondance
Microstructure development in drying latex coatings

Abstract The technical details of high-resolution cryo-scanning electron microscopy (cryo-SEM) in studying latex formation are presented. This technique was used to visualize the microstructure development during drying of monodisperse and bimodal latex coatings. The glass transition temperature of the monodisperse latexes ranged from 100 to −11 °C. The film formation process of these latexes, after they were coated onto silicon substrates, was followed. The micrographs showed particle ordering, formation of consolidation fronts, air invasion during drying, particles deformation, film coalescence and skinning phenomena, illuminating important physics that govern the drying process of latex coatings. The bimodal systems consisted of latex blends of large, hard and small, soft particles. Cryo-SEM revealed how porous, permeable structures were created by drying these latex blends. The porous structures were modulated by drying rate, the volume ratio and size ratio of the two kinds of particles. Binder migration phenomenon was observed at higher drying rate. In addition to microstructure investigation, permeability and strength in tension of the porous films were separately measured, illustrating the basic trade-off between integrity and strength on one hand, porosity and permeability on the other.
Axillary Cannulation for Proximal Aortic Surgery is as Safe in the Emergent Setting as in Elective Cases

Background Right axillary artery cannulation and selective antegrade cerebral perfusion (SCP) have become well-described strategies in the surgical treatment of proximal aortic disease. Many series report increases in adverse outcomes with SCP used in emergent settings. We compare outcomes in elective and emergent patients. Methods Over 21 months, SCP through right axillary cannulation with a side graft was performed in 61 patients. Thirty-three percent (20 of 61) underwent emergent operation for Stanford type A dissection or intramural hematoma, including 3 of 20 (4.7%) with pericardial tamponade; the remainder of SCP (41 of 61) was elective. The mean follow-up was 9.1 ± 0.40 months. Results Selective antegrade cerebral perfusion was used in 20 of 22 emergent cases (91%), with 2 unsuccessful cannulation attempts, and no peripheral arterial dissections encountered. The SCP flows averaged 16.3 ± 0.71 cc · kg −1 · min −1 for a mean perfusion period of 26.1 ± 1.9 minutes. The average cardiopulmonary bypass time for all patients was 173 ± 11 minutes. Average hospital stay was 8.1 ± 0.80 days. One case (1.3%) of permanent and 3 cases (4.8%) of temporary neurologic dysfunction occurred in SCP patients. The hospital mortality rate for emergent SCP cases (2 of 20, 10%) was not statistically different from the mortality rate for elective SCP cases (3 of 41, 7.3%, p = not significant), with no difference in complication rates. All 3 SCP patients with preoperative tamponade survived without complication. Cerebral oximetry data showed a trend toward decreased left-sided (contralateral) scalp perfusion. There was no association of emergent status with neurologic dysfunction, death, or any other adverse outcome. Conclusions Axillary cannulation and SCP in the surgical treatment of proximal aortic pathology is safe in both elective and emergent settings.
Vehicle-road interaction, evolution of road profiles and present serviceability index

ABSTRACT Starting with a 2-dimensinonal model for a road structure, we derive the expressions for the dynamic strain, stress, and displacement in the road structure by considering together pavement material properties, truck dynamic characteristics, and road surface profile characteristics in a unified framework. The change of the road surface profile is then predicted according the number of cumulative truckloads exerted on top of the road surface using three coupled difference equations. The evolution of surface profiles can be applied to predict the present serviceability index of roads, one of the most important indices for road design, rehabilitation and maintenance. The model can be further applied to assess the effect of axle loads applied by acceleration testing facilities. Moreover, the AC concrete material characteristics can be fed into the model for simulating its field performance.
Substitutional Nitrogen in Nanodiamond and Bucky-Diamond Particles

The inclusion of dopants (such as nitrogen) in diamond nanoparticles is expected to be important for use in future nanodevices, such as qubits for quantum computing. Although most commercial diamond nanoparticles contain a small fraction of nitrogen, it is still unclear whether it is located within the core or at the surface of the nanoparticle. Presented here are density functional tight binding simulations examining the configuration, potential energy surface, and electronic charge of substitutional nitrogen in nanodiamond and bucky-diamond particles. The results predict that nitrogen is likely to be positioned at the surface of both hydrogenated nanodiamond and (dehydrogenated) bucky-diamond, and that the coordination of the dopants within the particles is dependent upon the surface structure.