cssi/SciSciGPT-SciSciNet huggingface dataset:
Manganese: Uptake, Biological Function, and Role in Virulence

Recent data have demonstrated that bacterial homologs of eukaryotic Nramp transporters as well as members of the LraI family of proteins are both highly selective Mn2+ transporters. Mutation of these transporters in several pathogenic bacterial species causes decreased virulence in a variety of model systems. This implies that the Mn2+ ions are required for one or more processes essential for bacterial virulence. However, Mn2+ has few known enzymatic roles compared to other divalent cations. This review will describe what is currently known about the two classes of prokaryotic Mn2+ transporters, how each is regulated and the virulence deficits that arise when they are mutated. Finally, possible enzymatic roles for Mn2+ will be outlined, and their potential for a role in virulence discussed.
Cognitive-Affective Correlates of Suicide Ideation and Attempt: Mindfulness is Negatively Associated with Suicide Attempt History but not State Suicidality.

The objective of this study was to test whether 3 cognitive-affective correlates,--mindfulness, emotion reactivity, and depressive symptom severity—have different associations with current suicidal ideation (SI), a history of suicide attempt (SA) and SA + SI among emerging adults. Whether impulsive-aggression (IA) moderated associations between cognitive-affective correlates of suicidal behavior and suicidality was also tested. Survey data on current SI, SA history, mindfulness, emotion reactivity, depressive symptom severity, and IA were collected from 780 emerging adults. Results from multinomial logistic regression analysis showed greater depressive symptom severity among emerging adults with current SI, regardless of SA history. Those with a history of SA reported greater depressive symptom severity and less mindfulness than controls. IA did not moderate relationships of SI and/or SA and mindfulness, emotion reactivity, or depressive symptom severity. Mindfulness is a marker of SA, and depressive symp...
Valve of Guerin as a Cause of Dysuria and Hematuria in Young Boys: Presentation and Difficulties in Diagnosis

AbstractA valve of Guerin, or lacuna magna, is a common anatomical finding in young boys. It occasionally causes dysuria and/or bloody urethral discharge or spotting due to its location distal to the external urethral sphincter. We report on 10 patients who underwent transmeatal marsupialization of a valve of Guerin between 1984 and 1991, and review the embryology and clinical presentation. Despite evidence suggesting that a valve of Guerin is a frequent, normal anatomical variant, the incidence of clinical detection is extremely low. While many patients with this condition remain totally asymptomatic, a valve of Guerin should be suspected in boys presenting with bleeding distal to the urethral sphincter with or without voiding symptoms. In most cases physical examination is normal. A carefully performed voiding cystourethrogram visualizing the distal urethra, coupled with endoscopic examination and gentle probing of the fossa navicularis, optimizes the likelihood of correct diagnosis. Treatment is indica...
Wind Speed and Stress Over the Ocean: Scatterometer versus Surface Measurements

Once routine, global wind measurements of known accuracy become available from satellites, both oceanography and meteorology will be relieved of a great observational burden. The SEASAT experience demonstrated that its scatterometer system, SASS, could do the job, but the following problems still exist: i) The derivation of wind speed or stress requires a purely empirical algorithm. ii) There is evidence of systematic biases in the SASS winds. iii) The SASS algorithm is based on mid-latitude surface measurements during summer. iv) Differences in SASS and surface winds are sometimes attributed to spatial versus time averaging. v) It seems likely that backscatter depends on more parameters than have been considered in retrieval algorithms.
ZAS Zinc Finger Proteins: The Other κB-Binding Protein Family

The ZAS gene family includes ZAS1, ZAS2, and ZAS3 in mammals as well as Schnurri in Drosophila melanogaster. The ZAS genes encode large proteins with two separate C2H2 zinc finger pairs that independently bind to specific DNA sequences, including the κB motif. In vitro experiments have shown that ZAS proteins bind to target sequences and regulate transcription of a variety of genes involved in cell growth, development, and metastasis. ZAS proteins also function in signal transduction: Schnurri interacts with Smad homologs in TGF-β-related pathways and ZAS3 interacts with TNF receptor-associated factors in TNF-α pathways. In vivo experiments have shown that disruption of ZAS expression alters normal cell growth as well as proliferation and results in spontaneous tumor formation and impaired lymphocyte development.
Docking studies of tetra substituted pyrazolone derivatives as potential antiviral agents

In an attempt to find potential antiviral agents, a series of pyrazolones ( PA1 - PA6 & PC1 - PC6 ) were designed and evaluated for their DENVNS5 (RNA-dependent RNA polymerase) inhibitory activity. Molecular docking studies of all the designed compounds into the binding site of DENVNS5 (PDB Code: 4C11) were performed to gain a comprehensive understanding into rational binding modes. These compounds were also screened for in silico drug-likeliness properties on the basis of the absorption, distribution, metabolism and excretion (ADME) prediction. Among all the synthesized compounds, analogue PA6 showed superior inhibitory activity against RNA dependent RNA polymerase. SAR study indicated that the presence of an electron withdrawing substitution on pyrazolone derivatives significantly improves its binding interaction with the protein.Results of ADME prediction revealed that most of these compounds showed in silico drug-likeliness.
Split otoferlins reunited.

Gene therapy for genetic hearing loss is a nascent field with just a handful of studies published to date that demonstrate proof‐of‐concept recovery of auditory function (reviewed in Ahmed et al , 2017; Lustig & Akil, 2018). One challenge that faces the inner ear field, as well as the broader gene therapy field, is the need to deliver large gene sequences despite the limited genetic capacity (~4.5 kB) of delivery vehicles such as adeno‐associated viral vectors (AAV). In this issue, Al‐Moyed et al have overcome this conundrum by using two AAV vectors to deliver the coding sequence for otoferlin, which is ~6 kB. With dual‐AAV delivery of split otoferlin and a trans‐splicing approach, they demonstrate recombination of full‐length otoferlin in sensory hair cells of the inner ear, enabling partial restoration of auditory function in deaf, otoferlin‐null mice.
Abstract TP270: When Telestroke Programs Work, Bed Size Really Doesn’t Matter

Background: Telestroke rural networks are comprised of micro>small>medium>large sized hospitals without specialized neurology support. Many times the micro hospitals are <25 beds. In an examination...
Etched in Bone

An eight-year endeavour by Martin Thomas and Beatrice Bijon, Etched in Bone is a thoughtful and intimate exploration of the repatriation of human remains from the Smithsonian back to the Aboriginal...
Gardening as More than Urban Agriculture: Perspectives from Smaller Midwestern Cities on Urban Gardening Policies and Practices

For the most part, research and policymaking on urban gardening have focused on community gardens, whether in parks, vacant lots, or other public land. This emphasis, while important for many Midwestern cities, can obscure the significance of privately owned land such as front yard and back yard and their crucial connections with gardening on public land. In this case study, we examine how policies and practices related to gardening and the management of green space in two Midwestern cities exceed narrow visions of urban agriculture. The article explores the cultivation of vacant lot gardens and private yards as two modes of property in similar Midwestern contexts and argues that the management of green space is about more than urban agriculture. Instead, we show how urban gardening occurs across public/private property distinctions and involves a broader set of actors than those typically included in sustainability policies. Gardening also provides a key set of connections through which neighbors understand and practice sustainability in Midwestern cities.
B-type natriuretic peptide is upregulated by c-Jun N-terminal kinase and contributes to septic hypotension

B-type natriuretic peptide (BNP) is secreted by ventricular cardiomyocytes in response to various types of cardiac stress and has been used as a heart failure marker. In septic patients, increased BNP suggests poor prognosis; however, no causal link has been established. Among various effects, BNP decreases systemic vascular resistance and increases natriuresis that leads to lower blood pressure. We previously observed that JNK inhibition corrects cardiac dysfunction and suppresses cardiac BNP mRNA in endotoxemia. In this study, we investigated the transcriptional mechanism that regulates BNP expression and the involvement of plasma BNP in causing septic hypotension. Our in vitro and in vivo findings confirmed that activation of JNK signaling increases BNP expression in sepsis via direct binding of c-Jun in activating protein-1 (AP-1) regulatory elements of the Nppb promoter. Accordingly, genetic ablation of BNP, as well as treatment with a potentially novel neutralizing anti-BNP monoclonal antibody (19B3) or suppression of its expression via administration of JNK inhibitor SP600125 improved cardiac output, stabilized blood pressure, and improved survival in mice with polymicrobial sepsis. Therefore, inhibition of JNK signaling or BNP in sepsis appears to stabilize blood pressure and improve survival.
Effect of Interlayer Interval Time on the Microstructure and Mechanical Behavior of Additively Manufactured WE43 Mg Alloy

Additive manufacturing of magnesium (Mg) alloys has gained interest for the potential to fabricate complex geometries for extreme light-weighting or improved functionality. In this study, the effect of interlayer interval time and post-deposition processing (i.e., heat treatment and hot isostatic pressing (HIP)) on the microstructure and mechanical behavior of WE43 Mg specimens fabricated by laser powder directed energy deposition (LPDED) was investigated. Microstructure characterization was conducted using optical microscopy, scanning electron microscopy, scanning transmission electron microscopy, and energy dispersive X-ray spectroscopy. Mechanical behavior was evaluated using microhardness and uniaxial tensile testing. Post-processing resulted in improved yield strength, tensile strength, and ductility, which was attributed to a reduction in porosity and, to a lesser extent, the formation of second phase particles. The as-deposited specimens exhibited porosity below 3 pct and HIP treatment reduced porosity to below 0.1 pct. HIP specimens, processed with low interlayer interval time, exhibited the best combination of strength (~ 243 MPa tensile strength) and ductility (~ 9 pct elongation). Changes in interlayer interval time had limited impact on the grain size, hardness, or yield strength. However, increased interlayer interval time (~ 112 pct increase) caused a slight increase in gas porosity and dramatic reduction in tensile strength and ductility, which was attributed to the formation of lack-of-fusion defects in interlayer regions.
A practical gaze at the Warsaw Ghetto: revealing excess & lack in A Film Unfinished

Yael Hersonski’s Holocaust documentary A Film Unfinished has been read as an exercise in empathic unsettlement that destabilizes the propagandistic intentions of a Nazi gaze that produced footage o...
Does ‘Inspiration Porn’ Inspire? How Disability and Challenge Impact Attitudinal Evaluations of Advertising

Disability community members have voiced concerns about advertising’s representations of persons with disabilities (PWDs). “Inspiration porn” in advertising often takes the form of showing a PWD co...
Heterogeneous Pulmonary Phenotypes in Filamin A Mutation-Related Lung Disease

Background: Interstitial lung disease (ILD) has been recently reported in a few patients with pathogenic variants in the Filamin A (FLNA) gene with variable presentation and prognosis. This study evaluated the respiratory manifestations and clinical features in children with FLNA disease. Methods: We conducted a retrospective review of pediatric patients with variants in FLNA in a tertiary children's hospital. The clinical features, genotype, management, and outcomes were analyzed. Results: We identified 9 patients with variants in FLNA aged 15 months to 24 years, 4 females and 5 males. Six patients had abnormal chest imaging ranging from mild interstitial prominence to atelectasis, interstitial densities, and hyperinflation. Three patients with ILD presented during the neonatal period or early infancy with respiratory distress or respiratory failure requiring supplemental oxygen or assisted ventilation via tracheostomy. We report male twins with the same FLNA variant and lung disease, but different ages and clinical features at presentation eventually culminating in respiratory failure requiring assisted ventilation. All patients had FLNA variants identified by FLNA sequencing, had abnormal echocardiograms, and none of the patients underwent lung biopsy or lung transplantation. The outcomes were variable and could be as severe as chronic respiratory failure. Conclusion: The wide spectrum of respiratory manifestations and abnormal chest imaging in our study highlights the importance of evaluation for lung disease in patients with variants in FLNA. FLNA sequencing in suspected cases with ILD may obviate the need for a lung biopsy, prompt surveillance for progressive lung disease, and evaluation for associated clinical features.
Risk Factors for Mortality in an Older Veteran Population With infective Endocarditis.

Objective To determine 30-day and 1-year mortality in patients treated for infective endocarditis (IE) in a VA population. The secondary objective was to identify risk factors for increased risk of mortality in veterans diagnosed with IE. Design A retrospective cohort study. Setting Veterans Affairs Western New York Healthcare System PARTICIPANTS: Patients who had a diagnosis of IE between the years 2005 and 2016. Patients were identified via International Classification of Diseases (ICD) codes. Interventions None. Main outcome measures Factors for death and survival were compared using a bivariate analysis. Significant factors were built into a multivariate logistic regression analysis to determine risk factors for death at 30 days and 1 year. Results Between 2005 and 2016, there were 153 patients with IE. All-cause mortality at 30 days was 14% versus 39% at 1 year. Patients were more likely to die at 1 year with higher Pitt Bacteremia Scores, older age, and lower number of minor criteria according to Duke Criteria. Comorbidities were similar between groups. Conclusions Older patients with higher Pitt Bacteremia Scores and lower numbers of minor criteria are more likely to experience mortality at one year. Given the high rates of death at one year, close monitoring, even after completion of therapy may be necessary in older patients. Senior care pharmacists are in a unique position to monitor these patients.
Simulation for Colorectal Surgery.

Introduction: Colorectal surgery is a highly specialized field in surgery that deals with the surgical intervention of disease processes of the colon, rectum, and anus. Gaining proficiency in this field requires training both inside and outside of the operating room. Simulation plays a key role in training surgeons in colorectal surgery. The goal of this study is to review the currently available simulators for training in the field of colorectal surgery. Methods: A review of the literature was conducted to identify simulators that are both physical such as benchtop, live animal, and cadaver, as wells as virtual reality (VR) simulators. Any reported validity evidence for these simulators were also presented. Results: There are several benchtop physical models made of silicone for training in basic colorectal tasks, such as hand-sewn and stapled anastomosis. To improve realism, explanted animal and cadaveric specimens were also used for training. To improve repeatability, objective assessment, both commercial and VR simulators also exist for training in both open and laparoscopic colorectal surgery and emerging areas such as endoscopic submucosal dissection. Conclusion: Simulation-based training in colorectal surgery is here to stay and is going to play a significant role in training, credentialing, and quality improvements.
Heat transfer coefficients during baking of potato strips in a pilot scale radiant wall oven

A pilot scale radiant wall oven (RWO) was used to bake potato strips at 12 different time-temperature combinations within 16 min at 290°C to 6.5 min at 365°C. Radiant and overall heat transfer coef...
Microelectrical Mechanical Systems Actuator Array for Tactile Communication

Tactile perception of alpha-numerics is possible using a tactile illusion (TI). The illusory sensation of motion is produced by mechanical actuators applying points of pressure on the skin. Vibrating points induce a nonveridical perception of motion from point to point. Intact lemniscal and parietal cortex are necessary for perception of the TI and can be used as a neurophysiological testing tool and an additional human-machine communication channel. We describe a 4 × 5 actuator array of individual vibrating pixels for fingertip tactile communication. The array utilizes novel micro-clutch MEMS technology. Individual pixels are turned ON and OFF by pairs of microscopic thermal actuators, while the main vibration is generated by a vibrating piezo-electric plate. Physiological parameters required for inducing TI and the fabrication sequence for the thermal micro-actuators along with actuation results are presented. Fingertip perception of micro-actuators could be built into a variety of data acquisition interfaces for handicapped persons.
Non-flame atomic absorption in the vacuum ultraviolet region. The direct determination of mercury in air at the 184.9-nm resonance line.

Abstract Mercury in the atmosphere was analyzed continuously without prior scrubbing or sample collection. The mercury resonance line at 184.9 nm was utilized. This was made possible with an r.f. carbon rod atomizer and by pumping the monochromator with argon : the sensitivity was 0.1 μg Hg m-3. The method was sensitive to the type of mercury light source used. Strong reversal of the resonance lines on commercial hollow cathodes was indicated. Some anomalous temperature affects were observed.
Leveraging ISI Multi-Model Prediction for Navy Operations: Proposal to the Office of Naval Research

Abstract : The potential to leverage existing and planned efforts to produce intra-seasonal to seasonal and interannual climate predictions, by U.S. national laboratories participating in the National Multi- Model Ensemble (NMME) project and by U.S. Navy research and operational entities, for the purpose of advising and enhancing Navy operations will be exploited. The proposed work will build on a review of the existing and planned efforts at the relevant U.S. Navy centers and will enhance existing operational climatological products developed by the Climatology Division at NRL-Monterey and will seek to include Navy models in the NMME project. The accuracy, timeliness, and information content of Navy operational products intended to provide tailored long-range operational environmental information for planning and decision support can be significantly enhanced by the targeted application of dynamical ensemble predictions.
The Theorem of Pythagoras

The Pythagorean theorem is the most appropriate starting point for a book on mathematics and its history. It is not only the oldest mathematical theorem, but also the source of three great streams of mathematical thought numbers, geometry, and infinity. The number stream begins with Pythagorean triples; triples of integers \((a, b, c)\) such that \(a^2 + b^2 = c^2\). The geometry stream begins with the interpretation of \(a^2, b^2,\ \rm{and}\ c^2\) as squares on the sides of a right-angled triangle with sides a, b, and hypotenuse c. The infinity stream begins with the discovery that \(\sqrt{2}\), the hypotenuse of the right-angled triangle whose other sides are of length 1, is an irrational number. These three streams are followed separately through Greek mathematics in Chapters 2, 3, and 4. The geometry stream resurfaces in Chapter 7, where it takes an algebraic turn. The basis of algebraic geometry is the possibility of describing points by numbers—their coordinates—and describing each curve by an equation satisfied by the coordinates of its points. This fusion of numbers with geometry is briefly explored at the end of this chapter, where we use the formula \(a^2 + b^2 = c^2\) to define the concept of distance in terms of coordinates.
Analysis of Unsuccessful Tax Avoiders

A longstanding question is why an important fraction of public companies pay relatively large amounts in taxes, apparently forgoing the benefits of tax avoidance. This study finds that firms with high effective tax rates are, to some extent, unsuccessful tax avoiders. These firms engage in tax avoidance activities but later return part of their tax savings to tax authorities. Moreover, lenders penalize these firms with higher loan spreads and more restrictive contract terms. This effect is economically important and represents a cost of engaging in tax avoidance activities. Overall, this study contributes to our understanding of corporate tax behavior by presenting the first study that analyzes unsuccessful tax avoiders.
Planning for Same-Sex Couples in 2011

This article is the published version of a CLE outline prepared for ALI-ABA in January 2011 and then updated in March 2011. It includes citations to relevant authority regarding a number of tax issues that same-sex couples encounter both under the income tax and under the estate and gift tax system. The outline also includes a list of states that recognize the status of same-sex couples as married, registered domestic partners, civil unions, or similar forms of recognition, and identifies those states in which legislative action recognizing same-sex couples is possible and those in which it is not, due to restrictive state constitutional amendments.
A generalized forward recovery checkpointing scheme

We propose a generalized forward recovery checkpointing scheme, with lookahead execution and rollback validation. This method takes advantage of voting and comparison on multiple versions of the executing task. The proposed scheme is evaluated and compared with other existing checkpointing techniques. The processor assignment problem is studied and an optimal processor assignment is identified. Details on how to use this approach for tolerating both software and hardware faults are also discussed.
The unitary coupled-cluster approach and molecular properties. Applications of the UCC(4) method

Abstract The evaluation of the energy and analytical energy gradient of the new unitary coupled-cluster method, UCC(4), are described, and initial numerical results for this method are reported. UCC(4) energies, molecular geometries, vibrational frequencies, and dipole moments are compared with results given by other high-level techniques such as MBPT (4), CCSDT-1, CCSDT, CISDTQ and FCI.
Prediction of the CaO effect on P availability with a mechanistic model

Abstract Although the mechanisms are unclear, liming often reduces P availability over the pH range of 5.0–7.0. However, since P uptake can be predicted with a mechanistic model, this same model should be capable of determining P availability with only a knowledge of C1 (P in soil solution), Cs (P adsorbed on soil particles and in equilibrium with C1 ), and De, (effective diffusion coefficient for P) without a need to further our understanding of the underlying mechanisms of P fixation. Our objective was to test the ability of the model to predict the change in P availability in response to lime application and to compare that prediction with the prediction of the traditional Bray P, test. Corn (Zea mays L.) plants were grown in a Toronto silt loam soil limed with CaO to give a pH range of 5.1–7.1. Shoot dry weight and percentage of P decreased when pH was increased. However, although the percentage of P was lowest at the highest pH, shoot growth and root length actually increased at pH 7.1 after a decrea...
Dose-dependent Differential Effects of Risedronate on Gene Expression in Osteoblasts

Bisphosphonates have multiple effects on bone. Their actions on osteoclasts lead to inhibition of bone resorption, at least partially through apoptosis. Effects on osteoblasts vary, with modifications in the molecule and concentration both resulting in qualitatively different responses. To understand the mechanism of the differential effects of high and low bisphosphonate concentrations on osteoblast activity, we compared the effects of 10⁻⁸ M and 10⁻⁴ M risedronate on gene expression in UMR-106 rat osteoblastic cells. Two targeted arrays, an 84-gene signaling array and an 84-gene osteogeneic array were used. Gene expression was measured at 1 and 24 h. Although some genes were regulated similarly by low and high concentrations of the drug, there was also differential regulation. At 1 h, 11 genes (1 signaling and 10 osteogenesis) were solely regulated by the low concentration, and 7 genes (3 signaling, 4 osteogenesis) were solely regulated by the high concentration. At 24 h, 8 genes (3 signaling, 5 osteogenesis) were solely regulated by the low concentration and 30 genes (16 signaling and 14 osteogenesis) were solely regulated by the high concentration. Interestingly, the low, but not the high concentration of risedronate transiently and selectively upregulated several genes associated with cell differentiation. A number of genes related to apoptosis were regulated, and could be involved in effects of bisphosphonates to promote osteoblast apoptosis. Also, observed gene changes associated with decreased angiogenesis and decreased metastasis could, if they occur in other cell types, provide a basis for the effectiveness of bisphosphonates in the prevention of cancer metastases.
Localization of fiducial skin markers in MR images using correlation pattern recognition for PET/MRI nonrigid breast image registration

In most instances, multiple-modality visualization of pathologies will present advantages over single-modality studies. For many medical imaging procedures, it is desirable to produce a ldquofusedrdquo output that simultaneously exhibits characteristics of the data from each individual modality to reduce the difficulty of the decision-making process for radiologists. Preprocessing for most data fusion algorithms typically performs the necessary registration of the input data (from each modality). Fiducial markers may be used to display image locations that are common to each modality if the images exhibit very different spatial structure, as is the case with MRI and PET imagery. The process of automating the detection of these markers needs more investigation in the medical field, and the current state of the art often requires manual selection by a human observer throughout the 3-dimensional image stack. The objective of automated detection is to locate the centroid of each marker in a noisy background that contains additional objects that span a large range of intensity values. The correlation methods employed must somehow ldquonormalizerdquo the images to accommodate changes in the input image, so that ldquobrightnessrdquo of the region does not affect the correlation, thus reducing the false positive rate. The filter should accommodate within-class distortion, as the size and shape of the fiducial marker will vary through the image stack. For this work, a mean-subtracted MACH filter was constructed and applied to data that are mean-subtracted locally. The location of centroids in the output stack of correlation planes was determined by applying morphological operations to extract regions-of-interest. It is apparent that a relatively high probability of detection is obtained over a wide range of thresholds with an acceptable false positive rate.
Crystal structure of human cholesterol sulfotransferase (SULT2B1b) in the presence of pregnenolone and 3'-phosphoadenosine 5'-phosphate. Rationale for specificity differences between prototypical SULT2A1 and the SULT2BG1 isoforms.

The gene for human hydroxysteroid sulfotransferase (SULT2B1) encodes two peptides, SULT2B1a and SULT2B1b, that differ only at their amino termini. SULT2B1b has a predilection for cholesterol but is also capable of sulfonating pregnenolone, whereas SULT2B1a preferentially sulfonates pregnenolone and only minimally sulfonates cholesterol. We have determined the crystal structure of SULT2B1a and SULT2B1b bound to the substrate donor product 3′-phosphoadenosine 5′-phosphate at 2.9 and 2.4 A, respectively, as well as SULT2B1b in the presence of the acceptor substrate pregnenolone at 2.3 A. These structures reveal a different catalytic binding orientation for the substrate from a previously determined structure of hydroxysteroid sulfotransferase (SULT2A1) binding dehydroepiandrosterone. In addition, the amino-terminal helix comprising residues Asp19 to Lys26, which determines the specificity difference between the SULT2B1 isoforms, becomes ordered upon pregnenolone binding, covering the substrate binding pocket.
Analogs of tetrahydrofolic acid. XIX. On the mode of binding of the pyrimidyl moiety of n-(2-amino-4-hydroxy-6-methyl-5-pyrimidylpropionyl)-P-aminobenzoyl-l-glutamic acid to 5,10-methylenetetrahydrofolate dehydrogenase†

The synthesis of several analogs of the title compound (Ia) which had (a) replacement of the 4-hydroxy group by thiol, (XXVIIIa), (b) replacement of the 6-methyl group by 6-phenyl (Ib), (c) replacement of the 2-amino group by 2-thiol (XXVI), or (d) replacement of both the 4-hydroxyl and 6-methyl groups by 4-thiol and 6-phenyl, respectively, have been described. The key intermediate was the appropriate 2,4,6-trisubstituted5-pyrimidyl-propionic acids which were synthesized by suitable transformation of the 5-pyrimidyl-propionitriles (VIII and XII). Replacement (a) or (b) gave an improvement in inhibition of 5, 10 - methylenetetrahydrofolate dehydrogenase, but the two changes in the same molecule (d) did not further increase inhibition. The 2-amino group of the title compound (Ia) can be replaced by 2-thiol without decreasing the inhibitory properties of Ia.
Analysis of Transient Laminar Convective Heat Transfer Inside a Circular Duct

Calcul d'un transfert de chaleur transitoire par convection laminaire dans une conduite circulaire soumise a un saut de la temperature ambiante
Nuclear Factor of Activated T-cells (NFAT)c2 Inhibits Notch Receptor Signaling in Osteoblasts

Notch receptors regulate osteoblastogenesis, and Notch activation induces cleavage and nuclear translocation of the Notch intracellular domain (NICD), which associates with Epstein-Barr virus latency C-promoter binding factor-1/suppressor of hairless/lag-1 (CSL) and induces transcription of Notch target genes, such as hairy enhancer of split-related with YRPW motif (Hey)1 and Hey2. Nuclear factors of activated T-cells (NFAT) are transcription factors that regulate osteoclastogenesis, but their function in osteoblasts is not clear. Notch inhibits NFATc1 transcription, but interactions between Notch and NFAT are understood poorly. To determine the regulation of NFAT expression by Notch, osteoblasts from RosaNotch mice, where NICD is transcribed following excision of a loxP flanked STOP cassette, were used. Alternatively, wild-type C57BL/6 osteoblasts were exposed to the Notch ligand Delta-like (Dll)1 to induce Notch signaling or to bovine serum albumin as control. In RosaNotch osteoblasts, Notch suppressed NFATc1 expression, increased Nfatc2 mRNA by post-transcriptional mechanisms, and had no effect on NFATc3 and NFATc4 transcripts. Induction of Nfatc2 transcripts by Notch was confirmed in C57BL/6 osteoblasts exposed to Dll1. To investigate NFATc2 function in osteoblasts, constitutively active NFATc2 was overexpressed in RosaNotch osteoblasts. NFATc2 suppressed Notch transactivation and expression of Hey genes. Electrophoretic mobility shift assays revealed that NFATc2 and CSL bind to similar DNA sequences, and chromatin immunoprecipitation indicated that NFATc2 displaced CSL from the Hey2 promoter. The effects of NICD and NFATc2 in RosaNotch osteoblasts were assessed, and both proteins inhibited osteoblast function. In conclusion, Notch stabilizes Nfatc2 transcripts, NFATc2 suppresses Notch signaling, and both proteins inhibit osteoblast function.
Ion trap collisional activation of the (M + 2H)2+ - (M + 17H)17+ ions of human hemoglobin beta-chain.

The parent ions of human hemoglobin β-chain ranging in charge from 2+ to 17+ have been subjected to ion trap collisional activation. The highest charge-state ions (17+ to 13+) yielded series of products arising from dissociation of adjacent residues. The intermediate charge-state ions (12+ to 5+) tended to fragment preferentially at the N-terminal sides of proline residues and the C-terminal sides of acidic residues. Many, but not all, of the possible cleavages at proline, aspartic acid, and glutamic acid residues were represented in the spectra. The lowest charge-state ions were difficult to dissociate with high efficiency and yielded spectra with poorly defined product ion signals. This observation is attributed to sequential fragmentations arising from losses of small molecules such as water and/or ammonia. The poor fragmentation efficiency observed for the low charge states is due at least in part to the low trapping wells used to store the ions. Higher ion stabilities due to lower Coulombic repulsion...
Effects of Calcium and Kinetin on Growth and Cell Wall Composition of Pea Epicotyls

Kinetin and CaCl(2), in the presence of indoleacetic acid, promoted lateral expansion of epicotyls of decapitated and derooted Alaska pea seedlings (Pisum sativum L.) and inhibited their elongation. This growth response was correlated with the development of cell walls unusually rich in pectic uronic acids. Epicotyls in calcium-auxin solutions continued to enlarge and to add new wall material long after tissues in auxin only had stopped. Longitudinal enlargement, associated with the development of walls poor in pectic uronic acids, was favored by KCl, MgCl(2), and ethylenediaminetetraacetate. The last of these agents promoted the loss of (45)Ca from the epicotyls. Seedings grown in vermiculite moistened with CaCl(2), KCl, or MgCl(2) solutions did not differ in appearance or in the composition of their walls. They responded similarly to experimental treatment except that the decapitated epicotyls of the MgCl(2)-grown plants suffered an absolute loss of pectic uronate when incubated in that salt.
Water Transport Polymers – Structure/Property Relationships of a Series of Phosphazene Polymers

A study was undertaken to explore the water passing properties of a series of phosphazene polymers versus the attached pendant group structure. Pendant groups containing different numbers of ethyleneoxy groups were synthetically attached to the backbone of phosphazene polymers. Phosphazene polymers facilitate these types of studies because, during their synthesis, the polymer backbone is formed first and then the desired pendant groups are attached through nucleophilic substitution. For these studies, four polymer series were synthesized and tested for their water passing properties. The polymers contained different amounts of ethyleneoxy units. Two different polymer families were synthesized and compared in this work. The critical difference in the two polymer series is that one contained pendant groups with aromatic rings, in addition to the oligioethyleneoxy moieties, while the other has no aromatic rings in its structure. Polymers with phenyl group-containing pendant groups exhibited poor water permea...
Heterozygosity for fibrinogen results in efficient resolution of kidney ischemia reperfusion injury.

Fibrinogen (Fg) has been recognized to play a central role in coagulation, inflammation and tissue regeneration. Several studies have used Fg deficient mice (Fg−/−) in comparison with heterozygous mice (Fg+/−) to point the proinflammatory role of Fg in diverse pathological conditions and disease states. Although Fg+/− mice are considered ‘normal’, plasma Fg is reduced to ∼75% of the normal circulating levels present in wild type mice (Fg+/+). We report that this reduction in Fg protein production in the Fg+/− mice is enough to protect them from kidney ischemia reperfusion injury (IRI) as assessed by tubular injury, kidney dysfunction, necrosis, apoptosis and inflammatory immune cell infiltration. Mechanistically, we observed binding of Fg to ICAM-1 in kidney tissues of Fg+/+ mice at 24 h following IRI as compared to a complete absence of binding observed in the Fg+/− and Fg−/− mice. Raf-1 and ERK were highly activated as evident by significantly higher phosphorylation in the Fg+/+ kidneys at 24 h following IRI as compared to Fg+/− and Fg−/− mice kidneys. On the other hand Cyclin D1 and pRb, indicating higher cell proliferation, were significantly increased in the Fg+/− and Fg−/− as compared to Fg+/+ kidneys. These data suggest that Fg heterozygosity allows maintenance of a critical balance of Fg that enables regression of initial injury and promotes faster resolution of kidney damage.
Plasma membrane cyclic AMP-dependent protein phosphorylation system in L6 myoblasts.

Abstract Plasma membranes can be isolated without disruption of cells by the plasma membrane vesiculation technique (Scott, R.E. (1976) Science 194, 743–745). A major advantage of this technique is that it avoids contamination of plasma membranes with intracellular membrane components. Using this method, we prepared plasma membranes from L6 myoblasts grown in tissue culture and studied the characteristics of the protein phosphorylation system. We found that these plasma membrane preparations contain protein kinase which is tightly bound to the membrane and cannot be removed by washing in EDTA or in high ionic strength salt solutions. This protein kinase activity can catalyze the phosphorylation of several exogenous substrates with decreasing efficiency as acceptors of phosphate: calf thymus histones f2b, protamine and caseine. Cyclic AMP causes a dose-dependent stimulation of protein kinase activity; the highest stimulation (4-fold) is achieved at concentration 10−5 M cyclic AMP. Cyclic AMP-dependent stimulation can be completely inhibited by heat-stable protein kinase inhibitor isolated from rabbit skeletal muscle. On the other hand, cyclic GMP does not affect the activity of protein kinase. Plasma membrane-bound protein kinase also catalyzes the phosphorylation of endogenous membrane protein substrates and this is also stimulated by addition of cyclic AMP. Analysis of plasma membrane proteins by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis showed that specific polypeptides are phosphorylated by cyclic AMP-independent and by cyclic AMP-dependent protein kinase systems. The results of these studies demonstrate the presence of endogenous cyclic AMP-dependent and -independent protein phosphorylating systems (enzyme activity and substrates) in purified plasma membrane preparations. These data provide a basis for further investigations on the role of plasma membrane missing data
Health disparities in time to aneurysm clipping/coiling among aneurysmal subarachnoid hemorrhage patients: a national study.

Objective Previous studies have suggested disparities in quality of health care and time to treatment across socioeconomic groups. Such differences can be of greatest consequence in the setting of emergent medical conditions. Surgical or endovascular treatment of ruptured cerebral aneurysms within the first 3 days of aneurysmal subarachnoid hemorrhage (aSAH) is associated with improved outcome. We hypothesize that race and payer status disparities effect the time to treatment for ruptured aneurysms. Methods Discharge data were collected from the Nationwide Inpatient Sample during the years 2002−2010. International Classification of Diseases , 9th Edition; Clinical Modification codes were used to identify patients with aSAH who were treated by either surgical clipping or endovascular coil embolization. Time to procedure was dichotomized into 1) treatment in 3 days or less or 2) treatment in greater than 3 days. Time to treatment was evaluated according to demographic factors, including race, payer status, and median zip code income via multivariable analysis. Results A total of 78,070 aSAH admissions were treated by either aneurysm clip ligation or coil embolization. Hispanic race and Medicaid payer status were associated with increased time to treatment ( P Conclusion Racial and socioeconomic factors are associated with delayed time to treatment in aSAH. Identification of factors underlying these delays and standardization of care may allow for more uniform treatment protocols and improved patient care.
Employee benefits as context for intergenerational conflict

Abstract Researchers have illuminated our understanding of how employee benefits systems are designed to motivate employees to perform jobs in a variety of settings. Benefits systems in U.S. companies generally rest on the assumption that employees have similar attitudes toward and will be motivated similarly by these systems. Several demographic trends in the U.S. work force call into question this assumption. The purpose of this article is to encourage researchers to consider how employee benefits practices may detract from the primary goal of motivating workers to perform their jobs well in the context of the changing demographics of the U.S. workforce. We do so by demonstrating implications of age heterogeneity for the effectiveness of benefits practices. In order to do so, we draw on research from multiple disciplines to show how age related norms are institutionalized, how generational identities and values are created, how intergenerational conflict may manifest in the workplace, and how benefits systems that do not take into account the social dynamics pertinent to age may trigger/sustain intergenerational conflict in the workplace.
An evaluation of the measurement of pain catastrophizing by the coping strategies questionnaire.

Measurement and conceptual issues of pain catastrophizing have been raised in the literature. The issues of construct redundancy and measurement overlap have received particular attention, with suggestions that measures of pain catastrophizing are confounded with measures of negative mood, namely depression. The current study sought to investigate these issues in the coping strategies questionnaire-catastrophizing subscale (CSQ-CAT), a widely used measure of pain catastrophizing. Chronic pain patients (n = 152) were recruited from the University of Florida pain clinics and completed a battery of psychological measures. Regression analyses indicated that measures of depression, anxiety, and anger accounted for 69% and 19% of the variance in measures of pain catastrophizing and pain, respectively. Trait anger and the cognitive and fearful dimensions of depression and anxiety were uniquely associated with pain catastrophizing. After controlling for measures of negative mood, pain catastrophizing contributed minimally to the prediction of pain. This study suggests that the CSQ-CAT is highly related to measures of negative mood and raises doubts about its measurement of the construct of pain catastrophizing. Results also provide support for theoretical accounts of the relationships between pain catastrophizing, negative mood, and pain. Clinical implications, future research directions, and alternative measures of pain catastrophizing are discussed.
Multispectral microimager for astrobiology

A primary goal of the astrobiology program is the search for fossil records. The astrobiology exploration strategy calls for the location and return of samples indicative of environments conducive to life, and that best capture and preserve biomarkers. Successfully returning samples from environments conducive to life requires two primary capabilities: (1) in situ mapping of the mineralogy in order to determine whether the desired minerals are present; and (2) nondestructive screening of samples for additional in-situ testing and/or selection for return to laboratories for more in-depth examination. Two of the most powerful identification techniques are micro-imaging and visible/infrared spectroscopy. The design and test results are presented from a compact rugged instrument that combines micro-imaging and spectroscopic capability to provide in-situ analysis, mapping, and sample screening capabilities. Accurate reflectance spectra should be a measure of reflectance as a function of wavelength only. Other compact multispectral microimagers use separate LEDs (light-emitting diodes) for each wavelength and therefore vary the angles of illumination when changing wavelengths. When observing a specularly-reflecting sample, this produces grossly inaccurate spectra due to the variation in the angle of illumination. An advanced design and test results are presented for a multispectral microimager which demonstrates two key advances relative to previous LED-based microimagers: (i) acquisition of actual reflectance spectra in which the flux is a function of wavelength only, rather than a function of both wavelength and illumination geometry; and (ii) increase in the number of spectral bands to eight bands covering a spectral range of 468 to 975 nm.
Phanerozoic peridotitic and pyroxenitic komatiites from newfoundland.

Peridotitic and highly magnesian pyroxenitic komatiites, thus far known to occur almost exclusively in the Archean (before 2.5 x 109years ago) terranes, are reported from an Ordovician (0.5 x 109years) ophiolite suite in Newfoundland. Their occurrence as pillow lavas or as chilled dikes, their possession of quench textures and geochemical parameters such as high contents of magnesium oxide, nickel, and chromium and low contents of titanium dioxide and potassium monoxide, low ratios of iron to iron plus magnesium, and values of the ratio of calcium oxide to aluminum oxide of close to unity demonstrate that they were formed through the rapid cooling of a highly mobile komatiitic melt. These features resemble those of many Archean peridotitic-pyroxenitic komatiites and indicate that the Archean-type magmatism did prevail in the younger segments of the earth9s history although perhaps in a more erratc manner.