cssi/SciSciGPT-SciSciNet huggingface dataset:
A simplified method for HPLC determination of creatinine in mouse serum

Mouse models are frequently used to study renal function. However, mouse serum contains chromagens that interfere with standard picric acid-based assays for serum creatinine. Several alternative methods exist for serum creatinine measurements, including assay by high-performance liquid chromatography (HPLC), but only one has been adapted to mouse serum. Creatinine was measured in serum by acetonitrile deproteinization, followed by isocratic, cation exchange HPLC. The HPLC method was compared with a standard alkaline picrate colorimetric assay, using serum from animals with low-to-moderate renal injury. Acidification of acetonitrile with HCl in the deproteinization step produced variable results, including an extra peak that interfered with integration of the creatinine peak or loss of the creatinine peak. Deproteinizing with acetonitrile alone resulted in a more reliable measurement of serum creatinine, which was validated by a series of known additions of creatinine standard. The HPLC assay was reproducible with coefficients of variation from 1.6 to 5.1%. The picric acid assay overestimated serum creatinine, when directly compared with the HPLC assay. The extent of overestimation, up to sixfold, was greatest at normal (0.1 to 0.2 mg/dl) to moderately elevated (0.5 mg/dl) serum creatinine levels. Mouse serum contains substances that interfere with standard picric acid assays for creatinine. Our new HPLC assay can accurately detect creatinine from 5 μl of mouse serum. These results support the widespread adoption of HPLC to accurately measure serum creatinine in mouse models of renal injury.
Circulating immune complexes in adults with idiopathic nephrotic syndrome

Circulating immune complexes in adults with idiopathic nephrotic syndrome. A retrospective analysis of the prevalence of circulating immune complexes in adults with idiopathic nephrotic syndrome was conducted. Immune complexes were detected by the fluid and solid-phase C1q-binding and the Raji cell assays. Adults with idiopathic nephrotic syndrome were categorized by renal pathology as follows: minimal change disease (N = 14), focal glomerular disease (N = 27), and membranous nephropathy (N = 55). Patients were randomized into prednisone- and placebo-treated groups. Immune complexes as determined by reactivity in one or more assay techniques were more prevalent in patients with minimal change (11/14), focal glomerular disease (13/27), and membranous nephropathy (26/55) as compared with control sera (P Complexes immuns circulant chez l'adulte atteint de syndrome nephrotique. Une analyse retrospective de la frequence des complexes immuns circulants chez l'adulte atteint de syndrome nephrotique idiopathique a ete realisee. Les complexes immuns ont ete detectes par la liaison de C1q en phase solide et au moyen des cellules de Razi. Les adultes atteints de syndrome nephrotique ont ete classes en fonction de la morphologie renale de la facon suivante: modifications minimes (N = 14), atteinte glomerulaire focale (N = 27), et glomerulite extramembraneuse (N = 55). Les malades ont ete repartis en deux groupes de traitements par la prednisone ou au placebo. Les complexes immuns evalues par la reactivite dans une ou plusieurs techniques de mesure ont ete plus frequents chex les malades ayant des modifications minimes (11/14), une atteinte glomerulaire focale (13/27), et une glomerulite extramembraneuse (26/55) par comparaison avec les resultats obtenus pour des serums controles (P
A baculovirus blocks insect molting by producing ecdysteroid UDP-glucosyl transferase

The predicted amino acid sequence of a newly identified gene of the insect baculovirus Autographa californica nuclear polyhedrosis virus was similar to several uridine 5'-diphosphate (UDP)-glucuronosyl transferases and at least one UDP-glucosyl transferase. Genetic and biochemical studies confirmed that this gene encodes an ecdysteroid UDP-glucosyl transferase (egt). This enzyme catalyzes the transfer of glucose from UDP-glucose to ecdysteroids, which are insect molting hormones. Expression of the egt gene allowed the virus to interfere with normal insect development so that molting was blocked in infected larvae of fall armyworm (Spodoptera frugiperda).
Characteristics and factors impacting reunification outcomes among Vietnamese immigrant families in the child welfare system

Abstract Using a mixed methods approach, this study examined reunification processes and outcomes among Vietnamese immigrant families involved in the child welfare system. A quantitative design was used to describe characteristics and reunification outcomes of Vietnamese immigrant children and families who are involved in family reunification services. Qualitative methods were used to explore factors that may influence reunification outcomes among Vietnamese families. The quantitative portion of the study included an exploratory design using administrative data from one county in the Northern California. The quantitative sample (N = 32) included children entering the foster care system for 8 or more days between January 1, 2001 and December 31, 2007 from child welfare administrative data (CWS/CMS) which was merged with eligibility data (CalWIN) in order to obtain parent and child place of birth to determine country of origin. The qualitative study included an exploratory design using interview data from child welfare workers (N = 8) and Vietnamese immigrant parents who had successfully reunified (N = 7). Quantitative results indicated that the most common type of maltreatment leading to entry into care was caretaker absence or incapacity, an abuse category that is often used in cases of parental substance abuse. 53.8% of Vietnamese immigrant children in the quantitative sample reunified with their parents, which is close to the national rate of reunification. Qualitative findings pointed to the importance of the following factors within reunification: acculturation-related issues, parental substance abuse, child welfare worker cultural competency and issues related to service availability and effectiveness. Implications for social work practice and policy are discussed.
Caryolene-forming carbocation rearrangements

Density functional theory calculations on mechanisms of the formation of caryolene, a putative biosynthetic precursor to caryol-1(11)-en-10-ol, reveal two mechanisms for caryolene formation: one involves a base-catalyzed deprotonation/reprotonation sequence and tertiary carbocation minimum, whereas the other (with a higher energy barrier) involves intramolecular proton transfer and the generation of a secondary carbocation minimum and a hydrogen-bridged minimum. Both mechanisms are predicted to involve concerted suprafacial/suprafacial [2 + 2] cycloadditions, whose asynchronicity allows them to avoid the constraints of orbital symmetry.
Aseptic rearing of the aster leafhopper,Macrosteles fascifrons (Stål), on a chemically defined diet

The normal symbiotic aster leafhoppers,Macrosteles fascifrons, were reared under aseptic conditions on the holidic diet through 5 successive generations with normal rates of development, survival and reproduction. Thus the artificial diet is completely adequate for normal insects and dependence on gut organisms is not part of the physiology of this species.
A Cardiologist's View of Modern Cardiovascular Surgery

Several centuries ago, a cynical Gregory said of doctors: “Old men let their patients die, young men kill them,” and there are times when the first part could be paraphrased: “Physicians let their patients die,” the second part you can complete as you will. It is important to point out that the availability and acceptable risk of some surgical procedures may not be known to some physicians and the term “too ill for surgery” may be in grievous error. The remarkable resurrection of some patients with gross acute mitral or aortic regurgitation are cases in point. Be kindly to the physician as you continue to render him out of date; join with the physician in the support of basic research which may make much of the joint present labors unneeded. Remember that at the end of life, it may be more courageous to be accused of “doing nothing” (except relief of pain) than to forge ahead with dramatic surgical effort. In some instances, too, it is well to recall the old adage, “in the dying, surgeons need not hurry the hand of God.” I thus return to Ecclesiastes’ dictum “there is a time to be born and a time to die”—undoubtedly, then, when written, a reflection of passive fatalism, but in this age it would imply an active, sometimes agonizing human decision. I ask your indulgence for the chauvinistic and pejorative touches in my remarks and hope that the yoking together of many heterogeneous ideas will not cause immediate rejection reactions, and that such ideas may be better tolerogens than antigens for productive thoughts.
Quantity, exchange, and shift components of difference in a square contingency table

A common task is to measure the difference between two maps that show the same spatial extent for the same categorical variable, such as land-cover type. One popular technique is to express the overall difference as the sum of two components called quantity and allocation. This article shows how to take an additional step to express allocation difference as the sum of two components called exchange and shift. Exchange exists for a pair of pixels when one pixel is classified as category A in the first map and as category B in the second map, while simultaneously the paired pixel is classified as category B in the first map and as category A in the second map. If there are more than two categories, then it is possible to have a component called shift, which is allocation difference that is not exchange. Our article shows how to compute all three components of overall difference: quantity, exchange, and shift. We show also how to compute the three components for each category and to reveal the category pairs...
Online Senior Health Resources

Advances in medical care allow older adults to live long and active lives. Health information on a variety of topics can help older adults better maintain their health and make informed decisions regarding their care. Older adults have wide-ranging health information needs that may include diseases and conditions, health insurance options, and maintaining one's health. This article discusses some key topics of interest to older adults and provides an annotated webliography of select Internet resources that offer information on a wide array of issues of importance to older adults.
Public Opinion and American Federalism: Perspectives on Taxes, Spending, and Trust—An ACIR Update

The research reported here updates for 1999 some public opinion data previously provided by the U.S. Advisory Commission on Intergovernmental Relations. The 1999 survey results indicate a general continuation of opinion trends established by the late 1970s to the mid-1980s. Local government is viewed as giving citizens the mostfor their money, followed by state government and thefederal government. Americans still regard thefederal income tax as the worst tax, followed by the local property tax. Likewise, Americans express the most trust and confidence in local government and the least trust and confidence in the federal government, although confidence in all governments increased over comparable data for 1992. Race and party identification and, in one case, region are significant factors differentiating opinions about the federal, state, and local governments and their taxes.
Comparison of magnetic resonance imaging-based vocal tract area functions obtained from the same speaker in 1994 and 2002

A new set of area functions for vowels has been obtained with magnetic resonance imaging from the same speaker as that previously reported in 1996 [Story et al., J. Acoust. Soc. Am. 100, 537-554 (1996)]. The new area functions were derived from image data collected in 2002, whereas the previously reported area functions were based on magnetic resonance images obtained in 1994. When compared, the new area function sets indicated a tendency toward a constricted pharyngeal region and expanded oral cavity relative to the previous set. Based on calculated formant frequencies and sensitivity functions, these morphological differences were shown to have the primary acoustic effect of systematically shifting the second formant (F2) downward in frequency. Multiple instances of target vocal tract shapes from a specific speaker provide additional sampling of the possible area functions that may be produced during speech production. This may be of benefit for understanding intraspeaker variability in vowel production and for further development of speech synthesizers and speech models that utilize area function information.
Synaptic potentials induced by postganglionic stimulations in cat bladder parasympathetic neurones.

Intracellular recording techniques were used to examine and compare synaptic potentials evoked by stimulating pre- and postganglionic nerve trunks in cat bladder parasympathetic ganglia. In the 76 ganglion cells exammed, two types of responses were recorded on stimulating the postganglionic nerve: an antidromic action potential (type Post NS1;n=30) or a fast excitatory postsynaptic potential (f-EPSP; type PostNS2;n=46) which resulted in an orthodromic-like action potential. In some of the cells exhibiting a PostNS1 response (n=19), a fast depolarization was superimposed on the antidromic spike. This depolarization was due to the synaptic activation of nicotinic receptors. In many of the cells exhibiting either PostNS1 or PostNS2 responses, repetitive stimulation of the postganglionic nerve induced a slow hyperpolarization. Applying nicotinic (hexamethonium, methonium, 0.5–1 mM), muscarinic (atropine, 1 μM), alpha-adrenergic (phentolamine, 1 μM) and purinergic (caffeine, 0.5–1 mM) receptor antagonists completely inhibited the tetanus-induced slow hyperpolarization in some cells (n=5). In other cells (n=15), a slow hyperpolarization persisted in the presence of these antagonists. These results indicate that stimulation of the postganglionic nerve trunk of cat bladder parasympathetic ganglia can elicit not only an antidromic action potential, but also synaptic potentials which are mediated by the activation of cholinergic (nicotinic and muscarinic), noradrenergic and purinergic receptors, as well as a non-cholinergic, non-alpha-adrenergic and non-purinergic synaptic potential.
Characterization of Archaea Tetraether Hybrid Liposomal Doxorubicin

We have previously shown that liposomes made of the polar lipid fraction E (PLFE) isolated from the thermoacidophilic archaeon Sulfolobus acidocaldarius exhibit enhanced vesicle stability in comparison to conventional diester or diether lipids (reviewed in Chong et al (2012) Archaea, doi:10.1155/2012/138439). In the present study, we have characterized several physical properties of tetraether hybrid liposomes composed of PLFE and non-archaeal diester lipids such as dipalmitoylphosphatidylcholine or porcine brain sphingomyelins/cholesterol. Particle size, zeta-potential and membrane packing of the hybrid liposomes are examined using dynamic light scattering, laser Doppler electrophoresis, Laurdan's generalized polarization, respectively. In addition, entrapment efficiency and spontaneous release of anti-cancer drug doxorubicin is studied by using absorption spectroscopy and fluorescence de-quenching method. These physical measurements are performed on liposomes with varying PLFE molar ratios at different temperatures. The obtained results may help to optimize and design liposomal drugs with greater stability and higher therapeutic efficacy. (supported by NSF DMR1105277)
Vascular endothelial cells mediate mechanical stimulation-induced enhancement of endothelin hyperalgesia via activation of P2X2/3 receptors on nociceptors.

Endothelin-1 (ET-1) is unique among a broad range of hyperalgesic agents in that it induces hyperalgesia in rats that is markedly enhanced by repeated mechanical stimulation at the site of administration. Antagonists to the ET-1 receptors, ET(A) and ET(B), attenuated both initial as well as stimulation-induced enhancement of hyperalgesia (SIEH) by endothelin. However, administering antisense oligodeoxynucleotide to attenuate ET(A) receptor expression on nociceptors attenuated ET-1 hyperalgesia but had no effect on SIEH, suggesting that this is mediated via a non-neuronal cell. Because vascular endothelial cells are both stretch sensitive and express ET(A) and ET(B) receptors, we tested the hypothesis that SIEH is dependent on endothelial cells by impairing vascular endothelial function with octoxynol-9 administration; this procedure eliminated SIEH without attenuating ET-1 hyperalgesia. A role for protein kinase Ce (PKCe), a second messenger implicated in the induction and maintenance of chronic pain, was explored. Intrathecal antisense for PKCe did not inhibit either ET-1 hyperalgesia or SIEH, suggesting no role for neuronal PKCe; however, administration of a PKCe inhibitor at the site of testing selectively attenuated SIEH. Compatible with endothelial cells releasing ATP in response to mechanical stimulation, P2X(2/3) receptor antagonists eliminated SIEH. The endothelium also appears to contribute to hyperalgesia in two ergonomic pain models (eccentric exercise and hindlimb vibration) and in a model of endometriosis. We propose that SIEH is produced by an effect of ET-1 on vascular endothelial cells, sensitizing its release of ATP in response to mechanical stimulation; ATP in turn acts at the nociceptor P2X(2/3) receptor.
Some problems in dissonance theory research

In exploring problems in dissonance research, the author postulates that findings in this area “may, in some cases, be the result of weak experimental designs. Further examination reveals that attitudes often do not change as easily as some of the investigations suggest, but changes are a product of repeated exposures and varieties of appeals.
Measurement of the cosmic ray proton and helium fluxes from 200 MeV nucl−1 to 100 GeV nucl−1 during the 1987 solar minimum

Abstract The galactic cosmic ray proton and helium spectra have been measured with a balloon-borne superconducting magnetic spectrometer over the energy range from 200 MeV nucl−1 to 100 GeV nucl−1 during the 1987 solar minimum between the 21st and 22nd solar cycle. The absolute fluxes were approximately equal to the highest fluxes observed at the previous solar minimum in 1977. Above 10 GV the observed spectra are represented by a power law in rigidity with spectral indices of 2.74± 0.02 for protons and 2.68 ± 0.03 for helium. The data are consistent with rigidity power law interstellar spectra modulated with the solar modulation parameter φ = 500 MV.
Effects of monitoring accuracy on thin film filter performance

Analytical techniques were applied for analysis of monitor data from many deposition runs to measure the end-pointing accuracy. Results show that the magnitude of transmission ripple in the filter pass-band spectrum bears a strong correlation to the standard deviation of the endpointing from the target.
Least possible time paths in stochastic time-varying networks

Abstract Selection of optimal routes for emergency response units, vehicles carrying hazardous material and individuals to and from various activities in congested city streets is vital to these systems' performance. Travel times in congested transportation systems are time-varying quantities that are at best known a priori with uncertainty. Methodologies that recognize the inherent stochastic and time-varying nature of travel conditions are important in many of the above applications, motivating the need for efficient algorithms for determining optimal paths in networks where the arc costs are time-varying random quantities, and for considering trade-offs among various risk dimensions in the selection process. This paper presents two efficient procedures to find the paths that have the least possible time from any origin to a given destination in such networks. These algorithms provide a well-defined and efficiently-computed benchmark against which to evaluate paths obtained using heuristic procedures (that may consider other risk dimensions); in addition they can be used to solve subproblems that arise as components of more elaborate procedures. These problems are encountered in a variety of areas, including intelligent transportation systems (ITS), emergency response systems operations (medical, police, fire) and communication networks. In this paper, two computationally efficient algorithms are presented for determining the least possible time paths for all origins to a single destination in networks where the arc weights are discrete random variables whose probability distribution functions vary with time. The first algorithm determines the least possible time path from each node for each departure time interval, the least possible travel time and a lower bound on the associated probability of the occurrence of this travel time. The second algorithm determines up to k least possible time paths, the associated travel times and the corresponding probabilities of occurrence of the travel times (or a lower bound on this probability). No such efficient algorithms for determining least time paths in stochastic, time-varying networks exist in the literature.
The evolution of plastic antibodies

Plastic antibodies, synthetic polymer nanoparticles with antibody-like functions, have emerged as potential alternatives to protein antibodies. This paper focuses on recent developments of plastic antibodies for biomacromolecules and their application as antitoxins.
Long-Term Care Research and Policy

This article provides a framework for understanding how long-term care (LTC) research contributes to policy, develops a typology of research contributions to policy with examples of each type, and suggests ways to ensure that contributions continue in the future. The article draws on in-depth interviews with LTC experts working at the interface between research and policy, as well as a small, informal Internet survey and the relevant political science and health policy literature. LTC research makes important contributions to policy, but its contributions easily go unrecognized because they are subtle and often depend on research investments made many years before policy is affected. Thus, it is important to consider what investments in LTC research initiatives and infrastructure are needed to ensure the future contributions of research to policy and to identify barriers to funding such investments. A number of steps that researchers can take to enhance the future contribution of research to LTC policy are proposed.
De subitaneis mortibus. XV. Hereditary stenosis of the His bundle in pug dogs

Syncope and sudden death occurs in certain purebred Pug dogs which have been found to have intermittent sinus pauses and paroxysmal second degree heart block on electrocardiographic (ECG) study. We have established a colony of such dogs to study this problem and here report the results of histological examination of the cardiac conduction system in twenty-one of them. These include a dam which may be considered the proband, three of her offspring (two littermates) and three fetal pups in an unborn litter of one of these; three of the four adult dogs died suddenly and unexpectedly. Two groups of puppies descendants of these lines were also studied after they all died within three days of birth. The first group of puppies (8) did not have suitable ECG studies but the second group (6) did and showed ECG changes similar to those in the adult dogs. In all 21 dogs the sinus node was anatomically normal, but in every one there was significant stenosis of the midportion of the His bundle. There was no abnormality of the atrioventricular (A-V) node or of the bundle branches, and the cardiac valves and coronary arteries were normal. Two pups had ventricular septal defects and one of these had an atrial defect as well. All the dogs were of the normal fawn color, had a normal physical appearance and no visible evidence of associated extracardiac abnormalities. The adult dogs were able to hear normally but the puppies died too early to test their hearing. The paroxysmal heart block may in part be attributable to the abnormality in the His bundle, but other factors possibly leading to heart block and long sinus pauses are discussed. Stenosis of the midportion of the His bundle appears to be a heritable trait in these purebred Pug dogs.
Systematic review of sexual risk among pregnant and mothering teens in the USA: pregnancy as an opportunity for integrated prevention of STD and repeat pregnancy

Behaviors that lead to teen pregnancy also place young women at risk for STDs and repeat pregnancy. Compared to the broad literature on adolescent sexual risk behavior, our understanding of sexual risk in pregnant/mothering teens lags far behind. Primary objectives of this systematic review (1981-2003) of pregnant/mothering teens were to: (1) document rates of STD, repeat pregnancy, condom use, and contraception; (2) identify correlates of these biological and behavioral outcomes; (3) review sexual risk reduction interventions; and (4) discuss directions for future research and implications for clinical care. Fifty-one studies met inclusion criteria. Rates of STD and repeat pregnancy were high, with the majority of teens engaging in unprotected sex during and after pregnancy. An Ecological Model of Sexual Risk, based on Bronfenbrenner's (1989) Ecological Systems Theory, was proposed to organize findings on correlates of sexual risk. Improvements in research, including integration of outcomes and risk factors, stronger methodologies, and standardized assessments, are essential. Results suggest that teen pregnancy is a marker for future sexual risk behavior and adverse outcomes, and that pregnant/mothering teens need hybrid interventions promoting dual use of condoms and hormonal contraception. Pregnancy may provide a critical "window of opportunity" for sexual risk reduction.
Why and how we should treat elderly patients with hypertension

Double-blind, randomized, placebo-controlled studies have documented that antihypertensive drug therapy decreases cardiovascular events in older persons. In the Hypertension in the Very Elderly Trial, patients aged 80 years and older treated with antihypertensive drug therapy had at 1.8-year follow-up, a 30% insignificant decrease in fatal or nonfatal stroke, a 39% significant decrease in fatal stroke, a 21% significant decrease in all-cause mortality, a 23% insignificant decrease in death from cardiovascular causes, and a 64% significant decrease in heart failure. The goal of treatment of hypertension in older persons is to decrease the blood pressure to 20/10 mm Hg above the goal blood pressure, drug therapy should be initiated with 2 antihypertensive drugs. Other coronary risk factors must be treated.
Reconceptualizing perceptual development: The identification of some dimensions of spatial competence in young children☆

Abstract In this examination of young children's acquisition of geometric skills, spatial performances were conceptualized as specific combinations of actions applied within stimulus contexts. Since both actions and context can vary, a number of different combinations can be specified. In this study, the relationships among eight such combinations were examined and predicted patterns compared with observed ones. Fifty-four 3-, 4-, and 5-year-old children were presented with 24 geometric displays depicting a variety of geometric relations. Subjects were required to either match or recall the displays in both a reconstruction and a recognition task format thereby responding across different types of action demands. The geometric displays depicted information organized either around a single axis (horizontal or vertical) or around both axes, the variation in context. The results of a mixed design ANOVA revealed a good fit with the hypothesized predictions. The findings are discussed in terms of the development of spatial skills, information theory, and of skill generalization.
A ROG(ue) in charge of the (natural) killers.

Natural killer (NK) cells are innate lymphocytes that exhibit many features of adaptive immunity, such as long-lived memory. This can now be extended to the transcriptional circuits that control the proliferation of NK cells and lymphocytes.
Credit constraints and human capital accumulation in the open economy

Abstract This paper analyzes the implications of capital market imperfections for understanding the causes and consequences of international trade. Credit constraints in financing education and exogenous income distribution affect patterns of comparative advantage and are crucial in determining the impact of international trade. Unlike the standard results in the trade literature, in the model here, trade liberalization in a skill-scarce country leads to higher investments in human capital.
NONLINEAR RADIATION PRESSURE AND STOCHASTICITY IN ULTRAINTENSE LASER FIELDS

The drift acceleration due to radiation reaction for a single electron in an ultraintense plane wave $(a=eE/mc\ensuremath{\omega}\ensuremath{\sim}1)$ of arbitrary wave form and polarization is calculated and shown to be proportional to ${a}^{3}$ in the high-$a$ limit. The resulting average drift acceleration is independent of polarization, even though the average radiated power is polarization-dependent. The cyclotron motion of an electron in a constant magnetic field and an ultraintense plane wave is numerically found to be quasiperiodic even in the high-$a$ limit if the magnetic field is not too strong, as suggested by previous analytical work. A strong magnetic field causes highly chaotic electron motion and the boundary of the highly chaotic region of parameter space is determined numerically and shown to agree with analytical predictions.
Oxidative stress is responsible for maternal diabetes-impaired transforming growth factor beta signaling in the developing mouse heart.

Objective Oxidative stress plays a causal role in diabetic embryopathy. Maternal diabetes induces heart defects and impaired transforming growth factor beta (TGFβ) signaling, which is essential for cardiogenesis. We hypothesize that mitigating oxidative stress through superoxide dismutase 1 (SOD1) overexpression in transgenic (Tg) mice reverses maternal hyperglycemia-impaired TGFβ signaling and its downstream effectors. Study Design Day 12.5 embryonic hearts from wild-type (WT) and SOD1 overexpressing embryos of nondiabetic (ND) and diabetic mellitus (DM) dams were used for the detection of oxidative stress markers: 4-hydroxynonenal (4-HNE) and malondlaldehyde (MDA), and TGFβ1, 2, and 3, phosphor (p)-TGFβ receptor II (TβRII), p-phosphorylated mothers against decapentaplegic (Smad)2, and p-Smad3. The expression of 3 TGFβ-responsive genes was also assessed. Day 11.5 embryonic hearts were explanted and cultured ex vivo, with or without treatments of a SOD1 mimetic (Tempol; Enzo Life Science, Farmingdale, NY) or a TGFβ recombinant protein for the detection of TGFβ signaling intermediates. Results Levels of 4-HNE and MDA were significantly increased by maternal diabetes, and SOD1 overexpression blocked the increase of these 2 oxidative stress markers. Maternal diabetes suppresses the TGFβ signaling pathway by down-regulating TGFβ1 and TGFβ3 expression. Consequently, phosphorylation of TβRII, Smad2, and Smad3, downstream effectors of TGFβ, and expression of 3 TGFβ-responsive genes were reduced by maternal diabetes, and these reductions were prevented by SOD1 overexpression. Treatment with Tempol or TGFβ recombinant protein restored high-glucose–suppressed TGFβ signaling intermediates and responsive gene expression. Conclusion Oxidative stress mediates the inhibitory effect of hyperglycemia in the developing heart. Antioxidants, TGFβ recombinant proteins, or TGFβ agonists may have potential therapeutic values in the prevention of heart defects in diabetic pregnancies.
Genome-wide Mapping and Characterization of Notch-Regulated Long Noncoding RNAs in Acute Leukemia

Notch signaling is a key developmental pathway that is subject to frequent genetic and epigenetic perturbations in many different human tumors. Here we investigate whether long noncoding RNA (lncRNA) genes, in addition to mRNAs, are key downstream targets of oncogenic Notch1 in human T cell acute lymphoblastic leukemia (T-ALL). By integrating transcriptome profiles with chromatin state maps, we have uncovered many previously unreported T-ALL-specific lncRNA genes, a fraction of which are directly controlled by the Notch1/Rpbjκ activator complex. Finally we have shown that one specific Notch-regulated lncRNA, LUNAR1, is required for efficient T-ALL growth in vitro and in vivo due to its ability to enhance IGF1R mRNA expression and sustain IGF1 signaling. These results confirm that lncRNAs are important downstream targets of the Notch signaling pathway, and additionally they are key regulators of the oncogenic state in T-ALL.
Centerless groups—an algebraic formulation of Gottlieb’s theorem

D. GOTTLIEB [I] has proved that the center of the fundamental group of a finite, aspherical polyhedron, whose Euler characteristic is non-zero, is trivial. His proof uses an idea of Nielsen [2] and Wecken [3], who classify the fixed points of a mapping K + K according to certain homotopy properties. This proof of Gottlieb’s can be transformed into algebra, and that is what will be done here. We discuss the Lefschetz fixed point theorem in an algebraic context; we define “trace” in such a way that homotopic endomorphisms of a chain complex have the same “Lefschetz number”. We are able to define “rank” of a finitely generated projective module and the “Euler characteristic” of a complex; and then we prove Gottlieb’s theorem. An algebraic interpretation of the Nielsen-Wecken fixed-point theory is described in [3], part II. Gottlieb’s theorem involves only the simple case of maps K -+ K homotopic to the identity; the technique seems to be previously unused in group theory.
Stereoselective analysis of fenoprofen and its metabolites.

Abstract Reversed-phase high-performance liquid chromatographic assays have been developed to quantitate simultaneously fenoprofen and its major metabolites as well as to distinguish between their R - and S -enantiomers following a single oral dose of 600 mg racemic fenoprofen to healthy volunteers. The compounds are extracted from plasma (after precipitation of plasma protein) or assayed directly in diluted urine samples employing a gradient solution on a C 18 column and ultraviolet detection. Two internal standards, ketoprofen and flunoxaprofen, are used to allow measurement of very low (0.05 μg/ml) and high (70 μg/ml) concentrations in each sample. R - and S -fenoprofen glucoronides can be separated directly; the 4′-hydroxyfenoprofen conjugates are measured via an indirect method by comparing the concentration of 4′-hydroxyfenoprofen before and after hydrolysis. The R - and S -enantiomers of both parent and 4′-hydroxy metabolite are derivatized with l -leucinamide via an ethyl choloroformate intermediate and subsequently analyzed on a C 18 column. Concentrations of metabolites found in plasma were low when compared to parent drug. The S/R ratio of fenoprofen in plasma always exceeds 1 and increases with time after dosage while the S/R ratio of its 4′-hydroxy metabolite remains almost unchanged at 1.1. R -Fenoprofen glucoronide disappears rapidly from plasma as compared to its S -antipode; a less pronounced difference is noted between R - and S -4′-hydroxyfenoprofen conjugates. Fenoprofen is almost completely excreted as its S -acyl glucuronides; the renal clearance of unchanged drug is very low.
Anomalous abundances of deep-sea fauna on a rocky bottom exposed to strong currents

Abstract Unusually high abundances of sponges and gorgonian corals, covering as much as 25% of the bottom, occur at depths greater than 3.5 km on the Blake Spur, a rocky cliff-dominated feature on the western Atlantic continental margin. This is the first report of such high abundances of megafauna from a non-hydrothermal or otherwise chemosynthetically enriched site in abyssal depths. Animal densities at other steep rocky sites at similar depths are usually lower by more than an order of magnitude. The deep slope of the Blake Spur is exposed to the vigorous Western Boundary Undercurrent, with local flow speeds that may exceed 100 cm s−1. Currents can control this anomalous animal abundance by removing sediments and by enhancing fluxes, rather than concentrations, of food particles to the dominant suspension feeders.
Intracellular accumulation of pIgA-R and regulators of transcytotic trafficking in cholestatic rat hepatocytes*

Bile duct ligation (BDL) impairs basolateral-to-apical transcytosis in hepatocytes, causing accumulation of transcytotic carriers for the polymeric IgA receptor (pIgA-R) and redistribution of secretory component (SC) from bile to blood. To gain insight into the mechanisms regulating transcytosis and the pathophysiology of cholestasis, we investigated nascent protein trafficking in control and BDL livers using cell fractionation in the context of in vivo pulse-chase experiments and immunoblot analysis. Control and cholestatic hepatocytes trafficked [35S]-labeled serum proteins and the pIgA-R along the secretory pathway with identical kinetics. However, BDL impaired transcytosis, causing (1) accumulation of the pIgA-R, rab3D, rab11a, and other candidate regulators of apical-directed secretion in a crude vesicle carrier fraction (CVCF) enriched in transcytotic carriers; (2) slow delivery of [35S]-labeled SC to bile; and (3) paracellular reflux of SC from bile to blood. In conclusion, these data indicate that the secretory and transcytotic pathways remain polarized in cholestatic hepatocytes and suggest that the pIgA-R traffics through postendosomal rab3D-, rab11a-, and syntaxin 2-associated compartments, implicating these proteins in the regulation of transcytosis.
Postgraduate Essay Prize Winner for 2005 A New Look at the Affluent Worker: The Good Working Mother in Post-War Britain

The number of married women working outside their homes after the Second World War rose rapidly despite widespread criticism of working wives and mothers. This article discusses threemain trends associated with this change. First, many women reacted to the discourse criticizing working mothers by trying to change the view of ideal motherhood as exclusively domestically bound. They defended their actions by arguing that a good mother was not solely one who stayed at the beck and call of her family, but one who nurtured their self-reliance and independence by not being constantly available and provided goods and pleasures otherwise out of reach of the family. Second, the criticism of working mothers combined with the dual burden that most women faced in choosing employment to create an unprecedented demand for part-time jobs. The change in women's workforceparticipation since WorldWar IIis almostentirelyattributable to the rise in part-time workers. Third, because observers and the women themselves so often described wives' work as providing extras for the family, the value of women's work was debased. This obscured women's role in creating the affluent society and allowed the male breadwinner ideal to continue unaffected despite major social change, as the public still generally viewed men as having primary responsibility for family support.
The Curious Case of the Yen as a Safe Haven Currency: A Forensic Analysis

During risk-off episodes, the yen is a safe haven currency and on average appreciates against the U.S. dollar. We investigate the proximate causes of yen risk-off appreciations. We find that neither capital inflows nor expectations of the future monetary policy stancecan explain the yen’s safe haven behavior. In contrast, we find evidence that changes in market participants’ risk perceptions trigger derivatives trading, which in turn lead to changes in the spot exchange rate without capital flows. Specifically, we find that risk-offepisodes coincide with forward hedging and reduced net short positions or a buildup of net long positions in yen. These empirical findings suggest that offshore and complex financial transactions should be part of spillover analyses and that the effectiveness of capital flow management measures or monetary policy coordination to address excessive exchange rate volatility might be limited in certain cases.
Pulmonary histopathology in cocaine abusers

Lung histopathology was reviewed from 52 autopsies with positive toxicologic tests for cocaine from the medical examiners' offices in Dallas and Austin, TX. The median patient age was 34.7 years, and the male to female ratio was 2:1. Twelve individuals primarily used the drug intravenously and six primarily smoked it, but in most patients usage history was not known. The most frequent manner of death was accidental, consisting predominantly of cocaine overdoses. Other frequent manners of death included both natural causes and homicides. Subjects with chest trauma were excluded from the study. Twenty-three age-matched control cases with negative cocaine histories and toxicologic tests also were obtained from medical examiner autopsies. Histopathologic findings in the cocaine abuse group included acute hemorrhage, 58% (P = .05); chronic hemorrhage, 40% (P < .01), interstitial pneumonitis/fibrosis, 38% (P < 0.01); congestion, 88% (P < .01); and intra-alveolar edema, 77% (P < .01). These changes were remarkably consistent regardless of locale or method of use. Our findings demonstrate that pulmonary hemorrhage is more frequent than suggested by clinical hemoptysis and that chronic pulmonary diseases such as interstitial fibrosis may develop in long-term users.
A simplified analysis of spherical and cylindrical blast waves

Investigations into the behaviour of the gas flowbehind spherical or cylindrical blasts have shown that secondary shocks arise within the original detonation gases. The secondary shock, at first weak, is carried outward with the expanding gases. Subsequently it strengthens and bends back toward the origin, arriving there with high intensity.By using some recently developed techniques in shock dynamics and extending them where necessary, a theory is developed by which the motion of the main shock wave, as well as the formation and subsequent motion of the secondary shock, are given by explicit formulae. In addition, a method for determining, also by explicit formulae, the location of the contact surface between the detonation gases and the outside atmosphere is given. The results of a specific problem, which has been solved by numerically integrating the total equations of motion, and has also been checked experimentally, are compared with the results of the present theory.
PTP1B as a drug target: recent developments in PTP1B inhibitor discovery

Protein tyrosine phosphatase 1B (PTP1B) is an effective target for the treatment of both type 2 diabetes and obesity; however, targeting PTP1B for drug discovery is challenging because of the highly conserved and positively charged active-site pocket. Tremendous progress has been made in the development of potent and selective PTP1B inhibitors that engage both the active site and no catalytic sites. Several strategies are being pursued to improve the pharmacological properties of PTP1B inhibitors. These new developments suggest that it is feasible to acquire PTP1B-based, small-molecule therapeutics with the requisite potency and selectivity. Future efforts will probably transform the potent and selective PTP1B inhibitors into orally available drugs with desirable physicochemical properties and in vivo efficacies.
Tissue factor-mediated endocytosis, recycling, and degradation of factor VIIa by a clathrin-independent mechanism not requiring the cytoplasmic domain of tissue factor.

Endocytosis and recycling of coagulation factor VIIa (VIIa) bound to tissue factor (TF) was investigated in baby hamster kidney (BHK) cells stably transfected with TF or TF derivatives. Cell surface expression of TF on BHK cells was required for VIIa internalization and degradation. Approximately 50% of cell surface–bound VIIa was internalized in one hour, and a majority of the internalized VIIa was degraded soon thereafter. Similar rates of VIIa internalization and degradation were obtained with BHK cells transfected with a cytoplasmic domain-deleted TF variant or with a substitution of serine for cysteine at amino acid residue 245 (C245S). Endocytosis of VIIa bound to TF was an active process. Acidification of the cytosol, known to inhibit the internalization via clathrin-coated pits, did not affect the internalization of VIIa. Furthermore, receptor-associated protein, known to block binding of all established ligands to members of the low-density lipoprotein receptor family, was without an effect on the internalization of VIIa. Addition of tissue factor pathway inhibitor/factor Xa complex did not affect the internalization rate significantly. A substantial portion (20% to 25%) of internalized VIIa was recycled back to the cell surface as an intact and functional protein. Although the recycled VIIa constitutes to only approximately 10% of available cell surface TF/VIIa sites, it accounts for 65% of the maximal activation of factor X by the cell surface TF/VIIa. In summary, the present data provide evidence that TF-dependent internalization of VIIa in kidney cells occurs through a clathrin-independent mechanism and does not require the cytoplasmic domain of TF.
The use of coroners'/medical examiners' data by forensic nurses.

The role of the forensic nurse clinician is a critically important component of database development. Information that forensic nurses collect and chart may play a role in future research projects.
''Inflammatory'' changes in breast: how to provide a better care to our patients

“Inflammatory” changes of the breast can be seen in many different entities ranging from benign self-limited processes, for example puerperal mastitis, to highly aggressive malignant tumors, such as inflammatory carcinoma. While clinically many of these “inflammatory” processes may look alike, there are some characteristics that allow an accurate differential diagnosis and accordingly a correct treatment. A worldwide effort is made everyday to promote breast health awareness, to facilitate prevention, early detection, and effective treatment. Nevertheless, breast cancer still remains as the number one female cancer and as the second cause of death for cancer in women. Physicians involved in the care of female patients are the first line of defense in the battle against cancer. Therefore, it is important to keep in mind a broad differential diagnosis in patients that seek medical attention complaining of a breast problem. Herein is a summary of the most common causes of inflammatory and inflammatory-like changes in breast with special emphasis on clinical presentation and differential diagnosis.
Noncoding RNAs New Players in Chronic Pain

Chronic pain, a common clinical symptom, is often treated inadequately or ineffectively in part due to the incomplete understanding of molecular mechanisms that initiate and maintain this disorder. Newly identified noncoding RNAs govern gene expression. Recent studies have shown that peripheral noxious stimuli drive expressional changes in noncoding RNAs and that these changes are associated with pain hypersensitivity under chronic pain conditions. This review first presents current evidence for the peripheral inflammation/nerve injury-induced change in the expression of two types of noncoding RNAs, microRNAs, and Kcna2 antisense RNA, in pain-related regions, particularly in the dorsal root ganglion. The authors then discuss how peripheral noxious stimuli induce such changes. The authors finally explore potential mechanisms of how expressional changes in dorsal root ganglion microRNAs and Kcna2 antisense RNA contribute to the development and maintenance of chronic pain. An understanding of these mechanisms may propose novel therapeutic strategies for preventing and/or treating chronic pain.