cssi/SciSciGPT-SciSciNet huggingface dataset:
Ectopic CRYPTOCHROME Renders TIM Light Sensitive in the Drosophila Ovary

The period (per) and timeless (tim) genes play a central role in the Drosophila circadian clock mechanism. PERIOD (PER) and TIMELESS (TIM) proteins periodically accumulate in the nuclei of pace-making cells in the fly brain and many cells in peripheral organs. In contrast, TIM and PER in the ovarian follicle cells remain cytoplasmic and do not show daily oscillations in their levels. Moreover, TIM is not light sensitive in the ovary, while it is highly sensitive to this input in circadian tissues. The mechanism underlying this intriguing difference is addressed here. It is demonstrated that the circadian photoreceptor CRYPTOCHROME (CRY) is not expressed in ovarian tissues. Remarkably, ectopic cry expression in the ovary is sufficient to cause degradation of TIM after exposure to light. In addition, PER levels are reduced in response to light when CRY is present, as observed in circadian cells. Hence, CRY is the key component of the light input pathway missing in the ovary. However, the factors regulating PER and TIM levels downstream of light/cry action appear to be present in this non-circadian organ.
The Combinatorial Laplacian of the Tutte Complex

Abstract Let M be an ordered matroid and C••(M) be an exterior algebra over its underlying set E, graded by both corank and nullity. Then C•0(M) is the simplicial chain complex of IN(M), the simplicial complex whose simplices are indexed by the independent sets of the matroid. Dually, C0•(M) is the cochain complex of IN(M*). We give a combinatorial description of a basis of eigenvectors for the combinatorial Laplacian of a family of boundary maps on the double complex, extending work by W. Kook, V. Reiner, and D. Stanton [2000, J. Amer. Math. Soc.13, 129–148] on IN(M). The eigenvalues are enumerated by a weighted version of the Tutte polynomial, using an identity of G. Etienne and M. Las Vergnas [1998, Discrete Math.179, 111–119]. As an application, we prove a duality theorem for the cohomology of Orlik–Solomon algebras.
Analysis of EMG patterns of control subjects and subjects with ACL deficiency during an unanticipated walking cut task

Abstract Purpose The purpose of this study was to describe the muscle activation patterns of the vastus lateralis (VL), medial hamstrings (MH) and lateral hamstrings (LH) associated with subjects that were anterior cruciate ligament (ACL) deficient and controls. Methods A total of 54 subjects participated in this study including 25 ACL deficient subjects subdivided into copers (n = 9) and non-copers (n = 16) using clinical criteria. Muscle activation patterns were recorded at 1000 Hz during an unanticipated side step cut task. The root mean square processed data (time constant 11 ms) were ensemble averaged from 20% of stance before heel strike to toe off. Using the first five harmonics of the Fourier Coefficients as features, muscle activation patterns were divided using a cluster analysis algorithm. Results A majority (76–93%) of control subjects used three muscle activation patterns for each muscle. The coper group preferentially used a particular VL and MH activation pattern >2 times more frequently than controls. The non-coper group also preferentially used a MH activation pattern >2 times more frequently than controls and utilized a unique MH and LH activation pattern, distinct from the copers and controls. Conclusions Specific muscle activation patterns distinguish subsets of subjects that are healthy and injured, suggesting possible patterns of muscle activation that contribute to coping status.
Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis

Hedgehog signalling--an essential pathway during embryonic pancreatic development, the misregulation of which has been implicated in several forms of cancer--may also be an important mediator in human pancreatic carcinoma. Here we report that sonic hedgehog, a secreted hedgehog ligand, is abnormally expressed in pancreatic adenocarcinoma and its precursor lesions: pancreatic intraepithelial neoplasia (PanIN). Pancreata of Pdx-Shh mice (in which Shh is misexpressed in the pancreatic endoderm) develop abnormal tubular structures, a phenocopy of human PanIN-1 and -2. Moreover, these PanIN-like lesions also contain mutations in K-ras and overexpress HER-2/neu, which are genetic mutations found early in the progression of human pancreatic cancer. Furthermore, hedgehog signalling remains active in cell lines established from primary and metastatic pancreatic adenocarcinomas. Notably, inhibition of hedgehog signalling by cyclopamine induced apoptosis and blocked proliferation in a subset of the pancreatic cancer cell lines both in vitro and in vivo. These data suggest that this pathway may have an early and critical role in the genesis of this cancer, and that maintenance of hedgehog signalling is important for aberrant proliferation and tumorigenesis.
Microscale nonreductive release of O-linked glycans for subsequent analysis through MALDI mass spectrometry and capillary electrophoresis.

A new β-elimination-based procedure has been devised for a microscale release of O-linked oligosaccharides from glycoproteins. Unlike the conventional Carlson degradation, which leads to formation of alditols, the procedure reported here renders the reducing end intact. Conversion of the liberated oligosaccharides to glycosylamines in ammonia medium is followed by the production of the reducing oligosaccharides through the addition of boric acid. The quantitatively generated oligosaccharides with the reducing end can subsequently be derivatized with a fluorophoric reagent for capillary electrophoresis or, alternatively, analyzed through MALDI mass spectrometry. The microscale version of these chemical steps permits us to investigate structurally O-linked oligosaccharides at very low levels.
Chemistry of singlet oxygen--48. Isolation and structure of the primary product of photooxygenation of 3,5-di-t-butyl catechol.

The dye-sensitized photooxygenation of t-butyl substituted catechols has been investigated. The primary product from 3,5-di-t-butyl catechol has been isolated and shown to be a hydroperoxydienone by single crystal X-ray diffraction. The absence of sensitizer effects and the faster reaction rate in polar solvents suggest that the reaction proceeds with singlet oxygen as the primary oxygenating species. Charge-transfer or full electron-transfer from the catechol to singlet oxygen is probably involved. Substituent effects are in agreement with this mechanism. The products from thermal breakdown of the hydroperoxydienone are inconsistent with a Baeyer-Villiger mechanism.
Computer science and information technology associate-level curricular guidelines

This poster presentation will feature draft curriculum guidelines recently developed by the Two-Year College Education Committee (TYCEC), a standing committee of the ACM Education Board. The TYCEC is charged with developing and updating computing curricula guidelines for associate-degree granting institutions worldwide. To this end, the TYCEC is in the process of substantial revisions of the associate-level curriculum guidelines for transfer Computer Science degree programs and career Information Technology degree programs.
Atrial natriuretic peptide inhibits the stimulation of aldosterone secretion but not the transient increase in intracellular free calcium concentration induced by angiotensin II addition.

The effect of atrial natriuretic peptide (ANP) on cellular calcium metabolism was evaluated in bovine adrenal glomerulosa cells stimulated by agonists that use the Ca2+- phosphoinositide messenger system. The calcium-sensitive probe aequorin was used to measure intracellular free calcium concentration, and the aldosterone secretory rate was simultaneously monitored. ANP did not block the calcium transient induced by β-[Asp1]angiotensin II (β-[Asp1]All), an All analog, but markedly reduced the stimulated rate of aldosterone secretion. Consistent with these findings, radiolabeled 45Ca efflux stimulated by All and carbachol was not altered by the concurrent addition of ANP. These results indicate that ANP has no effect on the phosphoinositide-mediated calcium transient and the associated rise in cellular calcium efflux, suggesting that these parameters of calcium metabolism are not the locus of ANP's inhibitory action. (Endocrinology 122: 1460–1465,1988)
Integrin α5β1 and Fibronectin Regulate Polarized Cell Protrusions Required for Xenopus Convergence and Extension

Summary Background Integrin recognition of fibronectin is required for normal gastrulation including the mediolateral cell intercalation behaviors that drive convergent extension and the elongation of the frog dorsal axis; however, the cellular and molecular mechanisms involved are unclear. Results We report that depletion of fibronectin with antisense morpholinos blocks both convergent extension and mediolateral protrusive behaviors in explant preparations. Both chronic depletion of fibronectin and acute disruptions of integrin α 5 β 1 binding to fibronectin increases the frequency and randomizes the orientation of polarized cellular protrusions, suggesting that integrin-fibronectin interactions normally repress frequent random protrusions in favor of fewer mediolaterally oriented ones. In the absence of integrin α 5 β 1 binding to fibronectin, convergence movements still occur but result in convergent thickening instead of convergent extension. Conclusions These findings support a role for integrin signaling in regulating the protrusive activity that drives axial extension. We hypothesize that the planar spatial arrangement of the fibrillar fibronectin matrix, which delineates tissue compartments within the embryo, is critical for promoting productive oriented protrusions in intercalating cells.
Unexpected recovery in a newborn with severe hypomyelinating neuropathy

We report the case of a severely hypotonic and weak term newborn who required ventilatory support from the time of birth. Serial neurophysiologic studies were consistent with severe demyelinating polyneuropathy. The infant's condition deteriorated over several weeks despite treatment with corticosteroids and intravenous immunoglobulin (IVIG) for presumed inflammatory demyelinating polyneuropathy. Histopathologic findings in a sural nerve biopsy, however, were similar to those previously reported in congenital hypomyelinating neuropathies. After 12 weeks of hospitalization and after discontinuation of corticosteroids, the patient began to recover and required no further ventilatory support. Remarkable improvement has continued for 18 months. This patient raises questions about the underlying mechanisms of hypomyelinating neuropathies in early infancy.
The complete cDNA and deduced amino acid sequence of equine IgE.

Abstract The cDNA from a transcript encoding the complete heavy chain of the equine immunoglobulin IgE has been cloned and sequenced. A fragment of the equine epsilon gene was amplified from cDNA using PCR and this fragment was then used to probe a horse cDNA library prepared from peripheral blood lymphocytes. A recombinant clone containing the cDNA encoding the complete horse epsilon chain and its associated V-D-J and leader, was subsequently isolated and sequenced. Comparison of the deduced amino acid sequence of equine IgE with the Cϵ heavy chains of other species indicates it to be most similar to human Cϵ (54%), followed by sheep Cϵ (52%); the greatest sequence similarity was found in the Cϵ3 and Cϵ4 domains among the species compared. The associated V-region had greatest similarity in FR1 to those reported for sheep and the cow (>80%) but less than 60% to the V H sequences of other species in FR3.
Successful reversal of Barrett's esophagus with multipolar electrocoagulation despite inadequate acid suppression

Abstract Background: Barrett's epithelium is a risk factor for esophageal cancer. In this study we attempted to reverse Barrett's epithelium in an acid-reduced environment by using multipolar electrocoagulation. Methods: All patients had specialized columnar epithelium of at least 2 cm in length. Patients with dysplasia on successive screening examinations were excluded. Esophageal motility and 24-hour pH studies were performed before therapy and at 9 and 18 weeks. All patients received lansoprazole 30 mg twice a day regardless of pH study results. Multipolar electrocoagulation was applied to one side of the esophagus (2 to 3 cm per session) with the contralateral side serving as control. Biopsies were obtained from each 2 cm length at each endoscopy and reviewed by a single, blinded pathologist. At the 9-week evaluation of the treatment side, all patients elected to undergo multipolar electrocoagulation therapy for the control side. Results: Twenty-seven patients completed the study: 21 men and 6 women, ages 33 to 81 years, length of specialized columnar epithelium 2 to 10 cm. Endoscopy at the 18-week follow-up showed normal mucosa (n = 16), residual small ( Conclusions: Multipolar electrocoagulation therapy can induce re-epithelialization with normal squamous mucosa in most patients with specialized columnar epithelium and does not adversely affect esophageal motility. Adequate acid suppression is not mandatory for therapy to be effective in the short term. (Gastrointest Endosc 1999;49:547-53.)
The violence of heteronormativity in communication studies: notes on injury, healing, and queer world-making

Heteronormativity is everywhere. It is always already present in our individual and collective psyches, social institutions, cultural practices, and knowledge systems. In this essay, I provide some sketches for a critical analysis of heteronormativity in the communication discipline. More specifically, I examine the symbolic, discursive, psychological, and material violence of heteronormativity, and begin exploring ways to heal, grow, transform, and contemplate new possibilities in our social world. To accomplish this, this essay is divided into live sections. First, I discuss the study of sexuality in Communication. Next, through the notion of injury, I focus on the violence of heteronormativity. Third, using the concept of healing, I discuss ways of unpacking heteronormativity through a critique of hegemonic heterosexuality. Further, I offer potential ways for queer world-making through the lens of queer theory. I conclude by exploring the need for more sexuality research in the discipline by engaging the productive tensions between constructive and deconstructive impulses.
Characterization of beta-conglycinin and glycinin soy protein fractions from four selected soybean genotypes

The beta-conglycinin and glycinin fractions of soy protein were isolated from Macon, Ohio FG1, Enrei, and IL2 genotypes that were grown under the same environmental conditions. The soy protein fractions were evaluated to determine whether chemical composition and gel-forming properties were related. Amino acid analyses suggested that the hydrophobic residues may be the primary cause of differences in soy protein gel characteristics as the storage moduli increased with higher percentages of hydrophobic residues. Reversed-phase high-performance liquid chromatography profiles revealed variations in the composition of each fraction that corresponded to differences observed among the storage moduli. The gel-forming properties may be related to more than just protein content, such as the amount and type of amino acid in the fraction.
Dual antigenic recognition by cloned human gamma delta T cells.

Abstract The function of gamma delta T cells is still elusive. The nature of the antigens that they recognize and the mode of presentation of these antigens are largely unknown. The majority of human peripheral gamma delta T cells bear a V gamma 9/V delta 2 T cell receptor, and display nonclonal reactivity to mycobacteria, without restriction by MHC. It is unknown whether these cells have clonal antigenic specificity as well. Here we describe rheumatoid arthritis-derived V gamma 9/V delta 2 T cell clones, displaying dual antigenic recognition: a nonclonal, MHC-unrestricted recognition of mycobacteria, and a clonal recognition of a short tetanus toxin peptide presented by HLA-DRw53, a nonpolymorphic class II MHC molecule associated with susceptibility to rheumatoid arthritis. This is the first evidence that V gamma 9/V delta 2 T cells can recognize nominal antigenic peptides presented by class II MHC molecules. These results suggest that much like alpha beta T cells, V gamma 9/V delta 2 cells may contribute to the immune response against foreign antigens in an antigen-specific and MHC-restricted manner. The reactivity of these gamma delta T cells to mycobacteria may represent a superantigen-like phenomenon.
The clinical use of anticholinergic drugs as treatment for extrapyramidal side effects of neuroleptic drugs

The clinician using neuroleptic drugs for the treatment of psychotic patients must face a number of questions regarding whether and how to use anticholinergic drugs when extrapyramidal side effects appear. This article explores some of these questions, suggests how they might best be answered, reviews the studies which address the questions, and notes some of the deficiencies in the available data base. Strategies for anticholinergic drug use, given the limited information available, are offered.
Role of tensor force in charge exchange reactions

Abstract The discrepancy between theory and experiment in the analysis of the 54 Fe( 3 He, t) 54 Co reaction is removed by including tensor force in the effective interaction.
Successful cochlear implantation in a patient with superficial siderosis.

Abstract Objective To define the presentation and outcome of cochlear implantation in a patient with profound sensorineural hearing loss due to superficial siderosis. Study design Retrospective case review. Results Postimplantation speech reception threshold was 34 dB, and hearing in noise testing sentences were 71% demonstrating a successful outcome. These results have been maintained for 5 years after implantation. Conclusion Cochlear implantation is a potentially successful rehabilitation option for certain patients with profound sensorineural hearing loss due to superficial siderosis.
Comparison of l-Selectin and CD11b on Neutrophils of Adults and Neonates during the First Month of Life

The newborn infant is particularly susceptible to infection in the first weeks of life and this may be, in part, related to functional impairment of neonatal neutrophils in regard to adherence, chemotaxis, and migration. Differences in expression of the neutrophil adherence molecules, l-selectin and CD11b/CD18 (Mac-1), have been previously demonstrated in cord blood and in very young infants (≤ 48 h) compared with adults, but it is unknown for how long these differences persist. We measured surface expression of neutrophil l-selectin and CD11b using flow cytometry in healthy term human newborns from 24 h through 4 wk of age. We also measured levels of soluble l-selectin using an ELISA in neonates though the age of 4 wk. Compared with adults, neonates expressed significantly less l-selectin on resting neutrophils through 4 wk of age, with the lowest levels being at 24 h. Expression of l-selectin on the neutrophil after activation with N-formyl-methionyl-leucyl-phenylalanine was less in the neonate than in the adult (p < 0.05) for the first week of life. Soluble l-selectin showed a steady increase with age in the neonates. Soluble l-selectin was significantly lower in the 24-h neonate compared with the adult and was higher in the 4-wk neonate compared with the adult. CD11b expression was similar between neonates and adults on unstimulated neutrophils, but upon activation, the neonatal neutrophil demonstrated significantly lower up-regulation of CD11b on the neutrophil surface through 4 wk of age compared with adults (p < 0.05 for all ages except 1 wk). These findings that differences in expression of l-selectin and CD11b from that in adults persist throughout the neonatal period provide further evidence that these differences may play a role in the neutrophil defects observed during the neonatal period.
Pituitary and hypothalamic insulin-like growth factor-I (IGF-I) and IGF-I receptor expression in food-deprived rats.

Abstract The present study was designed to evaluate a possible role for the insulin-like growth factor-I (IGF-I) system in mediating the suppression of growth hormone (GH) secretion observed in food-deprived rats by measuring IGF-I mRNA, receptor concentration and receptor mRNA in neuroendocrine tissues (hypothalamus and pituitary). Rats were deprived of food (food-deprived) for 72 h or had free access to food (fed). Tissues were processed for measurement of steady-state levels of: (a) IGF-I and IGF-I receptor mRNA (by solution hybridization/RNase protection assay); (b) IGF-I in serum and tissue extracts (by RIA) and (c) IGF-I displacable [125I]IGF-I binding to plasma membrane preparations. Food deprivation resulted in decreased serum and liver levels of IGF-I. Kidney IGF-I mRNA levels were reduced 80% in food-deprived rats with a concomitant increase in IGF-I receptor concentration and mRNA levels. Refeeding of food-deprived rats fully normalized these perturbations. Pituitary IGF-I content was reduced 50% in food-deprived rats while IGF-I mRNA levels were unaffected. A modest increase was seen in pituitary IGF-I receptor concentration; however, IGF-I receptor mRNA levels were not changed. Hypothalamic IGF-I mRNA content was reduced in 72 h food-deprived rats while IGF-I receptor binding capacity and mRNA were unaffected. In conclusion, IGF-I mRNA levels are decreased in liver, kidney and hypothalamus together with a reduction in plasma IGF-I in food-deprived rats but is unaffected in anterior pituitary. IGF-I receptor gene expression and binding capacity are coordinately regulated in kidney and hypothalamus, but not in the pituitary. Thus, nutrient signals appear to differentially influence the pituitary compared to peripheral tissues, suggesting that IGF-I may play a unique role in pituitary GH regulation.
Influence of Composition on Continuous Cooling Sensitization of Type 304 Stainless Steel

Abstract This study focuses on the influence of composition (primarily the carbon content) on continuous cooling sensitization. The carbon content dependence of the critical cooling rate for sensit...
NW Pacific slab rheology, the seismicity cutoff, and the olivine to spinel phase change

Along the Kamchatka-Kuril-Japan-Izu-Bonin-Mariana subduction zones, the old age of the subducting Pacific Plate and the rapid subduction rate together suggest that earthquakes should occur to the bottom of the transition zone. However, the seismicity cutoff varies in depth between 350 km and 650 km. Along these subduction zones, the largest deep-focus earthquakes invariably occur near the depth of the local seismicity cutoff regardless of its depth. The events near the seismicity cutoffs also have systematically different focal mechanisms than shallower events. Furthermore, data from S660P arrivals, residual sphere analysis, and tomographic studies all show that the slab dip consistently steepens to a near-vertical orientation at the seismicity cutoff. This change in slab dip indicates a strength loss in the slab. We hypothesize the following causal connection among all these observations: The cold temperatures in the slab kinetically hinder the olivine to spinel phase change and allow the olivine to persist metastably to depths well below its equilibrium pressure. When the phase transition occurs, it nucleates very fine-grained spinel which acts as a lubricant, allowing the initiation of earthquake faulting at high confining pressures which further nucleates additional fine-grained spinel. The cold anomaly of the slab severely inhibits the growth of the nucleated spinel crystals. The presence of the fine-grained spinel crystals reduces the strength of the coldest part of the slab by several orders of magnitude, allowing high slab deformation rates. Additionally, the phase change, by increasing the density, provides a negative buoyancy force. Combined, these processes reduce the slab membrane strength and allow the slab to descend at a steeper dip.
Capabilities and Uses of a Graphic Display System as an Interface between the Zero Gradient Synchrotron Computer and the Human Operator

The control computer system at the Zero Gradient Synchrotron (ZGS) contains a 20" cathoderay graphic display system that can generate points, vectors, and characters. A variety of software routines have been written to operate the ZGS monitor on-line to obtain the required data, to perform the necessary calculations, and to generate the specific display patterns. Two dimensional displays describe accelerator parameters that are functions of time, of a space coordinate, or of a second machine parameter such as ring magnet field. "Three dimensional", displays (isometric), such as tune as a function of radial position and of ring magnet field, can also be generated. Many of the display patterns can be updated quickly enough so that the operator can follow the changes during an adjustment or optimization procedure. Experience shows that this display system can present complex information to the ZGS operator in a form that is easily understood. Permanent records of display information can be made by photography, by using the 30" X-Y plotter system, and by using the line printer. A variety of examples are discussed.
Resonant instability of ducted free supersonic mixing layers induced by periodic Mach waves

It is known that the mixing or spreading rate of free mixing layers decreases with an increase in the convective Mach number of the flow. At supersonic convective Mach number the natural rate of mixing of the shear layers is very small. It is believed that the decrease in mixing rate is directly related to the decrease in the rate of growth of the instabilities of these flows. In an earlier study (Tarn & Hu 1989) it was found that inside a rectangular channel supersonic free shear layers can support two families of instability waves and two families of acoustic wave modes. In this paper the possibility of driving these normal acoustic wave modes into resonant instability by using a periodic Mach wave system is investigated. The Mach waves can be generated by wavy walls. By properly choosing the wavelength of the periodic Mach wave system mutual secular excitation of two selected acoustic wave modes can be achieved. In undergoing resonant instability, the acoustic modes are locked into mutual simultaneous forcing. The periodic Mach waves serve as a catalyst without actually being involved in energy transfer. The resonant instability process is analysed by the method of multiple scales. Numerical results indicate that by using wavy walls with an amplitude-to-wavelength ratio of 1½% it is possible to obtain a total spatial growth of e9 folds over a distance of ten channel heights. This offers reasonable promise for mixing enhancement. The results of a parametric study of the effects of flow Mach numbers, temperature ratio, shear-layer thickness, modal numbers as well as three-dimensional effects on the spatial growth rate of the resonant instability are reported and examined so as to provide basic information needed for future feasibility analysis.
Predictable Surprises: The Disasters You Should Have Seen Coming, and How to Prevent Them

The article reviews the book “Predictable Surprises: The Disasters You Should Have Seen Coming, and How to Prevent Them,” by Max H. Bazerman and Michael D. Watkins.
Transfer RNA: three-dimensional structure and biological function

The participation of transfer RNA in the expression of genetic information is as universal as the genetic code. Recent work on the three-dimensional structure of one transfer RNA from yeast strongly suggests that the three-dimensional structure of all transfer RNA molecules are very similar to each other.
A multifunctional peptide based on the neutrophil immune defense molecule, CAP37, has antibacterial and wound-healing properties

CAP37, a protein constitutively expressed in human neutrophils and induced in response to infection in corneal epithelial cells, plays a significant role in host defense against infection. Initially identified through its potent bactericidal activity for Gram-negative bacteria, it is now known that CAP37 regulates numerous host cell functions, including corneal epithelial cell chemotaxis. Our long-term goal is to delineate the domains of CAP37 that define these functions and synthesize bioactive peptides for therapeutic use. We report the novel finding of a multifunctional domain between aa 120 and 146. Peptide analogs 120-146 QR, 120-146 QH, 120-146 WR, and 120-146 WH were synthesized and screened for induction of corneal epithelial cell migration by use of the modified Boyden chamber assay, antibacterial activity, and LPS-binding activity. In vivo activity was demonstrated by use of mouse models of sterile and infected corneal wounds. The identity of the amino acid at position 132 (H vs. R) was important for cell migration and in vivo corneal wound healing. All analogs demonstrated antimicrobial activity. However, analogs containing a W at position 131 showed significantly greater antibacterial activity against the Gram-negative pathogen Pseudomonas aeruginosa. All analogs bound P. aeruginosa LPS. Topical administration of analog 120-146 WH, in addition to accelerating corneal wound healing, effectively cleared a corneal infection as a result of P. aeruginosa. In conclusion, we have identified a multifunctional bioactive peptide, based on CAP37, that induces cell migration, possesses antibacterial and LPS-binding activity, and is effective at healing infected and noninfected corneal wounds in vivo.
Probiotics to Prevent Antibiotic-Related Diarrhea

Probiotics are microorganisms that provide a health benefit when consumed in adequate amounts; a common example is dairy products containing live cultures. Does a probiotic beverage containing acti...
Evidence for generation of a large amount of nitric oxide-like vascular smooth muscle relaxant by cholesterol-rich neutrophils

To determine the effect of cholesterol incorporation on the ability of neutrophils to generate superoxide radicals and nitric oxide-like vasorelaxant material, isolated human neutrophils were incubated with cholesterol-rich liposomes, which increased total cholesterol content by 141% and esterified cholesterol content by 523%. Cholesterol loading resulted in 5 to 7 fold increase in cytosolic calcium in resting as well as in PMA or f-MLP-stimulated cells, but a marked (P l -NMMA, thus suggesting that the vasorelaxant material was nitric oxide. The greater generation of nitric oxide by cholesterol-rich neutrophils occurs perhaps in response to increased cytosolic calcium.
Progressive beta cell failure in type 2 diabetes mellitus of youth.

The pathophysiology of type 2 diabetes mellitus (T2DM) involves insulin resistance and insulin deficiency. We report the progression in insulin sensitivity and secretion over a 6-year period in an adolescent with T2DM. This report further demonstrates that the earliest abnormality in youth T2DM is insulin resistance followed by progressive β-cell failure.
A comprehensive test of the 'limiting resources' framework applied to plant tolerance to apical meristem damage

Tolerance to apical meristem damage (AMD) is a form of plant defense against herbivory. Theoretical models come to different conclusions about the effects of inorganic soil nutrient levels on tolerance to AMD, and different plants have shown different relationships between these variables. To assign some order to these disparate patterns and to resolve conflicts among the models, the ‘limiting resources model’ (LRM) was developed. However, we believe that the LRM is actually comprised of several different models, which we describe. Our study marks the first comprehensive and simultaneous test of the entire LRM framework, treating it explicitly as separate models, which also evaluates the models’ underlying assumptions. We studied tolerance to AMD in laboratory-reared natural populations of Arabidopsis thaliana from three different regions of Europe, spanning a wide latitudinal gradient. We show that, in different populations of this species, basic responses to nutrients and damage are best described by different models, which are based on different assumptions and make different predictions. This demonstrates the need for complexity in our explanations, and suggests that no one existing model can account for all relationships between tolerance to AMD and nutrients. Our results also demonstrate that fruit production can provide a misleading approximation of fitness in A. thaliana, contrary to the common assumption in the literature.
Assessing the impact of an educational program on decreasing prescribing errors at a university hospital.

BACKGROUND: Several complex and costly interventions reduce medication errors. Little exists on the effectiveness of providing education and feedback to institutional clinicians as a means of reducing errors. OBJECTIVE: To determine the impact on prescribing errors of a pharmacist-led educational intervention. DESIGN: Prospective, interrupted time series study. SETTING: This study was conducted among internal medicine residents at the 320-bed University of Toledo Medical Center. INTERVENTION: The educational intervention was conducted during a 6-month period beginning in November 2006. The intervention included an initial hour-long lecture followed by biweekly and then monthly discussions that used timely, institution-specific examples of prescribing errors. MEASUREMENTS: Data were collected at 5 time points: month 0 (preintervention period); months 1, 3, and 6 (intervention period); and month 7 (postintervention period). Errors were identified, transcribed, coded, and entered into a database. The primary outcome was the frequency of prescribing errors during each period. A Bonferroni-adjusted chi-square analysis was conducted with an a priori experiment-wise alpha of 0.05. RESULTS: A reduction in prescribing errors of 33% following the first intervention month and a mean 26% reduction during the study period were observed (P < 0.0025). The frequencies of preintervention and postintervention errors did not differ significantly. CONCLUSIONS: A straightforward educational intervention reduced prescribing errors during the period of active intervention, but this effect was not sustained. Ongoing communication and education about institution-specific medication errors appear warranted. Journal of Hospital Medicine 2009;4:97–101. © 2009 Society of Hospital Medicine.
A Mutation in the Voltage-Sensor of Kv7.1 Prevents PKA Activation of IKs to Elicit Concealed Type 1 Long QT Syndrome during Stress

Long QT syndrome is associated with prolongation of the corrected QT interval (QTc) and increased risk for ventricular arrhythmias. LQT1 is caused by loss-of-function mutations in the KCNQ1-encoded Kv7.1 α-subunit which mediates the slowly activating delayed rectifier K+ current (IKs) in the heart. A family with a KCNQ1 missense mutation (I235N) in the voltage-sensor of Kv7.1 has concealed LQT1 at rest (QTc, 452±5ms) but shows marked paradoxical QTc prolongation (534±16ms) during the recovery phase of treadmill stress testing. This abnormal recovery response is blunted in patients taking β-adrenergic blockers (487±11ms). Voltage-clamping experiments using HEK293 cells expressing WT or I235N with the Kv7.1 β-subunit KCNE1 showed that I235N decreased KCNQ1 current (IKCNQ1) by 93% and caused a large positive shift in the midpoint potential for activation (V1/2). However, cells co-expressing WT and I235N (to mimic the patients' genotypes) showed only a small decrease in IKCNQ1 (∼30%) and shift in V1/2. Since excessive QTc prolongation in I235N patients appears secondary to β-adrenergic stimulation, we tested whether I235N prevented PKA activation of IKCNQ1. In cells expressing WT, PKA stimulation with forskolin and IBMX increased IKCNQ1 by 64%, but it did not increase IKCNQ1 in cells co-expressing WT and I235N. Computational simulations using a ventricular action potential (AP) model showed that reducing the IKs component by 30% increased the AP duration at 90% repolarization (APD90) by only 1.6%. However, incorporating β-adrenergic signaling showed that reducing the IKs component by 30% and preventing its activation by PKA increased the APD90 by 7.1%. We conclude I235N modestly affects basal QTc, IKs, and APD90, but it prevents PKA activation of IKs to cause a dangerous prolongation in the QTc/APD90 during β-adrenergic stimulation.
Explanation is Not the Point: Domestic Work, Islamic Dawa and Becoming Muslim in Kuwait

Over the past two decades, tens of thousands of migrant domestic workers in Kuwait have developed new-found ‘Islamic piety’.1 Occurring in a much maligned and understudied region—the Arabian Peninsula—this widespread phenomenon has either been elided, cynically dismissed or the motivations for these conversions and their sociohistorical conditions of possibility assumed. Domestic workers’ own articulations focus on ‘house talk’ and suggest a shift in analytic focus, with an emphasis on everyday relationships and activities within households as generative of their new-found Islamic piety. Domestic workers experience becoming Muslim not as a radical break from their previous relationships and religious practices, but as a gradual reworking of them. The domestic workers’ expression of their new-found Islamic faith points to the household as a space of confluence between Islamic ethical practice and the affective and immaterial labour entailed by domestic work, as well as between global Islam and the feminisa...
Coordinate Notch3-Hairy-related Transcription Factor Pathway Regulation in Response to Arterial Injury MEDIATOR ROLE OF PLATELET-DERIVED GROWTH FACTOR AND ERK

The Notch family of receptors and downstream effectors plays a critical role in cell fate determination during vascular ontogeny. Moreover, the human cerebral autosomal dominant artriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) syndrome of premature stroke and dementia is a heritable arteriopathy with alterations in vascular smooth muscle cells (VSMCs) resulting from mutations within Notch3. However, the expression and regulation of the Notch and hairy-related transcription factor (HRT) pathway in adult VSMCs in vitro and in vivo remain poorly characterized. The present study documents that the well-described modulation of VSMC fate in response to vascular injury and growth factor activation involves a coordinate regulation of the Notch and HRT pathways. Furthermore, platelet-derived growth factor promotes a similar coordinate down-regulation of the Notch receptors and HRT genes in cultured VSMCs via an ERK-dependent signaling pathway. Moreover, we established that HRT1 and HRT2 are direct downstream target genes of Notch3 signaling in VSMCs and determined that the activity of the nuclear protein RBP-Jk is essential for their regulation. These findings provide initial insight into the context- and cell type-dependent coordinate regulation of Notch3 and downstream HRT transcriptional pathway effector genes in VSMCs in vitro and in vivo that may have important implications for understanding the role of Notch signaling in human health and vascular disease.
Application Of Diffuse Energy Transfer To Dosimetry In Photodynamic Therapy

This approach to optical dosimetry in photodynamic therapy is based on the hypothesis that tumor eradication requires a minimum absorbed energy density by tissue-localized hematoporphyrin derivative. The required incident fluence is calculated from absorption profiles based on the diffusion approximation to radiative transfer. The results are in satisfactory agreement with empirical light dose levels reported in the clinical literature.
Rosiglitazone, a PPAR-γ Ligand, Reduces Burn Progression in Rats

Burns induce the activation of an inflammatory cascade that generates reactive oxygen radicals and lipid peroxidation leading to burn wound progression and extension. Peroxisome proliferation-activated receptor-gamma is a nuclear hormone receptor that is activated by transcription factors and plays an important role in the regulation of cellular proliferation and inflammation. We hypothesized that treatment of burns with rosiglitazone, a peroxisome proliferation-activated receptor-gamma ligand, would reduce burn wound progression. This is a randomized controlled study of 20 Sprague-Dawley rats. Two burns were created on each animal's dorsum using a brass comb with four rectangular prongs preheated in boiling water and applied for 30 seconds resulting in four rectangular 10 x 20 mm full thickness burns separated by three 5 x 20 mm unburned interspaces (zone of ischemia). Animals were randomized to rosiglitazone 4 mg/kg or vehicle by oral gavage 30 minutes after injury and at 24 and 48 hours after injury. Wounds were observed at 1, 2, 3, and 4 days after injury for visual evidence of necrosis in the unburned interspaces. Full thickness biopsies from the interspaces were evaluated with hematoxylin and eosin staining 7 days after injury for evidence of necrosis. The percentage of interspaces that progressed to necrosis was compared with chi tests. Forty comb burns with 120 unburned interspaces were evenly distributed between rosiglitazone and vehicle. The number of interspaces that progressed to full thickness necrosis at 1, 2, 3, 4, and 7 days after injury in the rosiglitazone and vehicle groups were 9/60 (15%) versus 13/60 (21%) (P = .48), 16/60 (27%) versus 15/60 (20%) (P = 1.00), 24/60 (40%) versus 46/60 (77%) (P = .001), 35/60 (58%) versus 53/60 (88%) (P = .001), and 43/60 (72%) versus 54/60 (90%) (P = .02), respectively. Treatment with oral rosiglitazone reduces the percentage of unburned skin interspaces that progress to full necrosis in a rat comb burn model.
Maternal PD-1 regulates accumulation of fetal antigen-specific CD8+ T cells in pregnancy

The failure to reject the semi-allogeneic fetus suggests that maternal T lymphocytes are regulated by potent mechanisms in pregnancy. The T cell immunoinhibitory receptor, Programmed Death-1 (PD-1), and its ligand, B7-H1, maintain peripheral tolerance by inhibiting activation of self-reactive lymphocytes. Here, we investigated the role of the PD-1/B7-H1 pathway in maternal tolerance of the fetus. Antigen-specific maternal T cells both proliferate and upregulate PD-1 in vivo at mid-gestation in response to paternally inherited fetal antigen. In addition, when these cells carry a null deletion of PD-1, they accumulate excessively in the uterus-draining lymph nodes (P<0.001) without a concomitant increase in proliferation. In vitro assays showed that apoptosis of antigen-specific CD8(+) PD-1(-/-) cells was reduced following peptide stimulation, suggesting that the accumulation of these cells in maternal lymph nodes is due to decreased cell death. However, the absence of neither maternal PD-1 nor B7-H1 had detectable effects on gestation length, litter size, or pup weight at birth in either syngeneic or allogeneic pregnancies. These results suggest that PD-1 plays a previously unrecognized role in maternal-fetal tolerance by inducing apoptosis of paternal antigen-specific T cells during pregnancy, thereby controlling their abundance.
Occupational exposures and risk of systemic lupus erythematosus

This review summarizes the growing body of epidemiologic and experimental research pertaining to the relationship between SLE and occupational exposures, such as crystalline silica, solvents, and pesticides. Epidemiologic studies, using different designs in different settings, have demonstrated moderate to strong associations between occupational silica exposure and SLE. Recent experimental studies of silica in lupus-prone mice provide support for the idea that, in addition to its known adjuvant effect, silica exposure increases the generation of apoptotic material, an important source of self-antigen. Despite compelling experimental studies of the organic solvent trichloroethylene (TCE) in lupus-prone mice, there is little evidence of an overall association of SLE and occupational exposure to a broad classification of solvents in humans. However, there is a lack of data on SLE in occupational cohorts with exposures to TCE or other specific solvents. One epidemiologic study reported an association of pesticide mixing and SLE, while a recent experimental study reported accelerated disease in pesticide-treated lupus-prone mice. Other occupational exposures worth investigating include asbestos, metals, and UV radiation. Attention should also be given to the role of gene-environment interactions, which may require large, multi-site studies that collect both genetic material and occupational exposure data. The quality of exposure assessment is an important consideration in designing and evaluating these studies. The use of pre-clinical endpoints (e.g. high-titer autoantibodies) in occupational cohorts with well-characterized exposure histories may reveal occupational risk factors for autoimmunity, and may also provide baseline data for studies of determinants of progression to SLE.
A photoelastic study of a split palatal major connector

A study was made to determine if the split palatal design of maxillary major connectors used on distal-extension removable partial dentures would result in a reduction of torquing stresses on the abutment teeth when the bases were loaded. A photoelastic model to simulate the maxillary arch, abutment teeth with their periodontal ligaments, edentulous ridges, and mucoperiosteum of the palate and ridges was constructed. Two Kennedy Class II removable partial denture frameworks of chrome-nickel alloy were constructed to fit the photoelastic model. One framework had an intact palatal major connector, and the other had a split in the major connector to separate the base from the abutment tooth as a stress-breaker. The frameworks were placed on the model, loaded, and photographed with polarized light to record the stress pattern in the model. The results of this study showed that the split palatal major connector did reduce the stress delivered to the distal-extension abutment when the base was loaded on the experimental model. A significant amount of stress from loading of the framework was removed from the abutment tooth and transferred to the regions of the model underlying the base.
Migraine: association with personality characteristics and psychopathology

The relationship between migraine and psychopathology has been discussed far more often than it has been systematically studied. Twentieth-century investigators have frequently described the obsessional, rigid, angry personality postulated to characterize migraine sufferers. More recent population-based studies have demonstrated associations between migraine and depression and migraine and panic disorder. This article discusses the relationship of migraine and personality and migraine and psycho-pathology.