cssi/SciSciGPT-SciSciNet huggingface dataset:
Alternative modalities for asthma that reduce stress and modify mood states: evidence for underlying psychobiologic mechanisms.

Objective To review the evidence supporting a role for psychological interventions in the treatment of asthma, with particular emphasis on underlying psychobiological mechanisms. Data Sources Independent literature searches on MEDLINE, PREMEDLINE, Cochrane Library, and PSYCHINFO from their respective inception to 2003 were performed. Separate searches were performed for psychological stress and asthma, psychoneuroimmunology and asthma, stress management, relaxation, asthma, complementary and alternative medicine and asthma, and immune function and psychological intervention . The search was not limited based on language of publication. Study Selection Supportive evidence from overlapping research was included based on the expert opinion of the author and through discussions with consultants in the field. Results This review first discusses human and animal studies focused on psychological stress and the effects of stress on the neuroendocrine and immune system, emphasizing the implication of these effects on asthma. Second, studies that evaluated the influence of stress reduction modalities on neuroendocrine and immune function were examined. Existing evidence from human clinical studies that explored the role of psychological interventions for asthma is reexamined in this context. Conclusions A growing appreciation of the interactions among behavioral, neural, endocrine, and immune processes suggests possible mechanisms through which psychological interventions for asthma may be operating. This review provides a framework in which we can begin to see links among these systems that might provide new insights to guide future explorations.
Abstract 1108: B-cell lymphoma-derived exosomes are reservoirs of inhibitors of apoptosis

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA B-cells, along with other normal and cancerous cells, secrete 50-150 nm vesicles called exosomes. Exosomes carry proteins, mRNA, and miRNA that can be functional upon cellular uptake and are often specific to cell of origin, offering potential as disease biomarkers. Our lab has identified within exosomes from solid tumor cells a cancer-specific protein, Survivin, which is a member of the Inhibitors of Apoptosis (IAP) family. Whether Survivin and other IAP family members such as XIAP, cIAP1 or cIAP2 are also expressed in exosomes from hematopoietic malignancies is yet to be determined. In this study, we aim to investigate the exosomes released from B-cell lymphoma cells and determine the IAP content under basal and sublethal stress conditions. Three human non EBV-transformed B-cell lymphoma lines developed at Wayne State University were used. WSU-FSCCL (follicular small cleaved cell), WSU-DLCL-2 (diffuse large cell), and WSU-WM (Waldenstrom Macroglobulinemia) represent different levels of aggressiveness. Cells were cultured for 24 or 48 hours before exosome isolation from the conditioned media using either ultracentrifugation on a sucrose cushion or ExoQuick (System Biosciences). Sublethal levels of UV irradiation were determined for each cell line by analyzing DNA content by propidium iodide staining with a FACSCalibur. Protein quantity of exosomes was measured using a BCA assay, and protein content was studied using Western blotting. Corresponding gene expression was identified using RT-PCR. Here we report IAP protein and mRNA (except XIAP) within exosomes from basal cells. We are currently probing exosomes from stressed cells for comparison. We hypothesize that the IAP exosomal profile may change under stressed conditions. The specificity and variability in exosomal content offers capabilities not only as disease biomarkers, but also in the immunomodulating activity of exosomes which have shown roles in both stimulating and inhibiting the immune system, We have found evidence that exosomal Survivin plays an immune role in skewing Th1/Th2 populations and decreasing cytotoxic function. Changes in exosome content between basal and stressed cells may have roles in the immunomodulation of the tumor microenvironment which facilitates the evasion of lymphoma cells to immune destruction, as well as possible prognostic benefit as to whether treatments are being effective or detrimental. Citation Format: Heather R. Ferguson Bennit, Malyn M. Asuncion Valenzuela, Jessica S. Jutzy, Nathan R. Wall. B-cell lymphoma-derived exosomes are reservoirs of inhibitors of apoptosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1108. doi:10.1158/1538-7445.AM2014-1108
Organometallic chemical vapor deposition of superconducting, high Tc Pb‐doped Bi‐Sr‐Ca‐Cu‐O thin films

Highly oriented films of the high Tc Bi‐Pb‐Sr‐Ca‐Cu‐O (BPSCCO)superconductor have been prepared by two organometallic chemical vapor deposition (OMCVD) approaches. In the first approach, Pb is introduced by alternate deposition of BSCCO and PbOx films using the volatile metalorganic precursors Cu(acetylacetonate)2, Sr(dipivaloylmethanate)2, Ca(dipivaloylmethanate)2, triphenyl bismuth, and tetraphenyl lead. In the second approach, Pb is incorporated into an OMCVD‐derived BSCCO film by vapor diffusion using PbO as the source. X‐ray diffractometry and scanning electron microscopy reveal that Pb doping significantly improves the crystalline orientation and the film morphology. Films deposited by both methods on [100] single‐crystal MgO consist predominantly of the Bi2(Sr,Ca)3Cu2Ox phase and have a high preferential orientation of the crystallite c axes perpendicular to the substrate surface. Four‐probe resistivity measurements indicate the onset of film superconductivity at ∼110 K and zero resistance by 80 K.
Energy savings in the total site heat integration across many plants

In this paper, an extension of previous work performed for a system of two plants is presented. For a set of n plants, heat transfer leading effectively to energy savings occurs at temperature levels between the pinch points of supplying and receiving plants. In some cases, additional heat transfer in other regions is required to attain maximum savings. A systematic procedure, based on LP and MILP models, is used to identify energy-saving targets for the two forms of integration and find the location of the intermediate fluid circuits. Finally, the optimal location of these circuits allowing restricted operation is discussed. Alternative solutions exist, which allow flexibility for the subsequent design of the multipurpose heat exchanger network.
New Techniques in the Cosmic-Ray Field and Some of the Results Obtained With Them

Each new field of scientific study goes through a period of development which may be likened to the development of a man child. Up to the age of six or seven a boy interests everybody intensely. In babyhood he is new and sweet and altogether charming because of the awakening qualities which bloom forth as he becomes a real person, and from then on up to seven or eight he is intensely interesting because he is revealing day by day what kind of a person he is likely to be. Then from say eight to thirteen he goes through a period in which he is in general best described as a whining brat who knows no law, is always against the government, and has no real friend except his mother. From about thirteen on he begins to find himself as a member of the human family, and by the time he is twenty-one is ready to don the toga and be admitted regularly into the ordered society of adults.
Cell Cycle Activation Contributes to Increased Neuronal Activity in the Posterior Thalamic Nucleus and Associated Chronic Hyperesthesia after Rat Spinal Cord Contusion

Spinal cord injury (SCI) causes not only sensorimotor and cognitive deficits, but frequently also severe chronic pain that is difficult to treat (SCI pain). We previously showed that hyperesthesia, as well as spontaneous pain induced by electrolytic lesions in the rat spinothalamic tract, is associated with increased spontaneous and sensory-evoked activity in the posterior thalamic nucleus (PO). We have also demonstrated that rodent impact SCI increases cell cycle activation (CCA) in the injury region and that post-traumatic treatment with cyclin dependent kinase inhibitors reduces lesion volume and motor dysfunction. Here we examined whether CCA contributes to neuronal hyperexcitability of PO and hyperpathia after rat contusion SCI, as well as to microglial and astroglial activation (gliopathy) that has been implicated in delayed SCI pain. Trauma caused enhanced pain sensitivity, which developed weeks after injury and was correlated with increased PO neuronal activity. Increased CCA was found at the thoracic spinal lesion site, the lumbar dorsal horn, and the PO. Increased microglial activation and cysteine-cysteine chemokine ligand 21 expression was also observed in the PO after SCI. In vitro, neurons co-cultured with activated microglia showed up-regulation of cyclin D1 and cysteine-cysteine chemokine ligand 21 expression. In vivo, post-injury treatment with a selective cyclin dependent kinase inhibitor (CR8) significantly reduced cell cycle protein induction, microglial activation, and neuronal activity in the PO nucleus, as well as limiting chronic SCI-induced hyperpathia. These results suggest a mechanistic role for CCA in the development of SCI pain, through effects mediated in part by the PO nucleus. Moreover, cell cycle modulation may provide an effective therapeutic strategy to improve reduce both hyperpathia and motor dysfunction after SCI.
Parotid gland basement membrane variation in diabetes mellitus

Post-mortem samples of parotid gland were obtained from 15 patients with a history of diabetes mellitus for a minimum of 5 years, and from 15 age- and sex-matched controls. The tissue was studied by direct immunofluorescence for abnormal binding of selected serum proteins, including IgG, IgM, IgA, C3, fibrinogen, polyvalent immunoglobulin and albumin, to acinar and ductal basement membranes of the gland. Thickness of these basement membranes was also assessed using a calibrated magnifier on uniformly enlarged photomicrographs of the tissue which had been stained by the chromotrope silver methenamine method to highlight basement membranes. Results of this investigation revealed parotid gland basement membrane abnormalities in all diabetic subjects as indicated by the binding of IgG, albumin and polyvalent immunoglobulins to ductal and acinar basement membranes. These basement membranes were uniformly negative in control subjects for the binding of all serum proteins tested. Binding of IgA was also noted in 7 of 15 experimental subjects, with 6 of these representing Type I diabetics. Basement membrane measurements revealed no difference in thickness between diabetic and non-diabetic subjects. Variations in parotid diabetic basement membranes evidenced in this study further substantiate the idea that membranopathy in this disease is systemic in nature.
Optimization of sources for focusing wave energy in targeted formations

We discuss a numerical approach for identifying the surface excitation that is necessary to maximize the response of a targeted subsurface formation. The motivation stems from observations in the aftermath of earthquakes, and from limited field experiments, whereby increased oil production rates were recorded and were solely attributable to the induced reservoir shaking. The observations suggest that focusing wave energy to the reservoir could serve as an effective low-cost enhanced oil recovery method. In this paper, we report on a general method that allows the determination of the source excitation, when provided with a desired maximization outcome at the targeted formation. We discuss, for example, how to construct the excitation that will maximize the kinetic energy in the target zone, while keeping silent the neighbouring zones. To this end, we cast the problem as an inverse-source problem, and use a partial-differential-equation-constrained optimization approach to arrive at an optimized source signal. We seek to satisfy stationarity of an augmented functional, which formally leads to a triplet of state, adjoint and control problems. We use finite elements to resolve the state and adjoint problems, and an iterative scheme to satisfy the control problem to converge to the sought source signal. We report on one-dimensional numerical experiments in the time domain involving a layered medium of semi-infinite extent. The numerical results show that the targeted formation's kinetic energy resulting from an optimized wave source could be several times greater than the one resulting from a blind source choice, and could overcome the mobility threshold of entrapped reservoir oil.
Binding of bovine growth hormone to bovine liver membranes.

The binding of [125I]bGH and [125I]hGH to bovine liver membranes is compared to characterize the somatotrophic hormone-receptor interaction. [125I]bGH binding exhibits higher nonspecific binding than [125I]hGH while the time-course of binding and displacement with unlabeled GH are similar. Divalent and monovalent cations enhance [125I]hGH binding with well-defined peaks of binding at specific cation concentrations. Monovalent cations do not enhance [125I]bGH binding at concentrations of 100 mM while divalent cations enhance binding over a range of cation concentration (4–80 mM). The binding of [125I]bGH is dependent upon the presence of divalent cations, with minimal effect of pH upon binding in the absence of calcium. Scatchard plots of bGH and hGH binding data indicate at least two binding sites. We conclude that somatotrophic GH exhibits unique and distinguishing characteristics of binding. The characteristics of hGH binding to the bovine liver membranes suggest that its binding may differ from bGH binding to its homologous receptor.
Peripheral bulge of a foreland basin in the Oslo Region during the Early Silurian

Abstract On the basis of detailed bathymetric analyses, the Lower and Middle Llandovery succession of the Oslo Region shows signs of a transitory uplift which advanced from the present north-northwest across a gently east-sloping epicontinental shelf. In Late Llandovery time a graptolitic shale basin developed in the north-northwestern part of the region, where earlier land-marginal conditions had existed. This basin was previously interpreted as a trough in front of advancing Caledonian nappes. The two concepts are here linked together and a model featuring a low peripheral bulge followed by a foreland basin is outlined. Some information on the shape, height, and speed of the peripheral bulge is deduced. The present interpretation provides important clues for dating movements of the Caledonian thrust front in its later phases.
Profit from the Priceless: Heritage Sites, Property Rights and the Duty to Preserve

This article suggests that corporate responsibility should be interpreted to include concern about resources that cannot easily be treated as commodities. Heritage Sites are places of historical and cultural importance. Given the primacy of contingent valuation methods in creating policy, these sites are often at risk from development or tourism since there is pressure to treat them as revenue centers. The article moves to looking at the status of sites in terms of property rights, drawing on Locke's original formulation. The article concludes that there is a normative justification for treating these sites as collective property that may warrant maintenance, preservation and restricted access.
Design Vulnerability Analysis and Design Improvement by Using Warranty Data

Continuous improvement in reliability is one of the key factors to success in the world automobile market. Good reliability can only be achieved through good design and manufacturing practice. Manufacturers want to allocate their limited resources to improvement in such a way that they can get the highest benefits. The warranty claims database contains more information than any other test for the reliability of products in actual use. Assisted by a design vulnerability index derived from the axiomatic design principle, warranty data can be used to identify the areas of the product such that the improvement of these areas will maximize the gain in reliability improvement. In this paper, we provide a methodology of utilizing warranty data to prioritize design improvement efforts based on design vulnerability and the feedback from warranty data. The methodology is illustrated with an example case. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis and anti-HIV activity of bi-functional betulinic acid derivatives

Betulinic acid (BA) derivatives with a side chain at C-3 can inhibit HIV-1 maturation. On the other hand, BA derivatives with a side chain at C-28 can block HIV-1 entry. In order to combine the anti-maturation and anti-entry activities in a single molecule, new bi-functional BA derivatives containing side chains at C-3 and C-28 have been synthesized. The most potent compound ([[N-[3beta-O-(3',3'-dimethylsuccinyl)-lup-20(29)-en-28-oyl]-7-aminoheptyl]-carbamoyl]methane) inhibited HIV-1 at an EC50 of 0.0026 microM and was at least 20 times more potent than either the anti-maturation lead compound DSB or the anti-entry lead compound IC9564. This bi-functional BA derivative was active against both HIV entry and maturation. These results suggest that bi-functional BA derivatives with dual mechanisms of action have the potential to become clinically useful for AIDS therapy.
Role of tidally periodic density stratification in the creation of estuarine subtidal circulation

[1] Tidally periodic stratification is explored as a mechanism for estuarine subtidal flow creation through the use of a numerical water column model. Using a two equation turbulence closure, a tidally periodic steady state is established and the subtidal circulation is calculated. The results demonstrate that the subtidal circulation caused by this forcing is of the same vertical structure as the expected estuarine exchange flow. Further, the subtidal exchange is of similar magnitude to that given by typical scalings of the baroclinic circulation driven by the longitudinal salinity gradient, but is strongly dependent upon the timing of the stratification event within the tidal cycle, even reversing sign for certain phases. The dependence of this subtidal flow mechanism on the local depth, the tidal forcing and the magnitude of the stratification is explored through the use of a bulk Richardson number, for which the subtidal circulation is maximal at intermediate values, and is reduced for both large and small bulk Richardson numbers. This dependence of the subtidal circulation on the bulk Richardson number is demonstrated to be consistent with an analysis of the energetics of mixing and buoyancy on the tidal timescale.
Macrocycle-mediated cation transport using hollow fiber supported liquid membranes

Abstract Macrocycle-mediated separation and transport of cations using a stable hollow-fiber supported liquid membrane system have been investigated. Mathematical models describing membrane diffusion-limited, macrocycle-mediated transport in cylindrical coordinates have been derived and found to model experimental cation fluxes within a few percent. The effects of flow rate and macrocycle concentration on facilitated transport through hollow fibers have proven analogous to those of stirring speed and macrocycle concentration, respectively, in thin-sheet supported liquid membrane studies. The selectivities observed in the transport of K+ over Na+, K+ over Li+, and Sr2+ over Ba2+ as the NO3 - salts and of Cd (SCN)2 over Zn (SCN2 are identical to those found using thin-sheet supported liquid membrane systems. Similar selectivities were found using emulsion and bulk liquid membrane systems in which the only variation in the chemistry was that macrocycle substituent groups were less hydrophobic and the membrane solvent was different.
Pharmacotherapy: inhibiting LV remodeling—the need for a targeted approach.

The renin–angiotensin system is thought to have a key role in the structural remodeling of the left ventricle that accompanies healing after acute myocardial infarction and is an important determinant of long-term prognosis. Does a direct renin inhibitor provide additive benefit to patients already treated with β-blockers and either angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers?
Spectral signatures for RDX-based explosives in the 3 micron region

Explosive compounds such as RDX, and HMX present significant challenges to optically based sensors. This difficulty is due in part to the low vapor pressures these compounds possess. One approach for sensing explosives that circumvents the low explosive vapor pressure problem, involves focusing on the trace amounts of relatively high vapor pressure impurities that will be present in the vapor signature. In order to effectively detect these volatile impurities, the spectral signature databases must be readily available. One of our goals therefore, is the generation of a database of high resolution spectral signatures for these volatile organic impurities. Some rather formidable spectroscopic measurement challenges have been encountered while working to extend the spectral signature effort to the 3 micron region. Here we will outline progress to date, with a focus on the volatile organic compounds formaldehyde, acetaldehyde, nitromethane, acetone, isobutene, and cyclohexanone.
PHSColograms® and rotated PHSColograms

Abstract This paper discusses the computer-interleaving method of producing autostereoscopic imagery. This method is based in lenticular photography, but replaces the lenticular camera with a computer program and output on a high-resolution imaging device. We call these images PHSColograms ‡ . We present significant new research in improving the capabilities of computer interleaved autostereoscopic imagery in the form of rotated interleaved barrier strip autostereograms. This new advance removes the dependence of pitch and number of images on the resolution of the output device.
Localization of an obstructing esophageal lesion. Is the patient accurate

There are many opinions as to the accuracy of a patient's subjective localization of an obstructing esophageal lesion. However, there are few studies specifically examining this issue. Over a 35-month period, all patients evaluated by our gastroenterology service undergoing endoscopy for dysphagia were prospectively identified. The patient's subjective localization for the level of obstruction was evaluated by an investigator blinded to the results of prior barium esophagography and recorded on a schematic of the bony skeleton. At the time of endoscopy, the most proximal level of the obstructing lesion was documented. In all, 139 patients with dysphagia and an esophageal stricture were evaluated. Barium esophagograms were performed prior to endoscopy in all but nine patients (6.5%). The most common lesions causing dysphagia were carcinoma (34.5%), gastroesophageal reflux disease (22.3%), and a Schatzki's ring (15.8%). The level of obstruction was localized exactly in 30 patients (21.6%), within ±2 cm in 72 (52%), and within ±4 cm in 31 additional patients (74%). Eight patients (15%) with a distal esophageal lesion localized the obstruction to the proximal esophagus, whereas only two patients (5%) with a lesion in the proximal esophagus localized the level of obstruction to the distal esophagus. Overall, patients with distal obstructing lesions were more likely to have referral >6 cm proximally than proximal lesions with referral to the distal esophagus (P=0.003). There were no significant differences in accuracy based on the cause of dysphagia. In conclusion, a patient's subjective localization of the level of an esophageal stricture is highly accurate. Patients appear to be most accurate in localizing proximal rather than distal lesions.
A Note on “Strength of Association”

(1963). A Note on “Strength of Association”. The Journal of Psychology: Vol. 55, No. 1, pp. 199-209.
Theological Strategies, Constructing Meaning, and Coping with Breast Cancer: A Qualitative Study

Examines ways in which the experience of breast cancer has impacted the theology and the ability to create meaning for 10 female breast cancer patients. Discusses three theological strategies emerging from participant interviews: 1) God causes cancer for a purpose, 2) God does not cause cancer, but there can still be meaning in illness, and 3) cancer is just part of life and has no inherent meaning, though meaning can be constructed through the experience.
A New Politics of the Principalship? Accountability-Driven Change in New York City

How do principals adjust to new standards and measurement rulers of school performance when they are coupled with high-stakes consequences? Adopting a contingent view of leadership and a multiple accountabilities framework, this qualitative study explores how high school principals enacted their accountability in New York City, by comparing two periods: just before such policy changes took effect and just after. We observed large differences in principals' attention to external political, bureaucratic, and market accountabilities; how much accountability conflict or alignment was experienced; and how principals' sense of professionalism was constructed. These differences may portend a new politics of the principalship.
PHARMACOKINETICS OF AMIKACIN IN CHILDREN

Pharmacokinetics of aminoglycoside antibiotics vary both within and between different age groups. To determine proper dosing level and interval for children, sequential pharmacokinetics were studied in 10 patients (age = 8.7 yrs). All children had normal renal function. Mean weight and surface area were 29.5 kg and 0.99 m2 respectively. A dose of 7.5 mg/kg was administered IM q12h. Utilizing an acetyl transferase radioenzymatic assay, sequential serum levels were determined and were as follows (μg/ml ± SD) : Oh=0; ½h=13.0 ± 4.0; 1h=12.2 ± 3.3; 2h=8.9 ± 3.3; 4h=3.1 ± 1.8; 6h=1.5 ± 1.3; 8h=< 1.0. Drug was undetectable in serum after 8 hrs. No accumulation was observed. Mean peak serum: mean urine (0-12h) ratio was 1:20. There was no evidence of toxiclty. Utilizing this dosage regimen, the t½ in our patients (1.7h) was 23% shorter than that in adult subjects (2.2h). The mean peak serum level (13μg/ml) was 35% lower than in adults (20μg/ml). These data suggest that children require larger doses of amikacin administered at more frequent intervals than those utilized in this study.
Introduction of fast MR imaging in the assessment of hepatic steatosis

We determined the utility of fast gradient echo techniques (modified Dixon method) in the assessment of hepatic fat content. Fast spoiled gradient echo was performed on bovine liver/corn oil homogenates with known fat fractions (FFE) to assess the accuracy of fat quantitation (FFMRI). The pulse sequence was manipulated via alterations in TE (echo time), TR (repetition time), and alpha (flip angle). In vivo studies were then performed using breath-holding maneuvers on normal adult volunteers and subjects at risk to develop hepatic steatosis, with cystic fibrosis or morbid obesity. At out-of-phase, TE, TR, and alpha were 2.1 ms, 7.3 ms, and 30-50 degrees and in-phase TE, TR, and alpha were 4.2 ms, 9.3 ms, and 30-50 degrees; FFMRI correlated well with FFE. An elevated fat fraction was observed in a high percentage of subjects with cystic fibrosis and morbid obesity. Fast gradient echo techniques were used successfully in the assessment of hepatic steatosis. The reduced acquisition times permitted in vivo analysis on adults and children using breath hold maneuvers.
Vision loss after spine surgery: a new hypothesis.

To the Editor: As new reports concerning vision loss after spine surgery continue to be published,1,2 it is crucial to explore possible mechanisms. The incidence of vision loss after noncardiac surgery is 0.0008%,3 while it is 0.2% following spine surgery,4 with the causes usually taken to be anemia or hypotension.5 We hypothesize a possible additional mechanism: that the use of large amounts of crystalloids in such cases can lead to an accumulation of edema in the eye socket with the production of an “eye compartment syndrome”. Presumably, increased eye socket pressure in this setting can lead to ischemia of the optic nerve, especially in the posterior segment having a single blood supply derived from the ophthalmic artery.6,7 Our hypothesis is supported by the frequent observation of facial edema and chemosis in long spine cases carried out in the prone position, as well as by occasional cases of blindness after bilateral neck dissection where the internal jugular veins have been sacrificed.8 Here, the loss of vision is attributed to back pressure from the distended ophthalmic veins, leading to ischemic neuropathy. Experience suggests that prone positioning for spine surgery may play a particularly important role. We recommend that, where possible, prone patients should be positioned so that their heads are higher than the heart, and that any position that might impair venous drainage of the head be avoided. In addition, anything that might lead to direct pressure on the orbit must be carefully prevented. We believe that eye compartment syndrome as a cause of blindness should be considered in any prone spine case managed with extensive use of crystalloids and where anemia and hypotension have been excluded. We also speculate that the use of colloids for spine cases in the prone position may offer the potential to reduce eye socket edema and subsequent vision loss.
Sister-chromatid exchange and chromosome aberrations for 4 aliphatic epoxides in mice

Abstract Sister-chromatid exchange (SCE) and chromosome aberrations (CA) in bone marrow cells were analyzed after in vivo exposure in mice to 4 aliphatic epoxides, namely 1-naphthyl glycidyl ether (NGE), 1-naphthyl propylene oxide (NPO), 4-nitrophenyl glycidyl ether (NPGE) and trichloropropylene oxide (TCPO). These compounds were selected as being among the most mutagenic aliphatic epoxides in our previous structure-mutagenicity studies with the Ames test. There were significant dose-related increases in SCE and CA results for all 4 epoxides. The order of genotoxicity as established through SCE was NGE > NPO > NPGE ≅ TCPO > solvent control. It is of interest that Ames Salmonella results are consistent with in vivo genotoxicity for these compounds. However, only the plate test version of the Ames procedure is consistent with this order of in vivo genotoxicity and neither preincubation Ames testing results nor chemical alkylation rates would have predicted this order.
Formative evaluation: a technique for attaining people-oriented systems

Let me tell you what I mean by formative evaluation. For example, in the design of something like Sesame Street or FreeStyle, social science researchers have gotten away from the role they're usually cast in - that is, to come in afterwards and explain why things failed. Instead, they get in right near the beginning and try to make sure that things turn out to be successes. You've all heard of the success of Sesame Street, and you're probably beginning to hear of the success of FreeStyle. When you have a big project and there is a great disparity between the people who are doing it and the people they're supposed to be impacting or who are going to be their users, the possibilities of misunderstanding and potential failure are great. This is a very common problem with large systems that are being designed today. Even though people think they are talking the same language, they find out they aren't. We have a lot of systems that are designed now where the system designers or the system analysts come up with specifications, let out bids, someone gets the bid, and that supposedly is it. Although misunderstandings between the systems analysts and the contractors may exist, that doesn't guarantee that the system analysts have a very good understanding of the end users. The idea in formative evaluation is that as you're getting the design put together and putting the concepts in place, you go out and start gathering representative data from the end user population to see whether in fact it is possible to attain the goals. Everybody knows that design is an iterative process, and evaluation should be a component of it. We give it lip service but very rarely do we do it, and the cliches are, "Well, you know the users don't know what they're going to want, they're going to keep on changing." To some extent that is true, but that is very often used as an excuse to skip the data gathering completely. By focusing on the misunderstandings, by trying to clarify the goals, one can early on learn whether in fact a system can be developed that is useable and satisfactory to those users.
Cloning and Chromosomal Mapping of Mouse Ladinin, a Novel Basement Membrane Zone Component

Abstract Linear IgA disease is characterized by circulating IgA autoantibodies recognizing basement membrane zone components, including an anchoring filament protein, ladinin. In this study, we have cloned the mouse ladinin cDNA, elucidated the intron–exon organization of the corresponding gene (Lad1), and determined its chromosomal assignment. We have also characterized the promoter region ofLad1and examined its tissue-specific expression. The mouseLad1gene consists of 10 exons spanning ∼13.4 kb of the mouse genome on chromosome 1, and Southern analysis suggested thatLad1is a single-copy gene. The coding region comprises 1584 nucleotides and encodes a 528-amino-acid polypeptide with a calculated molecular mass of 59 kDa. The deduced polypeptide contained two putativeN-glycosylation and twoO-glycosylation sites, and sequence analysis predicted a 15-amino-acid signal peptide. The 5′ upstream region demonstrated the presence of consensuscis-elements for AP2 and SP1 and was GC rich, consistent with eukaryotic promoter. Northern analysis revealed expression in cultured keratinocytes, but not in fibroblasts, with the mRNA transcript being ∼2.5 kb in size. A significant level of expression was also noted in the kidney and lung, and to a lesser degree in the liver, spleen, and brain. Ladinin is a novel component of the basement membranes and may function in contributing to the stability of the association of the epithelial layers with the underlying mesenchyme.
Vector symmetry and heavy quark decays

Abstract We discuss the consequences of the vector symmetry recently suggested by one of us for the decays of heavy quarks, b and c.
Role for the BRCA1 C-terminal repeats (BRCT) protein 53BP1 in maintaining genomic stability.

p53-binding protein-1 (53BP1) is phosphorylated in response to DNA damage and rapidly relocalizes to presumptive sites of DNA damage along with Mre11 and the phosphorylated histone 2A variant, γ-H2AX. 53BP1 associates with the BRCA1 tumor suppressor, and knock-down experiments with small interfering RNA have revealed a role for the protein in the checkpoint response to DNA damage. By generating mice defective in m53BP1(m53BP1tr/tr), we have created an animal model to further explore its biochemical and genetic roles in vivo. We find that m53BP1tr/tr animals are growth-retarded and show various immune deficiencies including a specific reduction in thymus size and T cell count. Consistent with a role in responding to DNA damage, we find thatm53BP1tr/tr mice are sensitive to ionizing radiation (γ-IR), and cells from these animals exhibit chromosomal abnormalities consistent with defects in DNA repair. Thus, 53BP1 is a critical element in the DNA damage response and plays an integral role in maintaining genomic stability.
Receptor activation: what does the rhodopsin structure tell us?

G-protein-coupled receptors (GPCRs) are a large family of seven-transmembrane-helix proteins that mediate responses to hormones, neurotransmitters and, in the case of rhodopsin, photons. The recent determination of the structure of rhodopsin at atomic resolution opens avenues to a deeper understanding of GPCR activation and transmembrane signaling. Data from previous crosslinking, spin labeling and scanning accessibility experiments on rhodopsin have been mapped onto the high-resolution structure. These data correlate well and are consistent with the structure, and suggest that activation by light opens a cleft at the cytoplasmic end of the seven-helix bundle of rhodopsin. Furthermore, lessons learned from rhodopsin might also apply to other members of this essential family of receptors. (For an animation of the crystal structure of rhodopsin see http://archive.bmn.com/supp/tips/tips2211a.html)
Injury to Research Volunteers — The Clinical-Research Nightmare

In March, after receiving injections of TGN1412, six volunteers became desperately ill, had multiple-organ failure, and were transferred to an intensive care unit. TGN1412 is a humanized monoclonal antibody agonist of the CD28 receptor. Drs. Alastair Wood and Janet Darbyshire write that the serious injuries to these volunteers compel us to reassess the safety of such clinical trials.
On the Assignment of Co-ordinate Numbers to Meteoritlc Falls

AND INTRODUCTION The preceding paper by Dr. Lincoln La Paz on “Meteoritical Position Problems raises some interesting questions concerning the assignment of coordinate numbers1 to meteoritic falls. These matters are briefly discussed in the following paragraphs. There is an addendum on the observational determination of the coordinates of a place.
Recent results from the DIII-D tokamak and implications for future devices

Abstract Improvements to the DIII-D tokamak have led to significant new research results and enhanced performance of the tokamak systems. These results provide important inputs to the design of next-generation divertor systems including the upgrade of the DIII-D divertor. Key results have been obtained in understanding the divertor configuration and developing effective configurations for new devices. The use of graphite for the plasma facing components and careful wall preparation has enabled the routine achievement of regimes of enhanced energy confinement. In elongated discharges, triangularity has been found to be important in attaining good discharge performance as measured by the product of the normalized plasma pressure and the energy confinement time βτ E . This constrains the design of the divertor configuration (X-point location). Active pumping of the divertor region using an in-situ toroidal cryogenic pump has demonstrated control of the plasma density in H-mode discharges and allowed the dependence of confinement on plasma density and current to be separately determined. Helium removal from the plasma edge sufficient to achieve effective ash removal in reactor discharges has also been demonstrated using this pumping configuration. The reduction of the heat flux to the divertor plates has been demonstrated using two different techniques to increase the radiation in the boundary regions of the plasma and thus to reduce the heat flux to the divertor plates; deuterium gas injection has been used to create a strongly radiating localized zone near the X point, and impurity (neon) injection to enhance the radiation from the plasma mantle. Precise shaping of the plasma current profile has been found to be important in achieving enhanced tokamak performance. Transiently shaped current profiles have been used to demonstrate regimes of plasmas with high β and good confinement. Control of the current profile also is important to sustaining the plasma in the very high (VH) mode of energy confinement. Ongoing and planned enhancements to the DIII-D tokamak systems will allow us to exploit these gains further. The recent upgrade of the ICRF system to 6 MW should allow sufficient current drive to begin independent control of the plasma current. Work is beginning on a radiative divertor modification to the vessel interior which will combine the desirable features of highly triangular plasma shape with strong pumping and baffling to minimize the back-streaming of gas and impurities.
Low-dose aspirin therapy is not a reason for repeating head computed tomographic scans in traumatic brain injury: a prospective study.

Background: Most studies have categorized all antiplatelet drugs into one category. The aim of our study was to evaluate the utility of repeat head computed tomography (RHCT) and outcomes in patients on low-dose aspirin (acetylsalicylic acid; ASA) therapy. Methods: Patients with traumatic brain injury with intracranial hemorrhage on initial head computed tomography (CT) were prospectively enrolled. Patients on prehospital low-dose (81 mg) aspirin therapy were matched with patients exclusive of antiplatelet and anticoagulation therapy using propensity score matching in a 1:1 ratio for age, Glasgow Coma Scale, head Abbreviated Injury Scale score, Injury Severity Score, and neurological examination. Outcome measures were progression on RHCT and subsequent neurosurgical intervention.
Chromatin Relaxation by Overexpression of Mutant p53, HPV16-E6, or Cyclin G Transgenes

In this study, using a cell line that carries endogenous wild-type p53 genes, we show that transfection of cells with mutant p53, HPV16-E6, or cyclin G transgenes results in the disruption of higher-order chromatin structure, as evidenced by enhanced sensitivity to micrococcal nuclease. Multiple mechanisms may contribute to this phenotype, including histone H1 phosphorylation, direct binding of oncoproteins to nuclear matrix attachment sites, and altered expression of component genes of the p53 pathway, whose products may function in maintenance of chromatin structure.
Preventing HIV/AIDS among high-risk urban women: the cost-effectiveness of a behavioral group intervention.

OBJECTIVES: A human immunodeficiency virus (HIV) intervention trial for women at high risk for acquired immunodeficiency syndrome and attending an urban clinic was reported previously. The behavioral group intervention was shown to increase condom use behaviors significantly. This study retrospectively assessed the intervention's cost-effectiveness. METHODS: Standard methods of cost and cost-utility analysis were used. RESULTS: The intervention cost was just over $2000 for each quality-adjusted life-year saved; this is favorable compared with other life-saving programs. However, the results are sensitive to changes in some model assumptions. CONCLUSIONS: Under most scenarios, the HIV prevention intervention was cost-effective.
Using a Transcriptional Network to Approach the Mechanism of Fungal Meningitis

C. neoformans is the most common cause of fungal meningitis, but the molecular mechanisms of pathogenesis remain poorly understood. The pivotal pathogen transcriptional regulator Gat201 inhibits phagocytosis independently of the polysaccharide capsule and plays a central role in virulence (1). To define the corresponding transcriptional network, we performed chromatin immunoprecipitation and sequencing (ChIP-Seq) and expression profiling (RNA-Seq) experiments of Gat201 and two other transcription factors, also required for virulence, regulated by Gat201 that comprise a regulatory network intimately tied to C. neoformans' virulence. Within the set of genes whose promoters are bound by all three transcription factors assayed, there are three members of a six-member protein family in C. neoformans (Blp1-6), characterized by an N-terminal signal sequence and a double-psi beta barrel motif. One member of this family, Blp1, inhibits phagocytosis through an unknown mechanism (1). In addition, we found that the promoter of a peptide required for low-density growth of a C. neoformans tup1Δ mutant strain background is also bound by all three transcription factors (2). We are currently investigating the functional roles of these secreted proteins and their biochemical mechanisms of action.(1) Chun CD, Brown JCS, and Madhani HD. (2011) A Major Role for Capsule-Independent Phagocytosis-Inhibitory Mechanisms in Mammalian Infection by Cryptococcus neoformans. Cell Host & Microbe, 9: 243-251.(2) Lee H, Chang YC, Nardone G, Kwon-Chung KJ. (2007) TUP1 disruption in Cryptococcus neoformans uncovers a peptide-mediated density-dependent growth phenomenon that mimics quorum sensing. Molecular Microbiology 64(3): 591-601.
MANAGING STATE‐OWNED ENTERPRISES: LESSONS FROM INDIA

State‐owned enterprises (SOEs), in general, have not been successful. Their indifferent performance has been at the center of the debate about the role of the state in the economy. To economists, the performance of SOEs is evidence of what is wrong with state intervention. And in recent years privatization has increasingly been regarded as the only way of improving the performance of SOEs. Yet, while unsuccessful SOEs abound, a few high‐performing SOEs such as POSCO (South Korea), Airbus Industrie (France), EMBRAER (Brazil), and MUL (India) can also be found.
Postexposure prophylaxis implementation issues: programmatic concerns in hospitals.

The administration of a human immuno-deficiency virus (HIV) postexposure care program can be particularly difficult in complex medical centers that have multiple sites, diverse programs, and numerous types of patient interactions. The concern to optimize such programs is heightened if the institution cares for populations in which the prevalence of HIV positivity is high, as is the case in many urban healthcare facilities. This article discusses issues concerning implementation of a program of postexposure prophylaxis.
Negative dietary effects of Colorado potato beetle eggs for the larvae of native and introduced ladybird beetles

Aphidophagous ladybird beetles (Coleoptera: Coccinellidae) are attracted to and feed heavily on aphids, but many species will also feed opportunistically on other prey that they encounter. In potatoes (Solanum tuberosum L.) in Washington State, USA, coccinellids feed on both green peach aphids (“GPA,” Myzus persicae Sulzer) and eggs of the Colorado potato beetle (“CPB,” Leptinotarsa decemlineata Say). The guild of aphidophagous ladybirds includes two native species, Hippodamia convergens Guerin-Meneville and Coccinella transversoguttata Brown. Recently, an introduced species, Coccinella septempunctata L., has invaded and apparently displaced its native congener. A second exotic, Harmonia axyridis Pallas, has colonized the area and is becoming more abundant. We compared larval development of each species on a monotypic diet of GPA, a monotypic diet of CPB eggs, or a mixed diet of both GPA and CPB eggs. Our goal was to answer two questions: (1) do larvae of the four ladybird species benefit from including CPB eggs in their diet and (2) do the four ladybird species differ in their ability to utilize CPB eggs as prey? No larva of any species completed development on a pure diet of CPB eggs, and survivorship was highest for all species when they fed on a pure diet of GPA. One native species, H. convergens, and one exotic species, H. axyridis, exhibited significantly lower survivorship on a mixed diet of both CPB eggs and GPA, compared to a pure GPA diet; H. axyridis also took longer to develop from egg to adult when both prey were provided. Survivorship of the two Coccinella spp. was not altered by the inclusion of CPB eggs with GPA, although CPB eggs lengthened the development time of C. transversoguttata. Adult size was not consistently affected by diet for any of the coccinellids. Overall, no ladybird species benefited from the inclusion of potato beetle eggs in its diet. The two Coccinella species responded similarly to the inclusion of CPB eggs, and so we would not expect any difference in the success of coccinellid larval development in potato fields following the replacement of C. transversoguttata by C. septempunctata. Hippodamia convergens and H. axyridis, the two species whose survivorship was depressed by combining CPB egg and aphid prey, were also the two species that consumed the greatest number of CPB eggs during successful larval development. A comparison of total egg consumption by each species cohort suggested that displacement of the other species by H. axyridis would not alter CPB biological control, because the higher per capita feeding rate by H. axyridis larvae compensated for individuals’ greater mortality risk on a diet including CPB eggs.