cssi/SciSciGPT-SciSciNet huggingface dataset:
THE DEVELOPMENTAL GENETICS OF THE TEMPERATURE-SENSITIVE LETHAL ALLELE OF THE SUPPRESSOR OF FORKED, l(1)su(f)ts67g, IN DROSOPHILA MELANOGASTER

A temperature-sensitive lethal allele of suppressor of forked, l(1)su(f)ts67g (ts67), has been discovered and characterized as follows: Flies which are hemizygous for ts67 live at 18° and 25° but die at 30° primarily as larvae. The temperature-sensitive period for ts67 homozygotes or hemizygotes begins in second instar and ends at pupation. ts67 is lethal at 30° when heterozygous with suppressor of forked (su(f)), a deficiency for suppressor of forked (su(f)-), and a non-conditional lethal allele of suppressor of forked (3DES). It is viable at 30° when heterozygous with the wild-type allele of suppressor of forked. At 25° but not at 18° forked bristles are suppressed in flies of the following genotypes: fsts67/Y, fsts67/fsts67, fsts67/fssu(f), futs67/fs3DES, futs67/fssu(f)-, futs67/fssu(f). There is some suppression of forked bristles at 25° in the heterozygote, fsts67/fs+su(f). The forked bristle phenotype is not suppressed at either temperature in flies of the genotypes futs67/Y, futs67/futs67/ (fs and fu indicating suppressible and unsuppressible alleles of forked). The temperature-sensitive period for suppression of forked bristles begins at pupation and extends through the period of bristle synthesis. The deficiency phenotype (bristles reduced in size or absent, wing wrinkled or blistered, eyes rough) typical of flies of the genotype fssu(f)/fssu(f)- at 18° and 25°, is exhibited by flies of the genotypes fsts67/fssu(f)- at 25° and futs67/fssu(f) at 29°. An allele of lozenge (lz1) which can be suppressed by su(f) is suppressed at 25° but not at 18° in lz1ts67/Y males. ts67 homozygous females are fertile at 25° but sterile at 30°. The hypothesis is discussed that the su(f) locus codes for a ribosomal protein and that suppression and enhancement are affected by mutations at the locus by mutant ribosome-induced misreading. The possibility is presented that ts67 may be used to determine the translation time in development of any gene.
Creative problem solving as sequential BVSR: Exploration (total ignorance) versus elimination (informed guess)

Abstract Although the theory that creativity requires blind variation and selective retention (BVSR) is now more than a half-century old, only recently has BVSR theory undergone appreciable conceptual development, including formal three-parameter definitions of both creativity and sightedness. In this article, these new developments are for the first time extended to encompass sequential BVSR, that is, when ideas are generated and tested consecutively rather than simultaneously. Formulated in terms of creative problem solving, sequential BVSR is shown to have two forms: (a) exploratory in which the person decreases total ignorance and (b) eliminatory in which the person vets informed guesses. Only in the latter case does sightedness for both single potential solutions and the set of potential solutions necessarily increase with each generation-and-test trial. Exploratory BVSR is illustrated by Edison's search for a practical incandescent filament, whereas eliminatory BVSR is exemplified by Watson's discovery of the DNA base code. Hence, although epistemologically and psychologically distinct, both represent important forms of creative problem solving.
DNase I–hypersensitive sites enhance α1(I) collagen gene expression in hepatic stellate cells

Liver fibrosis is characterized by a dramatic increase in the expression of type I collagen. Several deoxyribonuclease (DNase) I-hypersensitive sites (HS) have been located in the distal 5'-flanking region of the alpha1(I) collagen gene that are specific to collagen-producing cells. To assess the role of the DNase I-HS in regulating alpha1(I) collagen gene expression in hepatic stellate cells (HSCs), 3 transgenic mouse lines expressing collagen-alpha1(I) reporter genes were used (Krempen et al. Gene Expr 1999;8:151-163). The pCol9GFP transgene contains the collagen gene promoter (-3122 to +111) linked to the green fluorescent protein (GFP) reporter gene. The pCol9GFP-HS4,5 transgene contains HS4,5 and pColGFP-HS8,9 contains HS8,9 positioned upstream of the collagen promoter in pCol9GFP. HSCs isolated from transgenic mice containing pCol9GFPHS4,5 and pColGFP-HS8,9 showed earlier and higher GFP expression patterns than HSCs isolated from pCol9GFP mice. HSCs from pCol9GFP-HS4,5 showed the highest levels of GFP expression and culture-induced expression correlated with induction of the endogenous alpha1(I) collagen gene. After CCl(4) administration, pCol9GFP-HS4,5 mice showed increased GFP expression compared with pCol9GFP mice in both whole liver extracts and isolated HSCs. Several sites for DNA-protein interactions in both HS4 and HS5 were identified that included a binding site for activator protein 1. In conclusion, DNase I-HS4,5 enhance expression of the alpha1(I) collagen gene promoter in HSCs both in vitro and in vivo after a fibrogenic stimulus. The collagen-GFP transgenic mice provide a convenient and reliable model system to investigate the molecular mechanisms controlling increased collagen expression during fibrosis.
The use of the hypoglycaemic clamp in the assessment of pituitary function

OBJECTIVE The standard dynamic test used to diagnose hypopituitarism is the insulin tolerance test (ITT), in which insulin-induced secretion of ACTH, GH and cortisol is measured. However, because of differences in insulin sensitivity some patients fail achieve sufficient hypoglycaemia to assess pituitary function and colleagues experience severe hypoglycaemia and are at risk for cardiac dysrhythmia, seizure or coma. This risk may be particularly pertinent in the evaluation of older adults. We hypothesized that the hypoglycaemic clamp may be useful in assessing pituitary function in some patients. PATIENTS AND MEASUREMENTS Twenty-one normal subjects (14 old [50–76 years] and 7 young [18–36 years]) and 7 hypopituitary subjects were studied. A clamp study was performed in which insulin infusion was given at 2 mU/kg/min and increased to 4 mU/kg/min if the target glucose concentration was not reached after 40 min. Dextrose was infused as needed to clamp the plasma glucose concentration at 2.2 mmol/l for 30 min. On a separate day, 7 young controls also underwent an ITT in which 0.15 U/kg insulin was administered as a bolus intravenous injection at time 0. In both studies, baseline values were taken at - 10, - 5 and 0 min. Samples were then collected every 5 min for plasma glucose and every 10 min for insulin, ACTH, cortisol and GH. RESULTS ACTH and GH secretion during each test were similar in younger controls (P = NS) but cortisol secretion was lower during ITT (P < 0.01 vs. clamp). Hypopituitary subjects had significantly less ACTH, cortisol and GH secretion than controls of all ages (P < 0.001 for all). Peak GH secretion was significantly lower in the old controls than in young controls (22 ± 12 vs. 48 ± 26 mU/l, respectively; P < 0.01) but significantly higher than the hypopituitary subjects (2 ± 2 mu/l; P < 0.001). CONCLUSION These data demonstrate that the hypoglycaemic clamp can be used in the assessment of pituitary function and suggest that this technique may be particularly beneficial in the evaluation of GH deficiency in older adults who may not tolerate the ITT.
Integrating expert systems and operations research: A conceptual framework

Abstract Expert System technologies can provide significant benefits if integrated with operations research (OR) applications, either by using free-standing systems or by integrating them into existing OR tools. This paper first distinguishes between physical and functional integration, and then focuses on aspects of the latter. Process and technique-oriented functional integration are defined, and several conceptual issues reviewed. These include the need for and resources necessary for such integration, difficulties associated with achieving successful integrated ES-OR applications, and the integration's impact on operations researchers and their organizations.
Interactive query formulation over web service-accessed sources

Integration systems typically support only a restricted set of queries over the schema they export. The reason is that the participating information sources contribute limited content and limited access methods. In prior work, these limited access methods have often been specified using a set of parameterized views, with the understanding that the integration system accepts only queries which have an equivalent rewriting using the views. These queries are called feasible. Infeasible queries are rejected without an explanatory feedback. To help a developer, who is building an integration application, avoid a frustrating trial-and-error cycle, we introduce the CLIDE query formulation interface, which extends the QBE-like query builder of Microsoft's SQL Server with a coloring scheme that guides the user toward formulating feasible queries. We provide guarantees that the suggested query edit actions are complete (i.e. each feasible query can be built by following only suggestions), rapidly convergent (the suggestions are tuned to lead to the closest feasible completions of the query) and suitably summarized (at each interaction step, only a minimal number of actions needed to preserve completeness are suggested). We present the algorithms, implementation and performance evaluation showing that CLIDE is a viable on-line tool.
Strategic Improvement of Workplace Competence I: Breaking Out of the Incompetence Trap

Workplace competence is necessary for organizational survival in todayws world. Development of a competent workforce must occur in spite of growing shortages of qualified people, increasing technological complexity, and increasing international competition. Workplace competence can be improved significantly by using a strategy that enables everyone from top managers to entry level workers to learn new knowledge, skills, and attitudes while they do worthwhile projects. However, three major challenges must be met before the strategy can be used widely enough to have a positive economic and social impact at local, state, regional and national levels. We must 1) improve the supply of human performance technologists capable of serving the needs of small organizations, 2) help managers learn to exert strong leadership without disrupting teamwork, and 3) build a track record so that the strategy can be adopted by the prudent business person and supported by the financial and educational communities.
Treatment and prevention of bone complications from prostate cancer

Bone metastases and skeletal complications are major causes of morbidity in prostate cancer patients. Despite the osteoblastic appearance of bone metastases on imaging studies, patients have elevated serum and urinary markers of bone resorption, indicative of high osteoclast activity. Increased osteoclast activity is independently associated with higher risk of subsequent skeletal complications, disease progression, and death. Osteoclast-targeted therapies are therefore a rational approach to reduction of risk for disease-related skeletal complications, bone metastases, and treatment-related fractures. This review focuses on recent advances in osteoclast-targeted therapy in prostate cancer. Bisphosphonates have been extensively studied in men with prostate cancer. Zoledronic acid significantly decreased the risk of skeletal complications in men with castration-resistant prostate cancer and bone metastases, and it is FDA-approved for this indication. Denosumab is a human monoclonal antibody that binds and inactivates RANKL, a critical mediator of osteoclast differentiation, activation, and survival. Recent global phase 3 clinic trials demonstrated an emerging role for denosumab in the treatment of prostate cancer bone metastases and prevention of fractures associated with androgen deprivation therapy.
Micro-scale S isotope studies of the Kharaelakh intrusion, Noril’sk region, Siberia: Constraints on the genesis of coexisting anhydrite and sulfide minerals

Abstract The coexistence of magmatic anhydrite and sulfide minerals in non-arc-related mafic magmas has only rarely been documented. Likewise the S isotope fractionation between sulfate and sulfide in mafic rocks has infrequently been measured. In the Kharaelakh intrusion associated with the world-famous Noril’sk ore district in Siberia coexisting magmatic anhydrite and sulfide minerals have been identified. Sulfur isotope compositions of the anhydrite–sulfide assemblages have been measured via both ion microprobe and conventional analyses to help elucidate the origin of the anhydrite–sulfide pairs. Magmatic anhydrite and chalcopyrite are characterized by δ 34 S values between 18.8‰ and 22.8‰, and 9.3‰ and 13.2‰, respectfully. Coexisting anhydrite and chalcopyrite show Δ values that fall between 8.5‰ and 11.9‰. Anhydrite in the Kharaelakh intrusion is most readily explained by the assimilation of sulfate from country rocks; partial reduction to sulfide led to mixing between sulfate-derived sulfide and sulfide of mantle origin. The variable anhydrite and sulfide δ 34 S values are a function of differing degrees of sulfate reduction, variable mixing of sulfate-derived and mantle sulfide, incomplete isotopic homogenization of the magma, and a lack of uniform attainment of isotopic equilibrium during subsolidus cooling. The δ 34 S values of sulfide minerals have changed much less with cooling than have anhydrite values due in large part to the high sulfide/sulfate ratio. Variations in both sulfide and anhydrite δ 34 S values indicate that isotopically distinct domains existed on a centimeter scale. Late stage hydrothermal anhydrite and pyrite also occur associated with Ca-rich hydrous alteration assemblages (e.g., thomsonite, prehnite, pectolite, epidote, xonotlite). δ 34 S values of secondary hydrothermal anhydrite and pyrite determined by conventional analyses are in the same range as those of the magmatic minerals. Anhydrite–pyrite Δ values are in the 9.1–10.1‰ range, and are smaller than anticipated for the low temperatures indicated by the silicate alteration assemblages. The small Δ values are suggestive of either sulfate–sulfide isotopic disequilibrium or closure of the system to further exchange between ∼550 and 600 °C. Our results confirm the importance of the assimilation of externally derived sulfur in the generation of the elevated δ 34 S values in the Kharaelakh intrusion, but highlight the sulfur isotopic variability that may occur in magmatic systems. In addition, our results confirm the need for more precise experimental determination of sulfate–sulfide sulfur isotope fractionation factors in high-T systems.
The Impact of Taoism on Chinese Leisure

Abstract Taoism has been one of the most influential philosophies and religions during the past 2,500 years in China, and it affects every aspect of Chinese life, including leisure. Although typical Western understandings and practices of leisure differ quite markedly from those in China, leisure is, in fact, readily identifiable in the daily lives of common Chinese people through the influence of both philosophical and religious Taoism. These influences can be seen in Chinese people's close connection to the natural world, the concepts of holistic wellness and health care, the practice of martial arts, traditional arts such as painting and poetry, enjoyment of cultural activities and celebrations, and tourism. As Chinese scholars strive to introduce leisure studies and services in their home country, it is important for the global community to continue to identify both the similarities and differences in the understanding and practice of leisure between North America and China. This paper begins that pro...
Flag leaf area in five spring wheat crosses and the relationship to grain yield

Five spring wheat crosses were evaluated over a 6-year period using comparisons between F2 and F3 data and between near-isogenic F4 populations selected for flag leaf area. Nonsignificant r values for F2 vs. F3 flag leaf measurements may be due to the effect of environment on flag leaf area, but are probably also an indication of low heritability for this plant character. Near-isogenic populations selected on the basis of flag leaf area showed little difference in grain yield, an indication that other plant parts must be more influential in determining grain yield. Flag leaf area, by itself, appears not to be a good index to plant performance.
IP geolocation in metropolitan areas

Current IP geoloation techniques can geolocate an IP address to a region approximately 700 square miles, roughly the size of a metropolitan area. We model geolocation as a pattern-recognition problem, and introduce techniques that geolocate addresses to within 5 miles inside a metropolitan area. We propose two complementary algorithms: The first algorithm, Pattern Based Geolocation (PBG), models the distribution of latencies to the target and compares it to those of the reference landmarks to resolve an address to within 5 miles in a metropolitan area. The second approach, Perturbation Augmented PBG (PAPBG), provides higher resolution by sending extra traffic in the network. While sending an aggregate of 600 Kbps extra traffic to 20 nodes for approximately 2 minutes, PAPBG geolocates addresses to within 3 miles.
Cultural constructions of “obesity”: Understanding body size, social class and gender in Morocco

This article presents data from an in-depth qualitative study of overweight and diabetic women in Morocco, a North African country experiencing a rapid increase in obesity according to national statistics. This case study explores the heterogeneous relationship among health, culture and religion in Morocco by highlighting the relationship between the intricacies of women's everyday lives and their body sizes. My findings suggest that although the Body Mass Index (BMI) of adult women has been documented to have increased in Morocco along with other macroeconomic changes (i.e., increases in urbanization, etc.), "obesity" has yet to be universally medicalized in the Moroccan context. As such women do not generally utilize a medicalized concept of obesity in reference to their larger body sizes. Rather, cultural constructions of "obesity" are understood through cultural understandings of a larger body size, religious beliefs about health and illness, and the nature of women's religious participation. This stands in contrast to dominant accounts about the region that promote an overall veneration of a larger body size for women.
Use of a camp setting to provide medical information to siblings of pediatric cancer patients.

It has been reported that siblings of children with cancer often lack information and understanding about their brother's or sister's disease and treatment. The purpose of this paper is twofold: (1) to describe a camping program for siblings, which was designed, in part, to provide these children with age-appropriate medical information; and (2) to report the results of a study which examined how this intervention influenced siblings' knowledge and understanding of their brother's or sister's disease. Ninety siblings between the ages of 6 and 17 who completed a pre/post camp medical information questionnaire participated in this investigation. The results revealed that younger (6- to 11-year-old) siblings attending camp for at least the second time and older (12- to 17-year-old) siblings attending camp for the first time experienced significant (p less than .05) improvement in their overall knowledge and understanding of their brother's or sister's cancer. The results also revealed positive changes in the desired direction with respect to siblings' fear or their friends' fear about catching their brother's or sister's cancer. The results of this study provide a conceptual model for other pediatric cancer facilities engaged in developing intervention programs for siblings.
The RET/PTC3 oncogene activates classical NF-κB by stabilizing NIK

The oncogenic fusion protein RET/PTC3 (RP3) that is expressed in papillary thyroid carcinoma (PTC) and thyroid epithelia in Hashimoto's thyroiditis activates nuclear factor-kappa B (NF-κB) and induces pro-inflammatory gene expression; however, the mechanism of this activation is unknown. To address this, we expressed RP3 in murine embryonic fibroblasts (MEFs) lacking key classical and noncanonical NF-κB signaling components. In wild-type MEFs, RP3 upregulated CCL2, CXCL1, granulocyte-macrophage colony-stimulating factor and tumor necrosis factor expression and activated classical but not noncanonical NF-κB. RP3-activated NF-κB in IκB kinase (IKK)β(-/-) MEFs but not IKKα- or NF-κB essential modulator (NEMO)-deficient cells and activation was inhibited by a peptide that blocks NEMO binding to the IKKs. RP3 increased the levels of NF-κB-inducing kinase (NIK) and did not activate NF-κB in NIK-deficient MEFs. Notably, NIK stabilization was not accompanied by TRAF3 degradation demonstrating that RP3 disrupts normal basal NIK regulation. Dominant-negative NIK blocked RP3-induced NF-κB activation and an RP3 signaling mutant (RP3(Y588F)) did not stabilize NIK. Finally, examination of PTC specimens revealed strong positive staining for NIK. We therefore conclude that RP3 activates classical NF-κB via NIK, NEMO and IKKα. Importantly, our findings reveal a novel mechanism for oncogene-induced NF-κB activation via stabilization of NIK.
Philosophical Counseling as an Alternative Process to Bioethics Mediation

Closure is indeed a neglected end of many clinical ethics consultations. And Dialogue-Focused Models do offer “the best hope for closure” in a clinical ethics conflict (Feister 2015, 34). By involv...
The effect of the CdCl2 treatment on CdTe/CdS thin film solar cells studied using deep level transient spectroscopy

Abstract Thin film CdTe/CdS solar cells have been studied using deep level transient spectroscopy. The correlation-deep level transient spectroscopy (DLTS) technique was utilized as conventional analysis methods such as the boxcar-based approach were found to be inadequate under certain experimental conditions. The primary objective was to study the effect of a key processing step in the fabrication of thin film CdTe solar cells, namely the post-deposition heat treatment in the presence of CdCl2. The substrate temperature as well as the ambient used during this process were varied around predetermined conditions for optimum solar cell performance, in order to identify performance-limiting defects, and in general improve our understanding of thin film CdTe solar cells. Solar cells without the CdCl2 heat treatment were also fabricated. A series of electron and hole traps were found in the various devices studied, with electron traps being present primarily in solar cells with limited performance.
Proline Residues at the C Terminus of Nascent Chains Induce SsrA Tagging during Translation Termination

The SsrA or tmRNA quality control system relieves ribosome stalling and directs the addition of a degradation tag to the C terminus of the nascent chain. In some instances, SsrA tagging of otherwise full-length proteins occurs when the ribosome pauses at stop codons during normal translation termination. Here, the identities of the C-terminal residues of the nascent chain are shown to play an important role in full-length protein tagging. Specifically, a subset of C-terminal Xaa-Pro sequences caused SsrA tagging of the full-length YbeL protein from Escherichia coli. This tagging increased when a less efficient stop codon was used, increased in cells lacking protein release factor-3, and decreased when protein release factor-1 was overexpressed. Incorporation of the analog azetidine-2-carboxylic acid in place of proline suppressed tagging, whereas incorporation of 3,4-dehydroproline increased SsrA tagging of full-length YbeL. These results suggest that the detailed chemical or conformational properties of the C-terminal residues of the nascent polypeptide can affect the rate of translation termination, thereby influencing ribosome pausing and SsrA tagging at stop codons.
Corrigendum: Corrigendum to Hierarchical trajectory refinement for a class of nonlinear systems [Automatica 41(4) (2005) 701-708]

It was recently brought to our attention by Dr. Mario Sigalotti that Theorem 3.2 in Tabuada and Pappas (2005) does not hold under the stated assumptions. In particular, the following example presented by Dr. Mario Sigalotti contradicts Corollary 3.3. Let r = k = 1, X0 M(y, z)= arctan(z) / y, X1 M(y, z)= / z, (y, z)= y. It is easy to check that A.I, A.II, A.III, and (3.4) hold true. Using (2.3) we get FN(y, ( , , ))= . Therefore, every smooth trajectory y(·) inR should be a solution of N . If |ẏ(t)|> /2 for some t ∈ R, however, then y(·) cannot be refined to a trajectory of M . The problem lies in Lemma 3.1 which does not hold under the stated assumptions. However, it does hold under the stronger assumption [ker(T ), [ker(T ),AM ]] ⊆ ker(T ) (1)
Digital radiotherapy simulator

We describe a prototype digital radiotherapy simulator which consists of a conventional simulator gantry, digital spot imager, and image correction and reconstruction software. The ability of the digital spot imager to acquire a diagnostic quality image directly in digital format during simulation offers unique possibilities in clinical practice. Applications include prescription of multileaf collimator, on-line patient setup verification, remote consultation and treatment planning. In addition, we discuss the possibility of using the digital simulator as a volume-CT scanner capable of obtaining three-dimensional anatomical information in a single scan.
Comparison of the effects of viscoelastic agents on clinical properties of the unfolder lens injection system

Abstract Purpose To evaluate the effect of 7 viscoelastic materials on the physical properties of the Unfolder™ lens injection system. Setting John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. Methods New sterile SI-40NB intraocular lenses (IOLs) were loaded into the Unfolder (AMO® PhacoFlex II® SofTip™ insertion system (Allergan) using 7 viscoelastic materials: sodium hyaluronate 1.0% (Healon®, Provisc®), sodium hyaluronate 1.4% (Healon GV®), sodium hyaluronate 1.6% (Amvisc Plus®), hydroxypropyl methylcellulose 2.0% (Occucoat®), sodium chondroitin 4.0%–sodium hyaluronate 3.0% (Viscoat®), and hyaluronate 3.0% (Vitrax®). The IOLs were then injected after 10 or 120 seconds in the chamber (chamber dwell time) and 10, 60, or 180 seconds in the barrel of the Unfolder cartridge (barrel dwell time). Torque values (g/cm) required to extrude the lenses were measured with a torque gauge, and the cartridges and IOLs were inspected for damage. Results Longer chamber dwell times resulted in lower torque values to extrude the IOLs ( P P P Conclusion Increasing chamber dwell time and decreasing barrel dwell time resulted in lower torque values to extrude IOLs from the Unfolder and increased successful use. Moreover, dispersive viscoelastic agents tended to be more forgiving of changing dwell times and therefore had lower torque values and adverse event rates overall.
Tunable gold nanostructures with nanocapsules as template reaction vessels

Hollow, polymeric, thiol-ene resorcinarene nanocapsules can act as template reaction vessels for the synthesis of gold nanoshells or spherical aggregates of gold nanoparticles depending on the reaction conditions. The spherical nanoparticle aggregates were evaluated as catalysts in the biphasic reduction of 4-nitrophenol.
A general method for stability analysis of rotating shafts

A general method is presented for the stability analysis of rotating shafts. A continuous rotor with any number of discontinuities and linear and nonlinear external forces has been modeled by way of a number of finite elements and degrees of freedom, and a number of comparison functions which have been chosen as the static deflection between nodes. A transfer matrix approach was used for this purpose. Kinetic and elastic deformation energy and application of Lagrange's equations yielded the equations of motion. Due to the bearing nonlinearity, these equations are nonlinear.
Correlation of aqueous and lipid solubilities with flux for prodrugs of 5‐fluorouracil, theophylline, and 6‐mercaptopurine: A potts–Guy approach

Abstract The Potts and Guy equation that has been used to predict permeability coefficients for molecules being delivered from aqueous vehicles has been transformed to accommodate lipid vehicles that are less polar than skin, and polar vehicles that are less polar than water. Solubilities in pH 4.0 aqueous buffer ( S AQ ), solubilities in isopropyl myristate ( S IPM ), and molecular weights (MW) of prodrugs of 5‐fluorouracil (5‐FU), theophylline (Th), and 6‐mercaptopurine (6‐MP) have been regressed against their fluxes from suspensions in IPM ( J M ). Seven series ( n = 39) of alkylcarbonyloxymethyl (ACOM), alkyloxycarbonyl (AOC), alkylcarbonyl (AC), and alkylaminocarbonyl (AAC) prodrugs were used to determine the best fit to the transformed Potts and Guy equation (eq 6): log J M = x + y log S IPM + (1 − y )log S AQ − z MW. The estimated values for x , y , and z were −0 .193, ±0.525, and +0.00364, respectively, with r 2 = 0.945 for n = 39. Inclusion of a miscellaneous series comprised of the parent drugs and a branched alkyl chain prodrug gave an equally good fit only if 6‐MP was excluded from the analysis. The best performer (largest J M ) in each series was usually correctly identified. The values for x , y , and z were consistent with values obtained by Potts and Guy, but the inclusion of the (l − y )log S AQ term in eq 6 and the value for y , shows that water solubility is almost as important as lipid solubility in predicting flux. There were no significant changes in predicted log J M or x i for each series if their log J M or x i were calculated using y and z coefficients obtained for solutions to eq 6 from which the data for the series had been excluded. This suggests that the data from all the series is homogeneous. Data from Kasting, Smith, and Cooper for S IPM , S PG , and MW of unrelated molecules were regressed against their fluxes from propylene glycol (PG) using eq 7: log J M = x + y log S IPM + (1 − y ) log S PG − z MW. The estimated values for x , y , and z were −1.673, +0.599, and +0.00595, respectively, with r 2 = 0.852 for n = 28. These values for x , y , and z are also consistent with those previously reported by Potts and Guy, and, together with the results for fluxes from IPM, show the general utility of the transformed Potts and Guy equation in predicting flux from vehicles other than water and in showing the importance of solubility in a polar solvent as well as a nonpolar solvent in predicting flux.
Invited Review Article: Review of centrifugal microfluidic and bio-optical disks

Spinning biodisks have advantages that make them attractive for specialized biochip applications. The two main classes of spinning biodisks are microfluidic disks and bio-optical compact disks (BioCD). Microfluidic biodisks take advantage of noninertial pumping for lab-on-a-chip devices using noninertial valves and switches under centrifugal and Coriolis forces to distribute fluids about the disks. BioCDs use spinning-disk interferometry, under the condition of common-path phase quadrature, to perform interferometric label-free detection of molecular recognition and binding. The optical detection of bound molecules on a disk is facilitated by rapid spinning that enables high-speed repetitive sampling to eliminate 1/f noise through common-mode rejection of intensity fluctuations and extensive signal averaging. Multiple quadrature classes have been developed, such as microdiffraction, in-line, phase contrast, and holographic adaptive optics. Thin molecular films are detected through the surface dipole density with a surface height sensitivity for the detection of protein spots that is approximately 1 pm. This sensitivity easily resolves a submonolayer of solid-support immobilized antibodies and their antigen targets. Fluorescence and light scattering provide additional optical detection techniques on spinning disks. Immunoassays have been applied to haptoglobin using protein A/G immobilization of antibodies and to prostate specific antigen. Small protein spots enable scalability to many spots per disk for high-throughput and highly multiplexed immonoassays.
Disseminated Mycobacterium chelonae Infection in a Patient Receiving an Epidermal Growth Factor Receptor Inhibitor for Advanced Head and Neck Cancer

We report a case of disseminated cutaneous Mycobacterium chelonae infection in a patient with head and neck cancer on salvage chemotherapy, including the epidermal growth factor receptor inhibitor cetuximab. Mycobacterium chelonae should be considered in the differential diagnosis of cutaneous infections in cancer patients receiving epidermal growth factor receptor inhibitors.
The upregulation of specific interleukin (IL) receptor antagonists and paradoxical enhancement of neuronal apoptosis due to electrode induced strain and brain micromotion

The high mechanical mismatch between stiffness of silicon and metal microelectrodes and soft cortical tissue, induces strain at the neural interface which likely contributes to failure of the neural interface. However, little is known about the molecular outcomes of electrode induced low-magnitude strain (1–5%) on primary astrocytes, microglia and neurons. In this study we simulated brain micromotion at the electrode–brain interface by subjecting astrocytes, microglia and primary cortical neurons to low-magnitude cyclical strain using a biaxial stretch device, and investigated the molecular outcomes of induced strain in vitro. In addition, we explored the functional consequence of astrocytic and microglial strain on neural health, when they are themselves subjected to strain. Quantitative real-time PCR array (qRT-PCR Array) analysis of stretched astrocytes and microglia showed strain specific upregulation of an Interleukin receptor antagonist – IL-36Ra (previously IL-1F5), to ∼1018 and ∼236 fold respectively. Further, IL-36Ra gene expression remained unchanged in astrocytes and microglia treated with bacterial lipopolysaccharide (LPS) indicating that the observed upregulation in stretched astrocytes and microglia is potentially strain specific. Zymogram and western blot analysis revealed that mechanically strained astrocytes and microglia upregulated matrix metalloproteinases (MMPs) 2 and 9, and other markers of reactive gliosis such as glial fibrillary acidic protein (GFAP) and neurocan when compared to controls. Primary cortical neurons when stretched with and without IL-36Ra, showed a ∼400 fold downregulation of tumor necrosis factor receptor superfamily, member 11b (TNFRSF11b). Significant upregulation of members of the caspase cysteine proteinase family and other pro-apoptotic genes was also observed in the presence of IL-36Ra than in the absence of IL-36Ra. Adult rats when implanted with microwire electrodes showed upregulation of IL-36Ra (∼20 fold) and IL-1Ra (∼1500 fold) 3 days post-implantation (3 DPI), corroborating in vitro results, although these transcripts were drastically down regulated by ∼20 fold and ∼1488 fold relative to expression levels 3 DPI, at the end of 12 weeks post-implantation (12 WPI). These results demonstrate that IL receptor antagonists may be negatively contributing to neuronal health at acute time-points post-electrode implantation.
Plasma cells in the central nervous system in the Theiler's virus model of multiple sclerosis.

Abstract Background Immunoglobulin production within the central nervous system (CNS) is a prominent feature of multiple sclerosis and its animal model induced by infection with Theiler's meningoencephalitis virus, as well as of other inflammatory and infectious neurological diseases. However, relatively little is known about the plasma cells (PCs) responsible for producing Ig within the CNS. Methodology We induced Theiler's-induced demyelinating disease, characterized by disability, inflammation, and demyelination. We used immunofluorescence to localize and characterize IgG-producing cells, and correlated the morphology with results from CSF and tissue analysis. Results Confidence that IgG production occurred within the CNS was gained by demonstrating high levels of IgG in the cerebrospinal fluid in the absence of blood-CSF barrier or blood-brain barrier breakdown. CNS IgG-producing cells were CD138+, like IgG-producing cells elsewhere in the body. Less than 5% of IgG-positive cells were Ki67-positive, indicating that most were nonproliferative PCs. The PCs were present primarily in perivascular infiltrates and in the meninges. Isolated PCs could be found in the CNS parenchyma, and, when present, were largely in demyelinated regions of the cord. Significance These results demonstrate that PCs are a significant part of this chronic progressive disabling demyelinating disease, and suggest the possibility that these cells play a role in CNS injury by their secretion of immunoglobulin.
Characterization of mycobacterial triacylglycerols and monomeromycolyl diacylglycerols from Mycobacterium smegmatis biofilm by electrospray ionization multiple-stage and high-resolution mass spectrometry

The storage of triacylglycerols (TAGs) is essential for non-replicating persistence relevant to survival and the re-growth of mycobacteria during their exit from non-replicating state stress conditions. However, the detailed structures of this lipid family in mycobacteria largely remain unexplored. In this contribution, we describe a multiple-stage linear ion-trap mass spectrometric approach with high resolution mass spectrometry toward direct structural analysis of the TAGs, including a novel lipid subclass previously defined as monomeromycolyl diacylglycerol (MMDAG) isolated from biofilm of Mycobacterium smegmatis, a rapidly growing, non-pathogenic mycobacterium that has been used as a tool for molecular analysis of mycobacteria. Our results demonstrate that the major isomer in each of the molecular species of TAGs and MMDAGs consists of the common structure in which Δ918:1- and 16:0-fatty acyl substituents are exclusively located at sn-1 and sn-2, respectively. Several isomers were found for most of the molecular species, and thus hundreds of structures are present in this lipid family. More importantly, this study revealed the structures of MMDAG, a novel subclass of TAG that has not been previously reported by direct mass spectrometric approaches.
KINETICS OF CELL DEATH IN THE CYANOBACTERIUM ANABAENA FLOS-AQUAE AND THE PRODUCTION OF DISSOLVED ORGANIC CARBON1

Kinetics of cell death and the production of dissolved organic carbon (DOC) were investigated in Anabaena flos-aquae (Lyngb.) Breb grown on three different N sources (N2nitrate, and ammonium) in a phosphorus (P)-limited chemostat. The fraction of live cells in the total population increased as growth rate increased with decreasing P limitation. Cell death was less in nitrate and ammonium media than in N2. The specific death rate (γ), when calculated as the slope ofv−1x vs. D−1, where vxand D are live cell fraction (or cell viability) and dilution rate, respectively, was 0. 0082 day−1 in N2and 0.0042 day−1 in nitrate. The slope of the plot in ammonium culture was not significant; however, the value of the live cell fraction was within the range for the NO−3culture. The fraction of live vegetative cells in N2 culture was constant at all growth rates and the increase in the overall live cell fraction with growth rate was due entirely to an increase in live heterocysts. Live heterocysts comprised 3.5% of the total cells at a growth rate of 0.25 day−1 and increased to 6.3% at 0.75 day−1 with the ratio of live heterocysts to live vegetative cells linearly increasing with growth rate. The fraction of live vegetative cells was invariant in nitrate cultures us in N2cultures. The live heterocysts fraction also increased with growth rate in nitrate cultures, along with the live heterocysts : live vegetative cells ratio, but the level was lower than in N2cultures. DOC released from dead cells increased inversely with growth rate in N2from 36.4% of the total DOC at a growth rate of 0.75 day−1 to 54.15% at 0.25 day−1. The contribution of cell death to the total DOC production in nitrate and ammonium media was significantly less than that under N2DOC from dead cells consisted mainly of high-molecular-weight compounds, whereas DOC excreted from live cells was largely of low molecular weight.
Factors affecting parathyroid hormone-induced hypophosphatemia and32P specific activity in thyroparathyroidectomized rats

Plasma changes in calcium, phosphate, and their radionuclides were studied in thyroparathyroidectomized (TPTX) rats treated with parathyroid hormone (PTH) for 8 h, this treatment starting 10 h after injection of45Ca and32P. Prior to intravenous infusion or hourly injections of PTH (10 mU/g/h), rats were maintained in one of three ways: on an extended fast (24 h); on a partial fast (10 h); or provided with 10% glucose and 1% calcium lactate overnight as a substitution for solid food. The pattern of change for plasma calcium,45Ca, and45Ca specific activity (S.A.) produced by PTH was not affected by these dietary conditions. The changes in phosphate were as follows: During the experimental (8 h) period, the rate of loss of32P from plasma in control rats was proportional to the length of the fast. This suggests that32P was released into plasma during the experimental period proportional to the ready availability of soft tissue glucose. In rats on an extended fast, PTH was phosphaturic, hypophosphatemic, and increased the rate of loss of32P from plasma without affecting32P S.A. values. In rats fasted for only 10 h, PTH produced similar effects on plasma phosphate and plasma32P values, but also caused a significant fall in plasma32P S.A. After glucose and calcium lactate treatment, PTH-induced phosphaturia was temporarily lost and the marked hypophosphatemia was replaced with a slight hyperphosphatemia. Plasma32P values also rose slightly; therefore, no effect on32P S.A. was produced. It is concluded from these studies that as the result of the phosphaturia caused by PTH, the hypophosphatemia which is produced automatically changes the phosphate gradient between various body compartments, causing phosphate entry into plasma. The authors postulate that this phosphate entering plasma is withdrawn primarily from bone fluid and bone.
Diminished renal kallikrein responses to mineralocorticoid stimulation in African Americans: determinants of an intermediate phenotype for hypertension

Abstract Background Hypertension is a complex trait with an ill-defined genetic predisposition, in which renal mechanisms seem to be involved even at the early stages. Renal kallikrein excretion is diminished in patients with hypertension, and perhaps even in the early, prehypertensive phases of the syndrome. African Americans, a group at increased risk of developing hypertension, have especially diminished kallikrein expression, coupled with decreased renal excretion of K+, a known stimulant of kallikrein expression, suggesting an environmental mechanism for their kallikrein deficit. We, therefore, tested whether short-term indirect (K+) or direct (fludrocortisone) stimulation of mineralocorticoid activity might be capable of restoring kallikrein excretion in African Americans. Methods Nineteen healthy normotensive young men (n = 10 white, n = 9 African Americans) were treated with the following sequence of four oral medications, each for 1 week: placebo, KCl (120 mEq/day), placebo, and the mineralocorticoid fludrocortisone (0.4 mg/day). At each stage, we measured vital signs, excretion of kallikrein, aldosterone and electrolytes, and serum renin. Results were evaluated by two-way, repeated measures ANOVA. Results African Americans had diminished urinary excretion of not only kallikrein (P = .007), but also K+ (P .4). Conclusions Restoration of K+ and aldosterone secretion to levels found in whites does not normalize kallikrein excretion or lower BP in African Americans, at least in the short term. Nor does exogenous mineralocorticoid stimulation fully restore kallikrein expression in African Americans. Therefore, the diminution of kallikrein biosynthesis in African Americans seems to involve mechanisms at or distal to the aldosterone receptor, and perhaps at the level of the kallikrein gene itself.
Particulate contamination in selected parenteral drugs

The particulate contamination of five frequently prescribed drugs was studied. Samples were obtained in a laminar flow workbench according to millipore technique. The dry sample filters were examined with a binocular microscope at 50× and 100×. Particles were sized as to fibers, > 100 microns, 51 to 100 microns, 25 to 50 microns, and 10 to 24 microns. The results show the variability of contamination. Particulate counts appear to correlate with the manufacturing process. Bulk powders are highly contaminated, followed by lyophilize powders, then stable solutions. Until the clinical importance is resolved and manufacturing processes improved, in-line filters may be of value in selected patients.
MEAT MASSAGING: THE EFFECTS OF SALT, PHOSPHATE AND MASSAGING ON THE PRESENCE OF SPECIFIC SKELETAL MUSCLE PROTEINS IN THE EXUDATE OF A SECTIONED AND FORMED HAM

Samples of the tacky exudate formed on meat surfaces as a result of salt, phosphate and massaging were removed at intervals during 24 hr of massaging, and analyzed by SDS polyacrylamide gel electrophoresis to determine the relative percentage of various myofibrillar proteins present. The results showed that phosphate exerts the greatest effect on the relative percentages of actin, myosin and tropomyosin, and its action occurs primarily on meat surfaces before the massaging process is initiated. The massaging process involves great degrees of tissue destruction at the cellular level which aids in the extraction, solubilization, concentration and distribution of the major myofibrillar proteins on surfaces and in interiors of muscle chunks, which is beneficial in the improvement of binding.
Quality Improvement: Boon or Boondoggle?

Abstract Is quality improvement (QI) reducing healthcare costs while improving patient care? Researchers find that QI has improved employee satisfaction and morale, but it was de signed to do more. One solution is to use problem-solving techniques to help teams identify the level at which they want to address a problem, whether that be the subinstitutional, institutional, or system level. If QI is to fulfill its promise, skilled managers must create effective teams capable of defining and solving complex problems.
Ethnic-Group Strength Among Bosnian Refugees in St. Louis, Missouri, and Host Receptivity and Conformity Pressure

Leaving by force makes the refugee experience different from the immigrant experience and affects the resettlement process in the new homeland. Using a cross-sectional survey design and a purposive sample of 315 respondents, this study addressed the role of environmental factors in the resettlement process of Bosnian refugees. Four research questions were examined using correlation analysis. Results indicated that, contrary to the common belief that the receptivity and conformity pressure of the host environment are at odds with the interests of a strong ethnic group, a strong ethnic group can facilitate cross-cultural adaptation.