cssi/SciSciGPT-SciSciNet huggingface dataset:
Serial Assessment of Depression and Anxiety by Patients and Providers in Women Receiving Chemotherapy for Early Breast Cancer.

Background Depression and anxiety are common in patients with breast cancer and associated with worse quality of life and treatment outcomes. Yet, these symptoms are often underrecognized and undermanaged in oncology practice. The objective of this study was to describe depression and anxiety severity and associated patient factors during adjuvant or neoadjuvant chemotherapy in women with early breast cancer using repeated single-item reports. Materials and methods Depression and anxiety were measured from consecutive patients and their clinicians during chemotherapy infusion visits. Associations between psychiatric symptoms and patient characteristics were assessed using Fisher's exact tests for categorical variables and t tests for continuous variables. The joint relationship of covariates significant in unadjusted analyses was evaluated using log-binomial regression. Cohen's kappa was used to assess agreement between patient- and clinician-reported symptoms. Results In a sample of 256 patients, 26% reported at least moderately severe depression, and 41% reported at least moderately severe anxiety during chemotherapy, representing a near doubling in the prevalence of these symptoms compared with before chemotherapy. Patient-provider agreement was fair (depression: κ = 0.31; anxiety: κ = 0.28). More severe psychiatric symptoms were associated with being unmarried, having worse function, endorsing social activity limitations, using psychotropic medications, and having a mental health provider. In multivariable analysis, social activity limitations were associated with more severe depression (relative risk [RR], 2.17; 95% confidence interval [CI], 1.36-3.45) and anxiety (RR, 1.48; 95% CI, 1.05-2.09). Conclusion Oncologists frequently underestimate patients' depression and anxiety and should consider incorporating patient-reported outcomes to enhance monitoring of mental health symptoms. Implications for practice In this sample of 256 patients with breast cancer, depression and anxiety, measured using single-item toxicity reports completed by patients and providers, were very common during adjuvant or neoadjuvant chemotherapy. Patient-reported depression and anxiety of at least moderate severity were associated with multiple objective indicators of psychiatric need. Unfortunately, providers underrecognized the severity of their patients' mental health symptoms. The use of patient-reported, single-item toxicity reports can be incorporated into routine oncology practice and provide clinically meaningful information regarding patients' psychological health.
America’s Continuing Current Crisis: The Matter of Black Lives

Amid today’s global coronavirus pandemic, the widespread crash of the global economy, and insidious efforts of President Donald J. Trump to undercut American constitutional government to win by hoo...
Breadth and Depth

This essay is designed to help students do a little self-advocacy. They’ll get a chance to edit a document that plays an essential role in the professional world and their own career prospects, particularly when facing an uncertain job market: their resume.
Intra-Arterial, but Not Intrathecal, Baclofen and Codeine Attenuates Cough in the Cat.

Centrally-acting antitussive drugs are thought to act solely in the brainstem. However, the role of the spinal cord in the mechanism of action of these drugs is unknown. The purpose of this study was to determine if antitussive drugs act in the spinal cord to reduce the magnitude of tracheobronchial (TB) cough-related expiratory activity. Experiments were conducted in anesthetized, spontaneously breathing cats (n=28). Electromyograms (EMG) were recorded from the parasternal (PS) and transversus abdominis (TA) or rectus abdominis muscles. Mechanical stimulation of the trachea or larynx was used to elicit TB cough. Baclofen (10 and 100 g/kg, GABA-B receptor agonist) or codeine (30 g/kg, opioid receptor agonist) was administered into the intrathecal space and also into brainstem circulation via the vertebral artery. Cumulative doses of intrathecal baclofen or codeine had no effect on PS, abdominal muscle EMGs or cough number during the TB cough. Subsequent intra-arterial administration of baclofen or codeine significantly reduced magnitude of abdominal and PS muscles during TB cough. Furthermore, TB cough number was significantly suppressed by intra-arterial baclofen. The influence of these drugs on other behaviors that activate abdominal motors pathways was also assessed. The abdominal EMG response to noxious pinch of the tail was suppressed by intrathecal baclofen, suggesting that the doses of baclofen that were employed were sufficient to affect spinal pathways. However, the abdominal EMG response to expiratory threshold loading was unaffected by intrathecal administration of either baclofen or codeine. These results indicate that neither baclofen nor codeine suppress cough via a spinal action and support the concept that the antitussive effect of these drugs is restricted to the brainstem.
Cardiomyocytes recruit monocytes upon SARS-CoV-2 infection by secreting CCL2.

Heart injury has been reported in up to 20% of COVID-19 patients, yet the cause of myocardial histopathology remains unknown. Here, using an established in vivo hamster model, we demonstrate that SARS-CoV-2 can be detected in cardiomyocytes of infected animals. Furthermore, we found damaged cardiomyocytes in hamsters and COVID-19 autopsy samples. To explore the mechanism, we show that both human pluripotent stem cell-derived cardiomyocytes (hPSC-derived CMs) and adult cardiomyocytes (CMs) can be productively infected by SARS-CoV-2, leading to secretion of the monocyte chemoattractant cytokine CCL2 and subsequent monocyte recruitment. Increased CCL2 expression and monocyte infiltration was also observed in the hearts of infected hamsters. Although infected CMs suffer damage, we find that the presence of macrophages significantly reduces SARS-CoV-2-infected CMs. Overall, our study provides direct evidence that SARS-CoV-2 infects CMs in vivo and suggests a mechanism of immune cell infiltration and histopathology in heart tissues of COVID-19 patients.
The Na+/H+ Exchanger-3 (NHE3) Activity Requires Ezrin Binding to Phosphoinositide and Its Phosphorylation

Na+/H+ exchanger-3 (NHE3) plays an essential role in maintaining sodium and fluid homeostasis in the intestine and kidney epithelium. Thus, NHE3 is highly regulated and its function depends on binding to multiple regulatory proteins. Ezrin complexed with NHE3 affects its activity via not well-defined mechanisms. This study investigates mechanisms by which ezrin regulates NHE3 activity in epithelial Opossum Kidney cells. Ezrin is activated sequentially by phosphatidylinositol-4,5-bisphosphate (PIP2) binding and phosphorylation of threonine 567. Expression of ezrin lacking PIP2 binding sites inhibited NHE3 activity (-40%) indicating that ezrin binding to PIP2 is required for preserving NHE3 activity. Expression of a phosphomimetic ezrin mutated at the PIP2 binding region was sufficient not only to reverse NHE3 activity to control levels but also to increase its activity (+80%) similar to that of the expression of ezrin carrying the phosphomimetic mutation alone. Calcineurin Homologous Protein-1 (CHP1) is part, with ezrin, of the NHE3 regulatory complex. CHP1-mediated activation of NHE3 activity was blocked by expression of an ezrin variant that could not be phosphorylated but not by an ezrin variant unable to bind PIP2. Thus, for NHE3 activity under baseline conditions not only ezrin phosphorylation, but also ezrin spatial-temporal targeting on the plasma membrane via PIP2 binding is required; however, phosphorylation of ezrin appears to overcome the control of NHE3 transport. CHP1 action on NHE3 activity is not contingent on ezrin binding to PIP2 but rather on ezrin phosphorylation. These findings are important in understanding the interrelation and dynamics of a CHP1-ezrin-NHE3 regulatory complex.
Some results on value distribution of meromorphic functions in the unit disk

Let C and D be the unit circle and the open unit disk respectively. We shall use p ( z,z′ ) to represent the non-Euclidean distance [3, p. 263] between the two points z and z′ in D , and X ( w, w′ ) to represent the chordal distance between the two points w and w′ on the Riemann Sphere Ω .
Numerical Investigation of Nonlinear Internal Wave Generation and Breaking in Straits

Abstract : My long-term goals are to develop a physical understanding of the processes which lead to mixing in the ocean, with the aim of using this understanding to develop parameterizations of mixing suitable for global and regional models, and applying such models to societally relevant problems. A particular focus is the mixing induced by tidal flow over topography, and mixing induced by breaking nonlinear internal waves.
Immunologic sequelae of thermal injury: I. Frequency and relationship of epithelial antibodies to extent of burn

Abstract Anti-nuclear antibodies and antibodies reactive with the intercellular area (“pemphigus-like”), basement-membrane zone and basal cells of squamous epithelium were observed in the sera of acute and convalescent burn patients by the method of indirect immunofluorescence (IF). Tests for the presence of lymphocytotoxic and anti-IgG (rheumatoid factor) antibodies were negative. Irrespective of the extent (percentage) of thermal injury, higher titers of “pemphigus-like” and basal cell antibodies were observed in the acute than convalescent patients. When viewed according to the percentage of total body surface and third degree (3°) burn area, initial empirical observations suggested an increased frequency and higher titers of pemphigus-like and basal cell antibodies in patients with a 21–50% total body surface burn area, with higher titers of pemphigus-like antibodies observed in patients with ≤20% 3° burn vs those patients with >20% 3° burn area. However, statistical evaluation of these observations showed that there was no significance (P > 0.05) between the frequency and IF staining titer of these antibodies to the percentage of total body surface or 3° burn area. Comparison of the incidence of epithelial antibodies in the present and previous studies of burn patients suggests the presence of variations in the tissue and species specificities of these antibodies for various types of epithelia (substrates). Such variations may explain, in part, the different frequencies of epithelial antibodies observed in this and previous studies and suggest, if valid comparisons and the possible significance of these antibodies are to be made, that a mutually available agreed-upon substrate be used. Consideration of the etiology and significance of the development of epithelial antibodies and speculation as to their relationship to increased mortality and exacerbation of pathology following thermal injury are alluded to.
Integrated Health Monitoring for Multiple Air Vehicles

This chapter proposes an integrated health monitoring system whose objective is to maintain the integrity of a fleet of small unmanned aerial vehicles, or UAVs, despite the occurrence of actuator faults and body damage. The monitoring system relies on distributed, team-level abrupt and nonabrupt fault detectors (NaFDs) and enables UAV teams to compensate for an ineffective individual vehicle fault detection and recovery system, if any. The abrupt and nonabrupt fault detectors utilize relative positions and speeds of vehicles within sensor range, in addition to exploiting information available through the communication network. A special attention is given to the selection of the detector thresholds, at the design phase, to minimize the average time of detection and the probability of missed detections, while constraining the probability of false alarms to an acceptable limit. For such purpose, an automated procedure based on stochastic search is proposed. Integrated health monitoring and control is demonstrated numerically by means of high-fidelity, nonlinear 6-degree-of-freedom (6-DOF) simulations of teaming small-scale UAVs. The chapter shows that concurrent nonabrupt and abrupt faults can be detected and effectively compensated for, thus preserving the integrity of a formation. Keywords: autonomous vehicle; robustness; stochastic optimization; fault detection; distributed control; estimation
Human Pathogenic Viruses in Food

This chapter focuses primarily on those viruses for which food-borne transmission is well documented (hepatitis A virus (HAV) and noroviruses (NoV)), and therefore, control in food production, processing, and preparation is considered relevant. General information about structural, molecular, and environmental properties of those viruses specifically implicated in food-borne illness is detailed. Three types of food commodities are usually associated with viral disease outbreaks, those being (i) molluscan shellfish contaminated during production; (ii) fresh produce items contaminated during production, harvesting, or packing; and (iii) prepared foods contaminated during preparation. Poor personal hygiene practices of infected food handlers provide the source of contamination for prepared foods. This appears to be the most important factor influencing the food-borne transmission of enteric viruses, as U.S. Centers for Disease Control and Prevention (CDC) data indicate that 50 to 95% of viral food-borne disease outbreaks are attributable to poor personal hygiene of infected food handlers. In Europe, researchers compiled data from 10 surveillance systems in the European Foodborne Virus Network, finding NoV to be the cause of >85% of all acute nonbacterial outbreaks of gastroenteritis reported between 1995 and 2000. Intrinsic and extrinsic parameters commonly used by food processors include manipulation of temperature (cooking and heating, freezing, and refrigeration), water activity, pH, gaseous environment, natural and intentionally added inhibitors, and the presence of competitive microflora. Our understanding of the importance of enteric viruses in the overall burden of food-borne disease has increased dramatically over the past 20 years.
Antibodies to surface antigens of herpesvirus type 1- and type 2-infected cells among women with cervical cancer and control women.

Cells infected with herpesvirus type 1 or type 2 develop surface antigens which can be detected by immunofluorescence. Using the indirect immunofluorescence technique, we determined antibody titers to the surface antigens in 20 sera from persons with known type 1 virus infections, 20 sera from persons with known type 2 virus infections, 30 sera from women with cervical cancer, and 30 sera from matched control women. There was a good correlation between antibody activity to the surface antigens and neutralizing antibody activity for both herpesvirus type 1 and herpesvirus type 2 in all groups of sera examined. Women with cervical cancer did not have unusually high or low titers of antibody activity to the surface antigens. In the selected sera examined, analysis of antibodies to the surface antigens was not superior to the microneutralization test in distinguishing women with cervical cancer from control women. Images
A structural synthesis capability for integrally stiffened cylindrical shells.

Stiffened cylindrical shell structural synthesis by transforming strained minimization inequality into unconstrained minimization problem
Robust floor determination for indoor positioning

In recent years, indoor positioning system using existing Wi-Fi infrastructure and MEMS sensors have received significant attention. A key requirement for a complete 3-dimensional indoor positioning algorithm is to provide an accurate and robust user floor location estimate in a multi-floor building. In this paper, we propose novel techniques to estimate user floor location based on the received radio signal strengths from Wi-Fi access points in the building. We illustrate its performance advantages through simulations and multiple field test results across typical use case scenarios. We further discuss Wi-Fi outage scenarios during which the performance of the Wi-Fi based floor determination algorithm is limited. We then propose a method to blend the Wi-Fi access points based floor estimate with pressure sensor measurements to enhance the overall performance of the algorithm. Finally, we present performance results from field tests to validate the efficacy and robustness of our proposed techniques.
Abstract B62: Zinc supplementation reduces forestomach tumor burden in N-nitrosomethylbenzylamine-treated mice

Zinc deficiency is associated with high incidences of esophageal and other human cancers. In addition, zinc status in plasma and white blood cells is a better indicator of tumor burden and stage of the disease in head and neck cancer patients than overall nutritional status. Research in rodents found that zinc insufficiency leads to a highly proliferative hyperplastic condition in the upper gastrointestinal tract. Zn replenishment reduces the incidence of lingual, esophageal, and forestomach tumors in Zn-deficient rats and mice. While previous animal studies focused on the effect of Zn deficiency on cancer prevention and development, in this study we investigated the effect of Zn supplementation on carcinogenesis in Zn-sufficient mice of wild type and three tumor suppressor-deficient mouse strains, Fhit−/−, Fhit−/−Nit1−/−, and Fhit−/−Rassf1a−/−. About fifty mice from each strain received 6-8 doses of N-nitrosomethylbenzylamine (NMBA). Half the mice then received Zn supplemented water while another half received regular water. Sixteen weeks after last NMBA administration, mice were sacrificed and tumors were found only in forestomach. Mice without Zn supplementation had developed more tumors than Zn-supplemented mice: wild type C57BL/6 mice developed an average of 7.0 vs 5.0 tumors for Zn supplemented (p Citation Information: Cancer Prev Res 2010;3(12 Suppl):B62.
The Ihog Cell-Surface Proteins Bind Hedgehog and Mediate Pathway Activation

The ihog gene (interference hedgehog), identified by RNA interference in Drosophila cultured cells, encodes a type 1 membrane protein shown here to bind and to mediate response to the active Hedgehog (Hh) protein signal. ihog mutations produce defects characteristic of Hh signaling loss in embryos and imaginal discs, and epistasis analysis places ihog action at or upstream of the negatively acting receptor component, Patched (Ptc). The first of two extracellular fibronectin type III (FNIII) domains of the Ihog protein mediates a specific interaction with Hh protein in vitro, but the second FNIII domain is additionally required for in vivo signaling activity and for Ihog-enhanced binding of Hh protein to cells coexpressing Ptc. Other members of the Ihog family, including Drosophila Boi and mammalian CDO and BOC, also interact with Hh ligands via a specific FNIII domain, thus identifying an evolutionarily conserved family of membrane proteins that function in Hh signal response.
Continuous assessment of relative cerebral blood volume in transient ischemia using steady state susceptibility‐contrast MRI

The utility of a noninvasive steady state susceptibility-contrast MRI technique for continuous measurement of relative cerebral blood volume (rCBV) during global transient ischemia and subsequent hyperemia in a feline ischemia model is demonstrated. The measurements were obtained during a 10-min period of occlusion and 1-h period of reperfusion. Maximal hyperemic responses in gray matter, basal ganglia, and white matter (observed at 7,7, and 5 min, respectively) were 1.9 +/- 0.5, 1.8 +/- 0.3, and 1.7 +/- 0.6 times greater than baseline CBV (mean +/- SEM). Thirty to forty minutes after onset of reperfusion, CBV returned to normal. Thereafter, it decreased below baseline, nearing the control level by 1 h after onset of reperfusion. Steady state susceptibility-contrast MRI permits continuous, in vivo mapping of alterations in CBV.
Angiography in unstable angina.

Abstract Within the last decade, it has been appreciated that the acute coronary syndromes of unstable angina, non-Q-wave, and Q-wave myocardial infarction often share a common pathogenesis based on plaque disruption and thrombosis. Such “acute” lesions frequently have a characteristic angiographic appearance with sharp overhanging edges, irregular borders, and intraluminal lucency. This review focuses on the benefits and limitations of qualitative assessment of coronary lesion morphology, with respect to the sensitivity, specificity, and prognostic significance of complex lesions and intracoronary thrombi. Angiographic findings following thrombolysis for unstable angina are discussed, as well as the possible role for thrombolytic therapy as an adjunct to angioplasty in unstable angina.
STUDIES ON THE REDUCTION OF A TETRAZOLIUM SALT BY GREEN PLANT TISSUE

ALL PREPARATIONS of grana or chloroplasts isolated from green plants and still capable of performing the photochemical reductions known as the Hill reaction suffer to an unknown degree from structural deformations and from contaminations with cytoplasmic material. From the standpoint of correlating chloroplast structure and function, it would be of considerable help if fractionation experiments could be supplemented by a cytochemical method to localize the Hill reaction in individual chloroplasts of intact cells. Tetrazolium salts are compounds which have been valuable in localizing enzymatic reductions in many plant and animal cells because their colorless, water-soluble form is reduced to a colored, insoluble pigment at the site of activity; the literature on tetrazolium salts has been reviewed recently by Smith (1951). A method has been devised in which a tetrazolium salt is photochemically reduced and may possibly serve as an indicator of the Hill reaction. Results of preliminary experiments using the method are reported in this paper. MATERIALS AND METHODS.-The tetrazolium salt used in these experiments was "blue tetrazolium" (BT), a new ditetrazolium salt described by Rutenburg et al. (1950) and supplied by the Dajac Laboratories. This compound turns reddish purple when partially reduced and yields a stable, insoluble, blue-black diformazan when completely reduced. 2, 3, 5-triphenyltetrazolium chloride was tried and was found to be unsuitable for these experiments because the solution is unstable when exposed to light. The test solution ordinarily contained 1 part BT stock solution (1 mg./ml.), 1 part M/10 phosphate buffer, pH 6, and 2 parts water. In some experiments solutions of organic acids or sugars were substituted for part of the water. Phosphate buffer with a pH of 7.5 was used for blue-green algae. The solution used for marine algae contained 1 part BT solution and 3 parts sea water. With most of the plant materials the reaction was only slight when the experiments were conducted in air but was satisfactory when the material was under nitrogen, under hydrogen, or in evacuated tubes. For most of the experiments the solutions and plant material were placed in Thunberg tubes and evacuated 3 min. with a vacuum pump giving a pressure less than 1 cm. Hg. The tubes were placed immediately either into a water bath in a dark, 33?C. incubator or into an illuminated water bath kept at approximately 33?C. by running tap water. The water bath was a glass vessel illuminated from below by a 100 w. tungsten bulb in a white reflector;
Cable pili and the associated 22 kDa adhesin contribute to Burkholderia cenocepacia persistence in vivo.

Background Infection by Burkholderia cenocepacia in cystic fibrosis (CF) patients is associated with poor clinical prognosis. Previously, we demonstrated that one of the highly transmissible strains, BC7, expresses cable pili and the associated 22 kDa adhesin, both of which contribute to BC7 binding to airway epithelial cells. However, the contribution of these factors to induce inflammation and bacterial persistence in vivo is not known. Methodology/Principal Findings Wild-type BC7 stimulated higher IL-8 responses than the BC7 cbl and BC7 adhA mutants in both CF and normal bronchial epithelial cells. To determine the role of cable pili and the associated adhesin, we characterized a mouse model of B. cenocepacia, where BC7 are suspended in Pseudomonas aeruginosa alginate. C57BL/6 mice were infected intratracheally with wild-type BC7 suspended in either alginate or PBS and were monitored for lung bacterial load and inflammation. Mice infected with BC7 suspended in PBS completely cleared the bacteria by 3 days and resolved the inflammation. In contrast, mice infected with BC7 suspended in alginate showed persistence of bacteria and moderate lung inflammation up to 5 days post-infection. Using this model, mice infected with the BC7 cbl and BC7 adhA mutants showed lower bacterial loads and mild inflammation compared to mice infected with wild-type BC7. Complementation of the BC7 cblS mutation in trans restored the capacity of this strain to persist in vivo. Immunolocalization of bacteria revealed wild-type BC7 in both airway lumen and alveoli, while the BC7 cbl and BC7 adhA mutants were found mainly in airway lumen and peribronchiolar region. Conclusions and Significance B. cenocepacia suspended in alginate can be used to determine the capacity of bacteria to persist and cause lung inflammation in normal mice. Both cable pili and adhesin contribute to BC7-stimulated IL-8 response in vitro, and BC7 persistence and resultant inflammation in vivo.
Clinical trials of angiotensin receptor blockers in heart failure: what do we know and what will we learn?

Abstract Although interruption of the renin-angiotensin system with angiotensin converting enzyme (ACE) inhibitors has evolved as the therapy of choice in heart failure based on large-scale morbidity and mortality clinical studies, treatment with angiotensin type 1 receptor blockers (ARB) offers an alternative and potentially superior method of treating this condition. Early pilot studies were quite promising; however, two well designed, large-scale trials have shown that the reduction in heart failure mortality with ARB is not significantly different from the reduction with ACE inhibitors. Possible reasons for lack of ARB superiority include insufficient dosing of ARB, differences in effects mediated through angiotensin II type 2 receptors, interaction with β-blockers, and bradykinin-mediated effects specific to ACE inhibitors. The ACE inhibitors remain the current therapy of choice in treating heart failure until further outcomes trial data become available; however, ARB are a reasonable alternative in patients intolerant of ACE inhibitors.
Calculation of photon dose distributions in an inhomogeneous medium using convolutions.

A formulation of the single energy photon transport problem is cast in the form of a series of convolutions over the primary fluence distribution with invariant kernels. A method is developed for compensating for the variant intervoxel attenuation in the scattered dose distribution by means of an invariant correction kernel. Results of applying the formulation to 6 0Co distributions in the presence of slab and block inhomogeneities are presented.
Classical free-electron lasing in an undulating electrostatic field in the axial direction

It is shown that the phase of the electromagnetic wave emitted through stimulated emission is intrinsically random. The insensitivity of the phase of the laser field to any disturbance in the laser cavity parameter derives from the fact that stimulated and spontaneous emissions take place concurrently at the same wave vector, the phases of spontaneous emission are mildly bunched, and the central limit theorem can be applied to the phase of the laser field. The two spectral lines observed in the Smith-Purcell free-electron laser experiment show that both classical and quantum-mechanical free-electron lasings, in which the wigglers behave as classical waves and wiggler quanta respectively, take place concurrently at different laser wavelengths in the case of the electric wiggler. It is shown that the coherence of the classical free-electron laser is achieved through modulation of the relativistic electron mass by the electric wiggler. The classical free-electron lasing is calculated using the quantum-augmented classical theory. In this, the probability of stimulated emission is first evaluated by interpreting the classically derived energy exchange between an electron and the laser field from a quantum-mechanical viewpoint. Then the laser gain is obtained from this probability by using a relationship between the two quantities derived by quantum kinetics. The wavelength of the fundamental line of classical free-electron lasing is twice the wavelength of the fundamental line of the free-electron two-quantum Stark emission, which is the quantum free-electron lasing in the electric wiggler. The gain of the classical free-electron lasing appears to scale as λ3w/γ3, where γ is the Lorentz factor of the electron beam and λw is the wavelength of the wiggler.
Foldon-guided self-assembly of ultra-stable protein fibers.

A common objective in protein engineering is the enhancement of the thermodynamic properties of recombinant proteins for possible applications in nanobiotechnology. The performance of proteins can be improved by the rational design of chimeras that contain structural elements with the desired properties, thus resulting in a more effective exploitation of protein folds designed by nature. In this paper, we report the design and characterization of an ultra-stable self-refolding protein fiber, which rapidly reassembles in solution after denaturation induced by harsh chemical treatment or high temperature. This engineered protein fiber was constructed on the molecular framework of bacteriophage P22 tail needle gp26, by fusing its helical core to the foldon domain of phage T4 fibritin. Using protein engineering, we rationally permuted the foldon upstream and downstream from the gp26 helical core and characterized gp26-foldon chimeras by biophysical analysis. Our data demonstrate that one specific protein chimera containing the foldon immediately downstream from the gp26 helical core, gp26(1-140)-F, displays the highest thermodynamic and structural stability and refolds spontaneously in solution following denaturation. The gp26-foldon chimeric fiber remains stable in 6.0 M guanidine hydrochloride, or at 80°C, rapidly refolds after denaturation, and has both N and C termini accessible for chemical/biological modification, thereby representing an ideal platform for the design of self-assembling nanoblocks.
Bone-Mimetic Laminated Nano-Structures for Regeneration of Skeletal Tissues

Bone exhibits hierarchical levels of organization from macroscopic to microscopic to nanoscale. The objective of this work was to develop a bonemimetic composite matrix to provide structural support to the regenerating region and to support the cascade of osteogenic differentiation of progenitor marrow stromal (BMS) cells. Sheets of poly(L-lactide) (L-PLA) nanofibers, fabricated by electrospinning, were coated with a hydrogel/apatite precursor solution, stacked and pressed together, and allowed to crosslink by photopolymerization to form a peptide-reinforced hydrogel/apatite laminated composite. Addition of an osteonectin-derived glutamic acid peptide (Glu6) and lamination resulted in an order of magnitude increase in modulus of the composite to within the range reported for wet human cancellous bone. Lamination significantly increased the extent of mineralization of BMS cells and the laminates reinforced with apatite nanocrystals and conjugated with integrin-binding focal-point adhesion RGD peptide (Lam-RGD-HA) had 3-fold higher calcium content and higher expression of osteogenic markers osteopontin and osteocalcin (compared to laminates without apatite or RGD) after 21 days of incubation in osteogenic media. Laminated osteon-mimetic structures have the potential to provide mechanical strength to the regenerating region as well as supporting the differentiation of progenitor cells to the osteogenic lineage.
Thermal analgesia and substance P depletion induced by capsaicin in guinea-pigs.

Abstract Treatment of adult guinea-pigs with subcutaneous doses of capsaicin of 1, 5, 50, 200, 200, 500, 500 mg/kg in daily succession increased skin flinch latency and depleted substance P from dorsal root ganglia. Similar treatment of animals with doses of 50, 100, 100, 100, 100 mg/kg significantly increased skin flinch latency and hot-plate escape latency and depleted substance P from dorsal root ganglia and dorsal spinal cord. Capsaicin had no effect on levels of substance P in other CNS regions or in any region of the gastrointestinal tract. Responses to mechanical pressure were not altered by capsaicin treatment. Depletion of primary afferent substance P in guinea-pigs appears to result in substantial thermal antinociception without producing comparable pressure antinociception.
The adolescent with slipped capital femoral epiphysis

Slipped capital femoral epiphysis (SCFE) is an orthopedic disorder that occurs primarily in individuals in their early teen years. The disorder is one that requires immediate hospitalization for treatment purposes. This article discusses the symptoms of the disorder and the various treatments that are available for preventing future disability for the early adolescent. Because the adolescent has special needs and a long recovery period, nursing interventions must not only help in the resolution of the immediate orthopedic problems, but also be directed toward promotion of normal adolescent growth and development.
Dead pixel correction techniques for dual-band infrared imagery

Abstract We present two new dead pixel correction algorithms for dual-band infrared imagery. Specifically, we address the problem of repairing unresponsive elements in the sensor array using signal processing techniques to overcome deficiencies in image quality that are present following the nonuniformity correction process. Traditionally, dead pixel correction has been performed almost exclusively using variations of the nearest neighbor technique, where the value of the dead pixel is estimated based on pixel values associated with the neighboring image structure. Our approach differs from existing techniques, for the first time we estimate the values of dead pixels using information from both thermal bands collaboratively. The proposed dual-band statistical lookup (DSL) and dual-band inpainting (DIP) algorithms use intensity and local gradient information to estimate the values of dead pixels based on the values of unaffected pixels in the supplementary infrared band. The DSL algorithm is a regression technique that uses the image intensities from the reference band to estimate the dead pixel values in the band undergoing correction. The DIP algorithm is an energy minimization technique that uses the local image gradient from the reference band and the boundary values from the affected band to estimate the dead pixel values. We evaluate the effectiveness of the proposed algorithms with 50 dual-band videos. Simulation results indicate that the proposed techniques achieve perceptually and quantitatively superior results compared to existing methods.
Refinements in the determination of "free pregnanediol".

Pregnanediol, as a progesterone metabolite, has been the subject of much discussion both in relation to its interpretation and to the method of its determination (1–6). Because of its application to clinical problems we have been concerned with a more precise method of assay. Pregnanediol may be measured either as sodium pregnanediol glucuronidate by the classic method of Venning (7), or as “free” pregnanediol by various modifications of the Astwood-Jones (8) method. The present paper deals with the determination of “free” pregnanediol and with the elimination of some of the steroids which may tend to give high pregnanediol values.
Neck geometry and shape transitions in vesicles with co-existing fluid phases: Role of Gaussian curvature stiffness vs. spontaneous curvature

Lipid bilayer vesicles with fluid/fluid phase coexistence are promising model systems for biological cell membranes. They permit the investigation of the mechanical properties of lipid membranes that are important for understanding mechanistic aspects of biological membrane function. Comparison of experimentally obtained vesicle shapes to mechanical membrane theories has enabled us to determine the values of line tension and mean-curvature bending stiffness of liquid-ordered and -disordered membranes. An additional important parameter that controls membrane geometry is the spontaneous curvature, driven, for example, by peripheral protein coats or asymmetric lipid composition. We examine to what extent effects of differing spontaneous curvature and Gauss curvature stiffness between coexisting fluid phases can be distinguished by membrane shape analysis. We find that the equilibrium neck geometries of dumbbell-shaped vesicles and the shapes of vesicles close to budding are very similar for vesicles that differ in spontaneous curvature or Gauss curvature stiffness differences. However, the two parameters have qualitatively different influence on discontinuous budding transitions.
The Cajeput tree - a boon and an affliction.

The cajeput tree, native from Australia through Burma, is planted in forestry projects, for reclamation of swamps, and as an ornamental in warm climates; often escapes and invades vast areas of low land. The hard wood is durable underground and under water; checks and warps unless slowly seasoned, but is handsome when finished and prized for cabinetwork. The bark, chemically similar to cork, has many uses. Cajeput oil, obtained from the leaves, is in limited pharmaceutical demand, being more costly than oil of eucalyptus. Formerly acclaimed as an “antiseptic” tree, “subduing malarial vapors,” the cajeput has become in Florida a prime respiratory irritant. Since the pollen is not airborne, the irritant factor is apparently the volatile properly. Florida beekeepers, previously in opposition to the spread of the nectar-rich cajeput because of the unpleasant odor and taste of the honey, now have found it valuable for brood-rearing and salable after standing and blending.
Detection of ascorbic acid in the eye of the early chicken embryo by silver staining.

Abstract Ascorbate is found in high concentrations in the aqueous, lens and retina of a variety of animal species. Several functions have been proposed for this, including a vital role in aqueous secretion. We investigated the possible presence of ascorbate in the early embryonic chicken eye as a marker for the differentiation of the ciliary epithelium. Embryonic chicken eyes were processed for histochemical demonstration of ascorbate by silver staining. A strongly positive reaction was found in the interstitial matrix between the lens rudiment and the optic vesicle of the 2-day chicken embryo. By 3 days, with lens and optic cup separating from each other, the silver grains were concentrated in the vitreous cavity, primarily in a band-like configuration between the lens equator and the rim of the optic cup, which is the presumptive ciliary epithelium. A weaker reaction was seen in the lens vesicle and primitive neural retina. During the second and third day of incubation the optic vesicle is just beginning to expand. The appearance of ascorbic acid in the newly formed vitreous cavity at this time may indicate its importance in the biosynthesis of the matrix that is filling the expanding optic vesicle.
A statistical problem in genetic complementation experiments.

Abstract An estimate of the frequency of each type of enzyme dimer resulting from genetic complementation can be made without assuming that the frequency of monomer is constant from cell to cell. The estimate for hybrid dimers is always less than would be obtained if the frequency were constant and helps to explain why the amount of enzymic activity observed is less than that predicted. The deviation between the amount observed and that predicted is a measure of the cell to cell variation and can in turn provide an estimate of the number of polysomes per cell that are producing the monomer.
Cardiovascular and metabolic risks associated with PCOS

Polycystic ovary syndrome, the most common endocrine disorder of reproductive age women, is often associated with insulin resistance and associated disorders. The frequency of type 2 diabetes, hyperlipidemia, cardiac risk markers, structural vascular disease, and clinical disease events are increased in this population of women. PCOS, however, represents a broad spectrum of clinical presentations, as defined by different criteria proposed in Europe and the United States. The role of insulin resistance and hence the risk of cardiometabolic disorders may in part be determined by the definition of PCOS used. Epidemiologic studies and clinical trials support the need to identify women with PCOS to determine their risk of cardiometabolic disorders to prevent and/or treat their serious consequences.
Structural dynamics of CaMKII activation

The ubiquitously expressed calcium/calmodulin dependent protein kinase II (CaMKII) functions as a transducer of calcium (Ca2+) signaling by responding to the amplitude, duration, and frequency of Ca2+ transients. During periods of elevated Ca2+, CaMKII is activated by calcium-calmodulin (Ca2+/CaM) binding. A subsequent autophosphorylation at Thr286 allows for Ca2+-independent activity and endows this enzyme with a conformational memory of prior activation. CaMKII activity is regulated by a myriad of factors including CaM binding, autophosphorylation, and catalytic-regulatory domain interactions referred to as autoinhibition. While these variables have been linked to CaMKII function, the underlying structural and dynamic framework of activation and conformational memory is poorly understood. Here we utilize site-directed spin labeling and electron paramagnetic resonance (SDSL-EPR) to explore the conformational changes associated with CaMKII activation and conformational memory. EPR parameters were collected for the regulatory domain where CaM binding and autophosphorylation sites are located. Our results indicate the regulatory domain undergoes significant structural changes between several discrete conformations dependent on autophosphorylation and CaM binding. The CaM binding region is flexible in the apo state but has an induced rigidity in the presence of Ca2+/CaM indicative of a binding event. Investigation of the regulatory domain outside the CaM binding region revealed an increase in protein backbone dynamics with a Thr286Glu autophosphorylation mimic and/or in the presence of Ca2+/CaM. This data provides a structural and dynamic perspective consistent with the current biochemical activation model where CaM binding disrupts autoinhibition by disengaging regulatory and catalytic domains. We predict the enhanced flexibility facilitates Ca2+/CaM binding and may play a role in Ca2+ independent activity. The adjacent regulatory loop showed similar flexibility suggesting this region functions as a hinge between regulatory and catalytic domains allowing for release and reinstatement of autoinhibition.
Mindful Music Listening as a Potential Treatment for Depression

This column is designed to underscore relationally based creative interventions used by counselors and psychotherapists in their practices. Our intention is to provide examples of novel, innovative ways of working with clients in their efforts to deepen self-awareness and their connections with others. Although the interventions within this column will be presented in a linear “how-to” manner, an essential premise of this column is that interventions submitted for publication have a contextual and relational basis. Basic to this column is the therapeutic focus of working through latent hurts and impediments to our clients' health and happiness. Client goals generally involve creating the requisite emotional space needed for genuine relational choice for connection to manifest. If you have created a useful therapy tool or if you have adapted an existing creative tool that you would like to share with readers, please follow submission guidelines in the author information packet available at http://www.creat...
Membrane damage thresholds for pulsed or continuous ultrasound in phagocytic cells loaded with contrast agent gas bodies

Cell membrane damage induced by pulsed or continuous ultrasound (US) activation of attached contrast agent gas bodies was examined in an in vitro model system. Monolayers of mouse macrophage-like cells were cultured on the inside of one window of an exposure chamber. The monolayers were incubated with Optison (Amersham Health Inc., Princeton, NJ) or Definity (Bristol-Myers Squib Medical Imaging, North Billerica, MA) and then rinsed to remove unattached gas bodies. A 3.5-MHz focused transducer was aimed at the chamber 3.7 cm away in a 37 degrees C water bath. The cells were scored for Trypan blue dye exclusion, with stained nuclei indicative of cell membrane damage. Exposure-response functions were approximated with exposure levels spaced 3-dB apart. Thresholds were located between the lowest exposure with statistically significant counts of blue-stained cells relative to sham exposures, and the next lower level. Thresholds with Optison included 0.05 MPa for 60-s continuous exposure duration, and 0.21 MPa for 0.6-micros pulses with 60-micros repetition period for 60-s pulsed exposure duration. Results were similar for Definity. Thresholds changed slowly with changes in timing parameters; for example, the threshold for a 0.6-micros continuous exposure (i.e., one pulse) was 0.84 MPa. Compared to 60-s exposure, this represents a factor of 16.8 increase in threshold for a factor of 10(8) decrease in exposure duration. The thresholds are less than the pressure amplitudes needed for nucleation of inertial cavitation, which suggests classification of the phenomenon as a form of gas body activation.
Variation of diffusion length with processing in dielectrically isolated &#960;-silicon tubs

The variation of minority-electron diffusion length with processing in dielectrically isolated π-silicon tubs is investigated using electron-beam-induced current measurements. The analysis of these measurements is complicated by the six boundary conditions on the π-silicon. The diffusion lengths measured in virgin π-tub silicon are ≤ 250 µm while those in π-silicon undergoing a phosphorus getter are >> 250 µm. The determination of exact values for the diffusion lengths as a function of processing are not possible without a more complete understanding of the parasitic effects of the inversion region at the tub walls. Trends in the diffusion lengths are indicative of trends in the carrier lifetime, which are critical in the high-voltage applications for silicon tubs.