cssi/SciSciGPT-SciSciNet huggingface dataset:
Recapitulating cancer cell invasion in vitro

Confocal microscopy can visualize cancer cell metastasis in the vicinity of a primary tumor site in animal models of cancer in real time. However, spatial resolution of current microscopes in vivo remains limited and subcellular structures cannot be readily imaged, reducing the molecular mechanistic insights that can be directly obtained from in vivo models of cancer metastasis. Moreover, therapeutic approaches that are successful in rodent models do not always translate into actual therapeutic approaches to human cancers. Hence, in vitro models remain useful not only to further our basic understanding of cancer cell biology and the metastatic cascade but also for clinical applications, such as high-throughput drug screening and testing. In particular, in vitro structures that acknowledge the three-dimensionality of the stromal space during invasions may have a significant impact on oncology in the near future (1).
Development and validation of a 6-day standard for the identification of frequent mental distress

The goals of the current study were to assess the concurrent validity of a single-item measure of general mental distress with established, multi-item mental health measures used in population-level surveillance and to establish the optimal cutpoint for determining psychological distress (previously identified as frequent mental distress) using recently available data from the Behavioral Risk Factor Surveillance System survey. Data for this study were obtained from the core questionnaire and two optional modules available as part of the 2006 and 2007 Behavioral Risk Factor Surveillance System (BRFSS) surveys. Frequent mental distress (FMD) was identified by the number of days of self-reported poor mental health during the last 30 days. Comparisons of the number of days with poor mental health and positive scores for measures of depression and serious mental illness were calculated to identify the most efficient cutpoint for establishing FMD. Comparisons of results obtained from ROC analyses using the PHQ-8 and K6 reported 0.867 (95% CI 0.861–0.872) and 0.840 (95% CI 0.836–0.845) of the area under the curve, respectively, suggesting good accuracy. Using the Youden index, 6 days of poor mental health in the past 30 days, rather than the existing 14-day standard, was identified as the point at which the sum of the sensitivity and specificity was greatest. Results from this study suggest that a 6-day standard (FMD-6) can be used as a valid and reliable indicator of generalized mental distress with strong associations to both diagnosable depressive symptomology and serious mental illness.
A unique and essential role for insulin in the phenotypic expression of rat mammary epithelial cells unrelated to its function in cell maintenance

Abstract Mammary explants from pregnant rats can be induced in regard to casein synthesis and α-lactalbumin activity when cultured in the presence of hydrocortisone, prolactin and levels of insulin approaching physiological concentrations. No detectable induction occurs in the absence of insulin. Although epidermal growth factor and multiplication stimulating activity, in the presence of hydrocortisone, can maintain the initial level of NADH-cytochrome c reductase as well as insulin, neither can substitute effectively for insulin in the induction of the milk proteins. Proinsulin, nerve growth factor, platelet-derived growth factor and fibroblast growth factor are also ineffective substitutes for insulin in this regard. Whereas prolonged tissue exposure to multiplication stimulating activity, hydrocortisone and prolactin does not result in induction of α-lactalbumin activity, subsequent addition of insulin leads to prompt response. The results suggest that the ability of insulin to function as a unique, essential factor in the induction of rat milk proteins is independent of its cell-maintenance activity. Thus, in addition to its well established functions in metabolic processes, insulin appears to play a vital role in certain developmental processes.
Role of Molecular Charge in Nucleocytoplasmic Transport

Transport of genetic materials and proteins between the nucleus and cytoplasm of eukaryotic cells is mediated by nuclear pore complexes (NPCs). A selective barrier formed by phenylalanine-glycine (FG) nucleoporins (Nups) with net positive charges in the NPC allows for passive diffusion of signal-independent small molecules and transport-receptor facilitated translocation of signal-dependent cargo molecules. Recently, negative surface charge was postulated to be another essential criterion for selective passage through the NPC. However, the charge-driven mechanism in determining the transport kinetics and spatial transport route for either passive diffusion or facilitated translocation remains obscure. Here we employed high-speed single-molecule fluorescence microscopy with an unprecedented spatiotemporal resolution of 9 nm and 400 µs to uncover these mechanistic fundamentals for nuclear transport of charged substrates through native NPCs. We found that electrostatic interaction between negative surface charges on transiting molecules and the positively charged FG Nups, although enhancing their probability of binding to the NPC, never plays a dominant role in determining their nuclear transport mode or spatial transport route. A 3D reconstruction of transport routes revealed that small signal-dependent endogenous cargo protein constructs with high positive surface charges that are destined to the nucleus, rather than repelled from the NPC as suggested in previous models, passively diffused through an axial central channel of the NPC in the absence of transport receptors. Finally, we postulated a comprehensive map of interactions between transiting molecules and FG Nups during nucleocytoplasmic transport by combining the effects of molecular size, signal and surface charge.
The Impact of Hopelessness and Hope on the Social Work Profession

Burnout and turnover are detrimental to social service organizations, social service providers and clients. Very often organizational characteristics are part of the cause for burnout. Burnout in a job can lead to hopelessness for social service providers and begin a vicious cycle of continued burnout and increased hopelessness. Knowing the characteristics of hopelessness can help social welfare institutions nurture their employee's level of hope thus impacting the way the social service providers work with their clients.
The sharing of cDNA microarray data

During the initial development of microarrays, much discussion revolved around the technology itself. The discussion has now shifted to data analysis and data sharing. There is great interest in the sharing of cDNA microarray data, but several issues related to format, quality and validation will need to be resolved before microarray data can be meaningfully integrated into other molecular databases.
Noradrenergic Function in Suicide

Although abnormalities in serotonergic function have been the major focus of studies on suicidal behavior, several studies indicate that abnormalities of noradrenergic function may also be involved in the pathophysiology of suicide. In this paper, we have reviewed some of the noradrenergic studies in suicide, including studies of the biosynthetic enzyme for norepinephrine, tyrosine hydroxylase (TH), the receptors for norepinephrine, alpha- and beta-adrenergic receptors, as well as the signaling cascades linked to beta-adrenergic receptors. In general, these studies indicate that the protein expression of TH, as well as alpha2- and beta2-adrenergic receptors, is increased in the postmortem brain of suicide victims. More studies are needed in order to examine extensively the role of noradrenergic function in suicidal behavior.
Experimental evaluation of a new composite mesh with the selective property of incorporation to the abdominal wall without adhering to the intestines

This preliminary study examined the possibility of preventing intestinal adhesions to biomaterials while preserving their incorporation with the abdominal wall. White New Zealand rabbits received intraperitoneal implants of different biomaterials for repair of defects created on the abdominal wall. The following biomaterials were used: polypropylene, polyester, expanded polytetraflueroethylene, polypropylene mesh/polypropylene sheeting (polypropylene mesh covered with polypropylene sheeting on the peritoneal side), polypropylene/silastic, polypropylene/polyglactin, polypropylene/polyglycolic acid, and polypropylene/fibrin. All biomaterials evaluated caused adhesions to the intestines except for polypropylene mesh/polypropylene sheeting and polypropylene mesh/silastic composites. Because adhesion of the intestine to the biomaterial is the first stage of biomaterial-related intestinal fistula, its prevention is logical for the elimination of this complication. Composites with the selective property of adhering to the abdominal wall, yet sparing the viscera, would facilitate thoracic and abdominal wall surgeries, as well as intraperitoneal laparoscopic hernioplasties.
Replacement of Threonine 558, a Critical Site of Phosphorylation of Moesin in Vivo, with Aspartate Activates F-actin Binding of Moesin REGULATION BY CONFORMATIONAL CHANGE

Point and deletion mutants of moesin were examined for F-actin binding by blot overlay and co-sedimentation, and for intra- and intermolecular interactions with N- and C-terminal domains with yeast two-hybrid and in vitro binding assays. Wild-type moesin molecules interact poorly with F-actin and each other, and bind neither C- nor N-terminal fragments. Interaction with F-actin is strongly enhanced by replacement of Thr558 with aspartate (T558D), by deletion of 11 N-terminal residues (DelN11), by deletion of the entire N-terminal membrane-binding domain of both wild type and T558D mutant molecules, and by exposure to phosphatidylinositol 4,5-diphosphate. Activation of F-actin binding is accompanied by changes in inter- and intramolecular domain interactions. The T558D mutation renders moesin capable of binding wild type but not mutated (T558D) C-terminal or wild type N-terminal fragments. The interaction between the latter two is prevented. DelN11 truncation enables binding of wild type N and C domain fragments. These changes suggest that the T558D mutation, mimicking phosphorylation of Thr558, promotes F-actin binding by disruption of interdomain interactions between N and C domains and exposure of the high affinity F-actin binding site in the C-terminal domain. Oscillation between activated and resting state could thus provide the structural basis for transient interactions between moesin and the actin cytoskeleton in protruding and retracting microextensions.
Pleiotrophin gene expression is highly restricted and is regulated by platelet-derived growth factor

Pleiotrophin (PTN) is a growth and neurite extension promoting polypeptide which is highly expressed in brain and in tissues derived from mesenchyme. The PTN gene is developmentally regulated and is closely related to the MK and RI-HB genes, both of which are developmentally regulated and induced by retinoic acid. We now have screened 17 cell lines and report that expression of the PTN gene in these cells is restricted to embryo fibroblasts and intestinal smooth muscle cells. However, NIH 3T3 cells stimulated by the platelet-derived growth factor (PDGF) express a marked increase in levels of PTN mRNA whereas retinoic acid failed to increase levels of PTN mRNA in NIH 3T3 cells or in F9 embryonal carcinoma cells within 72 hours of exposure. The results suggest that expression of the PTN gene is highly restricted and that the PTN gene is a new member of the PDGF-induced cytokine family.
Development of the Perceptions of Mentoring Relationships Survey: A Mixed Methods Approach

This paper reports the development and construct-related validity of the Perceptions of Mentoring Relationships Survey (PMRS). I used a sequential, exploratory, mixed methods design to develop the survey. Multistage purposeful sampling was used to recruit participants from a small southeastern university. I used open-ended questions in Study 1 to obtain participants' perceptions of mentors' and mentees' roles in mentoring relationships and to obtain their perceptions of the benefits of mentoring relationships. Results led to the development of a 24-item instrument. I assessed the score reliability and construct-related validity of the PMRS in Study 2. Results showed that scores from the instrument yielded coefficient alphas that ranged from 0.81-0.92. Results from an exploratory factor analysis revealed that the a priori three-factor structure accounted for 52.18% of variance in the data. Results revealed that the PMRS is a construct-related valid instrument that reliably generates data regarding individual perceptions of mentoring relationships.
Lack of correlation between agglutinability, the surface distribution of con A and post-confluence inhibition of cell division in ten cell lines

Agglutinability by concanavalin A, distribution of surface-bound concanavalin A, and maximal cell density in monolayer culture were examined under similar conditions in parallel cultures of ten established cell lines. The degree of agglutinability of the cell lines did not correlate with the presence or absence of patching of concanavalin A bound to the cell surface, as determined with a hemocyanin marker. Agglutinability was also not always correlated with the loss of post-confluence inhibition of cell division. Two clones of mouse 3T3 fibroblasts that maintained post-confluence inhibition of cell division and low agglutinability differed substantially with respect to the surface distribution of concanavalin A. Patching of concanavalin A binding sites is neither necessary nor sufficient to explain differences in agglutinability between cell lines.
In vitro effects of human prolactin and oxytocin on sulfatase activity in isolated human decidual cells.

Homogeneous preparations of decidual cells were obtained from term decidual tissue adherent to fetal membranes by using a slightly modified version of a technique developed for the isolation of decidual cells from first and second trimester decidua. The effects of human PRL (hPRL) and oxytocin on the kinetics of the hydrolysis of estrone sulfate were determined in decidual cells prepared from tissue obtained before and after the onset of labor. In addition, sulfatase activity in decidual cells isolated from term decidua was compared with those of chorionic cells isolated from chorion laeve of the same pregnancy. Chorionic cells had significantly higher (mean, 2.5-fold) levels of sulfatase activity than the corresponding decidual cells. The mean sulfatase activity in decidual cells obtained after normal vaginal delivery [25 ± 19 (±SE) nmol⁄mg protein-15 min) was higher than that in decidual cells obtained from patients undergoing cesarean section before the onset of labor (1.7 ± 0.11). This difference was ...
Epitaxial Electrodeposition of a Crystalline Metal Oxide onto Single-Crystalline Silicon

Epitaxial films of cuprous oxide, Cu2O, are electrodeposited from aqueous solution onto single-crystalline Si(001). The epitaxial growth of Cu2O onto Si is an unexpected result, because there is a strong driving force for the oxidation of Si to form a native amorphous SiO2 layer. The Cu2O films are single-crystalline in nature, with little or no fiber texture. High-resolution X-ray diffraction shows that the very large lattice mismatch of −21.4% is reduced to +11.2% by the formation of a Cu2O(001)[100]//Si(001)[110] orientation relationship, in which the film is rotated 45° around the common [001] axis. Cross-sectional transmission electron microscopy studies suggest that the growth mechanism involves an initial electroless deposition of Cu2O epitaxial seeds in direct contact with the Si(001), with the concomitant oxidation of Si to form a layer of amorphous SiO2 about 3 nm thick. Electrochemical deposition of Cu2O then proceeds on the epitaxial seeds, with the deposit growing not only perpendicular to th...
Toward informative planning for cooperative underwater localization

This paper reports on an algorithm for planning a practical trajectory for a surface vehicle that provides range measurements to an autonomous underwater vehicle (AUV). We consider server-client cooperative localization in which a server vehicle provides relative range constraints to minimize the uncertainty of a client vehicle. Our approach assumes the nominal client mission plan is available and draws potential server trajectories from a set of parameterized trajectory classes. We provide a comparative evaluation over several simulations, for both a single client and multiple clients, demonstrating that our algorithm computes operationally practical server paths and performs well relative to existing planning frameworks.
Field-induced inter-ferroelectric phase transformations and domain mechanisms in high-strain piezoelectric materials: insights from phase field modeling and simulation

Large, reversible and anhysteretic strain induced by external field is desired for multifunctional materials used in sensors, actuators and transducers. However, these desired attributes usually compromise each other, leading to trade-offs in materials’ properties and limiting their applicability. This paper focuses on field-induced inter-ferroelectric phase transformations. Some fundamental principles and domain mechanisms are systematized based on insights learned from phase field modeling and simulations, whose synergistic operations are expected to provide unique combination of large, reversible, and anhysteretic strain attributes. These working principles are: (i) Field-induced inter-ferroelectric structural phase transformation to achieve large strain; (ii) Field-induced stable-metastable phase transformation to maximize reversibility; (iii) Heterogeneous nucleation-and-growth process at domain walls to enhance low-field responses; (iv) Deactivation of domain wall motion by applying external fields along nonpolar axes to minimize hysteresis; (v) Domain wall broadening mechanism and domain size effect to exploit nanoscale engineered domain microstructures; and (vi) Bridging domain mechanism and phase coexistence to promote ferroelectric shape memory effects. It is shown that special initial domain microstructures and preferred evolution kinetic pathways can be achieved by crystallographic domain engineering technique, which allow multiple principles to work together without compromising one another. Due to the commonalities and fundamental interrelations among ferroelectric, ferromagnetic and ferroelastic materials, the gained understanding of thermodynamic and kinetic principles has general implications to displacive phase transformations in ferroic materials and is helpful for design of new functional materials with advanced field-induced strain properties.
Recent studies of the melanin-dispersing effect of MSH on melanophores ☆

Abstract There can presently be no significant doubt that MSH produces melanin dispersion in melanophores by increasing the cyclic AMP content of the cell. MSH is capable of stimulating the adenylcyclase of melanoma and adrenocortical tissue. There is an increase in the cyclic AMP content of melanophore-bearing frog skin in response to MSH. Cyclic AMP has a melanin-dispersing action in vivo, in vitro, and in tissue culture. In addition, cyclic AMP causes processes to form on tissue-cultured melanophores, the first published case of such an effect known to the author. Finally, the action of melanin-aggregating agents is accompanied by a lowering of the cyclic AMP content of melanophore-bearing frog skin. The major question now involves the mechanism of the melanin-dispersing action of cyclic AMP. Sodium is not required for the effect. Calcium may be required, but this has not as yet been proven. Water uptake may occur during melanin dispersion, because the effect is inhibited by hypertonicity and enhanced by hypotonicity. However, the mechanism is as yet not elucidated.
Diabetes in heart failure: prevalence and impact on outcome in the population.

Abstract Purpose Little is known on the prevalence and prognostic importance of diabetes mellitus (DM) among individuals with heart failure (HF) in community-based cohorts. Methods Within Olmsted County, Minnesota, a random sample of all subjects with a first diagnosis of HF between 1979 and 1999 was validated using Framingham criteria. DM was validated using glycemic criteria. Results Among 665 subjects with HF (mean age 77±12 years, 46% male), 20% had prior DM. Subjects with DM were younger, had greater body mass index (BMI), and lower left ventricular ejection fraction than subjects without diabetes. The prevalence of DM increased markedly over time (3.8% per year; 95% confidence interval [CI], 0.8 to 6.9; P =.024), independently of BMI, particularly in older subjects (odds ratio of having DM in 1999 compared with 1979 was 3.93 [95% CI, 1.57 to 9.83] in subjects ≥75 years vs. 1.11 [95% CI, .40 to 3.05] in subjects P =.017). The risk of death associated with DM differed markedly according to clinical coronary artery disease (CAD) ( P =.025). Subjects with DM and no CAD had a higher risk of death (relative risk [RR]=1.79 [95% CI, 1.33 to 2.41]) than those with CAD (RR=1.11 [95% CI, .81 to 1.51]), independently of age, sex, BMI, renal function, calendar year of HF, comorbidity and EF. Conclusions Among community-dwelling patients with HF, the prevalence of DM increased markedly over time. DM is associated with a large increase in mortality, particularly among subjects without clinical CAD, underscoring the importance of aggressive management of DM in HF.
How do proteins locate specific targets in DNA

Many aspects of biology depend on the ability of DNA-binding proteins to locate specific binding sites within the genome. Interest in this target search problem has been reinvigorated through the recent development of microscopy-based technologies capable of tracking individual proteins in real-time as they search for binding sites. In this review we discuss how two different proteins, lac repressor and RNA polymerase, have solved the target search problem through seemingly different mechanisms, with an emphasis on how recent in vitro single-molecule studies have influenced our understanding of these reactions.
The negro in detroit

Review of the report prepared for the Mayor's Inter–racial Committee by a special survey staff under the general direction of the Detroit Bureau of Governmental Research
The Effect of Response Categories on Questionnaire Answers Context and Mode Effects

This article reports the effect that the ranges presented in answer categories for survey questions can have on respondent answers. Response categories were manipulated in a split-ballot survey conducted in both telephone and mail modes. These categories, presented in the separate ballots, overlapped in one category; the other categories were unique to each ballot. The experiment was conducted on four questions: two frequent and mundane and two rare and salient. It was found that the response categories significantly affected the response for frequent and mundane questions. One question demonstrated a significant difference in response between the mail and telephone modes. For this question, a response scale with a limited number of socially desirable alternatives resulted in a social desirability effect in the telephone mode. Alternatively, the telephone mode demonstrated an extremeness effect when the response scale comprised a greater number of socially desirable alternatives.
Nondifferential Reinforcements and Discrimination Learning by Retardates

Summ~y.-20 retarded subjects received 50 trials of nondifferential reinforcement in the presence of cues on the dimension of shape and subsequently learned either a shape discrimination with color irrelevant or a color discrimination with shape irrelevant. 20 control subjects simply learned the shape or color discrimination. Nondifferential reinforcement significantly facilitated learning of the color discrimination and only rended to nonsignificantly hinder learning of the shape discrimination. Results were discussed in terms of Mackintosh's attentional theory of discrimination learning. ' Mackintosh (1965) has proposed a two-stage model of discrimination learning in which he suggests that, in the course of discrimination learning, the subject learns both to attend to the relevant stimulus dimension and to respond differentially to specific cues along that dimension. For example, in a blackwhite discrimination the subject must learn to attend to the brightness cues (rather than, say, to position cues) and to respond differentially to black and white. In addition, Mackintosh suggests that nondifferential reinforcement of responses to cues along a dimension should cause a subject to ignore that dimension and hinder performance on a subsequent discrimination task with that dimension relevant. The results of a study by O'Malley, Amone, and Ziegenfus (1969) are consistent with this contention. It: was found that nondifferential reinforcement in the presence of black and white (the subject simply being fed in black and white striped home cages) facilitated the learning of a position task with brightness an irrelevant cue and nonsignificantly hindered the learning of a brightness discrimination. The present study involved a similar nondifferential reinforcement procedure with human retardates as subjects. MBTHOD Subjects anst Apparatus The subjects were 40 retardates (26 males and 14 females) ranging in MA from 734 to 12% yr. and in CA from 11 to 19 yr. The mean MA and CA were 9.85 yr. and 14.95 yr., respectively. Groups were matched on mean CA and MA. The subjects were students available at the Keystone Training and Rehabilitation Center, Scranton, Pa. The apparatus was a white wooden
Investigations concerning the theory of ‘spurt’ and ‘shunt’ muscles

Abstract The object of this study is to examine in some detail the theory of ‘spurt’ and ‘shunt’ muscles as proposed by MacConaill (1946, 1949) and MacConaill and Basmajian (1969). The prime application of the theory is to the flexors of the forearm, and the greater portion of this analysis concerns these muscles. The centripetal force required in rapid movements of the forearm is calculated. An electromyographic experiment demonstrated that the brachioradialis is not active in resisting a force of this magnitude tending to separate the bones forming the elbow joint. The theoretical ability of the brachioradialis to supply the required force is then determined. It is shown that, of the various muscles able to provide shunt force, the brachioradialis is not the best. Finally, the application of the theory of ‘spurt’ and ‘shunt’ muscles to other anatomical regions is analyzed and found to be unsupported by evidence.
Rheumatoid arthritis: When should we use rituximab to treat RA?

A decade and a half of rapid progress in treating rheumatoid arthritis (RA) has left clinicians with many options, yet few validated guidelines on how best to use them. What difference will new recommendations on the use of rituximab make to clinical practice?
The unintended consequences of digital technology: exploring the relationship between sexting and cybervictimization

Progress in cyber technology has created innovative ways for individuals to communicate with each other. Sophisticated cell phones, often with integrated cameras, have made it possible for users to instantly send photos, videos, and other materials back and forth to each other regardless of their physical separation. This same technology also makes sexting possible – sending nude or semi-nude images, often of oneself, to others electronically (e.g., by text message, email). Few studies examining sexting have been published, and most have focused on the legal issues associated with juvenile sexting. In general, lacking are empirical analyses of the prevalence of sexting, and its potential consequences (i.e., victimization) that are theoretically grounded. Accordingly, we explored the possible link between sexting and online personal victimization (i.e., cybervictimization) among a sample of college students. As hypothesized, respondents who engaged in sexting were more likely to not only experience cybervi...
Evaluation of the RIDAQuick norovirus immunochromatographic test kit.

Abstract Background Norovirus infections occur frequently and are widespread throughout the US population causing greater than half of all foodborne gastroenteritis cases. A rapid norovirus assay would be a useful clinical tool for identification of this common virus in gastroenteritis patient samples, thereby identifying outbreaks and facilitating rapid implementation of control measures. Objectives To determine the suitability of the RIDAQuick norovirus kit as a clinical tool by determining the specificity and sensitivity of the assay, and its cross-reactivity with other enteric viruses. Study design Archived stool specimens containing norovirus genogroup I or II or other viruses were tested using the RIDAQuick norovirus assay and results compared to those obtained with real-time RT-PCR. Results We tested 62 samples: 19 norovirus genogroup I, 25 genogroup II samples, and 18 norovirus negative samples. Compared to PCR results, RIDAQuick assay sensitivity was 61.4%, and specificity was 100%. The low sensitivity was mainly due to poor results with genogroup I specimens; only 11 of 19 were detected. Additionally, samples of four other common enteric viruses all tested negative with the RIDAQuick assay. Conclusions The RIDAQuick kit effectively detects norovirus genogroup II strains, but not genogroup I strains. We found no cross-reactivity with several common enteric viruses. As most norovirus cases are currently genogroup II strains, positive results with RIDAQuick can be used for rapid detection of norovirus in a large percentage of cases, thus also aiding in identification of outbreaks. However, final confirmation and negative results require further testing with more sensitive methods.
Applications of computer algebra to molecular spectroscopy

Abstract The vibrations and rotations of Morse oscillators are treated using algebraic techniques. Van Vleck transformations are performed using the algebraic computing system REDUCE to find an effective hamiltonian which describes the motions.
BLyS antagonists and peptide tolerance induction

The major impediment to drug development for systemic lupus erythematosus (SLE) is its heterogeneity. The unpredictable manner in which lupus targets different organs at varying intensity makes the study of new drugs and the optimization of their administration extremely difficult. With the advent of novel, targeted biologic agents for SLE, it can be hoped that more strategic, lupus-relevant immune modulation will lead to safer and more effective treatments. Two alternative new approaches to lupus treatment are reviewed. The first involves selective inhibition of a single protein (BLyS), which may play a central role in host defense and in the pathogenesis of SLE. Although this approach is finely targeted to the inhibition of a single protein which is known to be upregulated in SLE patients, the positioning of BLyS at a critical hub in the immune response suggests that more global adverse repercussions on immunity might still occur. The second strategy is the use of peptides designed to specifically induce tolerance in limited autoreactive immune responses. Immune repercussions might, at least in theory, be almost nonexistent with this kind of approach. Concerns that limited induction of tolerance might have equally limited impact on the complex immune disorder of SLE are not borne out in preliminary murine data. Specific development programs are ongoing using both of these strategies and have recently entered human trials.
Disposition of benzocaine in channel catfish

The concentration-time profile of total radioactivity and of unchanged benzocaine and each of its metabolites was characterized in male and female channel catfish (Ictalurus punctatus) after 25 °C water exposure of the fish to 70 mg 1−1 (ppm) 14C-benzocaine until anesthesia (about 5 min) and then to 35 mg 1−1 for 30 min. The average concentration of radioactivity in the tissues and fluids ranged from 19.4 ± 14.3 ppm in white muscle to 143 ± 9.87 ppm in liver immediately after exposure. Concentrations of radioactivity in most tissues reached about 1% of the time 0 values by 25 h, and thereafter, the residue concentration-time profiles were loglinear up to 20 days; half lives were about 8 days except for 3.2 days in bile. At 10 days, the rank-order of residue concentrations was bile > liver > trunk kidney > head kidney > skin ≈ red muscle > plasma > white muscle. At 0 and 4 h post exposure, benzocaine was generally the dominant species in all tissues and fluids, and p-aminobenzoic acid was also observed. While gender differences were generally not detected, males showed higher concentrations of p-aminobenzoic acid and acetyl-p-aminobenzoic acid in bile than did females. Autoradiograms of whole-body sagittal sections showed bands of radioactivity concentration in the fibrous connective tissue (myosepta) that separate adjacent myomeres and attach to the vertebrae.
Simultaneous Multisite Mapping of the Right and the Left Atrial Septum in the Canine Intact Beating Heart

Background—The spread of activation between the right atrium (RA) and left atrium (LA), particularly along the right and left aspects of the interatrial septum, is not clear. Methods and Results—Basket-shaped catheters carrying 64 electrodes were deployed into both the RA and LA of 10 dogs. Position and orientation of the baskets were determined by fluoroscopy and echocardiography. Basket unipolar electrograms were simultaneously recorded in each dog during sinus rhythm, right ventricular pacing, and pacing of the right septum through the basket in the superior and inferior regions. Isochrone maps depicting all aspects of the atria, including the septum, were compared. During sinus rhythm and superior right septal pacing, wave fronts propagated predominantly from superior to inferior regions on both the right and left septum. However, activation of the left septum was delayed compared with the right septum. During right ventricular pacing and inferior right septal pacing, activation of the septum was disc...
Economic implications of current surgical management of gastroesophageal reflux disease.

Abstract Background/Purpose: Surgical management of gastroesophageal reflux disease in children has evolved with the development of laparoscopy. Because concerns persist regarding increased costs associated with this technique, the authors studied the economic parameters of antireflux surgery at their institution. Methods: Seventy-eight patients undergoing either laparoscopic or open fundoplication were studied retrospectively between June 1998 and June 2000 comparing average operating room costs, total inpatient costs, and length of stay. Univariate comparisons were performed using Student's t test, and multivariate analysis was performed using multiple linear regression. Results: Univariate analysis showed that patients receiving the laparoscopic procedure had significantly shorter inpatient stays (2.4 v . 3.96 days; P = .004) than those receiving open procedures. Average operating room costs were similar (laparoscopic, $2,611; open, $2,162; P = .237), but total costs for the laparoscopic procedure were lower ($4,484 v $5,129; P = .006). Multivariate analysis results suggested that in addition to procedure type, patients who required an intensive care unit admission incurred $6,595 in additional total costs ( P [lt ] .0001) and 4.8 additional hospital days ( P [lt ] .0001). After controlling for other variables, the laparoscopic procedure did not significantly reduce total hospital costs ($447; P = .192) but was associated with a significant decrease in length of stay of 1.3 days ( P [lt ] .0001). Conclusion: These results suggest that laparoscopic procedures are comparable with open operations in terms of operative costs and that other factors are important determinants of the costs associated with antireflux surgery in children.
Primary hepatocellular carcinoma following non-A, non-B posttransfusion hepatitis

In 1964 a 42-year-old woman was hospitalized with clinical and laboratory signs of posttransfusion hepatitis five weeks after administration of six whole blood transfusions. During the following 17 years anicteric chronic liver disease was repeatedly documented by elevations of serum aspartate aminotransferase (SGOT) and alkaline phosphatase enzymes. In 1981 hepatomegaly, progressive jaundice, and a serum alphafetoprotein level of 516,000 ng/ml were observed. Percutaneous liver biopsy showed a primary hepatocellular carcinoma (PHC). Serologic examinations failed to reveal markers for hepatitis B virus including HBsAg, anti-HBs, and anti-HBc by radioimmunoassay; antibody to hepatitis A virus was also absent. This sequence of events demonstrates a presumptive association of PHC and the agent(s) of non-A, non-B viral hepatitis.
Re-membering Black Greeks: Racial Memory and Identity in Stomp the Yard

Critical sociological analysis suggests that the film Stomp the Yard immerses its audience in a myopic legend of African American fraternities and sororities. Combining historical photos of Civil Rights leaders, traditions of ‘stepping’, tales of meritocratic social uplift, and romanticized aspects of historically black college or university (HBCU) culture, Stomp the Yard reveals a hyper-individualistic, conservative, and politically blunted form of historiography. Specifically, five ideological mythologies ground the film’s construction of Civil Rights memory and racialized identities. These mythologies decisively fail to interrogate the complexity of black fraternities and sororities. In so doing, they invite a critical blindness to these organizations’ role in past Civil Rights struggles as well as their intersection with contemporary issues such as classism, hazing, and resistance to contemporary forms of racism and racial inequality.
Structure of microbial communities in ethanol biofilters

Despite its central role in biofiltration, the ecology of the microbial community in biofilters remains largely unknown, primarily because of the difficulty of making detailed observations. Recently developed molecular techniques now allow determination of community composition from DNA extracted from the biofilter, without the need to culture the organisms. This study examined the structure of the microbial communities in ethanol biofilters through the application of the molecular fingerprinting technique, automated ribosomal RNA intergenic spacer analysis (ARISA). Three communities were tracked through acclimation to ethanol in liquid culture, and two of these were followed through growth within two biofilters packed with sand or lava rock. One of these created a successful set of biofilters while the other failed because of acidification. Analysis of the fingerprints revealed a strong decrease in species diversity towards the end of the acclimation period. Diversity indices show a rise in diversity for the biofilter with inconsistent removal of ethanol and low diversities in the successful biofilters, which removed ethanol with an efficiency near 80% for both packing materials. The results indicate that community fingerprinting shows promise as a means of assessing biofilter microbial communities.
Mucoid Impaction of Upper Lobe Bronchi in the Absence of Proximal Bronchiectasis

Mucoid impaction is a complication of asthma and is frequently recurrent in patients with allergic bronchopulmonary aspergillosis (ABPA). This report describes a patient with asthma and recurrent bilateral well-circumscribed densities on chest roentgenogram in the absence of ABPA. Recognition of this clinical presentation may avoid the need for invasive diagnostic procedures or steroid therapy.
Positive Margin During Partial Nephrectomy: Does Cancer Remain in the Renal Remnant?

Objective To examine the outcomes of patients with a positive surgical margin by gross and/or frozen examination during partial nephrectomy, in whom a re-resection of the margin or a completion nephrectomy was performed. Methods Patients with renal cancer who underwent partial nephrectomy were considered. If the patient had a positive margin and underwent completion nephrectomy or re-excision of the margin, they were included. Patients with planned enucleation were excluded from the study. Clinical and pathologic information were reviewed to examine for residual cancer in the additionally resected tissue. Results In the final cohort, 29 patients with a positive margin and subsequent complete parenchymal re-resection or completion nephrectomy were identified. Eight patients underwent nephrectomy, after which no residual cancer was found in the renal remnant. Twenty-one patients underwent total re-resection of the margin, of which two were found to have carcinoma. Renal functional outcomes revealed a decrease in estimated glomerular filtration rate of 25 mL/min/1.73 m 2 in patients who underwent radical nephrectomy, and 4 mL/min/1.73 m 2 in patients who underwent re-resection of the margin with preservation of the renal unit. Conclusions A positive surgical margin does not necessarily mean that cancer remains in the renal remnant in most cases. Therefore, radical nephrectomy or re-resection of the margin is overtreatment in many cases, but a small percentage of patients will harbor residual malignancy. Clinical correlation is recommended before reexcision or completion nephrectomy after a positive surgical margin, with careful consideration of the impact on subsequent renal function weighed against the possibility of residual disease.
Probing the thermodynamics of aminofluorene-induced translesion DNA synthesis by differential scanning calorimetry.

Differential scanning calorimetry (DSC) was used to investigate the thermodynamic contribution to replication fidelity and specificity associated with translesion synthesis across FAF, N-(2‘-deoxyg...
Paleosol caliche in the New Haven Arkose, Connecticut: Record of semiaridity in Late Triassic Early Jurassic Time

Recently discovered caliche paleosol profiles are widely distributed in braided-stream sandstone and overbank mudstone in the 1,500- to 2,500-m sequence of red beds in the New Haven Arkose. During Late Triassic to Early Jurassic time, the tropical rift valley commonly was semiarid with an annual 100 to 500 mm of seasonal precipitation. The paleoclimate was much drier than is indicated by the view that these red beds are the classic example of accumulation in a tropical, wet regime with more than 1,250 mm of annual precipitation (Krynine, 1950).
The ArsR protein is a trans-acting regulatory protein.

Summary The arsR gene encodes the regulatory protein of the plasmid-encoded arsenical resistance operon. A series of in-frame fusions was constructed between the C-terminally truncated arsR gene and the coding region for the mature form of β-lactamase (blaM). Fusions containing most of the arsR gene were still inducible by arsenicals. Fusions containing less than 102 residues of the 117-residue ArsR protein were constitutive. When a wild-type arsR gene was placed in trans, the constitutive constructs were again inducible. The results demonstrate that the ArsR protein is a trans-acting regulatory protein which controls its own expression.
Initial stages of neural regeneration in Helisoma trivolvis are dependent upon PLA2 activity.

Neuronal regeneration after damage to an axon tract requires the rapid sealing of the injured plasma membrane and the subsequent formation of growth cones that can lead regenerating processes to their appropriate target. Membrane sealing and growth cone formation are Ca(2+)-dependent processes, but the signaling pathways activated by Ca(2+) to bring about these effects remain poorly understood. An in vitro injury model was employed in which neurites from identified snail neurons (Helisoma trivolvis) were transected with a glass microknife, and the formation of new growth cones from the distal portions of transected neurites was recorded at defined times after transection. This study presents three main results. First, phospholipase A(2) (PLA(2)), a calcium-activated enzyme, is necessary for membrane sealing in vitro. Second, PLA(2) activity is also required for the formation of a new growth cone after the membrane has sealed successfully. Thus, PLA(2) plays a dual role by affecting both growth cone formation and membrane sealing. Third, the injury-induced activation of PLA(2) by Ca(2+) controls growth cone formation through the production of leukotrienes, secondary metabolites of PLA(2) activity. Taken together, these results suggest that the injury-induced Ca(2+) influx acts via PLA(2) and leukotriene production to assure growth cone formation. These findings indicate that events that cause an inhibition of PLA(2) or lipoxygenases, enzymes that produce leukotrienes, could result in the inability of neurites to regenerate.
HERPES SIMPLEX VIRUS TYPE 1(HSV) GLYCOPROTEIN C(gC) PLAYS DIFFERENT ROLES IN EPITHELIAL AND NEURONAL CELL ENTRY. † 1027

HERPES SIMPLEX VIRUS TYPE 1(HSV) GLYCOPROTEIN C(gC) PLAYS DIFFERENT ROLES IN EPITHELIAL AND NEURONAL CELL ENTRY. † 1027
Convex Chance Constrained Predictive Control without Sampling

In this paper we consider finite-horizon predictive control of dynamic systems subject to stochastic uncertainty; such uncertainty arises due to exogenous disturbances, model- ing errors, and sensor noise. Stochastic robustness is typically defined using chance constraints, which require that the pro b- ability of state constraints being violated is below a presc ribed value. Prior work showed that in the case of linear system dynamics, Gaussian noise and convex state constraints, optimal chance- constrained predictive control results in a convex optimization problem. Solving this problem in practice, however, requires the evaluation of multivariate Gaussian densities through sampling, which is time-consuming and inaccurate. We propose a new approach to chance-constrained predictive control that does not require the evaluation of multivariate densities. We use a new bounding approach to ensure that chance constraints are satisfied, while showing empiricall y that the conservatism introduced is small. This is in contrast to prior bounding approaches that are extremely conservative. Furthermore we show that the resulting optimization is convex, and hence amenable to online control design.
Tools to Reduce Polypharmacy

Approximately one-third of drugs prescribed in the United States may be unnecessary. 1 Older adults use higher numbers of medications compared with younger age groups, primarily because of increased numbers of comorbid conditions and greater numbers of physicians involved in their care, putting them at higher risk of polypharmacy. The use of multiple medications increases the risk for adverse drug events and adverse health outcomes. 2,3 Medication management is of utmost significance in older adults because of changes in body composition, physical function, social environment, and limiting finances with increasing age. Adding or stopping a medication in an older person should focus on improving function or quality of life, a core principle in the management of chronic illnesses in the elderly (Box 1). Older adults are the largest consumers of prescription medications, and over-thecounter (OTC) medications and dietary supplements among older adults are on the rise in the United States. Qato and colleagues 4 conducted a survey in 3500 community-dwelling older adults and found that 29% took 5 or more prescription medications, 42% took at least 1 or more OTC medications, and 49% took at least 1 or more dietary supplements. Approximately 50 new medications enter the market each year, and the use of prescription drugs will continue to increase. Direct-toconsumer marketing and the continued focus on life-saving and life-sustaining therapies increases the reliance on medication therapy in older adults. Adverse drug reactions (ADRs) are likely with excessive medication use; the risk of an ADR increases with increased medication number. 5 ADRs may be caused by drug-drug or drug-disease interactions and by the use of medications considered inappropriate in the elderly, and ADRs are a major cause of costly hospitalization in