cssi/SciSciGPT-SciSciNet huggingface dataset:
A simple automated approach to measure mouse whole gut transit

Background Gastrointestinal (GI) motility is a complex physiological process that is critical for normal GI function. Disruption of GI motility frequently occurs in GI diseases or as side effects of therapeutics. Whole gut transit measurements, like carmine red leading-edge transit, in mice form the cornerstone of in vivo preclinical GI motility studies. Method We have developed an easily achievable, labor-saving method to measure whole gut transit time in mice. This approach uses inexpensive, commercially available materials to monitor pellet production over time via high definition cameras capturing time-lapse video for offline analysis. Key result We describe the assembly of our automated gut transit setup and validate this approach by comparing the results with loperamide to delay transit and conventional transit measurements. We demonstrate that compared to the control group, the loperamide group had slowed transit, evidenced by a decrease in total pellet production and prolonged whole gut transit time. The control group had an extended transit time compared with the results reported in the literature. Whole gut transit rates accelerated to times comparable to the literature by disrupting cages every 10-15 min to imitate the conventional approach, suggesting that disruption affects the assay and supports the use of an automated approach. Conclusion & inferences A novel automated, inexpensive, and easily assembled whole gut transit setup is labor-saving and allows minimal disruption to animal behavior compared with the conventional approach.
Burkholderia multivorans requires species-specific GltJK for entry of a contact-dependent growth inhibition system protein

Interbacterial antagonism and communication are driving forces behind microbial community development. In many Gram-negative bacteria, contact-dependent growth inhibition (CDI) systems contribute to these microbial interactions. CDI systems deliver the toxic C-terminus of a large surface exposed protein to the cytoplasm of neighboring bacteria upon cell-contact. Termed the BcpA-CT, import of this toxic effector domain is mediated by specific, yet largely unknown receptors on the recipient cell outer and inner membranes. In this study, we demonstrated that cytoplasmic membrane proteins GltJK, components of a predicted ABC-type transporter, are required for entry of CDI system protein BcpA-2 into Burkholderia multivorans recipient cells. Consistent with current CDI models, gltJK were also required for recipient cell susceptibility to a distinct BcpA-CT that shared sequences within the predicted "translocation domain" of BcpA-2. Strikingly, this translocation domain showed low sequence identity to the analogous region of an Escherichia coli GltJK-utilizing CDI system protein. Our results demonstrated that recipient bacteria expressing E. coli gltJK were resistant to BcpA-2-mediated interbacterial antagonism, suggesting that BcpA-2 specifically recognizes Burkholderia GltJK. Using a series of chimeric proteins, the specificity determinant was mapped to Burkholderia-specific sequences at the GltK C-terminus, providing insight into BcpA transport across the recipient cell cytoplasmic membrane.
TNT Sensor: Stern–Volmer Analysis of Luminescence Quenching of Ruthenium Bipyridine

TNT is both toxic and explosive, and therefore, the detection of TNT represents an environmental concern and a security concern. Dogs are often used for detection, but other methods are needed. This laboratory investigates a ruthenium bipyridine ([Ru(bpy)3]2+) luminescence-based trinitrotoluene (TNT) sensor. Students will synthesize [Ru(bpy)3]2+, investigate sensors, and consider possible mechanistic pathways of quenching. Students are unlikely to have analyzed luminescence quenching data previously, and using TNT shows how important the technique is for problems like national security, environmental contamination, and land mine deactivation. The content of the lab is ideal for upper-level laboratories, when students have the foundational coursework to appreciate the interdisciplinary nature of chemistry as the experiment integrates inorganic, analytical, and physical chemistry.
Supported Decision-Making: Non-Domination Rather than Mental Prosthesis

Recently, bioethicists and the UNCRPD have advocated for supported medical decision-making on behalf of patients with intellectual disabilities. But what does supported decision-making really entai...
Effect of Turbulence Level of Incident Air Stream on Local Heat Transfer and Skin Friction on a Cylinder

At the conclusion of a previous investigation of local heattransfer and local pressure coefficients around a cylinder, the need for simultaneous local skin-friction coefficient measurements was indicated. In addition, the results of the skin-friction measurements of Fage and Falkner suggested that the influence of the turbulence level in the free air stream on the local heat transfer should be investigated. Data were therefore taken and are presented herein for the local heat-transfer coefficient, pressure coefficient, and skin-friction coefficient on a cylinder below and in the critical range of Reynolds Number. The effect of artificially increased turbulence in the free air stream on these local quantities was also determined. Data for these quantities, taken under identical flow conditions and on models of the same geometry, have not been available previously. The results are partly explicable in terms of available theory and experience and in part present new effects requiring further consideration.
Forms of Catholic Millenarianism: A Brief Overview

On July 21, 1944, the Vatican Congregation of the Holy Office, whose duty it is to defend the faith, issued a decree condemning “Mitigated Millenarianism” (systema Millenarismi mitigati), which it defined as the view that Christ would visibly appear in order to rule on earth before the Last Judgment.2 This document demonstrates the opposition of modern Roman Catholicism to any form of literal interpretation of the twentieth chapter of the Apocalypse of John. Apocalypse 20:1–6, one of the few positive apocalyptic texts in the New Testament, predicts that after the defeat of the Beast and his False Prophet, the Devil will be bound for a thousand years in the pit (Apoc. 20:2–3), and the saints who had died for their faith will come back to life in the “first resurrection”...“and reign with Christ for a thousand years” (Apoc. 20:4–5).
Phylogeography and biogeography of the lower Central American Neotropics: diversification between two continents and between two seas

Lower Central America (LCA) provides a geologically complex and dynamic, richly biodiverse model for studying the recent assembly and diversification of a Neotropical biota. Here, we review the growing literature of LCA phylogeography studies and their contribution to understanding the origins, assembly, and diversification of the LCA biota against the backdrop of regional geologic and climatic history, and previous biogeographical inquiry. Studies to date reveal that phylogeographical signal within taxa of differing distributions reflects a diversity of patterns and processes rivalling the complexities of LCA landscapes themselves. Even so, phylogeography is providing novel insights into regional diversification (e.g. cryptic lineage divergences), and general evolutionary patterns are emerging. Congruent multi-taxon phylogeographic breaks are found across the Nicaraguan depression, Chorotega volcanic front, western and central Panama, and the Darien isthmus, indicating that a potentially shared history of responses to regional-scale (e.g. geological) processes has shaped the genetic diversity of LCA communities. By contrast, other species show unique demographic histories in response to overriding historical events, including no phylogeographic structure at all. These low-structure or incongruent patterns provide some evidence for a role of local, ecological factors (e.g. long-distance dispersal and gene flow in plants and bats) in shaping LCA communities. Temporally, comparative phylogeographical structuring reflects Pliocene-Pleistocene dispersal and vicariance events consistent with the timeline of emergence of the LCA isthmus and its major physiographic features, e.g. cordilleras. We emphasise the need to improve biogeographic inferences in LCA through in-depth comparative phylogeography projects capitalising on the latest statistical phylogeographical methods. While meeting the challenges of reconstructing the biogeographical history of this complex region, phylogeographers should also take up the critical service to society of applying their work to the conservation of its fascinating biodiversity.
Gate-Induced Source Tunneling FET (GISTFET)

We propose a device, the gate-induced source tunneling FET (GISTFET), that uses two gate work functions to modulate lateral tunneling. The performance of the device is largely independent of the details of the chemical doping profile, potentially freeing device design from issues related to solid solubility, junction abruptness, and dopant variability. We demonstrate the advantages of the device over conventional TFETs using ballistic quantum transport simulations and discuss the possible role of scattering. The proposed device can be used to make all types of tunneling devices, but is particularly important for enabling steep swing, high current p-type transistors.
Variational and statistical methods for an electron plasma with self-consistent field interaction

The Lagrange and Hamilton functions, and the Liouville equation are developed for an adiabatic electron plasma in which the charged particles interact by the self-consistent electric field. The electrohydrodynamic field equations are obtained by variation of the Lagrangian and functional derivation of the Hamiltonian. As an application, the statistical distribution function of the fluctuations in the Lagrangian conjugate fields is derived for the case of fully developed turbulence as that solution of the Liouville equation which maximizes the entropy of turbulence. It is shown that the statistical distribution is in form quasi-Gaussian relative to the velocity field fluctuations and the electric field fluctuations. The deviations from the Gaussian are produced by nonlinear terms of higher order resulting from adiabatic density and electric field fluctuations.
Studies on p-Hydroxybenzoate Hydroxylase from Pseudomonas putida

Enzymatic hydroxylation mechanism of p- hydroxybenzoate hydroxylase from Pseudomonas putidas, describing product separation and purification
Explaining social class differences in growth of reading skills from beginning kindergarten through fourth-grade: The role of phonological awareness, rate of access, and print knowledge

The aim of this longitudinal study was to further ourunderstanding of the reasons for social classdifferences in growth of decoding and readingcomprehension skills from beginning kindergarten throughchildren's fourth grade year. Participants wereenrolled in five public schools in a moderately sizedsouthern American city (n = 197). We examined ifbeginning kindergarten levels of three kinds ofreading related abilities explained social classdifferences in growth of reading skills during thetime periods of beginning kindergarten to children'sfirst-, second-, third-, and fourth-grade years. Thereading related abilities were phonological awareness,rate of access to phonological information inlong-term memory, and print knowledge. We found thatthe reasons for social class differences in growth ofreading skills depended on the time interval that wasconsidered. During the earliest time interval, socialclass differences in growth of decoding skills werecompletely accounted for by performance on the controlmeasures of general verbal intelligence and prior wordreading skills. During the remaining time periods,social class differences in growth of decoding andreading comprehension skills persisted whenperformance on the three kinds of reading relatedabilities and the control measures were accounted for. The greatest attenuation of SES differences in growthof reading skills occurred when beginning kindergartenlevels of print knowledge were taken into account.
Rapidly progressive non-A, non-B hepatitis in patients with human immunodeficiency virus infection

No information is available on the role of non-A, non-B hepatitis in the various hepatic abnormalities described in patients with the acquired immune deficiency syndrome. Of 97 patients referred with suspected non-A, non-B hepatitis, 3 were found to have antibody to the human immunodeficiency virus. These latter 3 patients all developed symptomatic cirrhosis within 3 yr of onset of hepatitis. Such a rapid progression of liver disease was rare in patients with non-A, non-B hepatitis who did not have simultaneous human immunodeficiency infection. These findings suggest that human immunodeficiency virus infection may potentiate the liver injury of chronic non-A, non-B hepatitis.
Forest-based point process for event prediction from Electronic Health Records

Accurate prediction of future onset of disease from Electronic Health Records (EHRs) has important clinical and economic implications. In this domain the arrival of data comes at semi-irregular intervals and makes the prediction task challenging. We propose a method called multiplicative-forest point processes (MFPPs) that learns the rate of future events based on an event history. MFPPs join previous theory in multiplicative forest continuous-time Bayesian networks and piecewise-continuous conditional intensity models. We analyze the advantages of using MFPPs over previous methods and show that on synthetic and real EHR forecasting of heart attacks, MFPPs outperform earlier methods and augment off-the-shelf machine learning algorithms.
Performance modeling as the key to extreme scale computing

Parallel computing is primarily about achieving greater performance than is possible without using parallelism. Especially for the high-end, where systems cost tens to hundreds of millions of dollars, making the best use of these valuable and scarce systems is important. Yet few applications really understand how well they are performing with respect to the achievable performance on the system. The Blue Waters system, currently being installed at the University of Illinois, will offer sustained performance in excess of 1 PetaFLOPS for many applications. However, achieving this level of performance requires careful attention to many details, as this system has many features that must be used to get the best performance. To address this problem, the Blue Waters project is exploring the use of performance models that provide enough information to guide the development and tuning of applications, ranging from improving the performance of small loops to identifying the need for new algorithms. Using Blue Waters as an example of an extreme scale system, this talk will describe some of the challenges faced by applications at this scale, the role that performance modeling can play in preparing applications for extreme scale, and some ways in which performance modeling has guided performance enhancements for those applications.
Overproduction of DNA Cytosine Methyltransferases Causes Methylation and C T Mutations at Non-canonical Sites

Multicopy clones of Escherichia coli cytosine methyltransferases Dcm and EcoRII methylase (M. EcoRII) cause an approximately 50-fold increase in C --> T mutations at their canonical site of methylation, 5'-CmeCAGG (meC is 5-methylcytosine). These plasmids also cause transition mutations at the second cytosine in the sequences CCGGG at approximately 10-fold lower frequency. Similarly, M. HpaII was found to cause a significant increase in C --> T mutations at a CCAG site, in addition to causing mutations at its canonical site of methylation, CCGG. Using a plasmid that substantially overproduces M. EcoRII, in vivo methylation at CCSGG (S is C or G) and other non-canonical sites could be detected using a gel electrophoretic assay. There is a direct correlation between the level of M. EcoRII activity in cells, the extent of methylation at non-canonical sites and frequency of mutations at these same sites. Overproduction of M. EcoRII in cells also causes degradation of DNA and induction of the SOS response. In vitro, M. EcoRII methylates an oligonucleotide duplex containing a CCGGG site at a slow rate, suggesting that overproduction of the enzyme is essential for significant amounts of such methylation to occur. Together these results show that cytosine methyltransferases occasionally methylate cellular DNA at non-canonical sites and suggest that in E. coli, methylation-specific restriction systems and sequence specificity of the DNA mismatch correction systems may have evolved to accommodate this fact. These results also suggest that mutational effects of cytosine methyltransferases may be much broader than previously imagined.
Diode-laser production of collimated slow cold potassium beams and crossover resonances

We describe the results of three sets of experiments to investigate producing cold slow collimated potassium atoms for applications with no access available for the introduction of counterpropagating laser light along the exiting atomic beam's axis. Velocity profiles are obtained via fluorescence from D1 excitation at perpendicular and nearly parallel incidence by a probe laser. Spatial profiles of both the cold- and residual hot-beam components are measured with a position-scanned hot-wire detector. Velocity-component holes and decelerated cold components are observed, along with direct evidence of perpendicular heating of the cold components. A first set of experiments uses a variant of conventional chirp cooling and/or hole burning. Light is introduced by a heated inclined mirror, while atoms exit through a slit in the mirror. Loss of intensity at low velocity is observed and discussed. A second set of experiments investigates velocity-selective optical-pumping crossover resonances that occur near the mirror, where the incident and reflected beams overlap for several alternative geometries. A third set of experiments investigates cold-beam production using laser-induced velocity selection and deflection. It provides a higher cold-atom intensity, along with the means to perform high-resolution spectroscopy.
Gender differences of placental dysfunction in severe prematurity.

Objective Rates of several obstetric complications have been reported to vary with fetal gender. We investigated whether a sex difference exists in findings at placental histology of extreme prematurity. Design Case–control study. Setting University Hospital. Population Four hundred and thirty-seven consecutive deliveries before 32 weeks of gestation of singleton, liveborn, non-anomalous infants. Methods Obstetric, neonatal and placental histologic findings were compared between male (n= 232) and female (n= 205) neonates. Main outcome measures Histologic evidence of acute placental inflammation, uteroplacental vascular pathology, intraplacental vascular pathology and chronic placental inflammation. Results Male fetuses had similar racial distributions, rate of nulliparity, maternal age, gestational age at delivery, placental weight and fetoplacental weight ratio as female fetuses, but higher birthweight centiles (41 [27] vs 33 [26]). Placental histology showed no association between fetal gender and lesions of acute inflammation (P= 0.08), intraplacental vascular pathology (P= 0.16) or uteroplacental vascular pathology (P= 0.83). However, lesions of chronic inflammation had a significantly higher score in male than in female fetuses (P= 0.001). When we examined the distribution of chronic placental inflammation, significantly more severe lesions were noted in male than in female fetuses at the implantation site (i.e. the area of interstitial trophoblast invasion of the maternal decidua and maternal endovascular trophoblast remodelling), than within the placental villi (chronic villitis) or in the amniochorionic membranes (where interstitial trophoblast invasion is minimal). Conclusion In premature deliveries at <32 weeks, male fetal gender is associated with placental lesions suggestive of a maternal immune response against the invading interstitial trophoblast. The immunologic basis of these findings deserves further studies.
MAIN EFFECTS AND INTERACTIONS OF CORTISONE, GROWTH HORMONE AND TRIIODOTHYRONINE IN PRODUCTION OF TEMPORARY DIABETES IN THE RAT1

The diabetogenic effects of cortisone, triiodothyronine, growth hormone, and all possible combinations thereof were studied in the intact tube-fed rat. The design of the experiment was factorial, suitable for the analysis of variance. Growth hormone produced hypergtycemia, glycosuria, nitrogen retention and a gain in weight. The other hormones produced hyperglycemia and gly-cosuria with nitrogen wastage and weight loss. Every combination of hormones produced changes in each parameter equivalent to the additive effect of the individual hormones. No significant synergistic or antagonistic interactions were demonstrated. SEVERAL workers have produced temporary diabetes in the intact rat with various single hormonal agents: growth hormone (1), adrenocortical hormone (2), and thyroid hormone (3). However, the knowledge gained from these studies does not permit prediction of the effects of various combinations of these diabetogenic hormones, and investigation of such effects has not produced conclusive results.
Enumeration of K-Trees and Applications

A k-tree is constructed from a single distinguished k-cycle by repeatedly gluing other k-cycles to existing ones along an edge. If K is any nonempty subset of {2, 3, 4, . . .}, then a K-tree is obtained as above using k-cycles with $ k \in K $ . In this paper, we enumerate ordered K-trees, show that the ratio of terminal edges to total number of edges in K-trees is $ \frac{k-1}{k} $ , and use the K-trees as models to enumerate planted plane cacti.
Spheres of clinical nurse specialist practice influence evidence-based care for patients with atrial fibrillation.

PURPOSE The purpose of this article is to review atrial fibrillation (AF) and its consequences, to present sources of published evidence-based guidelines for management of AF, and to highlight multifaceted clinical nurse specialist (CNS) interventions that promote positive outcomes for patients with AF. RATIONALE The number of people with AF is expected to increase from 2.3 million to more than 5 million in the next 50 years. AF is associated with increased mortality, morbidity, healthcare expenditures, and decreased quality of life. Recognition of the growing number of AF cases and adverse consequences of AF led to development of evidence-based guidelines for AF management. Although nurses in diverse settings are accountable for providing evidence-based care for patients with AF, the guidelines have not been widely disseminated to nurses. DESCRIPTION This discussion includes a review of the adverse consequences of AF and a summary of management of recently detected AF with a focus on recommendations for nursing activities/interventions that are supported by evidence-based guidelines. Multifaceted strategies directed toward nurses and nursing practice, patients/clients, and organizations/systems that are linked to published CNS competencies and outcomes are highlighted. OUTCOMES CNS influence in all 3 spheres of CNS practice promotes positive outcomes that include improved patient/client functioning and self-management, reduced complications of treatment, decreased fragmentation of care, advancement of professional nursing practice, adherence to regulatory standards, and development of patient care processes that are supported by published guidelines. CONCLUSIONS With the use of the strategies discussed, clinical nurse specialists, whose spheres of influence include nursing and nursing practice, patients/clients, and organizations/systems, promote improved patient outcomes through implementation of evidence-based guidelines for AF management.
EFFECT OF REDUCTION AND PARTIAL REPLACEMENT OF SODIUM ON BOLOGNA CHARACTERISTICS AND ACCEPTABILITY

Nine combinations of sodium chloride (NaCl), potassium chloride (KCI), and magnesium chloride (MgCl2,) at high and low ionic strengths (IS) (0.42 and 0.21 respectively) and low IS with 0.13% tripotassium phosphate (K3PO4) were used to determine the effects of a reduction or partial replacement of sodium on bologna characteristics and acceptability. The NaCl-MgCl2 had significantly (P < 0.05) less stable and firm emulsion and compression hardness than NaCl or NaCl-KCl treatments. Low IS treatments had significantly less stable and firm emulsions and lower compression hardness than high IS treatments. Adding PO4 to low IS treatments produced products similar to high IS treatments. Only slight textural changes occurred in products after 14 days of cooler (1°C) storage. High IS NaCl and NaCl-KCl and low IS NaCl-PO4, NaCl-MgCl2 -PO4 and NaCl-KCl-PO4 were found acceptable for flavor, texture, and color by consumer panels.
Bend Geometries in Internal Cooling Channels for Improved Thermal Performance

The pressure drop and heat transfer in a two pass internal cooling channel with two different bend geometries is experimentally studied with the goal of improving the Thermal Performance Factor (TPF) in the coolant channel. The geometries studied are: (1) a baseline U-bend geometry with a rectangular divider wall, (2) a symmetrical bulb at the end of the divider wall, and (3) a combination of the symmetrical bulb and a bow on the opposite outer wall leading to a shaped flow contraction and expansion in the bend. Tests are conducted for four Reynolds number ranging from 10000 to 55000. The symmetrical bulb eliminates the separation due to the sharp turn and makes the heat transfer distribution in the bend portion more uniform. This modification reduces the bend pressure drop by 37% and augments the TPF by nearly 29% compared to the baseline case. The combination of bulb and bow case increases the local heat transfer in the bend region significantly, and reduces the bend pressure drop by nearly 27% leading to an augmentation of the TPF of 32% compared to the baseline case. These improvements in TPF point to the benefits of using the improved bend designs in internal cooling channels.Copyright © 2012 by ASME
Integrating principles of community-based participatory research (CBPR) with the injury prevention and control agenda.

Despite remarkable advances in injury and violence prevention, our research community remains limited in its ability to explain why and how certain disparities in unintentional and intentional injuries persist. There is increasing attention to generating evidence and translational research models that can rapidly disseminate injury prevention and control programmes and policies into practice to improve health, safety and wellbeing for all segments of society. 12 Community engagement in research is recognised as a successful approach integrating education and social action to improve health and reduce disparities. 3 Community-based participatory research (CBPR) is a unique type of community-engaged research that equitably involves community partners in the research process and recognises the unique strengths each party brings to understanding and addressing the issue. CBPR is about intentional, collaborative, long-term partnerships between academics and communities that undertake culturally sensitive and contextually relevant research. 4 Community engagement and CBPR begin with a topic of importance to the community with the aim of combining knowledge and action for social change. 5 Topics are explored from both academic and community perspectives so that together they can gain new understanding of the context in which unintentional and intentional injury outcomes occur. CBPR takes a participatory approach to examining the factors that underlie our injury and violence disparity data to engage both special populations (eg, American Indians, urban youth, rural workers, older adults) and special circumstances (eg, increased physical activity in dangerous environments). In addition, this approach ensures that translation and action are part of the research paradigm from the very beginning by sharing power in defining the problem, identifying and implementing appropriate research methods, interpreting data and applying findings in a timely and contextually relevant manner. CBPR is an approach and not a research methodology. While not universally appropriate, it is a versatile research approach which may include quantitative, qualitative and creative participatory methods aimed at cultivating partnerships while generating valuable data.
Positioning of cell growth and division after osmotic stress requires a MAP kinase pathway

The yeast Saccharomyces cerevisiae has a genetic program for selecting and assembling a bud site on the cell cortex. Yeast cells confine their growth to the emerging bud, a process directed by cortical patches of actin filaments within the bud. We have investigated how cells regulate budding in response to osmotic stress, focusing on the role of the high osmolarity glycerol response (HOG) pathway in mediating this regulation. An increase in external osmolarity induces a growth arrest in which actin filaments are lost from the bud. This is followed by a recovery phase in which actin filaments return to their original locations and growth of the original bud resumes. After recovery from osmotic stress, haploid cells retain an axial pattern of bud site selection while diploids change their bipolar budding pattern to an increased bias for forming a bud on the opposite side of the cell from the previous bud site. Mutants lacking the mitogen-activated protein (MAP) kinase encoded by HOG1 or the MAP kinase kinase encoded by PBS2 (previously HOG4) show a similar growth arrest after osmotic stress. However, in the recovery phase, the mutant cells (a) do not restart growth of the original bud but rather start a new bud, (b) fail to restore actin filaments to the original bud but move them to the new one, and (c) show a more random budding pattern. These defects are elicited by an increase in osmolarity and not by other environmental stresses (e.g., heat shock or change in carbon source) that also cause a temporary growth arrest and shift in actin distribution. Thus, the HOG pathway is required for repositioning of the actin cytoskeleton and the normal spatial patterns of cell growth after recovery from osmotic stress.
From separate systems to a hybrid order: Accumulative advantage across public and private science at Research One universities

Drawing on 18 years of panel data for the 89 most research-intensive US universities, this paper examines changing relationships between commercial and academic systems for the dissemination and use of new scientific findings. Increased patenting and commercial engagement on US campuses, I argue, has dramatically altered the rules that govern inter-university competition. From once separate systems with distinct stratification orders, commercial and academic standards for success have become integrated into a hybrid regime where achievement in one realm is dependent upon success in the other. Using observed variable structural equation models, I establish that the integration of public and private science occurred in progressive stages between 1981 and 1998. The implications of that periodization for organizational mobility in a hybrid academic/commercial stratification system are discussed.
The use of total reflectance X-ray fluorescence (TXRF) for the determination of metals in the pharmaceutical industry.

Abstract The control of residual metals in active pharmaceutical ingredients (API's) and intermediates is critical because of their potential toxic effects. A variety of technologies are available to measure residual metals in pharmaceutical compounds including, AAS, ICP-AES, and ICP-MS. The newest technology is total reflectance X-ray fluorescence spectroscopy (TXRF) which uses primary X-rays to excite atoms which then emit secondary X-rays. The emitted X-rays are characteristic of the individual elements present, and the intensities of the emitted X-rays are proportional to the concentrations of the elements present in the sample. The benefits of TXRF are that it is essentially unaffected by matrix effects, is very sensitive (ppb's), requires small amounts of sample (5–10 mg), and requires very little sample preparation time. During this study, TXRF was used to quantitatively measure residual metals in API's and intermediates and such topics as sample preparation, sensitivity, linearity, reproducibility and accuracy are discussed. The results obtained by TXRF were compared with those obtained by ICP-MS for the same samples for Pd and Cu measurement, and statistical analysis indicated that the results obtained by the two technologies are equivalent at the 95% confidence level. A comparison is also made of the capabilities of the instruments using a tungsten (W) or a molybdenum (Mo) source for excitation. Both instruments could be used for the quantitative determination of residual metals in pharmaceuticals.
Adjunct Mentoring, a Vital Responsibility in a Changing Educational Climate: The Lesley University Adjunct Mentoring Program.

Lesley University in Cambridge, Massachusetts, USA, has established an adjunct mentoring process in response to its growing number of adjunct faculty. Lesley’s adjunct corps serves in Lesley programs offered both on and off campus. The primary goals of the mentoring program are to support excellence in teaching, and to engage in mentoring that begins at hiring and provides continued professional development to the adjunct faculty member. This article underscores the general need for adjunct mentoring in postsecondary institutions, and describes Lesley University’s Adjunct Mentoring Program – developed specifically in anticipation and response to this need. The article outlines the program’s main elements, the principles that underlie it, and the place of such a program in higher education today. It is precisely because part‐time faculty members in postsecondary institutions often assume a number of roles – teacher assistant, annually hired adjunct, internship supervisor – that adjunct mentoring programs a...
Astroglia as Metal Depots: Molecular Mechanisms for Metal Accumulation, Storage and Release

The brain is an organ that concentrates metals, and these metals are often localized to astroglia. An examination of metal physiology of brain cells, particularly astroglia, offers insights into the developmental neurotoxicity of certain metals, including lead (Pb), mercury (Hg), manganese (Mn), and copper (Cu). Xenobiotic metals probably accumulate in cells by exploiting the normal functions of proteins that transport and handle essential metals. In addition, essential metals may become toxic by accumulating at levels that exceed the normal metal buffering capacity of the cell. This review considers the uptake, accumulation, storage, and release of two xenobiotic metals, Pb and Hg, as well as two essential nutrient metals that are neurotoxic in high amounts, Mn and Cu. Evidence that each metal accumulates in astroglia is evaluated, together with the mechanisms the host cell may invoke to protect itself from cytoxicity.
Galectin-3 mediates the endocytosis of β-1 integrins by breast carcinoma cells

Galectin-3, a β-galactoside binding lectin, has been demonstrated to play a key role(s) in cell to extracellular matrix interaction. The precise mechanism by which it modulates cellular adhesion is presently unclear and warrants further studies. We hereby report that galectin-3 mediates the endocytosis of β-1 integrins in a lactose-dependent manner. Interestingly we observed that galectin-3 was also rapidly internalized by the cells via the same pathway and the internalization was completely blocked by lactose. The endocytosis process was temperature dependent and was inhibited by filipin but not chlorpromazine. The endocytosis of galectin-3 and β-1 integrins by the cells was accompanied by rapid cell spreading due to cytoskeletal reorganization. The data suggest a novel mechanism by which galectin-3 and β-1 integrins are internalized into breast carcinoma cells via a cavaleolae-like pathway of endocytosis.
The N-Terminal Domain of Nup159 Forms a β-Propeller that Functions in mRNA Export by Tethering the Helicase Dbp5 to the Nuclear Pore

Nuclear export of mRNA in eukaryotic cells is mediated by soluble transport factors and components of the nuclear pore complex (NPC). The cytoplasmically oriented nuclear pore protein Nup159 plays a critical role in mRNA export through its conserved N-terminal domain (NTD). Here, we report the crystal structure of the Nup159 NTD, refined to 2.5 A. The structure reveals an unusually asymmetric seven-bladed β-propeller that is structurally conserved throughout eukarya. Using structure-based conservation analysis, we have targeted specific surface residues for mutagenesis. Residue substitutions in a conserved loop of the NTD abolish in vitro binding to Dbp5, a DEAD box helicase required for mRNA export. In vivo, these mutations cause Dbp5 mislocalization and block mRNA export. These findings suggest that the Nup159 NTD functions in mRNA export as a binding platform, tethering shuttling Dbp5 molecules at the nuclear periphery and locally concentrating this mRNA remodeling factor at the cytoplasmic face of the NPC.
Are we living in the end of the blockbuster drug era

For the last two decades, we have seen remarkable growth in the pharmaceutical industry. This growth has mainly been due to the approximately 100 new blockbuster drugs, such as Lipitor® (atorvastatin) and Plavix® (clopidogrel). More than half of the revenue of major pharmaceutical companies and above one-third of the total pharmaceutical revenues came from the sales of these blockbuster drugs. Questions concerning the fate of these blockbuster drugs are beginning to surface as they are approaching their patent expiration dates, and as they are expected to face significant competition from generic versions. Branded drugs with more than USD 120 billion in sales (as of 2008) are expected to lose their patent protection in the next 3 to 4 years, while the less expensive generic versions are ready to enter the market. It is plausible that a major paradigm shift in our thinking is needed to stay innovative, competitive and economically feasible in this new era of drug development. A new wave of innovations is expected to boost the blockbuster regime. Herein, we discuss the different threats facing the branded monopoly, as well as some of the hopeful expectations for the blockbuster drug.
ANALYSIS OF TRANSCRIPTS EXPRESSED BY EIMERIA TENELLA OOCYSTS USING SUBTRACTIVE HYBRIDIZATION METHODS

To characterize the genes expressed by Eimeria tenella oocysts, the sequence of 499 expressed sequence tags (ESTs) was obtained from complementary DNA (cDNAs) enriched for transcripts expressed by unsporulated or sporulated oocysts. Of these, 225 clones were isolated from cDNA of sporulated oocysts and 274 from unsporulated oocysts. A total of 163 unique sequences were found, and the majority of these (64%) represent novel genes with no significant homology to the proteins in GenBank. Approximately half of the unique transcripts generated from sporulated oocysts are also expressed by sporozoites and merozoites, whereas the expression of most (79%) of the transcripts from unsporulated oocysts has not yet been detected at other stages of development. The expression of 4 transcripts obtained from the subtracted cDNAs was confirmed by quantitative reverse transcriptase–polymerase chain reaction. The results confirmed that these transcripts are in fact differentially expressed between sporulated and unsporulat...
Regulation of prostate 5α‐reductase‐2 gene expression and prostate weight by dietary fat and caloric intake in the rat

Background High-fat diet is a major risk factor for prostate cancer. 5α-reductases are potential targets of dietary fat. Methods Male ACI/Seg rats given either a low-fat or a high-fat diet at weaning or adulthood were sacrificed at 2, 4, and 10 weeks after dietary treatment. Prostate 5α-reductase mRNAs, plasma androgens, food consumption, prostate, and body weight were determined. Results Prostate 5α-reductase-2 mRNA and plasma dihydrotestosterone levels were elevated at 2 weeks, and prostate weight was increased at 10 weeks in neonatal rats fed the high-fat diet. Animals fed the high-fat diet consumed more calories in the first 4 weeks. 5α-reductase-1 mRNA, plasma testosterone, and body weight were not different between the two dietary groups. These dietary effects were not observed in adult rats fed the same diets. Conclusion A high-dietary fat and caloric intake upregulates prostate 5α-reductase-2 gene expression, and stimulates prostate growth in neonatal, but not adult rats. © 2006 Wiley-Liss, Inc.
Suppression of immune responses by herpes virus type 2-transformed murine tumor cells

Work done in our laboratories, using a murine model, indicates that suppression of host immune responses might be due to secretion of soluble factors by tumor cells. The H238 cells (BALB/c embryonic fibroblasts transformed by UV-inactivated herpes simplex virus Type 2) exhibit progressive tumor growth with subsequent decrease in lymphoproliferation. To further study the suppressive effects of a tumor, H238 conditioned medium (CM) was tested for its ability to block murine and human mitogenic and allogeneic lymphocyte responses. PHA, Con A and LPS were used as mitogens. Lymphoproliferation, in the presence of increasing amounts of H238 CM, resulted in a greater degree of suppression of [3H]thymidine ([3H]Tdr) uptake, in both human and mouse systems. The kinetics of proliferation in the presence of concentrated H238 CM (cCM) showed that depression was evident regardless of the time of cCM addition, thereby affecting it at any stage of the cell cycle. Treatment of H238 cCM using acid (pH 2.3), base (pH 9.6), trypsin (100 micrograms/ml), heat (56 degrees C, 100 degrees C) and freeze-thawing, restored PHA-stimulated lymphoproliferation. Dialysis of H238 cCM showed that the molecular weight of the suppressor lies between 15 and 25 kDa. Northern blot analysis demonstrated the presence of a TGF-beta transcript in H238 cells. Neutralization of the H238 cCM with monoclonal antibody to TGF-beta resulted in complete abrogation of suppressive activity in spleen cell lymphoblastogenesis. These results suggest that TGF-beta appears to be the main inhibitor of immune responses found in this HSV-2-induced murine tumor cell line. Such tumor-induced modulations may contribute to the outcome of immunotherapy in the tumor-bearing host.
Effects of oxidation and reduction on the membrane activity of a cysteine dimerizable peptide

Abstract Reversibly associating peptides present an attractive strategy for the intracellular delivery and release of therapeutic compounds or polynucleotides. We have explored the efficacy of the small, cysteine-containing heptapeptide (KL) 3 C for model membrane disruption. The peptide can reversibly dimerize via cysteine oxidation and cystine reduction; the differing redox potentials inside and outside cells should stabilize the dimeric form extracellularly, and the monomeric form intracellularly. The peptide did not show detectable permeabilization activity with zwitterionic phosphatidylcholine (PC) vesicles, but was active toward anionic (fatty-acid-containing) vesicles with either phosphatidylethanolamine or PC lipids. In all cases, the dimeric form of the peptide was more active than the monomer, at equal concentrations. Binding measurements show that the dimer binds much more strongly to the anionic membranes than does the monomer, but quantitative fitting suggests that this is due almost entirely to a greater charge on the dimer (which concentrates the peptide near the membrane surface), rather than to its increased hydrophobicity. Correlation between membrane binding and leakage rates shows that the membrane destabilization does not require peptide cooperativity. Moreover, the effectiveness of bound dimer is not higher than that of bound monomer: the greater efficacy of the dimer is thus a consequence of its increased binding. These model membrane studies show that cysteine-mediated dimerization is a useful approach to controlling membrane properties in an environment-sensitive manner.
Consumer attitudes toward prepaid dentistry

Data from 5 studies show favorable consumer attitudes toward prepaid dentistry. Whether it will achieve the extent of growth realized by voluntary hospital and physician care plans in the United States is doubtful because of the competition from other, often higher-priority items, for scarce consumer dollars.
Cell-cell interactions in spheroids maintained in suspension

We have developed a system of mixed aggregates of cultured cells, to model in situ cell interactions. This three-dimensional (3D) system of floating cell aggregates, termed spheroids for their round shape, enables one to monitor their growth in both size and number of constituent clonogens and to measure survival curves for cells having 3D cell-cell interactions. This system was used to measure the three-dimensional cell-cell interactions on growth, and clonogenicity of either AG1522 fibroblasts, or HeLa cervical cancer cells (pure spheroids, or if both feeder and test cells are the same type, pseudohybrid spheroids), and/or of mixtures of both (hybrid spheroids). By following the increase or decrease in size of, or number of clonogens per, spheroid over time, one obtains growth or inhibition curves. By relating these clonogen numbers, one obtains, after a suitable growth period, relative survival. The system allows one to score the effects of irradiation and of other treatments, as well as the effect of interaction of the constituent cells on their survival. Floating pure, or pseudohybrid (composed of 10% live fibroblasts and 90% supralethally irradiated fibroblast feeder cells) spheroids, shrank to about 10-20% of their volume in three days and then remained at that size for up to six days. In contrast, pure spheroids composed of live HeLa cells increased their volume by an order of magnitude over the same period. Survival of cells in spheroids was measured by the ability of individual spheroids to grow beyond a size implying a ten-fold increase. A caveat to be observed is to correct survival for cellular multiplicity, i.e. reduce survival values to compensate for more than one colony former at the time of irradiation. The system of spheroids floating and growing in nutrient medium provides a selective system for evaluating growth of HeLa, and by implication, other neoplastic cells, without interference from (overgrowth by) normal fibroblasts. Thus it is possible to discriminate between normal and neoplastic cells by virtue of whether or not cells grow in suspension. Such a system seems ideal for testing novel strategies (radiation in combination with chemicals), in an in vivo-like environment.
Absorption of liquids by rubber vulcanizates

Abstract The effect of liquid absorption by rubber vulcanizates (swelling) can lead to very large reductions in both the rupture stress and the rupture strain. These reductions occur because the solvent reduces the glass transition temperature of the elastomer. The extent to which a solvent lowers T g depends, among other things, on the quantity of solvent imbibed. In this paper it is shown that under some restrictions, it is possible to estimate the quilibrium absorption of liquids from a knowledge of the chemical structure of the polymer and the solvent.