cssi/SciSciGPT-SciSciNet huggingface dataset:
Tus and the terminators: the arrest of replication in prokaryotes.

Bidirectional replication of prokaryotic circular chromosomes concludes when the two replication forks converge opposite the origin of replication in a region called the terminus. The terminus regions of several replicons contain sites referred to as terminators that arrest DNA replication and prevent replication forks from exiting the terminus. Function of the terminators is absolutely dependent upon a DNA binding protein that specifically binds the terminator sites and impedes replication forks. Studies on prokaryotic termination systems have now progressed to the point where termination sites have been sequenced and DNA binding proteins have been purified to near homogeneity. Very recently, several laboratories have completed the initial biochemical characterization of the mechanism of replication fork arrest, and one of these papers appears in this issue of cell. The studies that elucidated the components of the termination systems in Escherichia coli, Bacillus subtiiis, and the R6K plasmid will be reviewed here, as well as the more recent mechanistic studies. Tsrmlnator Sites The terminus of the E. coli chromosome is a large region (~360 kb) flanked on both sides by terminator sites, WA, Ter8, TerC, and TerD, that arrest replication forks (see figure; nomenclature for these sites is presented in the footnote). Before proceeding to the details of this inhibition of replication, the role of these sites in the replication cycle should be considered. inhibition is polar, and the important concept was developed that the terminus region functions as a replication-fork trap (Hill et al., 1987; deMassy et al., 1987). Specifically, replication forks from either direction are not prevented from entering the terminus region, but they are inhibited when they progress across the terminus and reach the other side. With respect to bidirectional replication of the chromosome, this means that if the two forks
General mechanisms of metastasis

In the present article, the steps involved in the process of tumor metastasis are discussed. Several events are required for malignant cells to leave the primary tumor and proliferate at a distant site: vessel formation (angiogenesis), cell attachment, invasion (matrix degradation, cell motility), and cell proliferation. Molecular mechanisms underlying each of these steps are described. Based on blocking these processes, new anti-metastasis therapies are being developed.
Degradation and Recovery of NMOS Subthreshold Leakage Current by Off-state Hot Carrier Stress

We have studied the degradation in the off-state channel surface leakage current. This shift in the device leakage was found to be driven by a hot carrier mechanism in NMOS devices. The observed subthreshold current increase was studied and its origin was determined to be charging traps. The subsequent recovery of this electrical stress induced leakage current by the application of various gate bias conditions has also been documented and explained in this work. The implications of temperature, channel length and voltage conditions have been characterized.
Regulation of ABCA1 Functions by Signaling Pathways

ATP-binding cassette transporter A1 (ABCA1) is an integral cell membrane protein that protects cardiovascular disease by at least two mechanisms: by export of excess cholesterol from cells and by suppression of inflammation. ABCA1 exports cholesterol and phospholipids from cells by multiple steps that involve forming cell surface lipid domains, binding of apolipoproteins to ABCA1, activating signaling pathways, and solubilizing these lipids by apolipoproteins. ABCA1 executes its anti-inflammatory effect by modifying cell membrane lipid rafts and directly activating signaling pathways. The interaction of apolipoproteins with ABCA1 activates multiple signaling pathways, including Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3), protein kinase A, Rho family G protein CDC42 and protein kinase C. Activating protein kinase A and Rho family G protein CDC42 regulates ABCA1-mediated lipid efflux, activating PKC stabilizes ABCA1 protein, and activating JAK2/STAT3 regulates both ABCA1-mediated lipid efflux and anti-inflammation. Thus, ABCA1 behaves both as a lipid exporter and a signaling receptor. Targeting ABCA1 receptor-like property using agonists for ABCA1 protein could become a promising new therapeutic target for increasing ABCA1 function and treating cardiovascular disease. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010).
Age Differences in Orofacial Sensory Thresholds

Declines in sensory functioning with aging are evident for many of the senses. In the present study, thresholds were determined for somatosensory (warming and cooling temperature, pain, touch, and two-point discrimination) and taste stimuli in 178 healthy individuals aged 20-89 yrs. Somatosensory stimuli were applied to the upper lip (glabrous skin) and the chin (hairy skin). The sample was divided into two groups, based on a bimodal split “< 45 yrs” and “≥ 65 yrs”. In all instances, there were elevations in thresholds for the older individuals. Further, males were less sensitive than females for cool at the chin site, for touch, and for sour taste. We conclude that there are elevations in sensory thresholds with age for multimodal somatosensory and gustatory senses.
Future of imaging photon counting detectors for ground-based astronomy

Silicon Charge-Coupled Devices (CCDs) are the ubiquitous detector of choice for most ground based optical cameras given their high QE, low readout noise, good spatial resolution and large array size. However, they are integrating detectors, and as such have a limited temporal resolution determined by the readout frame rate. Imaging photon counters, on the other hand, can determine the location and arrival time of an individual detected photon which lends itself to studies of the intrinsic variability of astronomical sources. This topic is of fundamental importance, especially for the case of compact objects in stellar binary systems, stellar flares, and accretion disk phenomena. Most of these timing observations are currently performed by satellite-born X-ray instruments, but similar data can also be obtained from ground-based observatories at visible wavelengths using photon counting detectors. In this paper we review the recent and future improvements in the performance of imaging, photon counters, especially their optical QE, array size, spatial and temporal resolution and dark counting rates. We will compare them to conventional CCD devices and discuss the observational applications for which either or both can excel. We find that for certain applications (such as high time resolution observations, faint spectra and wavefront sensors for adaptive optics) imaging photon counting detectors can provide observations of superior signal-to-noise to CCD's.
THE ESTABLISHMENT OF AN ALBINO RAT COLONY FREE FROM MIDDLE EAR DISEASE

A special colony of albino rats was built up by selection and isolation from a population in which middle ear disease was highly prevalent. No cases of aural infection occurred in the selected group, whereas its precursor showed a crude incidence of 57 per cent. The subjection of selected rats to a rachitic diet and to overcrowding did not predispose to the development of middle ear disease. The incidence of pneumonia was not similarly affected; thus, 52 per cent of the adult selected rats showed pulmonary lesions, and 78 per cent of the adult stock rats. There was, however, a significant reduction in the number of cases which showed advanced pulmonary lesions. Certain theoretical considerations of middle ear disease and of pneumonia are discussed.
A bioenergetic model of a mixed production fermentation

A bioenergetic model has been developed for the fermentation of glucose by Bacillus polymyxa. This model uses energy balances to determine which pathways are utilized by the substrate. The model can predict substrate consumption, biomass formation, and the product distribution for this fermentation. The products are carbon dioxide, water, 2,3-butanediol, and ethanol, where ethanol represents lumped anaerobic products.
Development of a new 10% liquid, triple virus reduced intravenous immune globulin product, new generation IGIV

Abstract Rationale While immune globulin products after introduction of dedicated virus inactivation steps have an excellent safety record, patient concerns around transmission of particularly viruses still exist, and are fueled by newly emerging viruses. Methods To address these concerns, the manufacturing process of this new liquid IGIV contains three dedicated virus reduction steps: (1) a three component solvent-detergent (SD) treatment, (2) a 35 N nanofiltration step, and (3) a prolonged incubation period at low pH and elevated temperature. Results (1) SD treatment resulted in complete inactivation of all the lipid-enveloped viruses tested, already after only 1 minute of the 60 minutes treatment, and also at drastically reduced concentrations of the SD reagents. (2) Nanofiltration effectively removed lipid-enveloped viruses. Also, HAV and parvovirus B19, viruses which are smaller than the nominal pore size of the filter used, were reproducibly and robustly removed by antibody-enhanced nanofiltration which occurred at a wide range of HAV and B19 antibody concentrations. (3) Incubation at low pH and elevated temperature effectively inactivated lipid-enveloped viruses, and resulted in significant levels of inactivation for non-lipid enveloped viruses, including parvoviruses. Inactivation was shown to depend on a combination of low pH and elevated temperature. Conclusions The incorporation of three dedicated and mechanistically different virus reduction steps for this new liquid immunoglobulin product results in unprecedented safety margins.
Hard-Rock Tunneling Using Pulsed Electron Beams

It has been demonstrated that intense sub-microsecond bursts of energetic electrons cause significant pulverization and surface spalling of a variety of rock types. The spall debris generally consists of sand, dust, and small flakes. If carried out at rapid repetition rate this can lead to a promising technique for increasing the speed and reducing the cost of underground excavation of tunnels, mines, and storage spaces. The conceptual design features of a Pulsed Electron Tunnel Excavator capable of tunneling approximately ten times faster than conventional drill/blast methods is presented.
Diversity and dynamics of microbial communities in soils from agro‐ecosystems

Soil microbial communities are integrally involved in biogeochemical cycles and their activities are crucial to the productivity of terrestrial ecosystems. Despite the importance of soil microorganisms, little is known about the distribution of microorganisms in the soil or the manner in which microbial community structure responds to changes in land management. We investigated the structure of microbial communities in the soil over two years in a series of replicated plots, that included, cultivated fields, fields abandoned from cultivation and fields with no history of cultivation. Microbial community structure was examined by monitoring the relative abundance of ribosomal RNA (rRNA) from seven of the most common bacterial groups in soil (the Alpha and Beta Proteobacteria, Actinobacteria, Cytophagales, Planctomycetes, Verrucomicrobia and the Acidobacteria) and the Eukarya. These data reveal that soil microbial communities are dynamic, capable of significant change at temporal scales relative to seasonal events. However, despite temporal change in microbial community structure, the rRNA relative abundance of particular microbial groups is affected by the local environment such that recognizable patterns of community structure exist in relation to field management.
Characterization of a 30S ribosomal subunit assembly intermediate found in Escherichia coli cells growing with neomycin or paromomycin

Neomycin and paromomycin are aminoglycoside antibiotics that specifically stimulate the misreading of mRNA by binding to the decoding site of 16S rRNA in the 30S ribosomal subunit. Recent work has shown that both antibiotics also inhibit 30S subunit assembly in Escherichia coli and Staphylococcus aureus cells. This work describes the characteristics of an assembly intermediate produced in E. coli cells grown with neomycin or paromomycin. Antibiotic treatment stimulated the accumulation of a 30S assembly precursor with a sedimentation coefficient of 21S. The particle was able to bind radio-labeled antibiotics in vivo and in vitro. Hybridization experiments showed that the 21S precursor particle contained unprocessed 16S rRNA with both 5' and 3' extensions. Ten 30S ribosomal proteins were found in the precursor after inhibition by each drug. In addition, cell free reconstitution assays generated a 21S particle after incubation with either aminoglycoside. This work helps to define the features of the ribosome structure as a target for antimicrobial agents and may provide information needed for the design of more effective antibiotics.
Occupation and environmental heat-associated deaths in Maricopa county, Arizona: a case-control study.

BACKGROUND: Prior research shows that work in agriculture and construction/extraction occupations increases the risk of environmental heat-associated death. PURPOSE: To assess the risk of environmental heat-associated death by occupation. METHODS: This was a case-control study. Cases were heat-caused and heat-related deaths occurring from May-October during the period 2002-2009 in Maricopa County, Arizona. Controls were selected at random from non-heat-associated deaths during the same period in Maricopa County. Information on occupation, age, sex, and race-ethnicity was obtained from death certificates. Logistic regression analysis was used to estimate odds ratios for heat-associated death. RESULTS: There were 444 cases of heat-associated deaths in adults (18+ years) and 925 adult controls. Of heat-associated deaths, 332 (75%) occurred in men; a construction/extraction or agriculture occupation was described on the death certificate in 115 (35%) of these men. In men, the age-adjusted odds ratios for heat-associated death were 2.32 (95% confidence interval 1.55, 3.48) in association with construction/extraction and 3.50 (95% confidence interval 1.94, 6.32) in association with agriculture occupations. The odds ratio for heat-associated death was 10.17 (95% confidence interval 5.38, 19.23) in men with unknown occupation. In women, the age-adjusted odds ratio for heat-associated death was 6.32 (95% confidence interval 1.48, 27.08) in association with unknown occupation. Men age 65 years and older in agriculture occupations were at especially high risk of heat-associated death. CONCLUSION: The occurrence of environmental heat-associated death in men in agriculture and construction/extraction occupations in a setting with predictable periods of high summer temperatures presents opportunities for prevention. Language: en
An integrated design system for cable reinforced membranes using interactive computer graphics

Abstract A computer-aided design program for cable reinforced membrane structures is described. The program makes extensive use of interactive computer graphics techniques for data entry and visual feedback on the current status of the design. Nonlinear finite element analysis is used as the basis of design. Routines are provided for automated generation of finite element meshes using discrete transfinite mappings; solution of the initial equilibrium problem through least squares force adjustment methods, iterative shape smoothing, or nonlinear displacement analysis; and nonlinear stiffness analysis including frictional slip behavior between membrane material and reinforcing cables. The program is capable of handling both pretensioned and air-supported structures. The overall design approach and structure of the program are emphasized.
Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study

We evaluated bevacizumab with metronomic etoposide among recurrent malignant glioma patients in a phase 2, open-label trial. A total of59 patients, including 27 with glioblastoma (GBM) and 32 with grade 3 malignant glioma, received 10 mg kg−1 bevacizumab biweekly and 50 mg m−2 etoposide daily for 21 consecutive days each month. The primary end point was a 6-month progression-free survival, and secondary end points included safety and overall survival. Vascular endothelial growth factor (VEGF), VEGFR-2, carbonic anhydrase 9 (CA9) and hypoxia-inducible factor-2α (HIF-2α) were assessed semiquantitatively in archival tumours using immunohistochemistry and were correlated with outcome. Among grade 3 and GBM patients, the 6-month progression-free survivals were 40.6% and 44.4%, the radiographic response rates were 22% and 37% and the median survivals were 63.1 and 44.4 weeks, respectively. Hypertension predicted better outcome among both grade 3 and GBM patients, whereas high CA9 and low VEGF were associated with poorer progression-free survival (PFS) among those with GBM. The most common grade ⩾3 adverse events included neutropaenia (24%), thrombosis (12%), infection (8%) and hypertension (3%). Two patients had asymptomatic, grade 1 intracranial haemorrhage and one on-study death occurred because of pulmonary embolism. Bevacizumab with metronomic etoposide has increased toxicity compared with previous reports of bevacizumab monotherapy. Its anti-tumour activity is similar to that of bevacizumab monotherapy or bevacizumab plus irinotecan. (ClinicalTrials.gov: NCT00612430).
One Europe, Many Electorates?: Models of Turnout in European Parliament Elections After 2004

The 2004 European Parliament (EP) elections were marked by continued decline in voter turnout and wide variation in turnout levels among the member states. The addition of 10 new members for the 2004 election results presents a unique opportunity to test established explanations of turnout in EP elections. The authors re-examine models developed from general participation studies and applied in earlier research on turnout in EP elections. The updated and revised analysis continues to point to the importance of both national and European Union—level influences in explaining EP election turnout. Thus, although the second-order model of European elections still holds considerable appeal, the increasing divergence of turnout patterns in 2004 and through time suggests that European issues may be important in some countries.
Inverse correlation of cellular immune responses specific to synthetic peptides from the E6 and E7 oncoproteins of HPV-16 with recurrence of cervical intraepithelial neoplasia in a cross-sectional study

Abstract Background. Epidemiological studies have clearly established that human papillomavirus (HPV) infection is the major risk factor for cervical cancer. Most cervical cancers and pre-cancers are HPV-positive. Not all pre-cancers progress to cancer; a significant number regress. The immunological basis for either spontaneous or treatment-mediated recovery from HPV-associated CIN is not clear. Currently, prophylactic vaccines are successfully inducing antibody responses in HPV negative patients. Therapeutic vaccines for HPV-positive patients with disease are needed. There is a need to understand the immunologic basis for the Cell-Mediated Immune (CMI) response and for histological regression to help the formulation of therapeutic vaccines. Material and methods. Four groups of women were identified for this cross-sectional study of CMI. Group 1 consisted of six women without cytological or histological diagnosis of CIN and with an HPV negative test (CIN (−) /HPV (−) ). Group 2 included 31 women with a new histological diagnosis of CIN and HPV positive test (CIN (+) /HPV (+) ). Groups 3 and 4 were selected from women who had undergone ablative or excisional treatment for CIN at the colposcopy clinic at least 6 months before the study. The women in groups 3 and 4 were (CIN (+) /HPV (+) ) before CIN treatment. Group 3 consisted of 22 women without evidence of recurrence of CIN (Recur (−) ), and group 4 included 10 with histological diagnosis of recurrent CIN (Recur (+) ). In particular, we investigated CMI responses to synthetic peptides from the E6 and E7 oncoproteins of HPV-16. Results. Compared to patients with disease recurrence (Recur (+) , n = 10), the majority of individuals who remained recurrence-free post-treatment (Recur (−) , n = 22) exhibited significant proliferative responses to synthetic peptides from the E6 ( P = 0.001) and the E7 ( P = P = 0.006) and the E7 peptide Q19D (aa 44–62, P = 0.002) in Recur (−) patients but not Recur (+) individuals. Additionally, PBMC from women in the Recur (−) group, but not the Recur (+) group, produced predominantly TH1 cytokines upon stimulation with the peptides Q15L or Q19D. Conclusions. These results indicate an association between significant cellular immune responses specific to synthetic peptides from the E6 and E7 oncoproteins of HPV-16 and recurrence-free survival in HPV patients treated for CIN. We predict that these peptides may be useful as indicators of protective immunity for recovery from CIN and also for potential inclusion in designing immunotherapeutic and immunoprophylactic reagents for HPV-associated CIN.
Monte Carlo analysis of the internal structure of light scattering particles with slit-scan illumination

An algorithm based upon a Monte Carlo procedure for calculating the scattering and absorption by a host particle containing a distribution of particulate inclusions is described. The host particle is sufficiently large so that ray optics can be applied. The inclusions are too small for ray optics but sufficiently large so that the full boundary-value formalism must be used. A major consideration is to determine whether the internal structure is better resolved when slit-scan illumination is utilized rather than plane wave illumination. The algorithm is tested for a layered sphere for which the boundary value solution is available.
Correlation of process nonlinearity with closed-loop disturbance rejection

In this work, correlations between control-relevant nonlinearity and the achievable performance of a variety of control structures are investigated for two processes. Each process' degree of open-loop nonlinearity is assessed using a numerical nonlinearity measure and then compared to the performance results for a set of controllers of varying complexity in disturbance rejection. The results for an experimental quadruple-tank process indicate an extremely low degree of control-relevant nonlinearity, agreeing with the open-loop nonlinearity assessment and the mild performance specification. Given tunings optimized for low-frequency output disturbance rejection, a bioreactor model demonstrates a mild degree of control-relevant nonlinearity when output disturbances are considered and a relatively high degree of control-relevant nonlinearity for input disturbance rejection. The bioreactor thus demonstrates the need to assess properly control-relevant nonlinearity in terms of desired performance and to consider the effects of controller tuning on the nonlinearity of the closed-loop operators.
AN ANALYTICAL NONLINEAR THEORY OF RICHTMYER-MESHKOV INSTABILITY

Abstract Richtmyer-Meshkov instability is a fingering instability which occurs at a material interface accelerated by a shock wave. We present an analytic, explicit prediction for the growth rate of the unstable interface. The theoretical prediction agrees, for the first time, with the experimental data on air-SF 6 , and is in remarkable agreement with the results of recent full nonlinear numerical simulations from early to late times. Previous theoretical predictions of the growth rate for air-SF 6 unstable interfaces were about two times larger than the experimental data.
Distributed Relaxation Response for Two Classes of Material Temperature Behavior

Expressions for the transient and frequency response of materials showing exponential distributions of transition rates are summarized and related to recent work in the field. Responses arising from temperature-independent distributions (class I) are contrasted to those that depend in a simple way on temperature (class II). The distinction between dielectric and conducting systems is particularly emphasized, and the different temperature dependences of their frequency power-law exponents for class-1) situations are discussed in detail. Besides presenting model frequency-response curves, it is shown that an exponential distribution of activation energies can lead to conductance frequency response very similar to that recently found by Lee et al. for two glasses and several ionically conducting single crystals. Ausdrucke fur das Transient-und Frequenzverhalten von Materialien, welche exponentielle Verteilungen von Ubergangsraten zeigen, werden zusammengefast in Verbindung mit kurzlich erschienenen Arbeiten auf diesem Gebiet. Das Verhalten, welches von temperaturunabhangigen Verteilungen stammt (Klasse I), wird verglichen mit dem, welches in einfacher Weise von der Temperatur abhangt (Klasse II). Der Unterschied zwischen dielektrischen und leitenden Systemen wird besonders hervorgehoben, und die unterschiedlichen Temperaturabhangigkeiten ihrer Frequenz-Exponenten fur Klasse-I Situationen werden ausfuhrlich behandelt. Zusatzlich zu dem modellierten Frequenzverhalten wird gezeigt, das eine exponentielle Verteilung von Aktivierungsenergien zu einem Frequenzverhalten der Leitfahigkeit fuhren kann, welches praktisch mit dem kurzlich von Lee et al. gefundenen fur zwei Glaser und mehrere ionisch-leitende Einkristalle ubereinstimmt.
Localization and proteomic characterization of cholesterol-rich membrane microdomains in the inner ear

Abstract Biological membranes organize and compartmentalize cell signaling into discrete microdomains, a process that often involves stable, cholesterol-rich platforms that facilitate protein–protein interactions. Polarized cells with distinct apical and basolateral cell processes rely on such compartmentalization to maintain proper function. In the cochlea, a variety of highly polarized sensory and non-sensory cells are responsible for the early stages of sound processing in the ear, yet little is known about the mechanisms that traffic and organize signaling complexes within these cells. We sought to determine the prevalence, localization, and protein composition of cholesterol-rich lipid microdomains in the cochlea. Lipid raft components, including the scaffolding protein caveolin and the ganglioside GM1, were found in sensory, neural, and glial cells. Mass spectrometry of detergent-resistant membrane (DRM) fractions revealed over 600 putative raft proteins associated with subcellular localization, trafficking, and metabolism. Among the DRM constituents were several proteins involved in human forms of deafness including those involved in ion homeostasis, such as the potassium channel KCNQ1, the co-transporter SLC12A2, and gap junction proteins GJA1 and GJB6. The presence of caveolin in the cochlea and the abundance of proteins in cholesterol-rich DRM suggest that lipid microdomains play a significant role in cochlear physiology. Biological significance Although mechanisms underlying cholesterol synthesis, homeostasis, and compartmentalization in the ear are poorly understood, there are several lines of evidence indicating that cholesterol is a key modulator of cochlear function. Depletion of cholesterol in mature sensory cells alters calcium signaling, changes excitability during development, and affects the biomechanical processes in outer hair cells that are responsible for hearing acuity. More recently, we have established that the cholesterol-modulator beta-cyclodextrin is capable of inducing significant and permanent hearing loss when delivered subcutaneously at high doses. We hypothesize that proteins involved in cochlear homeostasis and otopathology are partitioned into cholesterol-rich domains. The results of a large-scale proteomic analysis point to metabolic processes, scaffolding/trafficking, and ion homeostasis as particularly associated with cholesterol microdomains. These data offer insight into the proteins and protein families that may underlie cholesterol-mediated effects in sensory cell excitability and cyclodextrin ototoxicity.
High frequency shaking induced by low frequency forcing: Periodic oscillations in a spring–cable system

Abstract We investigate the response of a piecewise linear spring to very low frequency forcing. It has been observed that the bifurcation picture is very complicated with many multiple periodic responses with a high frequency component. We show many new aspects of this phenomenon, including what happens if the nonlinearity is smoothed out. Methods used include Newton’s method, in combination with continuation algorithms, and a steepest descent method for finding new isolated branches of solutions.
Posterior ischemic optic neuropathy after uncomplicated cataract extraction.

Abstract PURPOSE: We report a case of posterior ischemic optic neuropathy after uncomplicated cataract extraction. DESIGN: Observational case report METHODS: Retrospective description of the natural course of posterior ischemic optic neuropathy in one patient seen at an academic institution. RESULTS: The patient had sudden vision loss after uncomplicated cataract surgery with the features of an optic neuropathy, no acute disk swelling, and delayed optic nerve head perfusion on fluorescein angiography. CONCLUSIONS: Posterior ischemic optic neuropathy rarely occurs after uncomplicated cataract surgery, and should be considered in the setting of postoperative vision loss.
Cellular and molecular mechanics by atomic force microscopy: Capturing the exocytotic fusion pore in vivo?

The atomic force microscope (AFM) is a remarkably simple instrument that can measure forces down to piconewtons and can resolve force changes caused by the displacement of its probe by a fraction of a nanometer. Furthermore, these measurementscanbedoneunderwater,allowingforthestudy of biological material under conditions that resemble thosein vivo.TheAFMfunctionslikeaminiaturephonograph.Asharp tip,mountedonacantilever,interactswiththesample,causing minutedeflectionsthatcanbecalibratedasaforce.TheAFM, in its force-measuring mode, has been applied to the study of molecular mechanics. For example, the laboratory of Hermann Gaub in Munich succeeded in the remarkable feat of measuring the adhesion force between single avidin‐biotin pairs (’160 pN; ref. 1). These measurements were independently confirmed by molecular dynamic simulations of the avidin‐biotininteractionthatrevealedtheatomictrajectoryof a rupture and predicted the associated forces (2). Hence, the techniquesofmolecularmechanicsnowrivalthecapabilitiesof patch-clamp techniques (3) in describing the activity of single proteins. The patch-clamp technique seals a lipid membrane, containingionchannelproteins,ontoaglasspipetteelectrode. Ioniccurrentsflowingthroughasingleionchannelproteinare then easily measured, reporting on the conformational states of the transmembrane protein. In contrast to the patch-clamp technique, useful mainly for the characterization of ion channels, molecular mechanics studies can be done on single proteins or more complex structures that do not carry an associated electrical activity. ThemostfamiliaruseoftheAFMisincreatingtopographic imagesofasample.ThisisdonebyscanningtheAFMtipover the sample and recording the z axis displacement required to maintain a constant contact force. The nanometer resolution of the AFM imaging technique has been used to examine the structural features of proteins, producing data that is comparable to that obtained by x-ray crystallography (4). However, the biggest promise of the AFM technique is in the measurement of the activity of single protein structuresin vivoduring signaling events or during other types of cellular activities. Indeed, we may be getting close. A recent example demonstratedthatitispossibletoobserveconformationalchangesin the structure of a single nuclear pore in Xenopus oocyte nuclear envelopes (5). However, these measurements were doneinfixedtissue.RecentworkfromthelaboratoryofBhanu
Secretin receptors in the rat kidney: Adenylate cyclase activation and renal effects

In previous studies it has been demonstrated that pharmacological administration of secretin can alter urine output. Whether the effect is due to a direct action on kidney was investigated by examining the effect of secretin on renal output, and determining whether there were secretin receptors and a secretin sensitive adenylate cyclase in the kidney. Secretin had an antidiuretic action on kidney when administered intravenously to anesthetized hydrated rats. In addition, binding sites for (125I)-secretin, and a secretin sensitive adenylate cyclase were identified in rat kidney. Binding was saturable and reversable and was half maximally inhibited by 1 X 10(-7) M synthetic porcine secretin. Autoradiographic studies revealed a high density of secretin binding sites in the outer medulla of the kidney, a region that is composed mainly of the thick ascending limb of the loop of Henle, and is also the major site of action for the antidiuretic hormone, vasopressin. The data indicate that a functional secretin receptor system exists in kidney which may have a physiological role in regulating urine output.
Distribution and efficacy of pyrethrin aerosol to control Tribolium confusum (Coleoptera: Tenebrionidae) in food storage facilities

Abstract A field test was conducted whereby adult Tribolium confusum (du Val), the confused flour beetle, were exposed in Petri dishes lined with filter paper and containing 0–2000 mg of flour, to a pyrethrin–CO2 aerosol inside an empty warehouse. Applications were made according to label directions, and beetles were exposed to the aerosol for 2 h. After exposure, knockdown was assessed, and beetles were held for 2 weeks either in the same Petri dishes in which they were exposed or transferred with the flour to new Petri dishes lined with clean filter paper. Resident insect populations inside the test warehouse and outside were assessed through the use of pheromone traps. Virtually all beetles were knocked down at the time of removal from the exposure environment. Recovery from knockdown, or survival, increased with the presence of flour, and varied depending on the position of the exposure dishes inside the warehouse. Survival was also greater for beetles transferred along with the exposed flour to new Petri dishes lined with unexposed filter paper, compared to beetles that were held with the flour and the Petri dish that was exposed to the aerosol. Inside the warehouse, Plodia interpunctella (Hubner), the Indian meal moth, and Trogoderma variabile Ballion, the warehouse beetle, were the major species collected in pheromone traps. Large numbers of T. variabile were captured outside the warehouse, but their numbers declined during the study, while captures of P. interpunctella outside remained relatively constant. The intermittent aerosol treatments did not seem to affect these resident populations.
A PRESCHOOL-AGE CHILD WITH FIRST-TIME SEIZURE AND ATAXIA

We present a case of a 4-year-old previously healthy child who had a possible first-time seizure at home, and upon a second Emergency Department evaluation was found to have gross cerebellar ataxia suggestive of acute stroke. Initial computed tomography scan and metabolic work-up were unrevealing. Subsequent neuroimaging demonstrated stroke in the left medulla and cerebellum secondary to left vertebral artery dissection. Cervical artery dissection may cause up to 20% of strokes in childhood and adolescence. Unlike typical adult presentations, antecedent or concurrent head and neck pain occurs less often in pediatric dissections. Symptoms of posterior circulation ischemia resulting from vertebral artery dissection may include vertigo, vomiting, ataxia, dysarthria, and seizure. Willingness to utilize newer, non-invasive imaging modalities may lead to earlier recognition of cervical artery dissection when patients have prodromal symptoms or episodes of transient ischemia. Vertebral artery dissection should be included in the differential diagnosis when evaluating children with first time seizure, headache, or neck pain.
Synthesis and characterization of large-pore FDU-12 silica

Abstract Large-pore FDU-12 (LP-FDU-12) silicas with face-centered cubic structures of spherical mesopores of diameter 16–26 nm were synthesized using Pluronic F127 triblock copolymer template. The materials were characterized using small-angle X-ray scattering and nitrogen adsorption. The initial temperature range suitable for LP-FDU-12 synthesis was shown to be much wider than that reported earlier (7–15 °C vs. 14–15 °C). However, the degree of structural ordering was lower and the pore size distribution was broader in case of temperatures of 7–9 °C. The removal of the template by calcination resulted in a significant shrinkage (unit-cell parameter decrease by 10–16%) and afforded samples with low adsorption capacity, unless the synthesis involved a hydrothermal treatment in an HCl solution, which reduced the shrinkage and significantly increased the pore volume. The selection of time and temperature of the acid treatment allowed us to adjust the pore diameter of LP-FDU-12. However, the broadening of pore size distribution was observed for excessively long treatments at 130 °C. The treatment at 130 °C allowed us to tailor the pore entrance size in LP-FDU-12.
MUSCLE BREAKDOWN AND LYSOSOMAL ACTIVATION (BIOCHEMISTRY)

Muscle tissue levels of lysosomal catheptic enzymes, such as cathepsins D, A, B1, C, and dipeptidyl peptidase II, were measured in control subjects and patients with muscular dystrophies, polymyositis, and certain denervating diseases. The results show that, in general, the activities of these enzymes are increased in muscles of patients with muscular dystrophies and other diseases. The increases in cathepsin D and autolytic activities are not significant until the late stage of the disease process. Cathepsins A, B1, and C are, however, significantly elevated in mildly affected dystrophic and other diseased muscles. Of these catheptic enzymes, cathepsin B1 displays the highest rise at an early stage, suggesting that it may be one of the rate-controlling enzymes of proteolysis. Dipeptidyl peptidase II is increased slightly in dystrophic and other myopathic muscles but is unchanged in denervated muscle. These data clearly implicate the lysosomal group of proteinases as largely responsible for mediating muscle breakdown in the muscular dystrophies and certain other muscle and neuromuscular diseases in man.
Effects of Compression-Compression Fatigue Balanced Graphite/Epoxy Laminates with Holes

Experimental investigations have been conducted to determine the effect of stacking sequence and ply orientation on the compression-compression fatigue behavior of graphite/epoxy composites. Static compression tests of [±45/0]s and [0/±45]s laminates were carried out prior to compression-compression fatigue tests. These laminates, which were the facings of sandwich beams, were of three different configurations: 1) unflawed, 2) a 0.25-in.-diam hole and 3) a 0.25-in.-diam hole clamped by washers held together by a loose fitting bolt. A much larger number of compression-compression fatigue tests on laminates containing 0.25-in-diam circular holes were carried out on the laminate systems denoted by [0/±30]s, [ ±30/0]s, [0/±45]s, and [ ±45/0]s. Damage initiation and growth was monitored during the tests. Comparison was made of failure modes between static and fatigue tests.
Detailed Chemical Modeling of the Circumstellar Envelopes of Carbon Stars: Application to IRC +10216

We have constructed a detailed chemical model for the circumstellar envelope surrounding the nearby, carbon-rich star IRC +10216. This model extends previous approaches for the photochemistry. In particular, we consider the photodissociation of CO using the Sobolev approximation to study the effect of CO self-shielding, include H2 shielding, treat the effects of source geometry and continuum radiative transfer through dust, and construct a large, detailed gas phase chemical network to probe the effects of these processes on abundance variations of selected species. We then compare our results with previous models and observations to assess their validity and the necessity of including this level of detail. In general, we find that although CO self-shielding is important, one cannot ignore the effect of continuum radiative transfer. This can change the CO dissociation radius by about 30%. The change in the CO dissociation radius can propagate chemical differences into the chemical network. We find that our model predictions can reproduce the column densities inferred from observations as well as or better than previous comprehensive models. Our model also predicts the atomic carbon abundance peak to be significantly closer to the central source than previous photochemical models—a result consistent with strong C I lines observed by Keene et al.
Oil, Water, Blood and Diamonds:International Intervention in Resource Disputes

Violent conflicts over natural resources disrupt energy supply, distort economic development, weaken governments, and threaten international security. With looming resource scarcity and increasing energy demands, international powers position themselves to protect their access to vital resources abroad. Fierce competition for resources will increase the urgency with which international actors intervene in resource disputes. Yet strategies for resolving resource disputes are underdeveloped. The purpose of this research is to examine the use of political and economic strategies to resolve disputes over vital resources through negotiated settlements, in comparison to strategies that result in exacerbating conflict. This study develops a valuable new dataset on resource disputes and provides a systematic cross-national analysis of international intervention strategies. It tests the success or failure of leveraging international market access, financial aid, capacity building, transparency reforms, and levels of military mobilization for understanding the outcome of resource conflicts. The results identify specific international strategies that are effective in altering the costbenefit analysis of cooperation versus conflict, in the interest of achieving negotiated settlements for resource disputes.
A functional role for p38 MAPK in modulating mitotic transit in the absence of stress.

Although p38 MAPK is known to be activated in response to various environmental stresses and to have inhibitory roles in cell proliferation and tumor progression, its role in cell cycle progression in the absence of stress is unknown in most cell types. In the case of G2/M cell cycle control, p38 activation has been shown to trigger a rapid G2/M cell cycle checkpoint after DNA damage stress and a spindle checkpoint after microtubule disruption. In the course of our studies, we observed that p38 became actively phosphorylated, and its kinase activity increased transiently during G2/M cell cycle transition. Using an immunocytochemistry approach, the active form of p38 was found at the centrosome from late G2 throughout mitosis, which suggests functional relevance for active p38 protein during mitotic entry. A closer examination reveals that p38 inhibition by pharmacologic inhibitors significantly accelerated the timing of mitotic entry. In addition, long term exposure of the inhibitor enhanced Cdc2 activity. These results indicate that p38 activity during G2/M may be involved in a mechanism for fine tuning the initiation of mitosis and perhaps transit of mitosis. Consistent with our previous findings, Cdc25B was phosphorylated on serine 309 at the centrosome during G2/M when p38 was active at this site; Cdc25B phosphorylation inhibits Cdc25B activity, and this phosphorylation was found to be p38-dependent. Taken together, our findings suggest that p38 regulates the timing of mitotic entry via modulation of Cdc25B activity under normal nonstress conditions.
Reduction in brain serotonin synthesis rate following chronic methamphetamine administration in rats.

Chronic administration of methamphetamine (20 mg/kg i.p., every 12 h for 6 days) produced significant decreased in brain 5-hydroxytryptophan accumulation following decarboxylase inhibition and 5-hydroxyindoleacetic acid accumulation following probenecid treatment in rats. Administration of fluoxetine prior to each methamphetamine injection prevented these neurochemical changes. Acute methamphetamine treatment produced no changes in these neurochemical measures. These data demonstrate that chronic, but not acute, methamphetamine treatment reduces brain serotonin synthesis rate.
Detection of high- and low-frequency vibrations using a feedback-stabilized differential fiber optic interferometer

Highly sensitive and stable detection of minute ac and pseudo-dc (i.e. , very low frequency) vibrations is performed by means of a differential fiber optic Michelson interferometer. Any residual instabilities are eliminated by means of an ac feedback control loop. The stabilization technique is not affected by the variations in the reflectivity of the sample and by launch inefficiencies into the fiber. This approach also provides a simple, quantitative method for calibrating sample vibrations. Results are presented on the operation of the system in stabilizing its output as well as on the detection of the vibration of a silicon sample.
Neighbor properties of some classes of BIBRCs and their efficiencies for correlated errors

Some series of previously known balanced incomplete block designs with nested rows and columns are shown to be balanced for neighbors in rows, in columns, and in diagonals when blocks are assumed to be on toruses and/or on cylinders. These series of designs with planar blocks are found to be highly efficient within the class of binary designs when error covariance matrix follows three parameter conditional autonormal process.
Quantitative Infrared Spectroscopy of Interstitial Oxygen in Silicon Wafers Using Multivariate Calibration

A PLS multivariate calibration method is used to create a reliable means for the determination of the interstitial oxygen content in silicon wafers. The multivariate calibration, derived from silicon standards with various backside treatments, provides similar precision measurement capability when compared to peak area calibration curves established from individual backside treatments. In this case, the significant advantage of the multivariate calibration is that a single calibration can yield interstitial oxygen results that correlate favorably with vendor values over a wide range (20 to 40 ppma), regardless of the backside condition of the wafers.
Evaluation of the diagnostic utility of the TRH-induced TSH response in psychiatric disorders

To evaluate the diagnostic utility of TSH blunting, the TRH-induced TSH response was measured in 168 normal subjects and 176 psychiatric patients. It was blunted in some acutely depressed, alcoholic, and borderline patients, but not in schizophrenic patients. In both depression and alcoholism the fault also occurred during symptomatic recovery, though with reduced frequency. Although TSH blunting was useful in distinguishing between borderline and schizophrenic patients, its diagnostic utility in identifying or confirming an existing psychiatric disorder appears to be limited. TSH blunting is not specific for any particular psychiatric diagnosis, and its sensitivity generally is low. However, the fault has promising research utility, particularly for study of the biologic interface between depression, alcoholism and borderline personality disorder. Beyond this, further study of the possible trait nature of TSH blunting in both depression and alcoholism appears warranted.