cssi/SciSciGPT-SciSciNet huggingface dataset:
Condensing and Fluidizing Effects of Gangliosides on Various Phospholipid Films

In model membrane mixtures that mimic lipid raft compositions, the more ordered domains are enriched in the ganglioside, GM1, which contains four neutral sugars and a negatively charged sialic acid. To understand the organization and partitioning of GM1 in cell membranes, the outer leaflet of the cell membrane was modeled using Langmuir monolayers of DPPC and varying concentrations of GM1. At low biologically relevant concentrations, GM1 condenses the DPPC monolayer while at higher concentrations, it fluidizes, with a switch-over point between the two behaviors at a ratio of 3:1 DPPC:GM1. Atomic force microscopy performed on deposited monolayers indicated that GM1 is located in nanoscale clusters within the condensed DPPC domains. The total surface area of these nanosize domains is larger than that attributable to GM1 molecules alone, suggesting the regions are due to GM1 and DPPC packing preferentially in condensed complexes due to variations in molecular geometry.To further study this effect, geometry of the phospholipid was varied. The zwitterionic lipid, 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE), with its smaller headgroup cross-sectional area compared to DPPC, was combined with various ratios of GM1. Additivity plots constructed for the mixtures to show deviations from ideal mixing indicated a 3:2 DMPE:GM1 ratio was most condensed compared to the individual components. Molecular geometry of the phospholipid headgroup plays a role in the condensation effect of GM1 on neighboring phospholipids. Additional experiments on certain monolayer mixtures of 1,2-dilauroyl-sn-glycero-3-phosphoethanolamine (DLPE) and GM1, components that are each fluid in pure monolayers, showed formation of condensed domains. This indicates the condensation effect of GM1 is strong enough to induce biologically relevant ordering phase transitions. Results will also be shown from experiments combining phospholipids containing negatively charged phosphatidylglycerol headgroups with GM1 to show the effect of electrostatic repulsion on the induced condensation.
Hyperglycemia and reproductive defects in non-diabetic gravidas: a mouse model test of a new theory

Abstract The frequent association of various reproductive anomalies with maternal diabetes is explained by a theory that predicts such defects will occur even in transient moderate hyperglycemia in non-diabetic gravidae. A first test of this hypothesis produced strongly supportive results in a mouse model. Thirteen C57BL/6J dams on a grain (control) diet produced (in the 4th week after first mating) 64 pups, 62 surviving to maturity. In the same time interval on a high sucrose diet, fourteen isogenic dams produced only 5 pups, none surviving 5 days (p ⪡ .001). Additional ongoing studies of the underlying glucose-ascorbate antagonism and of early vs. perinatal hyperglycemia are described briefly.
Pleomorphic, Enveloped, Virus-Like Particles Associated with Gastrointestinal Illness in Neonates

Pleomorphic, enveloped, virus-like particles were detected by electron microscopy in the stools of symptomatic infants during an outbreak of gastrointestinal illness in a neonatal intensive-care unit. To determine the incidence of virus-like particles in the stool and their relation to gastrointestinal symptoms, eight surveys of stools for the particles were conducted over 40 weeks. The incidence of virus-like particles in the stool decreased from 69% to less than 10% over the study period. Most infants surveyed were premature; overall, 32 (36%) of 88 neonates were positive for virus-like particles. Statistically significant associations were found between virus-like particles in the stool and gastrointestinal symptoms within one week of each survey. These symptoms included water-loss stools, blood in the stool, gastric retention, bilious gastric aspirates, and abdominal distention. Several infants with virus-like particles whose mothers had gastrointestinal or "flu-like" symptoms before delivery were identified in the community (not part of the survey study).
Abstract 2325: The crystal structure of the ERK2/norathyriol complex

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Norathyriol is an active metabolite of mangiferin, one of the mango polyphenolic compounds that have been demonstrated to have anti-proliferative and pro-apoptotic activities against human leukemia, as well as human lung, breast, colon and prostate cancer cells. Norathyriol has been reported to inhibit the PMA-induced respiratory burst and aggregation of rat neutrophils by suppressing protein kinase C activity. We show that norathyriol targets extracellular signal-regulated kinase 2 (ERK2), which is activated in response to growth factors and cytokines, and is a key kinase in the Ras/Raf/MAPK signaling pathway, which is deregulated in many cancers. We determined the crystal structure of ERK2 complexed with norathyriol at 1.6 A resolution. Human recombinant ERK2 was expressed, purified from E.coli and successfully crystallized. The protein crystals were soaked with norathyriol solution prior to the data collection. The norathyriol molecule is clearly visible in the electron density map inside the ATP-binding site below the phosphate-binding loop. Norathyriol is anchored to the ERK2 hinge region that connects the kinase N- and C-lobes by several hydrogen bonds. The side chain carboxyl of the gatekeeper residue Gln105 hydrogen bonded with the 7-OH group of norathyriol. The backbone of Asp106 and Met108 form hydrogen bonds with 6-OH group of norathyriol. We mutated Gln105 to alanine to weaken the norathyriol interaction with ERK2, and showed that the recombinant Q105A mutant exhibited impaired in vitro binding affinity to norathyriol compared with wild type. The Ile31, Val39, and Ala52 residues from the N-lobe contribute to the hydrophobic interactions with the xanthone moiety of norathyriol. These results indicate that norathyriol directly binds to the ATP-binding site of ERK2. The Ras/Raf mutation in many cancers causes the hyperactivation of ERK2 and unregulated cell proliferation. Recent reports indicate that knockdown of ERK2 inhibits growth of tumor cells, suggesting that ERK2 inhibition is a potential approach for the treatment of cancer. Norathyriol thus might be a potential therapeutic and chemopreventive lead compound targeting ERK2 in cancer cells where activation of the ERK2 pathway mediates the anti-apoptotic response. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2325. doi:10.1158/1538-7445.AM2011-2325
Covalent linkage of prosthetic heme to CYP4 family P450 enzymes.

An extensive body of research on the structural properties of cytochrome P450 enzymes has established that these proteins possess a b-type heme prosthetic group which is noncovalently bound at the active site. Coordinate, electrostatic, and hydrogen bond interactions between the protein backbone and heme functional groups are readily overcome upon mild acid treatment of the enzyme, which releases free heme from the protein. In the present study, we have used a combination of HPLC, LC/ESI-MS, and SDS−PAGE techniques to demonstrate that members of the mammalian CYP4B, CYP4F, and CYP4A subfamilies bind their heme in an unusually tight manner. HPLC chromatography of CYP4B1 on a POROS R2 column under mild acidic conditions caused dissociation of less than one-third of the heme from the protein. Moreover, heme was not substantially removed from CYP4B1 under electrospray or electrophoresis conditions that readily release the prosthetic group from other non-CYP4 P450 isoforms. This was evidenced by an intact prot...
Application of Wave Propagation Analysis for Damage Identification in Composite Laminated Beams

Interpretation of data measurement is a major challenge for the development of a reliable and effective diagnostic system. This paper presents the experimental results of a proposed damage identification candidate based on the Lamb wave propagation analysis. From the measured time history data of the propagating wave, the traveling time, speed reduction, and wave attenuation parameters are extracted and used as the damage identification variables. Piezoelectric transducers (PZTs) are used as the wave transmitters and receivers. Carbon-epoxy-laminated composite beam specimens with various types of damage, i.e., delamination, saw cut, and impact damage, are evaluated. Post-processing of the recorded signals using wavelet transform allows the isolation of the interested propagation mode and the extraction of the traveling time, which enhance the accuracy of damage localization. The technique is capable of locating the damages and evaluating the damage magnitude. Further, the classification of damage types in...
A justification of a fast surface tracking algorithm

In many three-dimensional (3D) imaging applications in science, medicine, and engineering, object information captured in a 3D digital image is visualized and analyzed based on object surfaces extracted from the image. Recently Gordon and Udupa (Comput. Vision Graphics Image Process.45, 1989, 196–214) reported a fast algorithm for tracking such surfaces, whose correct behavior has only been a conjecture but observed nonetheless in all uses of this algorithm in a variety of biomedical applications. In the present paper, we prove the correctness of their algorithm by showing that the surfaces generated by the algorithm correspond to connected components of boundary elements and that they possess Jordan boundary properties.
Radiation myocardial fibrosis simulating constrictive pericarditis. A review of the literature and a case report.

This case report illustrates heart disease after radiation of the chest for metastatic carcinoma of the breast. The clinical and hemodynamic features of cardiac compression were present and were unresponsive to pericardiectomy. Pathologic examination revealed myocardial fibrosis analogous to those lesions produced experimentally in rat myocardium by x-irradiation.
INTENSITY-MODULATED RADIOTHERAPY USING IMPLANTED FIDUCIAL MARKERS WITH DAILY PORTAL IMAGING: ASSESSMENT OF PROSTATE ORGAN MOTION

Purpose: To assess our single institutional experience with daily localization, using fiducials for prostate radiotherapy. Methods and Materials: From January 2004 to September 2005, 33 patients were treated with 1,097 intensity-modulated radiation treatments, using three implanted fiducials. Daily portal images were obtained before treatments. Shifts were made for deviations ≥3 mm in the left–right (LR), superior–inferior (SI), and anterior–posterior (AP) dimensions. Results: Of 1,097 treatments, 987 (90%) required shifts. Shifts were made in the LR, SI, and AP dimensions in 51%, 67%, and 58% of treatments, respectively. In the LR dimension, the median distance shifted was 5 mm. Of 739 shifts in the SI dimension, 73% were in the superior direction for a median distance of 6 mm, and 27% were shifted inferiorly for a median distance of 5 mm. The majority of shifts in the AP dimension were in the anterior direction (87%). Median distances shifted in the anterior and posterior directions were 5 mm and 4 mm, respectively. The median percentage of treatments requiring shifts per patient was 93% (range, 57–100%). Median deviations in the LR, SI, and AP dimensions were 3 mm, 4 mm, and 3 mm, respectively. Deviations in the SI and AP dimensions were more often in the superior rather than inferior (60% vs. 29%) and in the anterior rather than posterior (70% vs. 16%) directions. Conclusions: Interfraction prostate motion is significant. Daily portal imaging with implanted fiducials improves localization of the prostate, and is necessary for the reduction of treatment margins.
Two-dimensional transesophageal echocardiographic determination of aortic valve area in adults with aortic stenosis

Abstract To determine if aortic stenosis severity could be accurately measured by two-dimensional transesophageal echocardiography (TEE), 62 adult subjects (mean age 66 ± 12 years) with aortic stenosis had their aortic valve area (AVA) determined by direct planimetry using TEE, and with the continuity equation using combined transthoracic Doppler and two-dimensional echocardiography (TTE). Eighteen subjects had AVA calculated by the Gorlin method during catheterization. An excellent correlation ( r = 0.93, SEE=0.17 cm 2 ) was found between AVA determined by TEE (mean 1.24 ± 0.49 cm 2 ; range 0.40 to 2.26 cm 2 ) and TTE (mean 1.23 ± 0.46 cm 2 ; range 0.40 to 2.23 cm 2 ). The absolute (0.13 ± 0.12 cm 2 ) and percent (10.8 ± 8.9%) differences between AVA determined by TEE versus TTE were small. Excellent correlations between AVA by TEE and TTE were also found in subjects with normal systolic function ( r = 0.95, SEE=0.14 cm 2 ; n = 38) and impaired function ( r = 0.91, SEE=0.21 cm 2 ; n = 24). AVA determined by catheterization correlated better with AVA measured by TEE ( r = 0.91, SEE=0.15 cm 2 ) than AVA measured with TTE ( r = 0.84, SEE=0.19 cm 2 ). These data demonstrate that AVA can be accurately measured by direct planimetry using TEE in subjects with aortic stenosis. TEE may become an important adjunct to transthoracic echocardiography in the assessment of aortic stenosis severity.
Achievement of Climate Planning Objectives among U.S. Member Cities of the International Council for Local Environmental Initiatives (ICLEI)

In an effort to address climate change, many cities have joined the International Council for Local Environmental Initiatives (ICLEI) whose members commit to work toward five specific program objectives designed to reduce greenhouse gas emissions. This study examines the extent to which 257 member cities in the U.S.have been successful in achieving these program milestones and identifies factors that may explain variation in the performance of member cities. Potential influences on milestone attainment include socioeconomic, political and ideological characteristics of residents, length of ICLEI membership, existence of other climate programs within the state, and local environmental pressures. Multiple regression results indicate that length of membership is the strongest predictor of milestone attainment, regardless of local socioeconomic conditions, ideological and political orientations of residents, or other climate-related initiatives within the state. This finding supports the general effectiveness of ICLEI’s network organizational model and its outreach and education efforts. However, member cities facing more “climate stress”, including higher levels of hazardous air pollutants (HAP’s) and greater automobile use among residents are making slower progress. The findings yield insight into the conditions under which cities engaged in climate planning are more likely to succeed in reducing local greenhouse gas emissions-relevant information for planners, community stakeholders and administrators of organizations like ICLEI.
SNARE Complex Assembly in Retinal Bipolar Neuron Exocytosis

Three kinetic components of exocytosis have been described in retinal bipolar neurons. They are thought to reflect the fusion of a docked pool of ribbon-tethered synaptic vesicles termed the rapid pool, the releasable pool of ribbon-tethered vesicles, and a cytoplasmic reserve pool. In neurons, assembly of SNARE proteins facilitates exocytosis. We asked whether these pools could be distinguished on the basis of SNARE complex formation. Syntaxin3B is a t-SNARE in ribbon synapses. We generated a fluorescent peptide based on the syntaxin3B SNARE binding motif from goldfish. The peptide was dialyzed into isolated synaptic terminals of goldfish retinal bipolar cells via a whole-terminal recording electrode. A scrambled peptide served as control. Exocytosis was monitored with membrane capacitance measurements. Beginning one minute after break-in, a 1s stimulation, sufficient to deplete the releasable pool, was given every 60 seconds. The first exocytotic response was not significantly altered by the syntaxin3B peptide. However, by the fourth pulse, the exocytotic response in terminals dialyzed with the syntaxin3B peptide was reduced by 89% relative to the first, whereas that with the control peptide was reduced by only 45% (p < 0.04). This effect was not due to a reduction in calcium influx. Next, we implemented a pulse train protocol that captures the three components of release. Control terminals showed both depletion and replenishment of the pools. Terminals dialyzed with the syntaxin3B peptide showed: 1) immediate loss of the exocytotic component attributed to the reserve pool 2) decreased refilling of the rapid and releasable pools. The results demonstrate that reserve pool vesicles are unlike those in the rapid and releasable pools. It is likely that pool refilling is inhibited by the syntaxin3B peptide because reserve vesicles establish new SNARE complexes when they join a fusion-competent vesicle pool.
Physiological consequences of changes in life form of the Mexican epiphyte Tillandsia deppeana (Bromeliaceae)

The heterophyllous epiphyte Tillandsia deppeana exhibits an atmospheric habit as a juvenile and a tank form as an adult. Both juveniles and adults utilize C3 photosynthesis. This is the first report of an atmospheric form of Tillandsia which does not exhibit CAM. Photosynthetic saturation occurred at approximately 10% of full sunlight in both forms, but the adults exhibited greater rates of photosynthesis at all levels of irradiance. The adults also had a higher and broader photosynthetic temperature optimum than did the juveniles. The adults transpired at greater rates than the juveniles; however, the water use efficiencies of both forms were similar and were high for C3 plants. In both forms the photosynthetic rate decreased in response to a decrease in humidity. After 8 days without water the juveniles were able to fix CO2 throughout the day. The adults, however, exhibited a net loss of CO2 on the second day without water and thereafter. These results indicate that the water-conservative atmospheric juvenile of T. deppeana is well adapted to establishment in the epiphytic habitat.
Adaptive Time Stepping–Operator Splitting Strategy to Couple Implicit Numerical Hydrodynamic and Water Quality Codes

AbstractHydrodynamic and water quality codes have been frequently linked. These have typically been linked with both the hydrodynamic and water quality models using similar explicit time steps, but for long-term simulations implicit models are required. The water quality codes linked to these hydrodynamic codes are forced to perform their computations using the hydrodynamic time step even though utilizing the same might result in drifting of the water quality solution. This technical note presents the development and testing of an operator splitting–derived method for linking hydrodynamic and water quality codes with adaptive time stepping. The resulting method provides high-fidelity solutions that compare well with analytic solutions and lends itself for extension to various other transported quantities.
Childhood CNS inflammatory demyelinating diseases

CNS inflammatory demyelinating diseases (CIDD) are rare. At first presentation children are diagnosed with acute disseminated encephalomyelitis (ADEM) or a clinically isolated syndrome (CIS) such as transverse myelitis (TM) or optic neuritis (ON). Many of these disorders are monophasic, however a small number of children relapse and are diagnosed with multiple sclerosis (MS) or neuromyelitis optica (NMO). Paediatric onset Multiple Sclerosis (POMS) is a chronic inflammatory neurodegenerative demyelinating disease of the CNS that is usually relapsing-remitting at onset. There has been significant recent interest and progress in these disorders. Encephalopathy (behavioural change or altered consciousness) distinguishes ADEM from other demyelinating conditions. A high index of suspicion for CIDD is required in children presenting with neurological deficits, encephalopathy or status epilepticus. Several UK and international studies are underway to further our understanding of these diseases. There has been significant development of new treatments for MS and NMO. A national service for these rare disorders will enable better management of these well deserving patients. In this review we describe current understanding of the epidemiology, pathogenesis, clinical features, outcome and management of childhood CIDD.
Fast Hadamard transform based on a simple matrix factorization

This correspondence presents a simple factorization of the Hadamard matrix which is used to develop a fast algorithm for the Hadamard transform. The matrix decomposition is of the form of the Kronecker products of identity matrices and successively lower order Hadamard matrices. This decomposition leads very clearly to a sparse-matrix factorization of the Hadamard matrix.
Electron-impact ionization of Be +

The electron-impact ionization cross section for ${\mathrm{Be}}^{+}$ has been measured from threshold to 1600 eV with an absolute uncertainty of 8%. The cross section has a peak value of 46.5 \ifmmode\times\else\texttimes\fi{} ${10}^{\ensuremath{-}18}$${\mathrm{cm}}^{2}$ at an energy of \ensuremath{\sim} 50 eV, and structure ascribed to the excitation autoionization of the $1s2s2p$ state at 118.5 eV is observed. Calculations using the semiempirical formula of Lotz for direct ionization and the semiempirical effective Gaunt-factor formula for excitation autoionization give summed cross-section values which agree well with the experiment over the entire energy range. Comparisons are also made with other calculations and cross sections in the literature.
Maximum Fiber-Packing Density in Electrostatic Flocking:

The maximum fiber-packing density expected in electrostatic flocking or any process involving random impingement of fibers onto a substrate has been calculated using a Monte Carlo technique. This v...
Forced expression of Genesis, a winged helix transcriptional repressor isolated from embryonic stem cells, blocks granulocytic differentiation of 32D myeloid cells.

We recently isolated and characterized a novel member of the winged helix (formerly HNF-3/Forkhead) transcriptional regulatory family, termed Genesis. Genesis was found to be a transcriptional repressor expressed almost exclusively in embryonic stem cells or embryonal carcinoma cells. This expression rapidly declined when these cells were stimulated to differentiate. This expression pattern suggested that Genesis may play a role in cellular differentiation. To explore that possibility in a heterologous system of differentiation, Genesis was stably transduced into the IL-3-dependent myeloid cell line 32D using a retroviral expression vector. 32D cells over-expressing Genesis failed to mature normally when stimulated with G-CSF but continued to proliferate and maintained a primitive phenotype. This finding implicates Genesis in the regulation of development, and also implies that there may be common transcription pathways for many developing tissues.
Selenite distribution in log and confluent growth phase murine mammary epithelial cells

Abstract Two highly selenite sensitive cell lines with different growth rates were used to evaluate the effect of cell growth phase on selenite retention, selenite distribution, selenite inhibition of DNa synthesis and presence of selenoproteins. Autoradiography of log and confluent phase MOD cells revealed a uniform retention of selenite in log phase cells and a marked lack of uniformity of selenite retention in confluent phase cells. A higher total percentage of selenite was retained and covalently incorporated into proteins by confluent phase cells. Levels of the 58K selenoprotein, but not the 26K and 23K selenoproteins, were higher in confluent versus log phase cells. The results suggest that the 58K selenoprotein accumulated in cell populations where DNA synthesis was inhibited in contrast to cells actively undergoing cell proliferation. In addition, the 58K selenoprotein was the only major seleno-protein present in both log and confluent phase cells during and before inhibition of DNA synthesis. The implications of these results are discussed in terms of potential combination chemoprevention protocols in animal tumor experiments.
Immune responses of pony foals during repeated infections of Strongylus vulgaris and regular ivermectin treatments

Ten helminth-free pony foals divided into three groups were used in this study. Eight foals were each experimentally infected per os with 50 Strongylus vulgaris infective larvae weekly for 4 weeks, at which time one foal died of acute verminous arteritis. The remaining seven foals subsequently received 50 S. vulgaris infective larvae every 2 weeks for an additional 20 weeks. Four of the infected foals remained untreated (Group 1) and three of the infected foals were given ivermectin at 8, 16 and 24 weeks post initial infection (Group 2). Two foals served as controls (Group 3). Foals in Group 1 developed eosinophilia, which was sustained throughout the course of infection. A mild eosinophilia also developed in Group 2 foals; however, the eosinophil numbers were markedly reduced for 3 weeks after each ivermectin treatment. Only foals in Group 1 developed significant (P < 0.05) hyperproteinemia, hyperbetaglobulinemia and a reversal of the albumin/globulin (A/G) ratio 4 weeks after initial infection. Significant (P < 0.05) IgG anti-S. vulgaris ELISA titers developed in foals in Groups 1 and 2 3 weeks after infection and were sustained for the duration of the experiment. Western blot analysis of soluble somatic antigens of S. vulgaris adult female and male worms probed with sera from foals in Groups 1 and 2 revealed only subtle differences between these animals. The blastogenic reactivity of peripheral blood mononuclear cells (PBMC) to phytohemagglutinin and concanavalin A was not significantly different between groups. Peripheral blood mononuclear cells from foals in Groups 1 and 2 developed significant (P < 0.05) blastogenic reactivity to S. vulgaris soluble adult somatic antigen when examined at 25 weeks after infection. Mesentric lymph node cells from foals in Group 2, although not statistically significant, were more reactive to antigen than were the mesentric lymph node cells from foals in Group 1 when examined at 27 weeks after infection. These results suggest that significant alterations in the immune response of ponies to S. vulgaris does not occur after intravascular killing of larvae by ivermectin treatments.
A Framework for Understanding the Association Between Food Insecurity and Children's Developmental Outcomes

ABSTRACT—Food insecurity, defined as limited or uncertain availability of nutritionally adequate and safe foods or limited or uncertain ability to acquire acceptable foods in socially acceptable ways, is still a problem in the United States. It is associated with poor parenting practices, poor health, and socioemotional and cognitive/academic difficulties in children. This review synthesizes some of these findings and suggest links among these outcomes. In this endeavor, it describes the concept of food insecurity and propose a mediational framework to anchor our discussions. Finally, it examines the implications of the review for research and policy.
Identification of Cardiac Dysfunction in Sepsis with B-Type Natriuretic Peptide

Background B-type natriuretic peptide (BNP) is secreted in response to myocardial stretch and has been used clinically to assess volume overload and predict death in congestive heart failure. More recently, BNP elevation has been demonstrated with septic shock and is predictive of death. How BNP levels relate to cardiac function in sepsis remains to be established. Study Design Retrospective review of prospectively gathered sepsis database from a surgical ICU in a tertiary academic hospital. Initial BNP levels, patient demographics, baseline central venous pressure levels, and in-hospital mortality were obtained. Transthoracic echocardiography was performed during initial resuscitation per protocol. Results During 24 months ending in September 2009, two hundred and thirty-one patients (59 ± 3 years of age, 43% male) were treated for sepsis. Baseline BNP increased with initial sepsis severity (ie, sepsis vs severe sepsis vs septic shock, by ANOVA; p R s = .001) for the entire sepsis population. Conclusions In surgical sepsis patients, BNP increases with sepsis severity and is associated with early systolic dysfunction, which in turn is associated with death. Monitoring BNP in early sepsis to identify occult systolic dysfunction might prompt earlier use of inotropic agents.
Polarized Raman scattering from oriented single microcrystals of d(A5T5)2 and d(pTpT).

Polarized Raman spectra have been obtained from single microcrystals of the duplex of the decamer d(A5T5)2 using a Raman microscope. This is the first report of Raman spectra from a crystal of a deoxyoligomer that contains only long, nonalternating sequences of adenine and thymine. Sequences containing d(A)n and d(T)n are of interest in view of recent suggestions that they induce bends in DNA and that they might exist in a nonstandard B-conformation. Polarized Raman spectra of a crystal of d(pTpT) have also been obtained. Both crystals display Raman bands whose intensities are very sensitive to the orientation of the crystal with respect to the direction of polarization of the incident laser beam. These spectra indicate that the helical axes of the oligonucleotides are parallel to the long axes of the crystals and that the d(A5T5)2 is not appreciably bent in the crystal. The Raman spectrum from the d(pTpT) crystal indicates that all of the furanose ring puckers are in a C2′-endo configuration since only the C2′-endo marker band at 835 ± 5 cm−1 is present. Crystals of d(A5T5)2 show measurable Raman intensities in both the 838- and 816-cm−1 bands. This indicates the presence of both the C2′-endo and C3′-endo, or possibly other non-C2′-endo, furanose conformations. The 816-cm−1 band is weak so that only a small fraction of the residues are estimated to be in the non-C2′-endo conformation. In both the d(pTpT) and d(A5T5)2 crystals the intensity of the bands due to vibrations of the backbone show only a small dependence on orientation of the crystals. This result is explained by the low symmetry of the puckered sugar rings. It is concluded that Raman spectra obtained from oligonucleotide crystals in which the orientation of the crystal axes to the laser polarization is not carefully controlled may contain intensity artifacts that are due to polarization effects.
Induction of apoptosis during development of hypertensive nephrosclerosis

Induction of apoptosis during development of hypertensive nephrosclerosis. Background As the biology of programmed cell death, or apoptosis, is clarified, a role for this process in the pathophysiology of organ dysfunction and fibrosis has been hypothesized. Hypertensive nephrosclerosis represents an important cause of end-stage renal disease. One model of the progressive, noninflammatory, sclerotic renal lesion of hypertension is the Dahl/Rapp salt-sensitive rat, which was examined in this study. Methods Male, Dahl/Rapp salt-sensitive (SS) and Sprague-Dawley rats were placed on either 0.3 or 8.0% NaCl diets for three weeks. Blood pressure was determined, and the kidneys were harvested for histochemical analysis and to obtain total RNA for RNase protection assays and total protein for Western blotting. Results An increase in apoptosis in the glomerular and tubular compartments was observed only in kidneys of SS rats on the high-salt diet. These findings occurred at a time when renal function was markedly impaired and irreversible changes in renal morphology developed. Temporally associated with this increase in apoptosis was augmented expression of pro-apoptotic molecules that included Fas, Bax, and Bcl-XS. Conclusions The inappropriate shift in expression of proteins that facilitate apoptosis in the nephron, along with ongoing cell death that manifested at a time when renal function was deteriorating, supported an important role for this process in development of hypertensive nephrosclerosis.
Mechanisms Regulating Endothelial Permeability

The endothelial monolayer partitioning underlying tissue from blood components in the vessel wall maintains tissue fluid balance and host defense through dynamically opening intercellular junctions. Edemagenic agonists disrupt endothelial barrier function by signaling the opening of the intercellular junctions leading to the formation of protein-rich edema in the interstitial tissue, a hallmark of tissue inflammation that, if left untreated, causes fatal diseases, such as acute respiratory distress syndrome. In this review, we discuss how intercellular junctions are maintained under normal conditions and after stimulation of endothelium with edemagenic agonists. We have focused on reviewing the new concepts dealing with the alteration of adherens junctions after inflammatory stimulus.
Phase-Locked Loop Bandwidth and Signal-to-Noise-Ratio Requirements for Deep-Space Communications

Properly designed phase-locked loops play a key role in deep-space communication links. The interrelationships among the loop band-width, acquisition time, and the loop signal-to-noise ratio are established for a given probability of acquisition. The Doppler rate tracking capability of the second-order loop is considered. The probability of time to lose lock is derived by the Fokker-Planck techniques. The results of the study are used to determine the loop bandwidth and the signal-to-noise ratio requirements of Venus and Jupiter probes' communication links.
Gastroesophageal Reflux Disease

A 53-year-old man, who is otherwise healthy and has a 20-year history of occasional heartburn, reports having had worsening heartburn for the past 12 months, with daily symptoms that disturb his sleep. He reports having had no dysphagia, gastrointestinal bleeding, or weight loss and in fact has recently gained 20 lb (9 kg). What would you advise regarding his evaluation and treatment?
Homeland Security and Public Health: A Critical Integration

In the wake of a series of tragic events impacting public health in the United States, the Department of Health and Human Services Centers for Disease Control and Prevention and the Department of Homeland Security have attempted to facilitate information sharing across public health and homeland security organizations. Data collected as part of a national assessment of law enforcement and homeland security information sharing, funded by the National Institute of Justice, indicate such efforts to date have been helpful in establishing a foundation for information sharing, yet fall short of creating mechanisms by which tangible information sharing can occur. Recent initiatives to remedy this shortcoming are presented and recommendations for further success are discussed.
The Developmental Priority of the Evaluative Dimension in Perceptions of Nonverbal Cues

Researchers who have attempted to map the basic structure of broad psychological domains (such as interpersonal behavior) have invariably pointed to the importance of the evaluative dimension. It was predicted that sensitivity to such a salient dimension would develop prior to sensitivity to other important but apparently weaker dimensions, such as dominance-submissiveness. The predicted developmental trend was supported in a study of nonverbal decoding. When judging pairs of emotional cues communicated by the face or body and by the tone of voice, younger subjects, compared to older ones, were more likely to notice discrepancies in the degree of expressed positivity than in the degree of expressed dominance.
Modulation of lung epithelial functions by Pseudomonas aeruginosa

Microorganisms gain access to the airways and respiratory epithelial surface during normal breathing. Most inhaled microbes are trapped on the mucous layer coating the nasal epithelium and upper respiratory tract, and are cleared by ciliary motion. Microorganisms reaching the alveolar spaces are deposited on the pulmonary epithelium. This contact initiates complex offensive and defensive strategies by both parties. Here, we briefly outline how the pulmonary pathogen Pseudomonas aeruginosa uses multi-pronged strategies that include cell surface appendages, and secreted and injected virulence determinants to switch from an unobtrusive soil bacterium to a pathogen for lung epithelium colonization. Understanding the complex interactions between the lung epithelium and P. aeruginosa might enable more effective therapeutic strategies against infection in cystic fibrosis and immuno-compromized individuals.
Appraisal of the Yonki Dam hydroelectric project

Work began in November 1986 on the construction of Yonki Dam in the Eastern Highlands Province of Papua New Guinea. By the time it is commissioned in 1990 the project is expected to cost about US$75 million in constant 1984 prices, making it the largest public sector project ever undertaken in Papua New Guinea. This paper describes how the decision was made to undertake the project. Attention is focused on the sensitivity of such projects to the load forecast for electricity and the significance of the ‘biases’ held by the various participants (such as engineers, aid agencies and government economists) in the decision-making process. It illustrates the difficulties involved in trying to carry out an ‘objective’ economic appraisal of a marginal project.
Cysteine-Disulfide Cross-linking to Monitor SNARE Complex Assembly during Endoplasmic Reticulum-Golgi Transport

Assembly of cognate SNARE proteins into SNARE complexes is required for many intracellular membrane fusion reactions. However, the mechanisms that govern SNARE complex assembly and disassembly during fusion are not well understood. We have devised a new in vitro cross-linking assay to monitor SNARE complex assembly during fusion of endoplasmic reticulum (ER)-derived vesicles with Golgi-acceptor membranes. In Saccharomyces cerevisiae, anterograde ER-Golgi transport requires four SNARE proteins: Sec22p, Bos1p, Bet1p, and Sed5p. After tethering of ER-derived vesicles to Golgi-acceptor membranes, SNARE proteins are thought to assemble into a four-helix coiled-coil bundle analogous to the structurally characterized neuronal and endosomal SNARE complexes. Molecular modeling was used to generate a structure of the four-helix ER-Golgi SNARE complex. Based on this structure, cysteine residues were introduced into adjacent SNARE proteins such that disulfide bonds would form if assembled into a SNARE complex. Our initial studies focused on disulfide bond formation between the SNARE motifs of Bet1p and Sec22p. Expression of SNARE cysteine derivatives in the same strain produced a cross-linked heterodimer of Bet1p and Sec22p under oxidizing conditions. Moreover, this Bet1p-Sec22p heterodimer formed during in vitro transport reactions when ER-derived vesicles containing the Bet1p derivative fused with Golgi membranes containing the Sec22p derivative. Using this disulfide cross-linking assay, we show that inhibition of transport with anti-Sly1p antibodies blocked formation of the Bet1p-Sec22p heterodimer. In contrast, chelation of divalent cations did not inhibit formation of the Bet1p-Sec22p heterodimer during in vitro transport but potently inhibited Golgi-specific carbohydrate modification of glyco-pro-α factor. This data suggests that Ca2+ is not directly required for membrane fusion between ER-derived vesicles and Golgi-acceptor membranes.
Detection of Alkaline Ultrafine Atmospheric Particles at Bakersfield, California

Two collocated micro-orifice uniform deposit impactors (MOUDIs) and a filter-based sampler were used to measure the size distribution and chemical composition of atmospheric particulate matter at Bakersfield, CA, between January 14 and 23, 1999. The peak number concentration of airborne ultrafine particles measured was 1.45 × 1011 m-3, which is a factor of approximately 3 higher than the peak airborne ultrafine-particle number concentration measured previously in Pasadena, CA. Chemical analysis revealed that airborne ultrafine particles (Dp < 0.1 μm) at Bakersfield contained significant amounts of water-soluble species, including calcium, sodium, ammonium ion, nitrate, and sulfate. Other chemical species detected in the ultrafine size range included potassium, iron, copper, zinc, and strontium. A balance of aqueous ions showed that ultrafine particles were alkaline in nature with calcium acting as the dominant cation. Bulk samples of airborne particles with diameter less than 2.0 μm (PM2.0) were essential...
Utility of network integrity methods in therapeutic target identification

Analysis of the biological gene networks involved in a disease may lead to the identification of therapeutic targets. Such analysis requires exploring network properties, in particular the importance of individual network nodes (i.e., genes). There are many measures that consider the importance of nodes in a network and some may shed light on the biological significance and potential optimality of a gene or set of genes as therapeutic targets. This has been shown to be the case in cancer therapy. A dilemma exists, however, in finding the best therapeutic targets based on network analysis since the optimal targets should be nodes that are highly influential in, but not toxic to, the functioning of the entire network. In addition, cancer therapeutics targeting a single gene often result in relapse since compensatory, feedback and redundancy loops in the network may offset the activity associated with the targeted gene. Thus, multiple genes reflecting parallel functional cascades in a network should be targeted simultaneously, but require the identification of such targets. We propose a methodology that exploits centrality statistics characterizing the importance of nodes within a gene network that is constructed from the gene expression patterns in that network. We consider centrality measures based on both graph theory and spectral graph theory. We also consider the origins of a network topology, and show how different available representations yield different node importance results. We apply our techniques to tumor gene expression data and suggest that the identification of optimal therapeutic targets involving particular genes, pathways and sub-networks based on an analysis of the nodes in that network is possible and can facilitate individualized cancer treatments. The proposed methods also have the potential to identify candidate cancer therapeutic targets that are not thought to be oncogenes but nonetheless play important roles in the functioning of a cancer-related network or pathway.
Neotropical Tineidae VIII: Falsivalva, a new genus from Austral South America with extreme modification of the male postabdominal terga (Lepidoptera: Tineidae).

Abstract Falsivalva, new genus is described and illustrated. In addition to the previously named type species, “Tinea” prensoria Meyrick, three new species, F. clavata, F. nephophila, and F. paraprensoria, are described. The most conspicuous synapomorphy of Falsivalva is the highly specialized tergum IX (tegumen) of the male, which is greatly enlarged and almost completely divided to resemble the male gonopods (valvae). It is suggested, but not observed, that these paired structures may function either to guide or clasp the female oviscapt during copulation. The genus occurs in both coastal and Andean Nothofagus forests primarily in southern Chile from approximately 35°S in Maule Province south to about 45° in Chiloe Island and east to Neuquen Province, Argentina. The biology is unknown.
Interest Differentiation in High School and Vocational Indecision in College.

Abstract Vocational indecision was defined as being both a college upperclassman and having no major. In a sample of 1622 students in college for three years, 24% indecisive students were found and compared with vocationally decisive students (having majors) using precollege measures of achievement, aptitude, and interest. Measures of interest differentiation were of particular concern. Indecisiveness was best predicted from present and past achievement measures, e.g., cumulative college GPA or high school mathematics GPA. Interest predictors slightly augmented the multiple correlation including Outdoor interest, Business Contact interest, and interest differentiation. Most important to vocational indecision in these juniors and seniors, however, was lower academic achievement.
Calculations of pH-dependent binding of proteins to biological membranes

Binding of proteins to membranes is often accompanied by titration of ionizable residues and is, therefore, dependent on pH. We present a theoretical treatment and computational approach for predicting absolute, pH-dependent membrane binding free energies. The standard free energy of binding, ΔG, is defined as −RT ln(Pb/Pf), where Pb and Pf are the amounts of bound and free protein. The apparent pKa of binding is the pH value at which Pb and Pf are equal. Proteins bind to the membrane in the pH range where ΔG is negative. The components of the binding free energy are (a) the free energy cost of ionization state changes (ΔGion), (b) the effective energy of transfer from solvent to the membrane surface, (c) the translational/rotational entropy cost of binding, and (d) an ideal entropy term that depends on the relative volume of the bound and free state and therefore depends on lipid concentration. Calculation of the first term requires determination of pKa values in solvent and on the membrane surface. All ...
Short-run money demand functions: Estimated speeds of adjustment and serial correlation

Parameter estimates in short-run money demand functions begin to behave badly when the sample includes data before and after say 1973, when the “missing money” becomes important. For example, the estimated speed of adjustment becomes implausibly slow. In such cases, there are often multiple minima in the error sum of squares taken as a function of the autocorrelation parameter ρ. Low ρ's give implausible estimates, larger ρ's more plausible. The ESS should always be searched for such sensitivity. First differencing is not generally a good practice, but is sometimes useful.
A new technique for evaluating volume sensitivity of ion channels.

A new technique is described for evaluating the volume sensitivity of both endogenous and expressed ion channels in Xenopus oocytes. The technique utilizes vesicles derived from inside-out, excised patches and permits evaluation of volume sensitivity at the single-channel level, which is not possible with whole oocytes since removal of the vitelline membrane renders oocytes too fragile to withstand osmotic stress. Using this method, the volume sensitivity of the normally occurring oocyte mechanosensitive (SA-cat) channel was assessed. In 12 experiments, osmotic swelling increased vesicle volume by an average of 60 ± 8% and increased the surface area of the inner side of the vesicle by 47 ± 10%. This was associated with an increase in mean number of open channels (NP o) from zero (unswollen) to 0.1 ±0.02 (after 5 min). Hence, oocyte SA-cat channels are volume as well as stretch sensitive, where the volume sensitivity may involve cytoskeletal elements adhering to the membrane but probably does not involve freely diffusible components of the original oocyte.