bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of early visual cortex in visual integration: a neural model of recurrent interaction
Authors: Deco Gustavo , Lee Tai Sing
Published: August 2004

This paper presents a model on the potential functional roles of the early visual cortex in the primate visual system. Our hypothesis is that early visual areas, such as V1, are important for continual interaction among various higher order visual areas during visual processing. The interaction is mediated by recurrent connections between higher order visual areas and V1, manifested in the long‐latency context‐sensitive activities often observed in neurophysiological experiments, and is responsible for the re‐integration of information analysed by the higher visual areas. Specifically, we considered the case of integrating ‘what’ and ‘where’ information from the ventral and dorsal streams. We found that such a cortical architecture provides simple solutions and fresh insights into the problems of attentional routing and visual search. The computational viability of this architecture was tested by simulating a large‐scale neural dynamical network.
Expression and immunohistochemical localization of vesicular glutamate transporter 2 in the migratory pathway from the rat olfactory placode
Authors: Honma Shizuka , Kawano Michihiro , Hayashi Shinji , Kawano Hitoshi , Hisano Setsuji
Published: August 2004

The localization of vesicular glutamate transporter 2 (VGLUT2) was examined by immunohistochemistry and in situ hybridization histochemistry in the developing rat olfactory region with special relation to the spatiotemporal location of NCAM, a neural cell adhesion molecule expressed in differentiated neurons, and the calcium‐binding protein calbindin D‐28k, a marker of neurons migrating from the vomeronasal organ anlage (Y. Toba et al. (2001) J. Neuroendocrinol., 13, 683–694). Both VGLUT2 and NCAM immunoreactivities were first detected at embryonic day 11.5 (E11.5) in the neuronal cell mass beneath the telencephalic vesicle. After E12.5, VGLUT2‐immunoreactive cells were detected in the migratory pathways from both medial and lateral olfactory pits, anlagen of the vomeronasal organ and olfactory epithelium. Between E15.5 and E19.5, moderate to intense VGLUT2 immunoreactivity was observed in cell clusters situated along NCAM‐bearing vomeronasal nerves, and frequently colocalized with calbindin D‐28k immunoreactivity. Using in situ hybridization histochemistry, VGLUT2 mRNA signals were detected in the clustered cells as well as in cells of the vomeronasal and olfactory epithelium. After E20.5, migrating cells gradually decreased in number and VGLUT2 immunoreactivity attenuated in the clustered cells, although calbindin D‐28k immunoreactivity in these residual cells was still intense. The presence of intense VGLUT2 immunoreactivity in neurons actively migrating from the olfactory placode suggests that this transporter is involved in the migratory process of these neurons.
Changes in motoric, exploratory and emotional behaviours and neuronal acetylcholine content and 5‐HT turnover in histidine decarboxylase‐KO mice
Authors: Dere E. , De Souza‐Silva M. A. , Spieler R. E. , Lin J. S. , Ohtsu H. , Haas H. L. , Huston J. P.
Published: August 2004

Histamine has been implicated, inter alia, in mechanisms underlying arousal, exploratory behaviour and emotionality. Here, we investigated behavioural and neurochemical parameters related to these concepts, including open‐field activity, rotarod performance and anxiety, as well as brain acetylcholine and 5‐HT concentrations of mice deficient for the histidine decarboxylase (HDC) gene. These mice are unable to synthesize histamine from its precursor histidine. The HDC‐knockout mice showed reduced exploratory activity in an open‐field, but normal habituation to a novel environment. They behaved more anxious than the controls, as assessed by the height–fear task and the graded anxiety test, a modified elevated plus‐maze. Furthermore, motor coordination on the rotarod was superior to controls. Biochemical assessments revealed that the HDC‐knockout mice had higher acetylcholine concentrations and a significantly higher 5‐HT turnover in the frontal cortex, but reduced acetylcholine levels in the neostriatum. These results are suggestive of important interactions between neuronal histamine and these site‐specific neurotransmitters, which may be related to the behavioural changes found in the HDC‐deficient animals.
Differential expression of voltage‐activated calcium channels in III and XII motoneurones during development in the rat
Authors: Miles Gareth B. , Lipski Janusz , Lorier Amanda R. , Laslo Peter , Funk Gregory D.
Published: August 2004

To further our understanding of the role that voltage‐activated Ca2+ channels play in the development, physiology and pathophysiology of motoneurones (MNs), we used whole‐cell patch‐clamp recording to compare voltage‐activated Ca2+ currents in oculomotor (III) and hypoglossal (XII) MNs of neonatal [postnatal day (P)1–5] and juvenile (P14–19) rats. In contrast to III MNs that innervate extraocular muscles, XII MNs that innervate tongue muscles mature more rapidly, fire bursts of low frequency action potentials and are vulnerable to degeneration in amyotrophic lateral sclerosis. In neonates, low voltage‐activated (LVA) Ca2+ current densities are similar in XII and III MNs but high voltage‐activated (HVA) Ca2+ current densities are twofold higher in XII MNs. The HVA Ca2+ channel antagonists (nimodipine and nifedipine for L‐type, ω‐agatoxin‐TK for P/Q‐type and ω‐conotoxin‐GVIA for N‐type) revealed that, while N‐ and P/Q‐type HVA Ca2+ channels are present in both MN pools, a 3.5‐fold greater P/Q‐type Ca2+ current in XII MNs accounts for their greater HVA Ca2+ currents. Developmentally, LVA and HVA Ca2+ current densities decrease in III MNs but remain unchanged in XII MNs. Thus, the differences between these MN pools increase developmentally so that, in juveniles, the LVA Ca2+ current density is twofold greater and the HVA Ca2+ current density is threefold greater in XII compared with III MNs. We propose that this differential expression of LVA and HVA Ca2+ channels in XII and III MNs during development contributes to their distinct physiology and may also be a factor contributing to the greater susceptibility of XII MNs to degeneration as seen in amyotrophic lateral sclerosis.
TNF‐α accounts for short‐term persistence of oxidative status in rat brain after two weeks of repeated stress
Authors: Munhoz Carolina , Madrigal José L. M. , García‐Bueno Borja , Pradillo Jesús M. , Moro María A. , Lizasoain Ignacio , Lorenzo Pedro , Scavone Cristoforo , Leza Juan C.
Published: August 2004

Inducible nitric oxide synthase (NOS‐2) accounts for the accumulation of oxidative and nitrosative mediators in brain after stress. To determine whether and when repeated exposure to immobilization stress leads to persistent oxidative status in rat brain, male Wistar rats were immobilized for 6 h/day for 7 or 14 days (S7, S14). Cerebral cortices were obtained immediately after the last session of stress or 1 day later. Stress increased NOS‐2 activity after S7 or S14. This enzymatic activity returned to basal values 1 day after S7, but not 1 day after S14. Stress increased malondialdehyde (MDA) accumulation in cortex after S7 and S14. MDA levels returned to basal values 1 day after S7 but not 1 day after S14. In order to elucidate the possible mechanisms involved in this short‐term persistence of oxidative status, brain levels of the cytokine tumour necrosis factor alpha (TNF‐α) were determined. TNF‐α levels did not increase after S7 or 1 day after S7, but increased after S14 and 1 day after S14. This was paralleled by an increase in TNF‐α converting enzyme (TACE) activity in brain. When the increase in TNF‐α at S14 was blocked by BB1101, an inhibitor of TACE, or its effects were blocked with anti‐TNF‐α, the accumulation of MDA and NOS‐2 activity 1 day after S14 did not take place. These findings indicate that TACE and TNF‐α account for stress‐induced short‐term persistence of NOS‐2 activity and MDA accumulation after 14 days of repeated exposure and support a possible neuroprotective role for specific blockers of TNF‐α in this situation.
Quantifying the accessibility of the metagenome by random expression cloning techniques
Authors: Gabor Esther M. , Alkema Wynand B. L. , Janssen Dick B.
Published: August 2004

The exploitation of the metagenome for novel biocatalysts by functional screening is determined by the ability to express the respective genes in a surrogate host. The probability of recovering a certain gene thereby depends on its abundance in the environmental DNA used for library construction, the chosen insert size, the length of the target gene, and the presence of expression signals that are functional in the host organism. In this paper, we present a set of formulas that describe the chance of isolating a gene by random expression cloning, taking into account the three different modes of heterologous gene expression: independent expression, expression as a transcriptional fusion and expression as a translational fusion. Genes of the last category are shown to be virtually inaccessible by shotgun cloning because of the low frequency of functional constructs. To evaluate which part of the metagenome might in this way evade exploitation, 32 complete genome sequences of prokaryotic organisms were analysed for the presence of expression signals functional in E. coli hosts, using bioinformatics tools. Our study reveals significant differences in the predicted expression modes between distinct taxonomic groups of organisms and suggests that about 40% of the enzymatic activities may be readily recovered by random cloning in E. coli.
Phylogeny–function analysis of (meta)genomic libraries: screening for expression of ribosomal RNA genes by large‐insert library fluorescent in situ hybridization (LIL‐FISH)
Authors: Leveau Johan H. J. , Gerards Saskia , De Boer Wietse , Van Veen Johannes A.
Published: August 2004

We assessed the utility of fluorescent in situ hybridization (FISH) in the screening of clone libraries of (meta)genomic or environmental DNA for the presence and expression of bacterial ribosomal RNA (rRNA) genes. To establish proof‐of‐principle, we constructed a fosmid‐based library in Escherichia coli of large‐sized genomic DNA fragments of the mycophagous soil bacterium Collimonas fungivorans, and hybridized 768 library clones with the Collimonas‐specific fluorescent probe CTE998‐1015. Critical to the success of this approach (which we refer to as large‐insert library FISH or LIL‐FISH) was the ability to induce fosmid copy number, the exponential growth status of library clones in the FISH assay and the use of a simple pooling strategy to reduce the number of hybridizations. Twelve out of 768 E. coli clones were suspected to harbour and express Collimonas 16S rRNA genes based on their hybridization to CTE998‐1015. This was confirmed by the finding that all 12 clones were also identified in an independent polymerase chain reaction‐based screening of the same 768 clones using a primer set for the specific detection of Collimonas 16S ribosomal DNA (rDNA). Fosmids isolated from these clones were grouped by restriction analysis into two distinct contigs, confirming that C. fungivorans harbours at least two 16S rRNA genes. For one contig, representing 1–2% of the genome, the nucleotide sequence was determined, providing us with a narrow but informative view of Collimonas genome structure and content.
Mechanisms of Optimized Biventricular Pacing in Pulmonary Stenosis:
Authors: RABKIN DAVID G. , CABRERIZA SANTOS E. , CURTIS LAUREN J. , QUINN T. ALEXANDER , WEINBERG ALAN D. , HORDOF ALAN D. , SPOTNITZ HENRY M.
Published: August 2004

We tested the hypothesis that optimized biventricular pacing (BiVP) enhances cardiac output (CO) during critical pulmonary stenosis (PS) by attenuating distortions in left ventricular (LV) geometry. Following median sternotomy in six anesthetized pigs, heart block was induced by ethanol ablation. During epicardial, DDD BiVP, atrioventricular delay (AVD) was varied from 60 ms to 180 ms in 30 ms increments. At the AVD with the highest CO right‐left delay (RLD) was varied from (+) 80 ms (RV first) to (−) 80 ms (LV first) in 20 ms increments. At each pacing setting, aortic flow, ECG, and LV diameter were measured in the control state (CON) and during PS, created by snaring the pulmonary artery until CO decreased 50%. Short axis LV echocardiograms were obtained at (+) and (−) 80 ms. In CON, RLD had no effect on function or geometry. During PS optimum BiVP resulted in significant increases in CO (1.12 L/min ± 0.13 SEM at RLD =+ 40 ms versus 0.92 ± 0.12 at RLD = 0 and 0.73 ± 0.08 at RLD =−80), and LV fractional shortening (8.97%± 0.51% at RLD =+ 40 ms versus 7.34%± 0.58% at RLD = 0 and 6.21%± 0.66% at RLD =−80). In addition, LV eccentricity with (−) RLD was significantly different versus CON at both end‐diastole (0.79 ± 0.07 vs 1.02 ± 0.03, P = 0.011 Student's t‐test) and end‐systole (0.83 ± 0.05 vs 1.00 ± 0.02, P = 0.017). However, with (+) RLD differences versus CON were not significant at either end‐diastole (0.88 ± 0.06 vs 0.99 ± 0.03) or end‐systole (0.92 ± 0.03 vs 1.01 ± 0.03). In swine hearts with PS, optimized BiVP increases CO, fractional shortening, and LV symmetry. BiVP warrants further study as treatment for acute postoperative heart failure.
Immediate and 1‐Year Survival of Out‐of‐Hospital Cardiac Arrest Victims in Southern New Jersey:
Authors: GUGLIN MAYA E. , WILSON ALAN , KOSTIS JOHN B. , PARRILLO JOSEPH E. , WHITE MELVIN C. , GESSMAN LAWRENCE J.
Published: August 2004

Most studies report the out‐of‐hospital cardiac arrest (OHCA) survival to hospital discharge. One‐year survival and neurological outcomes in southern New Jersey in 1996–2000 were analyzed using a retrospective data review. There were 1,597 cases of OHCA. Initial survival ranged between 15% in 2000 and 19% in 1997. Survival to hospital discharge, taken as a percent of the initial survivors, decreased from 44% in 1997 to 22% in 2000. In relation to all OHCA victims, survival to discharge decreased from 7.2% to 2.4%, respectively. On discharge from the hospital 19–50% of people had the diagnosis of anoxic brain damage. In ventricular fibrillation, survival to discharge was 41%, 46.7%, 40.7%, 37.5%, and 17.4%, respectively, from 1996 to 2000. The response time increased from 6.6 to 8.1 minutes. Correlation coefficient between in‐hospital survival and response time was −0.73. The percent of people discharged with neurological damage increased from 38% to 50%. Initial survival was 29.2% in shockable and 7.5% in nonshockable rhythm (P < 0.001). Survival to discharge was 11.3% versus 1.6%, and survival to 1 year was 9.6% versus 0.7%, respectively (P < 0.001 for all). Overall, the neurologically favorable 1‐year survival rate was 2.3% of all OHCA victims. One‐year survival of OHCA victims without neurological deficits is low. In southern New Jersey the survival rate did not improve over the 5‐year study. Not only initial (prehospital) mortality, but also “delayed” (in‐hospital mortality) increases with increase of response time.
Upgrade of Single Chamber Pacemakers with Transvenous Leads to Dual Chamber Pacemakers in Pediatric and Young Adult Patients
Authors: SILVETTI MASSIMO STEFANO , DRAGO FABRIZIO
Published: August 2004

Children with single chamber pacemakers, in adolescence and young adulthood, may be upgraded to dual chamber systems, but there are no published data about indications, timing, and complications. Upgrading was attempted in 18 patients with transvenous pacing leads. A retrospective analysis of all collected data was performed. At initial pacemaker implantation (mean ± SD, 9.3 ± 4.1 years), the pacing mode was VVIR (n = 13 patients) and AAI/AAIR (n = 5 patients). After 72 ± 41 months of follow‐up, at the age of 15.5 ± 5.2 years, upgrade was undertaken because of the patient's age at elective generator replacement (n = 3 patients), ventricular dysfunction (n = 7), syncope/presyncope (n = 3) in patients with VVIR pacing, atrioventricular block (n = 2), and/or drug refractory supraventricular tachyarrhythmias (n = 4) in patients with atrial pacing. In comparison with single chamber pacemaker implantations, the average procedural time and the average fluoroscopy time were not significantly longer. All suitable preexisting leads were incorporated in the new pacing system. Leads were inserted via the ipsilateral subclavian vein in 16 patients. Venous occlusion was found in two patients: in the first the procedure was not performed; in the second, the contralateral vein was used and the old lead was abandoned. There were no procedural complications. During a follow‐up of 14 ± 11 months, ventricular dysfunction worsened in five of seven patients; other patients benefitted symptomatically. In conclusion, pacemaker upgrade is technically challenging but feasible and safe and may be beneficial for some patients.
The Spectrum of Inter‐ and Intraventricular Conduction Abnormalities in Patients Eligible for Cardiac Resynchronization Therapy
Authors: PEICHL PETR , KAUTZNER JOSEF , ČIHÁK ROBERT , BYTEŠNÍK JAN
Published: August 2004

Although cardiac resynchronization therapy (CRT) has clearly demonstrated its clinical benefit in patients with congestive heart failure (CHF) and intraventricular conduction abnormalities, selection of eligible patients and/or optimal pacing site are still a matter of debate. The aim of the study was to analyze the spectrum of conduction abnormalities in CRT candidates. A total of 26 patients (mean age 62 ± 9 years) with CHF and conduction disturbances (QRS ≥ 130 ms) were studied. The underlying heart disease was dilated cardiomyopathy (DCM) (n = 12) or coronary artery disease (CAD) (n = 14). High density, left ventricular endocardial activation maps were constructed using an electroanatomic mapping system (CARTO). Based on endocardial activation patterns, left ventricular conduction abnormalities were classified as left bundle branch block (LBBB) (n = 9), nonspecific intraventricular conduction disturbances (n = 10), and the bifascicular block (n = 7). In DCM patients the endocardial activation sequences corresponded with a 12‐lead ECG pattern with a homogeneous spread of activation wavefront and the latest activation laterally (LBBB) or anteriorly (bifascicular block), respectively. CAD patients presented with variable activation patterns that reflected the location of the postinfarct scar, and the 12‐lead ECG was less predictive. Although there was a trend for longer QRS durations for DCM subjects (170 ± 23 vs 156 ± 23 ms, P = NS), left ventricular activation time was significantly longer in the CAD group (115 ± 21 ms vs 134 ± 23 ms, P < 0.05). CRT candidates represent a broad spectrum of conduction abnormality patterns with variable inter‐ and intraventricular activation delays. CAD subjects have more pronounced intraventricular conduction abnormality. The standard ECG is less reliable in the characterization of complex conduction abnormalities.
Enhanced Specificity of a Dual Chamber ICD Arrhythmia Detection Algorithm by Rate Stability Criteria
Authors: MLETZKO RALPH , ANSELME FREDERIC , KLUG DIDIER , SCHOELS WOLFGANG , BOWES ROBERT , ISCOLO NICOLAS , NITZSCHÉ RÉMI , SADOUL NICOLAS ,   on behalf of the“Slow VT Study” Investigators
Published: August 2004

Inappropriate therapy remains an important limitation of implantable cardioverter defibrillators (ICD). PARAD+ was developed to increase the specificity conferred by the original PARAD detection algorithm in the detection of atrial fibrillation (AF). To compare the performances of the two different algorithms, we retrospectively analyzed all spontaneous and sustained episodes of AF and ventricular tachycardia (VT) documented by state‐of‐the‐art ICDs programmed with PARAD or PARAD+ at the physicians' discretion. The results were stratified according to tachycardia rates <150 versus ≥150 beats/min. The study included 329 men and 48 women (64 ± 10 years of age). PARAD was programmed in 263, and PARAD+ in 84 devices. During a mean follow‐up of 11 ± 3 months, 1,019 VT and 315 AF episodes were documented among 338 devices. For tachycardias with ventricular rates <150 beats/min, the sensitivity of PARAD versus PARAD+ was 96% versus 99% (NS), specificity 80% versus 93% (P < 0.002), positive predictive value (PPV) 94% versus 91% (NS), and negative predictive value (NPV) 86% versus 99% (P < 0.0001). In contrast, in the fast VT zone, the specificity and PPV of PARAD (95% versus 84% and 100% versus 96%) were higher than those of PARAD+ (NS, P < 0.001). Among 23 AF episodes treated in 16 patients, 3 episodes triggered an inappropriate shock in 3 patients, all in the PARAD population. PARAD+ significantly increased the ICD algorithm diagnostic specificity and NPV for AF in the slow VT zone without compromising patient safety.
Redundant Pacing in a Child
Authors: VILLAIN ELISABETH , ELIASSON HAKAN , SIDI DANIEL
Published: August 2004

A 4‐year‐old boy with congenital complete atrioventricular block (CCAVB) and pacemaker (PM) dependency, received a redundant pacemaker. Two separate leads were implanted in the right ventricle, and connected to a dual chamber PM. The two pacing channels were both programmed so that each lead could compensate for the other in case of threshold elevation. The follow‐up was uneventful despite exit block on one of the leads.
The Family Life Cycle: Developmental Crises and Their Structural Impact on Families in a Community Mental Health Center
Authors: GARTNER RICHARD B. , FULMER RICHARD H. , WEINSHEL MARGOT , GOLDKLANK SHELLY
Published: August 2004

A typology for troubled families was developed based on the configuration of family members and the position of the identified patient within the family structure. This typology was investigated by surveying the demographic and clinical characteristics of 110 families of patients treated in a day hospital. Four types or “constellations” were found in the sample population. The families in the four Constellations differed significantly from one another in the gender, age, and diagnoses of the identified patient and the income level of the families. The Constellations thus appeared to constitute distinct clinical entities in the population studied. The reasons for the differences among Constellations are discussed in terms of the stress families experience during developmental crises involving structural change.
Can't get to the library? Then we’ll come to you. A survey of library services to people in their own homes in the United Kingdom
Authors: Ryder Julie
Published: August 2004

Abstract Aims:  To determine the current level of library service to people in their own homes in the United Kingdom and to compare it with results from previous surveys. It is many years since a similar survey has been undertaken or guidelines produced and it is hoped that this work will help fill the gap.

Methods:  A questionnaire was sent in January 2004 to all public library authorities in the UK, a total of 208; 72% (149) were returned in the timescale allowed. The questionnaire covered the criteria for eligibility to receive a home library service; service structure and delivery: who delivers the service (specialist librarians or specialist non‐professional staff, branch library staff or volunteers); training; range of material and services provided; reading aids; materials for reminiscence; information provision; transporting people to the library; services to people in residential homes, sheltered accommodation, nursing homes and day centres; reader development; lifelong learning; and publicity and promotion. The focus of the survey was on quality issues and good practice wherever possible.

Results:  The number of customers receiving a service to ‘housebound’ readers in the UK in 2001/2 was 123 407. In 1984 it was 43 807 people in England. This still bears little relation to the number of people who should be receiving the service. The majority used paid staff (88%). Volunteers supported 52% of the services, with most having links with staff. There were opportunities to improve and develop services under the Disability Discrimination Act 1995. The service was publicized and promoted by only 62% of the respondents. Of those that use paid staff and that answered this question, 73% provide disability equality training for staff. Only 21% provide disability equality training for volunteers. Only 36% are involved in reader development or lifelong learning and only 23% provide a newsletter in print, 11% on tape and 3% in Braille; 12% take laptops into people's homes.

Conclusions:  Many authorities were still providing a tokenistic service and were reluctant to publicize for fear of not coping with demand, which makes them vulnerable legally under the DDA. However, there were some excellent examples of good practice where the full range of services are provided to a high standard.
POLARIZED MØLLER SCATTERING ASYMMETRIES
Authors: CZARNECKI ANDRZEJ , MARCIANO WILLIAM J.
Published: August 2004

The utility of polarized electron beams for precision electroweak studies is described. Parity violating Møller scattering asymmetries in e-e-→e-e- are discussed. Effects of electroweak radiative corrections and the running sin2θW(Q2) are reviewed. The sensitivity of E158 (a fixed target e-e- experiment at SLAC) and future e-e- collider studies to "new physics" is briefly outlined.
RADIATIVE EFFECTS IN POLARIZED MØLLER SCATTERING
Authors: MOSSOLOV V. A. , SHUMEIKO N. M. , SUAREZ J. G.
Published: August 2004

The lowest-order QED radiative corrections to Møller scattering are calculated in covariant form. The results of analytical and Monte Carlo calculations are presented. The significance of radiative corrections for the future e-e- colliders is discussed.
EXPERIMENTAL SIGNATURES OF SPLIT FERMIONS IN EXTRA DIMENSIONS
Authors: GROSSMAN YUVAL
Published: August 2004

The smallness and hierarchy of the fermion parameters could be explained in theories with extra dimensions where doublets and singlets are localized at slightly separated points. Scattering cross sections for collisions of such fermions vanish exponentially at energies high enough to probe the separation distance. This is because the separation puts a lower bound on the attainable impact parameter in the collision. The NLC, and in particular the combination of the e+e- and e-e- modes, can probe this scenario, even if the inverse fermion separation is of order tens of TeVs.
HEAVY MAJORANA NEUTRINOS IN HIGH-ENERGY e-e- COLLISIONS COMPARED WITH THEIR EFFECTS INDUCING NEUTRINOLESS DOUBLE BETA DECAY
Authors: HEUSCH CLEMENS A. , MINKOWSKI PETER
Published: August 2004

We discuss the potential of e-e- collisions at energies comparable to the masses of heavy Majorana neutrinos to reveal their mass and mixing parameters. This potential is compared with the low-energy environment in neutrinoless double beta decay of complex nuclei. We give estimates for the short-range repulsion between any pair of valence quarks bound inside two different nucleons giving rise to suppression factors in the range of 50–100 in amplitude for decays mediated by heavy flavors.
HOW NEUTRINOLESS DOUBLE BETA DECAY ADDRESSES THE PROBLEM OF LIGHT NEUTRINO MASS
Authors: WODECKI A. , KAMIŃSKI W. A.
Published: August 2004

Neutrinoless double beta decay is one of the exotic processes which is forbidden in the standard model (SM). Its discovery is expected to shed some light on various aspects of nonstandard physics. But also from present experimental lower limits on the lifetime of this process one can extract important information about the effective electron Majorana neutrino mass, effective right handed weak interaction parameters, the Majoron coupling constant, R-parity violation SUSY parameters etc. The e-e- scattering connected directly with the inverse process to 0νββ can also provide us with such interesting physics beyond SM. In this contribution we discuss the formalism which allows deduction of this valuable knowledge from the 0νββ experiments. Results on physics of the R-parity violation are also presented to some extent.
CHARGED PARTICLE AND NEUTRON BACKGROUNDS IN AN e-e- INTERACTION REGION AT THE NLC
Authors: GRONBERG JEFF
Published: August 2004

We compare the detector background situation in an e-e- interaction region at the NLC with previous studies done of the NLC e+e- interaction region. We note from previous studies that the dominant source of detector backgrounds are the beamstrahlung pairs. Since these scale with luminosity, the reduction in luminosity in e-e- collisions leads to a reduction in detector backgrounds compared to the e+e- situation.
FUTURE LEPTON COLLIDERS AND LASER ACCELERATION
Authors: PARSA ZOHREH
Published: August 2004

Future high energy colliders along with their physics potential, and relationship to new laser technology are discussed. Experimental approaches and requirements for "New Physics" exploration are also described.
PRECISION MASS DETERMINATION OF THE HIGGS BOSON AT PHOTON–PHOTON COLLIDERS
Authors: OHGAKI TOMOMI
Published: August 2004

We demonstrate a measurement of the Higgs boson mass by the method of energy scanning at photon–photon colliders, using the high energy edge of the photon spectrum. With an integrated luminosity of 50 fb-1 it is possible to measure the standard model Higgs mass to within 110 MeV in photon–photon collisions for mh=100 GeV. As for the total width of the Higgs boson, the statistical error ΔΓh/Γh SM=0.06 is expected for mh=100 GeV, if both Γ(h→γγ) and [Formula: see text] are fixed at the predicted standard model value.
SIGNATURES OF EXTRA DIMENSIONS AT eγ AND γγ COLLIDERS
Authors: DAVOUDIASL HOOMAN
Published: August 2004

We study the processes γe→γe and γγ→γγ, in the context of the proposal for Weak Scale Quantum Gravity (WSQG) with large extra dimensions. With an ultraviolet cutoff MS~1 TeV for the effective gravity theory, the cross sections obtained for these processes at the Next Linear Collider (NLC), with the eγ an γγ options, deviate from the predictions of the Standard Model significantly. Our results suggest that, for typical proposed NLC energies and luminosities, the predictions of WSQG can be tested in the range 1 TeV≲MS≲10 TeV, making eγ an γγ colliders important tools for probing WSQG.
Abnormal renal, hepatic, and muscle glucose metabolism following glucose ingestion in type 2 diabetes
Authors: Meyer Christian , Woerle Hans J. , Dostou Jean M. , Welle Stephen L. , Gerich John E.
Published: August 2004

Recent studies indicate an important role of the kidney in postprandial glucose homeostasis in normal humans. To determine its role in the abnormal postprandial glucose metabolism in type 2 diabetes mellitus (T2DM), we used a combination of the dual-isotope technique and net balance measurements across kidney and skeletal muscle in 10 subjects with T2DM and 10 age-, weight-, and sex-matched nondiabetic volunteers after ingestion of 75 g of glucose. Over the 4.5-h postprandial period, diabetic subjects had increased mean blood glucose levels (14.1 ± 1.1 vs. 6.2 ± 0.2 mM, P < 0.001) and increased systemic glucose appearance (100.0 ± 6.3 vs. 70.0 ± 3.3 g, P < 0.001). The latter was mainly due to ∼23 g greater endogenous glucose release (39.8 ± 5.9 vs. 17.0 ± 1.8 g, P < 0.002), since systemic appearance of the ingested glucose was increased by only ∼7 g (60.2 ± 1.4 vs. 53.0 ± 2.2 g, P < 0.02). Approximately 40% of the diabetic subjects’ increased endogenous glucose release was due to increased renal glucose release (19.6 ± 3.1 vs. 10.6 ± 2.4 g, P < 0.05). Postprandial systemic tissue glucose uptake was also increased in the diabetic subjects (82.3 ± 4.7 vs. 69.8 ± 3.5 g, P < 0.05), and its distribution was altered; renal glucose uptake was increased (21.0 ± 3.5 vs. 9.8 ± 2.3 g, P < 0.03), whereas muscle glucose uptake was normal (18.5 ± 1.8 vs. 25.9 ± 3.3 g, P = 0.16). We conclude that, in T2DM, 1) both liver and kidney contribute to postprandial overproduction of glucose, and 2) postprandial renal glucose uptake is increased, resulting in a shift in the relative importance of muscle and kidney for glucose disposal. The latter may provide an explanation for the renal glycogen accumulation characteristic of diabetes mellitus as well as a mechanism by which hyperglycemia may lead to diabetic nephropathy.
Insulin facilitation of muscle protein synthesis following resistance exercise in hindlimb-suspended rats is independent of a rapamycin-sensitive pathway
Authors: Fluckey James D. , Dupont-Versteegden Esther E. , Knox Micheal , Gaddy Dana , Tesch Per A. , Peterson Charlotte A.
Published: August 2004

Hindlimb suspension (HS) results in rapid losses of muscle mass, which may in part be explained by attenuated rates of protein synthesis. Mammalian target of rapamycin (mTOR) regulates protein synthesis and has been implicated as a potential mediator of the muscle mass decrement with HS. This study examined the effect of resistance exercise, a muscle hypertrophy stimulant, on rates of protein synthesis after 4 days of HS in mature male Sprague-Dawley rats. Flywheel resistance exercise (2 sets × 25 repetitions) was conducted on days 2 and 4 of HS (HSRE). Sixteen hours after the last exercise bout, soleus muscles were assessed for in vitro rates of protein synthesis, with and without insulin (signaling agonist) and/or rapamycin (mTOR inhibitor). Results demonstrated that soleus mass was reduced ( P < 0.05) with HS, but this loss of mass was not observed ( P > 0.05) with HSRE. Muscle protein synthesis was diminished ( P < 0.05) with HS, with or without insulin. HSRE also had reduced rates of synthesis without insulin; however, insulin administration yielded higher ( P < 0.05) rates in HSRE compared with HS or control. Rapamycin diminished protein synthesis in all groups ( P < 0.05), but insulin rescued synthesis rates in HS and HSRE to levels similar to insulin alone for each group, suggesting that alternate signaling pathways develop to increase protein synthesis with HS. These results demonstrate that the capacity for an augmented anabolic response to resistance exercise is maintained after 4 days of HS and is independent of a rapamycin-sensitive pathway.
Acid and base secretion in the Calu-3 model of human serous cells
Authors: Krouse Mauri E. , Talbott Jason F. , Lee Martin M. , Joo Nam Soo , Wine Jeffrey J.
Published: August 2004

Submucosal glands are the primary source of airway mucus, a critical component of lung innate defenses. Airway glands are defective in cystic fibrosis (CF), showing a complete absence of secretion to vasoactive intestinal peptide or forskolin, which increase intracellular cAMP concentration. This defect is attributed to gland serous cells, which express the cystic fibrosis transmembrane conductance regulator. Calu-3 cells, which mimic many features of serous cells, secrete Cl− and HCO3−, with HCO3− secretion predominating for forskolin stimulation and Cl− secretion predominating for stimuli that open basolateral K+ channels to hyperpolarize the cells. We used pH stat and ion substitution experiments to clarify the mechanisms and consequences of these two modes of secretion. We confirm that Calu-3 cells secrete primarily HCO3− in response to forskolin. Unexpectedly, HCO3− secretion continued in response to K+ channel openers, with Cl− secretion being added to it. Secretion of HCO3− from hyperpolarized cells occurs via the conversion of CO2 to HCO3− and is reduced by ∼50% with acetazolamide. A gap between the base equivalent current and short-circuit current was observed in all experiments and was traced to secretion of H+ via a ouabain-sensitive, K+-dependent process (possibly H+-K+-ATPase), which partially neutralized the secreted HCO3−. The conjoint secretion of HCO3− and H+ may help explain the puzzling finding that mucus secreted from normal and CF glands has the same acidic pH as does mucus from glands stimulated with forskolin or ACh. It may also help explain how human airway glands produce mucus that is hypotonic.
GM-CSF mediates alveolar epithelial type II cell changes, but not emphysema-like pathology, in SP-D-deficient mice
Authors: Ochs Matthias , Knudsen Lars , Allen Lennell , Stumbaugh Amber , Levitt Stacey , Nyengaard Jens R. , Hawgood Samuel
Published: August 2004

Surfactant protein D (SP-D) is a member of the collectin subfamily of C-type lectins, pattern recognition proteins participating in the innate immune response. Gene-targeted mice deficient in SP-D develop abnormalities in surfactant homeostasis, hyperplasia of alveolar epithelial type II cells, and emphysema-like pathology. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is required for terminal differentiation and subsequent activation of alveolar macrophages, including the expression of matrix metalloproteinases and reactive oxygen species, factors thought to contribute to lung remodeling. Type II cells also express the GM-CSF receptor. Thus we hypothesized GM-CSF might mediate some or all of the cellular and structural abnormalities in the lungs of SP-D-deficient mice. To test this, SP-D (D−G+) and GM-CSF (D+G−) single knockout mice as well as double knockout mice deficient for both SP-D and GM-CSF (D−G−) were analyzed by design-based stereology. Compared with wild type, D−G+ as well as D+G− mice showed decreased alveolar numbers, increased alveolar sizes, and decreased alveolar epithelial surface areas. These emphysema-like changes were present to a greater extent in D−G− mice. D−G+ mice developed type II cell hyperplasia and hypertrophy with increased intracellular surfactant pools, whereas D+G− mice had smaller type II cells with decreased intracellular surfactant pools. In contrast to the emphysematous changes, the type II cell alterations were mostly corrected in D−G− mice. These results indicate that GM-CSF-dependent macrophage activity is not necessary for emphysema development in SP-D-deficient mice, but that type II cell metabolism and proliferation are, either directly or indirectly, regulated by GM-CSF in this model.
Chronic hypoxia augments protein kinase G-mediated Ca2+ desensitization in pulmonary vascular smooth muscle through inhibition of RhoA/Rho kinase signaling
Authors: Jernigan Nikki L. , Walker Benjimen R. , Resta Thomas C.
Published: August 2004

Pulmonary vascular smooth muscle (VSM) sensitivity to nitric oxide (NO) is enhanced in pulmonary arteries from rats exposed to chronic hypoxia (CH) compared with controls. Furthermore, in contrast to control arteries, relaxation to NO following CH is not reliant on a decrease in VSM intracellular free calcium ([Ca2+]i). We hypothesized that enhanced NO-dependent pulmonary vasodilation following CH is a function of VSM myofilament Ca2+ desensitization via inhibition of the RhoA/Rho kinase (ROK) pathway. To test this hypothesis, we compared the ability of the NO donor, spermine NONOate, to reverse VSM tone generated by UTP, the ROK agonist sphingosylphosphorylcholine, or the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate in Ca2+-permeabilized, endothelium-denuded pulmonary arteries (150- to 300-μm inner diameter) from control and CH (4 wk at 0.5 atm) rats. Arteries were loaded with fura-2 AM to continuously monitor VSM [Ca2+]i. We further examined effects of NO on levels of GTP-bound RhoA and ROK membrane translocation as indexes of enzyme activity in arteries from each group. We found that spermine NONOate reversed Y-27632-sensitive Ca2+ sensitization and inhibited both RhoA and ROK activity in vessels from CH rats but not control animals. In contrast, spermine NONOate was without effect on PKC-mediated vasoconstriction in either group. We conclude that CH mediates a shift in NO signaling to promote pulmonary VSM Ca2+ desensitization through inhibition of RhoA/ROK.
Disparate effects of two phosphatidylcholine binding proteins, C-reactive protein and surfactant protein A, on pulmonary surfactant structure and function
Authors: Nag Kaushik , Rodriguez-Capote Karina , Panda Amiya Kumar , Frederick Laura , Hearn Stephen A. , Petersen Nils O. , Schürch Samuel , Possmayer Fred
Published: August 2004

C-reactive protein (CRP) and surfactant protein A (SP-A) are phosphatidylcholine (PC) binding proteins that function in the innate host defense system. We examined the effects of CRP and SP-A on the surface activity of bovine lipid extract surfactant (BLES), a clinically applied modified natural surfactant. CRP inhibited BLES adsorption to form a surface-active film and the film's ability to lower surface tension (γ) to low values near 0 mN/m during surface area reduction. The inhibitory effects of CRP were reversed by phosphorylcholine, a water-soluble CRP ligand. SP-A enhanced BLES adsorption and its ability to lower γ to low values. Small amounts of SP-A blocked the inhibitory effects of CRP. Electron microscopy showed CRP has little effect on the lipid structure of BLES. SP-A altered BLES multilamellar vesicular structure by generating large, loose bilayer structures that were separated by a fuzzy amorphous material, likely SP-A. These studies indicate that although SP-A and CRP both bind PC, there is a difference in the manner in which they interact with surface films.
Regulation of caspase-3 and -9 activation in oxidant stress to RTE by forkhead transcription factors, Bcl-2 proteins, and MAP kinases
Authors: Kaushal Gur P. , Liu Ling , Kaushal Varsha , Hong Xiaoman , Melnyk Oksana , Seth Rohit , Safirstein Robert , Shah Sudhir V.
Published: August 2004

Cytotoxicity to renal tubular epithelial cells (RTE) is dependent on the relative response of cell survival and cell death signals triggered by the injury. Forkhead transcription factors, Bcl-2 family member Bad, and mitogen-activated protein kinases are regulated by phosphorylation that plays crucial roles in determining cell fate. We examined the role of phosphorylation of these proteins in regulation of H2O2-induced caspase activation in RTE. The phosphorylation of FKHR, FKHRL, and Bcl-2 family member Bad was markedly increased in response to oxidant injury, and this increase was associated with elevated levels of basal phosphorylation of Akt/protein kinase B. Phosphoinositol (PI) 3-kinase inhibitors abolished this phosphorylation and also decreased expression of antiapoptotic proteins Bcl-2 and BclxL. Inhibition of phosphorylation of forkhead proteins resulted in a marked increase in the proapoptotic protein Bim. These downstream effects of PI 3-kinase inhibition promoted the oxidant-induced activation of caspase-3 and -9, but not caspase-8 and -1. The impact of enhanced activation of caspases by PI 3-kinase inhibition was reflected on accelerated oxidant-induced cell death. Oxidant stress also induced marked phosphorylation of ERK1/2, P38, and JNK kinases. Inhibition of ERK1/2 phosphorylation but not P38 and JNK kinase increased caspase-3 and -9 activation; however, this activation was far less than induced by inhibition of Akt phosphorylation. Thus the Akt-mediated phosphorylation pathway, ERK signaling, and the antiapoptotic Bcl-2 proteins distinctly regulate caspase activation during oxidant injury to RTE. These studies suggest that enhancing renal-specific survival signals may lead to preservation of renal function during oxidant injury.
Regulation of Egr-1, SRF, and Sp1 mRNA expression in contracting skeletal muscle cells
Authors: Irrcher Isabella , Hood David A.
Published: August 2004

The early cellular signals associated with contractile activity initiate the activation and induction of transcription factors that regulate changes in skeletal muscle phenotype. The transcription factors Egr-1, Sp1, and serum response factor (SRF) are potentially important mediators of mitochondrial biogenesis based on the prevalence of binding sites for them in the promoter regions of genes encoding mitochondrial proteins, including PGC-1α, the important regulator of mitochondrial biogenesis. Thus, to further define a role for transcription factors at the onset of contractile activity, we examined the time-dependent alterations in Egr-1, Sp1, and SRF mRNA and the levels in electrically stimulated mouse C2C12skeletal muscle cells. Early transient increases in Egr-1 mRNA levels within 30 min ( P < 0.05) of contractile activity led to threefold increases ( P < 0.05) in Egr-1 protein by 60 min. The increase in Egr-1 mRNA was not because of increased stability, as Egr-1 mRNA half-life after 30 min of stimulation showed only a 58% decline. Stimulation of muscle cells had no effect on Sp1 mRNA but led to progressive increases ( P < 0.05) in SRF mRNA by 30 and 60 min. This was not matched by increases in SRF protein but occurred coincident with increases ( P < 0.05) in SRF-serum response element DNA binding at 30 and 60 min as a result of SRF phosphorylation on serine-103. To assess the importance of the recovery period, 12 h of continuous contractile activity was compared with four successive 3-h bouts, with an intervening 21-h recovery period after each bout. Continuous contractile activity led to a twofold increase ( P < 0.05) in Egr-1 mRNA, no change in SRF mRNA, and a 43% decrease in Sp1 mRNA expression. The recovery period prevented the decline in Sp1 mRNA, produced a decrease in Egr-1 mRNA, and had no effect on SRF mRNA. Thus continuous and intermittent contractile activity evoked different specific transcription factor expression patterns, which may ultimately contribute to divergent qualitative, or temporal patterns of, phenotypic adaptation in muscle.
Regional hemodynamics during postexercise hypotension. I. Splanchnic and renal circulations
Authors: Pricher Mollie P. , Holowatz Lacy A. , Williams Jay T. , Lockwood Jennifer M. , Halliwill John R.
Published: August 2004

Moderate exercise elicits a relative postexercise hypotension that is caused by an increase in systemic vascular conductance. Previous studies have shown that skeletal muscle vascular conductance is increased postexercise. It is unclear whether these hemodynamic changes are limited to skeletal muscle vascular beds. The aim of this study was to determine whether the splanchnic and/or renal vascular beds also contribute to the rise in systemic vascular conductance during postexercise hypotension. A companion study aims to determine whether the cutaneous vascular bed is involved in postexercise hypotension (Wilkins BW, Minson CT, and Halliwill JR. J Appl Physiol 97: 2071–2076, 2004). Heart rate, arterial pressure, cardiac output, leg blood flow, splanchnic blood flow, and renal blood flow were measured in 13 men and 3 women before and through 120 min after a 60-min bout of exercise at 60% of peak oxygen uptake. Vascular conductances of leg, splanchnic, and renal vascular beds were calculated. One hour postexercise, mean arterial pressure was reduced (79.1 ± 1.7 vs. 83.4 ± 1.8 mmHg; P < 0.05), systemic vascular conductance was increased by ∼10%, leg vascular conductance was increased by ∼65%, whereas splanchnic (16.0 ± 1.8 vs. 18.5 ± 2.4 ml·min−1·mmHg−1; P = 0.13) and renal (20.4 ± 3.3 vs. 17.6 ± 2.6 ml·min−1·mmHg−1; P = 0.14) vascular conductances were unchanged compared with preexercise. This suggests there is neither vasoconstriction nor vasodilation in the splanchnic and renal vasculature during postexercise hypotension. Thus the splanchnic and renal vascular beds neither directly contribute to nor attenuate postexercise hypotension.