bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of long‐term depression is associated with decreased dendritic length and spine density in layers III and V of sensorimotor neocortex
Authors: Monfils Marie‐H. , Teskey G. Campbell 
Published: May 2004

AbstractLong‐term potentiation (LTP) and long‐term depression (LTD) are currently the most widely investigated models of the synaptic mechanisms underlying learning and memory. Previous research has shown that induction of LTP increases measures of pyramidal cell dendritic morphology in the hippocampus and layers III and V of the neocortex. However, to date there are no reports on the direct effects of LTD induction on dendritic morphology. Here, we investigated the effects of LTD induction on sensorimotor pyramidal cell dendritic morphology. Rats carried a stimulating electrode in the corpus callosum (midline) and a recording electrode in the right sensorimotor cortex. Each rat received low‐frequency stimulation composed of 900 pulses at 1 Hz or handling daily for a total 15 days. Evoked potentials (EPs) of the transcallosal pathway were recorded in the right hemisphere before and after the 15 days of stimulation or handling. The rats were then perfused with saline and the brains were immediately processed for Golgi‐Cox staining. Our results show that LTD induction is related to decreases in dendritic length and spine density both in layers III and V as well as a decrease in dendritic branch complexity in layer V of the sensorimotor cortex. Thus, neuronal alterations following modifications in neocortical synaptic efficacy may provide a general mechanism for the physical instantiation of learning and memory. Synapse 53:114–121, 2004. © 2004 Wiley‐Liss, Inc.
The role of load‐carrying in the evolution of modern body proportions
Authors: Wang W.‐J. , Crompton R. H. 
Published: May 2004

AbstractThe first unquestionably bipedal early human ancestors, the species Australopithecus afarensis, were markedly different to ourselves in body proportions, having a long trunk and short legs. Some have argued that ′chimpanzee‐like′ features such as these suggest a ‘bent‐hip, bent‐knee’ (BHBK) posture would have been adopted during gait. Computer modelling studies, however, indicate that this early human ancestor could have walked in a reasonably efficient upright posture, whereas BHBK posture would have nearly doubled the mechanical energy cost of locomotion, as it does the physiological cost of locomotion in ourselves. More modern body proportions first appear at around 1.8–1.5 Ma, with Homo ergaster (early African Homo erectus), represented by the Nariokotome skeleton KNM‐WT 15000, in which the legs were considerably longer in relation to the trunk than they are in human adults, although this skeleton represents an adolescent. Several authors have suggested that this morphology would have allowed faster, more endurant walking. But during the same period, the archaeological record indicates a sharp rise in distances over which stone tools or raw materials are transported. Is this coincidental, or can load‐carrying also be implicated in selection for a more modern morphology? Computer simulations of loaded walking, verified against kinetic data for humans, show that BHBK gait is even more ineffective while load‐carrying. However, walking erect, the Nariokotome individual could have carried loads of 10–15% body mass for less cost, relative to body size, than AL 288‐1 walking erect but unloaded. In fact, to the extent that our sample of humans is typical, KNM‐WT 15000 would have had better mechanical effectiveness in bearing light loads on the back than modern human adults. Thus, selection for effectiveness in load‐carrying, as well as in endurant walking, is indeed likely to have been implicated in the evolution of modern body proportions.
Quantitative optical microscope with enhanced resolution using a pixelated liquid crystal spatial light modulator
Authors: NG A. Y. M. , SEE C. W. , SOMEKH M. G. 
Published: May 2004

SummaryThis paper presents a brief account of a novel optical microscope, which combines the advantages of two well‐known techniques, namely phase contrast and phase stepping, to provide high contrast imaging and precision measurements. The inclusion of a programmable liquid crystal spatial light modulator provides for the phase stepping required, while also allowing flexibility for future improvements. The results shown reveal an important aspect of the system to facilitate quantitative sample measurements, with an enhancement of optical resolution compared with conventional optical imaging systems.
Off‐axis electron holography of electrostatic potentials in unbiased and reverse biased focused ion beam milled semiconductor devices
Authors: TWITCHETT A. C. , DUNIN‐BORKOWSKI R. E. , HALLIFAX R. J. , BROOM R. F. , MIDGLEY P. A. 
Published: May 2004

SummaryOff‐axis electron holography in the transmission electron microscope (TEM) is used to measure two‐dimensional electrostatic potentials in both unbiased and reverse biased silicon specimens that each contain a single p–n junction. All the specimens are prepared for examination in the TEM using focused ion beam (FIB) milling. The in situ electrical biasing experiments make use of a novel specimen geometry, which is based on a combination of cleaving and FIB milling. The design and construction of an electrical biasing holder are described, and the effects of TEM specimen preparation on the electrostatic potential in the specimen, as well as on fringing fields beyond the specimen surface, are assessed.
Circuit editing of copper and low‐k dielectrics in nanotechnology devices
Authors: MOSSELVELD F. , MAKAROV V. V. , LUNDQUIST T. R. , GRIFFIS D. P. , RUSSELL P. E. 
Published: May 2004

SummaryCircuit editing of integrated circuit (IC) devices fabricated in 100‐nm and smaller technologies has moved IC microsurgery into nanosurgery. Although the dimensions are challenging, an additional challenge is to mill the dielectric materials that are employed controllably. There are interesting biological similarities as carbon content and porosity increase in order to minimize the dielectric constant. These porous organic materials are extremely delicate and are readily carbonized under the ion beam. Besides minimizing carbonization, the etching of these materials must be minimized during the removal of a metallized area. A further challenge has been caused by the continuing tightening of fabrication specifications; the dielectric materials are dispersed (although not randomly) within the metallizations in order to reduce variations during a planarization process. In addition, to improve planarization tolerances, dummy metallizations are placed in regions where the need is only mechanical and not electrical. Neither of these ‘extra’ structures is readily available to assist in edit planning. To address these dielectrics and the structures in which they are found, several techniques – including chemistries – have been developed. Methods to increase the etching of metallization relative to the dielectric are reviewed, including chemistries that improve the selectivity of copper to dielectric.
Thermal stability of Ti and Pt nanowires manufactured by Ga+ focused ion beam
Authors: INKSON B. J. , DEHM G. , WAGNER T. 
Published: May 2004

SummaryTi and Pt nanowires have been produced by ultra high‐vacuum molecular beam epitaxy deposition of Ti thin films and focused ion beam (FIB) deposition of Pt thin films, followed by cross‐sectional FIB sputtering to form electron‐transparent nanowires. The thermal stability of the nanowires has been investigated by in situ thermal cycling in a transmission electron microscope. Epitaxial single crystal Ti nanowires on (0001)Al2O3 substrates are microstructurally stable up to 550–600 °C, above which limited dislocation motion is activated shortly before the Ti‐wires oxidize. The amorphous FIB‐deposited Pt wires are stable up to 580–650 °C where partial crystallization is observed in vacuum. Faceted nanoparticles grow on the wire surface, growing into free space by surface diffusion and minimizing contact area with the underlying wire. The particles are face‐centred cubic (fcc) Pt with some dissolved Ga. Continued heating results in particle spheroidization, coalescence and growth, retaining the fcc structure.
A quantitative, three‐dimensional depositional model of gravelly braided rivers
Authors: Lunt I. A. , Bridge J. S. , Tye R. S. 
Published: May 2004

AbstractA quantitative, three‐dimensional depositional model of gravelly, braided rivers has been developed based largely on the deposits of the Sagavanirktok River in northern Alaska. These deposits were described using cores, wireline logs, trenches and ground‐penetrating radar profiles. The origin of the deposits was inferred from observations of: (1) channel and bar formation and migration and channel filling, interpreted from aerial photographs; (2) water flow during floods; and (3) the topography and texture of the river bed at low‐flow stage. This depositional model quantitatively represents the geometry of the different scales of strataset, the spatial relationships among them and their sediment texture distribution. Porosity and permeability in the model are related to sediment texture. The geometry of a particular type and scale of strataset is related to the geometry and migration of the bedform type (e.g. ripples, dunes, bedload sheets, bars) associated with deposition of the strataset. In particular, the length‐to‐thickness ratio of stratasets is similar to the wavelength‐to‐height ratio of associated bedforms. Furthermore, the wavelength and height of bedforms such as dunes and bars are related to channel depth and width. Therefore, the thickness of a particular scale of strataset (i.e. medium‐scale cross‐sets and large‐scale sets of inclined strata) will vary with river dimensions. These relationships between the dimensions of stratasets, bedforms and channels mean that this depositional model can be applied to other gravelly fluvial deposits. The depositional model can be used to interpret the origin of ancient gravelly fluvial deposits and to aid in the characterization of gravelly fluvial aquifers and hydrocarbon reservoirs.
Fluidization and injection in the deep‐water sandstones of the Eocene Alba Formation (UK North Sea)
Authors: Duranti Davide , Hurst Andrew 
Published: May 2004

AbstractThe Nauchlan Member of the Late Eocene Alba Formation (UK North Sea) consists of a deep‐water channel fill that was extensively modified by post‐depositional sand remobilization and injection. Sandstone textures, facies associations and the geometry of the channel fill were affected. A suite of sand‐rich facies was produced by large‐scale fluidization and injection within the channel fill and above it. These facies, termed here unstratified facies, are characterized by the absence of stratification surfaces and by discordant relationships with bedding in the adjacent succession. They reflect variable degrees of disruption of the primary sedimentary structures caused by escaping pore fluid, the velocity of which is estimated at least in the order of 0·1 ms−1. Adjacent mudstones were severely disrupted by hydraulic fracturing, and fragments of fractured mudstone were incorporated into the fluidized sand. Average porosity was decreased in the sandstones affected by fluidization. Two main phases of sand injection are inferred to occur at different burial depths. A shallow burial phase (below 100 m) produced thin dykes with ptygmatic folds. The second phase occurred at the boundary between Eocene and Oligocene (≈ 300 m burial depth) and resulted in large‐scale tabular wing‐like dykes that project from the edges of the channel fill. The significant pore‐fluid overpressure, which was required to hydraulically fracture the thick mudstone seal and to fluidize the large volume of sand, was likely to be built up by static liquefaction of the source sand and was possibly enhanced by hydrocarbon gas influx.
Implications of the fault scaling law for the growth of topography: mountain ranges in the broken foreland of north‐east Tibet
Authors: Hetzel Ralf , Tao Mingxin , Niedermann Samuel , Strecker Manfred R. , Ivy‐Ochs Susan , Kubik Peter W. , Gao Bo 
Published: May 2004

AbstractA fault scaling law suggests that, over eight orders of magnitude, fault lengthLis linearly related to maximum displacementD. Individual faults may therefore retain a constant ratio ofD/Las they grow. If erosion is minor compared with tectonic uplift, the length and along‐strike relief of young mountain ranges should thus reflect fault growth. Topographic profiles along the crests of mountain ranges in the actively deforming foreland of north‐east Tibet exhibit a characteristic shape with maximum height near their centre and decreasing elevation toward the tips. We interpret the along‐strike relief of these ranges to reflect the slip distribution on high‐angle reverse faults. A geometric model illustrates that the lateral propagation rate of such mountain ranges may be deciphered if their length‐to‐height ratio has remained constant. As an application of the model, we reconstruct the growth of the Heli Shan using a long‐term uplift rate of ∼1.3 mm yr−1derived from21Ne and10Be exposure dating.
Initial reactions in sapwood of Norway spruce and Scots pine after wounding and infection by Heterobasidion parviporum and H. annosum
Authors: Johansson S. M. , Lundgren L. N. , Asiegbu F. O. 
Published: May 2004

SummaryThe xylem surface of seedlings, stem material and roots of Norway spruce (Picea abies) and Scots pine (Pinus sylvestris) were inoculated with strains of Heterobasidion annosum s. str. and H. parviporum s. str. The depth of necrosis in wounded spruce increased at a linear rate for at least seven weeks of incubation, but the rate of necrotic spread was significantly faster in infected wounds. In wounded pine the necrosis was maintained at a more superficial level for several weeks. Both spruce and pine sapwood were initially infected by hyphae of both species. In spruce, the hyphae advanced at a constant rate behind the necrotic front. On the contrary, after 1–2 weeks living H. parviporum hyphae were rare in pine rays. Heterobasidion annosum hyphae survived in pine rays, phloem and tracheids, despite a heavy accumulation of phenolics and resins and were able to penetrate into the sapwood at a linear rate although slower than infections in spruce. Histochemistry and quantitative estimates demonstrated that peroxidase activity was initially higher in spruce sapwood than in pine. Within three days of incubation, the activity in spruce sapwood disappeared concurrently with deepening necrosis. However, in pine, in both control and infected samples, there was a significant increase in peroxidase activity in the area surrounding the superficial necrosis, up to the wound surface and in the cambium and phloem around the wound. After wounding and infection, the content of soluble protein increased significantly in wood of older trees but not in seedlings. Infection resulted in an increased formation of lipophilic extractives in both spruce and pine but to a significantly greater degree in the latter, whereas the amount of hydrophilic compounds decreased in both. High‐performance liquid chromatography (HPLC) analyses of lipophilic extracts showed that inoculation of pine with the two species of Heterobasidion increased the amounts of pinosylvin, its monomethylether and several other phenolics as also resinous compounds. The results obtained may be relevant in explaining the known higher resistance of Scots pine to H. parviporum.
Mercury Inactivates Transcription and the Generalized Transcription Factor TFB in the Archaeon
Sulfolobus solfataricus
Authors: Dixit Vidula , Bini Elisabetta , Drozda Melissa , Blum Paul 
Published: May 2004

ABSTRACT

Mercury has a long history as an antimicrobial agent effective against eukaryotic and prokaryotic organisms. Despite its prolonged use, the basis for mercury toxicity in prokaryotes is not well understood. Archaea, like bacteria, are prokaryotes but they use a simplified version of the eukaryotic transcription apparatus. This study examined the mechanism of mercury toxicity to the archaeal prokaryote
Sulfolobus solfataricus
. In vivo challenge with mercuric chloride instantaneously blocked cell division, eliciting a cytostatic response at submicromolar concentrations and a cytocidal response at micromolar concentrations. The cytostatic response was accompanied by a 70% reduction in bulk RNA synthesis and elevated rates of degradation of several transcripts, including
tfb-1
,
tfb-2
, and
lacS
. Whole-cell extracts prepared from mercuric chloride-treated cells or from cell extracts treated in vitro failed to support in vitro transcription of 16S rRNAp and
lacSp
promoters. Extract-mixing experiments with treated and untreated extracts excluded the occurrence of negative-acting factors in the mercury-treated cell extracts. Addition of transcription factor B (TFB), a general transcription factor homolog of eukaryotic TFIIB, to mercury-treated cell extracts restored >50% of in vitro transcription activity. Consistent with this finding, mercuric ion treatment of TFB in vitro inactivated its ability to restore the in vitro transcription activity of TFB-immunodepleted cell extracts. These findings indicate that the toxicity of mercuric ion in
S. solfataricus
is in part the consequence of transcription inhibition due to TFB-1 inactivation.
α-Galactosylceramide and Novel Synthetic Glycolipids Directly Induce the Innate Host Defense Pathway and Have Direct Activity against Hepatitis B and C Viruses
Authors: Mehta Anand S. , Gu Baohua , Conyers Bertha , Ouzounov Serguey , Wang Lijuan , Moriarty Robert M. , Dwek Raymond A. , Block Timothy M. 
Published: May 2004

ABSTRACT
α-Galactosylceramide is a glycolipid derived from marine sponges that is currently in human clinical trials as an anticancer agent. It has also been shown to be effective in reducing the amount of hepatitis B virus (HBV) DNA detected in mice that produce HBV constitutively from a transgene. It was assumed that all of the antiviral and antitumor activities associated with α-galactosylceramide were mediated through the activation of NK T cells. However, we report here an additional unpredicted activity of α-galactosylceramide as a direct antiviral agent and inducer of the innate host defense pathway. To exploit this activity, we have developed a new class of smaller, orally available glycolipids that also induce the innate host defense pathway and have direct activity against HBV and hepatitis C virus.
Application of Real-Time Quantitative PCR to Molecular Analysis of
Candida albicans
Strains Exhibiting Reduced Susceptibility to Azoles
Authors: Chau Andrew S. , Mendrick Cara A. , Sabatelli Frank J. , Loebenberg David , McNicholas Paul M. 
Published: May 2004

ABSTRACT

Real-time quantitative PCR was used to measure expression levels of genes encoding efflux pumps,
ERG11
and two control genes,
ACT1
and
PMA1
, in a collection of 14 fluconazole-susceptible
Candida albicans
isolates. For each gene, average expression levels and variations within the population were determined. These values were then used as reference points to make predictions about the molecular basis of resistance in 38 clinical isolates (the majority of which were resistant to fluconazole) obtained from 18 patients treated with posaconazole for refractory oropharyngeal candidiasis. For each of the 38 isolates, the expression levels of genes encoding efflux pumps,
ERG11
and the control genes, were measured as above. Comparison of the two data sets revealed that expression of
ACT1
and
PMA1
did not vary significantly between the two sets of isolates. In contrast,
MDR1, ERG11
,
CDR1
, and
CDR2
were overexpressed in 3, 4, 14, and 35, respectively, of the isolates from patients treated with azoles. In addition to these changes, the patient isolates all had at least one and often multiple missense mutations in
ERG11
. Select
ERG11
alleles were expressed in
Saccharomyces cerevisiae
; all of the alleles tested conferred reduced susceptibility to fluconazole. Despite both the increases in pump expression and the
ERG11
mutations, only one of the patient isolates exhibited a large decrease in posaconazole susceptibility.
Mutation D30N Is Not Preferentially Selected by Human Immunodeficiency Virus Type 1 Subtype C in the Development of Resistance to Nelfinavir
Authors: Grossman Zehava , Paxinos Ellen E. , Averbuch Diana , Maayan Shlomo , Parkin Neil T. , Engelhard Dan , Lorber Margalit , Istomin Valery , Shaked Yael , Mendelson Ella , Ram Daniela , Petropoulos Chris J. , Schapiro Jonathan M. 
Published: May 2004

ABSTRACT

Differences in baseline polymorphisms between subtypes may result in development of diverse mutational pathways during antiretroviral treatment. We compared drug resistance in patients with human immunodeficiency virus subtype C (referred to herein as “subtype-C-infected patients”) versus subtype-B-infected patients following protease inhibitor (PI) therapy. Genotype, phenotype, and replication capacity (Phenosense; Virologic) were determined. We evaluated 159 subtype-C- and 65 subtype-B-infected patients failing first PI treatment. Following nelfinavir treatment, the unique nelfinavir mutation D30N was substantially less frequent in C (7%) than in B (23%;
P
= 0.03) while L90M was similar (
P
< 0.5). Significant differences were found in the rates of M36I (98 and 36%), L63P (35 and 59%), A71V (3 and 32%), V77I (0 and 36%), and I93L (91 and 32%) (0.0001 <
P
< 0.05) in C and B, respectively. Other mutations were L10I/V, K20R, M46I, V82A/I, I84V, N88D, and N88S. Subtype C samples with mutation D30N showed a 50% inhibitory concentration (IC
50
) change in susceptibility to nelfinavir only. Other mutations increased IC
50
correlates to all PIs. Following accumulation of mutations, replication capacity of the C virus was reduced from 43% ± 22% to 22% ± 15% (
P
= 0.04). We confirmed the selective nature of the D30N mutation in C, and the broader cross-resistance of other common protease inhibitor mutations. The rates at which these mutational pathways develop differ in C and subtype-B-infected patients failing therapy, possibly due to the differential impact of baseline polymorphisms. Because mutation D30N is not preferentially selected in nelfinavir-treated subtype-C-infected patients, as it is in those infected with subtype B, the consideration of using this drug initially to preserve future protease inhibitor options is less relevant for subtype-C-infected patients.
Pyruvate Decarboxylase, the Target for Omeprazole in Metronidazole-Resistant and Iron-Restricted
Tritrichomonas foetus
Authors: Sutak Róbert , Tachezy Jan , Kulda Jaroslav , Hrdý Ivan 
Published: May 2004

ABSTRACT

The substituted benzimidazole omeprazole, used for the treatment of human peptic ulcer disease, inhibits the growth of the metronidazole-resistant bovine pathogen
Tritrichomonas foetus
in vitro (MIC at which the growth of parasite cultures is inhibited by 50%, 22 μg/ml [63 μM]). The antitrichomonad activity appears to be due to the inhibition of pyruvate decarboxylase (PDC), which is the key enzyme responsible for ethanol production and which is strongly upregulated in metronidazole-resistant trichomonads. PDC was purified to homogeneity from the cytosol of metronidazole-resistant strain. The tetrameric enzyme of 60-kDa subunits is inhibited by omeprazole (50% inhibitory concentration, 16 μg/ml). Metronidazole-susceptible
T. foetus
, which expresses very little PDC, is only slightly affected. Omeprazole has the same inhibitory effect on
T. foetus
cells grown under iron-limited conditions. Similarly to metronidazole-resistant cells,
T. foetus
cells grown under iron-limited conditions have nonfunctional hydrogenosomal metabolism and rely on cytosolic PDC-mediated ethanol fermentation.