julilili42/papers huggingface dataset:
Cochlear Pharmacokinetics with Local Inner Ear Drug Delivery Using a Three-Dimensional Finite-Element Computer Model
2006-11-17

&lt;i&gt;Hypothesis:&lt;/i&gt; Cochlear fluid pharmacokinetics can be better represented by three-dimensional (3D) finite-element simulations of drug dispersal. &lt;i&gt;Background:&lt;/i&gt; Local drug deliveries to the round window membrane are increasingly being used to treat inner ear disorders. Crucial to the development of safe therapies is knowledge of drug distribution in the inner ear with different delivery methods. Computer simulations allow application protocols and drug delivery systems to be evaluated, and may permit animal studies to be extrapolated to the larger cochlea of the human. &lt;i&gt;Methods:&lt;/i&gt; A finite-element 3D model of the cochlea was constructed based on geometric dimensions of the guinea pig cochlea. Drug propagation along and between compartments was described by passive diffusion. To demonstrate the potential value of the model, methylprednisolone distribution in the cochlea was calculated for two clinically relevant application protocols using pharmacokinetic parameters derived from a prior one-dimensional (1D) model. In addition, a simplified geometry was used to compare results from 3D with 1D simulations. &lt;i&gt;Results:&lt;/i&gt; For the simplified geometry, calculated concentration profiles with distance were in excellent agreement between the 1D and the 3D models. Different drug delivery strategies produce very different concentration time courses, peak concentrations and basal-apical concentration gradients of drug. In addition, 3D computations demonstrate the existence of substantial gradients across the scalae in the basal turn. &lt;i&gt;Conclusion:&lt;/i&gt; The 3D model clearly shows the presence of drug gradients across the basal scalae of guinea pigs, demonstrating the necessity of a 3D approach to predict drug movements across and between scalae with larger cross-sectional areas, such as the human, with accuracy. This is the first model to incorporate the volume of the spiral ligament and to calculate diffusion through this structure. Further development of the 3D model will have to incorporate a more accurate geometry of the entire inner ear and incorporate more of the specific processes that contribute to drug removal from the inner ear fluids. Appropriate computer models may assist in both drug and drug delivery system design and can thus accelerate the development of a rationale-based local drug delivery to the inner ear and its successful establishment in clinical practice.
Cytomegalovirus Pneumonia After Stem Cell Transplantation: Correlation of CT Findings with Clinical Outcome in 30 Patients
2006-11-17

The initial high-resolution CT findings in immunocompromised patients with CMV pneumonia seem to predict the patient's outcome being unfavorable in those forms of disease beginning mostly bilaterally as diffuse or patchy ground-glass opacity followed by progressive air-space consolidation. Also, a change in the CT morphology of pulmonary lesions toward diffuse ground-glass opacity seems to correlate with an unfavorable disease course.
Density-dependent host choice by disease vectors: epidemiological implications of the ideal free distribution
2006-11-17

The proportion of vector blood meals taken on humans (the human blood index, h) appears as a squared term in classical expressions of the basic reproduction ratio (R(0)) for vector-borne infections. Consequently, R(0) varies non-linearly with h. Estimates of h, however, constitute mere snapshots of a parameter that is predicted, from evolutionary theory, to vary with vector and host abundance. We test this prediction using a population dynamics model of river blindness assuming that, before initiation of vector control or chemotherapy, recorded measures of vector density and human infection accurately represent endemic equilibrium. We obtain values of h that satisfy the condition that the effective reproduction ratio (R(e)) must equal 1 at equilibrium. Values of h thus obtained decrease with vector density, decrease with the vector:human ratio and make R(0) respond non-linearly rather than increase linearly with vector density. We conclude that if vectors are less able to obtain human blood meals as their density increases, antivectorial measures may not lead to proportional reductions in R(0) until very low vector levels are achieved. Density dependence in the contact rate of infectious diseases transmitted by insects may be an important non-linear process with implications for their epidemiology and control.
Albumin in Immunohistochemistry: Foe and Friend
2006-11-20

Immunohistochemical procedures constitute a high methodological value in both pathologic diagnostics and research. Staining quality depends on a large variety of interference factors. Primarily, background staining reduces the quality of evaluation by reducing the chromatic discrimination. For the identification of important interference factors, various incubation steps and composition of solutions recommended in routine protocols were altered or omitted in our study. Surprisingly, the most important effect concerning background staining reduction could be significantly attributed to the omission of albumin which usually is recommended as a reducer of background stainings. However, in contrast to this negative effect, albumin could also increase specific staining intensity. These findings lead to the recommendation of a careful use of albumin in immunohistochemistry because of the dichotomous effects mentioned above. Furthermore, these results imply that in case of a good specific staining pattern, the use of albumin in immunohistochemical solutions merely exerts significant negative background staining effects.
A splice site mutation in the murine Opa1 gene features pathology of autosomal dominant optic atrophy
2006-11-21

Autosomal dominant optic atrophy (adOA) is a juvenile onset, progressive ocular disorder characterized by bilateral loss of vision, central visual field defects, colour vision disturbances, and optic disc pallor. adOA is most frequently associated with mutations in OPA1 encoding a dynamin-related large GTPase that localizes to mitochondria. Histopathological studies in adOA patients have shown a degeneration of retinal ganglion cells (RGCs) and a loss of axons in the optic nerve. However little is known about the molecular mechanism and pathophysiology of adOA due to the lack of appropriate in vivo models. Here we report a first mouse model carrying a splice site mutation (c.1065 + 5G --> A) in the Opa1 gene. The mutation induces a skipping of exon 10 during transcript processing and leads to an in-frame deletion of 27 amino acid residues in the GTPase domain. Western blot analysis showed no evidence of a shortened mutant protein but a approximately 50% reduced OPA1 protein level supporting haploinsufficiency as a major disease mechanism in adOA. Homozygous mutant mice die in utero during embryogenesis with first notable developmental delay at E8.5 as detected by magnetic resonance imaging (MRI). Heterozygous mutants are viable and of normal habitus but exhibit an age-dependent loss of RGCs that eventually progresses to a severe degeneration of the ganglion cell and nerve fibre layer. In addition optic nerves of mutant mice showed a reduced number of axons, and a swelling and abnormal shape of the remaining axons. Mitochondria in these axons showed disorganized cristae structures. All these defects recapitulate crucial features of adOA in humans and therefore document the validity and importance of this model for future research.
Tinnitus Sensitization
2006-11-23

According to the tinnitus sensitization model, a tinnitus signal originates (as a type I-IV tinnitus) in the cochlea. In the brain, concerned with perception and cognition, the 1) conditioned associations, as postulated by the tinnitus model of Jastreboff, and the 2) unconditioned sensitized stimulus responses, as postulated in the present ACTS model, are actively connected with and attributed to the tinnitus signal. Attention to the tinnitus constitutes a typical undesired sensitized response. Some of the tinnitus-associated attributes may be called essential, unconditioned sensitization attributes. By a process called facilitation, the tinnitus' essential attributes are suggested to activate the tinnitus response. The result is an undesired increase in responsivity, such as an increase in attentional focus to the eliciting tinnitus stimulus. The mechanisms underlying sensitization are known as a specific nonassociative learning process producing a structural fixation of long-term facilitation at the synaptic level. This sensitization model may be important for the development of a sensitization-specific treatment if extinction procedures alone do not lead to satisfactory outcome. Inasmuch as this model considers sensitization as a nonassociative learning process based on cortical plasticity, it is reasonable to assume that this learning process can be altered by counteracting learning procedures. These counteracting learning procedures may consist of tinnitus-specific cognitive and behavioral procedures.
Unexpected Conformational Properties of 1‐Trifluoromethyl‐1‐Silacyclohexane, C5H10SiHCF3: Gas Electron Diffraction, Low‐Temperature NMR Spectropic Studies, and Quantum Chemical Calculations
2006-11-23

Abstract The molecular structure of axial and equatorial conformers of 1‐trifluoromethyl‐1‐silacyclohexane, (C 5 H 10 SiHCF 3 ), as well as the thermodynamic equilibrium between these species was investigated by means of gas electron diffraction (GED), dynamic nuclear magnetic resonance (DNMR) spectroscopy, and quantum chemical calculations (B3LYP, MP2, and CBS‐QB3). According to GED, the compound exists as a mixture of two C s symmetry conformers possessing the chair conformation of the six‐membered ring and differing in the axial or equatorial position of the CF 3 group (axial=58(12) mol %/equatorial=42(12) mol %) at T =293 K. This result is in a good agreement with the theoretical prediction. This is, however, in sharp contrast to the conformational properties of the cyclohexane analogue. The main structural feature for both conformers is the unusually long exocyclic bond length SiC 1.934(10) Å. A low‐temperature 19 F NMR experiment results in an axial/equatorial ratio of 17(2) mol %:83(2) mol % at 113 K and a Δ G ≠ of 5.5(2) kcal mol −1 . CBS‐QB3 calculations in the gas‐phase and solvation effect calculations using the PCM(B3LYP/6‐311G*) and IPCM(B3LYP/6‐311G*) models were applied to estimate the axial/equatorial ratio in the 100–300 K temperature range, which showed excellent agreement with the experimental results. The minimum energy pathways for the chair‐to‐chair inversion of trifluoromethylsilacyclohexane and methylsilacyclohexane were also calculated using the STQN(Path) method.
Molecular replacement in the `twilight zone': structure determination of the non-haem iron oxygenase NovR fromStreptomyces spheroidesthrough repeated density modification of a poor molecular-replacement solution
2006-11-23

Crystals of recombinant NovR (subunit MW = 29 924 Da; 270 amino acids), a non-haem iron oxygenase from Streptomyces spheroides, were grown by vapour diffusion. The protein crystallized in space group C2, with unit-cell parameters a = 86.69, b = 139.38, c = 100.82 A, beta = 101.18 degrees . Native data were collected to a resolution of 2.1 A from a single crystal at a synchrotron and a molecular-replacement solution was obtained using the program AMoRe. The starting phase information was very poor and did not permit model building. Phases were subsequently improved using a combination of fourfold averaging and very gradual phase extension in the program DM to yield an interpretable map. NovR belongs to a novel class of non-haem iron oxygenases that share sequence similarity with class II aldolases. It is predicted to perform two consecutive oxidative decarboxylation steps in the biosynthesis of the prenylated hydroxybenzoic acid moiety of the aminocoumarin antibiotic novobiocin.
Guidelines for clinical trials in melasma
2006-11-24

There have been very few well-conducted trials in melasma and this makes the process of comparing treatment outcome between trials difficult. The Pigmentary Disorders Academy has examined the issues relating to clinical trials on melasma, and has proposed recommendations on how they should be conducted. This covers all aspects including correct diagnosis of the condition, evaluation of efficacy and safety outcome, and overall clinical trial design. It is anticipated that the establishment of accepted guidelines on the conduct of clinical trials in melasma will greatly assist the dermatological community.
Primary particle acceleration above 100 TeV in the shell-type supernova remnant RX J1713.7-3946 with deep HESS observations
2006-11-27

The shell-type supernova remnant RX J1713.7--3946 was observed during three years with the H.E.S.S. Cherenkov telescope system. The first observation campaign in 2003 yielded the first-ever resolved TeV gamma-ray image. Follow-up observations in 2004 and 2005 revealed the very-high-energy gamma-ray morphology with unprecedented precision and enabled spatially resolved spectral studies. Combining the data of three years, we obtain significantly increased statistics and energy coverage of the gamma-ray spectrum as compared to earlier H.E.S.S. results. We present the analysis of the data of different years separately for comparison and demonstrate that the telescope system operates stably over the course of three years. When combining the data sets, a gamma-ray image is obtained with a superb angular resolution of 0.06 degrees. The combined spectrum extends over three orders of magnitude, with significant gamma-ray emission approaching 100 TeV. For realistic scenarios of very-high-energy gamma-ray production, the measured gamma-ray energies imply efficient particle acceleration of primary particles, electrons or protons, to energies exceeding 100 TeV in the shell of RX J1713.7--3946.
Properties of Indium Oxide Semiconducting Sensors Deposited by Different Techniques
2006-11-27

Semiconducting In2O3 gas sensors have been fabricated by two different deposition techniques, i.e., spin-coating and screen-printing. In both cases the same starting material – sol-gel-prepared cubic In2O3 – was used for the deposition in order to ensure a better comparability of the different sensing layers. The morphology of the layers has been characterized using scanning electron microscopy (SEM) technique. The layers deposited by different methods show similar grain size and porosity. Furthermore, Dc electrical tests have been performed to analyze the sensing properties of the different gas sensors. Reducing gases (CO and propanal) as well as oxidizing gases (NO2 and ozone) were used as test gases in the background of dry and humidified synthetic air. All measurements were performed at several temperatures. It was found that the spin-coated and screen-printed layers show different sensing properties, i.e., screen-printed sensors showed higher sensor signals than spin-coated sensors for CO, propanal, and NO2. The most striking differences appeared in the detection of ozone. In this case, spin-coated sensors showed a higher performance than screen-printed sensors. Higher ozone concentrations led to saturation effects for the latter.
Error Detection Techniques Applicable in an Architecture Framework and Design Methodology for Autonomic SoCs
2006-11-27

This work-in-progress paper surveys error detection techniques for transient, timing, permanent and logical errors in system-on-chip (SoC) design and discusses their applicability in the design of monitors for our Autonomic SoC architecture framework. These monitors will be needed to deliver necessary signals to achieve fault-tolerance, self-healing and self-calibration in our Autonomic SoC architecture. The framework combines the monitors with a well-tailored design methodology that explores how the Autonomic SoC (ASoC) can cope with malfunctioning subcomponents.
Formation in a Rat Median Nerve Model – Influence of Distal Stump and Muscular Coating
2006-11-27

The purpose of this study was to investigate neuroma formation and the impact of distal stump factors on this process in a rat median nerve model. In three different groups, the median nerve was exposed in the axilla and a gap was created. In the first group, a short gap of 1 cm (short gap group) was created while, in the second, a long gap of 2 cm (long gap group) was made between the proximal and distal nerve stump. A further group of animals was used to analyze the development of neuroma formation under circumstances of burying the proximal stump into adjacent muscle with the presence of a long gap of 2 cm (muscle-covered group). The use of different gap lengths between the proximal and distal stump should allow one to gain more information about possible dilution effects of distal nerve stump factors that may contribute to the size of neuroma formation. In the muscle-covered group, burying the proximal stump into the pectoral muscle was used in combination with a long defect of 2 cm. Nine months post procedure, animals were sacrificed and histologic analysis was performed. The area of the neuromas in cross section was measured and the neural-to-connective-tissue ratio was estimated.
Regulation of emotional responses elicited by threat‐related stimuli
2006-11-28

Abstract The capacity to voluntarily regulate emotions is critical for mental health, especially when coping with aversive events. Several neuroimaging studies of emotion regulation found the amygdala to be a target for downregulation and prefrontal regions to be associated with downregulation. To characterize the role of prefrontal regions in bidirectional emotion regulation and to investigate regulatory influences on amygdala activity and peripheral physiological measures, a functional magnetic resonance imaging (fMRI) study with simultaneous recording of self‐report, startle eyeblink, and skin conductance responses was carried out. Subjects viewed threat‐related pictures and were asked to up‐ and downregulate their emotional responses using reappraisal strategies. While startle eyeblink responses (in successful regulators) and skin conductance responses were amplified during upregulation, but showed no consistent effect during downregulation, amygdala activity was increased and decreased according to the regulation instructions. Trial‐by‐trial ratings of regulation success correlated positively with activity in amygdala during upregulation and orbitofrontal cortex during downregulation. Downregulation was characterized by left‐hemispheric activation peaks in anterior cingulate cortex, dorsolateral prefrontal cortex, and orbitofrontal cortex and upregulation was characterized by a pattern of prefrontal activation not restricted to the left hemisphere. Further analyses showed significant overlap of prefrontal activation across both regulation conditions, possibly reflecting cognitive processes underlying both up‐ and downregulation, but also showed distinct activations in each condition. The present study demonstrates that amygdala responses to threat‐related stimuli can be controlled through the use of cognitive strategies depending on recruitment of prefrontal areas, thereby changing the subject's affective state. Hum Brain Mapp, 2007. © 2006 Wiley‐Liss, Inc.
Boswellic Acids: Biological Actions and Molecular Targets
2006-11-28

Gum resin extracts of Boswellia species have been traditionally applied in folk medicine for centuries to treat various chronic inflammatory diseases, and experimental data from animal models and studies with human subjects confirmed the potential of B. spec extracts for the treatment of not only inflammation but also of cancer. Analysis of the ingredients of these extracts revealed that the pentacyclic triterpenes boswellic acids (BAs) possess biological activities and appear to be responsible for the respective pharmacological actions. Approaches in order to elucidate the molecular mechanisms underlying the biological effects of BAs identified 5-lipoxygenase, human leukocyte elastase, toposiomerase I and II, as well as IkappaB kinases as molecular targets of BAs. Moreover, it was shown that depending on the cell type and the structure of the BAs, the compounds differentially interfere with signal transduction pathways including Ca(2+/-) and MAPK signaling in various blood cells, related to functional cellular processes important for inflammatory reactions and tumor growth. This review summarizes the biological actions of BAs on the cellular and molecular level and attempts to put the data into perspective of the beneficial effects manifested in animal studies and trials with human subjects related to inflammation and cancer.
Substantia nigra hypoechogenicity: Definition and findings in restless legs syndrome
2006-11-28

Abstract Pathological studies demonstrate a decreased iron content in the substantia nigra (SN) contributing to the pathophysiology of restless legs syndrome (RLS). SN echogenicity as measured by transcranial sonography (TCS) correlates with the SN iron content. The objective of this study was to determine a critical value to define SN hypoechogenicity as a potential marker for RLS. There were 49 RLS patients (39 idiopathic, 10 secondary) and 49 age‐ and sex‐matched controls who underwent TCS by 2 independent and blinded examiners to determine the area of SN echogenicity. We found that SN echogenicity is significantly decreased in RLS patients compared to healthy controls ( P &lt; 0.001). SN hypoechogenicity (sum area of SN echogenicity of both sides &lt; 0.2 cm 2 ) is more common in idiopathic than in secondary RLS patients. The area under curve for idiopathic RLS versus controls (receiver operating characteristics) is 0.91, specificity is 0.90, and sensitivity is 0.82. TCS provides an interesting additional instrument in the diagnosis of RLS. Therefore, SN hypoechogenicity (SN sum area &lt; 0.2 cm 2 ), which is supposed to indicate a decreased SN iron content, is a marker for RLS. Further studies are needed to investigate its significance for the pathophysiology of this frequent movement disorder and possible clinical applications. © 2006 Movement Disorder Society
Strong genetic evidence for association of TOR1A/TOR1B with idiopathic dystonia
2006-11-28

Recently, association of a TOR1A(DYT1)/TOR1B risk haplotype with common forms of idiopathic dystonia has been reported in the Icelandic population. Here we report a strong association of two single nucleotide polymorphisms within or in close proximity to the TOR1A 3'UTR, with the lowest p value being 0.000008, in a larger cohort of German and Austrian patients with predominantly focal sporadic dystonia.
Enzyme‐Catalyzed Sulfide Ring Formation in Lantibiotics
2006-11-28

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.