julilili42/papers huggingface dataset:
A phase II study of alemtuzumab, fludarabine, cyclophosphamide, and doxorubicin (Campath-FCD) in peripheral T-cell lymphomas
2010-02-08

The clinical course of peripheral T-cell lymphoma (PTCL) is usually aggressive and the prognosis unfavorable. Therefore, there is a need for improvement of treatment options. Patients with newly diagnosed (n = 27) or refractory/relapsed (n = 11) PTCL received a combination of alemtuzumab, fludarabine, cyclophosphamide, and doxorubicin. The overall response rate (ORR) was 61%, with a complete response rate of 39%. In newly diagnosed patients the ORR was 63%, the median overall survival 25.9 months, and progression-free survival 11.8 months. In relapsed/refractory patients the median OS was 6.1 months. The most frequent grade 3/4 toxicities were leukopenia (95% of patients) and thrombocytopenia (58%). Cytomegalovirus (CMV) reactivation occurred in 12 patients, but only two had CMV disease. Treatment-related deaths occurred in six newly diagnosed patients and one with relapsed/refractory disease. In conclusion, Campath-FCD is active in PTCL but is associated with significant toxicity and is, therefore, not recommended for use or further study. Further studies are warranted to investigate other approaches to combining alemtuzumab with chemotherapy for the treatment of PTCL.
Achilles tendon ossification after treatment with acitretin
2010-02-08

Achilles tendon ossifications are rare. Usually they develop after surgery or trauma. The present case report illustrates a severe and tender Achilles tendon ossification of 10cm in length a few months after treatment with acitretin for lichen ruber. With discontinuation of acitretin therapy, regression of pain was achieved but the ossification was irreversible. This case should raise awareness for possible and severe calcifications in the use of retinoid therapy.
Fungal carbohydrate support in the ectomycorrhizal symbiosis: a review
2010-02-09

Abstract Ectomycorrhizal (ECM) symbiosis is a mutualistic interaction between certain soil fungi and fine roots of perennial plants, mainly forest trees, by which both partners become capable of efficiently colonising nutrient‐limited environments. The success of this interaction is reflected in the dominance of ECM forest ecosystems in the Northern hemisphere. Apart from their economic importance (wood production), forest ecosystems are essential for large‐scale carbon sequestration, leading to substantial reductions in anthropogenic CO 2 release. The biological function of ECM symbiosis is the exchange of fungus‐derived mineral nutrients for plant‐derived carbohydrates. Improved plant nutrition as a result of this interaction, however, has a price. Together with their fungal partner, root systems of ECM plants can receive about half of the photosynthetically fixed carbon. To enable such a strong carbohydrate sink, the monosaccharide uptake capacity and carbohydrate flux through glycolysis and intermediate carbohydrate storage pools (trehalose and/or mannitol) of mycorrhizal fungi is strongly increased at the plant–fungus interface. Apart from their function as a carbohydrate store, trehalose/mannitol are additionally considered to be involved in carbon allocation within the fungal colony. Dependent on the fungal species involved in the symbiosis, regulation and fine‐tuning of fungal carbohydrate uptake and metabolism seems to be controlled either by developmental mechanisms or by the apoplastic sugar content. As a consequence of the increased carbohydrate demand in symbiosis, trees increase their photosynthetic capacity. In addition, host plants control and restrict carbohydrate flux towards their partner to avoid fungal parasitism. The mechanisms behind this phenomenon are still largely unknown but rates of local sucrose hydrolysis and hexose uptake by rhizodermal cells are thought to restrict fungal carbohydrate nutrition under certain conditions ( e.g . , reduced fungal nutrient export).
Deficient forward transduction and enhanced reverse transduction in the alpha tectorin C1509G human hearing loss mutation
2010-02-09

SUMMARY Most forms of hearing loss are associated with loss of cochlear outer hair cells (OHCs). OHCs require the tectorial membrane (TM) for stereociliary bundle stimulation (forward transduction) and active feedback (reverse transduction). Alpha tectorin is a protein constituent of the TM and the C1509G mutation in alpha tectorin in humans results in autosomal dominant hearing loss. We engineered and validated this mutation in mice and found that the TM was shortened in heterozygous TectaC1509G/+ mice, reaching only the first row of OHCs. Thus, deficient forward transduction renders OHCs within the second and third rows non-functional, producing partial hearing loss. Surprisingly, both TectaC1509G/+ and TectaC1509G/C1509G mice were found to have increased reverse transduction as assessed by sound- and electrically-evoked otoacoustic emissions. We show that an increase in prestin, a protein necessary for electromotility, in all three rows of OHCs underlies this phenomenon. This mouse model demonstrates a human hearing loss mutation in which OHC function is altered through a non-cell-autonomous variation in prestin.
Reconstitution of natural killer cell receptors influences natural killer activity and relapse rate after haploidentical transplantation of T- and B-cell depleted grafts in children
2010-02-09

Our results indicate a fast recovery of functional and alloreactive natural killer cells with a constant KIR pattern after haploidentical transplantation with T- and B-cell depleted grafts. Moreover, these natural killer cells can mediate antibody-dependent cellular cytotoxicity and therefore may allow for an early use of antibodies against residual malignant cells.
Amorphous silicon based p‐i‐i‐n photodetectors for point‐of‐care testing
2010-02-09

Abstract Modern medical diagnostics demands point‐of‐care testing (POCT) systems for quick tests in clinical or out‐patient environments. This investigation combines the Reflectometric Interference Spectroscopy (RIfS) with thin film technology for a highly sensitive, direct optical and label‐free detection of proteins, e.g. inflammation or cardiovascular markers. Amorphous silicon (a‐Si) based thin film photodetectors replace the so far needed spectrometer and permit downsizing of the POCT system. Photodetectors with p‐i‐i‐n structure adjust their spectral sensitivity according to the applied read‐out voltage. The use of amorphous silicon carbide in the p‐type and the first intrinsic layer enhances the sensitivity through very low dark currents of the photodetectors and enables the adjustment of their absorption characteristics. Integrating the thin film photodetectors on the rear side of the RIfS substrate eliminates optical losses and distortions, as compared to the standard RIfS setup. An integrated Application Specific Integrated Circuit (ASIC) chip performs a current‐frequency conversion to accurately detect the photocurrent of up to eight parallel photodetector channels. In addition to the optimization of the photo‐detectors, this contribution presents first successful direct optical and label‐free RIfS measurements of C‐reactive protein (CRP) and D‐dimer in buffer solution in physiological relevant concentrations. (© 2010 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Nucleophilic [18F]Fluorination and subsequent decarbonylation of methoxy‐substituted nitro‐ and halogen‐benzenes activated by one or two formyl groups
2010-02-09

Abstract As model reactions for the introduction of 18 F into protected aromatic amino acids, the replacement of NO 2 , Cl, Br and F by [ 18 F]fluoride in 2‐isophthalaldehyde and 2‐terephthalaldehyde derivatives which model 18 F‐DOPA and 18 F‐tyrosine was investigated by comparing labelling yields and reaction rates with those of corresponding mono‐aldehyde compounds. All isophthalaldehydes showed maximum radiochemical yields (79 to 86%) at 140°C and in comparison with the corresponding mono‐aldehydes the reaction proceeded faster. At lower temperature the reaction already resulted in high yields, e.g. 2‐nitroisophthalaldehyde was labelled with a yield of 78% at 25°C after 7 min, whereas 2‐nitrobenzaldehyde only reached a yield of 1.7% under the same reaction conditions. The 18 F/NO 2 exchange in nitroterephthalaldehydes proceeded more slowly and with lower radiochemical yields when compared with corresponding isophthalaldehydes and monoaldehydes. The decarbonylation of 18 F‐labelled aromatic dialdehydic compounds with 4 eq. of Wilkinson's catalyst at 150°C in benzonitrile resulted in high yields, e.g. 2‐[ 18 F]fluoro‐5‐methoxyisophthalaldehyde and 4‐[ 18 F]fluoro‐2‐methoxy‐5‐methylisophthalaldehyde were decarbonylated efficiently with yields of 67±3% and 72±2%, respectively. Copyright © 2010 John Wiley &amp; Sons, Ltd.
Sorting of plant vacuolar proteins is initiated in the ER
2010-02-10

Transport of soluble cargo molecules to the lytic vacuole of plants requires vacuolar sorting receptors (VSRs) to divert transport of vacuolar cargo from the default secretory route to the cell surface. Just as important is the trafficking of the VSRs themselves, a process that encompasses anterograde transport of receptor-ligand complexes from a donor compartment, dissociation of these complexes upon arrival at the target compartment, and recycling of the receptor back to the donor compartment for a further round of ligand transport. We have previously shown that retromer-mediated recycling of the plant VSR BP80 starts at the trans-Golgi network (TGN). Here we demonstrate that inhibition of retromer function by either RNAi knockdown of sorting nexins (SNXs) or co-expression of mutants of SNX1/2a specifically inhibits the ER export of VSRs as well as soluble vacuolar cargo molecules, but does not influence cargo molecules destined for the COPII-mediated transport route. Retention of soluble cargo despite ongoing COPII-mediated bulk flow can only be explained by an interaction with membrane-bound proteins. Therefore, we examined whether VSRs are capable of binding their ligands in the lumen of the ER by expressing ER-anchored VSR derivatives. These experiments resulted in drastic accumulation of soluble vacuolar cargo molecules in the ER. This demonstrates that the ER, rather than the TGN, is the location of the initial VSR-ligand interaction. It also implies that the retromer-mediated recycling route for the VSRs leads from the TGN back to the ER.
Integration of Vibrotactile Signals for Whisker-Related Perception in Rats Is Governed by Short Time Constants: Comparison of Neurometric and Psychometric Detection Performance
2010-02-10

Rats explore environments by sweeping their whiskers across objects and surfaces. Both sensor movement and repetitive sweeping typical for this behavior require that vibrotactile signals are integrated over time. While temporal integration properties of neurons along the whisker somatosensory pathway have been studied extensively, the consequences for behavior are unknown. Here, we investigate the ability of head-fixed rats to integrate information over time for the detection of near-threshold pulsatile deflection sequences applied to a single whisker. Psychometric detection performance was assessed with whisker stimuli composed of different numbers of pulses (1-31) delivered at varying frequencies (10, 20, 100 Hz). Detection performance indeed improved with increasing number and frequency of pulses, albeit this improvement was much lower than predicted by probabilistic combination, suggesting highly sublinear integration of pulses. This behavioral observation was reflected in the firing properties of concomitantly recorded barrel cortex neurons, which showed substantial response adaptation to repetitive whisker deflection. To estimate the integration time with which barrel cortex neuronal activity must be read out to match behavior, we constructed a model monitoring spiking activity of simulated neuronal pools, where spike trains were channeled through a leaky integrator with exponential decay. Detection was accomplished by simple threshold crossings. This simple model gave an excellent match of neurometric and psychometric data at surprisingly small time constants τ of 5–8 ms, thus limiting integration largely to &lt;25 ms. This result carries important implications regarding sensory processing for whisker-mediated perception.
Spontaneous pneumomediastinum in anorexia nervosa: A case report and review of the literature on pneumomediastinum and pneumothorax
2010-02-10

Abstract We report a case of a 20‐year‐old white woman with the history of anorexia nervosa presenting with spontaneous pneumomediastinum (SPM). On admission, her body mass index (BMI) was 9.9 kg/m 2 . Physical examination revealed subcutaneous crepitation especially in the axillae, the intercostal spaces, between the scapulae and along the spine. A chest X‐ray showed extensive tissue emphysema, especially in the upper mediastinum. In a computed tomography (CT) scan, additional air was found in the upper retroperitoneal space adjacent to the stomach and to the left of the aorta. The patient recovered clinically within three weeks, and a CT scan showed a complete remission of the pneumomediastinum and subcutaneous emphysema. Based on this, case review of the literature about the frequency of pneumomediastinum in young patients with low weight is presented concerning epidemiology, etiology, symptoms, diagnosis, treatment, time to recovery and prognosis. Copyright © 2010 John Wiley &amp; Sons, Ltd and Eating Disorders Association.
Prevalence and Incidence of Endocrine Disorders in Children: Results of a Survey in Baden-Wuerttemberg and Bavaria (EndoPrIn BB) 2000–2001
2010-02-10

A pioneer study has been established in Germany for investigating the frequency of AGS (CAH), PP, PCH, MB, UTS, and GHD among children and adolescents. Our data shows that these disorders occur in approx. 2,700 children per year in total Germany, and about 12 000 of these children need to be treated in specialized paediatric endocrinological centres.
PET/MRI: Paving the Way for the Next Generation of Clinical Multimodality Imaging Applications
2010-02-11

Multimodality imaging and, more specifically, the combination of PET and CT has matured into an important diagnostic tool. During the same period, concepts for PET scanners integrated into an MR tomograph have emerged. The excellent soft-tissue contrast of MRI and the multifunctional imaging options it offers, such as spectroscopy, functional MRI, and arterial spin labeling, complement the molecular information of PET. The development of a fully integrated PET/MRI system is technologically challenging. It requires not only significant modifications of the PET detector to make it compact and insensitive to magnetic fields but also a major redesign of the MRI hardware.
Excessive HDAC activation is critical for neurodegeneration in the rd1 mouse
2010-02-11

Inherited retinal degenerations, collectively termed retinitis pigmentosa (RP), constitute one of the leading causes of blindness in the developed world. RP is at present untreatable and the underlying neurodegenerative mechanisms are unknown, even though the genetic causes are often established. Acetylation and deacetylation of histones, carried out by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively, affects cellular division, differentiation, death and survival. We found acetylation of histones and probably other proteins to be dramatically reduced in degenerating photoreceptors in the rd1 human homologous mouse model for RP. Using a custom developed in situ HDAC activity assay, we show that overactivation of HDAC classes I/II temporally precedes photoreceptor degeneration. Moreover, pharmacological inhibition of HDACs I/II activity in rd1 organotypic retinal explants decreased activity of poly-ADP-ribose-polymerase and strongly reduced photoreceptor cell death. These findings highlight the importance of protein acetylation for photoreceptor cell death and survival and propose certain HDAC classes as novel targets for the pharmacological intervention in RP.
The imposed gift of Versailles: the fiscal effects of restricting the size of Germany's armed forces, 1924–9
2010-02-11

Weimar's politicians used to attribute the continuous budget crises after the currency stabilization of 1923–4 to the burden put on the German economy by the Treaty of Versailles, in particular the reparation payments. This argument, which is still popular, neglects the fact that the restriction of the German military to 115,000 men relieved the German central budget considerably. In a counterfactual analysis we assess the savings in additional military costs and compare them to the reparation payments. Depending on the character of the foreign policy pursued by an unrestricted Germany, we find that the net effect of the Treaty's stipulations on the German central budgets was either much lower than hitherto thought or even positive. This finding gives support to the argument that Germany suffered from home‐made political failure even in the relatively stable period from 1924 to 1929.
Bimodal single molecule microscopy: multiparameter spectroscopy gives insight into photodegradation processes
2010-02-11

The triumphal course of optical single molecule studies mainly focuses on fluorescence based techniques. However, the structural insight, which can be gained by these methods, is often rather limited due to the broad and unstructured fluorescence spectra. This restriction may be overcome by surface enhanced Raman spectroscopy (SERS), which provides a chemical fingerprint of the investigated species. Nevertheless, for complex systems such as e. g. proteins, the interpretation of the obtained spectra is often too intricate. We present a novel bimodal microscopy approach to correlate the information content of the two spectroscopic modes on the single molecule level. By performing both, fluorescence and SERS spectroscopy on the same individual bichromophoric autofluorescent protein, we are able to assign distinct Raman bands to isolated fluorescence forms. On basis of these data we compare Raman spectra of native and photobleached proteins independently for the two distinct spectral forms. This in turn enables us to study the individual photodegradation processes and to open the field of elucidating the chemical structure of these compounds by spectroscopic methods in the single molecule level.
Total Synthesis of Myrtucommulone A
2010-02-12

In a one-step conversion, commercially available or known compounds are connected to form myrtucommulone A, an anti-inflammatory and apoptosis-inducing substance from the common myrtle Myrtus communis (see scheme). This strategy can be used, as well to prepare myrtucommulone libraries.
Pionic contribution to neutrinoless double beta decay
2010-02-12

It is well known that neutrinoless double decay is going to play a crucial role in settling the neutrino properties, which cannot be extracted from the neutrino oscillation data. It is, in particular, expected to settle the absolute scale of neutrino mass and determine whether the neutrinos are Majorana particles, i.e. they coincide with their own antiparticles. In order to extract the average neutrino mass from the data one must be able to estimate the contribution all possible high mass intermediate particles. The latter, which occur in practically all extensions of the standard model, can, in principle, be differentiated from the usual mass term, if data from various targets are available. One, however, must first be able reliably calculate the corresponding nuclear matrix elements. Such calculations are extremely difficult since the effective transition operators are very short ranged. For such operators processes like pionic contributions, which are usually negligible, turn out to be dominant. We study such an effect in a non relativistic quark model for the pion and the nucleon.
TRPM3 is expressed in sphingosine‐responsive myelinating oligodendrocytes
2010-02-15

J. Neurochem. (2010) 114 , 654–665. Abstract Oligodendrocytes are the myelin‐forming cells of the CNS and guarantee proper nerve conduction. Sphingosine, one major component of myelin, has recently been identified to activate TRPM3, a member of the melastatin‐related subfamily of transient receptor potential (TRP) channels. TRPM3 has been demonstrated to be expressed in brain with unknown cellular distribution. Here, we show for the first time that TRPM3 is expressed in oligodendrocytes in vitro and in vivo . TRPM3 is present during oligodendrocyte differentiation. Immunohistochemistry of adult rat brain slices revealed staining of white matter areas, which co‐localized with oligodendrocyte markers. Analysis of the developmental distribution revealed that, prior to myelination, TRPM3 channels are localized on neurons. On oligodendrocytes they are found after the onset of myelination. RT‐PCR studies showed that the transcription of TRPM3 splice variants is also developmentally regulated in vitro . Ca 2+ imaging approaches revealed the presence of a sphingosine‐induced Ca 2+ entry mechanism in oligodendrocytes – with a pharmacological profile similar to the profile published for heterologously expressed TRPM3. These findings indicate that TRPM3 participates as a Ca 2+ ‐permeable and sphingosine‐activated channel in oligodendrocyte differentiation and CNS myelination.
Neuroimaging of eye position reveals spatial neglect
2010-02-15

Conjugate eye deviation describes the tonic horizontal deviation of the eyes in acute stroke patients. Here we investigate whether measuring patients' eye-in-head position in clinical magnetic resonance imaging or computed tomography scans obtained at admission shows a specific relationship to spatial neglect. We investigated 124 continuously admitted subjects with unilateral, first-ever left- or right-sided stroke. To control for the possibility that the degree of eye deviation is related to lesion size rather than spatial neglect, overall lesion volume was used as a covariate in the statistical analysis. Horizontal eye-in-head deviation on clinical brain scans appeared to be associated with spatial neglect rather than with brain damage per se. In contrast to the subject groups without the disorder, the patients with spatial neglect showed an eye-in-head position that was significantly deviated towards the ipsilesional right. Evaluation of eye-in-head position on clinical scans thus may be an additional helpful tool for diagnosing spatial neglect, particularly in the very early period of the stroke.
Multi-walled carbon nanotubes affect drug transport across cell membrane in rat astrocytes
2010-02-15

The impact of carbon nanotubes on the cell membrane is an aspect of particular importance and interest in the study of carbon nanotubes' interactions with living systems. One of the many functions of the cell membrane is to execute substance transport into and out of the cell. We investigated the influence of multi-walled carbon nanotubes (MWCNTs) on the transport of several compounds across in the cell membrane of rat astrocytes using flow cytometry. These compounds are fluorescein diacetate, carboxyfluorescein diacetate, rhodamine 123 and doxorubicin, which are prosubstrate/substrates of multidrug transporter proteins. Results showed that MWCNTs significantly inhibited cellular uptake of doxorubicin but not the other drugs and the mode of loading made a significant difference in doxorubicin uptake. Retention of fluorescein, carboxyfluorescein and rhodamine 123 was remarkably higher in MWCNT-exposed cells after an efflux period. A kinetics study also demonstrated slower efflux of intracellular fluorescein and rhodamine 123. Data presented in this paper suggest that MWCNTs could affect drug transport across cell membranes. The implications of the findings are discussed.