julilili42/papers huggingface dataset:
Diagnostic Value of EAAT-1 and Kir7.1 for Distinguishing Endolymphatic Sac Tumors From Choroid Plexus Tumors
2012-06-16

The endolymphatic sac tumor (ELST) is a low-grade carcinoma originating in the ear. These extremely rare tumors are capable of invading the cerebellopontine angle and might be mistaken for choroid plexus tumors (CPTs) in this region. Currently, these tumors are distinguished by conventional morphologic and immunohistochemical studies for S-100, cytokeratin, and GFAP expression, but all markers are variably expressed by both tumors. Therefore, we examined new promising markers such as EAAT-1 and Kir7.1 in 4 ELSTs and 35 CPTs located in the fourth ventricle or at the cerebellopontine angle in adults. Immunohistochemical expression of Kir7.1 was found in 30 (100%) of 30 and EAAT-1 in 32 (91%) of 35 CPTs tested and was absent in all ELSTs. Expression of GFAP was found in 16 (55%) and S-100 in 29 (100%) of 29 CPTs tested, but both markers were also expressed in 2 of 4 ELSTs examined. Specificity and sensitivity of Kir7.1 (both 100%) and EAAT-1 (100% and 91%, respectively) were superior to the values for S-100 (50% and 100%, respectively) and GFAP (50% and 55%, respectively) for distinguishing CPT from ELST.
Defective Macrophage Migration in Gαi2- but Not Gαi3-Deficient Mice
2012-06-17

Abstract Various heterotrimeric Gi proteins are considered to be involved in cell migration and effector function of immune cells. The underlying mechanisms, how they control the activation of myeloid effector cells, are not well understood. To elucidate isoform-redundant and -specific roles for Gαi proteins in these processes, we analyzed mice genetically deficient in Gαi2 or Gαi3. First, we show an altered distribution of tissue macrophages and blood monocytes in the absence of Gαi2 but not Gαi3. Gαi2-deficient but not wild-type or Gαi3-deficient mice exhibited reduced recruitment of macrophages in experimental models of thioglycollate-induced peritonitis and LPS-triggered lung injury. In contrast, genetic ablation of Gαi2 had no effect on Gαi-dependent peritoneal cytokine production in vitro and the phagocytosis-promoting function of the Gαi-coupled C5a anaphylatoxin receptor by liver macrophages in vivo. Interestingly, actin rearrangement and CCL2- and C5a anaphylatoxin receptor-induced chemotaxis but not macrophage CCR2 and C5a anaphylatoxin receptor expression were reduced in the specific absence of Gαi2. Furthermore, knockdown of Gαi2 caused decreased cell migration and motility of RAW 264.7 cells, which was rescued by transfection of Gαi2 but not Gαi3. These results indicate that Gαi2, albeit redundant to Gαi3 in some macrophage activation processes, clearly exhibits a Gαi isoform-specific role in the regulation of macrophage migration.
Clofarabine‐containing conditioning regimen for allo‐SCT in AML/ALL patients: a survey from the Acute Leukemia Working Party of EBMT
2012-06-17

Abstract Clofarabine ( CLO ), a second‐generation purine analogue, has demonstrated an efficient anti‐leukemia activity while showing a favorable toxicity profile. This retrospective multicenter report assessed the outcome of 90 patients who received a CLO ‐containing conditioning regimen before allo‐ SCT for AML ( n = 69) or ALL ( n = 21). Median age was 42 yr at transplant. The majority of cases ( n = 66) presented with an active disease at transplant while 38 patients had received previous transplantation(s). A total of 88 and two patients received a reduced‐intensity conditioning or a myeloablative regimen, respectively. Engraftment was achieved in 97% of evaluable patients. With a median follow‐up of 14 months (range, 1–45), the 2‐year OS , LFS , relapse, and NRM rates were 28 ± 5%, 23 ± 5%, 41 ± 6%, and 35 ± 5%, respectively. When comparing AML and ALL patients, OS and LFS were significantly higher for AML ( OS , 35 ± 6% vs. 0%, P &lt; 0.0001); LFS : 30 ± 6% vs. 0%, P &lt; 0.0001). In a Cox multivariate analysis, an AML diagnosis was the only factor associated with a better LFS ( HR = 0.37; 95% CI , 0.21–0.66; P = 0.001). We conclude that a CLO ‐containing conditioning regimen prior to allo‐ SCT might be an effective treatment. Prospective studies are needed to evaluate the potential role of CLO as part of conditioning regimens in acute leukemias.
Computing cartograms with optimal complexity
2012-06-17

In a rectilinear dual of a planar graph vertices are represented by simple rectilinear polygons, while edges are represented by side-contact between the corresponding polygons. A rectilinear dual is called a cartogram if the area of each region is equal to a pre-specified weight.
Cluster headache and neuropsychological functioning
2012-06-18

Background: Despite significant advances in unravelling the pathophysiology of cluster headache (CH), little is known about neuropsychological functioning. Apart from neuroimaging studies indicating involvement of posterior hypothalamic and other areas frequently involved in nociception, some studies suggest involvement of prefrontal areas. Among others, these mediate executive functioning (EF). Methods: Therefore, three neuropsychological tests (Trail Making Test (TMT), Go/Nogo Task and Stroop Task) were completed by four headache patient samples (chronic CH, episodic CH in the active or inactive period, and migraine patients) and compared to healthy controls. Results: Analyses revealed that patients especially with chronic and active episodic CH were particularly impaired in tests relying more on intact EF (i.e. TMT-B, Stroop interference) than on basal cognitive processes (i.e. TMT-A, Stroop naming). Within the CH groups performance decreased linearly with increasing severity. Discussion: These findings are in line with a recently proposed involvement of prefrontal structures in CH pathophysiology as patients performed worse on neuropsychological tasks relying on these structures. Impaired EF could also result from medication and sleep disturbances due to active CH. Because the decreased performance was also present outside the attacks it may hint at generally altered brain functions, but do not necessarily reflect clinically relevant behaviour.
High‐resolution water content estimation from surface‐based ground‐penetrating radar reflection data by impedance inversion
2012-06-19

Mapping hydrological parameter distributions in high resolution is essential to understand and simulate groundwater flow and contaminant transport. Of particular interest is surface‐based ground‐penetrating radar (GPR) reflection imaging in electrically resistive sediments because of the expected close link between the subsurface water content and the dielectric permittivity, which controls GPR wave velocity and reflectivity. Conventional tools like common midpoint (CMP) velocity analysis provide physical parameter models of limited resolution only. We present a novel reflection amplitude inversion workflow for surface‐based GPR data capable of resolving the subsurface dielectric permittivity and related water content distribution with markedly improved resolution. Our scheme is an adaptation of a seismic reflection impedance inversion scheme to surface‐based GPR data. Key is relative‐amplitude‐preserving data preconditioning including GPR deconvolution, which results in traces with the source‐wavelet distortions and propagation effects largely removed. The subsequent inversion for the underlying dielectric permittivity and water content structure is constrained by in situ dielectric permittivity data obtained by direct‐push logging. After demonstrating the potential of our novel scheme on a realistic synthetic data set, we apply it to two 2‐D 100 MHz GPR profiles acquired over a shallow sedimentary aquifer resulting in water content images of the shallow (3–7 m depth) saturated zone having decimeter resolution.
Alterations of the RANKL pathway in blood and bone marrow samples of prostate cancer patients without bone metastases
2012-06-19

Abstract OBJECTIVES The receptor activator of the NF‐kB ligand (RANKL) pathway is a key mediator of prostate cancer (PC)‐induced bone disease. However, little is known about this pathway in patients with non‐metastatic PC. We aimed to investigate whether changes of RANKL, its inhibitor osteoprotegerin (OPG) and bone marrow‐mesenchymal stromal cells (BM‐MSCs) occur in PC patients without manifest bone metastases. PATIENTS AND METHODS We determined OPG and soluble RANKL (sRANKL) in serum and corresponding bone marrow (BM) samples of 140 patients before radical prostatectomy by enzyme‐linked immunosorbent assay (ELISA). As control serum samples of 50 patients with benign prostate hyperplasia were analyzed. BM mononuclear cells (BMNCs) of 16 PC patients were analyzed for expression of RANKL and CD271 (as marker for MSCs) by flow cytometry. RESULTS PC patients had significantly lower serum levels of OPG compared to BPH patients ( P = 0.007), whereas no differences were observed for serum sRANKL ( P = 0.74). Both OPG and sRANKL concentrations of serum and corresponding BM samples correlated significantly ( P &lt; 0.0001 each). Interestingly, in PC patients, lower serum and BM OPG levels were associated with a higher proportion of BM‐MSCs ( P = 0.04 and 0.0016, respectively). No correlations were observed for sRANKL, OPG, BM‐MSCs, and established risk parameters of PC. DISCUSSION The results of the study indicate that localized PC is associated with early specific changes of the RANKL pathway in serum and bone marrow (BM). These changes might be part of the pre‐metastatic niche of PC and implicate a potential benefit of RANKL inhibition in patients with localized PC. Prostate 73: 162–168, 2013. © 2012 Wiley Periodicals, Inc.
Detection of DNA Adducts Originating from 1-Methoxy-3-indolylmethyl Glucosinolate Using Isotope-Dilution UPLC-ESI-MS/MS
2012-06-19

1-Methoxy-3-indolylmethyl (1-MIM) glucosinolate, present at substantial levels in several food crops (e.g., broccoli and cabbage), forms DNA adducts in vitro and is mutagenic to bacterial and mammalian cells after activation by the plant enzyme myrosinase. Moreover, a breakdown product, 1-MIM alcohol, is metabolized to a secondary reactive intermediate by some mammalian sulfotransferases (SULTs). First, we incubated herring-sperm DNA with 1-MIM glucosinolate in the presence of myrosinase. We identified and synthesized the predominant adducts, N(2)-(1-MIM)-dG and N(6)-(1-MIM)-dA, and developed an UPLC-ESI-MS/MS method for their specific detection using isotopic dilution. Second, we demonstrated both DNA adducts in target cells (Salmonella typhimurium TA100 and Chinese hamster V79) of standard mutagenicity tests treated with 1-MIM glucosinolate/myrosinase as well as in 1-MIM alcohol-treated Salmonella and V79 cells engineered for expression of human SULT1A1. Similar excesses of N(2)-(1-MIM)-dG over N(6)-(1-MIM)-dA adducts were found in all cellular models independent of the test compound (1-MIM glucosinolate or alcohol), whereas dA adducts predominated in the cell-free system. Finally, we detected both DNA adducts in colon tissue of a mouse orally treated with 1-MIM glucosinolate. We are going to use this specific and sensitive method for investigating genotoxic risks of food-borne exposure to 1-MIM glucosinolate in animal and human studies.
Lack of Brain-Derived Neurotrophic Factor Hampers Inner Hair Cell Synapse Physiology, But Protects against Noise-Induced Hearing Loss
2012-06-20

The precision of sound information transmitted to the brain depends on the transfer characteristics of the inner hair cell (IHC) ribbon synapse and its multiple contacting auditory fibers. We found that brain derived neurotrophic factor (BDNF) differentially influences IHC characteristics in the intact and injured cochlea. Using conditional knock-out mice (BDNF(Pax2) KO) we found that resting membrane potentials, membrane capacitance and resting linear leak conductance of adult BDNF(Pax2) KO IHCs showed a normal maturation. Likewise, in BDNF(Pax2) KO membrane capacitance (ΔC(m)) as a function of inward calcium current (I(Ca)) follows the linear relationship typical for normal adult IHCs. In contrast the maximal ΔC(m), but not the maximal size of the calcium current, was significantly reduced by 45% in basal but not in apical cochlear turns in BDNF(Pax2) KO IHCs. Maximal ΔC(m) correlated with a loss of IHC ribbons in these cochlear turns and a reduced activity of the auditory nerve (auditory brainstem response wave I). Remarkably, a noise-induced loss of IHC ribbons, followed by reduced activity of the auditory nerve and reduced centrally generated wave II and III observed in control mice, was prevented in equally noise-exposed BDNF(Pax2) KO mice. Data suggest that BDNF expressed in the cochlea is essential for maintenance of adult IHC transmitter release sites and that BDNF upholds opposing afferents in high-frequency turns and scales them down following noise exposure.
Regulation of Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) Channel Activity by cCMP
2012-06-20

Activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is facilitated in vivo by direct binding of the second messenger cAMP. This process plays a fundamental role in the fine-tuning of HCN channel activity and is critical for the modulation of cardiac and neuronal rhythmicity. Here, we identify the pyrimidine cyclic nucleotide cCMP as another regulator of HCN channels. We demonstrate that cCMP shifts the activation curves of two members of the HCN channel family, HCN2 and HCN4, to more depolarized voltages. Moreover, cCMP speeds up activation and slows down deactivation kinetics of these channels. The two other members of the HCN channel family, HCN1 and HCN3, are not sensitive to cCMP. The modulatory effect of cCMP is reversible and requires the presence of a functional cyclic nucleotide-binding domain. We determined an EC(50) value of ∼30 μm for cCMP compared with 1 μm for cAMP. Notably, cCMP is a partial agonist of HCN channels, displaying an efficacy of ∼0.6. cCMP increases the frequency of pacemaker potentials from isolated sinoatrial pacemaker cells in the presence of endogenous cAMP concentrations. Electrophysiological recordings indicated that this increase is caused by a depolarizing shift in the activation curve of the native HCN current, which in turn leads to an enhancement of the slope of the diastolic depolarization of sinoatrial node cells. In conclusion, our findings establish cCMP as a gating regulator of HCN channels and indicate that this cyclic nucleotide has to be considered in HCN channel-regulated processes.
Caught in the act: the first record of copulating fossil vertebrates
2012-06-20

The behaviour of fossil organisms can typically be inferred only indirectly, but rare fossil finds can provide surprising insights. Here, we report from the Eocene Messel Pit Fossil Site between Darmstadt and Frankfurt, Germany numerous pairs of the fossil carettochelyid turtle Allaeochelys crassesculpta that represent for the first time among fossil vertebrates couples that perished during copulation. Females of this taxon can be distinguished from males by their relatively shorter tails and development of plastral kinesis. The preservation of mating pairs has important taphonomic implications for the Messel Pit Fossil Site, as it is unlikely that the turtles would mate in poisonous surface waters. Instead, the turtles initiated copulation in habitable surface waters, but perished when their skin absorbed poisons while sinking into toxic layers. The mating pairs from Messel are therefore more consistent with a stratified, volcanic maar lake with inhabitable surface waters and a deadly abyss.
Eye Proprioception Used for Visual Localization Only If in Conflict with the Oculomotor Plan
2012-06-20

Both the corollary discharge of the oculomotor command and eye muscle proprioception provide eye position information to the brain. Two contradictory models have been suggested about how these two sources contribute to visual localization: (1) only the efference copy is used whereas proprioception is a slow recalibrator of the forward model, and (2) both signals are used together as a weighted average. We had the opportunity to test these hypotheses in a patient (R.W.) with a circumscribed lesion of the right postcentral gyrus that overlapped the human eye proprioceptive representation. R.W. was as accurate and precise as the control group (n = 19) in locating a lit LED that she viewed through the eye contralateral to the lesion. However, when the task was preceded by a brief (<1 s), gentle push to the closed eye, which perturbed eye position and stimulated eye proprioceptors in the absence of a motor command, R.W.'s accuracy significantly decreased compared with both her own baseline and the healthy control group. The data suggest that in normal conditions, eye proprioception is not used for visual localization. Eye proprioception is, however, continuously monitored to be incorporated into the eye position estimate when a mismatch with the efference copy of the motor command is detected. Our result thus supports the first model and, furthermore, identifies the limits for its operation.
Deconfinement phase transition in the Hamiltonian approach to Yang-Mills theory in Coulomb gauge
2012-06-20

\\nRecent results obtained for the deconfinement phase transition within the Hamiltonian approach to Yang–Mills theory are reviewed. Assuming a quasiparticle picture for the grand canonical gluon ensemble the thermal equilibrium state is found by minimizing the free energy with respect to the quasi-gluon energy. The deconfinement phase transition is accompanied by a drastic change of the infrared exponents of the ghost and gluon propagators. Above the phase transition the ghost form factor remains infrared divergent but its infrared exponent is approximately halved. The gluon energy being infrared divergent in the confined phase becomes infrared finite in the deconfined phase. Furthermore, the effective potential of the order parameter for confinement is calculated for SU(N) Yang–Mills theory in the Hamiltonian approach by compactifying one spatial dimension and using a background gauge fixing. In the simplest truncation, neglecting the ghost and using the ultraviolet form of the gluon energy, we recover the Weiss potential. From the full non-perturbative potential (with the ghost included) we extract a critical temperature of the deconfinement phase transition of 269 MeV for the gauge group SU(2) and 283 MeV for SU(3).\\n
Refined Analysis of the Critical Age Ranges of Childhood Overweight: Implications for Primary Prevention
2012-06-20

Prevention‐interventions would certainly benefit from a precise knowledge of the age range when the most pronounced increases in prevalence of overweight and obesity occur in the general population. Data of 15,662 subjects aged 2–18 years were obtained from a national representative health survey (German Health Interview and Examination Survey for Children and Adolescents (KiGGS)) conducted in Germany. Weight, height, and BMI z ‐scores were calculated relative to the UK 1990 reference, and prevalence of overweight and obesity was defined according to the IOTF (International Obesity Task Force) age‐ and sex‐specific cut‐offs. Univariate ANOVAs for overweight, obesity, weight, height, and BMI z ‐scores as dependent variables were employed to assess significant differences for these measures across various age levels. Significant analysis was followed by post‐hoc comparisons using Bonferroni adjustments. The main effect of age was estimated using a multinomial logistic regression model, and by defining the first derivative of a polynomial spline function. Different eclectic slopes over the entire age range from 2 to 18 years have been observed. Prevalence of overweight substantially increases between the 5th and the 8th year (12.5–21.4% P ≤ 0.001). Maximum increase of the polynomial fit was detected at 7.2 years. Our findings suggest a relatively narrow age range at the first school year when overweight in German children especially increases. We therefore propose that psychosocial correlates may be related to the general life‐time event around the age of entering school.
Modulations of neural activity in auditory streaming caused by spectral and temporal alternation in subsequent stimuli: a magnetoencephalographic study
2012-06-20

Abstract Background The aim of the present study was to identify a specific neuronal correlate underlying the pre-attentive auditory stream segregation of subsequent sound patterns alternating in spectral or temporal cues. Fifteen participants with normal hearing were presented with series’ of two consecutive ABA auditory tone-triplet sequences, the initial triplets being the Adaptation sequence and the subsequent triplets being the Test sequence. In the first experiment, the frequency separation (delta-f) between A and B tones in the sequences was varied by 2, 4 and 10 semitones. In the second experiment, a constant delta-f of 6 semitones was maintained but the Inter-Stimulus Intervals (ISIs) between A and B tones were varied. Auditory evoked magnetic fields (AEFs) were recorded using magnetoencephalography (MEG). Participants watched a muted video of their choice and ignored the auditory stimuli. In a subsequent behavioral study both MEG experiments were replicated to provide information about the participants’ perceptual state. Results MEG measurements showed a significant increase in the amplitude of the B-tone related P1 component of the AEFs as delta-f increased. This effect was seen predominantly in the left hemisphere. A significant increase in the amplitude of the N1 component was only obtained for a Test sequence delta-f of 10 semitones with a prior Adaptation sequence of 2 semitones. This effect was more pronounced in the right hemisphere. The additional behavioral data indicated an increased probability of two-stream perception for delta-f = 4 and delta-f = 10 semitones with a preceding Adaptation sequence of 2 semitones. However, neither the neural activity nor the perception of the successive streaming sequences were modulated when the ISIs were alternated. Conclusions Our MEG experiment demonstrated differences in the behavior of P1 and N1 components during the automatic segregation of sounds when induced by an initial Adaptation sequence. The P1 component appeared enhanced in all Test-conditions and thus demonstrates the preceding context effect, whereas N1 was specifically modulated only by large delta-f Test sequences induced by a preceding small delta-f Adaptation sequence. These results suggest that P1 and N1 components represent at least partially-different systems that underlie the neural representation of auditory streaming.
Contrast-Enhanced Ultrasound (CEUS) in the Diagnostic Algorithm of Hepatocellular and Cholangiocellular Carcinoma, Comments on the AASLD Guidelines
2012-06-21

Contrast-enhanced ultrasound (CEUS) has long been present in important guidelines and recommendations for the diagnostic work-up of focal liver lesions in patients with cirrhosis. These guidelines have included the guidelines of the American Association for the Study of Liver Diseases (AASLD) 2005, the Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma, the recommendations of the Japanese Society of Hepatology, and the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines 2004, 2008 and 2012 (in preparation). Recently, the AASLD removed CEUS from their guidelines in part because of the perceived possibility of false-positive hepatocellular carcinoma (HCC) diagnosis in patients with intrahepatic cholangiocarcinoma (ICC), and in part because CEUS is not available in the USA. This latter factor means that published results are not entirely applicable to a North American population. The present manuscript discusses the diagnostic algorithm of hepatocellular carcinoma and provides information on the differential diagnosis between HCC and ICC.