julilili42/papers huggingface dataset:
CT of Gastrointestinal Complications Associated with Hematopoietic Stem Cell Transplantation
2008-02-21

Although some overlap exists in the CT appearances of the different causes of bowel wall inflammation, the findings are frequently unique enough to suggest a specific diagnosis. Awareness of the specific time of occurrence, intensity of clinical symptoms, preferred localization, and extent of accompanying extraintestinal findings help to distinguish the different pathologic entities.
Natural female mating rate maximizes hatchling size in a marine invertebrate
2008-02-21

1. Males and females often differ in their optimal mating rates, resulting potentially in conflicts over remating. In species with separate sexes, females typically have a lower optimal mating rate than males, and can regulate contacts with males accordingly. The realized mating rate may therefore be closer to the female's optimum. In simultaneous hermaphrodites, however, it has been suggested that the intraindividual optimization between 'male' and 'female' interests generates more 'male'-driven mating rates. 2. In order to assess the consequences of variation in mating rate on 'female' reproductive output, we exposed the simultaneously hermaphroditic sea slug Chelidonura sandrana to four mating rate regimes and recorded the effects on a variety of fitness components. 3. In focal 'females', we found (i) a slight but significant linear decrease in fecundity with mating rate, whereas (ii) maternal investment in egg capsule volume peaked at an intermediate mating rate. 4. Combining the observed fecundity cost with the apparent benefits of larger offspring size suggests that total female fitness is maximized at an intermediate mating rate. With the latter being close to the natural mating rate of C. sandrana in the field, our findings challenge the assumption of 'male'-driven mating systems in simultaneous hermaphrodites. 5. Our study provides experimental evidence for various mathematical models in which female fitness is maximized at intermediate mating rates.
In‐situ X‐ray scattering studies of OFET interfaces
2008-02-21

Abstract We review recent work in the field of organic thin films and organic‐inorganic interfaces which is relevant for device applications and particularly organic field effect transistors (OFETs). Focussing on the structural properties of these systems we discuss results obtained mostly through X‐ray scattering techniques. We address the growth behaviour and interface formation of organic thin films including roughness evolution and crystal structure. In particular, we review real‐time studies of pentacene, diindenoperylene, and PTCDA deposition on different subtrates which illustrate their specific growth kinetics. Covering different thickness regimes we show how the molecular orientation depends on the substrate and the growth conditions. Finally, we address the structural properties of organic heterostructures, i.e. metal and insulator films on organics, demonstrating how to assess and control interdiffusion and thermal stability of the capping layers. (© 2008 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Chemical Sensors Based on Catalytic Reactions
2008-02-21

Abstract The sections in this article are Introduction Definitions and Classifications Typical Examples Calorimetric Sensors Electronic Conductance Sensors Sensing Process and Signal Transduction Modeling the Sensor Response Role of Contacts Materials Tin Oxide (SnO 2 ) Tungsten Oxide ( WO 3 ) Chromium Titanium Oxide ( Cr 2− x Ti x O 3 ) Gallium Oxide ( Ga 2 O 3 ) Solid‐State Electrochemical Sensors Conclusions
The maize (Zea maysL.)roothairless3gene encodes a putative GPI‐anchored, monocot‐specific, COBRA‐like protein that significantly affects grain yield
2008-02-23

Summary The rth3 ( roothairless 3 ) mutant is specifically affected in root hair elongation. We report here the cloning of the rth3 gene via a PCR‐based strategy (amplification of insertion mutagenized sites) and demonstrate that it encodes a COBRA‐like protein that displays all the structural features of a glycosylphosphatidylinositol anchor. Genes of the COBRA family are involved in various types of cell expansion and cell wall biosynthesis. The rth3 gene belongs to a monocot‐specific clade of the COBRA gene family comprising two maize and two rice genes. While the rice ( Oryza sativa ) gene OsBC1L1 appears to be orthologous to rth3 based on sequence similarity (86% identity at the protein level) and maize/rice synteny, the maize ( Zea mays L.) rth3‐like gene does not appear to be a functional homolog of rth3 based on their distinct expression profiles. Massively parallel signature sequencing analysis detected rth3 expression in all analyzed tissues, but at relatively low levels, with the most abundant expression in primary roots where the root hair phenotype is manifested. In situ hybridization experiments confine rth3 expression to root hair‐forming epidermal cells and lateral root primordia. Remarkably, in replicated field trials involving near‐isogenic lines, the rth3 mutant conferred significant losses in grain yield.
Cortical processing of residual ano‐rectal sensation in patients with spinal cord injury: an fMRI study
2008-02-24

Abstract Eleven paraplegic patients with complete traumatic spinal cord injuries (SCI) [according to American Spinal Injury Association (ASIA) criteria] at different levels (Th3–L3) were investigated during non‐painful stimulation of the distal rectum and anal canal, using event related functional magnetic resonance imaging. Although a complete lesion was clinically diagnosed in all, four of them experienced reproducible sensations during anal and/or rectal stimulation. In six patients, individual data analysis revealed significant activation in the right secondary somatosensory cortex SII, the posterior cingular gyrus, the prefrontal cortex, and the left posterior cerebellar lobe during either anal or rectal stimulation or both. A Region of interest analysis using a data mask from healthy controls confirmed that SCI patients demonstrate cortical activation in areas similar to those activated in healthy volunteers, but to a less extensive degree. This supports the notion that the diagnosis of complete spinal cord transsection by ASIA criteria alone may be insufficient for assessment of ‘completeness’ of cord lesions, and that visceral sensitivity testing may be required in addition.
6-mercaptopurine and 9-(2-phosphonyl-methoxyethyl) adenine (PMEA) transport altered by two missense mutations in the drug transporter gene ABCC4
2008-02-25

Multiple drug resistance protein 4 (MRP4, ABCC4) belongs to the C subfamily of the ATP-binding cassette (ABC) transporter superfamily and participates in the transport of diverse antiviral and chemotherapeutic agents such as 6-mercaptopurine (6-MP) and 9-(2-phosphonyl methoxyethyl) adenine (PMEA). We have undertaken a comprehensive functional characterization of protein variants of MRP4 found in Caucasians and other ethnicities. A total of 11 MRP4 missense genetic variants (nonsynonymous SNPs), fused to green fluorescent protein (GFP), were examined in Xenopus laevis oocytes for their effect on expression, localization, and function of the transporter. Radiolabeled 6-MP and PMEA were chosen as transport substrates. All MRP4 protein variants were found to be expressed predominantly in the oocyte membrane. A total of four variants (Y556C, E757 K, V776I, and T1142 M) exhibited a 20% to 40% reduced expression level compared to the wild type. Efflux studies showed that 6-MP is transported by MRP4 in unmodified form. Compared to wild-type MRP4, the transmembrane variant V776I, revealed a significant lower activity in 6-MP transport, while the amino acid exchange Y556C in the Walker(B) motif displayed significantly higher transport of PMEA. The transport properties of the other variants were comparable to wild-type MRP4. Our study shows that Xenopus oocytes are well suited to characterize MRP4 and its protein variants. Carriers of the rare MRP4 variants Y556C and V776I may have altered disposition of MRP4 substrates.
Growth modelling of non-functioning pituitary adenomas in patients referred for surgery
2008-02-25

Objective Recent observational studies have established progression and recurrence rates of pituitary adenomas. However, it is still unknown how individual pituitary adenomas grow over years and whether growth kinetics follow a distinct growth model. The objective of this study was to define a growth model for non-functioning pituitary adenomas. Methods Fifteen patients who had five or more serial high-quality examinations with magnetic resonance images or computerized tomography scans were identified among 216 patients with non-functioning pituitary adenomas. Tumour volumes were assessed using a stereological method based on the Cavalieri principle. Tumour growth during the observation period was analysed and different growth models were fitted to the data. Results Fifteen pituitary adenomas (12 recurrent tumours and 3 newly diagnosed tumours) were longitudinally observed during a median observation period of 7.4 years (range: 2.3–11.9 years). Growth kinetics could be described either by an exponential growth model (nine patients) or by a logistic model (five patients) with initial exponential growth followed by deceleration of growth. One tumour remained unchanged in size during the observation period. None of the adenomas showed accelerated growth during the observation period. Overall, the linear growth model was not suitable to describe the growth kinetics of non-functioning pituitary adenomas. Conclusions Our study shows that growth of pituitary adenomas can be described by distinct growth models. Knowledge of growth dynamics has implications for clinical practice and helps to adjust scanning protocols for follow-up investigations.
Neoadjuvant letrozole in postmenopausal estrogen and/or progesterone receptor positive breast cancer: A phase IIb/III trial to investigate optimal duration of preoperative endocrine therapy
2008-02-26

Abstract Background In recent years, preoperative volume reduction of locally advanced breast cancers, resulting in higher rates of breast-conserving surgery (BCS), has become increasingly important also in postmenopausal women. Clinical interest has come to center on the third-generation nonsteroidal aromatase inhibitors (AIs), including letrozole, for such neoadjuvant endocrine treatment. This usually lasts 3–4 months and has been extended to up to 12 months, but optimal treatment duration has not been fully established. Methods This study was designed as a multicenter, open-label, single-arm, exploratory phase IIb/III clinical trial of letrozole 2.5 mg, one tablet daily, for 4–8 months. The primary objective was to investigate the effect of neoadjuvant treatment duration on tumor regression and BCS eligibility to identify optimal treatment duration. Tumor regression (by clinical examination, mammography, and ultrasound), shift towards BCS eligibility, and safety assessments were the main outcome measures. Standard parametric and nonparametric descriptive statistics were performed. Results Letrozole treatment was received by 32 of the enrolled 33 postmenopausal women (median (range): 67.0 (56–85) years) with unilateral, initially BCS-ineligible primary breast cancer (clinical stage ≥ T2, N0, M0). Letrozole treatment duration in the modified intent-to-treat (ITT; required 4 months' letrozole treatment) analysis population (29 patients) was 4 months in 14 patients and &gt; 4 months in 15 patients. The respective per-protocol (PP) subgroup sizes were 14 and 11. The majority of partial or complete responses were observed at 4 months, though some beneficial responses occurred during prolonged letrozole treatment. Compared with baseline, median tumor size in the ITT population was reduced by 62.5% at Month 4 and by 70.0% at final study visit (Individual End). Similarly, in the PP population, respective reductions were 64.0% and 67.0%. Whereas initially all patients were mastectomy candidates, letrozole treatment enabled BCS (lumpectomy) in 22 ITT (75.9%) and 18 PP (72.0%) patients. Conclusion Over half of patients become BCS-eligible within 4 months of preoperative letrozole treatment. While prolonged treatment for up to 8 months can result in further tumor volume reduction in some patients, there is no clear optimum for treatment duration. Letrozole has a favorable overall safety and tolerability profile. Trial registration ClinicalTrials.gov identifier NCT00535418.
Effects of Plasmodium falciparum Parasite Population Size and Patient Age on Early and Late Parasitological Outcomes of Antimalarial Treatment in Children
2008-02-26

ABSTRACT The design and interpretation of trials assessing the chemotherapeutic effects of antimalarial drugs depend on our understanding of how different selection criteria affect treatment outcomes. In this study, we analyzed the effects of baseline parameters on the initial parasite elimination rate and the risk of subsequent recrudescence as a marker for incompletely eliminated asexual blood-stage parasites in pediatric patients with uncomplicated Plasmodium falciparum infection treated with amodiaquine in a high-transmission area. We found that (i) parasite population size and patient age independently determine early and late parasitological treatment outcome measurements; (ii) the rate of recrudescence is higher in patients 1 to 3 years of age than in patients aged &lt;1 or &gt;3 years; (iii) patients aged &gt;5 years with parasite densities between 2,000 and 10,000/μl have a lower recrudescence rate (13%; 95% confidence interval [CI], 8% to 21%) than patients aged &lt;5 years with parasite densities of &gt;10,000/μl (40%; 95% CI, 30% to 50%); and (iv) the sensitivity of detecting recrudescences outside this high-risk group, i.e., in patients of &gt;5 years of age or with parasite densities of &lt;10,000/μl, is as low as 27% or 22%, respectively. In conclusion, these findings highlight the need to use adequate selection criteria and to report parasitological outcome results adjusted for the readily available determinants of chemotherapeutic failure, i.e., patient age and baseline parasitemia. The thresholds may vary by transmission intensity and drug regimen. A better understanding of the limitations of antimalarial regimens in high-risk subgroups of patients has important implications for setting policy recommendations.
Temporal Generalization under Time Pressure in Humans
2008-02-26

In two experiments, participants performed a temporal generalization task in which they were asked to decide whether or not the durations of comparison stimuli were different from those of standard stimuli (750 ms, 1,000 ms, or 1,250 ms). One half of the participants was instructed to respond as quickly as possible, while the other half received no instruction concerning the speed of response. The relationship between stimulus duration and the time of response and the effect of time pressure on duration discrimination were examined. Response time increased as a linear function of the duration of the to-be-judged stimuli until a certain instant, which was defined as T 2 = s/(1 – b), where s refers to the internal representation of the standard duration and b to the decision threshold. Moreover, the participants systematically overestimated the presented intervals if they were asked to respond as fast as possible when the standard duration was either 1,000 ms or 1,250 ms, but not when the standard duration was 750 ms.
External vs. Internal Interactions in the Enantiodiscrimination of Fluorinated α‐Amino Acid Derivatives by Heptakis[2,3‐di‐O‐acetyl‐6‐O‐(tert‐butyldimethylsilyl)]‐β‐cyclodextrin, a Powerful Chiral Solvating Agent for NMR Spectroscopy
2008-02-26

Abstract NMR spectroscopic investigations involving extensive use of ROESY and DOSY techniques and comparison withsilylated‐acetylated linear dextrins as acyclic model compounds shed light on the origin of the phenomenon ofenantiodiscrimination of fluorinated α‐amino acid derivatives by heptakis[2,3‐di‐ O ‐acetyl‐6‐ O ‐( tert ‐butyldimethylsilyl)]‐β‐cyclodextrin. The effectiveness and versatility of the cyclic derivatized oligosaccharide as a chiral solvating agent for the NMR determination of enantiomeric purity in the same class of compounds is demonstrated. A regular correlation between the relative positions of enantiomers' signals and absolute configurations is observed. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)
Age and gender are significant independent predictors of survival in primary cutaneous melanoma
2008-02-27

Abstract BACKGROUND The aim was to identify age‐ related and gender‐related differences in the clinical presentation and outcome of patients with primary cutaneous melanoma (CM). METHODS A total of 4785 CM patients without clinical evidence of metastasis diagnosed during the period 1976–2001 in southern Germany included in the analysis. Kaplan‐Meier analyses were performed to estimate and to compare disease‐specific survival (DSS) and survival after first recurrence (SAR). The Cox proportional hazards model was used to evaluate the effect of multiple variables on DSS and SAR. RESULTS Increasing age and male gender were independently associated with thicker tumors (&gt;2 mm) and histologic ulceration ( P &lt; .001). Patients older than 65 years had lower 10‐year DSS than younger patients (81.8% vs 88.4%, P &lt; .001) and this difference was more pronounced in women ( P &lt; .001) than in men ( P = .06). Males had lower 10‐year DSS than females (83.5% vs 88.5%, P &lt; .001) but this difference did not reach statistical significance in patients older than 65 years ( P = .162). In multivariate analysis adjusted for tumor thickness, ulceration, anatomic site, histologic subtype, DSS, site of first recurrence, time trend, sentinel lymph node status, age, and gender were independent predictors of DSS and SAR ( P &lt; .05). CONCLUSIONS Older age and male gender are associated with prognostically unfavorable primary CM. Expansion of current preventive strategies to target these subgroups is warranted. Moreover, age and gender are independent predictors of the outcome of CM patients. Females have a better prognosis than males but this difference disappears after the age of 65. Younger patients have a more favorable prognosis than older patients, a difference more pronounced in women. Cancer 2008. © 2008 American Cancer Society.
Arousal and Attention: Self-chosen Stimulation Optimizes Cortical Excitability and Minimizes Compensatory Effort
2008-02-27

Abstract Cortical excitability is assumed to depend on cortical arousal level in an inverted U-shaped fashion: Largest (optimal) excitability is usually associated with medium levels of arousal. It has been proposed that under conditions of low arousal, compensatory effort is exerted if attentional demands persist. People tend to avoid this resource-consuming top–down compensation by creating or selecting environmental conditions that provide sufficient bottom–up stimulation. These assumptions were tested in an attention-demanding dual-task situation: We combined a simulated driving task to induce three different arousal levels by varying stimulation (high vs. low vs. self-chosen) with a visual two-stimulus paradigm to assess cortical excitability by the initial contingent negative variation (iCNV) component of the event-related potential. Additionally, we analyzed the oscillatory power of the beta2 band of the electroencephalogram at anterior frontal sites, which is assumed to reflect low-arousal compensatory activity. The iCNV amplitude differed in all three arousal conditions as expected: It was highest in the condition of self-chosen stimulation and lowest in the low- and high-arousal conditions. Additionally, in the low-arousal condition, anterior frontal beta2 power was found to be significantly higher than in the other two conditions and correlated positively with subjective strain. This pattern of results suggests that subjects select medium levels of stimulation which optimize cortical excitability under attentional demand conditions. The elevated fronto-central beta2 power in the low-stimulation condition may indicate the involvement of the anterior cingulate cortex in compensating for reduced arousal by top–down stimulation of the noradrenergic arousal system.
Formal Total Synthesis of Neopeltolide
2008-02-27

A concise synthesis of the core structure of the macrolide neopeltolide was developed featuring a Prins cyclization to fashion the pyran ring. Key steps in the synthesis of aldehyde 16 were a Leighton allylation and a Feringa-Minnaard asymmetric methyl cuprate addition to an unsaturated thioester. For lactonization, a classical Yamaguchi macrolactonization was used. The longest linear sequence consists of 17 steps providing lactone 26 with an overall yield of 23%.
Synthesis and Biological Evaluation of Cruentaren A Analogues
2008-02-27

Abstract The complex macrolide cruentaren A is a highly selective and potent inhibitor of F‐ATPase (F‐type adenosine triphosphatase). As it shows some resemblance to benzolactone enamides like apicularen A, it was of interest to perform some structure–activity studies to delineate the key functional groups that are responsible for the activity. Building upon our previously developed route to cruentaren A, which is based on a ring‐closing alkyne metathesis reaction (RCAM), several cruentaren analogues were prepared. Replacement of the 3‐hydroxy hexanoic part with acids that lack the hydroxy group function resulted in a significant drop in cytotoxicity and F‐ATPase inhibition. Furthermore, two enamide analogues 23 and 50 were synthesized. However, these compounds were only cytotoxic in the micromolar range. Under the conditions for cleavage of the C3 aromatic methyl ether, the enamide function was transformed to the corresponding oxazinanone, resulting in analogues 25 and 52 .
Tumor Promotion in Liver of Mice with a Conditional Cx26 Knockout
2008-02-27

Connexin (Cx) 26 and 32 are the major gap junction proteins in liver. We recently demonstrated that Cx32 is essential for phenobarbital (PB)-mediated tumor promotion in mouse liver. To investigate whether Cx26 plays a similar role, an initiation-promotion experiment was conducted using mice with a liver-specific knockout of Cx26. Control and Cx26-deficient mice were injected a single dose of N-nitrosodiethylamine (DEN, 90 microg/g b.wt.) at 6 weeks of age and groups of mice were subsequently kept on a PB (0.05%) containing or control diet for 35 weeks. At the end of the experiment, the carcinogenic response in the liver was monitored. Mice from PB treatment groups showed strongly increased liver weights compared with mice treated with DEN alone, which was mostly due to a much higher tumor burden. The tumor response in PB-treated mice of both strains was quite similar, but the number of smaller tumors and of enzyme-altered neoplastic lesions was somewhat larger in PB-treated Cx26 knockout (Cx26 KO) compared with wild-type mice, whereas the volume fraction of enzyme-altered lesions was slightly reduced in PB-treated Cx26-deficient mice. There was no significant difference in tumor prevalence between Cx26 KO and wild-type mice. Altogether our present data show that elimination of Cx26 has only minor effects on chemically induced mouse hepatocarcinogenesis, in striking contrast to the effects seen in Cx32 KO mice.