bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of Histidine‐Containing Oligopeptides via Histidine‐Promoted Peptide Ligation
Authors: Huang Kai‐Jin , Huang Yi‐Chen , Lin Yuya A. 
Published: January 2018

AbstractHistidine‐containing peptides are valuable therapeutic agents for a treatment of neurodegenerative diseases. However, the synthesis of histidine‐containing peptides is not trivial due to the potential of imidazole sidechain of histidine to act as a nucleophile if unprotected. A peptide ligation method utilizing the imidazole sidechain of histidine has been developed. The key imidazolate intermediate that acts as an internal acyl transfer catalyst during ligation is generated by deprotonation. Transesterification with amino acids or peptides tethered with C‐terminal thioester followed by N→N acyl shifts led to the final ligated products. A range of histidine‐containing dipeptides could be synthesized in moderate to good yields via this method without protecting the imidazole sidechain. The protocol was further extended to tripeptide synthesis via a long‐range N→N acyl transfer, and tetrapeptide synthesis.
NPTX1 inhibits colon cancer cell proliferation through down‐regulating cyclin A2 and CDK2 expression
Authors: Peng Xiaofeng , Pan Kangming , Zhao Wenli , Zhang Jianzhu , Yuan Shicheng , Wen Xiang , Zhou Wenquan , Yu Zhijin 
Published: January 2018

AbstractColon cancer is the third most common malignancy and one of the leading causes of cancer‐associated mortality worldwide. Neuronal pentraxin 1 (NPTX1) is associated with tumor progression in some types of tumors. However, its expression and role in colon cancer has not been yet reported. Here we observed that NPTX1 was down‐regulated in colon cancer. Additionally, we explored the functional significance of NPTX1 in colon cancer. We found that over‐expression of NPTX1 inhibited colon cancer cell growth by performing MTT, colony formation, Edu corporation assays, and cell cycle analysis. In vivo mouse experiments also confirmed the anti‐proliferative role of NPTX1 in colon cancer. Further mechanistic study showed that over‐expression of NPTX1 inhibited the expression of cyclin A2 and CDK2 in colon cancer cells, thereby regulating the Rb‐E2F signaling. In summary, these findings reveal that NPTX1 suppress the colon cancer cell growth and might serve as a useful potential target for treatment of colon cancer.
Versatile Modes of Cooperative B−H Bond Activation Reactions in Ruthenium‐Carbene Complexes: Addition, Ring‐Opening and Insertion
Authors: Scharf Lennart T. , Weismann Julia , Feichtner Kai‐Stephan , Lindl Felix , Gessner Viktoria H. 
Published: January 2018

AbstractCooperative B−H bond activation reactions with thio‐ and iminophosphoryl tethered ruthenium‐carbene complexes are reported. The complexes show surprisingly different reactivities towards the commonly employed boranes CatBH, PinBH and BH3⋅LB as a result of different modes of metal–ligand cooperation. Although the iminophosphoryl system allows for selective 1,2‐addition of the B−H bond across the Ru=C double bond, the sulfur analogue only delivers the 1,2‐addition product for CatBH, whereas activation of BH3 and PinBH lead to further insertion reactions in one or more sides of the Ru‐C‐P‐S‐ring. The different reactivities can be explained by the differences in the electronics of the carbene complexes and the phosphoryl tether and by the Lewis acidities of the boranes. DFT calculations show that the mechanism of the reactions either proceeds by an addition across the Ru=C bond with different regioselectivities or across the Ru−S linkage.
Targeting the BCL2 Gene Promoter G‐Quadruplex with a New Class of Furopyridazinone‐Based Molecules
Authors: Amato Jussara , Pagano Alessia , Capasso Domenica , Di Gaetano Sonia , Giustiniano Mariateresa , Novellino Ettore , Randazzo Antonio , Pagano Bruno 
Published: January 2018

AbstractTargeting of G‐quadruplex‐forming DNA in the BCL2 gene promoter to inhibit the expression of anti‐apoptotic Bcl‐2 protein is an attractive approach to cancer treatment. So far, efforts made in the discovery of molecules that are able to target the BCL2 G‐quadruplex have succeeded mainly in the identification of ligands with poor drug‐like properties. Here, a small series of furo[2,3‐d]pyridazin‐4(5H)‐one derivatives were evaluated as a new class of drug‐like G‐quadruplex‐targeting compounds. Biophysical studies showed that two derivatives could effectively bind to BCL2 G‐quadruplex with good selectivity. Moreover, one such ligand was found to appreciably inhibit BCL2 gene transcription, with a substantial decrease in protein expression levels, and also showed significant cytotoxicity toward the Jurkat human T‐lymphoblastoid cell line.
Maximizing the GPU resource usage by reordering concurrent kernels submission
Authors: Cruz Rommel A.Q. , Bentes Cristiana , Breder Bernardo , Vasconcellos Eduardo , Clua Esteban , de Carvalho Pablo M.C. , Drummond Lúcia M.A. 
Published: January 2018

SummaryThe increasing amount of resources available on current GPUs sparked new interest in the problem of sharing its resources by different kernels. While new generations of GPUs support concurrent kernel execution, their scheduling decisions are taken by the hardware at runtime. The hardware decisions, however, heavily depend on the order at which the kernels are submitted to execution. In this work, we propose a novel optimization approach to reorder the kernels invocation focusing on maximizing the resources utilization, improving the average turnaround time. We model the kernel assignments to the hardware resources as a series of knapsack problems and use a dynamic programming approach to solve them. We evaluate our method using kernels with different sizes and resource requirements. Our results show significant gains in the average turnaround time and system throughput compared to the kernels submission implemented in modern GPUs.
A Pdgf‐cCreERT2 knock‐in mouse model for tracing PDGF‐C cell lineages during development
Authors: Wu Xiaoli , Liu Wenjun , Ding Hao 
Published: January 2018

SummaryPDGF‐C, a member of the platelet‐derived growth factor (PDGF) family, plays important roles in the development of craniofacial structures, the neural system, the vascular system, and tumors. PDGF‐C could also be required for the regulation of certain types of stem or progenitor cells as suggested by its expression in the regions where these cells are located. To further characterize the role of PDGF‐C in development, we generated a Pdgf‐cCreERT2 mouse strain, in which a tamoxifen‐inducible Cre (CreERT2) cDNA was specifically targeted into the Pdgf‐c genomic locus and controlled by the endogenous Pdgf‐c regulatory elements. We also showed that Cre activity in this mouse strain could be specifically induced by tamoxifen, which allowed the fate of PDGF‐C‐expressing cells to be traced at various stages of development. Using this model system, we demonstrated for the first time that PDGF‐C‐expressing cells could be multipotent, generating multiple cell lineages required for the formation of the cerebellum. Therefore, the Pdgf‐cCreERT2 mouse strain generated in this study will be a valuable transgenic tool for exploring the function of PDGF‐C in development and stem cell biology.
Economic evaluation of cognitive behavioral therapy and Internet‐based guided self‐help for binge‐eating disorder
Authors: König Hans‐Helmut , Bleibler Florian , Friederich Hans‐Christoph , Herpertz Stephan , Lam Tony , Mayr Andreas , Schmidt Frauke , Svaldi Jennifer , Zipfel Stephan , Brettschneider Christian , Hilbert Anja , de Zwaan Martina , Egger Nina 
Published: January 2018

AbstractObjectiveTo determine the cost‐effectiveness of individual face‐to‐face cognitive behavioral therapy (CBT) compared to therapist guided Internet‐based self‐help (GSH‐I) in overweight or obese adults with binge‐eating disorder (BED).MethodAnalysis was conducted alongside the multicenter randomized controlled INTERBED trial. CBT (n = 76) consisted of up to 20 individual therapy sessions over 4 months. GSH‐I (n = 71) consisted of 11 modules combining behavioral interventions, exercises including a self‐monitoring food diary, psychoeducation, and 2 face‐to‐face coaching sessions over 4 months. Assessments at baseline, after 4 months (post‐treatment), as well as 6 and 18 months after the end of treatment included health care utilization and sick leave days to calculate direct and indirect costs. Binge‐free days (BFD) were calculated as effect measure based on the German version of the Eating Disorder Examination. The incremental cost‐effectiveness ratio (ICER) was determined, and net benefit regressions, adjusted for comorbidities and baseline differences, were used to derive cost‐effectiveness acceptability curves.ResultsAfter controlling for baseline differences, CBT was associated with non‐significantly more costs (+€2,539) and BFDs (+40.1) compared with GSH‐I during the 22‐month observation period, resulting in an adjusted ICER of €63 per additional BFD. CBTs probability of being cost‐effective increased above 80% only if societal willingness to pay (WTP) was ≥€250 per BFD.DiscussionWe did not find clear evidence for one of the treatments being more cost‐effective. CBT tends to be more effective but also more costly. If the societal WTP for an additional BFD is low, then our results suggest that GSH‐I should rather be adopted.
Community‐level plant–soil feedbacks explain landscape distribution of native and non‐native plants
Authors: Kulmatiski Andrew 
Published: January 2018

AbstractPlant–soil feedbacks (PSFs) have gained attention for their potential role in explaining plant growth and invasion. While promising, most PSF research has measured plant monoculture growth on different soils in short‐term, greenhouse experiments. Here, five soil types were conditioned by growing one native species, three non‐native species, or a mixed plant community in different plots in a common‐garden experiment. After 4 years, plants were removed and one native and one non‐native plant community were planted into replicate plots of each soil type. After three additional years, the percentage cover of each of the three target species in each community was measured. These data were used to parameterize a plant community growth model. Model predictions were compared to native and non‐native abundance on the landscape. Native community cover was lowest on soil conditioned by the dominant non‐native, Centaurea diffusa, and non‐native community cover was lowest on soil cultivated by the dominant native, Pseudoroegneria spicata. Consistent with plant growth on the landscape, the plant growth model predicted that the positive PSFs observed in the common‐garden experiment would result in two distinct communities on the landscape: a native plant community on native soils and a non‐native plant community on non‐native soils. In contrast, when PSF effects were removed, the model predicted that non‐native plants would dominate all soils, which was not consistent with plant growth on the landscape. Results provide an example where PSF effects were large enough to change the rank‐order abundance of native and non‐native plant communities and to explain plant distributions on the landscape. The positive PSFs that contributed to this effect reflected the ability of the two dominant plant species to suppress each other's growth. Results suggest that plant dominance, at least in this system, reflects the ability of a species to suppress the growth of dominant competitors through soil‐mediated effects.
The effect of diuresis on extravascular lung water and pulmonary function in acute decompensated heart failure
Authors: Chase Steven C. , Fermoyle Caitlin C. , Wheatley Courtney M. , Schaefer Jacob J. , Olson Lyle J. , Johnson Bruce D. 
Published: January 2018

AbstractAimsThe effect of extravascular lung water (EVLW) and relationship to functional status as a result of acute decompensated heart failure (ADHF) are not well understood. We sought to quantify changes in clinical variables, EVLW, airway anatomy, spirometry, and diffusing capacity for carbon monoxide before and after treatment for ADHF.Methods and resultsFifteen patients were recruited within 24 h of hospital admission. Spirometry, diffusing capacity for carbon monoxide, and surrogates of EVLW by computed tomography were measured and were then repeated within 24 h of discharge. From the computed tomography (CT) scan, surrogates of EVLW were calculated from the distribution of CT attenuation of the lung tissue. Airways were segmented using the VIDA Apollo software. Patients were hospitalized for 4.6 ± 2.1 days, had 10 ± 4.8 L of fluid removed (7.0 ± 4.2 L between study visits), and lost 7.1 ± 4.9 kg. Patients had significant clearance of fluid from the lungs (per cent change: mean, 4.2 ± 6.1%; skew, 17.5 ± 27.0%; kurtosis, 37.6 ± 56.7%; full‐width half‐maximum, 10.2 ± 13.5%). Static lung volumes and maximal flows improved significantly (per cent change: forced vital capacity, 14.5 ± 13.6%; forced expiratory volume in 1 s, 15.9 ± 14.0%; forced expiratory flow at 25–75% of forced vital capacity, 27.2 ± 42.9%). The ratio of membrane conductance to capillary blood volume improved significantly (per cent change: alveolar–capillary membrane conductance/capillary blood volume, 23.4 ± 22.8%). Weight loss during hospitalization was significantly correlated with improved spirometry and diffusing capacity.ConclusionsExtravascular lung water contributes to the pulmonary congestive syndrome in ADHF patients, and its clearance is an important component of the improvement in pulmonary function as a result of inpatient treatment.
Rhamnolipid as new bio‐agent for cleaning of ultrafiltration membrane fouled by whey
Authors: Aghajani Mehdi , Rahimpour Ahmad , Amani Hossein , Taherzadeh Mohammad J. 
Published: January 2018

AbstractIn this work, rhamnolipid biosurfactant as an eco‐friendly and biodegradable cleaning agent was produced by Pseudomonas aeruginosa bacteria and was used to evaluate the chemical cleaning efficiency of whey fouled ultrafiltration membranes. Thin layer chromatography (TLC) and Fourier transform infrared spectroscopy (FTIR) confirmed the successful synthesis of rhamnolipid. The produced rhamnolipid was compared to chemical cleaners including sodium hydroxide (NaOH), sodium dodecyl sulfate (SDS) and Tween 20. Ultrafiltration membranes used for fouling and cleaning analysis were prepared using phase inversion via immersion precipitation technique. For studying the fouling mechanisms, Hermia's model adapted to cross‐flow was used. From the fouling mechanism experiments, it was found that the complete blocking and cake formation were the dominant fouling mechanisms. The highest values of cleaning efficiency were achieved using rhamnolipid and NaOH as cleaning agents with the flux recovery of 100%, but with considering the low concentration of the rhamnolipid used in the cleaning solution compared to NaOH (0.3 versus 4 g/L for NaOH), its application is preferred.
Do SST gradients drive the monthly climatological surface wind convergence over the tropical Atlantic?
Authors: Diakhaté Moussa , Lazar Alban , de Coëtlogon Gaëlle , Gaye Amadou T. 
Published: January 2018

ABSTRACTThis article presents a climatological study of the tropical Atlantic surface wind convergence, one of the main drivers of the marine intertropical convergence zone (ITCZ) precipitations, including coastal northeastern Brazilian and West African rainfalls. Climatological monthly mean surface wind convergence budget, as well as that of their month‐to‐month variations, is analysed over the 2000–2009 decade, using ocean–atmosphere reanalyses and satellite‐derived data sets. Sea surface temperature (SST) influence is particularly investigated via comparison of its Laplacian with that of sea level pressure. Results for monthly means reveal that the Lindzen‐Nigam paradigm does hold in regions of deep convection but only on their flanks. In deep convection regions, the budget analysis suggests the entrainment due to elevated heating by cumulus convection as the leading term. Elsewhere, over the ‘open ocean ITCZ’ meridional flanks, as well as over the ‘coastal one’ (Gulf of Guinea and northeastern Brazilian coasts), the pressure contribution is positive and largely dominated by its component below the boundary layer closely related to the SST. Horizontal advection is also found important over these areas, but with the pressure as the first‐order driver. Otherwise, month‐to‐month variations of ITCZ are controlled by the geostrophy within the pressure contribution tightly dominated by the free tropospheric component.
Online 1H‐MRS measurements of time‐varying lactate production in an animal model of glioma during administration of an anti‐tumoral drug
Authors: Crémillieux Yannick , Salvati Roberto , Dumont Ursule , Pinaud Noël , Bouchaud Véronique , Sanchez Stéphane , Glöggler Stefan , Wong Alan 
Published: January 2018

The aims of this study were to implement a magnetic resonance spectroscopy (MRS) protocol for the online profiling of subnanomolar quantities of metabolites sampled from the extracellular fluid using implanted microdialysis and to apply this protocol in glioma‐bearing rats for the quantification of lactate concentration and the measurement of time‐varying lactate concentration during drug administration. MRS acquisitions on the brain microdialysate were performed using a home‐built, proton‐tuned, microsolenoid with an active volume of 2 μL. The microcoil was placed at the outlet of the microdialysis probe inside a preclinical magnetic resonance imaging (MRI) scanner. C6‐bearing rats were implanted with microdialysis probes perfused with artificial cerebrospinal fluid solution and the lactate dehydrogenase (LDH) inhibitor oxamate. Microcoil magnetic resonance spectra were continuously updated using a single‐pulse sequence. Localized in vivo spectra and high‐resolution spectra on the dialysate were also acquired. The limit of detection and limit of quantification per unit time of the lactate methyl peak were determined as 0.37 nmol/√min and 1.23 nmol/√min, respectively. Signal‐to‐noise ratios (SNRs) of the lactate methyl peak above 120 were obtained from brain tumor microdialysate in an acquisition time of 4 min. On average, the lactate methyl peak amplitude measured in vivo using the nuclear magnetic resonance (NMR) microcoil was 193 ± 46% higher in tumor dialysate relative to healthy brain dialysate. A similar ratio was obtained from high‐resolution NMR spectra performed on the collected dialysate. Following oxamate addition in the perfusate, a monotonic decrease in the lactate peaks was observed in all animals with an average time constant of 4.6 min. In the absence of overlapping NMR peaks, robust profiling of extracellular lactate can be obtained online using a dedicated sensitive NMR microcoil. MRS measurements of the dynamic changes in lactate production induced by anti‐tumoral drugs can be assessed accurately with temporal resolutions on the order of minutes. The MRS protocol can be readily transferred to the clinical environment with the use of suitable clinical microdialysis probes.
Cerebellar activation during a motor task in conversion disorder with motor paralysis: A case report and fMRI study
Authors: Shimada Takamitsu , Ohi Kazutaka , Yasuyama Toshiki , Uehara Takashi , Kawasaki Yasuhiro 
Published: January 2018

AbstractBackgroundMotor conversion disorders are characterized by movement symptoms without a neurological cause. A psychogenic etiology is presumed for these disorders, but little is known about their underlying neural mechanisms. Functional magnetic resonance imaging (fMRI) has been utilized to understand the mechanisms associated with unexplained motor symptoms. Here, we used fMRI to investigate the cerebral response to motor stimulation in a patient with conversion disorder with motor paralysis to determine the underlying neural mechanisms of this disorder.MethodsBrain activation induced by movements of the bilateral ankle joints (repeated plantar flexion and dorsiflexion) was recorded using fMRI in a patient with conversion disorder with unexplained motor paralysis. We acquired 2 types of imaging data: (i) data obtained while motor paralysis remained present and (ii) data obtained after motor paralysis had completely improved. We used a within‐subject fMRI block design to compare the patient's brain activities during the motor task and at rest.ResultsCerebral motor areas were significantly activated during the motor task relative to at rest, both when motor paralysis remained present and when paralysis had improved (FWE‐corrected P < .05), although there was greater activation in motor areas when motor paralysis had improved than when motor paralysis remained. Notably, activation in the cerebellum posterior lobe during the motor task when motor paralysis remained (FWE‐corrected P < .05) disappeared after motor paralysis had completely improved.ConclusionsThe cerebellum is a region that is closely associated with voluntary motion. We suggest that complementary abnormal function in the cerebellum might be associated with the neural basis of conversion disorder with motor paralysis.
Mixed ductal‐lobular carcinomas: evidence for progression from ductal to lobular morphology
Authors: McCart Reed Amy E , Kutasovic Jamie R , Nones Katia , Saunus Jodi M , Da Silva Leonard , Newell Felicity , Kazakoff Stephen , Melville Lewis , Jayanthan Janani , Vargas Ana Cristina , Reid Lynne E , Beesley Jonathan , Chen Xiao Qing , Patch Anne-Marie , Clouston David , Porter Alan , Evans Elizabeth , Pearson John V , Chenevix‐Trench Georgia , Cummings Margaret C , Waddell Nicola , Lakhani Sunil R , Simpson Peter T 
Published: January 2018

AbstractMixed ductal–lobular carcinomas (MDLs) show both ductal and lobular morphology, and constitute an archetypal example of intratumoural morphological heterogeneity. The mechanisms underlying the coexistence of these different morphological entities are poorly understood, although theories include that these components either represent ‘collision’ of independent tumours or evolve from a common ancestor. We performed comprehensive clinicopathological analysis of a cohort of 82 MDLs, and found that: (1) MDLs more frequently coexist with ductal carcinoma in situ (DCIS) than with lobular carcinoma in situ (LCIS); (2) the E‐cadherin–catenin complex was normal in the ductal component in 77.6% of tumours; and (3) in the lobular component, E‐cadherin was almost always aberrantly located in the cytoplasm, in contrast to invasive lobular carcinoma (ILC), where E‐cadherin is typically absent. Comparative genomic hybridization and multiregion whole exome sequencing of four representative cases revealed that all morphologically distinct components within an individual case were clonally related. The mutations identified varied between cases; those associated with a common clonal ancestry included BRCA2, TBX3, and TP53, whereas those associated with clonal divergence included CDH1 and ESR1. Together, these data support a model in which separate morphological components of MDLs arise from a common ancestor, and lobular morphology can arise via a ductal pathway of tumour progression. In MDLs that present with LCIS and DCIS, the clonal divergence probably occurs early, and is frequently associated with complete loss of E‐cadherin expression, as in ILC, whereas, in the majority of MDLs, which present with DCIS but not LCIS, direct clonal divergence from the ductal to the lobular phenotype occurs late in tumour evolution, and is associated with aberrant expression of E‐cadherin. The mechanisms driving the phenotypic change may involve E‐cadherin–catenin complex deregulation, but are yet to be fully elucidated, as there is significant intertumoural heterogeneity, and each case may have a unique molecular mechanism. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.