Miracle-dz/UniFAR-FTUs huggingface dataset:
Neighbor‐directed histidine N (τ)–alkylation: A route to imidazolium‐containing phosphopeptide macrocycles

Our recently discovered, selective, on‐resin route to N(τ)‐alkylated imidazolium‐containing histidine residues affords new strategies for peptide mimetic design. In this, we demonstrate the use of this chemistry to prepare a series of macrocyclic phosphopeptides, in which imidazolium groups serve as ring‐forming junctions. Interestingly, these cationic moieties subsequently serve to charge‐mask the phosphoamino acid group that directed their formation. Neighbor‐directed histidine N(τ)‐alkylation opens the door to new families of phosphopeptidomimetics for use in a range of chemical biology contexts. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 663–673, 2015.
Comparative distribution of mRNAs for glutamic acid decatrboxylase, tyrosine hydroxylase, and tachykinins in the basal ganglia: An in situ hybridization study in the rodent brain

Neurotransmitter‐related messenger RNAs were detected by in situ hybridization in sections of rat and mouse brains by using 35S‐radiolabelled RNA probes transcribed from cDNAs cloned in SP6 promoter‐containing vectors. The distribution of messenger RNAs for glutamic acid decarboxylase, tachykinins (substance P and K), and tyrosine hydroxylase was examined in the striatum, pallidum, and substantia nigra. Dense clusters of silver grains were observed with the RNA probe complementary of the cellular messenger RNA for glutamic acid decarboxylase (antisense RNA) over most large neurons in the substantia nigra pars reticulata and medium‐sized to large neurons in all pallidal subdivisions. A few very densely and numerous lightly labelled medium‐sized neurons were present in the striatum. Among the areas examined, only the striatum contained neurons labelled with the antisense tachykinin RNA. Most of these neurons were of medium size, and a few were large. With the antisense tyrosine hydroxylase RNA, silver grains were found over neurons of the substantia nigra pars compacta and adjacent A10 and A8 dopaminergic cell groups. No signal was observed with RNAs identical to the cellular messenger RNA for glutamic acid decarboxylase or tachykinin (sense RNA). These results show a good correlation with immunohistochemical studies, suggesting that documented differences in the distribution and the level of glutamic acid decarboxylase, tyrosine hydroxylase, and substance P immunoreactivities in neurons of the basal ganglia are related to differences in the level of expression of the corresponding genes rather than to translation accessibility, stability, or transport of the gene products.
A simulation study on effects of exposure to a combination of pesticides used in an orchard and tuber crop on the recovery time of a vulnerable aquatic invertebrate

The aim of the present study was to assess whether population effects and recovery times increase when a population of a vulnerable aquatic invertebrate is exposed to concentrations of 1 or multiple pesticides. The 2 sets of pesticide combinations tested are typical for orchard and tuber crops in The Netherlands. Exposure concentrations were predicted using the FOCUS step 3 modeling framework and the Dutch drainage ditch scenario. Recovery times were assessed using the MASTEP population model. We simulated the population dynamics and pesticide effects in a Monte Carlo style by using median effective concentration values drawn from an arthropod species sensitivity distribution. In the tuber scenario, exposure to λ‐cyhalothrin resulted in long‐term effects, whereas exposure to the co‐occurring compound fluazinam hardly resulted in (additional) effects. In the orchard scenario, 3 pesticides resulted in large effects just after exposure, but pulse exposures to these compounds did not coincide. The probabilities of effects for the single compounds added up for the combination; in contrast, the recovery times were not higher for the combination compared to those associated with exposure to the individual compounds. The conclusion from the present study's simulations is that exposure to the evaluated pesticide packages may lead to increased mortality probabilities and effect sizes of the combination, but does not lead to longer recovery times for populations with synchronized reproduction than when exposed to the individual compounds. Environ Toxicol Chem 2014;33:1489–1498. © 2013 SETAC
Multi-OAM-mode microwave communication with the partial arc sampling receiving scheme

An orbital angular momentum (OAM) multiplexed radio data link with the novel partial arc sampling receiving (PASR) scheme is experimentally demonstrated. These four coaxially propagating OAM waves with modes of l = -6, -2, +2 and +6 are generated by a Cassegrain antenna based on the dual ring-slot radiators. Over 10 m free-space transmission, four identical horn antennas uniformly located at the π/2 arc with a fixed radius of 45 cm are used to capture the four overlapped OAM waves. The de-multiplexing is then performed by digital phase-shift (DPS) at digital baseband. Experiment results show that the bit-error rates (BER) can reach below the forward error correction limit of 3.8 × 10-3 for all the four OAM channels. Multi-OAM-mode communications with the PASR scheme is capable of providing the receiving end with desired properties of compact size as well as easy realization.
Expression and prognostic role of molecular markers in 99 KIT-positive gastric stromal tumors in Taiwanese.

AIM To elucidate the prognostic role and relationship of three molecular markers such as tumor suppressor gene p53, proliferating cell nuclear antigen (PCNA) and Ki-67 in gastric stromal tumor. METHODS A total of 108 surgically resected gastric smooth muscle tumor specimens were collected from January 1987 to December 1999. Immunohistochemical studies were performed on the paraffin sections of 99 of 108 CD117-positive tumors with antibodies of p53, PCNA, and Ki-67. Immunoreactivity of three molecular markers was recorded by labeling index (LI, %) and was analyzed for clinicopathologic and survival correlation. RESULTS Of the 99 cases, immunostaining revealed that 52 patients (52.5%) had p53, and 37 patients (37.3%) had Ki-67 immunoreactivity (defined as >10% of LI). All patients (100%) had PCNA immunoreactivity ranging from 12% to 93% of LI, divided into high or low by median. Statistics revealed that LI of three markers positively correlate to each other (P<0.01) and to microscopic tumor mitotic counts (P<0.001). By combination, patients with >=2 markers (positive or high) in tumors had early tumor recurrence (P<0.001) and unfavorable outcome (P<0.001). Univariate analysis indicated that patients with tumor size >5 cm (P=0.003), tumor mitosis >5/50 HPF (P<0.001), p53 immunoreactivity (P=0.001), Ki-67 immunoreactivity (P=0.026), high PCNA LI (P=0.015) and male gender (P=0.036) were six predictors for early disease recurrence. Subsequent multivariate analysis revealed that mitotic counts, tumor size, and p53 immunoreactivity were three independent prognostic factors for both disease free and overall survival of patients. By combination of three independent prognostic factors for grouping, we found higher tumor recurrence rate (P<0.001) and shorter survival (P<0.001) existed in groups with increasing factors. CONCLUSION We first provide the prognostic value and linkage of three molecular markers in GISTs. The combination of three factors (p53, tumor size, and tumor mitosis) provides a more powerful prediction of prognosis than any single factor does.
The economic rehabilitation of offenders: Recommendations of the model penal code (second)

The project to produce a Model Penal Code (Second) of Sentencing is nearly finished. It is the first-ever revision of the Model Penal Code (MPC or Code), more than fifty years after the original Code was completed. The most recent Tentative Draft to win approval by the American Law Institute (ALI) (the third of four volumes for the project as a whole) addresses economic penalties, along with a number of other subjects relating to “offenders in the community. ” 1
Gait Patterns Differ Between ACL-Reconstructed Athletes Who Pass Return-to-Sport Criteria and Those Who Fail

Background: The current standard of practice for an athlete to return to sport after anterior cruciate ligament (ACL) reconstruction is varied. Attempt to return to activity is typically advised 6 months after surgery, but functional performance deficits and gait abnormalities are often still evident and may have important implications on future function. Hypothesis: When comparing the involved and uninvolved limbs, patients who failed return-to-sport (RTS) criteria would demonstrate (1) smaller peak knee angles, extensor moments, and peak power absorption at the knee of the involved limb and (2) larger peak hip angles, extensor moments, and peak power generation of the involved limb. Study Design: Controlled laboratory study. Methods: A total of 42 patients completed functional and biomechanical gait assessment 6 months after ACL reconstruction. Functional testing involved an isometric quadriceps strength test, 4 single-legged hop tests, and 2 self-report questionnaires. Three-dimensional motion analysis was used to measure sagittal plane kinematics and kinetics of the hip and knee. A mixed-model analysis of variance and post hoc t tests were used to compare the limb symmetry of those who passed and those who did not pass RTS criteria. Minimal clinically important differences were calculated from healthy gait data and used to further define meaningful limb asymmetries. Results: Twenty of the 42 (48%) patients passed RTS criteria 6 months after ACL reconstruction. Patients who did not pass the criteria demonstrated statistically significant differences between limbs on all kinematic and kinetic variables at the knee (P ≤ .027). Clinically meaningful asymmetries at the hip were also identified in this group. Only kinetic asymmetries at the knee were identified in the patients who passed RTS criteria. Conclusion: Athletes who demonstrate superior functional performance 6 months after ACL reconstruction may have fewer abnormal and asymmetrical gait behaviors than their poorer performing counterparts. Patients who did not pass RTS criteria not only demonstrated larger kinematic and kinetic asymmetries between limbs but also appeared to use a gait strategy more closely aligned with athletes early after ACL rupture. Clinical Relevance: Poor performance on a battery of functional performance measures may be related to the presence of movement asymmetries in athletes after ACL reconstruction. Objective RTS criteria have the potential to provide information to clinicians who determine when these athletes return to activity, and may aid in the prescription of targeted rehabilitation to address underlying movement asymmetry.
Morphology‐based mammalian stem cell tests reveal potential developmental toxicity of donepezil

Various compounds, including therapeutic drugs, can adversely impact the survival and development of embryos in the uterus. Identification of such development‐interfering agents is a challenging task, although multi‐angle approaches—including the use of in vitro toxicology studies involving embryonic stem cells—should alleviate some of the current difficulties. In the present study, we utilized the in vitro elongation of embryoid bodies (EBs) derived from mouse embryonal carcinoma stem cell line P19C5 as a model of early embryological events, specifically that of gastrulation and axial patterning. From our study, we identified donepezil, a medication indicated for the management of Alzheimer's disease, as a potential developmental toxicant. The extent of P19C5 EB axial elongation was diminished by donepezil in a dose‐dependent manner. Although donepezil is a known inhibitor of acetylcholinesterase, interference of elongation was not mediated through this enzyme. Quantitative reverse‐transcriptase PCR revealed that donepezil altered the expression pattern of a specific set of developmental regulator genes involved in patterning along the anterior–posterior body axis. When tested in mouse whole embryo culture, donepezil caused morphological abnormalities including impaired somitogenesis. Donepezil also diminished elongation morphogenesis of EBs generated from human embryonic stem cells. These results suggest that donepezil interferes with axial elongation morphogenesis of early embryos by altering the expression pattern of regulators of axial development. Mol. Reprod. Dev. 81: 994–1008, 2014. © 2014 Wiley Periodicals, Inc.
Comparison of 18F Flurodeoxyglucose PET with Ga-67 scintigraphy and conventional imaging modalities in pediatric lymphoma

Flurodeoxyglucose PET (FDG PET) is very useful for staging and restaging adult lymphomas. Its effectiveness in childhood lymphomas is less established. To evaluate the potential utility of FDG PET in the care of pediatric patients with lymphomas, we examined the clinical data and imaging findings of 26 patients, 8 – 19 years of age (14 HD, 12 NHL) who underwent 55 FDG PET studies. Results were compared with CT/MRI and gallium scans. FDG PET provided incremental, clinically important information in 21% of HD cases and 33% of NHL cases. It was especially useful in distinguishing scar tissue from residual disease at the end of therapy. In both HD and NHL, FDG PET had higher sensitivity (94%, 90%) and specificity (100%, 88%) than CT/MRI and gallium scanning. These results indicate that FDG PET is useful in the management of pediatric lymphomas.
Description Logics and Guarded Fragments of First Order Logic

A locking mechanism for orthopedic braces includes upper and lower brace members pivotably jointed together, notched or recessed plates being fixedly secured to the lower brace member while a U-shaped locking bar is pivotably secured to the upper brace member for lockingly cooperating with the notched or recessed plates, a spring-biased actuating lever being operatively associated with the U-shaped locking bar. The upper and lower brace members are also provided with drilled holes or bores which are angularly oriented with respect to the longitudinal axes of the upper and lower brace members, the bores being aligned with each other when the longitudinal axes of the brace members are likewise aligned. A freely movable pin is slidably disposed within the bores, the outer ends of the bores being suitably capped so as to retain the pin therewithin, and when the brace is vertically disposed so as to simulate standing or walking conditions, both brace members also being longitudinally aligned, the U-shaped locking bar automatically lockingly engages the recessed or notched plates while the slidable pin is interposed between both brace members and within both bores thereof, thereby preventing the occurrence of relative pivoting between the brace members. When the brace is altneratively disposed in a suitably inclined position, corresponding to simulated sitting conditions, the pin moves solely into the bore of the upper brace member thereby permitting relative pivoting to occur between the brace members when the U-shaped locking bar is disengaged from the notched plates by means of the actuating lever.
Growth and Characterization of InAs/GaAs Quantum Dots and Diode Lasers

This paper discusses the self-assembled growth of InAs/GaAs quantum dots by metal organic chemical vapor deposition and the lasing characteristics of diode lasers incorporating either 3 or 5 stacked quantum dot layers. Lasing occurred from the quantum dot excited state when 3-stacked layers were used. However by incorporating 5 stacked layers of quantum dots into a device, the increased gain volume enabled lasing from the ground state for cavity lengths as short as 1.5 mm.
Factors Affecting Short-term Mortality in Women With Ovarian, Tubal, or Primary Peritoneal Cancer: Population-Based Cohort Analysis of English National Cancer Registration Data

Objective International studies show lower survival rates in the United Kingdom than other countries with comparable health care systems. We report on factors associated with excess mortality in the first year after diagnosis of primary invasive epithelial ovarian, tubal, and primary peritoneal cancer. Methods Routinely collected national data were used for patients diagnosed in England in 2008 to 2010. A multivariate Poisson model was used to model excess mortality in 3 periods covering the first year after diagnosis, adjusting for various factors including age at diagnosis, route to diagnosis, tumor stage, tumor morphology, and treatment received. Results Of 14,827 women diagnosed as having ovarian cancer, 5296 (36%) died in the first year, with 1673 deaths in the first month after diagnosis. Age older than 70 years, diagnosis after an emergency presentation or by an unknown route, and unspecified or unclassified epithelial morphologies were strongly and independently associated with excess mortality in the first year after diagnosis. Of the 2100 (14%) women who fulfilled all 3 criteria, 1553 (74%) did not receive any treatment and 1774 (85%) died in the first year after diagnosis. In contrast, only 193 (4%) of the 4414 women without any of these characteristics did not receive any treatment, and only 427 (9%) died in the first year after diagnosis. Conclusions Although our results are based on data from England, they are likely to have implications for cancer care pathways worldwide because most of the identified factors are not specific to the UK health care system. Our results suggest the need to increase symptom awareness, promote timely general practitioner referral, and optimize diagnostic and early treatment pathways within secondary care to increase access to treatment for women with advanced-stage invasive epithelial ovarian, tubal, and primary peritoneal cancer. This process should be pursued alongside continued efforts to develop primary prevention and screening strategies.
The Tissue-Reconstructing Ability of Colon CSCs Is Enhanced by FK506 and Suppressed by GSK3 Inhibition

Cancer stem cells (CSC) are capable of reconstructing cancer tissues, are involved in both recurrence and metastasis, and contribute to therapeutic resistance. Therefore, elucidating the molecular mechanism in CSCs is important to successfully treat unresectable cancers. Previously, we observed that colon cancer stem-like cells can be induced from human colon cancer cell lines by retrovirally introducing OCT3/4, SOX2, and KLF4, and we have designated such cells as induced cancer stem cells (iCSC). In the current study, we used iCSCs to evaluate the molecular mechanism of colon CSCs and developed new methods to control them. The spheres that were derived in vitro from the iCSCs, but not those from parental cells, mimicked human colon cancer tissues in terms of their immunohistologic patterns; therefore, sphere-forming ability was assessed as a measure of the tissue-reconstructing ability of iCSCs. Interestingly, the calcineurin inhibitor FK506 enhanced the sphere-forming ability of iCSCs, whereas GSK3 inhibition by RNAi, CHIR99021, and valproic acid (VPA) impeded the sphere-forming ability and expansion of iCSCs. FK506 and GSK3 inhibition showed the opposite effect regarding the NFATc3 localization of iCSCs. These data reveal the crucial role that NFAT localization, as regulated by calcineurin and GSK3, plays in the tissue-reconstructing ability of colon cancer stem cells and the potential of GSK3 inhibitors, such as VPA, in colon cancer stem cell–targeting therapy. Implications: This study identifies signaling pathways that contribute to the tissue-reconstructing capacity of colon CSCs and suggests that clinically used drugs could be repurposed to improve unresectable colon cancers. Mol Cancer Res; 15(10); 1455–66. ©2017 AACR.
A novel fairness-driven approach for heterogeneous gateways' link scheduling in IoT networks

Internet of Things (IoT) in a real world scenario involves collecting data by sensor devices and communicating the sensed data, through gateway devices, to the IoT Cloud (or the Internet) using direct or multi-hop communication. A gateway typically supports multiple wireless sensor networks (WSNs) and each WSN might use a different technology for communication. Hence gateways are designed to be heterogeneous, having necessary hardware support only for those technologies corresponding to their associated WSNs. Due to their heterogeneity, the technology specific channel access mechanisms need not provide fairness in data communication at each gateway. In this paper, we propose two centralized techniques that involve an efficient link selection per technology and time based scheduling among gateways. This improves fairness in data transmission for every gateway, resulting in an increased data transmission. The first technique uses a multinomial probability based link selection thereby reducing contention within each technology link for a given network topology. The second technique incorporates adaptation to the changing traffic patterns in the network. Our extensive simulation results show that the proposed techniques outperform default technology specific channel access mechanism in IoT networks in terms of total data transmitted, packet delivery ratio, and fairness.
The High-Affinity Maltose/Trehalose ABC Transporter in the Extremely Thermophilic Bacterium Thermus thermophilus HB27 Also Recognizes Sucrose and Palatinose

ABSTRACT We have studied the transport of trehalose and maltose in the thernophilic bacterium Thermus thermophilus HB27, which grows optimally in the range of 70 to 75°C. The Km values at 70°C were 109 nM for trehalose and 114 nM for maltose; also, a high Km (424 nM) was found for the uptake of sucrose. Competition studies showed that a single transporter recognizes trehalose, maltose, and sucrose, while d-galactose, d-fucose, l-rhamnose, l-arabinose, and d-mannose were not competitive inhibitors. In the recently published genome of T. thermophilus HB27, two gene clusters designated malEFG1 (TTC1627 to -1629) and malEFG2 (TTC1288 to -1286) and two monocistronic genes designated malK1 (TTC0211) and malK2 (TTC0611) are annotated as trehalose/maltose and maltose/maltodextrin transport systems, respectively. To find out whether any of these systems is responsible for the transport of trehalose, the malE1 and malE2 genes, lacking the sequence encoding the signal peptides, were expressed in Escherichia coli. The binding activity of pure recombinant proteins was analyzed by equilibrium dialysis. MalE1 was able to bind maltose, trehalose, and sucrose but not glucose or maltotetraose (Kd values of 103, 67, and 401 nM, respectively). Mutants with disruptions in either malF1 or malK1 were unable to grow on maltose, trehalose, sucrose, or palatinose, whereas mutants with disruption in malK2 or malF2 showed no growth defect on any of these sugars. Therefore, malEFG1 encodes the binding protein and the two transmembrane subunits of the trehalose/maltose/sucrose/palatinose ABC transporter, and malK1 encodes the ATP-binding subunit of this transporter. Despite the presence of an efficient transporter for trehalose, this compound was not used by HB27 for osmoprotection. MalE1 and MalE2 exhibited extremely high thermal stability: melting temperatures of 90°C for MalE1 and 105°C for MalE2 in the presence of 2.3 M guanidinium chloride. The latter protein did not bind any of the sugars examined and is not implicated in a maltose/maltodextrin transport system. This work demonstrates that malEFG1 and malK1 constitute the high-affinity ABC transport system of T. thermophilus HB27 for trehalose, maltose, sucrose, and palatinose.