Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I Study of the Investigational Anti-Guanylyl Cyclase Antibody–Drug Conjugate TAK-264 (MLN0264) in Adult Patients with Advanced Gastrointestinal Malignancies

Purpose: To assess the safety, tolerability, and preliminary antitumor activity of the investigational anti–guanylyl cyclase C (GCC) antibody–drug conjugate TAK-264 (formerly MLN0264) in adult patients with advanced gastrointestinal malignancies. Experimental Design: Adult patients with GCC-expressing gastrointestinal malignancies (H-score ≥ 10) were eligible for inclusion. TAK-264 was administered as a 30-minute intravenous infusion once every 3 weeks for up to 17 cycles. Dose escalation proceeded using a Bayesian continual reassessment method. At the maximum tolerated dose (MTD), 25 patients with metastatic colorectal cancer were enrolled in a prespecified dose expansion cohort. Results: Forty-one patients were enrolled, including 35 (85%) with metastatic colorectal cancer. During dose escalation (0.3–2.4 mg/kg), four of 19 patients experienced dose-limiting toxicities of grade 4 neutropenia; the MTD was determined as 1.8 mg/kg. Patients received a median of two cycles of TAK-264 (range, 1–12); nine received ≥four cycles. Common drug-related adverse events (AEs) included nausea and decreased appetite (each 41%), fatigue (32%), diarrhea, anemia, alopecia, and neutropenia (each 27%); grade ≥3 AEs included neutropenia (22%), hypokalemia, and febrile neutropenia (each 7%). Peripheral neuropathy was reported in four (10%) patients. Pharmacokinetic data showed approximately dose proportional systemic exposure and a mean plasma half-life of around 4 days, supporting the dosing schedule. Overall, 39 patients were response-evaluable; three experienced durable stable disease; and one with gastric adenocarcinoma had a partial response. GCC expression did not appear to correlate with treatment duration. Conclusions: These findings suggest that TAK-264 has a manageable safety profile, with preliminary evidence of potential antitumor activity in specific gastrointestinal malignancies. Further investigation is underway. Clin Cancer Res; 22(20); 5049–57. ©2016 AACR.
Cloning and Phylogenetic Analysis of Sid-1-Like Genes from Aphids

Abstract The sid-1 (systemic interference defective) gene encodes a transmembrane protein that is an important participator in the systemic RNAi pathway and has been reported in several organisms. In insects, sid-1-like genes were described from Tribolium castaneum, Apis mellifera, Bombyx mori and Schistocerca americana, but were not found in Drosophila melanogaster and Anopheles gambiae. To investigate whether this gene occurs in aphid species, RT-PCRs were performed using degenerate primers designed using the conserved motif of sid-1-like genes. An sid-1-like full-length transcript was amplified from the cotton/melon aphid, Aphis gossypii Glover (Homopera: Aphididae), and a fragment was amplified from the grain aphid, Sitobion avenae (F.). The trancript from A. gossypii was 3067 bp long, with an open reading frame encoding 766 amino acids. Sequence analysis indicated that this transcript shares highest similarity with the reported sid-1-like gene in Schistocerca americana (53%, fragment), followed by A. mellifera (44%), T. castaneum (32–44%), B. mori (38–42%) and Caenorhabditis elegans (25%). Analysis of the transmembrane protein topological structure indicated that the protein encoded by this gene has a similar structure to SID-1 of C. elegans. A phylogenetic tree with all available sid-1-like genes suggests that sid-1-like genes may have had a long evolutionary history. Considering its importance in the RNAi pathway, the absence of a sid-1-like gene in D. melanogaster and A. gambiae is worthy of further investigation.
Observation of a liquid-gas-type transition in the pyrochlore spin ice compound Dy2Ti2O7 in a magnetic field.

Low temperature magnetization measurements on the pyrochlore spin ice compound Dy2Ti2O7 reveal that the ice-rule breaking spin flip, appearing at H approximately 0.9 T applied parallel to the [111] direction, turns into a novel first-order transition for T<0.36 K which is most probably of a liquid-gas type. T-linear variation of the critical field observed down to 0.03 K suggests the unusual situation that the entropy release across the transition remains finite [approximately 0.5 (J/K) x mol-Dy] as T-->0, in accordance with a breaking of the macroscopic degeneracy in the intermediate "kagomé ice" state.
A systematic review on the chemical constituents of Centella asiatica

Several reviews have examined various aspects of C. asiatica including the chemistry, pharmacology, and clinical uses but none of these reviews use the systematic review approach to locate and condense all the findings. The aim of this study was to systematically review the chemical constituents of C. asiatica. Electronic databases were searched for studies examining the chemical constituents of C. asiatica published from 1949 to 2011. Specialised journals, conference proceedings were also searched. Two review authors independently scrutinised search results and extracted data from eligible studies. From the 183 potentially relevant studies, 49 studies met the inclusion criteria and were included in the review. The review showed that C. asiatica has diverse and complex chemical constituents which included terpenes (monoterpenes, sesquiterpenes, diterpenes, triterpenes, tetraterpenes), phenolic compounds (flavonoids, phenylpropanoids, tannins), polyacetylenes group, alkaloids, carbohydrates, vitamin, mineral and amino acid. Most of the pharmacological activities of C. asiatica were examined in animal models using the extract or a mixture of chemical constituents. The most tested constituent was asiaticoside and it may be responsible for most of the pharmacological activities of C. asiatica. This review highlights that C. asiatica has diverse and complex chemical constituents and triterpenes were the major constituents.
Transcriptional activation by the parvoviral nonstructural protein NS-1 is mediated via a direct interaction with Sp1

The nonstructural protein NS-1, encoded by the parvovirus minute virus of mice, is a potent regulator of viral gene expression. NS-1 does not bind DNA in a sequence-specific manner, and the mechanism by which it modulates viral promoter function is unclear. We have used Gal4-NS-1 fusion protein constructs to identify and characterize an activating domain encoded within the C-terminal 88 amino acids of NS-1 which competes effectively with the acidic activator domain of the herpes simplex virus VP16 protein. DNA affinity chromatography and immunoprecipitation experiments demonstrate that protein-protein interactions between the transcription factor Sp1 and NS-1 are required to bind NS-1 to promoter DNA in vitro. Cotransfection of Gal4-NS-1 and Sp1-VP16 acidic activator constructs into Drosophila melanogaster Schneider cells, which lack endogenous Sp1, stimulates transcription from a minimal promoter containing five Gal4 binding sites, while single-construct transfections do not. Cotransfection of Schneider cells with wild-type NS-1 and Sp1 constructs activates transcription from a simian virus 40 promoter 10- to 30-fold over that of either construct alone. Thus, Sp1-NS-1 interactions in vivo can stimulate transcription from a heterologous promoter containing Sp1 binding sites.
The prevalence and the predictors of insomnia among refugees

This study aimed to investigate the prevalence of insomnia and associated sociodemographic factors among refugees in Jordan. A cross-sectional survey was undertaken with a representative sample of 373 refugees. The majority of refugees had moderate to severe insomnia (n = 196, 52.2%). Older age, living in the city of Mafraq, having secondary education or below, unemployed, and lacking easy access to medication were the predictors of higher insomnia. More attention by health care providers including nurses should be given to older refugees and those with a lower level of education, as these groups tend to be more liable to suffer from insomnia.
Mitochondrial DNA depletion

Background: The mitochondrial DNA (mtDNA) depletion syndrome (MDS) is an autosomal recessive disorder of early childhood characterized by decreased mtDNA copy number in affected tissues. Recently, MDS has been linked to mutations in two genes involved in deoxyribonucleotide (dNTP) metabolism: thymidine kinase 2 (TK2) and deoxy-guanosine kinase (dGK). Mutations in TK2 have been associated with the myopathic form of MDS, and mutations in dGK with the hepatoencephalopathic form. Objectives: To further characterize the frequency and clinical spectrum of these mutations, the authors screened 20 patients with myopathic MDS. Results: No patient had dGK gene mutations, but four patients from two families had TK2 mutations. Two siblings were compound heterozygous for a previously reported H90N mutation and a novel T77M mutation. The other siblings harbored a homozygous I22M mutation, and one of them had evidence of lower motor neuron disease. The pathogenicity of these mutations was confirmed by reduced TK2 activity in muscle (28% to 37% of controls). Conclusions: These results show that the clinical expression of TK2 mutations is not limited to myopathy and that the myopathic form of MDS is genetically heterogeneous.
Modeling the Complex Activity of Sickle Cell and Thalassemia Specialist Nurses in England

Objective: Specialist advanced practice nursing in hemoglobinopathies has a rich historical and descriptive literature. Subsequent work has shown that the role is valued by patients and families and also by other professionals. However, there is little empirical research on the complexity of activity of these services in terms of interventions offered. In addition, the work of clinical nurse specialists in England has been devalued through a perception of oversimplification. Purpose: The purpose of this study was to understand the complexity of expert nursing practice in sickle cell and thalassemia. Design: The approach taken to modeling complexity was used from common methods in mathematical modeling and computational mathematics. Knowledge discovery through data was the underpinning framework used in this study using a priori mined data. This allowed categorization of activity and articulation of complexity. Result: In total, 8966 nursing events were captured over 1639 hours from a total of 22.8 whole time equivalents, and several data sources were mined. The work of specialist nurses in this area is complex in terms of the physical and psychosocial care they provide. The nurses also undertook case management activity such as utilizing a very large network of professionals, and others participated in admission avoidance work and education of patients’ families and other staff. Conclusion: The work of nurses specializing in hemoglobinopathy care is complex and multidimensional and is likely to contribute to the quality of care in a cost-effective way. An understanding of this complexity can be used as an underpinning to establishing key performance indicators, optimum caseload calculations, and economic evaluation.
Detecting composite events in active database systems using Petri nets

The detection of events in an active database system turns out to be a difficult problem due to the expressive event specification languages proposed in the recent past which include, among others, complexly defined events (composite events). Therefore, a mechanism is required that is suitable to model the semantics of composite events and to implement the event detector. We demonstrate how Petri nets can be used as the basis of such a mechanism in the context of the SAMOS active database system prototype. <<ETX>>
A New Manganese Dinuclear Complex with Phenolate Ligands and a Single Unsupported Oxo Bridge. Storage of Two Positive Charges within Less than 500 mV. Relevance to Photosynthesis.

The compound [Mn(III)(2)OL(2)](ClO(4))(2). 2.23CHCl(3). 0.65CH(2)Cl(2) where L(-) is the monoanionic N,N-bis(2-pyridylmethyl)-N'-salicyliden-1,2-diaminoethane ligand, has been synthesized. The complex dication [Mn(III)(2)OL(2)](2+) contains a linear Mn(III)-O-Mn(III) unit with a Mn-Mn distance of 3.516 Å. The pentadentate ligand L(-) wraps around the Mn(III) ion. Electrochemically, it is possible to prepare the one electron oxidized trication [Mn(2)OL(2)](3+) which crystallizes as [Mn(2)OL(2)](ClO(4))(2.37)(PF(6))(0.63). 1.5CH(3)CN. The complex trication [Mn(2)OL(2)](3+) contains a Mn(III)-O-Mn(IV) unit with a Mn-Mn distance of 3.524 Å and a Mn-O-Mn angle of 178.7(2) degrees. The contraction of the coordination sphere around the Mn(IV) is clearly observed. The [Mn(2)OL(2)](2+) dication possesses a S = 0 electronic ground state with J = -216 cm(-)(1) (H = -JS(1)(). S(2)()), whereas the [Mn(2)OL(2)](3+) trication shows a S = (1)/(2) ground state with J = -353 cm(-)(1). The UV-visible spectrum of [Mn(2)OL(2)](3+) exhibits an intense absorption band (epsilon = 3040 M(-)(1) cm(-)(1)) centered at 570 nm assigned to a phenolate --> Mn(IV) charge-transfer transition. The potentials of the redox couples determined by cyclic voltammetry are E degrees ([Mn(2)OL(2)](3+)/[Mn(2)OL(2)](2+)) = 0.54 V/saturated calomel electrode (SCE) and E degrees ([Mn(2)OL(2)](4+)/[Mn(2)OL(2)](3+)) = 0.99 V/SCE. Upon oxidation at 1.3 V/SCE, the band at 570 nm shifts to 710 nm (epsilon = 2500 M(-)(1) cm(-)(1)) and a well-defined band appears at 400 nm which suggests the formation of a phenoxyl radical. The [Mn(2)OL(2)](3+)( )()complex exhibits a 18-line X-band electron paramagnetic resonance (EPR) spectrum which has been simulated with rhombic tensors |A(1)(x)()| = 160 x 10(-)(4) cm(-)(1); |A(1)(y)()| = 130 x 10(-)(4) cm(-)(1); |A(1)(z)()| = 91 x 10(-)(4) cm(-)(1); |A(2)(x)()| = 62 x 10(-)(4) cm(-)(1); |A(2)(y)()| = 59 x 10(-)(4) cm(-)(1); |A(2)(z)()| = 62 x 10(-)(4) cm(-)(1) and g(x)() = 2.006; g(y)() = 1.997; g(z)() = 1.982. This EPR spectrum( )()shows that the 16-line paradigm related to a large antiferromagnetic exchange coupling and a low anisotropy can be overcome by a large rhombic anisotropy. Molecular orbital calculations relate this rhombicity to the nature of the orbital describing the extra electron on Mn(III). This orbital has a majority but not pure d(z)()2 contribution (with the z axis perpendicular to the Mn-Mn axis). Low-temperature resonance Raman spectroscopy on an acetonitrile solution of [Mn(2)OL(2)](4+) prepared at -35 degrees C indicated the formation of a phenoxyl radical. This suggests that the ligand was oxidized rather than the Mn(III)Mn(IV) pair to Mn(IV)Mn(IV), which illustrates the difficulty to store a second positive charge in a short range of potential in a manganese mono-&mgr;-oxo pair. The relevance of these results to the study of the photosynthetic oxygen evolving complex is discussed.
Farmers' Involvement in Online Public Consultations and the Corresponding Configuration of the Democratic Divide

The institution of online public consultations was adopted in Greece in 2009 (www.opengov.gr.) Participation or non-participation of citizens in this institution constitutes part of the digital divide, referred to as democratic divide. This paper attempts to disclose components of the democratic gap in the Greek agricultural sector, with particular reference to farmers. This disclosure is attempted by two approaches. The first approach was to perform content analysis on 5078 comments that have been posted on 21 public consultations by the Greek Ministry of Rural Development, in order to identify the participation frequency of farmers. The second approach was part of wider research, and relates to the collection of primary data from 112 farmers of Heraklion, Crete, using a structured questionnaire. The objective of the second approach is to study the farmers' digital and socio-professional profiles and the correlation with their awareness about the institution of online public consultations. The results indicate the existence of a democratic divide, and identify proposals for its reduction.
League‐Level Attendance and Outcome Uncertainty in U.S. Pro Sports Leagues

We extend the breakpoint literature regarding annual league‐level attendance and the impact of outcome uncertainty to the National Basketball Association, National Football League, and National Hockey League. As our measures are different than past work on baseball, we also apply our model to the American and National Leagues. Attendance series for each league under consideration are not stationary overall, but are stationary with break points. No form of outcome uncertainty (game, play‐off, or across seasons) matters for attendance in hockey or baseball regardless of which game uncertainty variable is used. Under the measure of game uncertainty that recommends itself for football, only play‐off uncertainty matters for attendance. Whether outcome uncertainty matters for basketball depends on the measure of game uncertainty. Situational similarities in the break points across leagues suggest general areas for future research.
A novel space-vector PWM computations for a dual three-level T-type converter applied to an open end-winding induction machine

Space-vector pulse-width modulation (SVPWM) computations are complex particularly for multilevel converters. This paper introduces a novel SVPWM computation method for multilevel converters. General formulas for the region identification as well as for PWM intervals calculation are proposed. Then, the proposed formulas are applied to the advanced dual three-level T-type converter topology. The operation of this advanced topology applied to an open end winding induction machine (OEWIM) is discussed in more details. A simulation study for the proposed AC drive system is performed by using Matlab™/Simulink®. A hardware implementation based on a field-programmable gate array (FPGA) for the advanced topology supplying an OEWIM is presented, discussed and analysed. The computation algorithm is built within the FPGA digital controller. A comparison between experimental and simulation results is performed. It is observed that the simulation and the experimental results are agreed and verified the proposed algorithm.
Correlation of MFOLD‐predicted DNA secondary structures with separation patterns obtained by capillary electrophoresis single‐strand conformation polymorphism (CE‐SSCP) analysis

We have studied 57 different mutations within three β‐globin gene promoter fragments with sizes 52 bp, 77 bp, and 193 bp by fluorescent capillary electrophoresis CE‐SSCP analysis. For each mutation and wild type, energetically most‐favorable predicted secondary structures were calculated for sense and antisense strands using the MFOLD DNA‐folding algorithm in order to investigate if any correlation exists between predicted DNA structures and actual CE migration time shifts. The overall CE‐SSCP detection rate was 100% for all mutations in three studied DNA fragments. For shorter 52 bp and 77 bp DNA fragments we obtained a positive correlation between the migration time shifts and difference in free energy values of predicted secondary structures at all temperatures. For longer 193 bp β‐globin gene fragments with 46 mutations MFOLD predicted different secondary structures for 89% of mutated strands at 25°C and 40°C. However, the magnitude of the mobility shifts did not necessarily correlate with their secondary structures and free energy values except for the sense strand at 40°C where this correlation was statistically significant (r = 0.312, p = 0.033). Results of this study provided more direct insight into the mechanism of CE‐SSCP and showed that MFOLD prediction could be helpful in making decisions about the running temperatures and in prediction of CE‐SSCP data patterns, especially for shorter (50–100 bp) DNA fragments. Hum Mutat 19:384–394, 2002. © 2002 Wiley‐Liss, Inc.
PARAMETER ESTIMATION ON GRAVITATIONAL WAVES FROM NEUTRON-STAR BINARIES WITH SPINNING COMPONENTS

Inspiraling binary neutron stars (BNSs) are expected to be one of the most significant sources of gravitational-wave signals for the new generation of advanced ground-based detectors. We investigate how well we could hope to measure properties of these binaries using the Advanced LIGO detectors, which began operation in September 2015. We study an astrophysically motivated population of sources (binary components with masses and spins of less than 0.05) using the full LIGO analysis pipeline. While this simulated population covers the observed range of potential BNS sources, we do not exclude the possibility of sources with parameters outside these ranges; given the existing uncertainty in distributions of mass and spin, it is critical that analyses account for the full range of possible mass and spin configurations. We find that conservative prior assumptions on neutron-star mass and spin lead to average fractional uncertainties in component masses of ∼16%, with little constraint on spins (the median 90% upper limit on the spin of the more massive component is ∼0.7). Stronger prior constraints on neutron-star spins can further constrain mass estimates but only marginally. However, we find that the sky position and luminosity distance for these sources are not influenced by the inclusion of spin; therefore, if LIGO detects a low-spin population of BNS sources, less computationally expensive results calculated neglecting spin will be sufficient for guiding electromagnetic follow-up.
Visual servoing based on object motion estimation

The paper proposes a visual servoing scheme based on object motion estimation. A long term prediction algorithm with multiple motion models is developed. The object position and velocity of a few hundreds of samples ahead is predicted. Thus object tracking without visual information can be achieved during this period. As an example, pick up task of moving object is conducted. The task requires object motion prediction because the hand mounted camera loses the object when the hand approaches the object. Simulations show convergence of prediction. Real-time experiments of picking up a moving object demonstrate the effectiveness of the proposed long term predictor.