Miracle-dz/UniFAR-FTUs huggingface dataset:
FragKB: Structural and Literature Annotation Resource of Conserved Peptide Fragments and Residues

Background FragKB (Fragment Knowledgebase) is a repository of clusters of structurally similar fragments from proteins. Fragments are annotated with information at the level of sequence, structure and function, integrating biological descriptions derived from multiple existing resources and text mining. Methodology FragKB contains approximately 400,000 conserved fragments from 4,800 representative proteins from PDB. Literature annotations are extracted from more than 1,700 articles and are available for over 12,000 fragments. The underlying systematic annotation workflow of FragKB ensures efficient update and maintenance of this database. The information in FragKB can be accessed through a web interface that facilitates sequence and structural visualization of fragments together with known literature information on the consequences of specific residue mutations and functional annotations of proteins and fragment clusters. FragKB is accessible online at http://ubio.bioinfo. cnio.es/biotools/fragkb/. Significance The information presented in FragKB can be used for modeling protein structures, for designing novel proteins and for functional characterization of related fragments. The current release is focused on functional characterization of proteins through inspection of conservation of the fragments.
MMP‐2 alters VEGF expression via αVβ3 integrin‐mediated PI3K/AKT signaling in A549 lung cancer cells

Vascular endothelial growth factor (VEGF) is one of the most important angiogenic growth factors for tumor angiogenesis. Here, we sought to explore whether RNA interference (RNAi) targeting matrix metalloproteinase‐2 (MMP‐2) could disrupt VEGF‐mediated angiogenesis in lung cancer. MMP‐2 siRNA inhibited lung cancer cell‐induced tube formation of endothelial cells in vitro; addition of recombinant human‐MMP‐2 restored angiogenesis. MMP‐2 transcriptional suppression decreased VEGF, phosphatidylinositol 3‐kinase (PI3K) protein levels and AKT phosphorylation in lung cancer cells. In addition, MMP‐2 suppression decreased hypoxia inducible factor‐1α (HIF‐1α), a transcription factor for VEGF, as determined by electrophoretic mobility shift assay (EMSA). We also show that MMP‐2 suppression disrupted PI3K dependent VEGF expression; ectopic expression of myr‐AKT restored VEGF inhibition. Further, MMP‐2 suppression decreased the interaction of integrin‐αVβ3 and MMP‐2 as confirmed by immunoprecipitation analyses. Studies with either function blocking integrin‐αVβ3 antibody or MMP‐2 specific inhibitor (ARP‐100) indicate that suppression of MMP‐2 decreased integrin‐αVβ3‐mediated induction of PI3K/AKT leading to decreased VEGF expression. Moreover, A549 xenograft tissue sections from mice that treated with MMP‐2 siRNA showed reduced expression of VEGF and the angiogenic marker, factor‐VIII. The inhibition of tumor angiogenesis in MMP‐2 suppressed tumor sections was associated with decreased co‐localization of integrin‐αVβ3 and MMP‐2. In summary, these data provide new insights into the mechanisms underlying MMP‐2‐mediated VEGF expression in lung tumor angiogenesis.
Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equations for estimating glomerular filtration rates in cancer patients receiving cisplatin-based chemotherapy

Background Although the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has been recommended for accurate estimates of glomerular filtration rate (eGFR), there is little information regarding differences in GFR estimates obtained using the Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) equations in East Asian cancer patients. We investigated discrepancies in GFR and toxicities in patients treated with cisplatin-based chemotherapy using three equations equations. Methods A total of 229 patients were retrospectively recruited. We calculated eGFR using the three equations and separated patients into three categories based on GFR < 10 (group A), 10–50 (group B), and > 50 (group C) mL/min/1.73m2. We analyzed chemotherapy toxicities. Results The mean eGFR calculated using the CG was the lowest of the values derived using the three equations. Estimates using the MDRD and CKD-EPI equations resulted in reclassifying 32 (71.1%) and 33 (73.3%) of 45 patients, originally placed in group B using the CG into group C. However, only 1 (7.7%) of 13 patients placed in group B using the MDRD were reclassified into group C using the CKD-EPI. Twenty-eight of 45 patients classified into group B using the CG equation were treated with reduced doses of cisplatin. However, these patients did not show significant differences in toxicities compared with other patients taking full doses of cisplatin. Conclusion The CG equations underestimated GFR compared to the MDRD and CKD-EPI equations. Therefore, when GFR is estimated using CG equations, East Asian cancer patients may receive insufficient doses of chemotherapeutic agents, including cisplatin.
Exploring the role and place of the Permanent Representative Committee within the African Union

It can be confidently stated that, since its constitutive act came into effect in July, 2001, the African Union (AU) has enjoyed increasing attention at the administrative level from a number of scholars. Most of these scholars focus, however, on the evolution of the AU in general or on the Peace and Security Council and its components and how it links with regional organisations and the United Nations. This article adds to the existing literature by looking closely at the role and place of the Permanent Representatives Committee (PRC) in the decision-making framework of the AU. It also critically analyses the potential of the PRC and the challenges facing it as one of the most important decision-making committees of the AU. Lastly, it examines the evolution of the PRC and its functions. Finally, among other things, the article questions the lack of transparency practised by the PRC and proposes new approaches.
CKAP2 (cytoskeleton-associated protein2) is a new prognostic marker in HER2-negative luminal type breast cancer

Background Recently, we reported cytoskeleton-associated protein2 (CKAP2) as a possible new prognostic breast cancer marker. However, it has not yet been applied in clinic. Therefore, clinical significance of CKAP2 was evaluated in comparison with that of Ki-67 in a cohort of breast cancer patients, and the expression difference was analyzed in cell cycle-arrested cancer and fibroblast cells. Methods A total of 579 early breast cancer patients who underwent surgery at the National Cancer Center Hospital in Korea between 2001 and 2005 were accrued. CKAP2-positive cell count (CPCC) and Ki-67 labeling index (Ki-67LI) were evaluated by immunohistochemcal staining. The immunocytochemical staining patterns of CKAP2 and Ki-67 were analyzed in HeLa and human fibroblast cells after synchronization by double thymidine block. Results Although there was a significant correlation (R = 0.754, P < 0.001) between CPCC and Ki-67LI, only CPCC was correlated with DFS in overall population (HR, 2.029; 95% CI, 1.012–4.068; P = 0.046) and HER2-negative luminal subgroup (HR, 3.984; 95% CI, 1.350–11.762; P = 0.012) by multivariate analysis. In immunocytochemical staining, more than 50% of serum-starved or non-mitotic cell phase HeLa cells were positive for Ki-67, in comparison to the low CKAP2-positivity, which might explain the prognostic difference between CPCC and Ki-67LI. Conclusions The current study showed that CPCC but not Ki-67LI is an independent prognostic indicator in early breast cancer, more specifically in HER2-negative luminal breast cancer. The difference between two markers may be related to the lower background expression of CKAP2 in cancer cells.
Molecular and Structural Characterization of the Tegumental 20.6-kDa Protein in Clonorchis sinensis as a Potential Druggable Target

The tegument, representing the membrane-bound outer surface of platyhelminth parasites, plays an important role for the regulation of the host immune response and parasite survival. A comprehensive understanding of tegumental proteins can provide drug candidates for use against helminth-associated diseases, such as clonorchiasis caused by the liver fluke Clonorchis sinensis. However, little is known regarding the physicochemical properties of C. sinensis teguments. In this study, a novel 20.6-kDa tegumental protein of the C. sinensis adult worm (CsTegu20.6) was identified and characterized by molecular and in silico methods. The complete coding sequence of 525 bp was derived from cDNA clones and encodes a protein of 175 amino acids. Homology search using BLASTX showed CsTegu20.6 identity ranging from 29% to 39% with previously-known tegumental proteins in C. sinensis. Domain analysis indicated the presence of a calcium-binding EF-hand domain containing a basic helix-loop-helix structure and a dynein light chain domain exhibiting a ferredoxin fold. We used a modified method to obtain the accurate tertiary structure of the CsTegu20.6 protein because of the unavailability of appropriate templates. The CsTegu20.6 protein sequence was split into two domains based on the disordered region, and then, the structure of each domain was modeled using I-TASSER. A final full-length structure was obtained by combining two structures and refining the whole structure. A refined CsTegu20.6 structure was used to identify a potential CsTegu20.6 inhibitor based on protein structure-compound interaction analysis. The recombinant proteins were expressed in Escherichia coli and purified by nickel-nitrilotriacetic acid affinity chromatography. In C. sinensis, CsTegu20.6 mRNAs were abundant in adult and metacercariae, but not in the egg. Immunohistochemistry revealed that CsTegu20.6 localized to the surface of the tegument in the adult fluke. Collectively, our results contribute to a better understanding of the structural and functional characteristics of CsTegu20.6 and homologs of flukes. One compound is proposed as a putative inhibitor of CsTegu20.6 to facilitate further studies for anthelmintics.
Review of treatment of bronchiolitis related apnoea in two centres

Aims: To determine whether the use of negative pressure ventilation (NPV) was associated with a lower rate of endotracheal intubation in infants with recurrent apnoea secondary to acute bronchiolitis. Methods: Retrospective review of two paediatric intensive care units (PICU) databases and case notes; one PICU offered NPV. Results: Fifty two infants with bronchiolitis related apnoea were admitted to the two PICUs (31 to the NPV centre). There were no significant differences between infants in the two centres in age and weight on admission, gestational age at birth, birth weight, history of apnoea of prematurity or chronic lung disease, days ill before referral, respiratory syncytial virus status, oxygen requirement before support, and numbers retrieved from secondary care centres. Respiratory support was provided to all 31 infants in the NPV centre (23 NPV, 8 PPV), and 19/21 in the non-NPV centre (18 PPV, 1 CPAP); the NPV centre had lower rates of endotracheal intubation rates (8/31 v 18/21), shorter durations of stay (median 2 v 7 days), and less use of sedation (16/31 v 18/21). In the two years after the NPV centre discontinued use of NPV, 14/17 (82%) referred cases were intubated, with a median PICU stay of 7.5 days. Conclusions: The use of NPV was associated with a reduced rate of endotracheal intubation, and shorter PICU stay. A prospective randomised controlled trial of the use of NPV in the treatment of bronchiolitis related apnoea is warranted.
Various Regimens of Total Body Irradiation for Hematopoietic Stem Cell Transplant.

OBJECTIVES We aimed to evaluate the safety of total body irradiation before bone marrow transplant. MATERIALS AND METHODS We analyzed 110 patients (65 male, 45 female) who underwent total body irradiation for hematopoietic stem cell transplant between May 1998 and March 2013. Median age at total body irradiation was 17 years (range, 1-62 y). Median observation time was 777 days (range, 31-5494 d). Initial diagnoses were acute lymphoblastic leukemia (24 patients), acute myeloid leukemia (26 patients), chronic myeloid leukemia (7 patients), myelodysplastic syndrome (8 patients), malignant lymphoma (13 patients), mucopolysaccharidosis (12 patients), neuroblastoma (10 patients), and other diseases (10 patients). The total fractionated dose used for total body irradiation was 12 Gy in 69 patients and 6.0-10.8 Gy in 29 patients. Single-dose total body irradiation was administered to 12 patients. Most patients (63 of 110) received chemotherapy consisting of cyclophosphamide alone. RESULTS Ocular complications were observed in 29.5% of the patients. Hypothyroidism, interstitial pneumonia, obliterative bronchiolitis, and veno-occlusive disease developed in 8.2%, 1.8%, 0.9%, and 2.7% of patients. Growth abnormality was observed in 10 (20%) of the 50 pediatric patients. The use of a lower dose (< 12 Gy vs 12 Gy) of fractionated total body irradiation did not decrease the incidence of adverse events; however, nonmyeloablative conditioning with low-dose singlefraction total body irradiation reduced the incidence of adverse events. Three patients who underwent total body irradiation as reirradiation therapy achieved long-term survival without adverse events. CONCLUSIONS Fractionated total body irradiation given at a lower dose (<12 Gy vs 12 Gy) did not decrease the incidence of adverse events.
Learning from Data Stream Based on Random Projection and Hoeffding Tree Classifier

In this study, we introduce an ensemble-based approach for online machine learning. Here, instead of working on the original data, several Hoeffding tree classifiers classify and are updated on the lower dimensional projected data generated from originality by random projections. Since random projection is unstable, from one example, many diverse training data can be created to train the set of Hoeffding tree classifiers. The experiments conducted on a number of datasets chosen from different sources demonstrate that the proposed approach performs significantly better than the single Hoeffding tree and some well-known online learning algorithms including additive models and Online Bagging.
The brain-derived neurotrophic factor Val66Met polymorphism moderates early deprivation effects on attention problems

Abstract Adverse early care is associated with attention regulatory problems, but not all so exposed develop attention problems. In a sample of 612 youth (girls = 432, M = 11.82 years, SD = 1.5) adopted from institutions (e.g., orphanages) in 25 countries, we examined whether the Val66Met polymorphism of the brain-derived neurotrophic factor gene moderates attention problems associated with the duration of institutional care. Parent-reported attention problem symptoms were collected using the MacArthur Health and Behavior Questionnaire. DNA was genotyped for the brain-derived neurotrophic factor Val66Met (rs6265) single nucleotide polymorphism. Among youth from Southeast (SE) Asia, the predominant genotype was valine/methionine (Val/Met), whereas among youth from Russia/Europe and Caribbean/South America, the predominant genotype was Val/Val. For analysis, youth were grouped as carrying Val/Val or Met/Met alleles. Being female, being from SE Asia, and being younger when adopted were associated with fewer attention regulatory problem symptoms. Youth carrying at least one copy of the Met allele were more sensitive to the duration of deprivation, yielding an interaction that followed a differential susceptibility pattern. Thus, youth with Val/Met or Met/Met genotypes exhibited fewer symptoms than Val/Val genotypes when adoption was very early and more symptoms when adoption occurred later in development. Similar patterns were observed when SE Asian youth and youth from other parts of the world were analyzed separately.
Gait Learning-Based Regenerative Model: A Level Set Approach

We propose a learning method for gait synthesis from a sequence of shapes(frames) with the ability to extrapolate to novel data. It involves the application of PCA, first to reduce the data dimensionality to certain features, and second to model corresponding features derived from the training gait cycles as a Gaussian distribution. This approach transforms a non Gaussian shape deformation problem into a Gaussian one by considering features of entire gait cycles as vectors in a Gaussian space. We show that these features which we formulate as continuous functions can be modeled by PCA. We also use this model to in-between (generate intermediate unknown) shapes in the training cycle. Furthermore, this paper demonstrates that the derived features can be used in the identification of pedestrians.
A Linguistics-Driven Approach to Statistical Parsing for Low-Resourced Languages

Developing a practical and accurate statistical parser for low-resourced languages is a hard problem, because it requires large-scale treebanks, which are expensive and labor-intensive to build from scratch. Unsupervised grammar induction theoretically offers a way to overcome this hurdle by learning hidden syntactic structures from raw text automatically. The accuracy of grammar induction is still impractically low because frequent collocations of non-linguistically associable units are commonly found, resulting in dependency attachment errors. We introduce a novel approach to building a statistical parser for low-resourced languages by using language parameters as a guide for grammar induction. The intuition of this paper is: most dependency attachment errors are frequently used word orders which can be captured by a small prescribed set of linguistic constraints, while the rest of the language can be learned statistically by grammar induction. We then show that covering the most frequent grammar rules via our language parameters has a strong impact on the parsing accuracy in 12 languages. key words: statistical parsing, grammar induction, language parameters, Universal Grammar, treebank
Evaluation of a depression screening and treatment program in primary care for patients with diabetes mellitus: Insights and future directions

Purpose: To evaluate a collaborative depression care program by assessing adherence to the program by internal medicine clinic (IMC) staff, and the program's effectiveness in treating depression in patients with diabetes mellitus. We also describe the rate of depression among patients with diabetes in the IMC. Data sources: Data for this program were obtained from a deidentified disease registry and included 1312 outpatient IMC visits in adult patients with diabetes between March 2011 and September 2011. Conclusions: Collaborative depression care results in high rates of screening for and identification of depression, high rates of antidepressant utilization, and improved depression scores; however, more focused interventions are needed to improve diabetes outcomes in patients with depression and diabetes. Implications for practice: The results indicate that the multidisciplinary IMC staff can work together with patients to identify and monitor depression within primary care. This study provides valuable information about models of depression care that can be implemented and evaluated in a clinical setting.
In situ structure and dynamics of DNA origami determined through molecular dynamics simulations

Significance Folding of DNA strands into complex three-dimensional nanoscale objects—DNA origami—has emerged as a new paradigm for practical nanotechnology. Although computer-aided design tools are often used to illustrate the idealized shape of such objects, their structural behavior in solution has been poorly characterized. Using a large supercomputer system, we created trajectories of millions of atoms to obtain the first atomically precise portrait of DNA origami in solution. The DNA origami objects were found to undergo considerable structural fluctuations, significantly departing from their idealized conformations at the nanometer scale. Analysis of the fluctuations provided a detailed map of local mechanical properties of DNA origami. Our work demonstrates the potential for atomistic simulations to facilitate rational engineering of DNA origami objects. The DNA origami method permits folding of long single-stranded DNA into complex 3D structures with subnanometer precision. Transmission electron microscopy, atomic force microscopy, and recently cryo-EM tomography have been used to characterize the properties of such DNA origami objects, however their microscopic structures and dynamics have remained unknown. Here, we report the results of all-atom molecular dynamics simulations that characterized the structural and mechanical properties of DNA origami objects in unprecedented microscopic detail. When simulated in an aqueous environment, the structures of DNA origami objects depart from their idealized targets as a result of steric, electrostatic, and solvent-mediated forces. Whereas the global structural features of such relaxed conformations conform to the target designs, local deformations are abundant and vary in magnitude along the structures. In contrast to their free-solution conformation, the Holliday junctions in the DNA origami structures adopt a left-handed antiparallel conformation. We find the DNA origami structures undergo considerable temporal fluctuations on both local and global scales. Analysis of such structural fluctuations reveals the local mechanical properties of the DNA origami objects. The lattice type of the structures considerably affects global mechanical properties such as bending rigidity. Our study demonstrates the potential of all-atom molecular dynamics simulations to play a considerable role in future development of the DNA origami field by providing accurate, quantitative assessment of local and global structural and mechanical properties of DNA origami objects.