Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I trial of 90Y-ibritumomab tiuxetan in patients with relapsed B-cell non-Hodgkin's lymphoma following high-dose chemotherapy and autologous stem cell transplantation

Between January 2001 and September 2005, 19 patients with progressive B-cell non-Hodgkin's lymphoma were treated with a cohort-specific dose of yttrium-90 ibritumomab tiuxetan (0.10 – 0.20 mCi/kg) to determine appropriate dosing in patients who had previously received high-dose chemotherapy and autologous stem cell transplantation (ASCT). Patients were required to have adequate end organ function and bone marrow status. Patients had been treated with a median of three prior therapies (range, 1 – 9). The median time from ASCT to radioimmunotherapy was 28 months. Hematologic toxicities were dose-limiting and included grade 3 – 4 thrombocytopenia (53%), neutropenia (32%), and anemia (21%). The majority of grade 3 – 4 events occurred at the 0.2 mCi/kg dose level. Nine patients responded (complete response, complete response unconfirmed, or partial response) to the therapy. At a median follow-up of 37 months, the 1-year event-free and overall survival rates were 26% and 57%, respectively. A dose of 0.2 mCi/kg ibritumomab tiuxetan is safe and effective for patients with progressive disease after high-dose chemotherapy and ASCT.
TRF1 Controls Telomere Length and Mitotic Fidelity in Epithelial Homeostasis

ABSTRACT TRF1 is a component of the shelterin complex at mammalian telomeres; however, a role for TRF1 in telomere biology in the context of the organism is unclear. In this study, we generated mice with transgenic TRF1 expression targeted to epithelial tissues (K5TRF1 mice). K5TRF1 mice have shorter telomeres in the epidermis than wild-type controls do, and these are rescued in the absence of the XPF nuclease, indicating that TRF1 acts as a negative regulator of telomere length by controlling XPF activity at telomeres, similar to what was previously described for TRF2-overexpressing mice (K5TRF2 mice). K5TRF1 cells also show increased end-to-end chromosomal fusions, multitelomeric signals, and increased telomere recombination, indicating an impact of TRF1 on telomere integrity, again similar to the case in K5TRF2 cells. Intriguingly, K5TRF1 cells, but not K5TRF2 cells, show increased mitotic spindle aberrations. TRF1 colocalizes with the spindle assembly checkpoint proteins BubR1 and Mad2 at mouse telomeres, indicating a link between telomeres and the mitotic spindle. Together, these results demonstrate that TRF1, like TRF2, negatively regulates telomere length in vivo by controlling the action of the XPF nuclease at telomeres; in addition, TRF1 has a unique role in the mitotic spindle checkpoint.
SWAN prediction of nearshore wave climate at Nam Dinh coast in Vietnam

Among a variety of elements, the nearshore wave climate is considered to be the most important aspect to explain erosion problems along the coast. Due to the fact that available data is limited, numerical models are valuable and necessary tools to apply. This study is initiated with the main objective to study the nearshore wave climate of the project area at Nam Dinh coast in Viet Nam by a 2D wave SWAN model in order to investigate the erosion problem along the coast. SWAN (acronym for Simulating of Waves Nearshore) is a third generation wave model, which has been widely applied to simulate wave conditions in many complex field cases in the Netherlands. However, it has never been used in Viet Nam. Thus the achievement of the study may be considered as documentation for future researches of this model in Viet Nam cases. Within this research, at first a SWAN model was set-up based on available data. This includes a sensitivity analysis and model calibration. Then a series of computations were carried out for the application of the model for a mean statistical year. Subsequently, the computed results from the SWAN model were used to identify sediment transport rates. These were compared to actual values in order to investigate whether the 2D wave model can predict the erosion adequately. One of the main results of this study was that the observed sediment transport was qualitatively in accordance with the sediment transport result of the 2D wave model. This emphasized the importance 2D effects to obtain realistic results. In this study, several drawbacks of SWAN have been identified. They include the inconvenient procedure of pre- and post processing in applying SWAN and the convergence problem when activating all physical processes in the model simulations. The study also showed the importance of sufficient wind data in the computational grid. The assumption of uniform wind field in computational grid may lead to inaccurate results in particular with respect to the mean wave direction. For an improvement of the results, the study recommended amongst others that future research should try to generate a variable wind field in the computational grid.
A Survey on Cloud Computing Elasticity

Elasticity is a key feature in the cloud computing context, and perhaps what distinguishes this computing paradigm of the other ones, such as cluster and grid computing. Considering the importance of elasticity in cloud computing context, the objective of this paper is to present a comprehensive study about the elasticity mechanisms available today. Initially, we propose a classification for elasticity mechanisms, based on the main features found in the analysed commercial and academic solutions. In a second moment, diverse related works are reviewed in order to define the state of the art of elasticity in clouds. We also discuss some of the challenges and open issues associated with the use of elasticity features in cloud computing.
History of the Congenital Heart Surgeons’ Society

The Congenital Heart Surgeons’ Society is a group of over 100 pediatric heart surgeons representing 72 institutions that specialize in the treatment of patients with congenital heart defects. The Society began in 1972 and incorporated as a not-for-profit charitable organization in 2004. It has become the face and voice of congenital heart surgery in North America. In 1985, the Society established a data center for multicenter clinical research studies to encourage congenital heart professionals to participate in improving outcomes for our patients. The goals of the Congenital Heart Surgeons’ Society are to stimulate the study of congenital cardiac physiology, pathology, and management options which are instantiated in data collection, multi-institutional studies, and scientific meetings. Honest and open discussion of problems with possible solutions to the challenges facing congenital heart professionals have been the strength of the Congenital Heart Surgeons’ Society. It is imperative for the growth of an organization to know from where it came in order to know to where it is going. The purpose of this article is to review the history of the Congenital Heart Surgeons’ Society.
Comparison of cigarette smoking and non‐smoking in alcohol misusers

Aims: To investigate the psychosocial and environmental factors contributing towards the association between tobacco smoking and alcohol dependence. Methods: Twenty‐three pairs of alcohol‐dependent people were matched for age and gender and compared for sociodemographic and clinical characteristics. Results and conclusion: There was a statistically significant difference in social class between the two groups. There was no significance difference between the groups for any of the other clinical variables including severity of alcohol dependence, liver toxicity tests or presence of dissocial personality disorder.
The Lysyl Oxidase Propeptide Interacts with the Receptor-Type Protein Tyrosine Phosphatase Kappa and Inhibits β-Catenin Transcriptional Activity in Lung Cancer Cells

ABSTRACT The propeptide region of the lysyl oxidase proenzyme (LOX-PP) has been shown to inhibit Ras signaling in NIH 3T3 and lung cancer cells with activated RAS, but its mechanism of action is poorly understood. Here, a yeast two-hybrid assay of LOX-PP-interacting proteins identified a clone encoding the intracellular phosphatase domains of receptor-type protein tyrosine phosphatase kappa (RPTP-κ), and the interaction of the two proteins in mammalian cells was confirmed. RPTP-κ is proteolytically processed to isoforms that have opposing effects on β-catenin activity. The RPTP-κ transmembrane P subunit interacts with and sequesters β-catenin at the cell membrane, where it can associate with E-cadherin and promote intercellular interactions. At high cell density, further processing of the P subunit yields a phosphatase intracellular portion (PIC) subunit, which chaperones β-catenin to the nucleus, where it can function to activate transcription. Lung cancer cells were found to contain higher PIC levels than untransformed lung epithelial cells. In H1299 lung cancer cells, ectopic LOX-PP expression reduced the nuclear levels of PIC by increasing its turnover in the lysosome, thereby decreasing the nuclear levels and transcriptional activity of β-catenin while increasing β-catenin membrane localization. Thus, LOX-PP is shown to negatively regulate pro-oncogenic β-catenin signaling in lung cancer cells.
Application of G-CSF in the Nonneutropenic Host

After the cloning and expression of granulocyte colony-stimulating factor (G-CSF) had been achieved, a recombinant human cytokine (filgrastim and lenograstim) became available for broader use. Experimental data obtained in animal experiments and human volunteers showed a marked increase of granulocytopoiesis accompanied by peripheral granulocytosis so that the use of G-CSF has been essentially concentrated on the supportive administration in cases of acquired neutropenia. Many studies demonstrated good tolerability and efficacy with regard to the neutrophil count of this substance in different patient collectives. Therefore, G-CSF has been admitted for use in patients suffering from neutropenia after myelosuppressive chemotherapy and bone marrow transplantation as well as for the prevention of life-threatening infections in Application of G-CSF in the Nonneutropenic Host Short Review · Kurze Übersicht
Distinct Functions of Human Cohesin-SA1 and Cohesin-SA2 in Double-Strand Break Repair

ABSTRACT Cohesin is an essential multiprotein complex that mediates sister chromatid cohesion critical for proper segregation of chromosomes during cell division. Cohesin is also involved in DNA double-strand break (DSB) repair. In mammalian cells, cohesin is involved in both DSB repair and the damage checkpoint response, although the relationship between these two functions is unclear. Two cohesins differing by one subunit (SA1 or SA2) are present in somatic cells, but their functional specificities with regard to DNA repair remain enigmatic. We found that cohesin-SA2 is the main complex corecruited with the cohesin-loading factor NIPBL to DNA damage sites in an S/G2-phase-specific manner. Replacing the diverged C-terminal region of SA1 with the corresponding region of SA2 confers this activity on SA1. Depletion of SA2 but not SA1 decreased sister chromatid homologous recombination repair and affected repair pathway choice, indicating that DNA repair activity is specifically associated with cohesin recruited to damage sites. In contrast, both cohesin complexes function in the intra-S checkpoint, indicating that cell cycle-specific damage site accumulation is not a prerequisite for cohesin's intra-S checkpoint function. Our findings reveal the unique ways in which cohesin-SA1 and cohesin-SA2 participate in the DNA damage response, coordinately protecting genome integrity in human cells.
Blockchain-Based Publishing Layer for the Keyless Signing Infrastructure

A Keyless Signing Infrastructure (KSI) provides users with a means to timestamp documents on a per-second basis. The KSI consists of a global infrastructure with several server layers, by using Merkle hash trees, the root hash can be used to verify the integrity, timestamp of a document. Regular publication of root hashes, e.g., once per month, allows a document to be verified without support of the servers, but the previously proposed publication channels have several limitations. In this paper we address these limitations, show how a blockchain can be used as an additional publication layer on top of a KSI. Using the scripting capabilities in transactions, new features are introduced to the publication of root hashes. This includes faster publication, proof of origin for the publisher, the possibility for third parties to explicitly verify root hashes before they are published. These improvements will allow the verification of documents to be simpler, more flexible, more secure.
Loss of the Mammalian DREAM Complex Deregulates Chondrocyte Proliferation

ABSTRACT Mammalian DREAM is a conserved protein complex that functions in cellular quiescence. DREAM contains an E2F, a retinoblastoma (RB)-family protein, and the MuvB core (LIN9, LIN37, LIN52, LIN54, and RBBP4). In mammals, MuvB can alternatively bind to BMYB to form a complex that promotes mitotic gene expression. Because BMYB-MuvB is essential for proliferation, loss-of-function approaches to study MuvB have generated limited insight into DREAM function. Here, we report a gene-targeted mouse model that is uniquely deficient for DREAM complex assembly. We have targeted p107 (Rbl1) to prevent MuvB binding and combined it with deficiency for p130 (Rbl2). Our data demonstrate that cells from these mice preferentially assemble BMYB-MuvB complexes and fail to repress transcription. DREAM-deficient mice show defects in endochondral bone formation and die shortly after birth. Micro-computed tomography and histology demonstrate that in the absence of DREAM, chondrocytes fail to arrest proliferation. Since DREAM requires DYRK1A (dual-specificity tyrosine phosphorylation-regulated protein kinase 1A) phosphorylation of LIN52 for assembly, we utilized an embryonic bone culture system and pharmacologic inhibition of (DYRK) kinase to demonstrate a similar defect in endochondral bone growth. This reveals that assembly of mammalian DREAM is required to induce cell cycle exit in chondrocytes.
Fusing VE-Cadherin to α-Catenin Impairs Fetal Liver Hematopoiesis and Lymph but Not Blood Vessel Formation

ABSTRACT We have recently shown that genetic replacement of VE-cadherin by a VE-cadherin–α-catenin fusion construct strongly impairs opening of endothelial cell contacts during leukocyte extravasation and induction of vascular permeability in adult mice. Here we show that this mutation leads to lethality at midgestation on a clean C57BL/6 background. Investigating the reasons for embryonic lethality, we observed a lack of fetal liver hematopoiesis and severe lymphedema but no detectable defects in blood vessel formation and remodeling. As for the hematopoiesis defect, VE-cadherin–α-catenin affected neither the generation of hematopoietic stem and progenitor cells (HSPCs) from hemogenic endothelium nor their differentiation into multiple hematopoietic lineages. Instead, HSPCs accumulated in the fetal circulation, suggesting that their entry into the fetal liver was blocked. Edema formation was caused by disturbed lymphatic vessel development. Lymphatic progenitor cells of VE-cadherin–α-catenin-expressing embryos were able to leave the cardinal vein and migrate to the site of the first lymphatic vessel formation, yet subsequently, these cells failed to form large lumenized lymphatic vessels. Thus, stabilizing endothelial cell contacts by a covalent link between VE-cadherin and α-catenin affects recruitment of hematopoietic progenitors into the fetal liver and the development of lymph but not blood vessels.
Stability of Eukaryotic Translation Initiation Factor 4E mRNA Is Regulated by HuR, and This Activity Is Dysregulated in Cancer

ABSTRACT Eukaryotic translation initiation factor 4E (eIF4E) is encoded by a potent oncogene which is highly elevated in many human cancers. Few studies have investigated how the level, and thus activity, of eIF4E is regulated in healthy (noncancerous) cells and how they become elevated in malignant cells. Here, our studies reveal a novel mechanism by which eIF4E levels are regulated at the level of mRNA stability. Two factors known to modulate transcript stability, HuR and the p42 isoform of AUF1, compete for binding to the 3′ untranslated regions (3′UTRs) of eIF4E mRNAs. We identified a distinct AU-rich element in the 3′UTR of eIF4E which is responsible for HuR-mediated binding and stabilization. Our studies show that HuR is upregulated in malignant cancer specimens characterized by high eIF4E levels and that its depletion leads to reduction in eIF4E levels. Further, HuR and eIF4E regulate a common set of transcripts involved in cellular proliferation (cyclin D1 and c-myc) and neoangiogenesis (vascular endothelial growth factor), which suggests a functional connection between HuR and eIF4E in the regulation of these important processes. In summary, we present a novel model for the regulation of eIF4E expression and show that this model is relevant to elevation of eIF4E levels in malignant cells.
Acyl Coenzyme A Thioesterase 7 Regulates Neuronal Fatty Acid Metabolism To Prevent Neurotoxicity

ABSTRACT Numerous neurological diseases are associated with dysregulated lipid metabolism; however, the basic metabolic control of fatty acid metabolism in neurons remains enigmatic. Here we have shown that neurons have abundant expression and activity of the long-chain cytoplasmic acyl coenzyme A (acyl-CoA) thioesterase 7 (ACOT7) to regulate lipid retention and metabolism. Unbiased and targeted metabolomic analysis of fasted mice with a conditional knockout of ACOT7 in the nervous system, Acot7N−/−, revealed increased fatty acid flux into multiple long-chain acyl-CoA-dependent pathways. The alterations in brain fatty acid metabolism were concomitant with a loss of lean mass, hypermetabolism, hepatic steatosis, dyslipidemia, and behavioral hyperexcitability in Acot7N−/− mice. These failures in adaptive energy metabolism are common in neurodegenerative diseases. In agreement, Acot7N−/− mice exhibit neurological dysfunction and neurodegeneration. These data show that ACOT7 counterregulates fatty acid metabolism in neurons and protects against neurotoxicity.
Iris feature extraction method based on LBP and chunked encoding

Iris feature extraction is a key issue in iris recognition. This paper proposes a novel iris feature extraction method based on local binary pattern (LBP) images and the chunked encoding method. Firstly it applies the LBP to the normalized iris image and obtains the iris' LBP image, then extracts the iris's feature via the chunked encoding method based on the iris' statistical information. Finally it completes the iris recognition and classification using Hamming distance. Experimental results showed that this algorithm can get higher recognition rate than the traditional iris feature extraction method, which demonstrated the efficiency of the proposed method.
A Genome-Wide RNA Interference Screen Identifies a Differential Role of the Mediator CDK8 Module Subunits for GATA/ RUNX-Activated Transcription in Drosophila

ABSTRACT Transcription factors of the RUNX and GATA families play key roles in the control of cell fate choice and differentiation, notably in the hematopoietic system. During Drosophila hematopoiesis, the RUNX factor Lozenge and the GATA factor Serpent cooperate to induce crystal cell differentiation. We used Serpent/Lozenge-activated transcription as a paradigm to identify modulators of GATA/RUNX activity by a genome-wide RNA interference screen in cultured Drosophila blood cells. Among the 129 factors identified, several belong to the Mediator complex. Mediator is organized in three modules plus a regulatory “CDK8 module,” composed of Med12, Med13, CycC, and Cdk8, which has long been thought to behave as a single functional entity. Interestingly, our data demonstrate that Med12 and Med13 but not CycC or Cdk8 are essential for Serpent/Lozenge-induced transactivation in cell culture. Furthermore, our in vivo analysis of crystal cell development show that, while the four CDK8 module subunits control the emergence and the proliferation of this lineage, only Med12 and Med13 regulate its differentiation. We thus propose that Med12/Med13 acts as a coactivator for Serpent/Lozenge during crystal cell differentiation independently of CycC/Cdk8. More generally, we suggest that the set of conserved factors identified herein may regulate GATA/RUNX activity in mammals.
Cytotoxic, Antimutagenic, and Antioxidant Activities of Methanolic Extract and Chalcone Dimers (Lophirones B and C) Derived From Lophira alata (Van Tiegh. Ex Keay) Stem Bark

The cytotoxic, antimutagenic, and antioxidant activities of methanolic extract and lophirones B and C derived from Lophira alata stem bark were evaluated. The extract and lophirones B and C significantly (P < .05) reduced the viability of Ehrlich ascites carcinoma cells. There were concentration-dependent reduction in 4-nitro-o-aminophenylenediamine and benzo[a]pyrene–induced frame shift mutation as well as aflatoxin B1–induced base pair substitution by the extract and lophirones B and C. The extract and lophirones B and C concentration dependently scavenged DPPH radical, superoxide anion radical, hydrogen peroxide, hydroxyl radicals, and reduced ferric ion in the potassium hexacyanoferrate III reducing system. The results obtained from this study revealed that methanolic extract and lophirones B and C derived from Lophira alata stem bark posses anticancer, antimutagenic, and antioxidant activities, with lophirone C producing the best anticancer, antimutagenic, and antioxidant activities. The acclaimed anticancer activity of Lophira alata may be attributed to lophirones B and C.
Diagnostic Accuracy of Cytokine Levels (TNF-α, IL-2 and IFN-γ) in Bronchoalveolar Lavage Fluid of Smear-Negative Pulmonary Tuberculosis Patients

Background: The determination of cytokine concentrations in serum and bronchoalveolar lavage fluid (BALF) may contribute to the diagnosis of tuberculosis (TB) since cytokines have been ascribed an important role in TB pathogenesis. Objective: To assess the diagnostic accuracy of TNF-α, IFN-γ and IL-2 levels in serum and BALF of smear-negative pulmonary TB patients. Method: BALF was obtained from the affected lobe in patients with smear-negative TB or other pulmonary diseases (OPD), and from the right middle lobe in healthy controls. ELISA and a nephelometric method were used to detect cytokine and albumin levels. Results: TNF-α levels in BALF were significantly elevated in the TB group (n = 15) compared with the OPD patients (n = 40) and controls (n = 17; p < 0.001). Although these three cytokines correlated well with each other in BALF (p < 0.0001, and r ≧ 0.7, respectively), BALF IL-2 and IFN-γ levels were not significantly different among the groups (p > 0.05). BALF TNF-α or IFN-γ levels were significantly higher in patients with cavitary disease (n = 11) versus those without (n = 61; p < 0.05). However, no significant difference was found between cavitary (n = 7) and non-cavitary TB in cytokine levels (p > 0.05). Neither gender nor smoking status showed any statistical differences in cytokines in the groups (p > 0.05). Sensitivity and specificity of BALF TNF-α were found to be 73 and 76%, respectively. The positive and negative predictive values for BALF TNF-α were 44 and 91%, respectively. Conclusion: In cases of smear-negative TB, BALF TNF-α can be a useful tool to identify healthy subjects rather than smear-negative TB patients.