Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of CD146 as Target for Radioimmunotherapy against Osteosarcoma

Background Osteosarcoma is a rare form of cancer but with a substantial need for new active drugs. There is a particular need for targeted therapies to combat metastatic disease. One possible approach is to use an antibody drug conjugate or an antibody radionuclide conjugate to target the osteosarcoma metastases and circulating tumor cells. Herein we have evaluated a radiolabeled monoclonal antibody targeting CD146 both in vitro and in vivo. Methods and Results A murine monoclonal anti-CD146 IgG1 isotype antibody, named OI-3, was developed along with recombinant chimeric versions with human IgG1 or human IgG3 Fc sequences. Using flow cytometry, selective binding of OI-3 to human osteosarcoma cell lines OHS, KPDX and Saos-2 was confirmed. The results confirm a higher expression level of CD146 on human osteosarcoma cells than HER2 and EGFR; antigens targeted by commercially available therapeutic antibodies. The biodistribution of 125I-labeled OI-3 antibody variants was compared with 125I-labeled chimeric anti-EGFR antibody cetuximab in nude mice with subcutaneous OHS osteosarcoma xenografts. OI-3 was able to target CD146 expressing tumors in vivo and showed improved tumor to tissue targeting ratios compared with cetuximab. Subsequently, the three OI-3 variants were conjugated with p-SCN-Bn-DOTA and labeled with a more therapeutically relevant radionuclide, 177Lu, and their biodistributions were studied in the nude mouse model. The 177Lu-labeled OI-3 variants were stable and had therapeutically relevant biodistribution profiles. Dosimetry estimates showed higher absorbed radiation dose to tumor than all other tissues after administration of the chimeric IgG1 OI-3 variant. Conclusion Our results indicate that CD146 can be targeted in vivo by the radiolabeled OI-3 antibodies.
Protecting group-directed annulations of tetra-substituted oxindole olefins and sulfur ylides: regio- and chemoselective synthesis of cyclopropane- and dihydrofuran-fused spirooxindoles

Protecting group-controlled annulations of tetra-substituted oxindole olefins and sulfur ylides have been achieved for the synthesis of multifunctional cyclopropane- and dihydrofuran-fused spirooxindoles. Under precise annulation regulation, a variety of cyclopropane- and dihydrofuran-fused spirooxindoles containing vicinal quaternary carbon centers were produced in up to 90% yield with up to 20 : 1 dr. This reaction demonstrates high regio-, chemo- and diastereoselectivity, broad functional group tolerance and gram-scale capacity.
Randomized comparison of angioplasty of complex coronary lesions at a single center. Excimer Laser, Rotational Atherectomy, and Balloon Angioplasty Comparison (ERBAC) Study.

BACKGROUND The purpose of this study was to test whether coronary revascularization with ablation of either excimer laser or rotational atherectomy can improve the initial angiographic and clinical outcomes compared with dilatation (balloon angioplasty) alone. METHODS AND RESULTS At a single center, a total of 685 patients with symptomatic coronary disease warranting elective percutaneous revascularization for a complex lesion were randomly assigned to balloon angioplasty (n = 222), excimer laser angioplasty (n = 232), or rotational atherectomy (n = 231). The primary end point was procedural success (diameter stenosis < 50%, absence of death, Q-wave myocardial infarction, or coronary artery bypass surgery). The patients who underwent rotational atherectomy had a higher rate of procedural success than those who underwent excimer laser angioplasty or conventional balloon angioplasty (89% versus 77% and 80%, P = .0019), but no difference was observed in major in-hospital complications (3.2% versus 4.3% versus 3.1%, P = .71). At the 6-month follow-up, revascularization of the original target lesion was performed more frequently in the rotational atherectomy group (42.4%) and the excimer laser group (46.0%) than in the angioplasty group (31.9%, P = .013). CONCLUSIONS Procedural success of rotational atherectomy is superior to laser angioplasty and balloon angioplasty; however, it does not result in better late outcomes. The role of plaque debulking before balloon dilatation in percutaneous coronary revascularization remains to be fully defined.
Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history.

Recent reports have suggested that one or more genes may cause replication errors (RER) during colorectal tumorigenesis. Additional alleles are seen in the tumors when analyzing random microsatellite loci. We have studied seven dinucleotide repeat loci, located on seven different chromosomes, by use of polymerase chain reaction amplification and denaturing polyacrylamide gel electrophoresis. We found that 16.5% (40 of 243) colorectal cancers showed RER at one or several loci (RER+). This includes 31% (4 of 13) among cases with a strong positive family history according to previously published criteria and 17% (35 of 207) among cases with no history of familial cancer. Interestingly, no significant association was found between RER+ tumors and a general familial clustering of cancer. Microsatellite instability was significantly associated with DNA diploid status of the tumor (P < 0.001), with the location of the tumor in the proximal colon (P < 0.001), and with poorly differentiated tumor phenotype (P < 0.001). Patients with RER+ at > or = 2 loci tumors had an increased survival (P = 0.05). We further analyzed 84 breast cancers and 86 male germ cell cancers using the same seven markers. None of the tumors were RER+, indicating that this phenomenon may be specific to certain types of tumors.
Interleukin‐1β and Thymic Peptide Regulation of Pituitary and Glial Cell Cytokine Expression and Cellular Proliferation

Abstract: Interleukin‐6 (IL‐6) is a B‐cell differentiating and T‐cell activating cytokine that is expressed in T cells, neutrophils, monocytes, macrophages, and mast cells. Because IL‐6 is also synthesized and released by anterior pituitary cells and IL‐6 stimulates pituitary hormone release, this cytokine may serve a paracrine or autocrine role within the pituitary. Interleukin‐1β (IL‐1β) stimulates IL‐6 release from anterior pituitary cells through a mechanism that involves lysophosphatidylcholine (LPC 18:0) generation and protein kinase C activation. In the rat C6 glioma cell line, IL‐1β synergistically stimulates IL‐6 release in the presence of increased intracellular cAMP concentrations. The catecholamines and serotonin also synergistically stimulate IL‐6 release in the presence of IL‐1β. LPC 18:0 synergistically increases IL‐6 release in the presence of norepinephrine, and IL‐1β transiently increases LPC 18:0 formation in C6 cells. Therefore, IL‐1β induction of LPC 18:0 may lead to increases in IL‐6 production via activation of a kinase cascade. The bovine thymic preparation, thymosin fraction 5 (TF5), also stimulates IL‐6 release from C6 glioma cells in a protein kinase C‐dependent manner. Of interest, TF5 inhibits the proliferation of C6 cells, pituitary adenoma MMQ cells, and promyelocytic HL‐60 cells. We suggest that a thymic hormone immune surveillance mechanism may suppress neuroendocrine and hematopoietic tumor formation. Thus, IL‐1b and certain thymic peptides act to increase IL‐6 expression in neuroendocrine cells. The enhanced production of neuroendocrine cytokines may affect hormone secretion, neurotransmission, and the development of certain neurodegenerative disorders (e.g., Alzheimer's disease). The isolation of the active component of TF5 that inhibits neuroendocrine and hematopoietic tumor cell proliferation will provide a potential therapeutic strategy for the treatment of these tumors.
Deep Representation Learning with Target Coding

We consider the problem of learning deep representation when target labels are available. In this paper, we show that there exists intrinsic relationship between target coding and feature representation learning in deep networks. Specifically, we found that distributed binary acode with error correcting capability is more capable of encouraging discriminative features, in comparison tothe 1-of-K coding that is typically used in supervised deep learning. This new finding reveals additional benefit of using error-correcting code for deep model learning,apart from its well-known error correcting property. Extensive experiments are conducted on popular visual benchmark datasets.
Transforming growth factor-beta 1: histochemical localization with antibodies to different epitopes

We have localized transforming growth factor-beta (TGF-beta) in many cells and tissues with immunohistochemical methods, using two polyclonal antisera raised to different synthetic preparations of a peptide corresponding to the amino-terminal 30 amino acids of TGF-beta 1. These two antibodies give distinct staining patterns; the staining by anti-CC(1-30) is intracellular. This differential staining pattern is consistently observed in several systems, including cultured tumor cells; mouse embryonic, neonatal, and adult tissues; bovine fibropapillomas; and human colon carcinomas. The extracellular staining by anti-CC(1-30) partially resembles that seen with an antibody to fibronectin, suggesting that extracellular TGF-beta may be bound to matrix proteins. The intracellular staining by anti-LC(1-30) is similar to that seen with two other antibodies raised to peptides corresponding to either amino acids 266-278 of the TGF-beta 1 precursor sequence or to amino acids 50-75 of mature TGF-beta 1, suggesting that anti-LC(1- 30) stains sites of TGF-beta synthesis. Results from RIA and ELISAs indicate that anti-LC(1-30) and anti-CC(1-30) recognize different epitopes of this peptide and of TGF-beta 1 itself.
Quantification of myocardial blood volume during dipyridamole and doubtamine stress: a perfusion CMR study.

PURPOSE Myocardial blood volume (MBV) may provide complementary information about myocardial oxygen needs and viability. The aim of this study is to examine a Cardiovascular Magnetic Resonance (CMR) perfusion method to quantify the changes in MBV, in comparison with the radiolabeled 99mTc-Red-Blood-Cell (RBC) method. METHODS Normal mongrel dogs (n=12) were used in this study. Eight dogs were injected intravenously with dipyridamole, and 4 dogs were given dobutamine during the MR scans. CMR first-pass perfusion imaging was performed at rest and during the pharmacological stress. An intravascular contrast agent, Gadomer (Schering AG, Berlin, Germany), was injected (0.015 mmol/kg) as a bolus during the scans. A perfusion quantification method was applied to obtain MBV maps. Radiolabeled-RBCs were injected at the end of the study to measure reference MBV at rest (n=4), during dipyridamole vasodilation (n=4), and during dobutamine stress (n=4). RESULTS Myocardial blood flow (MBF) increased approximately 3-fold with both dipyridamole and dobutamine injections. Transmural MBV values measured by CMR were closely correlated with those measured by 99mTc method (CMR:MBV=6.2+/-1.3, 7.2+/-0.8, and 8.3+/-0.5 mL/100 g, at rest, with dipyridamole, and with dobutamine, respectively. 99mTc-RBC: MBV=6.1+/-0.5, 7.0+/-0.9, and 8.6+/-0.7 mL/100 g). Dobutamine stress significantly increased MBV by CMR (33%) and 99mTc methods (35%). During dipyridamole induced vasodilation, MBV increased non-significantly by 14% with the 99mTc method and 1% with CMR method, which agreed well with other reports. CONCLUSION First-pass perfusion CMR with the injection of intravascular contrast agents is a promising non-invasive approach for the assessment of MBV both at rest and pharmacologically induced stress.
Edmodo-Based Blended Learning Model as an Alternative of Science Learning to Motivate and Improve Junior High School Students' Scientific Critical Thinking Skills

Abstract—This study aims to analyze students' scientific critical thinking skills through learning with edmodo-based blended learning models. This study is Pre-Experimental using one group pre-test post-test design involving 35 class VIII students at Public Junior High School 10 Jember, Indonesia. The instru-ments used were teacher activity observation sheets, student activity observation sheets, scientific critical thinking skills assessment sheets, and student motivation sheets. Before and after learning activity, students are given the same initial test (pre-test) and final test (post-test). The collected data was analyzed by quantitative descriptive analysis. The results of the study show that: (1) students are motivated in classical learning by 78.13% with motivated criteria. The highest value is on the likes and active indicators using Edmodo, which is equal to 88.47% and the lowest value on the indicator of activity asks questions and opinions at edmodo, which is equal to 70.93%; and (2) there is an increase in scientific critical thinking skills of students with a mean n-gain of . 32, with the criteria being moderate. The highest value is achieved on the indicator of fact analysis, which is equal to . 55 and the lowest value on the indicators of delivery of argumentation, which is equal to . 19. The conclusion of this study is that science learning with an edmodo-based blended learning model can motivate learning and improve scientific critical thinking skills of junior high school students.
Protective Efficacy of a Single Immunization of a Chimeric Adenovirus Vector-Based Vaccine against Simian Immunodeficiency Virus Challenge in Rhesus Monkeys

ABSTRACT Rare serotype and chimeric recombinant adenovirus (rAd) vectors that evade anti-Ad5 immunity are currently being evaluated as potential vaccine vectors for human immunodeficiency virus type 1 and other pathogens. We have recently reported that a heterologous rAd prime-boost regimen expressing simian immunodeficiency virus (SIV) Gag afforded durable partial immune control of an SIV challenge in rhesus monkeys. However, single-shot immunization may ultimately be preferable for global vaccine delivery. We therefore evaluated the immunogenicity and protective efficacy of a single immunization of chimeric rAd5 hexon hypervariable region 48 (rAd5HVR48) vectors expressing SIV Gag, Pol, Nef, and Env against a homologous SIV challenge in rhesus monkeys. Inclusion of Env resulted in improved control of peak and set point SIV RNA levels following challenge. In contrast, DNA vaccine priming did not further improve the protective efficacy of rAd5HVR48 vectors in this system.
Alterations of The Stem-Like Properties in The Breast Cancer Cell Line MDA-MB-231 Induced by Single Pulsed Doxorubicin Treatment

Abstract Development of chemoresistance remains a significant limitation for the treatment of cancer and contributes to recurrence of the disease. Both intrinsic and acquired mechanisms of chemoresistance are characteristics of cancer stem cells (CSCs) or stem-like cells (SLCs). The aim of the study was to assess the stem-like properties in the breast cancer cell line MDA-MB-231 during and after pulsed treatment with doxorubicin (DOX) in comparison to the untreated controls.The experimental cultures were exposed to therapeutic concentration of DOX for 48 hours (treatment cultures), and subcultured to post-treatment cultures 24 hours after the removal of DOX. Stem-like properties of the cellular populations in the treatment and post--treatment cultures were assessed by the expression of the stem-cell marker genes (CD24, CD44, ITGA6, ITGB1, POU5F1, NANOG, ALDH1A1), colony-formation efficiency, growth rates, and sensitivity to DOX, 5-fluorouracil (5FU), cisplatin (CIS), and vinblastine (VBL). Exposure to DOX induced formation of giant polyploid cells that persisted in the post-treatment culture. The recovery period was characterised by a decrease in the proliferation rate, viability, and cellular adherence. The post-treatment cultures displayed decreased sensitivity to DOX and increased sensitivities to 5FU, CIS, and VBL. Cells treated with DOX displayed increased expression levels of CD24, CD44, and ALDH1A, while their expression levels at least partially normalised in the post-treatment culture. The post-treatment cultures demonstrated significantly increased colony-formation ability. During treatment with sub-lethal levels of doxorubicin and during the acute recovery period, the survival mechanisms in the breast cancer cell line MDA-MB-231 may be mediated by formation of the cellular population with stem-like properties.
Effects of carnitine and coenzyme Q10 on lipid profile and serum levels of lipoprotein(a) in maintenance hemodialysis patients on statin therapy.

INTRODUCTION Dyslipidemia and high serum lipoprotein(a) are among the risk factors for cardiovascular diseases in hemodialysis patients. Statins as a first line of therapy in hyperlipidemia does not always reduce the serum lipoprotein(a) level. Several studies have reported the lipid-lowering effects of carnitine and coenzyme Q10 in hemodialysis patients. This study was designed to investigate the effects of carnitine and coenzyme Q10 on serum lipid profile and lipoprotein(a) level in maintenance hemodialysis patients. MATERIALS AND METHODS This was a randomized placebo-controlled trial. We studied on hemodialysis patients who were on treatment with atorvastatin or lovastatin to assess the efficacy of supplement therapy. They were divided into 4 groups to receive carnitine, coenzyme Q10, both carnitine and coenzyme Q10, and placebo. After a 3-month experiment, blood samples were collected to measure serum levels of lipoprotein(a), triglyceride, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. RESULTS Fifty-two hemodialysis patients, 27 men and 25 women, completed the course of the study. Three months after supplement therapy, serum levels of lipoprotein(a) reduced significantly in the carnitine, coenzyme Q10, and combination groups compared to the baseline values and the 3-month value of lipoprotein(a) in the placebo group (P = .01). Serum levels of triglyceride and other lipoproteins did not significantly alter. CONCLUSIONS Our study showed that supplementation with carnitine and coenzyme Q10 could reduce serum levels of lipoprotein(a) in maintenance hemodialysis patients treated with statins.
CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

ABSTRACT Borna disease virus (BDV) frequently causes meningoencephalitis and fatal neurological disease in young but not old mice of strain MRL. Disease does not result from the virus-induced destruction of infected neurons. Rather, it is mediated by H-2k-restricted antiviral CD8 T cells that recognize a peptide derived from the BDV nucleoprotein N. Persistent BDV infection in mice is not spontaneously cleared. We report here that N-specific vaccination can protect wild-type MRL mice but not mutant MRL mice lacking gamma interferon (IFN-γ) from persistent infection with BDV. Furthermore, we observed a significant degree of resistance of old MRL mice to persistent BDV infection that depended on the presence of CD8 T cells. We found that virus initially infected hippocampal neurons around 2 weeks after intracerebral infection but was eventually cleared in most wild-type MRL mice. Unexpectedly, young as well as old IFN-γ-deficient MRL mice were completely susceptible to infection with BDV. Moreover, neurons in the CA1 region of the hippocampus were severely damaged in most diseased IFN-γ-deficient mice but not in wild-type mice. Furthermore, large numbers of eosinophils were present in the inflamed brains of IFN-γ-deficient mice but not in those of wild-type mice, presumably because of increased intracerebral synthesis of interleukin-13 and the chemokines CCL1 and CCL11, which can attract eosinophils. These results demonstrate that IFN-γ plays a central role in host resistance against infection of the central nervous system with BDV and in clearance of BDV from neurons. They further indicate that IFN-γ may function as a neuroprotective factor that can limit the loss of neurons in the course of antiviral immune responses in the brain.
Levels of acid-soluble polyphosphate in growing cultures of Saccharomyces cerevisiae

Short-chain acid-soluble polyphosphates were extracted from growing cultures of Saccharomyces cerevisiae, and the changes in the levels of these compounds were determined. The production of acid-soluble polyphosphates correlated with the mitochondrial activities since it occurred in two bursts in respiration-competent yeast cells and in only one burst in respiration-deficient yeast cells. The possible role of these compounds is discussed.
An Approach to Pose-Based Action Recognition

We address action recognition in videos by modeling the spatial-temporal structures of human poses. We start by improving a state of the art method for estimating human joint locations from videos. More precisely, we obtain the K-best estimations output by the existing method and incorporate additional segmentation cues and temporal constraints to select the ``best'' one. Then we group the estimated joints into five body parts (e.g. the left arm) and apply data mining techniques to obtain a representation for the spatial-temporal structures of human actions. This representation captures the spatial configurations of body parts in one frame (by spatial-part-sets) as well as the body part movements(by temporal-part-sets) which are characteristic of human actions. It is interpretable, compact, and also robust to errors on joint estimations. Experimental results first show that our approach is able to localize body joints more accurately than existing methods. Next we show that it outperforms state of the art action recognizers on the UCF sport, the Keck Gesture and the MSR-Action3D datasets.
Motor endplate disease affects neuromuscular junction maturation

Postnatal formation of the neuromuscular synapse requires complex interactions among nerve terminal, muscle fibres and terminal Schwann cells. In motor endplate disease (med) mice, neuromuscular transmission is severely impaired without alteration of axonal conduction and a lethal paralytic phenotype occurs during the postnatal period. The med phenotype appears at a crucial stage of the neuromuscular junction development, corresponding to the increase in terminal Schwann cell number, the elimination of the multiple innervations and the pre‐ and postsynaptic maturation. Here we investigated the early cellular and molecular consequences of the med mutation on neuromuscular junction development. We observed that cellular defects preceded overt clinical phenotype. The first detectable cellular effect of the mutation at the onset of the clinical phenotype was a drastic reduction in the number of terminal Schwann cells, in part due to an increase in glial apoptosis, and a delayed maturation of motor endplates. We also showed that, in terminally ill animals, mono‐innervation was not achieved, synaptic vesicles had accumulated in the presynaptic compartment and, finally, the size of motor endplates was reduced. All together, our findings suggested that the clinical weakness in these mutant mice was likely to be related to postnatal structural abnormalities of the neuromuscular junction maturation.