gebhart/patrepeval huggingface dataset:
Helios Controls a Limited Subset of Regulatory T Cell Functions (2015)

A subpopulation (60-70%) of Foxp3(+) regulatory T cells (Tregs) in both mouse and man expresses the transcription factor Helios, but its role in Treg function is still unknown. We generated Treg-specific Helios-deficient mice to examine the function of Helios in Tregs. We show that the selective deletion of Helios in Tregs leads to slow, progressive systemic immune activation, hypergammaglobulinemia, and enhanced germinal center formation in the absence of organ-specific autoimmunity. Helios-deficient Treg suppressor function was normal in vitro, as well as in an in vivo inflammatory bowel disease model. However, Helios-deficient Tregs failed to control the expansion of pathogenic T cells derived from scurfy mice, failed to mediate T follicular regulatory cell function, and failed to control both T follicular helper cell and Th1 effector cell responses. In competitive settings, Helios-deficient Tregs, particularly effector Tregs, were at a disadvantage, indicating that Helios regulates effector Treg fitness. Thus, we demonstrate that Helios controls certain aspects of Treg-suppressive function, differentiation, and survival.
Mammosides B and H1, new ionophoric resin-glycosides from the tuber of Merremia mammosa, an indonesian folk medicine. (1989)

Four new ionophoric resin-glycosides have been isolated from the tuber of Merremia mammosa (Convolvulaceae), an Indonesian folk medicine ("Bidara upas"). The structures of two major resin-glycosides, named mammosides B (1__∼) and H1 (2__∼), have been determined on the basis of chemical and physicochemical evidence including a synthesis of the glycosidic acid designated as mammoside I (3__∼).
Optical wavelength add-drop multiplexer in installedsubmarine WDM network (1995)

The authors present a simple, low-loss, wavelength add-drop multiplexer and evaluate its implications and performance in a 4 × 2.5 Gbit/s system, demonstrating for the first time four-channel WDM transmission with wavelength routing over an installed optically amplified submarine cable system.
Effect of cell culture medium components on color of formulated monoclonal antibody drug substance (2013)

As the industry moves toward subcutaneous delivery as a preferred route of drug administration, high drug substance concentrations are becoming the norm for monoclonal antibodies. At such high concentrations, the drug substance may display a more intense color than at the historically lower concentrations. The effect of process conditions and/or changes on color is more readily observed in the higher color, high concentration formulations. Since color is a product quality attribute that needs to be controlled, it is useful to study the impact of process conditions and/or modifications on color. This manuscript summarizes cell culture experiments and reports on findings regarding the effect of various media components that contribute to drug substance color for a specific monoclonal antibody. In this work, lower drug substance color was achieved via optimization of the cell culture medium. Specifically, lowering the concentrations of B-vitamins in the cell culture medium has the effect of reducing color intensity by as much as 25%. In addition, decreasing concentration of iron was also directly correlated color intensity decrease of as much as 37%. It was also shown that the color of the drug substance directly correlates with increased acidic variants, especially when increased iron levels cause increased color. Potential mechanisms that could lead to antibody coloration are briefly discussed.
Detection of Nucleic Acids with Graphene Nanopores: Ab Initio Characterization of a Novel Sequencing Device (2010)

We report an ab initio density functional theory study of the interaction of four nucleobases, cytosine, thymine, adenine, and guanine, with a novel graphene nanopore device for detecting the base sequence of a single-stranded nucleic acid (ssDNA or RNA). The nucleobases were inserted into a pore in a graphene nanoribbon, and the electrical current and conductance spectra were calculated as functions of voltage applied across the nanoribbon. The conductance spectra and charge densities were analyzed in the presence of each nucleobase in the graphene nanopore. The results indicate that due to significant differences in the conductance spectra the proposed device has adequate sensitivity to discriminate between different nucleotides. Moreover, we show that the nucleotide conductance spectrum is affected little by its orientation inside the graphene nanopore. The proposed technique may be extremely useful for real applications in developing ultrafast, low-cost DNA sequencing methods.
The worldwide magnitude of protein-energy malnutrition: an overview from the WHO Global Database on Child Growth. (1993)

Using the WHO Global Database on Child Growth, which covers 87% of the total population of under-5-year-olds in developing countries, we describe the worldwide distribution of protein-energy malnutrition, based on nationally representative cross-sectional data gathered between 1980 and 1992 in 79 developing countries in Africa, Asia, Latin America, and Oceania. The findings confirm that more than a third of the world's children are affected. For all the indicators (wasting, stunting, and underweight) the most favourable situation--low or moderate prevalences--occurs in Latin America; in Asia most countries have high or very high prevalences; and in Africa a combination of both these circumstances is found. A total 80% of the children affected live in Asia--mainly in southern Asia--15% in Africa, and 5% in Latin America. Approximately, 43% of children (230 million) in developing countries are stunted. Efforts to accelerate significantly economic development will be unsuccessful until optimal child growth and development are ensured for the majority.
DMH1, a Highly Selective Small Molecule BMP Inhibitor Promotes Neurogenesis of hiPSCs: Comparison of PAX6 and SOX1 Expression during Neural Induction (2012)

Recent successes in deriving human-induced pluripotent stem cells (hiPSCs) allow for the possibility of studying human neurons derived from patients with neurological diseases. Concomitant inhibition of the BMP and TGF-β1 branches of the TGF-β signaling pathways by the endogenous antagonist, Noggin, and the small molecule SB431542, respectively, induces efficient neuralization of hiPSCs, a method known as dual-SMAD inhibition. The use of small molecule inhibitors instead of their endogenous counterparts has several advantages including lower cost, consistent activity, and the maintenance of xeno-free culture conditions. We tested the efficacy of DMH1, a highly selective small molecule BMP-inhibitor for its potential to replace Noggin in the neuralization of hiPSCs. We compare Noggin and DMH1-induced neuralization of hiPSCs by measuring protein and mRNA levels of pluripotency and neural precursor markers over a period of seven days. The regulation of five of the six markers assessed was indistinguishable in the presence of concentrations of Noggin or DMH1 that have been shown to effectively inhibit BMP signaling in other systems. We observed that by varying the DMH1 or Noggin concentration, we could selectively modulate the number of SOX1 expressing cells, whereas PAX6, another neural precursor marker, remained the same. The level and timing of SOX1 expression have been shown to affect neural induction as well as neural lineage. Our observations, therefore, suggest that BMP-inhibitor concentrations need to be carefully monitored to ensure appropriate expression levels of all transcription factors necessary for the induction of a particular neuronal lineage. We further demonstrate that DMH1-induced neural progenitors can be differentiated into β3-tubulin expressing neurons, a subset of which also express tyrosine hydroxylase. Thus, the combined use of DMH1, a highly specific BMP-pathway inhibitor, and SB431542, a TGF-β1-pathway specific inhibitor, provides us with the tools to independently regulate these two pathways through the exclusive use of small molecule inhibitors.
RNA N-glycosidase activity of ricin A-chain. Mechanism of action of the toxic lectin ricin on eukaryotic ribosomes. (1987)

The modification reaction of 28 S rRNA in eukaryotic ribosomes by ricin A-chain was characterized. To examine whether ricin A-chain release any bases from 28 S rRNA, rat liver ribosomes were incubated with a catalytic amount of the toxin, and a fraction containing free bases and nucleosides was prepared from the postribosomal fraction of the reaction mixture by means of ion-exchange column chromatography. Thin-layer chromatographic analysis of this fraction revealed a release of 1 mol of adenine from 1 mol of ribosome. When the ribosomes or naked total RNAs were treated with ricin A-chain in the presence of [32P] phosphate, little incorporation of the radioactivity into 28 S rRNA was observed, indicating that the release is not mediated by phosphorolysis. Thus, considering together with the previous result (Endo, Y., Mitsui, K., Motizuki, M., and Tsurugi, K. (1987) J. Biol. Chem. 262, 5908-5912), the results in the present experiments demonstrated that ricin A-chain inactivates the ribosomes by cleaving the N-glycosidic bond of A4324 of 28 S rRNA in a hydrolytic fashion.
Supplementary pollination of tree fruits (1982)

Abstract Successful spray pollination of kiwifruit depends largely on maintaining pollen viability in aqueous suspensions and during drying of spray droplets on stigmas of open flowers. A medium composed of calcium, boron, and carboxymethyl cellulose (designated as CBC) with added gum acacia maintained pollen viability for up to 3 h in suspension and gave partial protection when pollen was dried on filter paper at 25°C and 60% RH for 1 h. Pollen germination was not influenced by medium pH but pollen tube growth was inhibited below pH 5.0. Pollen from early flowering staminate clones could be suspended directly in the CBC‐gum acacia medium without prior pollen hydration provided that the water used for medium preparation was free of inhibitory ions. Viable pollen suspended in CBC plus gum acacia or in CBC plus pentaerythritol and sprayed on to receptive flowers, increased seed numbers per fruit. For either medium, the minimum pollen concentration needed to increase fruit size was 0.5 g of pollen per litre.
Reconstruction of the complete human cytomegalovirus genome in a BAC reveals RL13 to be a potent inhibitor of replication (2010)

Human cytomegalovirus (HCMV) in clinical material cannot replicate efficiently in vitro until it has adapted by mutation. Consequently, wild-type HCMV differ fundamentally from the passaged strains used for research. To generate a genetically intact source of HCMV, we cloned strain Merlin into a self-excising BAC. The Merlin BAC clone had mutations in the RL13 gene and UL128 locus that were acquired during limited replication in vitro prior to cloning. The complete wild-type HCMV gene complement was reconstructed by reference to the original clinical sample. Characterization of viruses generated from repaired BACs revealed that RL13 efficiently repressed HCMV replication in multiple cell types; moreover, RL13 mutants rapidly and reproducibly emerged in transfectants. Virus also acquired mutations in genes UL128, UL130, or UL131A, which inhibited virus growth specifically in fibroblast cells in wild-type form. We further report that RL13 encodes a highly glycosylated virion envelope protein and thus has the potential to modulate tropism. To overcome rapid emergence of mutations in genetically intact HCMV, we developed a system in which RL13 and UL131A were conditionally repressed during virus propagation. This technological advance now permits studies to be undertaken with a clonal, characterized HCMV strain containing the complete wild-type gene complement and promises to enhance the clinical relevance of fundamental research on HCMV.
Synthesis of Diketopyrrolopyrrole Containing Copolymers: A Study of Their Optical and Photovoltaic Properties (2010)

The diketopyrrolopyrrole-based copolymers PDPP-BBT and TDPP-BBT were synthesized and used as a donor for bulk heterojunction photovoltaic devices. The photophysical properties of these polymers showed absorption in the range 500-600 nm with a maximum peak around 563 nm, while TDPP-BBT showed broadband absorption in the range 620-800 nm with a peak around 656 nm. The power conversion efficiencies (PCE) of the polymer solar cells based on these copolymers and [6,6]-phenyl C61 butyric acid methyl ester (PCBM) were 0.68% (as cast PDPP-BBT:PCBM), 1.51% (annealed PDPP-BBT:PCBM), 1.57% (as cast TDPP-BBT:PCBM), and 2.78% (annealed TDPP-BBT:PCBM), under illumination of AM 1.5 (100 mW/cm(2)). The higher PCE for TDPP-BBT-based polymer solar cells has been attributed to the low band gap of this copolymer as compared to PDPP-BBT, which increases the numbers of photogenerated excitons and corresponding photocurrent of the device. These results indicate that PDPP-BBT and TDPP-BBT act as excellent electron donors for bulk heterojunction devices.
Informed source separation: Source coding meets source separation (2011)

We consider the informed source separation (ISS) problem where, given the sources and the mixtures, any kind of side-information can be computed during a so-called encoding stage. This side-information is then used to assist source separation, given the mixtures only, at the so-called decoding stage. State of the art ISS approaches do not really consider ISS as a coding problem and rely on some purely source separation-inspired strategies, leading to performances that can at best reach those of oracle estimators. On the other hand, classical source coding strategies are not optimal either, since they do not benefit from the mixture availability. We introduce a general probabilistic framework called coding-based ISS (CISS) that consists in quantizing the sources using some posterior source distribution from those usually used in probabilistic model-based source separation. CISS benefits from both source coding, thanks to the source quantization, and source separation, thanks to the use of the posterior distribution that depends on the mixture. Our experiments show that CISS based on a particular model considerably outperforms for all rates both the conventional ISS approach and the source coding approach based on the same model.
Detection of AIDS Virus in Macrophages in Brain Tissue from AIDS Patients with Encephalopathy (1986)

One of the common neurological complications in patients with the acquired immune deficiency syndrome (AIDS) is a subacute encephalopathy with progressive dementia. By using the techniques of cocultivation for virus isolation, in situ hybridization, immunocytochemistry, and transmission electron microscopy, the identity of an important cell type that supports replication of the AIDS retrovirus in brain tissue was determined in two affected individuals. These cells were mononucleated and multinucleated macrophages that actively synthesized viral RNA and produced progeny virions in the brains of the patients. Infected brain macrophages may serve as a reservoir for virus and as a vehicle for viral dissemination in the infected host.
Changes in expression of putative antigens encoded by pigment genes in mouse melanomas at different stages of malignant progression. (1995)

Cutaneous melanomas of Tyr-SV40E transgenic mice (mice whose transgene consists of the tyrosinase promoter fused to the coding regions of simian virus 40 early genes) strikingly resemble human melanomas in their development and progression. Unlike human melanomas, the mouse tumors all arise in genetically identical individuals, thereby better enabling expression of specific genes to be characterized in relation to advancing malignancy. The products of pigment genes are of particular interest because peptides derived from these proteins have been reported to function as autoantigens with immunotherapeutic potential in some melanoma patients. However, the diminished pigmentation characteristic of many advanced melanomas raises the possibility that some of the relevant products may no longer be expressed in the most malignant cells. We have therefore investigated the contributions of several pigment genes in melanotic vs. relatively amelanotic components of primary and metastatic mouse melanomas. The analyses reveal marked differences within and among tumors in levels of mRNAs and proteins encoded by the wild-type alleles at the albino, brown, slaty, and silver loci. Tyrosinase (the protein encoded by the albino locus) was most often either absent or undetectable as melanization declined. The protein encoded by the slaty locus (tyrosinase-related protein 2) was the only one of those tested that was clearly present in all the tumor samples. These results suggest that sole reliance on targeting tyrosinase-based antigens might selectively favor survival of more malignant cells, whereas targeting the ensemble of the antigens tested might contribute toward a more inclusive and effective antimelanoma strategy.
MAGEC2, an epithelial-mesenchymal transition inducer, is associated with breast cancer metastasis (2014)

MAGEC2 is a member of melanoma antigen (MAGE) family of cancer-testis antigens and associated with tumor relapse and metastasis. Here, we investigated the expression of MAGEC2 in patients with breast cancer and its clinical effects with underlying mechanisms. The expression levels of MAGEC2 were compared between 420 invasive ductal carcinoma (IDC) and 120 ductal carcinoma in situ of the breast. Correlations between MAGEC2 expression and clinico-pathologic factors or survival of patients with IDC were analyzed. In addition, MAGEC2 expression levels in tumor tissues dissected from the primary focus and matched tumor-invaded axillary lymph nodes were analyzed in 8 breast cancer patients. The functional effects of MAGEC2 overexpression were assessed in vitro using scratch assay and transwell chamber assay. MAGEC2 expression was increased in metastatic breast cancer in comparison to the non-metastatic. MAGEC2 expression was significantly associated with ER negative expression (P = 0.037), high tumor grade (P = 0.014) and stage (P = 0.002), high incidence of axillary lymph node metastasis (P = 0.013), and distant metastasis (P = 0.004). Patients with tumor with MAGEC2 positive expression have a worse prognosis and a shorter metastasis free interval. Multivariate analyses showed that MAGEC2 expression was an independent risk factor for patient overall survival and metastasis-free survival. Breast cancer cells that overexpressed MAGEC2 had stronger migratory and invasive potential than control-treated cells. Epithelial markers (E-cadherin and cytokeratin) were down-regulated in MAGEC2-overexpressing cells compared to controls, whereas mesenchymal markers (vimentin and fibronectin) were upregulated. Our results indicate that MAGEC2 has a role in breast cancer metastasis through inducing epithelial-mesenchymal transition. In addition, MAGEC2 is a novel independent poor prognostic factor in patients with IDC. Thus, targeting MAGEC2 may provide a novel therapeutic strategy for breast cancer treatment.
Inhibition of integrin α5β1 function with a small peptide (ATN‐161) plus continuous 5‐FU infusion reduces colorectal liver metastases and improves survival in mice (2003)

Integrin alpha(5)beta(1) is expressed on activated endothelial cells and plays a critical role in tumor angiogenesis. We hypothesized that a novel integrin alpha(5)beta(1) antagonist, ATN-161, would inhibit angiogenesis and growth of liver metastases in a murine model. We further hypothesized that combining ATN-161 with 5-fluorouracil (5-FU) chemotherapy would enhance the antineoplastic effect. Murine colon cancer cells (CT26) were injected into spleens of BALB/c mice to produce liver metastases. Four days thereafter, mice were given either ATN-161 (100 mg/kg, every 3rd day) or saline by intraperitoneal injection, with or without combination of continuous-infusion 5-FU (100 mg/kg/2 weeks), which was started on day 7. On day 20 after tumor cell inoculation, mice were killed and liver weights and number of liver metastases were determined. A follow-up study on survival was also conducted in which mice were randomized to receive ATN-161, 5-FU or ATN-161+5-FU. Combination therapy with ATN-161+5-FU significantly reduced tumor burden (liver weight) and number of liver metastases (p<0.02). Liver tumors in the ATN-161 and ATN-161+5-FU groups had significantly fewer microvessels (p<0.05) than tumors in the control or 5-FU-treated groups. Unlike treatment with either agent alone, ATN-161+5-FU significantly increased tumor cell apoptosis and decreased tumor cell proliferation (p<0.03) and improved overall survival (p<0.03, log-rank test). Targeting integrin alpha(5)beta(1) in combination with 5-FU infusion reduced liver metastases formation and improved survival in this colon cancer model. The enhancement of antineoplastic activity from the combination of anti-angiogenic therapy and chemotherapy may be a promising approach for treating metastatic colorectal cancer.
Biohalogenation: Nature’s Way to Synthesize Halogenated Metabolites (2009)

Halogenated natural products are widely distributed in nature, some of them showing potent biological activities. Incorporation of halogen atoms in drug leads is a common strategy to modify molecules in order to vary their bioactivities and specificities. Chemical halogenation, however, often requires harsh reaction conditions and results in unwanted byproduct formation. It is thus of great interest to investigate the biosynthesis of halogenated natural products and the biotechnological potential of halogenating enzymes. This review aims to give a comprehensive overview on the current knowledge concerning biological halogenations.
Seroma prevention after modified radical mastectomy. (1992)

The most common mastectomy-associated complication is seroma formation. Seromas can be associated with other more serious complications such as skin flap necrosis, delayed wound healing, infection, and lymphedema. The flap tacking procedure that closes the axillary fossa dead space and tacks the mastectomy flaps to the chest wall has been suggested as one potential technique to reduce the incidence of postmastectomy seromas. This institution-wide study of modified radical mastectomies demonstrated a significant decrease (P < 0.0381) in the incidence of seroma when flap tacking was performed. Women who developed a seroma, compared to those who did not, averaged nearly twice as any office visits in the first 2 months after the operation. Distribution of office visits between the seroma patients and nonseroma patients was significant (P < 0.0001). When practiced by several surgeons, the flap tacking procedure 1) reduces postmastectomy seromas and 2) reduces the amount of postoperative patient office visits and care.