gebhart/patrepeval huggingface dataset:
Development of human CD4+FoxP3+ regulatory T cells in human stem cell factor–, granulocyte-macrophage colony-stimulating factor–, and interleukin-3–expressing NOD-SCID IL2Rγnull humanized mice (2011)

Human hematolymphoid mice have become valuable tools for the study of human hematopoiesis and uniquely human pathogens in vivo. Recent improvements in xenorecipient strains allow for long-term reconstitution with a human immune system. However, certain hematopoietic lineages, for example, the myeloid lineage, are underrepresented, possibly because of the limited cross-reactivity of murine and human cytokines. Therefore, we created a nonobese diabetic/severe combined immunodeficiency/interleukin-2 receptor-γ-null (NOD-SCID IL2Rγ(null)) mouse strain that expressed human stem cell factor, granulocyte-macrophage colony-stimulating factor, and interleukin-3, termed NSG-SGM3. Transplantation of CD34(+) human hematopoietic stem cells into NSG-SGM3 mice led to robust human hematopoietic reconstitution in blood, spleen, bone marrow, and liver. Human myeloid cell frequencies, specifically, myeloid dendritic cells, were elevated in the bone marrow of humanized NSG-SGM3 mice compared with nontransgenic NSG recipients. Most significant, however, was the increase in the CD4(+)FoxP3(+) regulatory T-cell population in all compartments analyzed. These CD4(+)FoxP3(+) regulatory T cells were functional, as evidenced by their ability to suppress T-cell proliferation. In conclusion, humanized NSG-SGM3 mice might serve as a useful model to study human regulatory T-cell development in vivo, but this unexpected lineage skewing also highlights the importance of adequate spatiotemporal expression of human cytokines for future xenorecipient strain development.
Dehydroepiandrosterone Inhibits Complex I of the Mitochondrial Respiratory Chain and is Neurotoxic In Vitro and In Vivo at High Concentrations (2006)

Dehydroepiandrosterone (DHEA) is widely used as a food supplement and considered to be relatively safe. In animal studies, however, additions of high concentrations of DHEA to the diet have led to hepatotoxicity as well as liver mitochondrial dysfunction. This study was therefore designed to find out whether DHEA is able to inhibit the respiratory activity also in neuronal mitochondria and to reveal whether this leads to functional disturbance in the brain. Using different mitochondrial substrates, we show here that DHEA suppresses the mitochondrial respiration in permeabilized neurons (half maximal inhibitory concentration 13 microM) by inhibiting complex I of the mitochondrial electron transport chain. Treatment with DHEA was associated with increased glucose expenditure in intact cultures and led to neuronal death. The latter was most prominent in hypoglycemic conditions. Mice fed with pellet containing 0.6% DHEA for 3 months showed a significant neuronal loss in the cerebral cortex and hippocampus, a slightly decreased dopamine/dihydroxyphenylacetic acid ratio, as well as motor impairment. The main conclusion of the present study is that high concentrations of DHEA inhibit complex I of the mitochondrial respiratory chain and are neurotoxic in vitro and in vivo.
Sustainability of Endovenous Iron Deficiency Anaemia Treatment: Hospital-Based Health Technology Assessment in IBD Patients (2017)

Iron deficiency anaemia (IDA) is the main extraintestinal manifestation affecting patients with inflammatory bowel disease (IBD). The Health Technology Assessment approach was applied to evaluate the sustainability of intravenous (IV) iron formulations in the Italian hospital setting, with particular focus on ferric carboxymaltose. Data on the epidemiology of IBD and associated IDA, in addition to the efficacy and safety of IV iron formulations currently used in Italy, were retrieved from scientific literature. A hospital-based cost-analysis of the outpatient delivery of IV iron treatments was performed. Organizational and ethical implications were discussed. IDA prevalence in IBD patients varies markedly from 9 to 73%. IV iron preparations were proven to have good efficacy and safety profiles, and ferric carboxymaltose provided a fast correction of haemoglobin and serum ferritin levels in iron-deficient patients. Despite a higher price, ferric carboxymaltose would confer a beneficial effect to the hospital, in terms of reduced cost related to individual patient management and additionally to the patient by reducing the number of infusions and admissions to healthcare facilities. Ethically, the evaluation is appropriate due to its efficacy and compliance. This assessment supports the introduction of ferric carboxymaltose in the Italian outpatient setting.
Optimal Resource Allocation for Network Protection Against Spreading Processes (2014)

We study the problem of containing spreading processes in arbitrary directed networks by distributing protection resources throughout the nodes of the network. We consider that two types of protection resources are available: 1) preventive resources able to defend nodes against the spreading (such as vaccines in a viral infection process) and 2) corrective resources able to neutralize the spreading after it has reached a node (such as antidotes). We assume that both preventive and corrective resources have an associated cost and study the problem of finding the cost-optimal distribution of resources throughout the nodes of the network. We analyze these questions in the context of viral spreading processes in directed networks. We study the following two problems: 1) given a fixed budget, find the optimal allocation of preventive and corrective resources in the network to achieve the highest level of containment and 2) when a budget is not specified, find the minimum budget required to control the spreading process. We show that both the resource allocation problems can be solved in polynomial time using geometric programming (GP) for arbitrary directed graphs of nonidentical nodes and a wide class of cost functions. We illustrate our approach by designing optimal protection strategies to contain an epidemic outbreak that propagates through an air transportation network.
Subtilisin Carlsberg (1968)

Evidence is presented for the complete amino acid sequence of subtilisin Carlsberg. The protein consists of a single peptide chain of 274 residues. Comparison with subtilisin BPN' shows 84 amino acid differences and 1 additional residue in BPN'. The 84 differences can be accounted for on the basis of single or double nucleotide replacements. Within the subtilisins, there are a number of distinct repetitions of sequence; this suggests that the proteins may have evolved from shorter peptide chains by some process of extension of the sequence. The subtilisins differ in structure from other proteinases sensitive to diisopropyl fluorophosphate, as well as from proteinases of other types.
A Dominant Role of GTRAP3-18 in Neuronal Glutathione Synthesis (2008)

Glutathione is an essential reductant which protects cells and is reduced in neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Neurons rely mainly on extracellular cysteine for glutathione synthesis and a cysteine transporter termed excitatory amino acid carrier 1 (EAAC1). However, the mechanisms underlying neuronal cysteine uptake have remained elusive. Herein, we show glutamate transport-associated protein for EAAC1 (GTRAP3-18) to interact with EAAC1 at the plasma membrane and thereby regulate neuronal glutathione levels. Glutathione increased in the mouse brain as well as in primary cultured neurons, when the GTRAP3-18 protein level was decreased by genetic manipulations, whereas glutathione decreased when GTRAP3-18 was increased. Furthermore, glutathione contents that had been increased, by a translocator and activator of EAAC1, were suppressed by increased cell surface GTRAP3-18 protein. Our results demonstrate GTRAP3-18 to dominantly and negatively determine the intracellular glutathione contents in neurons.
Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27 (2015)

The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans with an approximately 30% mortality rate. The envelope spike glycoprotein on the surface of MERS-CoV mediates receptor binding, membrane fusion, and viral entry. We previously reported two human monoclonal antibodies that target the receptor binding domain (RBD) of the spike and exhibit strong neutralization activity against live and pesudotyped MERS-CoV infection. Here we determined the crystal structure of MERS-CoV RBD bound to the Fab fragment of MERS-27 antibody at 3.20 Å resolution. The MERS-27 epitope in the RBD overlaps with the binding site of the MERS-CoV receptor DPP4. Further biochemical, viral entry, and neutralization analyses identified two critical residues in the RBD for both MERS-27 recognition and DPP4 binding. One of the residues, Trp535, was found to function as an anchor residue at the binding interface with MERS-27. Upon receptor binding, Trp535 interacts with the N-linked carbohydrate moiety of DPP4. Thus, MERS-27 inhibits MERS-CoV infection by directly blocking both protein-protein and protein-carbohydrate interactions between MERS-CoV RBD and DPP4. These results shed light on the molecular basis of MERS-27 neutralization and will assist in the optimization of MERS-27 as a tool to combat MERS-CoV infection.
Collagen as matrix for neo-organ formation by gene-transfected fibroblasts. (1997)

Biodegradable collagen matrices can serve as scaffolds for survival of transfected fibroblasts in vivo.
Efficient text summarization using lexical chains (2000)

The rapid growth of the Internet has resulted in enormous amounts of information that has become more difficult to access efficiently. Internet users require tools to help manage this vast quantity of information. The primary goal of this research is to create an efficient and effective tool that is able to summarize large documents quickly. This research presents a linear time algorithm for calculating lexical chains which is a method of capturing the “aboutness” of a document. This method is compared to previous, less efficient methods of lexical chain extraction. We also provide alternative methods for extracting and scoring lexical chains. We show that our method provides similar results to previous research, but is substantially more efficient. This efficiency is necessary in Internet search applications where many large documents may need to be summarized at once, and where the response time to the end user is extremely important.
DeepSDF: Learning Continuous Signed Distance Functions for Shape Representation (2019)

Computer graphics, 3D computer vision and robotics communities have produced multiple approaches to representing 3D geometry for rendering and reconstruction. These provide trade-offs across fidelity, efficiency and compression capabilities. In this work, we introduce DeepSDF, a learned continuous Signed Distance Function (SDF) representation of a class of shapes that enables high quality shape representation, interpolation and completion from partial and noisy 3D input data. DeepSDF, like its classical counterpart, represents a shape's surface by a continuous volumetric field: the magnitude of a point in the field represents the distance to the surface boundary and the sign indicates whether the region is inside (-) or outside (+) of the shape, hence our representation implicitly encodes a shape's boundary as the zero-level-set of the learned function while explicitly representing the classification of space as being part of the shapes interior or not. While classical SDF's both in analytical or discretized voxel form typically represent the surface of a single shape, DeepSDF can represent an entire class of shapes. Furthermore, we show state-of-the-art performance for learned 3D shape representation and completion while reducing the model size by an order of magnitude compared with previous work.
Thapsigargin-inducedgrp78 expression is mediated by the increase of cytosolic free calcium in 9L rat brain tumor cells (2000)

Exposure of 9L rat brain tumor cells to 300 nM thapsigargin (TG), a sarcoendoplasmic Ca(2+)-ATPases inhibitor, leads to an immediate suppression of general protein synthesis followed by an enhanced synthesis of the 78-kDa glucose-regulated protein, GRP78. Synthesis of GRP78 increases significantly and continues to rise after 4 h of treatment, and this process coincides with the accumulation of grp78 mRNA. TG-induced grp78 expression can be suppressed by the cytosolic free calcium ([Ca(2+)](c)) chelator dibromo-1, 2-bis(aminophenoxy)ethane N,N,N',N'-tetraacetic acid (BAPTA) in a concentration-dependent manner. Induction of grp78 is completely abolished in the presence of 20 microM BAPTA under which the TG-induced increase of [Ca(2+)](c) is also completely prevented. By adding ethyleneglycol bis(beta-aminoethyl)ether-N,N,N',N' tetraacetic acid in the foregoing experiments, in a condition such that endoplasmic reticulum calcium ([Ca(2+)](ER)) is depleted and calcium influx from outside is prevented, TG-induced grp78 expression is also abolished. These data lead us to conclude that increase in [Ca(2+)](c), together with the depletion of [Ca(2+)](ER), are the major causes of TG-induced grp78 expression in 9L rat brain tumor cells. By using electrophoretic mobility shift assays (EMSA), we found that the nuclear extracts prepared from TG-treated cells exhibit an increase in binding activity toward the extended grp78 promoter as well as the individual cis-acting regulatory elements, CRE and CORE. Moreover, this increase in binding activity is also reduced by BAPTA. By competitory assays using the cis-acting regulatory elements as the competitors as well as the EMSA probes, we further show that all of the tested cis elements-CRE, CORE, and C1-are involved in the basal as well as in the TG-induced expression of grp78 and that the protein factor(s) that binds to the C1 region plays an important role in the formation and maintenance of the transcription complex.
Tumor Necrosis Factor–Alpha Gene Expression in Human Whole Blood (1990)

Tumor necrosis factor-alpha (TNF) is recognized as a principal mediator of a variety of pathophysiologic and immunologic events. Lipopolysaccharide (LPS) challenge, either in vitro or in vivo, results in significant TNF production. In this study we present data demonstrating LPS-induced TNF mRNA expression and bioactivity using an in vitro tissue system of whole blood (WB). The kinetics of LPS-induced TNF production by WB was significantly accelerated as compared to isolated cultured peripheral blood monocytes (PBM). At post-LPS challenge, plasma from WB demonstrated a rapid rise in TNF bioactivity, peaking by 4 hr (1,021 units/ml/10(6) cells), plateauing between 4 and 8 hr, and then decreasing over the next 16 hr. In contrast, the highest measured TNF bioactivity from PBM did not occur until the 24-hr time-point (175 units/ml/10(6) cells). Whole blood buffy-coat TNF mRNA was assessed by Northern blot analysis, and demonstrated significant TNF mRNA accumulation at 1 hr and a peak 2 hr post-LPS challenge. By 8 hr TNF mRNA was undetectable. Concomitant administration of LPS with either prostaglandin E2 (10(-6)M) or Dexamethasone (10(-6)M) resulted in significant suppression of LPS-induced TNF production. This data supports WB as a useful in vitro medium for the molecular and cellular analysis of TNF. As specialized connective tissue, WB may provide an important environment to study the pharmacologic manipulation of TNF mRNA and bioactivity.
Novel mitosis-specific phosphorylation of histone H3 at Thr11 mediated by Dlk/ZIP kinase (2003)

Death-associated protein (DAP)-like kinase (Dlk), also known as Zipper interacting protein (ZIP) kinase, is a nuclear serine/threonine-specific kinase that phosphorylates core histones H3 and H4, and myosine light chain in vitro. It interacts with transcription and splicing factors as well as with pro-apoptotic protein Par-4 suggesting that it participates in multiple cellular processes. To explore the significance of histone phosphorylation by Dlk, we determined the phosphorylation site in H3 and generated phosphospecific antibodies for in vivo analyses. Interestingly, Dlk/ZIP kinase phosphorylated histone H3 at a novel site, Thr11, rather than Ser10, which is characteristic of mitotic chromosomes. Immunoblotting and confocal immunofluorescence analyses demonstrated that phosphorylation of H3 at Thr11 occurred in vivo and was restricted to mitosis as well. It was discernable from prophase to early anaphase and particularly enriched at centromeres. Strikingly, during this time interval, Dlk was associated with centromeres too, as revealed by stable expression of a green fluorescent protein (GFP)-Dlk fusion protein. These findings strongly suggest that Dlk is a centromere-specific histone kinase that might play a role in labeling centromere-specific chromatin for subsequent mitotic processes.
Performance of modulation-aware iterative equalization in uplink LTE systems (2010)

In this paper, advanced multi-user uplink reception algorithms for LTE systems are considered for realistic propagation channels. An iterative modulation-aware MMSE equalizer is implemented to detect parallel data streams from independent transmitters. The proposed algorithm performs iterative cancelation steps based on iterative matrix inversion methods. This process simultaneously reduces the cross-interference power, thus enhancing the overall system performance. Based on the intermediate signal variables, which are approximately marginally Gaussian distributed, the processor uses a conditional estimation function to generate soft symbols from previous iterations to minimize the error variance at the current cancelation step. The performance of this modulation-cognizant proposed equalizer is compared to the baseline linear MMSE processor in terms of bit error rate. It is shown that this new receiver significantly outperforms the baseline algorithm, in particular when simultaneous detection of the data streams is considered and rank deficiency prevents the classical MMSE algorithm from functioning properly.
Dual-enhanced photothermal conversion properties of reduced graphene oxide-coated gold superparticles for light-triggered acoustic and thermal theranostics (2015)

A rational design of highly efficient photothermal agents that possess excellent light-to-heat conversion properties is a fascinating topic in nanotheranostics. Herein, we present a facile route to fabricate size-tunable reduced graphene oxide (rGO)-coated gold superparticles (rGO-GSPs) and demonstrate their dual-enhanced photothermal conversion properties for photoacoustic imaging and photothermal therapy. For the first time, graphene oxide (GO) was directly used as an emulsifying agent for the preparation of gold superparticles (GSPs) with near-infrared absorption by the emulsion method. Moreover, GO spontaneously deposited on the surface of GSPs could also act as the precursor of the rGO shell. Importantly, both the plasmonic coupling of the self-assembled gold nanoparticles and the interaction between GSPs and rGO endow rGO-GSPs with enhanced photothermal conversion properties, allowing rGO-GSPs to be used for sensitive photoacoustic detection and efficient photothermal ablation of tumours in vivo. This study provides a facile approach to prepare colloidal superparticles-graphene hybrid nanostructures and will pave the way toward the design and optimization of photothermal nanomaterials with improved properties for theranostic applications.
Synthesis and Pharmacological Characterization of Two Novel, Brain Penetrating P2X7 Antagonists (2013)

The synthesis and preclinical characterization of two novel, brain penetrating P2X7 compounds will be described. Both compounds are shown to be high potency P2X7 antagonists in human, rat, and mouse cell lines and both were shown to have high brain concentrations and robust receptor occupancy in rat. Compound 7 is of particular interest as a probe compound for the preclinical assessment of P2X7 blockade in animal models of neuro-inflammation.
A carcinoembryonic antigen polynucleotide vaccine has in vivo antitumor activity. (1995)

We have constructed a plasmid DNA encoding the full-length cDNA for human carcinoembryonic antigen (CEA) driven by the cytomegalovirus early promoter/enhancer and demonstrated that this plasmid can function as a polynucleotide vaccine. The immune response elicited by the CEA polynucleotide vaccine is dose and schedule dependent. There appears to be a threshold dose of 50 micrograms capable of inducing CEA-specific lymphoblastic transformation, lymphokine release, and antibody response. Doses of 10 micrograms were significantly less effective. When 50-micrograms doses are employed, thrice weekly or weekly vaccination schedules more reliably elicit CEA-specific immune responses by day 43 than does an every-3-weeks schedule. Furthermore the CEA polynucleotide vaccine can immunoprotect against challenge with syngeneic CEA-transduced colon carcinoma cells as early as 3 weeks after the first vaccination. Studies are ongoing to demonstrate the ability of CEA polynucleotide vaccination to treat pre-existing syngeneic mouse colon and breast carcinomas expressing human CEA.
Cloning of B7-2: a CTLA-4 Counter-Receptor That Costimulates Human T Cell Proliferation (1993)

Although presentation of antigen to the T cell receptor is necessary for the initiation of an immune response, additional molecules expressed on antigen-presenting cells deliver essential costimulatory signals. T cell activation, in the absence of costimulation, results in T cell anergy. The B7-1 protein is a costimulator molecule that regulates interleukin-2 (IL-2) secretion by signaling through the pathway that uses CD28 and CTLA-4 (hereafter referred to as the CD28 pathway). We have cloned a counter-receptor of CD28 and CTLA-4, termed B7-2. Although only 26 percent identical to B7-1, B7-2 also costimulates IL-2 production and T cell proliferation. Unlike B7-1, B7-2 messenger RNA is constitutively expressed in unstimulated B cells. It is likely that B7-2 provides a critical early costimulatory signal determining if the T cell will contribute to an immune response or become anergic.
An investigation of array of piezoelectric transducer for raindrop energy harvesting application (2016)

It has been proven that, raindrop energy can be converted in to electricity by using piezoelectric mechanism. This paper presents an investigation of an array of Polyvinylidene Fluoride (PVDF) piezoelectric transducer for harvesting raindrop energy. The transducers with dimension of 4 mm × 40 mm × 25 µm setup in bridge structure were used to harvest raindrop energy. The output voltage of an array of piezoelectric transducer connected in series and parallel were analyzed and compared through experiment. Results showed that, the PVDF piezoelectric transducers connected in array of 3 × 2 in combination of parallel and series configuration generated higher voltage compared to 6 transducers connected in series and connected in parallel.
Effects of Congo Red on Aβ1−40 Fibril Formation Process and Morphology (2010)

Alzheimer's disease (AD), an age-related neurodegenerative disorder, is the most common form of dementia, and the seventh-leading cause of death in the United States. Current treatments offer only symptomatic relief; thus, there is a great need for new treatments with disease-modifying potential. One pathological hallmark of AD is so-called senile plaques, mainly made up of β-sheet-rich assemblies of 40- or 42-residue amyloid β-peptides (Aβ). Hence, inhibition of Aβ aggregation is actively explored as an option to prevent or treat AD. Congo red (CR) has been widely used as a model antiamyloid agent to prevent Aβ aggregation. Herein, we report detailed morphological studies on the effect of CR as an antiamyloid agent, by circular dichroism spectroscopy, photo-induced cross-linking reactions, and atomic force microscopy. We also demonstrate the effect of CR on a preaggregated sample of Aβ(1-40). Our result suggests that Aβ(1-40) follows a different path for aggregation in the presence of CR.