gebhart/patrepeval huggingface dataset:
Regulation of globin gene expression in human K562 cells by recombinant activin A (1992)

Recent studies indicate that a purified protein, activin A, belongs to the transforming growth factor beta (TGF-beta) superfamily. Similar to TGF-beta, activin A can have different biologic activities, depending on the target tissues. We used recombinant activin A to demonstrate a possible regulatory role of this protein in modulating human erythroid differentiation in the human erythroid cell line, K562. Using genomic probes containing the second exon of alpha, beta, gamma, and epsilon globins, relative abundance of various types of globin transcripts in untreated and activin-treated K562 cells was examined with S1 nuclease analysis. Despite considerable homology amongst various globin sequences, these globin probes were highly specific for their unique mRNA species in the analyses. It was shown that the abundance of specific globin probe fragments for gamma and epsilon globins (209 nucleotides) as well as alpha (180 nucleotides), which were protected from S1 digestion, increased many fold in K562 cells treated with activin A. In contrast, there were no specific transcripts of beta globin detected in either the control or activin-treated cells. The increases in the level of fetal and embryonic beta-like and alpha globin transcripts also confirmed earlier studies of Northern and slot- blot analyses using globin cDNA as probes. In addition, nuclear run-off transcription assay using isolated nuclei indicated that most of the increase in the globin transcripts after activin treatment could be attributed to the stimulation of transcription rate for globin genes. Transient transfection assays also provide evidence that activin A significantly stimulated transcriptional activity of an epsilon globin promoter in K562, but not in the nonerythroid Chinese hamster ovary cells. Therefore, it was concluded that activin A exerts its effects on globin gene expression at the level of transcription in erythroid cells.
Delineating the Structural Blueprint of the Pre-mRNA 3′-End Processing Machinery (2014)

Processing of mRNA precursors (pre-mRNAs) by polyadenylation is an essential step in gene expression. Polyadenylation consists of two steps, cleavage and poly(A) synthesis, and requires multiple cis elements in the pre-mRNA and a megadalton protein complex bearing the two essential enzymatic activities. While genetic and biochemical studies remain the major approaches in characterizing these factors, structural biology has emerged during the past decade to help understand the molecular assembly and mechanistic details of the process. With structural information about more proteins and higher-order complexes becoming available, we are coming closer to obtaining a structural blueprint of the polyadenylation machinery that explains both how this complex functions and how it is regulated and connected to other cellular processes.
Vascular endothelial growth factor chimeric toxin is highly active against endothelial cells. (1999)

Angiogenesis is a critical step in a benign tumor's evolution toward malignancy and metastasis. Tumor cells acquire such a phenotype by their ability to secrete angiogenic factors such as vascular endothelial growth factor (VEGF). VEGF receptors (VEGFRs) flt-1/VEGFR-1 and Flk-1/ KDR/VEGFR-2 are restricted to activated endothelial cells, with the highest expression being in the tumor vasculature. The present study was undertaken to target the VEGFRs. Targeted toxins were developed by recombinant methods by fusing VEGF165 or VEGF121 to the diphtheria toxin (DT) translocation and enzymatic domain (DT390-VEGF165 or DT390-VEGF121). Both fusion proteins were found to be highly toxic to proliferating endothelial cells but not to vascular smooth muscle cells. The fusion protein is also active in Kaposi's sarcoma, a tumor type that expresses high levels of VEGFRs. These fusion proteins completely inhibit the basic fibroblast growth factor-induced growth of new blood vessels in the chick chorioallantoic membrane assay. Furthermore, the fusion toxin substantially retards the growth of Kaposi's sarcoma tumors in mice. Because nearly all tumors induce local angiogenesis with high VEGFR expression, VEGF-derived toxins may have wide application in cancer therapy.
Release of Excess Amyloid β Protein from a Mutant Amyloid β Protein Precursor (1993)

The 4-kilodalton amyloid beta protein (A beta), which forms fibrillar deposits in Alzheimer's disease (AD), is derived from a large protein referred to as the amyloid beta protein precursor (beta APP). Human neuroblastoma (M17) cells transfected with constructs expressing wild-type beta APP or a mutant, beta APP delta NL, recently linked to familial AD were compared. After continuous metabolic labeling for 8 hours, cells expressing beta APP delta NL had five times more of an A beta-bearing, carboxyl terminal, beta APP derivative than cells expressing wild-type beta APP and they released six times more A beta into the medium. Thus this mutant beta APP may cause AD because its processing is altered in a way that releases increased amounts of A beta.
DC bus voltage control for a distributed power system (2003)

This paper addresses voltage control of distributed DC power systems. DC power systems have been discussed as a result of the introduction of renewable, small-scale power generation units. Also, telecommunication power systems featuring UPS properties might benefit from a broader introduction of DC power systems. Droop control is utilized to distribute the load between the source converters. In order to make the loading of the source converters equal, in per unit, the voltage control algorithm for each converter has to be designed to act similar. The DC side capacitor of each converter, needed for filtering, is also determined as a consequence. The root locus is investigated for varying DC bus impedance. It is found that the risk of entering converter over-modulation is a stronger limitation than stability, at least for reasonable DC bus cable parameters. The stationary and dynamic properties during load variations are also investigated.
Inclusion body myositis (2011)

sIBM understanding continues to advance, with progress regarding the mechanism of this disease.
Localization and Quantification of Platelet-Rich Thrombi in Large Blood Vessels With Near-Infrared Fluorescence Imaging (2006)

IR-786-labeled platelets provide sensitive, specific, and real-time visualization of thrombi in thick-walled blood vessels. In addition to immediate application in cardiac, transplant, and vascular surgery, the mechanisms that underlie thrombus formation in large blood vessels can now be investigated.
Thermal conductivity and diffusivity measurements in the sub-μm and sub-μs scale on centimeter area samples using a microthermocouple (1996)

A micro-thermocouple, made of tungsten versus gold-0.07% Fe, is used in a scanning tunnel microscopelike setup to measure temperature profiles with submicrometer (100 nm) and submicrosecond (50 ns) resolution on centimeter (cm) area thin film surfaces. The installation is equipped with a new type of three-directional piezoelectric inertia drive and enables measurements in the temperature range from 4 to 300 K. The thermal conductivity of a 10 μm gold foil and a silicon wafer (260 μm) has been measured from 8 to 300 K and the thermal boundary resistances of GE-7031 varnish and In-foil, used to mount the samples, were determined. The measured temperature profiles, as a function of time and tip location on the sample, were modeled and fitted by the finite element method. The installation has been designed for mesoscopic temperature profiling to investigate thermal conductivity and diffusivity of thin films, multilayers, and thermal boundary resistances. The results for gold films agree with data reported in the literature. The importance of the boundary resistance (and boundary conditions) in heat flow experiments is emphasized.
Protection of the Ischemic Myocardium during the Reperfusion: Between Hope and Reality (2012)

The heart is an organ that requires an important energy input to ensure its contractile function. Myocardial ischemia happens when there is a deficiency of blood flow that is responsible for the passage from an aerobic to anaerobic metabolism. Myocardial ischemia results from an imbalance between inputs and the needs of nutrient and oxygen to the myocardium. The restoration of myocardial perfusion called reperfusion is a way to save the ischemic myocardium. However, although reperfusion is beneficial for the survival of the ischemic myocardium, it also induces a deleterious effect in addition to that of ischemic stress. Three decade ago, while several studies, strived to elucidate the protective effect of preconditioning, a phenomenon performed before ischemia and having a powerful protective effects against ischemia/reperfusion injury, very few have believed in the possibility of protecting the myocardium after ischemia (during reperfusion). Actually, both ischemic and pharmacological postconditioning as well as controlled reperfusion methods to protect the ischemic heart have proved effective in the reduction of damage related to ischemia/reperfusion. The possibility of protecting the myocardium during reperfusion opens a new area in the research against damage caused by ischemia/reperfusion because these methods are easily transferable in a clinic setting.
Identification of a Novel Major Histocompatibility Complex Class II–restricted Tumor Antigen Resulting from a Chromosomal Rearrangement Recognized by CD4+ T Cells (1999)

CD4(+) T cells play an important role in antitumor immune responses and autoimmune and infectious diseases. Although many major histocompatibility complex (MHC) class I-restricted tumor antigens have been identified in the last few years, little is known about MHC class II- restricted human tumor antigens recognized by CD4(+) T cells. Here, we describe the identification of a novel melanoma antigen recognized by an human histocompatibility leukocyte antigen (HLA)-DR1-restricted CD4(+) tumor-infiltrating lymphocyte (TIL)1363 using a genetic cloning approach. DNA sequencing analysis indicated that this was a fusion gene generated by a low density lipid receptor (LDLR) gene in the 5' end fused to a GDP-L-fucose:beta-D-galactoside 2-alpha-L-fucosyltransferase (FUT) in an antisense orientation in the 3' end. The fusion gene encoded the first five ligand binding repeats of LDLR in the NH2 terminus followed by a new polypeptide translated in frame with LDLR from the FUT gene in an antisense direction. Southern blot analysis showed that chromosomal DNA rearrangements occurred in the 1363mel cell line. Northern blot analysis detected two fusion RNA transcripts present only in the autologous 1363mel, but not in other cell lines or normal tissues tested. Two minimal peptides were identified from the COOH terminus of the fusion protein. This represents the first demonstration that a fusion protein resulting from a chromosomal rearrangement in tumor cells serves as an immune target recognized by CD4(+) T cells.
Lanthanide-Containing Polymer Microspheres by Multiple-Stage Dispersion Polymerization for Highly Multiplexed Bioassays (2009)

We describe the synthesis and characterization of metal-encoded polystyrene microspheres by multiple-stage dispersion polymerization with diameters on the order of 2 mum and a very narrow size distribution. Different lanthanides were loaded into these microspheres through the addition of a mixture of lanthanide salts (LnCl(3)) and excess acrylic acid (AA) or acetoacetylethyl methacrylate (AAEM) dissolved in ethanol to the reaction after about 10% conversion of styrene, that is, well after the particle nucleation stage was complete. Individual microspheres contain ca. 10(6)-10(8) chelated lanthanide ions, of either a single element or a mixture of elements. These microspheres were characterized one-by-one utilizing a novel mass cytometer with an inductively coupled plasma (ICP) ionization source and time-of-flight (TOF) mass spectrometry detection. Microspheres containing a range of different metals at different levels of concentration were synthesized to meet the requirements of binary encoding and enumeration encoding protocols. With four different metals at five levels of concentration, we could achieve a variability of 624, and the strategy we report should allow one to obtain much larger variability. To demonstrate the usefulness of element-encoded beads for highly multiplexed immunoassays, we carried out a proof-of-principle model bioassay involving conjugation of mouse IgG to the surface of La and Tm containing particles and its detection by an antimouse IgG bearing a metal-chelating polymer with Pr.
Highly specific and sensitive detection of malignancy in urine samples from patients with urothelial cancer by CD44v8–10/CD44v10 competitive RT-PCR (1998)

CD44 is a widely expressed cell surface adhesion molecule in which various isoforms arise from alternative RNA splicing mechanism. Overexpression of specific CD44 splice variant, i.e., CD44v8-10, has been found in several human malignancies and is considered to be associated with tumor progression and metastasis. We have demonstrated a novel molecular approach, CD44v8-10/CD44v10 competitive reverse transcription-polymerase chain reaction (CC-RT-PCR) for the detection of cancer cells overexpressing CD44v8-10 by the measurement of the transcriptional level of CD44v8-10 relative to that of CD44v10 (v8-10/v10 ratio). In this study, we initially examined the expression of CD44 splice variants in human urothelial cancers and their adjacent normal urinary tissues by RT-PCR. Any CD44 variant isoforms were barely detectable in normal urinary tissues, whereas CD44v8-10 was predominantly expressed in 23 of the 30 (77%) urothelial cancer specimens. We then applied CC-RT-PCR to spontaneously voided urine samples from patients with 80 urothelial cancer and 50 various benign urologic diseases. The CC-RT-PCR analysis revealed that all of the samples associated with benign diseases presented a predominant expression of the CD44v10 transcript (the v8-10/v10 ratios = 0.00-0.87), whereas 62 of the 80 samples associated with urothelial cancers mostly expressed the CD44v8-10 transcript (the v8-10/v10 ratios > 1.00). In addition, the positivity rate obtained by the CC-RT-PCR analysis was high regardless of the pathological grade of the urothelial cancers, although the sensitivity of the cytological examination declined with decreasing tumor grade. Our findings suggest strongly that CC-RT-PCR is a non-invasive useful tool for the diagnosis of urine samples from patients with urothelial cancer.
Relationship of childhood maltreatment to the onset and course of major depression in adulthood (1999)

The objective of this research was to determine the prevalence of retrospectively recalled childhood trauma among depressed patients and to examine the relationship between retrospective recall of childhood maltreatment and the onset, course, and severity of major depression in adulthood. Forty-seven adults with DSM-IV major depression and forty-one healthy comparison subjects were administered the Childhood Trauma Questionnaire (CTQ), a self-report measure of traumatic experiences in childhood. Age at onset of first depressive episode, number of lifetime depressive episodes, current depressive severity, and presence of lifetime anxiety and substance use comorbidity were determined for the depressed patients using the Structured Clinical Interview for DSM-IV. Patients with major depression recalled significantly more severe emotional abuse, emotional neglect, and physical abuse than the healthy comparison subjects. Among the depressed subjects, the severity of childhood trauma (most notably emotional abuse) predicted 25-28% of the variance in age at onset of first depressive episode (earlier onset) and number of lifetime depressive episodes (more episodes). Depressed patients with recall of childhood trauma also experienced a significantly greater number of comorbid mental disorders (2.9 vs. 1.9) than depressed patients without trauma histories. The findings must be tempered by the possibility of a recall bias toward more adverse childhood experiences in the depressed patients. To the extent that these data are valid, they suggest that childhood maltreatment may influence the onset, course, and comorbid character of major depression.
Extensive Facial Landmark Localization with Coarse-to-Fine Convolutional Network Cascade (2013)

We present a new approach to localize extensive facial landmarks with a coarse-to-fine convolutional network cascade. Deep convolutional neural networks (DCNN) have been successfully utilized in facial landmark localization for two-fold advantages: 1) geometric constraints among facial points are implicitly utilized, 2) huge amount of training data can be leveraged. However, in the task of extensive facial landmark localization, a large number of facial landmarks (more than 50 points) are required to be located in a unified system, which poses great difficulty in the structure design and training process of traditional convolutional networks. In this paper, we design a four-level convolutional network cascade, which tackles the problem in a coarse-to-fine manner. In our system, each network level is trained to locally refine a subset of facial landmarks generated by previous network levels. In addition, each level predicts explicit geometric constraints (the position and rotation angles of a specific facial component) to rectify the inputs of the current network level. The combination of coarse-to-fine cascade and geometric refinement enables our system to locate extensive facial landmarks (68 points) accurately in the 300-W facial landmark localization challenge.
Severe acute respiratory syndrome coronavirus nucleocapsid protein expressed by an adenovirus vector is phosphorylated and immunogenic in mice (2004)

Severe acute respiratory syndrome coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. Thus, vaccination against SARS-CoV may represent an effective approach towards controlling SARS. The nucleocapsid (N) protein is thought to play a role in induction of cell-mediated immunity to SARS-CoV and thus it is important to characterize this protein. In the present study, an E1/partially E3-deleted, replication-defective human adenovirus 5 (Ad5) vector (Ad5-N-V) expressing the SARS-CoV N protein was constructed. The N protein, expressed in vitro by Ad5-N-V, was of the expected molecular mass of 50 kDa and was phosphorylated. Vaccination of C57BL/6 mice with Ad5-N-V generated potent SARS-CoV-specific humoral and T cell-mediated immune responses. These results show that Ad5-N-V may potentially be used as a SARS-CoV vaccine.
Online Segment to Segment Neural Transduction (2016)

We introduce an online neural sequence to sequence model that learns to alternate between encoding and decoding segments of the input as it is read. By independently tracking the encoding and decoding representations our algorithm permits exact polynomial marginalization of the latent segmentation during training, and during decoding beam search is employed to find the best alignment path together with the predicted output sequence. Our model tackles the bottleneck of vanilla encoder-decoders that have to read and memorize the entire input sequence in their fixed-length hidden states before producing any output. It is different from previous attentive models in that, instead of treating the attention weights as output of a deterministic function, our model assigns attention weights to a sequential latent variable which can be marginalized out and permits online generation. Experiments on abstractive sentence summarization and morphological inflection show significant performance gains over the baseline encoder-decoders.
Soluble Jagged 1 Represses the Function of Its Transmembrane Form to Induce the Formation of the Src-dependent Chord-like Phenotype (2001)

We have previously demonstrated that the expression of the soluble extracellular domain of the transmembrane ligand for Notch receptors, Jagged 1 (sJ1), in NIH 3T3 cells results in the formation of a matrix-dependent chord-like phenotype, the loss of contact inhibition of growth, and an inhibition of pro-alpha 1(I) collagen expression. In an effort to define the mechanism by which sJ1 induces this phenotype, we report that sJ1 transfectants display biochemical and cytoskeletal alterations consistent with the activation of Src. Indeed, cotransfection of sJ1 transfectants with a dominant-negative mutant of Src resulted in the loss of matrix-dependent chord formation and correlated with the restoration of type I collagen expression and contact inhibition of growth. We also report that the sJ1-mediated induction of Src activity and related phenotypes, including chord formation, may result from the inhibition of endogenous Jagged 1-mediated Notch signaling since it was not possible to detect an sJ1-dependent induction of CSL-dependent transcription in these cells. Interestingly, NIH 3T3 cells transfected with dominant-negative (but not constitutively active) mutants of either Notch 1 or Notch 2 displayed a similar Src-related phenotype as the sJ1 transfectants. These data suggest that the ability of sJ1 to mediate chord formation is Src-dependent and requires the repression of endogenous Jagged 1-mediated Notch signaling, which is tolerant to the destabilization of the actin cytoskeleton, a mediator of cell migration.
Constitutive activation of c-kit in FMA3 murine mastocytoma cells caused by deletion of seven amino acids at the juxtamembrane domain (1996)

A peculiar point mutation results in constitutive activation of c-kit receptor tyrosine kinase (KIT) in three different tumor mast cell lines; ie, the HMC-1, P-815, and RBL-2H3. Because constitutive activation of KIT was also observed in the FMA3 mouse mastocytoma cell line, we investigated the molecular mechanism. Sequencing of the whole coding region of the c-kit showed that the point mutation found in HMC-1, P-815, and RBL-2H3 cells was absent in FMA3 cells and that the c-kit cDNA of FMA3 cells carried an in-frame deletion of 21 base pairs (bp) encoding Thr-Gln-Leu-Pro-Tyr-Asp-His at codons 573 to 579 at the juxtamembrane domain. The FMA3-type c-kit cDNA with 21 bp deletion was introduced into the IC-2 cell line, which was derived from murine cultured mast cells. IC-2 cells were dependent on interleukin (IL)-3 and did not express KIT on the surface. In IC-2 cells introduced with the FMA3-type c-kit cDNA, KIT was constitutively phosphorylated on tyrosines and activated. Moreover, the FMA3-type KIT was dimerized without the stimulation by stem cell factor (SCF), a ligand for KIT. The spontaneously dimerized FMA3-type KIT without SCF binding was not internalized even after the activation. IC-2 cells expressing the FMA3-type KIT grew in suspension culture without IL-3 and SCF and became leukemic in nude athymic mice. The deletion of seven amino acids at the juxtamembrane domain appeared to be a new activating mutation of KIT that might be involved in neoplastic growth of mast cells.
Myocardial Infarction and Apoptosis After Myocardial Ischemia and Reperfusion (1998)

Anti-C5 therapy in the setting of MI/R significantly inhibits cell apoptosis, necrosis, and PMN infiltration in the rat despite C3 deposition. We conclude that the terminal complement components C5a and C5b-9 are key mediators of tissue injury in MI/R.