gebhart/patrepeval huggingface dataset:
Epileptic Seizure Detection: A Deep Learning Approach (2018)

Epilepsy is the second most common brain disorder after migraine. Automatic detection of epileptic seizures can considerably improve the patients' quality of life. Current Electroencephalogram (EEG)-based seizure detection systems encounter many challenges in real-life situations. The EEGs are non-stationary signals and seizure patterns vary across patients and recording sessions. Moreover, EEG data are prone to numerous noise types that negatively affect the detection accuracy of epileptic seizures. To address these challenges, we introduce the use of a deep learning-based approach that automatically learns the discriminative EEG features of epileptic seizures. Specifically, to reveal the correlation between successive data samples, the time-series EEG data are first segmented into a sequence of non-overlapping epochs. Second, Long Short-Term Memory (LSTM) network is used to learn the high-level representations of the normal and the seizure EEG patterns. Third, these representations are fed into Softmax function for training and classification. The results on a well-known benchmark clinical dataset demonstrate the superiority of the proposed approach over the existing state-of-the-art methods. Furthermore, our approach is shown to be robust in noisy and real-life conditions. Compared to current methods that are quite sensitive to noise, the proposed method maintains its high detection performance in the presence of common EEG artifacts (muscle activities and eye-blinking) as well as white noise.
Protein design of IgG/TCR chimeras for the co-expression of Fab-like moieties within bispecific antibodies (2015)

Immunoglobulins and T cell receptors (TCRs) share common sequences and structures. With the goal of creating novel bispecific antibodies (BsAbs), we generated chimeric molecules, denoted IgG_TCRs, where the Fv regions of several antibodies were fused to the constant domains of the α/β TCR. Replacing CH1 with Cα and CL with Cβ, respectively, was essential for achieving at least partial heavy chain/light chain assembly. Further optimization of the linker regions between the variable and constant domains, as well as replacement of the large FG loop of Cβ with a canonical β-turn, was necessary to consistently obtain full heavy chain/light chain assembly. The optimized IgG_TCR molecules were evaluated biophysically and shown to maintain the binding properties of their parental antibodies. A few BsAbs were generated by co-expressing native Fabs and IgG_TCR Fabs within the same molecular construct. We demonstrate that the IgG_TCR designs steered each of the light chains within the constructs to specifically pair with their cognate heavy chain counterparts. We did find that even with complete constant domain specificity between the CH1/CL and Cα/Cβ domains of the Fabs, strong variable domain interactions can dominate the pairing specificity and induce some mispairing. Overall, the IgG_TCR designs described here are a first step toward the generation of novel BsAbs that may be directed toward the treatment of multi-faceted and complex diseases.
The structure and function of cartilage proteoglycans (2006)

Cartilage contains a variety of proteoglycans that are essential for its normal function. These include aggrecan, decorin, biglycan, fibromodulin and lumican. Each proteoglycan serves several functions that are determined by both its core protein and its glycosaminoglycan chains. This review discusses the structure/function relationships of the cartilage proteoglycans, and the manner in which perturbations in proteoglycan structure or abundance can adversely affect tissue function.
Electrolytic Shaping of Germanium and Silicon (1956)

Properties of electrolyte-semiconductor barriers are described, with emphasis on germanium. The use of these barriers in localizing electrolytic etching is discussed. Other localization techniques are mentioned. Electrolytes for etching germanium and silicon are given.
Personality and Depression (1983)

• The Clinical Studies of the National Institute of Mental Health—Clinical Research Branch Collaborative Program on the Psychobiology of Depression offer an opportunity to clarify the relationship between personality and depression. Thirty-one female patients with primary nonbipolar major depressive disorder were assessed diagnostically using the Schedule for Affective Disorders and Schizophrenia and completed a battery of standard self-report personality inventories when they were completely symptom free. Their personality scale scores were compared with those of female relatives who had recovered from the same type of disorder, those of female relatives with no history of psychiatric illness, and published scale norms. Compared with the normal population, both groups of recovered depressives were introverted, submissive, and passive, with increased interpersonal dependency but normal emotional strength. Comparison to never-ill relatives yielded similar results except that the never-ill relatives had scores reflecting extraordinary emotional strength.
Design for Parallel Interactive Ray Tracing Systems (2006)

We describe the software architecture of the Manta interactive ray tracer and describe its application in engineering and scientific visualization. Although numerous ray tracing software packages have been developed, much of the traditional design wisdom needs to be updated to provide support for interactivity, high degrees of parallelism, and modern packet-based acceleration structures. We discuss situations that are normally not considered when designing a batch ray tracer and present methods to overcome those challenges. This paper advocates a forward looking programming model for interactive ray tracing that uses reconfigurable components to achieve flexibility while achieving scalability on large numbers of processors. Manta employs data structures motivated by modern microprocessor design that can exploit instruction-level parallelism. We discuss the design tradeoffs and the performance achieved for this system
Structural analysis of a series of antiviral agents complexed with human rhinovirus 14. (1988)

The binding to human rhinovirus 14 of a series of eight antiviral agents that inhibit picornaviral uncoating after entry into host cells has been characterized crystallographically. All of these bind into the same hydrophobic pocket within the viral protein VP1 beta-barrel structure, although the orientation and position of each compound within the pocket was found to differ. The compounds cause the protein shell to be less flexible, thereby inhibiting disassembly. Although the antiviral potency of these compounds varies by 120-fold, they all induce the same conformational changes on the virion. The interactions of these compounds with the viral capsid are consistent with their observed antiviral activities against human rhinovirus 14 drug-resistant mutants and other rhinovirus serotypes. Crystallographic studies of one of these mutants confirm the partial sequencing data and support the finding that this is a single mutation that occurs within the binding pocket.
Cloning and characterization of the goadsporin biosynthetic gene cluster from Streptomyces sp. TP-A0584 (2005)

The biosynthetic gene cluster of goadsporin, a polypeptide antibiotic containing thiazole and oxazole rings, was cloned from Streptomyces sp. TP-A0584. The cluster contains a structural gene, godA, and nine god (goadsporin) genes involved in post-translational modification, immunity and transcriptional regulation. Although the gene organization is similar to typical bacteriocin biosynthetic gene clusters, each goadsporin biosynthetic gene shows low homology to these genes. Goadsporin biosynthesis is initiated by the translation of godA, and the subsequent cyclization, dehydration and acetylation are probably catalysed by godD, godE, godF, godG and godH gene products. godI shows high similarity to the 54 kDa subunit of the signal recognition particle and plays an important role in goadsporin immunity. Furthermore, four goadsporin analogues were produced by site-directed mutagenesis of godA, suggesting that this biosynthesis machinery is used for the heterocyclization of peptides.
Generation of a bile salt export pump deficiency model using patient-specific induced pluripotent stem cell-derived hepatocyte-like cells (2017)

Bile salt export pump (BSEP) plays an important role in hepatic secretion of bile acids and its deficiency results in severe cholestasis and liver failure. Mutation of the ABCB11 gene encoding BSEP induces BSEP deficiency and progressive familial intrahepatic cholestasis type 2 (PFIC2). Because liver transplantation remains standard treatment for PFIC2, the development of a novel therapeutic option is desired. However, a well reproducible model, which is essential for the new drug development for PFIC2, has not been established. Therefore, we attempted to establish a PFIC2 model by using iPSC technology. Human iPSCs were generated from patients with BSEP-deficiency (BD-iPSC), and were differentiated into hepatocyte-like cells (HLCs). In the BD-iPSC derived HLCs (BD-HLCs), BSEP was not expressed on the cell surface and the biliary excretion capacity was significantly impaired. We also identified a novel mutation in the 5'-untranslated region of the ABCB11 gene that led to aberrant RNA splicing in BD-HLCs. Furthermore, to evaluate the drug efficacy, BD-HLCs were treated with 4-phenylbutyrate (4PBA). The membrane BSEP expression level and the biliary excretion capacity in BD-HLCs were rescued by 4PBA treatment. In summary, we succeeded in establishing a PFIC2 model, which may be useful for its pathophysiological analysis and drug development.
Cloning of a Novel Phosphatidylinositol Kinase-related Kinase (2001)

We have cloned and characterized a new member of the phosphatidylinositol kinase (PIK)-related kinase family. This gene, which we term human SMG-1 (hSMG-1), is orthologous to Caenorhabditis elegans SMG-1, a protein that functions in nonsense-mediated mRNA decay (NMD). cDNA sequencing revealed that hSMG-1 encodes a protein of 3031 amino acids containing a conserved kinase domain, a C-terminal domain unique to the PIK-related kinases and an FKBP12-rapamycin binding-like domain similar to that found in the PIK-related kinase mTOR. Immunopurified FLAG-tagged hSMG-1 exhibits protein kinase activity as measured by autophosphorylation and phosphorylation of the generic PIK-related kinase substrate PHAS-1. hSMG-1 kinase activity is inhibited by high nanomolar concentrations of wortmannin (IC(50) = 105 nm) but is not inhibited by a FKBP12-rapamycin complex. Mutation of conserved residues within the kinase domain of hSMG-1 abolishes both autophosphorylation and substrate phosphorylation, demonstrating that hSMG-1 exhibits intrinsic protein kinase activity. hSMG-1 phosphorylates purified hUpf1 protein, a phosphoprotein that plays a critical role in NMD, at sites that are also phosphorylated in whole cells. Based on these data, we conclude that hSMG-1 is the human orthologue to C. elegans SMG-1. Our data indicate that hSMG-1 may function in NMD by directly phosphorylating hUpf1 protein at physiologically relevant sites.
Effects of Brown Midrib 3 Mutation in Corn Silage on Productivity of Dairy Cows Fed Two Concentrations of Dietary Neutral Detergent Fiber: 1. Feeding Behavior and Nutrient Utilization (2000)

The effects of digestibility of corn silage neutral detergent fiber (NDF) and dietary NDF content on feeding behavior, dry matter intake (DMI), and energy utilization were evaluated with eight multiparous high producing dairy cows in a duplicated 4 4 Latin square design with 21-d periods. Experimental diets contained corn silage from a brown midrib (bm3) hybrid or its isogenic normal control at two concentrations of dietary NDF (29 and 38%). Both low NDF diets and bm3 corn silage treatments increased DMI and milk yield. However, an interaction between corn silage treatment and dietary NDF content was observed for meal size and for interval between meals, implying that different mechanisms regulating DMI dominate depending on the fermentation characteristics of diets. The bm3 treatment depressed milk fat concentration when fed in a low NDF diet. The bm3 corn silage increased solidscorrected milk yield, but did not affect daily body weight gain compared with control, whereas low NDF diets increased daily body weight gain, but did not affect solids-corrected milk yield compared to high NDF diets. Both bm3 treatments and low NDF diets reduced ruminal pH, but low NDF treatments increased fluctuation of ruminal pH and bm3 treatments did not. Feeding bm3 corn silage increased the energy utilized for milk production, possibly because of a consistent supply of metabolic fuels from the rumen. The beneficial effects of bm3 corn silage on productivity of lactating cows were greater for the cows fed a high NDF diet.
Chimeric NKG2D Receptor–Bearing T Cells as Immunotherapy for Ovarian Cancer (2007)

Despite advancements in the treatment of ovarian cancer, this disease continues to be a leading cause of cancer death in women. Adoptive transfer of tumor-reactive T cells is a promising antitumor therapy for many cancers. We designed a chimeric receptor linking NKG2D, a natural killer (NK) cell-activating receptor, to the CD3zeta chain of the T-cell receptor to target ovarian tumor cells. Engagement of chimeric NKG2D receptors (chNKG2D) with ligands for NKG2D, which are commonly expressed on tumor cells, leads to T-cell secretion of proinflammatory cytokines and tumor cytotoxicity. In this study, we show that >80% of primary human ovarian cancer samples expressed ligands for NKG2D on the cell surface. The tumor samples expressed MHC class I-related protein A, MICB, and UL-16 binding proteins 1 and 3. ChNKG2D-expressing T cells lysed ovarian cancer cell lines. We show that T cells from ovarian cancer patients that express chNKG2D secreted proinflammatory cytokines when cultured with autologous tumor cells. In addition, we show that chNKG2D T cells can be used therapeutically in a murine model of ovarian cancer. These data indicate that treatment with chNKG2D-expressing T cells is a potential immunotherapy for ovarian cancer.
Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells (2003)

Botulinum neurotoxins (BoNTs) cause botulism by entering neurons and cleaving proteins that mediate neurotransmitter release; disruption of exocytosis results in paralysis and death. The receptors for BoNTs are thought to be composed of both proteins and gangliosides; however, protein components that mediate toxin entry have not been identified. Using gain-of-function and loss-of-function approaches, we report here that the secretory vesicle proteins, synaptotagmins (syts) I and II, mediate the entry of BoNT/B (but not BoNT/A or E) into PC12 cells. Further, we demonstrate that BoNT/B entry into PC12 cells and rat diaphragm motor nerve terminals was activity dependent and can be blocked using fragments of syt II that contain the BoNT/B-binding domain. Finally, we show that syt II fragments, in conjunction with gangliosides, neutralized BoNT/B in intact mice. These findings establish that syts I and II can function as protein receptors for BoNT/B.
Functional Antagonism between CCAAT/Enhancer Binding Protein-α and Peroxisome Proliferator-activated Receptor-γ on the Leptin Promoter (1997)

The ob gene product, leptin, is a major hormonal regulator of appetite and fat cell mass. Recent work has suggested that the antidiabetic agents, the thiazolidinediones (TZ), which are also high affinity ligands of peroxisome proliferator-activated receptor-gamma (PPARgamma), inhibit leptin expression in rodents. To examine the effects of this class of drug on the leptin gene in adipocytes we performed Northern analysis on primary rat adipocytes cultured in the presence or absence of TZ. TZ reduced leptin mRNA levels by 75%. To determine whether this effect was mediated at the transcriptional level, we isolated 6510 base pairs of 5'-flanking sequence of the leptin promoter and studied reporter constructs in primary rat adipocytes and CV-1 cells. Sequence analysis demonstrated the presence of a consensus direct repeat with a 1-base-pair gap site between -3951 and -3939 as well as a consensus CCAAT/enhancer binding protein (C/EBP) site between -55 and -47. Our functional analysis in transfected primary rat adipocytes demonstrates that, despite the presence of a canonical direct repeat with a 1-base-pair gap site, TZ alone decreases reporter gene expression of leptin promoter constructs ranging from -6510 to +9 to -65 to +9. In CV-1 cells, which contain endogenous PPARgamma, TZ treatment alone had little effect on these constructs. However, TZ treatment did inhibit C/EBPalpha-mediated transactivation of the leptin promoter. This down-regulation of leptin reporter constructs mapped to a -65 to +9 promoter fragment which binds C/EBPalpha in gel-mobility shift assays but does not bind PPARgamma2 alone or as a heterodimer with 9-cis-retinoic acid receptor. Conversely, the promoter (-5400 to +24 base pairs) of the aP2 gene, another adipocyte-specific gene, was induced 7.3-fold by TZ. Co-transfection with C/EBPalpha minimally stimulated the aP2 promoter from basal levels but notably blocked activation by TZ. These data indicate that PPARgamma and C/EBPalpha can functionally antagonize each other on at least two separate promoters and that this mechanism may explain the down-regulation of leptin expression by thiazolidinediones.
Learning transportation mode from raw gps data for geographic applications on the web (2008)

Geographic information has spawned many novel Web applications where global positioning system (GPS) plays important roles in bridging the applications and end users. Learning knowledge from users' raw GPS data can provide rich context information for both geographic and mobile applications. However, so far, raw GPS data are still used directly without much understanding. In this paper, an approach based on supervised learning is proposed to automatically infer transportation mode from raw GPS data. The transportation mode, such as walking, driving, etc., implied in a user's GPS data can provide us valuable knowledge to understand the user. It also enables context-aware computing based on user's present transportation mode and design of an innovative user interface for Web users. Our approach consists of three parts: a change point-based segmentation method, an inference model and a post-processing algorithm based on conditional probability. The change point-based segmentation method was compared with two baselines including uniform duration based and uniform length based methods. Meanwhile, four different inference models including Decision Tree, Bayesian Net, Support Vector Machine (SVM) and Conditional Random Field (CRF) are studied in the experiments. We evaluated the approach using the GPS data collected by 45 users over six months period. As a result, beyond other two segmentation methods, the change point based method achieved a higher degree of accuracy in predicting transportation modes and detecting transitions between them. Decision Tree outperformed other inference models over the change point based segmentation method.
Hardware-based nonlinear filtering and segmentation using high-level shading languages (2004)

Non-linear filtering is an important task for volume analysis. This paper presents hardware-based implementations of various non-linear filters for volume smoothing with edge preservation. The Cg high-level shading language is used in combination with latest PC consumer graphics hardware. Filtering is divided into pervertex and per-fragment stages. In both stages we propose techniques to increase the filtering performance. The vertex program pre-computes texture coordinates in order to address all contributing input samples of the operator mask. Thus additional computations are avoided in the fragment program. The presented fragment programs preserve cache coherence, exploit 4D vector arithmetic, and internal fixed point arithmetic to increase performance. We show the applicability of non-linear filters as part of a GPU-based segmentation pipeline. The resulting binary mask is compressed and decompressed in the graphics memory on-the-fly.
Antigenic Variability of Borrelia burgdorferi (1988)

Borrelia burgdorferi strains (six isolates from North America and 28 isolates from Europe) were analyzed by physicochemical and immunological methods. By SDS-PAGE, all Borrelia burgdorferi strains tested had two major proteins with constant molecular weights of 60 and 41 kDa and one, two, or three variable low molecular weight proteins (OspA = 30-32 kDa, OspB = 34-36 kDa, pC = 21-22 kDa). All combinations--except OspB alone or OspB/pC--were observed. Borrelia burgdorferi strains were different from relapsing fever borreliae by strong reactivity with OspA- and/or pC-specific polyclonal antibodies, whereas relapsing fever borreliae were only weakly reactive. Among 25 Borrelia burgdorferi isolates, seven different serotypes of Borrelia burgdorferi were defined according to their reactivity in the Western blot with three monoclonal OspA-specific antibodies (H5332, H3TS, and LA5), four OspA- or OspB-specific polyclonal antibodies, and 12 polyclonal antibodies against whole borreliae. Antigenic differences between European CSF and skin isolates were observed, all skin isolates (n = 11) belonging to serotype 2 in contrast to only two out of seven CSF isolates. CSF isolates were antigenically heterogenous (serotypes 1, 2, 3, 4, and 5). Serotypes 6 and 7 were represented by two tick isolates, and the other European tick isolates are not yet fully characterized. Antigenic differences between European and North American strains may play a role in differences in the clinical picture of Lyme borreliosis.
Instability of repetitive DNA sequences: The role of replication in multiple mechanisms (2001)

Rearrangements between tandem sequence homologies of various lengths are a major source of genomic change and can be deleterious to the organism. These rearrangements can result in either deletion or duplication of genetic material flanked by direct sequence repeats. Molecular genetic analysis of repetitive sequence instability in Escherichia coli has provided several clues to the underlying mechanisms of these rearrangements. We present evidence for three mechanisms of RecA-independent sequence rearrangements: simple replication slippage, sister-chromosome exchange-associated slippage, and single-strand annealing. We discuss the constraints of these mechanisms and contrast their properties with RecA-dependent homologous recombination. Replication plays a critical role in the two slipped misalignment mechanisms, and difficulties in replication appear to trigger rearrangements via all these mechanisms.
Mouse model of ischemic acute kidney injury: technical notes and tricks (2012)

Renal ischemia-reperfusion leads to acute kidney injury (AKI), a major kidney disease associated with an increasing prevalence and high mortality rates. A variety of experimental models, both in vitro and in vivo, have been used to study the pathogenic mechanisms of ischemic AKI and to test renoprotective strategies. Among them, the mouse model of renal clamping is popular, mainly due to the availability of transgenic models and the relatively small animal size for drug testing. However, the mouse model is generally less stable, resulting in notable variations in results. Here, we describe a detailed protocol of the mouse model of bilateral renal ischemia-reperfusion. We share the lessons and experiences gained from our laboratory in the past decade. We further discuss the technical issues that account for the variability of this model and offer relevant solutions, which may help other investigators to establish a well-controlled, reliable animal model of ischemic AKI.