gebhart/patrepeval huggingface dataset:
PET-CT and MRI research on epileptogenic focal cortical dysplasia (2013)

Objective To investigate the PET-CT and MR imaging characteristics of patients with epileptogenic focal cortical dysplasia,and to evaluate their values in the foci localization of preoperative epilepsy surgery.Methods A retrospective analysis of the clinical data of patients with epileptogenic focal cortical dysplasia,resection of the epileptic focus,and confirmed pathologically in Zhujiang hospital,was carried out from January 2009 to October 2011.The data as distribution of the lesions,histologic subtypes,and MR and PET imaging characteristics and prognosis of 39 patients having complete data were concluded.The relations between each two indexes were analyzed.Results MR imaging showed positive lesions in 31 patients,mainly manifested as unclear junctions between the gray and white matter,local cortical thickening and abnormal morphology,and increased white matter signal on T2WI and Flair imaging.In high signals of T2WI,Flair imaging was very common in patients with the FCD Ⅱb subtype,while rare in patients with the FCD Ⅰ b subtype.PET-CT showed positive lesions in 36 patients; the detection rate was slightly higher than that of MR imaging.According to the Engel prognosis grading,74％ (29/39) of patients was in grade Ⅰ,18％ (7/39) in grade Ⅱ,5％ (2/39) in grade Ⅲ,and 3％ (1/39) in grade Ⅳ.Conclusion In patients with epileptogenic focal cortical dysplasia,unclear junctions between the gray and white matter,local cortical thickening and abnormal morphology,and increased white matter signal on T2WI,and Flair imaging are the main manifestations in MR imaging; PET-CT combined with MR imaging can improve the accuracy of detection.

Key words: 
Epilepsy;  Focal cortical dysplasia;  Positron-emission tomography;  Magnetic resonance imaging;  Diagnosis
Isolation and optimization for affinity and biophysical characteristics of anti-CCL17 antibodies from the VH1-69 germline gene (2014)

CCL17 is a homeostatic chemokine associated with several human inflammatory pathologies. This makes CCL17 a potential point of intervention in inflammatory diseases. Using a Fab-pIX phage display system we were able to select antibodies that specifically bind to CCL17 and neutralize CCL17-mediated signaling. Many of the selected antibodies belong to the VH1-69 germline gene family. The VH1-69 germline gene is represented at a high frequency in the human antibody repertoire and is seen in the early immune response to a variety of pathogens. The heavy chain CDR2 of this germline gene is notably hydrophobic and can insert into hydrophobic pockets of antigens, providing much of the binding energy for these antibodies. Affinity maturation of our primary binders by light chain mutagenesis produced antibodies with sub-nanomolar affinities, with affinity improvements up to 100-fold. These were screened for non-specific protein-protein interactions as a filter for solubility. All of our high affinity antibodies were found to have high levels of non-specific protein-protein interactions. We speculated that this was due to the hydrophobicity within the germline heavy chain CDR1 and CDR2. To ameliorate this problem, we generated a phage display library for one of the clones, where the surface-exposed residues within H-CDR1 and H-CDR2 were randomized. High stringency panning of this library against human CCL17 resulted in further affinity improvement, along with reduction in protein-protein interaction in some new variants. In addition, we improved the cross-reactivity to cynomolgus CCL17. We demonstrate that affinity maturation through targeted libraries in the VH1-69 germline gene can improve both affinity and biophysical characteristics of antibodies derived from this gene scaffold.
CLINICAL AND METABOLIC EFFECTS OF DIFFERENT PARENTERAL NUTRITION REGIMENS IN PATIENTS UNDERGOING ALLOGENEIC BONE MARROW TRANSPLANTATION1 (1998)

The results obtained suggest that the use of lipid-based TPN after allogeneic BMT is associated with lower incidence of lethal A-GVHD and hyperglycemia, without negatively affecting the EGT of infused cells. Intravenously administered lipids might have influenced the severity of A-GVHD likely via modulation of immune response and synthesis of cytokines, prostaglandins, and leukotrienes that participate in the pathogenesis of graft-versus-host disease.
[General Articles] Cannabinoids: Mechanisms and Therapeutic Applications in the CNS (2003)

Cannabinoids comprise three classes of compounds, the active components of marijuana (Cannabis sativa), as well as endogenous and synthetic derivatives. To date, two distinct cannabinoid receptors (CB1 and CB2) have been discovered, but evidence for further receptor types has been brought forward. The potential use of cannabinoids for medicinal purposes has long been known, but the mechanisms of action of both exogenously applied and endogenous cannabinoids are only partly established. For nervous system disorders, cannabinoids may be useful by modulating neurotransmission and calcium homeostasis as well as by anti-inflammatory and anti-oxidant actions. Some cannabinoids can also trigger cell death, which may be of therapeutic benefit in the treatment of malignant tumours. A number of both in vitro and in vivo models have provided promising but diverse evidence for cannabinoid protection in glutamate-mediated excitotoxicity, hypoxia and glucose deprivation, brain trauma, epilepsy and MS. Subsequent to many preclinical investigations, clinical trials are now underway in a variety of the above applications. Overall, the understanding of the therapeutic relevance of cannabinoids will rely on further investigations into the neuroprotective and neurotoxic potency of cannabinoids in animal models and humans, as much as on a further advancement of our general understanding of the endocannabinoid system and the development of specific compounds devoid of unwanted psychoactive side effects.
Occurrence of Interleukin‐6 in Cortical Plaques of Alzheimer's Disease Patients May Precede Transformation of Diffuse into Neuritic Plaquesa (1996)

Interleukin-6 (IL-6) immunoreactivity has previously been shown in plaques in Alzheimer's disease (AD), and elevated IL-6 concentrations have been measured biochemically in brains of AD patients. In this report, we present data on the appearance of IL-6 immunoreactivity in AD plaques according to the stage of plaque formation. Diffuse plaques are found in the early stages of plaque formation, whereas primitive and classic plaques are thought to represent later stages of plaque pathology. We classified plaques using the Bielschowsky silver stain method in serial sections of paraffin-embedded cortices of clinically diagnosed and histopathologically confirmed AD patients and patients with no clinical history of dementia. In the brains of nondemented and demented persons, we found plaques using the silver staining method or immunohistochemistry with antibodies against the amyloid precursor protein. In the nondemented group, diffuse plaques were the predominant plaque type, whereas primitive plaques formed the larger proportion of lesions in the group of AD brains. IL-6 was only detectable in plaques of demented patients. In AD cases, IL-6 was found in a significantly higher ratio in diffuse plaques as would have been expected from a random distribution of IL-6 in all plaque types. We conclude that the presence of IL-6 immunoreactivity correlates with clinically detectable dementia. In addition to the ubiquitous presence of amyloid in nondemented and demented brains, an IL-6-related immunological mechanism may be involved both in the transformation from diffuse to primitive plaques in AD and in the development of dementia.
FST in a hierarchical island model. (1991)

It is shown that in a hierarchical island model, in which demes within a neighborhood exchange migrants at a much higher rate than do demes in different neighborhoods, hierarchical F statistics introduced by S. Wright can indicate the extent of gene flow within and between neighborhoods. At equilibrium, the within-neighborhood inbreeding coefficient, FSN, is approximately 1/(1 + 4Nm1) where N is the deme size and m1 is the migration rate among demes in the same neighborhood. The between-neighborhood inbreeding coefficient, FNT, is approximately 1/(1 + 4Ndm2) where d is the number of demes in a neighborhood and m2 is the migration rate among demes in different neighborhoods.
The Stanford Dash multiprocessor (1992)

The overall goals and major features of the directory architecture for shared memory (Dash) are presented. The fundamental premise behind the architecture is that it is possible to build a scalable high-performance machine with a single address space and coherent caches. The Dash architecture is scalable in that it achieves linear or near-linear performance growth as the number of processors increases from a few to a few thousand. This performance results from distributing the memory among processing nodes and using a network with scalable bandwidth to connect the nodes. The architecture allows shared data to be cached, significantly reducing the latency of memory accesses and yielding higher processor utilization and higher overall performance. A distributed directory-based protocol that provides cache coherence without compromising scalability is discussed in detail. The Dash prototype machine and the corresponding software support are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The proteome targets of intracellular targeting antimicrobial peptides (2015)

Antimicrobial peptides have been considered well-deserving candidates to fight the battle against microorganisms due to their broad-spectrum antimicrobial activities. Several studies have suggested that membrane disruption is the basic mechanism of AMPs that leads to killing or inhibiting microorganisms. Also, AMPs have been reported to interact with macromolecules inside the microbial cells such as nucleic acids (DNA/RNA), protein synthesis, essential enzymes, membrane septum formation and cell wall synthesis. Proteins are associated with many intracellular mechanisms of cells, thus protein targets may be specifically involved in mechanisms of action of AMPs. AMPs like pyrrhocoricin, drosocin, apidecin and Bac 7 are documented to have protein targets, DnaK and GroEL. Moreover, the intracellular targeting AMPs are reported to influence more than one protein targets inside the cell, suggesting for the multiple modes of actions. This complex mechanism of intracellular targeting AMPs makes them more difficult for the development of resistance. Herein, we have summarized the current status of AMPs in terms of their mode of actions, entry to cytoplasm and inhibition of macromolecules. To reveal the mechanism of action, we have focused on AMPs with intracellular protein targets. We have also included the use of high-throughput proteome microarray to determine the unidentified AMP protein targets in this review.
Intra-chromosomal rearrangements generated by Cre-lox site-specific recombination (1995)

Chromosomal rearrangements are useful genetic and breeding tools but are often difficult to detect and characterize. To more easily identify and define chromosome deletions and inversions, we have used the bacteriophage P1 Cre-lox site-specific recombination system to generate these events in plants. This involves three steps: (i) the introduction of two lox sites into one locus in a plant genome, including one site within a modified Ds transposon; (ii) Ac transposase-mediated transposition of the Ds-lox element to a new locus on the same chromosome; (iii) Cre-mediated site-specific recombination between the two lox sites that bracket a chromosome segment. We report the production of a deletion and three inversion events in tobacco. The utility of chromosomal segments bracketed by lox sites for targeted manipulation and cloning is discussed.
Nucleotide sequence of peroxisomal catalase from the yeast Candida tropicalis pK233: identification of an upstream BamHI site polymorphism (1989)

Journal Article Nucleotide sequence of peroxisomal catalase from the yeast Candida tropicalis pK233: identification of an upstream BamHI site polymorphism Get access W.Wayne Murray, W.Wayne Murray * Department of Biochemistry, McMaster UniversityHamilton, Ontario L8N 3Z5, Canada To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard A. Rachubinski Richard A. Rachubinski Department of Biochemistry, McMaster UniversityHamilton, Ontario L8N 3Z5, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 17, Issue 9, 11 May 1989, Page 3600, https://doi.org/10.1093/nar/17.9.3600 Published: 11 May 1989 Article history Received: 23 January 1989 Published: 11 May 1989
Targeting human cytotoxic T lymphocytes to kill heterologous epidermal growth factor receptor-bearing tumor cells. Tumor-infiltrating lymphocyte/hormone receptor/recombinant antibody (1991)

A genetically engineered conjugate between an anti-CD3 antibody and epidermal growth factor (EGF) was tested for its ability to mediate the lysis of receptor-bearing cells by human CTL. This construct was made by fusing an EGF coding sequence to the 3' end of the human gamma-1 H chain gene sequence and expressing the modified gene in transfected cells together with the V regions of a mouse antibody specific for the human T cell marker, CD3. The resulting conjugate was able to compete with EGF for its receptor and, at extremely low concentrations, was able to mediate the lysis of receptor-bearing tumor targets by a tumor-infiltrating lymphocytes line or by a CTL line established from peripheral blood. The construction of such conjugates by genetic engineering represents a general approach to the direct expression of highly specific hetero-bifunctional reagents without the necessity of further in vitro manipulations.
Antioxidant approaches for the treatment of Alzheimer’s disease (2010)

Oxidative stress is an important factor, and one that acts in the earliest stages, of Alzheimer's disease (AD) pathogenesis. The reduction of oxidative stress has been tested as a therapy for AD. While the trial of vitamin E supplementation in moderately severe AD is the most promising so far, it also reveals the limitations of general antioxidant therapies that simply lower oxidative stress and, therefore, the complexity of the redox system. The multiple contributing factors that foster the clinical manifestations of AD should be considered when designing antioxidative stress therapy. In this article, we discuss the multiple pathogenic mechanisms of oxidative stress in AD and the potential targeting approaches.
Steady state photoinduced absorption of PbS quantum dots film (2008)

We have measured steady state photoinduced absorption (PIA) of PbS quantum dot (QD) film in an energy range of interband electronic transitions at low temperature. PIA spectra show both positive and negative PIAs corresponding to five consecutive interband transitions. The close resemblance between PIA spectrum and the second derivative of the linear optical absorption strongly suggests that these steady state PIAs may be caused by photoinduced local electric field, i.e., the linear Stark effect. We postulate this local electric field be generated by the trapped charges under laser excitations.
Autologous cytolytic T lymphocytes recognize a MAGE‐1 nonapeptide on melanomas expressing HLA‐Cw* 1601 (1994)

Human melanoma cell line MZ2-MEL expresses several antigens recognized by autologous cytolytic T lymphocyte (CTL) clones. We reported previously the identification of a gene, named MAGE-1, which codes for antigen MZ2-E which is presented by HLA-A1. Gene MAGE-1 is expressed in many tumors of several types but not in normal tissues except for testis. We show here that gene MAGE-1 directs the expression of another antigen recognized by CTL on the MZ2-MEL cells. This antigen, which was named MZ2-Bb, consists of MAGE-1-encoded peptide SAYGEPRKL bound to major histocompatibility molecule HLA-Cw*1601. The HLA-Cw*1601 allele was found to be expressed by 7 out of 99 individuals from a Caucasian population. Our results extend the range of tumor patients who could be eligible for immunization against MAGE antigens.
Regulation of β-Catenin by a Novel Nongenomic Action of Thyroid Hormone β Receptor (2008)

We previously created a knock-in mutant mouse harboring a dominantly negative mutant thyroid hormone receptor beta (TRbeta(PV/PV) mouse) that spontaneously develops a follicular thyroid carcinoma similar to human thyroid cancer. We found that beta-catenin, which plays a critical role in oncogenesis, was highly elevated in thyroid tumors of TRbeta(PV/PV) mice. We sought to understand the molecular basis underlying aberrant accumulation of beta-catenin by mutations of TRbeta in vivo. Cell-based studies showed that thyroid hormone (T3) induced the degradation of beta-catenin in cells expressing TRbeta via proteasomal pathways. In contrast, no T3-induced degradation occurred in cells expressing the mutant receptor (TRbetaPV). In vitro binding studies and cell-based analyses revealed that beta-catenin physically associated with unliganded TRbeta or TRbetaPV. However, in the presence of T3, beta-catenin was dissociated from TRbeta-beta-catenin complexes but not from TRbetaPV-beta-catenin complexes. beta-Catenin signaling was repressed by T3 in TRbeta-expressing cells through decreasing beta-catenin-mediated transcription activity and target gene expression, whereas sustained beta-catenin signaling was observed in TRbetaPV-expressing cells. The stabilization of beta-catenin, via association with a mutated TRbeta, represents a novel activating mechanism of the oncogenic protein beta-catenin that could contribute to thyroid carcinogenesis in TRbeta(PV/PV) mice.
Ice -COLD-PCR enables rapid amplification and robust enrichment for low-abundance unknown DNA mutations (2010)

Identifying low-abundance mutations within wild-type DNA is important in several fields of medicine, including cancer, prenatal diagnosis and infectious diseases. However, utilizing the clinical and diagnostic potential of rare mutations is limited by sensitivity of the molecular techniques employed, especially when the type and position of mutations are unknown. We have developed a novel platform that incorporates a synthetic reference sequence within a polymerase chain reaction (PCR) reaction, designed to enhance amplification of unknown mutant sequences during COLD-PCR (CO-amplification at Lower Denaturation temperature). This new platform enables an Improved and Complete Enrichment (ice-COLD-PCR) for all mutation types and eliminates shortcomings of previous formats of COLD-PCR. We evaluated ice-COLD-PCR enrichment in regions of TP53 in serially diluted mutant and wild-type DNA mixtures. Conventional-PCR, COLD-PCR and ice-COLD-PCR amplicons were run in parallel and sequenced to determine final mutation abundance for a range of mutations representing all possible single base changes. Amplification by ice-COLD-PCR enriched all mutation types and allowed identification of mutation abundances down to 1%, and 0.1% by Sanger sequencing or pyrosequencing, respectively, surpassing the capabilities of other forms of PCR. Ice-COLD-PCR will help elucidate the clinical significance of low-abundance mutations and our understanding of cancer origin, evolution, recurrence-risk and treatment diagnostics.
Extracellular Iron Reduction Is Mediated in Part by Neutral Red and Hydrogenase inEscherichia coli (2004)

Both microbial iron reduction and microbial reduction of anodes in fuel cells can occur by way of soluble electron mediators. To test whether neutral red (NR) mediates iron reduction, as it does anode reduction, by Escherichia coli, ferrous iron levels were monitored in anaerobic cultures grown with amorphous iron oxide. Ferrous iron levels were 19.4 times higher in cultures fermenting pyruvate in the presence of NR than in the absence of NR. NR did not stimulate iron reduction in cultures respiring with nitrate. To explore the mechanism of NR-mediated iron reduction, cell extracts of E. coli were used. Cell extract-NADH-NR mixtures had an enzymatic iron reduction rate almost 15-fold higher than the chemical NR-mediated iron reduction rate observed in controls with no cell extract. Hydrogen was consumed during stationary phase (in which iron reduction was detectable) especially in cultures containing both NR and iron oxide. An E. coli hypE mutant, with no hydrogenase activity, was also impaired in NR-mediated iron reduction activity. NR-mediated iron reduction rates by cell extracts were 1.5 to 2 times higher with hydrogen or formate as the electron source than with NADH. Our findings suggest that hydrogenase donates electrons to NR for extracellular iron reduction. This process appears to be analogous to those of iron reduction by bacteria that use soluble electron mediators (e.g., humic acids and 2,6-anthraquinone disulfonate) and of anode reduction by bacteria using soluble mediators (e.g., NR and thionin) in microbial fuel cells.
EFFECTS OF LIGHT BEAM SIZE ON FLUENCE DISTRIBUTION AND DEPTH OF NECROSIS IN SUPERFICIALLY APPLIED PHOTODYNAMIC THERAPY OF NORMAL RAT BRAIN (1992)

The light fluence distributions of 632.8 nm light incident on the exposed surface of normal rat brain in vivo have been measured using an interstitial, stereotactically-mounted optical fiber detector with isotropic response. The dependence of the relative fluence rate on depth and the spatial distribution of fluence were compared for incident beam diameters of 3 and 5 mm. The fluence rate at depth of 1-6 mm along the optical axis within the brain tissue was approximately 70% greater for a 5 mm diameter beam than for a 3 mm beam, at the same incident fluence rate, although the plots of the relative fluence rate vs depth were parallel over the depth range 1-6 mm. The depths of necrosis resulting from photodynamic treatment of brain tissue using the photosensitizer Photofrin and irradiation by 632 nm light with 3 and 5 mm incident beams were also measured. The observed difference in necrosis depths was consistent with the measured difference in fluence. The importance of beam size in photodynamic treatment with small diameter incident light fields is discussed.
The Event Tunnel: Interactive Visualization of Complex Event Streams for Business Process Pattern Analysis (2008)

Event-based systems are gaining increasing popularity for building loosely coupled and distributed systems. Since business processes are becoming more interconnected and event-driven, event-based systems fit well for supporting and monitoring business processes. In this paper, we present an event-based business intelligence tool, the Event Tunnel framework. It provides an interactive visualization of event streams to support business analysts in exploring business incidents. The visualization is based on the metaphor of considering the event stream as a cylindrical tunnel, which is presented to the user from multiple perspectives. The information of single events laid out in the Event Tunnel is encoded in event glyphs that allow for a selective mapping of event attributes to colors, size and position. Different policies for the placement of the events in the tunnel as well as a clustering mechanism generate various views on historical event data. The Event Tunnel is able to display the relationships between events. This facilitates users to discover root causes and causal dependencies of event patterns. Our framework couples the event-tunnel visualization with query tools that allow users to search for relevant events within a data repository. Using query, filler and highlighting operations the analyst can navigate through the Event Tunnel until the required information or event patterns become visible. We demonstrate our approach with use cases from the fraud management and logistics domain.