gebhart/patrepeval huggingface dataset:
Intracellular Trafficking of Histone Deacetylase 4 Regulates Neuronal Cell Death (2005)

Histone deacetylase 4 (HDAC4) undergoes signal-dependent shuttling between the cytoplasm and nucleus, which is regulated in part by calcium/calmodulin-dependent kinase (CaMK)-mediated phosphorylation. Here, we report that HDAC4 intracellular trafficking is important in regulating neuronal cell death. HDAC4 is normally localized to the cytoplasm in brain tissue and cultured cerebellar granule neurons (CGNs). However, in response to low-potassium or excitotoxic glutamate conditions that induce neuronal cell death, HDAC4 rapidly translocates into the nucleus of cultured CGNs. Treatment with the neuronal survival factor BDNF suppresses HDAC4 nuclear translocation, whereas a proapoptotic CaMK inhibitor stimulates HDAC4 nuclear accumulation. Moreover, ectopic expression of nuclear-localized HDAC4 promotes neuronal apoptosis and represses the transcriptional activities of myocyte enhancer factor 2 and cAMP response element-binding protein, survival factors in neurons. In contrast, inactivation of HDAC4 by small interfering RNA or HDAC inhibitors suppresses neuronal cell death. Finally, an increase of nuclear HDAC4 in granule neurons is also observed in weaver mice, which harbor a mutation that promotes CGN apoptosis. Our data identify HDAC4 and its intracellular trafficking as key effectors of multiple pathways that regulate neuronal cell death.
Diversity and Prevalence of PorA Types inNeisseria meningitidisSerogroup B in the United States, 1992–1998 (2000)

Two hundred eighty-one sporadic Neisseria meningitidis serogroup B isolates, collected through active laboratory-based surveillance, were selected to be analyzed by PorA variable region (VR) typing to determine the prevalence of PorA types in the United States. A substantial number of distinct VR types were identified, 31 in VR1 and 41 in VR2. A total of 73 different PorA types were found, and 76. 7% of these types comprise nonprototype sequences in VR1, VR2, or both. The most prevalent PorA types were P1.7,16-20 (previously P1.7, 16i), P1.22,14, P1.22-1,14 (previously P1.22a,14), P1.7,16, P1.7-1,1 (previously P1.7d,1), P1.19,15, and P1.17,16-3 (previously P1.B,16d). No correlation was observed between the PorA types and geographic origin of the isolates. These data may aid in the design of an efficacious outer membrane protein-based vaccine by identifying the most appropriate PorA types for vaccine formulation. Studies are needed to fully evaluate the extent of cross-protection in humans among the variants and prototypes in each PorA VR family.
Accuracy, lesion bypass, strand displacement and translocation by DNA polymerases (2004)

The structures of DNA polymerases from different families show common features and significant differences that shed light on the ability of these enzymes to accurately copy DNA and translocate. The structure of a B family DNA polymerase from phage RB69 exhibits an active-site closing conformational change in the fingers domain upon forming a ternary complex with primer template in deoxynucleoside triphosphate. The rotation of the fingers domain alpha-helices by 60 degrees upon dNTP binding is analogous to the changes seen in other families of polymerases. When the 3' terminus is bound to the editing 3' exonuclease active site, the orientation of the DNA helix axis changes by 40 degrees and the thumb domain re-orients with the DNA. Structures of substrate and product complexes of T7 RNA polymerase, a structural homologue of T7 DNA polymerase, show that family polymerases use the rotation conformational change of the fingers domain to translocate down the DNA. The fingers opening rotation that results in translocation is powered by the release of the product pyrophosphate and also enables the Pol I family polymerases to function as a helicase in displacing the downstream non-template strand from the template strand.
Key issues relating to the genetic stability and preservation of cells and cell banks. (1993)

The long term maintenance of genetically stable cells is important for ensuring reproducible results and continuity in the advance of microbiology, cell biology and biotechnology. As actively growing cultures, cells are constantly at risk of changing, and the necessity for subculturing living materials increases the chances for genetic change and contamination. Many techniques are available for stabilizing living cells; the method employed must be compatible with the intended use of the culture. The most commonly utilized means of preserving living cells are by freezing to cryogenic temperatures, and freeze-drying. Master stocks are usually maintained at liquid nitrogen or comparable temperatures, while working stocks can be frozen or freeze-dried, and maintained at more economical and easily managed temperatures where possible. However, low temperature techniques may cause damage that can result in genetic change, or potential selection when only a small portion of the population survives. Therefore, a good preservation program must include a comprehensive cell characterization regimen that is applied both before and after preserving the cells to ensure that changes are detected when they do occur. Assurance of long term stability necessitates well designed safekeeping and security measures that include minimizing specimen handling through well designed inventory systems, validation and monitoring of storage temperatures, provisions for backup inventory, and training of personnel. Cell banking also requires good cataloguing and data management practices to avoid duplication and misidentification, and to ensure proper tracking of specimens and ease of access.
Multimedia input in automated image annotation and content-based retrieval (1995)

This research explores the interaction of linguistic and photographic information in an integrated text/image database. By utilizing linguistic descriptions of a picture (speech and text input) coordinated with pointing references to the picture, we extract information useful in two aspects: image interpretation and image retrieval. In the image interpretation phase, objects and regions mentioned in the text are identified; the annotated image is stored in a database for future use. We incorporate techniques from our previous research on photo understanding using accompanying text: a system, PICTION, which identifies human faces in a newspaper photograph based on the caption. In the image retrieval phase, images matching natural language queries are presented to a user in a ranked order. This phase combines the output of (1) the image interpretation/annotation phase, (2) statistical text retrieval methods, and (3) image retrieval methods (e.g., color indexing). The system allows both point and click querying on a given image as well as intelligent querying across the entire text/image database.
Schwoebel-Ehrlich barrier: from two to three dimensions (2002)

The Schwoebel-Ehrlich barrier—the additional barrier for an adatom to diffuse down a surface step—dictates the growth modes of thin films. The conventional concept of this barrier is two dimensional (2D), with the surface step being one monolayer. We propose the concept of a three-dimensional (3D) Schwoebel-Ehrlich barrier, and identify the 2D to 3D transition, taking aluminum as a prototype and using the molecular statics method. Our results show that: (1) substantial differences exist between the 2D and 3D barriers; (2) the transition completes in four monolayers; and (3) there is a major disparity in the 3D barriers between two facets; further, alteration of this disparity using surfactants can lead to the dominance of surface facet against thermodynamics.
Enzyme Immunoassay Detecting Teichoic and Lipoteichoic Acids versus Cerebrospinal Fluid Culture and Latex Agglutination for Diagnosis of Streptococcus pneumoniae Meningitis (1998)

ABSTRACT A newly developed enzyme immunoassay (EIA) was used to detect the presence of pneumococcal teichoic and lipoteichoic acids in cerebrospinal fluid (CSF) from patients with Streptococcus pneumoniae meningitis who were being treated with antibiotics. All initial CSF samples, which on culture grew S. pneumoniae , were positive in the EIA. A total of 14 subsequent culture-negative samples gave clear signals in the EIA up to day 15 after the onset of antibiotic treatment. For 11 CSF specimens, culture, microscopy, and latex agglutination were negative while the EIA detected pneumococcal antigens. The EIA did not react either with CSF of patients with meningitis caused by bacteria other than S. pneumoniae or by viral pathogens. In conclusion, this EIA can be a valuable tool for the diagnosis of S. pneumoniae meningitis from CSF samples in cases in which prior antimicrobial therapy minimizes the usefulness of culture or other antigen detection tests.
A randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in North America (1997)

To test the safety and efficacy of tirilazad mesylate, a nonglucocorticoid 21-aminosteroid, in improving the outcome of patients with aneurysmal subarachnoid hemorrhage (SAH), 902 patients were enrolled in a prospective randomized, double-blind, vehicle-controlled trial at 54 North American neurosurgical centers. Five patients were excluded prior to receiving any study drug. Of 897 patients who received at least one dose of study medication, 300 received a placebo containing a citrate vehicle, 298 received 2 mg/kg per day tirilazad, and 299 received 6 mg/kg per day tirilazad, all administered intravenously beginning within 48 hours of the SAH and continuing through 10 days posthemorrhage. All patients were also treated with orally administered nimodipine. At 3 months post-SAH, there were no significant differences (p < 0.025) among the groups with regard to mortality rate, favorable outcome on the Glasgow Outcome Scale, or employment status. During the first 14 days after the SAH, there were no significant differences among the groups in the incidence or severity of clinically symptomatic or angiographically identifiable cerebral vasospasm. Mortality data stratified by gender and neurological grade on admission (assessed according to a modified World Federation of Neurological Surgeons scale) demonstrated that the men with Grades IV to V had a 33% mortality rate in the vehicle group, 52% in the 2 mg/kg per day tirilazad group (p = 0.29), and 5% in the 6 mg/kg per day tirilazad group (p = 0.03). Tirilazad was well tolerated at both dose levels. Tirilazad mesylate at dosage levels of up to 6 mg/kg per day for 8 to 10 days following SAH did not improve the overall outcome in patients with aneurysmal SAH in this trial. The differences in the efficacy of tirilazad in this trial and a previously reported trial in Europe, Australia, and New Zealand, in which dosage levels of tirilazad of 6 mg/kg per day reduced mortality rates and increased good recovery, may be a result of differences in admission characteristics of the patients and/or differences in management protocols, including the use of anticonvulsant medications.
The Retardation of Aging by Caloric Restriction: Studies in Rodents and Primates (1996)

Caloric restriction (CR), which has been investigated by gerontologists for more than 60 yr, provides the only intervention tested to date in mammals (typically mice and rats) that repeatedly and strongly increases maximum life span while retarding the appearance of age-associated pathologic and biologic changes. Although the large majority of rodent studies have initiated CR early in life (1-3 mo of age), CR started in midadulthood (at 12 mo) also extends maximum life span in mice. Two main questions now face gerontologists investigating CR. By what mechanisms does CR retard aging and disease processes in rodents? There is evidence to suggest that age-associated increases in oxidative damage may represent a primary aging process that is attenuated by CR. Will CR exert similar actions in primates? Studies in rhesus monkeys subjected to CR and limited human epidemiological data support the notion of human translatability. However, no matter what the answers are to these questions, the prolongation of the health span and life span of rodents by CR has major implications for many disciplines, including toxicologic pathology, and raises important questions about the desirability of ad libitum feeding.
Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite ofClostridiaspp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia (2010)

A compound identified as 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA) was found in higher concentrations in urine samples of children with autism compared to age and sex appropriate controls and in an adult with recurrent diarrhea due to Clostridium difficile infections. The highest value measured in urine samples was 7500 mmol/mol creatinine, a value 300 times the median normal adult value, in a patient with acute schizophrenia during an acute psychotic episode. The psychosis remitted after treatment with oral vancomycin with a concomitant marked decrease in HPHPA. The source of this compound appears to be multiple species of anaerobic bacteria of the Clostridium genus. The significance of this compound is that it is a probable metabolite of m-tyrosine (3-hydroxyphenylalanine), a tyrosine analog which depletes brain catecholamines and causes symptoms of autism (stereotypical behavior, hyperactivity, and hyper-reactivity) in experimental animals.
Molecular target therapies in endometrial cancer: From the basic research to the clinic (2008)

Molecular targeted therapies represent an interesting field of pharmacological research in endometrial cancer. The loss of PTEN (phosphatase and tensin homolog deleted on chromosome 10) function, with consequent activation of the PI3K (phosphatidylinositol-3-kinase)-AKT (serine/threonine-specific protein kinase)-mTOR (mammalian target of rapamycin) signaling pathway, occurs in 32-83% of endometrioid-type endometrial carcinomas, thus suggesting a role for mTOR inhibition in this malignancy. Some analogues of rapamycin (CCI-799, RAD-001, AP-23573) have been developed and tested in different tumors including endometrioid-type endometrial carcinoma. For example, AP-23573 achieved a clinical benefit response in 33% of 27 heavily pretreated patients, and CCI-799 obtained a 26% partial response rate and a 63% stable disease rate in 19 patients. Overexpression of ErbB-2 (epidermal growth factor type II receptor) has been detected in 18-80% of uterine papillary serous carcinomas (UPSCs), thus providing a biological rationale for the use of trastuzumab in these aggressive tumors. UPSC often overexpresses claudin-3 and claudin-4, which represent the epithelial receptors for Clostridium perfringens enterotoxin (CPE). CPE-mediated therapy might be a novel treatment modality for UPSC resistant to chemotherapy. A better understanding of the signaling transduction pathways that are dysregulated in endometrioid-type endometrial carcinoma and UPSC will allow the development of novel molecular targeted therapies.
Bacteria-mediated DNA transfer in gene therapy and vaccination (2004)

The use of live attenuated bacterial vaccine strains allows the targeted delivery of macromolecules to mammalian cells and tissues via the mucosal route. Depending on their specific virulence mechanisms and inherent metabolic preferences, bacteria invade certain cell types and body niches where they consequently deliver their cargo. Recently, the ability of attenuated strains of Salmonella, Shigella and Yersinia spp., as well as Listeria monocytogenes and invasive Escherichia coli, to deliver eukaryotic expression plasmids into mammalian cells in vitro and in vivo has been discovered. The great potential of bacteria-mediated transfer of plasmid DNA encoding vaccine antigens and/or therapeutic molecules was demonstrated in experimental animal models of infectious diseases, tumours and gene deficiencies. The exact mechanism of DNA transfer from the bacterial vector into the mammalian host is not yet completely known. The understanding of molecular events during bacterial DNA transfer, however, will further the development of bacterial vector systems with great promise for various clinical applications.
Acoustic cloak/anti-cloak device with realizable passive/active metamaterials (2012)

Abstract Utilizing the coordinate transformation method, together with exchange of variables between Maxwell's equations and the acoustic equations with axial-invariance in cylindrical coordinates, the acoustic parameters (anisotropic density and scalar bulk modulus) for an ideal cloak and an ideal anti-cloak are obtained. An anti-cloak allows the inside object to ‘see’ outside, but to be invisible from outside; whereas a cloak is invisible from outside, but ‘blind’ from inside. Utilizing a scattering algorithm developed in this paper, the pressure field calculation of the cloak/anti-cloak is performed and the concepts and characteristics of the acoustic cloak/anti-cloak are revisited. To be more easily achievable experimentally, a multilayered cloak/anti-cloak model with homogeneous isotropic materials is introduced, and its corresponding pressure distributions are calculated. Also, the total scattering cross-section curves for the multilayered cloak and anti-cloak over a certain frequency range are presented and compared. Finally, an active acoustic metamaterial made up of piezo-diaphragm cavity arrays is designed for the cloak/anti-cloak. Taking into account the coupling between adjacent cavity cells, a multi-control strategy for piezo-diaphragm cavity arrays is exploited, rendering possible wide ranges of effective densities and effective bulk moduli (or acoustic speeds), or even double-negative transformation medium (i.e. both density and bulk modulus parameters are negative). With such sets of active acoustic metamaterials, the cloak and anti-cloak may become both theoretically and experimentally realizable.
Structural and Kinetic Studies of a Cisplatin-modified DNA Icosamer Binding to HMG1 Domain B (1999)

The high mobility group (HMG) domain is a DNA-binding motif found in the non-histone chromosomal proteins, HMG1 and HMG2, and some transcription factors. Experimental evidence has demonstrated that HMG-domain proteins can play a role in sensitizing cells to the anticancer drug cisplatin. Fluorescence resonance energy transfer (FRET) experiments were performed in the present study to investigate structural changes that accompany complex formation between the HMG domain B of HMG1 and a cisplatin-modified, 20-base pair double-stranded DNA probe containing fluorescein and rhodamine tethered at its two ends. The binding affinity of HMG1 domain B for the cisplatin-modified DNA probe was investigated in fluorescence titration experiments, and a value of 60 +/- 30 nM was determined for the dissociation constant. Single photon counting methods were employed to measure the fluorescence lifetime of the fluorescein donor in the presence and absence of HMG1 domain B. These FRET experiments revealed a distance change that was used to estimate a bend angle of 80-95 degrees for the cisplatin-modified DNA upon protein binding. Stopped-flow fluorescence spectroscopic experiments afforded kinetic parameters for HMG1 domain B binding to the cisplatin-modified DNA probe, with kon = 1.1 +/- 0.1 x 10(9) M-1 s-1 and koff = 30 +/- 4 s-1.
Effects of dietary oleic, linoleic and alpha-linolenic acids on blood pressure, serum lipids, lipoproteins and the formation of eicosanoid precursors in patients with mild essential hypertension. (1990)

Forty-four male in-patients with mild essential hypertension were randomly allocated to three groups and put on diets supplemented with 60 ml/day of olive (n = 15), sunflowerseed (n = 15) or linseed oils (n = 14), respectively, for two weeks within a blind study. In the group receiving sunflowerseed oil an increase of linoleic acid in serum lipids could be observed, whereas arachidonic and eicosapentaenoic acids appeared unchanged in serum triglycerides and even significantly lower in cholesterol esters. The subjects ingesting the linseed oil-rich diet showed an increase of alpha-linolenic acid in serum lipids, whereas arachidonic and eicosapentaenoic acids remained unchanged in serum triglycerides. In cholesterol esters, however, arachidonic acid was significantly decreased and eicosapentaenoic acid appeared increased only to a low level of significance. In the group put on the olive oil-rich regimen only a significant fall of linoleic acid was obvious in serum triglycerides. The results might indicate a defective desaturation and elongation of linoleic and alpha-linolenic acids and, consequently, a slow formation of arachidonic and eicosapentaenoic acids in patients with mild essential hypertension, which should be considered in dietary studies. After the sunflowerseed oil-rich diet a significant decrease of total cholesterol, low density lipoprotein (LDL) cholesterol and the LDL/high density lipoprotein (HDL) cholesterol ratio was found. Systolic blood pressure during a psychophysiological stress test and urinary sodium excretion appeared significantly lower after the linoleic acid-rich diet. After the linseed oil-rich diet, in addition to total cholesterol, LDL cholesterol and the LDL/HDL cholesterol ratio, serum triglycerides and lecithin cholesterol acyl transferase (LCAT) activity were significantly depressed.(ABSTRACT TRUNCATED AT 250 WORDS)
<title>New optical configuration for flow cytometric sorting of aspherical cells</title> (1997)

The orthogonal axes of illumination, flow, and detection in conventional sorting flow cytometers can limit accuracy or throughput when making fluorescence measurements on a spherical cells. A new radially symmetric optical configuration has been designed to overcome these problems. Both illumination and fluorescence collection are performed by a single optical element which encircles the sample stream flow axis. Unlike existing epi-illumination flow cytometer designs, these optics are compatible with electrostatic sorting. The resolution of this system is currently being evaluated for DNA chromosome content measurement with an ultimate goal of separation of X- and Y- chromosome-bearing mammalian spermatozoa. We describe the new optical configuration and present preliminary results of instrument performance. Comparison with a conventional orthogonal optical geometry is made using fluorescent microspheres, chicken red blood cells and chinchilla sperm.
Gene delivery of neurturin to putamen and substantia nigra in Parkinson disease: A double‐blind, randomized, controlled trial (2015)

AAV2-neurturin delivery to the putamen and substantia nigra bilaterally in PD was not superior to sham surgery. The procedure was well tolerated, and there were no clinically significant adverse events related to AAV2-neurturin.
Cell-free Fetal DNA in Maternal Plasma (2008)

Since the discovery of cell-free fetal DNA (cffDNA) in peripheral maternal blood a decade ago, advances have been made in the identification and clinical application of these segments. Most studies of cffDNA have focused on using the segments for sex determination and fetal Rh genotyping, employing differences in genomic DNA between mother and fetus. Research has shifted toward targeting cffDNA for noninvasive aneuploidy detection. Over the last decade, a tremendous volume of research has focused on advancing the understanding of cffDNA structure, function, and detection. Despite this growing body of evidence, gaps in understanding of the biology of cffDNA and challenges in its isolation, enrichment, and processing have limited clinical applications in noninvasive prenatal diagnosis.