gebhart/patrepeval huggingface dataset:
Harm, ethics committees and the gene therapy death (2001)

<h3>Abstract</h3> <h3>Objective</h3> To assess the risk of meningioma associated with use of high dose cyproterone acetate, a progestogen indicated for clinical hyperandrogenism. <h3>Design</h3> Observational cohort study. <h3>Setting</h3> Data from SNDS, the French administrative healthcare database, between 2007 and 2015. <h3>Participants</h3> 253 777 girls and women aged 7-70 years living in France who started cyproterone acetate between 2007 and 2014. Participants had at least one reimbursement for high dose cyproterone acetate and no history of meningioma or benign brain tumour, or long term disease status. Participants were considered to be exposed when they had received a cumulative dose of at least 3 g during the first six months (139 222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114 555 participants). 10 876 transgender participants (male to female) were included in an additional analysis. <h3>Main outcome measure</h3> Surgery (resection or decompression) or radiotherapy for one or more intracranial meningiomas. <h3>Results</h3> Overall, 69 meningiomas in the exposed group (during 289 544 person years of follow-up) and 20 meningiomas in the control group (during 439 949 person years of follow-up) were treated by surgery or radiotherapy. The incidence of meningioma in the two groups was 23.8 and 4.5 per 100 000 person years, respectively (crude relative risk 5.2, 95% confidence interval 3.2 to 8.6; adjusted hazard ratio 6.6, 95% confidence interval 4.0 to 11.1). The adjusted hazard ratio for a cumulative dose of cyproterone acetate of more than 60 g was 21.7 (10.8 to 43.5). After discontinuation of cyproterone acetate for one year, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group. In a complementary analysis, 463 women with meningioma were observed among 123 997 already using cyproterone acetate in 2006 (risk of 383 per 100 000 person years in the group with the highest exposure in terms of cumulative dose). Meningiomas located in the anterior skull base and middle skull base, particularly the medial third of the middle skull base, involving the spheno-orbital region, appeared to be specific to cyproterone acetate. An additional analysis of transgender participants showed a high risk of meningioma (three per 14 460 person years; 20.7 per 100 000 person years). <h3>Conclusions</h3> A strong dose-effect relation was observed between use of cyproterone acetate and risk of intracranial meningiomas. A noticeable reduction in risk was observed after discontinuation of treatment.
13C‐breath tests for clinical investigation of liver mitochondrial function (2010)

Breath tests to assess in vivo mitochondrial function in humans represent a potentially useful diagnostic and prognostic tool in clinical investigation.
Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant (2011)

Viral infections cause morbidity and mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. We and others have successfully generated and infused T-cells specific for Epstein Barr virus (EBV), cytomegalovirus (CMV) and Adenovirus (Adv) using monocytes and EBV-transformed lymphoblastoid cell (EBV-LCL) gene-modified with an adenovirus vector as antigen presenting cells (APCs). As few as 2x10(5)/kg trivirus-specific cytotoxic T lymphocytes (CTL) proliferated by several logs after infusion and appeared to prevent and treat even severe viral disease resistant to other available therapies. The broader implementation of this encouraging approach is limited by high production costs, complexity of manufacture and the prolonged time (4-6 weeks for EBV-LCL generation, and 4-8 weeks for CTL manufacture--total 10-14 weeks) for preparation. To overcome these limitations we have developed a new, GMP-compliant CTL production protocol. First, in place of adenovectors to stimulate T-cells we use dendritic cells (DCs) nucleofected with DNA plasmids encoding LMP2, EBNA1 and BZLF1 (EBV), Hexon and Penton (Adv), and pp65 and IE1 (CMV) as antigen-presenting cells. These APCs reactivate T cells specific for all the stimulating antigens. Second, culture of activated T-cells in the presence of IL-4 (1,000 U/ml) and IL-7 (10 ng/ml) increases and sustains the repertoire and frequency of specific T cells in our lines. Third, we have used a new, gas permeable culture device (G-Rex) that promotes the expansion and survival of large cell numbers after a single stimulation, thus removing the requirement for EBV-LCLs and reducing technician intervention. By implementing these changes we can now produce multispecific CTL targeting EBV, CMV, and Adv at a cost per 10(6) cells that is reduced by >90%, and in just 10 days rather than 10 weeks using an approach that may be extended to additional protective viral antigens. Our FDA-approved approach should be of value for prophylactic and treatment applications for high risk allogeneic HSCT recipients.
Obesity‐related leptin regulates Alzheimer's Aβ (2004)

Abeta peptide is the major proteinateous component of the amyloid plaques found in the brains of Alzheimer's disease (AD) patients and is regarded by many as the culprit of the disorder. It is well documented that brain lipids are intricately involved in Abeta-related pathogenic pathways. An important modulator of lipid homeostasis is the pluripotent peptide leptin. Here we demonstrate leptin's ability to modify Abeta levels in vitro and in vivo. Similar to methyl-beta-cyclodextrin, leptin reduces beta-secretase activity in neuronal cells possibly by altering the lipid composition of membrane lipid rafts. This phenotype contrasts treatments with cholesterol and etomoxir, an inhibitor of carnitine-palmitoyl transferase-1. Conversely, inhibitors of acetyl CoA carboxylase and fatty acid synthase mimicked leptin's action. Leptin was also able to increase apoE-dependent Abeta uptake in vitro. Thus, leptin can modulate bidirectional Abeta kinesis, reducing its levels extracellularly. Most strikingly, chronic administration of leptin to AD-transgenic animals reduced the brain Abeta load, underlying its therapeutic potential.
cGMP-Dependent Protein Kinase I Mediates the Negative Inotropic Effect of cGMP in the Murine Myocardium (2002)

To study the role of cGMP-dependent protein kinase I (cGKI) for cardiac contractility, force of contraction (F(c)) was studied in electrically driven heart muscle from wild-type (WT) mice and from conventional and conditional cGKI knockout mice. Both 8-Br-cGMP and 8-pCPT-cGMP reduced Fc in cardiac muscle from juvenile WT but not from juvenile cGKI-null mutants. Similarly, the cGMP analogues reduced F(c) in forskolin-stimulated ventricular muscle from WT mice but not from cGKI-null mutants. In contrast, carbachol reduced F(c) in both groups of animals. 8-Br-cGMP reduced F(c) also in heart muscle from adult WT mice but not from adult cardiomyocyte-specific cGKI-knockout mice. These results demonstrate that cGKI mediates the negative inotropic effect of cGMP in the myocardium of juvenile and adult mice.
An N2S2 Bifunctional Chelator for Technetium-99m and Rhenium:  Complexation, Conjugation, and Epimerization to a Single Isomer (1999)

A bifunctional chelator 6 was prepared bearing an N2S2 core for binding rhenium or technetium and a carboxylic acid group for conjugation to amino groups of biomolecules. Complexation of 6 with rhenium(V) resulted in two kinetic isomers, anti-7 and syn-7, being formed in approximately equal amounts. Epimerization with 0.5 M NaOH yields a single isomer anti-7, as determined by NMR spectroscopy and single-crystal X-ray analysis. The 99mTc complex was prepared at the tracer level by reaction of the ligand with 99mTcO4-, tin(II) chloride and sodium gluconate giving a mixture of two isomers, but showing a preference for the anti isomer. Chelation in the presence of 1 M NaOH results in anti-8 being formed as the sole product. The bifunctional ability of the ligand was explored by amide formation with (S)-alpha-phenethylamine, either by direct DCC coupling or through the N-hydroxy succinimidyl ester 9 intermediate. The deprotected bioconjugate 11 was complexed with rhenium, yielding similar amounts of two isomeric rhenium complexes, anti-12 and syn-12, which were isolated and characterized by NMR spectroscopy. Treatment of the kinetic mixture of anti-12 and syn-12 with 1 M NaOH resulted in quantitative conversion to a single rhenium complex anti-12. With technetium-99m in 0.1 M sodium acetate, bioconjugate 11 yielded both technetium-99m complexes anti-13 and syn-13, in a 2:1 ratio, respectively. In contrast, complexation in the presence of 1 M NaOH gave only one technetium-99m complex, assigned the structure anti-13.
Immunofluorescent localization of the transforming protein of Rous sarcoma virus with antibodies against a synthetic src peptide. (1982)

Antisera were raised against a synthetic peptide (src-c) containing the six COOH-terminal amino acids of p60src, the transforming protein of Rous sarcoma virus (RSV). Antibodies specific for the src-c peptide were purified by affinity chromatography and then used to study the location of p60src in transformed cells. The distribution of p60src was compared to that of vinculin, a candidate cytoskeletal substrate of p60src, by indirect double immunofluorescence microscopy. In RSV-transformed rat, mouse, and chicken cells, an extensive codistribution of p60src with vinculin was observed. Both proteins were concentrated in the few remaining focal adhesion plaques, in transformation-induced rosette clusters at the ventral cell surface, and in cell-cell contact areas. In addition, antibodies to both proteins stained the cytoplasm diffusely. In all cells examined, the immunofluorescent staining patterns produced by antibodies to the src-c peptide were indistinguishable from those obtained by immunolabeling of p60src with sera from RSV-infected tumor-bearing rabbits. The excellent agreement of the results obtained with two completely independent antibody preparations indicates strongly that the observed immunolabeling patterns correctly define the intracellular distribution of p60src. The significance of the intracellular location of p60src to the transforming activities of the protein is discussed.
Secure database-as-a-service with Cipherbase (2013)

Data confidentiality is one of the main concerns for users of public cloud services. The key problem is protecting sensitive data from being accessed by cloud administrators who have root privileges and can remotely inspect the memory and disk contents of the cloud servers. While encryption is the basic mechanism that can leveraged to provide data confidentiality, providing an efficient database-as-a-service that can run on encrypted data raises several interesting challenges. In this demonstration we outline the functionality of Cipherbase --- a full fledged SQL database system that supports the full generality of a database system while providing high data confidentiality. Cipherbase has a novel architecture that tightly integrates custom-designed trusted hardware for performing operations on encrypted data securely such that an administrator cannot get access to any plaintext corresponding to sensitive data.
Acoustic tracking of a freely drifting sonobuoy field (2002)

This paper develops an acoustic inversion algorithm to track a field of freely drifting sonobuoys using travel-time measurements from a series of nonsimultaneous impulsive sources deployed around the field. In this scenario, the time interval between sources can be sufficiently long that significant independent movement of the individual sonobuoys occurs. In addition, the source transmission instants are unknown, and the source positions and initial sonobuoy positions are known only approximately. The formulation developed here solves for the track of each sonobuoy (parametrized by the sonobuoy positions at the time of each source transmission), allowing arbitrary, independent sonobuoy motion between transmissions, as well as for the source positions and transmission instants. This leads to a strongly underdetermined inverse problem. However, regularized inversion provides meaningful solutions by incorporating a priori information consisting of prior estimates (with uncertainties) for the source positions and initial sonobuoy positions, and a physical model for preferred sonobuoy motion. Several models for sonobuoy motion are evaluated, with the best results obtained by minimizing the second spatial derivative of the tracks to obtain the minimum-curvature or smoothest track, subject to fitting the acoustic data to a statistically appropriate level.
Does Head Cooling With Mild Systemic Hypothermia Affect Requirement for Blood Pressure Support? (2009)

Mild systemic hypothermia did not affect arterial blood pressure or initial treatment with inotropes or volume in infants with moderate-to-severe encephalopathy but was associated with an apparent change in physician behavior, with slower withdrawal of therapy in cooled infants.
An analysis of ecdysone receptor domains required for heterodimerization with ultraspiracle (1999)

We have prepared several truncated versions of the Choristoneura fumiferana ecdysone receptor (CfEcR) cDNA to identify domains required for heterodimerization with C. fumiferana ultraspiracle (CfUSP). The CfEcR protein containing all six domains bound to hsp27 EcRE in the presence of CfUSP protein. The only regions that could be deleted from CfEcR without losing DNA binding activity were A/B and F domains as well as a 29 amino acid region located at the C–terminal end of the E domain. This suggests that the minimum region required for DNA binding is a 363 amino acid peptide spanning C, D, and part of E domains. The CfEcR protein containing all six domains bound ponasterone A, in the presence of CfUSP protein. Removal of the F domain and the C-terminal 12 amino acids in the E domain completely abolished ponasterone A binding. Removal of A/B and C domains did not affect ligand binding. However, deleting the D domain abolished ligand binding completely. The minimum region required for ligand binding is a 333 amino acid peptide spanning the D, E, and F domains. The A/B region is the only domain that can be deleted without affecting both DNA and ligand binding of CfEcR. These results suggest that CfEcR has two sub domains in the D and E domains that are necessary for heterodimerization with the CfUSP protein. Arch. Insect Biochem. Physiol. 41:61–70, 1999. © 1999 Wiley-Liss, Inc.
In vivo invasion of modified chorioallantoic membrane by tumor cells: the role of cell surface-bound urokinase. (1988)

The ability of the chick embryo chorioallantoic membrane (CAM) to withstand invasion by tumor cells can be intentionally compromised by altering its morphological integrity. Using a newly developed quantitative assay of invasion we showed that intact CAMs were completely resistant to invasion by tumor cells, wounded CAMs did not pose a barrier to penetration, and CAMs that were wounded and then allowed to reseal displayed partial susceptibility to invasion. The invasion of resealed CAMs required catalytically active plasminogen activator (PA) of the urokinase type (uPA); the invasive efficiency of tumor cells was reduced by 75% when tumor uPA activity or tumor uPA production was inhibited. The invasive ability of human tumor cells, which have surface uPA receptors but which do not produce the enzyme, could be augmented by saturating their receptors with exogenous uPA. The mere stimulation of either uPA or tissue plasminogen activator production, in absence of binding to cell receptors, did not result in an enhancement of invasiveness. These findings suggest that the increased invasive potential of tumor cells is correlated with cell surface-associated proteolytic activity stemming from the interaction between uPA and its surface receptor.
Depletion and depolarizing effects in ferroelectric thin films and their manifestations in switching and fatigue (1995)

Abstract The manifestations of semiconductor depletion and depolarizing effects in switching and fatigue are studied and compared. It is shown that these effects play important but quite different roles in switching. The depletion effect strongly influences the values of the coercive field, Ec, and is responsible for its filmthickness dependence. The depolarizing effect influences significantly other parameters of the hysteresis loops. It is shown that the inverse thickness dependence of Ec can not be attributed to the presence of a non-switching layer. Contribution of the effects in question to fatigue of the loop parameters is discussed.
Cell Adhesion Molecules (1983)

It has been proposed that cell-cell recognition occurs by means of local cell surface modulation of a small number of proteins rather than by expression of large numbers of different cell surface markers. Several different cell adhesion molecules (CAM's) have now been found in a number of vertebrate species in different tissues such as liver and striated muscle and even in a single complex structure such as the brain, where different molecules specific for neurons and glia have been identified. The neuron-specific molecule is involved in early embryonic events but also mediates neurite fasciculation, neuromuscular interaction, and orderly layering of neural tissue. It undergoes local surface modulation with loss of sialic acid during development. A failure of this process is closely correlated with connectional disorders in the staggerer mutant of the mouse. The accumulated data on this and other CAM's favor modulation theories rather than strict chemoaffinity theories of cell-cell recognition.
New Lytic Peptides Based on thed,l-Amphipathic Helix Motif Preferentially Kill Tumor Cells Compared to Normal Cells (2003)

Despite significant advances in cancer therapy, there is an urgent need for drugs with a new mode of action that will preferentially kill cancer cells. Several cationic antimicrobial peptides, which bind strongly to negatively charged membranes, were shown to kill cancer cells slightly better than normal cells. This was explained by a slight increase (3−9%) in the level of the negatively charged membrane phosphatidylserine (PS) in many cancer cells compared to their normal counterparts. Unfortunately, however, these peptides are inactivated by serum components. Here we synthesized and investigated the anticancer activity and the role of peptide charge, peptide structure, and phospholipid headgroup charge on the activity of a new group of diastereomeric lytic peptides (containing d- and l-forms of leucine and lysine; 15−17 amino acids long). The peptides are highly toxic to cancer cells, to a degree similar to or larger than that of mitomycin C. However, compared with mitomycin C and many native antimicrobial peptides, they are more selective for cancer cells. The peptides were investigated for (i) their binding to mono- and bilayer membranes by using the surface plasmon resonance (SPR) technique, (ii) their ability to permeate membranes by using fluorescence spectroscopy, (iii) their structure and their effect on the lipid order by using ATR-FTIR spectroscopy, and (iv) their ability to bind to cancer versus normal cells by using confocal microscopy. The data suggest that the peptides disintegrate the cell membrane in a detergent-like manner. However, in contrast to native antimicrobial peptides, the diastereomers bind and permeate similarly zwitterionic and PS-containing model membranes. Therefore, cell selectivity is probably determined mainly by improved electrostatic attraction of the peptides to acidic components on the surface of cancer cells (e.g., O-glycosylation of mucines). The simple composition of the diastereomeric peptides and their stability regarding enzymatic degradation by serum components make them excellent candidates for new chemotherapeutic drugs.
Current-induced light emission from a porous silicon device (1991)

Experiments with light-emitting porous silicon (LEPOS) are described. The porous silicon was made from n-type silicon by anodization in an electrolytic cell by HF with an applied electrical current. Visible light emission was achieved by irradiation with ultraviolet light. Visible electroluminescence (EL) was achieved by applying a DC or AC voltage to a solid-state contact on top of the porous layer. Optical spectra from both experiments are shown.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Criticism of Lednev's mechanism for the influence of weak magnetic fields on biological systems (1992)

V. V. Lednev has proposed a mechanism that he suggests would allow very weak magnetic fields, at the cyclotron resonance frequency for Ca2+ ions in the earth's field, to induce biological effects. I show that for four independent reasons no such mechanism can operate.
Biomimetic self-assembled nanofibers (2006)

Peptide-amphiphiles, peptides to which a non-peptidic hydrophobic moiety has been added to the N or C terminal end, have been demonstrated to be a versatile method for simultaneously controlling nanostructure and chemical functionality. These amphiphiles are able to self-assemble, in a controlled fashion, into nanofibers with diameter between 6-10 nm and with length in excess of 1000 nm. At proper concentration these nanofibers form a viscoelastic gel capable of entrapping living cells and eliciting specific responses from them. Because of the flexibility of the display of chemical functionality on a controlled nanofibrous scaffold, applications for peptide-amphiphiles have been proposed including heterogeneous catalysis, nanoelectronics, drug delivery, and tissue engineering.
A flexible protein linker improves the function of epitope‐tagged proteins in Saccharomyces cerevisiae (2006)

Epitope tagging permits the detection of proteins when protein-specific antibodies are not available. However, the epitope tag can reduce the function of the tagged protein. Here we describe a cassette that can be used to introduce an eight amino acid flexible linker between multiple Myc epitopes and the open reading frame of a given gene. We show that inserting the linker improves the in vivo ability of the telomerase subunits Est2p and Est1p to maintain telomere length. The methods used here are generally applicable to improve the function of tagged proteins in both Saccharomyces cerevisiae and Schizosaccharomyces pombe.