gebhart/patrepeval huggingface dataset:
Placental-derived stem cells: Culture, differentiation and challenges (2015)

Stem cell therapy is a promising approach to clinical healing in several diseases. A great variety of tissues (bone marrow, adipose tissue, and placenta) are potentially sources of stem cells. Placenta-derived stem cells (p-SCs) are in between embryonic and mesenchymal stem cells, sharing characteristics with both, such as non-carcinogenic status and property to differentiate in all embryonic germ layers. Moreover, their use is not ethically restricted as fetal membranes are considered medical waste after birth. In this context, the present review will be focused on the biological properties, culture and potential cell therapy uses of placental-derived stem cells. Immunophenotype characterization, mainly for surface marker expression, and basic principles of p-SC isolation and culture (mechanical separation or enzymatic digestion of the tissues, the most used culture media, cell plating conditions) will be presented. In addition, some preclinical studies that were performed in different medical areas will be cited, focusing on neurological, liver, pancreatic, heart, muscle, pulmonary, and bone diseases and also in tissue engineering field. Finally, some challenges for stem cell therapy applications will be highlighted. The understanding of the mechanisms involved in the p-SCs differentiation and the achievement of pure cell populations (after differentiation) are key points that must be clarified before bringing the preclinical studies, performed at the bench, to the medical practice.
AXL Is a Potential Target for Therapeutic Intervention in Breast Cancer Progression (2008)

Protein kinases play important roles in tumor development and progression. A variety of members of this family of signal transduction enzymes serve as targets for therapeutic intervention in cancer. We have identified the receptor tyrosine kinase (RTK) AXL as a potential mediator of motility and invasivity of breast cancer cells. AXL is expressed in most highly invasive breast cancer cells, but not in breast cancer cells of low invasivity. Ectopic expression of AXL was sufficient to confer a highly invasive phenotype to weakly invasive MCF7 breast cancer cells. Experimental inhibition of AXL signaling by a dominant-negative AXL mutant, an antibody against the extracellular domain of AXL, or short hairpin RNA knockdown of AXL decreased motility and invasivity of highly invasive breast cancer cells. To selectively interfere with cancer cell properties defining the rate of disease progression, we identified 3-quinolinecarbonitrile compounds, which displayed potent inhibitory activity against AXL and showed strong interference with motility and invasivity of breast cancer cells. Our findings validated the RTK AXL as a critical element in the signaling network that governs motility and invasivity of breast cancer cells, and allowed the identification of experimental anti-AXL small molecular inhibitors that represent lead substances for the development of antimetastatic breast cancer therapy.
Immunotherapy of Tumors with Autologous Tumor-Derived Heat Shock Protein Preparations (1997)

Immunotherapy of mice with preexisting cancers with heat shock protein preparations derived from autologous cancer resulted in retarded progression of the primary cancer, a reduced metastatic load, and prolongation of life-span. Treatment with heat shock protein preparations derived from cancers other than the autologous cancer did not provide significant protection. Spontaneous cancers (lung cancer and melanoma), chemically induced cancers (fibrosarcoma and colon carcinoma), and an ultraviolet radiation-induced spindle cell carcinoma were tested, and the results support the efficacy of autologous cancer-derived heat shock protein-peptide complexes in immunotherapy of cancers without the need to identify specific tumor antigenic epitopes.
Localization of nicotinic receptor subunit mRNAs in monkey brain by in situ hybridization (2000)

Nicotinic receptors are implicated in memory, learning, locomotor activity, and addiction. Identification of the specific receptor subtypes that mediate these behaviors is essential for understanding their role in central nervous system (CNS) function. Although expression of nicotinic receptor transcript has been studied in rodent brain, their localization in the monkey CNS, which may be a better model for the human brain, is not yet known. We therefore investigated the distribution of alpha4, alpha6, alpha7, beta2, beta3, and beta4 receptors subunit mRNAs in the monkey brain by using in situ hybridization. alpha4 and alpha7 mRNAs were very widely expressed, with a substantial degree of overlap in their distribution, except for the reticular nucleus of the thalamus in which alpha7 mRNA was much more prominently expressed. beta2 and beta4 mRNA were also widely distributed, although beta4 was more prominently localized in thalamic nuclei than beta2. The distribution of alpha6 and beta3 mRNA was very distinct from that of the other transcripts, being restricted to catecholaminergic nuclei, the cerebellum, and a few other areas. Although there were similarities in distribution of the nicotinic receptor subunit mRNAs in monkey and rodent brain, there were prominent differences in areas such as the caudate, putamen, locus coeruleus, medial habenula, and cerebellum. In fact, the distribution of alpha4 and alpha7 mRNAs in the monkey caudate and putamen was more similar to that reported in the human than rodent brain. These findings have implications for the development of drug therapies for neurological disorders, such as Alzheimer's and Parkinson's disease, in which nicotinic receptors are decreased.
Probing the heparin‐binding domain of human antithrombin III with V8 protease (1987)

From structural analysis on genetically abnormal and chemically modified human antithrombin III [Koide, T., Odani, S., Takahashi, K., Ono, T. and Sakuragawa, N. (1984) Proc. Natl Acad. Sci. USA 81, 289-293; Chang, J.-Y. and Tran, T. H., (1986) J. Biol. Chem. 261, 1174-1176; Blackburn, M. N., Smith, R. L., Carson, J. and Sibley, C. C. (1984) J. Biol. Chem. 259, 939-941], the heparin-binding site of antithrombin III has been suggested to be in the region of Pro-41, Arg-47 and Trp-49. In this study the heparin-binding site was probed by preferential cleavage of V8 protease on heparin-treated and non-treated native antithrombin III. The study has been based on the presumption that the heparin-binding site of antithrombin III is situated at exposed surface domain and may be preferentially attacked during limited proteolytic digestion. Partially digested antithrombin III samples were monitored by quantitative amino-terminal analysis and amino acid sequencing to identify the preferential cleavage sites. 1-h-digested antithrombin III was separated on HPLC and peptide fragments were isolated and characterized both qualitatively and quantitatively. The results reveal that Glu-Gly (residues 34-35), Glu-Ala (residues 42-43) and Glu-Leu (residues 50-51) are three preferential cleavage sites for V8 protease and their cleavage, especially the Glu-Ala and the Glu-Leu sites, was drastically inhibited when antithrombin III was preincubated with heparin. Both high-affinity and low-affinity antithrombin-III-binding heparins were shown to inhibit the V8 protease digestion of native antithrombin III, but the high-affinity sample exhibited a higher inhibition activity than the low-affinity heparin. These findings (a) imply that the segment containing residues 34-51 is among the most exposed region of native antithrombin III and (b) support the previous conclusions that this region may play a pivotal role in the heparin binding.
Time-domain electromagnetic migration in the solution of inverse problems (1997)

Time-domain electromagnetic (TDEM) migration is based on downward extrapolation of the observed field in reverse time. In fact, the migrated EM field is the solution of the boundary-value problem for the adjoint Maxwell's equations. The important question is how this imaging technique can be related to the solution of the geoelectrical inverse problem. In this paper we introduce a new formulation of the inverse problem, based on the minimization of the residual-field energy flow through the surface or profile of observations. We demonstrate that TDEM migration can be interpreted as the first step in the solution of this specially formulated TDEM inverse problem. However, in many practical situations this first step produces a very efficient approximation to the geoelectrical model, which makes electromagnetic migration so attractive for practical applications. We demonstrate the effectiveness of this approach in inverting synthetic and practical TDEM data.
Weak Binding of VX-478 to Human Plasma Proteins and Implications for Anti-Human Immunodeficiency Virus Therapy (1995)

VX-478 is a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) protease (Ki, 0.6 nM) and of HIV-1 replication in antiviral assays (IC90, 80 nM). The fractional binding of VX-478 to human plasma and to purified plasma proteins was determined by equilibrium dialysis and difference UV spectrophotometry. Binding to alpha 1-acid glycoprotein (89% at 2 microM total drug concentration, Kd of 4 microM) accounts for its fractional binding in plasma (93%). Stopped-flow spectrophotometry methods showed that binding is a reversible two-step process. The measured dissociation rate constant approaches 100 s-1. The antiviral effect of VX-478 was determined in the presence of 45% human plasma, in which the IC90 increased by 1.5-fold compared with control experiments in the presence of 15% fetal bovine serum. The effects of protein binding on the antiviral activity of VX-478 are minor, as expected for a weak drug-protein interaction.
Iron-binding fragments from the N-terminal and C-terminal regions of human lactoferrin (1978)

Digestion of lactoferrin with pepsin at pH3.0 gave an iron-binding half-molecule that represents the C-terminal part of the native protein. Tryptic or chymotryptic digestion of 30%-iron-saturated lactoferrin yielded the N- and C-terminal half molecules, which could be separated by DEAE-Sephadex chromatography. The N- and C-terminal fragments did not show any immunological cross-reaction. The carbohydrate of lactoferrin was distributed equally between the two fragments.
A high‐throughput screen for genes from castor that boost hydroxy fatty acid accumulation in seed oils of transgenic Arabidopsis (2006)

It is desirable to produce high homogeneity of novel fatty acids in oilseeds through genetic engineering to meet the increasing demands of the oleo-chemical industry. However, expression of key enzymes for biosynthesis of industrial fatty acids usually results in low levels of desired fatty acids in transgenic oilseeds. The abundance of derivatized fatty acids in their natural species suggests that additional genes are needed for high production in transgenic plants. We used the model oilseed plant Arabidopsis thaliana expressing a castor fatty acid hydroxylase (FAH12) to identify genes that can boost hydroxy fatty acid accumulation in transgenic seeds. Here we describe a high-throughput approach that, in principle, can allow testing of the entire transcriptome of developing castor seed endosperm by shotgun transforming a full-length cDNA library into an FAH12-expressing Arabidopsis line. The resulting transgenic seeds were screened by high-throughput gas chromatography. We obtained several lines transformed with castor cDNAs that contained increased amounts of hydroxy fatty acids in transgenic Arabidopsis. These cDNAs were then isolated by PCR and retransformed into the FAH12-expressing line, thus confirming their beneficial contributions to hydroxy fatty acid accumulation in transgenic Arabidopsis seeds. Although we describe an approach that is targeted to oilseed engineering, the methods we developed can be applied in many areas of plant biotechnology and functional genomic research.
Morphological Features of Cell Death (2004)

Cell death is discriminated into two main forms: apoptosis and necrosis. In contrast to necrosis, apoptosis is a regulated, energy-dependent form of cell death leading to phagocytosis of cellular remnants by neighboring cells. Characteristic morphological features of these two forms of cell death will be discussed and correlated to underlying molecular mechanisms.
Application of Phosphoramidate ProTide Technology Significantly Improves Antiviral Potency of Carbocyclic Adenosine Derivatives (2006)

We report the application of phosphoramidate pronucleotide (ProTide) technology to the antiviral agent carbocyclic L-d4A (L-Cd4A). The phenyl methyl alaninyl parent ProTide of L-Cd4A was prepared by Grignard-mediated phosphorochloridate reaction and resulted in a compound with significantly improved anti-HIV (2600-fold) and HBV activity. We describe modifications of the aryl, ester, and amino acid regions of the ProTide and how these changes affect antiviral activity and metabolic stability. Separate and distinct SARs were noted for HIV and HBV. Additionally, ProTides were prepared from the D-nucleoside D-Cd4A and the dideoxy analogues L-CddA and D-CddA. These compounds showed more modest potency improvements over the parent drug. In conclusion, the ProTide approach is highly successful when applied to L-Cd4A with potency improvements in vitro as high as 9000-fold against HIV. With a view to preclinical candidate selection we carried out metabolic stability studies using cynomolgus monkey liver and intestinal S9 fractions.
Osteopontin mRNA is expressed by smooth muscle-derived foam cells in human atherosclerotic lesions of the aorta. (1993)

Osteopontin is a phosphorylated, sialic acid-rich, noncollagenous bone matrix protein containing the Arg-Gly-Asp-Ser amino acid sequence responsible for cell adhesion. The protein strongly binds to hydroxyapatite and play an important role in calcification. Expression of osteopontin mRNA was analyzed in human aortic atherosclerotic lesion by Northern blot hybridization, as well as by in situ hybridization. The expression of osteopontin mRNA was detected in 24 out of 25 samples of aorta obtained from 17 autopsy cases, but not in one normal aortic sample. The magnitude of expression was proportional to the stage of atherosclerosis. In situ hybridization revealed that the cells expressing osteopontin mRNA were detected in the wall surrounding atheroma and closely associated with calcification. They were morphologically identified as foam cells and immunohistologically positive with HHF35, appearing to be derived from smooth muscle cells. These findings have suggested that smooth muscle cell-derived foam cells express osteopontin mRNA and play an important role in calcification of the atherosclerotic lesions.
Hypothyroidism Increases Substance P Concentrations in the Heterotopic Anterior Pituitary* (1988)

The regulatory effects of thyroid hormone on adenohypophysial substance P (SP) were studied in heterotopically implanted anterior pituitaries. Three or four anterior pituitaries from 21-day-old rat pups were implanted under the renal capsule in 175- to 200-g adult rats. The donor and recipient animals were sex matched. One week after implantation, animals were thyroidectomized or sham operated. A separate group of animals received daily T4 treatment (1.5 g/100 g, ip). After 2 weeks, the native and heterotopic pituitaries were assayed for SP, TSH, PRL, and LH. Thyroidectomy resulted in a 3- to 10-fold increase in the SP concentration in both the heterotopic and native pituitaries compared to euthyroid values. T4 treatment suppressed the SP levels in the heterotopic pituitaries of the thyroidectomized rats. In contrast to the reduction of TSH concentrations in native pituitaries in thyroidectomized animals vs. controls, TSH concentrations in the heterotopic pituitaries of thyroidectomized rats were approximately 10 times greater than those in euthyroid animals. PRL concentrations were unaffected by hypothyroidism in native and heterotopic pituitaries. Thyroidectomy resulted in a decrease in LH concentrations in the native anterior pituitary, without affecting LH concentrations in the implanted pituitary. These findings indicate that a direct link from the hypothalamus to the anterior pituitary is not required for the pituitary SP response to hypothyroidism.
Shopmobia: An Emotion-Based Shop Rating System (2013)

This work proposes a system for rating shops and for monitoring the cell phone-based emotion responses of customers in a shopping mall environment. To measure customer satisfaction in a shopping environment, a mobile, non-intrusive and comfortable wearable biosensor is used to measure the Electro dermal Activity (EDA) of the shopper. The users' proximity to the store is detected using NFC tags that report to the custom application on the mobile phone. The custom emotion recognition software analyses these streams of data in real-time and associates emotion levels to each event. The aim of this project is to demonstrate the possibility of using pervasive affective computing to explicate consumer behavior towards the stores in shopping malls. By triggering positive emotions through enhancing services and improving advertising campaigns, retailers can trigger positive emotional states, which ultimately contribute to a positive and memorable shopping experience.
MOOD DISORDERS IN STROKE PATIENTS: IMPORTANCE OF LOCATION OF LESION (1984)

In a selected group of right-handed patients with single stroke lesions of either the right (n = 14) or left (n = 22) hemisphere and no predisposing factors for psychiatric disorder, we found that the severity of depression was significantly increased in patients with left anterior lesions as opposed to any other lesion location. In addition, the severity of depression correlated significantly with proximity of the lesion on CT scan to the frontal pole in the left anterior group. The right hemisphere lesion group showed the reverse trend: patients with right posterior lesions were more depressed than patients with right anterior lesions, who were unduly cheerful and apathetic. These findings suggest that intrahemispheric lesion location is in some way related to mood disorder in stroke patients and that there is a graded effect of lesion location on severity of mood change. The neuroanatomy of the biogenic amine-containing pathways in the cerebral cortex might explain this graded effect and provide a neurochemical basis for the mood change.
Statin Treatment and Mortality in Bacterial Infections – A Systematic Review and Meta-Analysis (2010)

According to the meta-analysis of observational studies presented here, patients on statin therapy seem to have a better outcome in bacterial infections. However, the association did not reach statistical significance after adjustment for apparent publication bias. Thus, there is a great need for randomised controlled trials investigating the possible beneficial effect of statins in bacterial infections.
Antistasin, an Inhibitor of Coagulation and Metastasis, Binds to Sulfatide (Gal(3-SO4)/β1-1Cer) and Has a Sequence Homology with Other Proteins That Bind Sulfated Glycoconjugates (1989)

Antistasin, a 15-kDa salivary protein from the Mexican leech Haementeria officinalis, inhibits both blood coagulation and the metastasis of tumors (Tuszynski, G. P., Gasic, T. B., and Gasic, G. J. (1987) J. Biol. Chem. 262, 9718-9723). Antistasin binds to heparin-agarose, suggesting the protein interacts with sulfated glycoconjugates. The specificity of the interaction between antistasin and heparin was tested by measuring the binding of antistasin to various lipids and by comparing the ability of several charged glycoconjugates to inhibit binding. Of the lipids tested, antistasin binds with high affinity only to sulfatide (Gal(3-SO4)beta 1-1Cer) and does not bind to comparable levels of phospholipids, neutral glycosphingolipids, gangliosides, or cholesterol-3-SO4. The binding of antistasin to sulfatide is inhibited by dextran sulfate, fucoidan, and heparin, with I50 values of 1.5, 9.2, and 16 micrograms/ml, respectively. Comparable levels of chondroitin sulfates A, B, C, keratan sulfate, or hyaluronic acid do not inhibit binding. Comparisons of the amino acid sequences of antistasin and other sulfatide or heparin-binding proteins revealed a region of homology, based around the sequence Cys-Ser-Val-Thr-Cys-Gly-X-Gly-X-X-X-Arg-X-Arg, which may be a sulfated glycoconjugate binding domain. In addition, homologies were found with the alternate complement pathway protein properdin and coat proteins from malaria circumsporozoites and Herpes simplex I.
Phage-Induced Expression of CRISPR-Associated Proteins Is Revealed by Shotgun Proteomics in Streptococcus thermophilus (2012)

The CRISPR/Cas system, comprised of clustered regularly interspaced short palindromic repeats along with their associated (Cas) proteins, protects bacteria and archaea from viral predation and invading nucleic acids. While the mechanism of action for this acquired immunity is currently under investigation, the response of Cas protein expression to phage infection has yet to be elucidated. In this study, we employed shotgun proteomics to measure the global proteome expression in a model system for studying the CRISPR/Cas response in S. thermophilus DGCC7710 infected with phage 2972. Host and viral proteins were simultaneously measured following inoculation at two different multiplicities of infection and across various time points using two-dimensional liquid chromatography tandem mass spectrometry. Thirty-seven out of forty predicted viral proteins were detected, including all proteins of the structural virome and viral effector proteins. In total, 1,013 of 2,079 predicted S. thermophilus proteins were detected, facilitating the monitoring of host protein synthesis changes in response to virus infection. Importantly, Cas proteins from all four CRISPR loci in the S. thermophilus DGCC7710 genome were detected, including loci previously thought to be inactive. Many Cas proteins were found to be constitutively expressed, but several demonstrated increased abundance following infection, including the signature Cas9 proteins from the CRISPR1 and CRISPR3 loci, which are key players in the interference phase of the CRISPR/Cas response. Altogether, these results provide novel insights into the proteomic response of S. thermophilus, specifically CRISPR-associated proteins, upon phage 2972 infection.
Estimation of crystallinity in polyethylene by Raman spectroscopy (1993)

Abstract The quantitative determination of crystallinites of polyethylene samples from the analysis of vibrational bands due to δ(CH 2 ) twisting and v (CC) stretching in the Raman spectra between 950 and 1500 cm −1 was assessed. Several methods based on manual resolution of band envelopes and on computer‐derived information using Gaussian and Lorentzian profiles were compared. The major source of error was found to be the estimation of the amorphous and crystalline interphase content, α b . A new method for the determination of sample crystallinity is proposed based on the time‐dependent Fourier transform deconvolution of the spectral region between 950 and 1500 cm −1 , which takes into account the baseline corrections and the influence of vibrational band shoulders in this region to obtain consistent values of α a , α b and α c .