gebhart/patrepeval huggingface dataset:
Myelosuppressive conditioning is required to achieve engraftment of pluripotent stem cells contained in moderate doses of syngeneic bone marrow (1994)

We have investigated the requirement for whole body irradiation (WBI) to achieve engraftment of syngeneic pluripotent hematopoietic stem cells (HSCs). Recipient B6 (H-2b; Ly-5.2) mice received various doses of WBI (0 to 3.0 Gy) and were reconstituted with 1.5 x 10(7) T-cell-depleted (TCD) bone marrow cells (BMCs) from congenic Ly-5.1 donors. Using anti-Ly-5.1 and anti-Ly-5.2 monoclonal antibodies and flow cytometry, the origins of lymphoid and myeloid cells reconstituting the animals were observed over time. Chimerism was at least initially detectable in all groups. However, between 1.5 and 3 Gy WBI was the minimum irradiation dose required to permit induction of long-term (at least 30 weeks), multilineage mixed chimerism in 100% of recipient mice. In these mice, stable reconstitution with approximately 70% to 90% donor-type lymphocytes, granulocytes, and monocytes was observed, suggesting that pluripotent HSC engraftment was achieved. About 50% of animals conditioned with 1.5 Gy WBI showed evidence for donor pluripotent HSC engraftment. Although low levels of chimerism were detected in untreated and 0.5-Gy-irradiated recipients in the early post-BM transplantation (BMT) period, donor cells disappeared completely by 12 to 20 weeks post-BMT. BM colony assays and adoptive transfers into secondary lethally irradiated recipients confirmed the absence of donor progenitors and HSCs, respectively, in the marrow of animals originally conditioned with only 0.5 Gy WBI. These results suggest that syngeneic pluripotent HSCs cannot readily engraft unless host HSCs sustain a significant level of injury, as is induced by 1.5 to 3.0 Gy WBI. We also attempted to determine the duration of the permissive period for syngeneic marrow engraftment in animals conditioned with 3 Gy WBI. Stable multilineage chimerism was uniformly established in 3-Gy-irradiated Ly-5.2 mice only when Ly-5.1 BMC were injected within 7 days of irradiation, suggesting that repair of damaged host stem cells or loss of factors stimulating engraftment may prevent syngeneic marrow engraftment after day 7.
Superelastic leg design optimization for an endoscopic capsule with active locomotion (2008)

Nowadays Nitinol structures are accepted and highly exploited in the medical field. Therefore, studying the mechanical properties of this material—which is not trivial by considering the thermal behaviour of the alloy—is very important in order to get quantitative data for a reliable design of novel Nitinol components. In particular, this study focuses on the design optimization of superelastic Nitinol legs to be integrated into an endoscopic capsule for biomedical applications. The leg is provided with an elastic knee that adds a passive degree of freedom to the structure; this solution allows us to achieve a good locomotion adaptability in the unstructured environment of the gastrointestinal tract, characterized by different diameters. First, the mechanical behaviour of Nitinol was analysed. Tensile tests were carried on in order to extract the peculiar stress–strain curve of the material. The hysteretic behaviour was observed through 100 loading–unloading cycles. The acquired data were used to model the leg design by finite element methods (FEM) and to estimate the stress–strain internal state during the operative work. These data were used to optimize the leg, which was finally fabricated and tested, demonstrating an improvement of five times regarding the number of cycles before leg failure.
Age-Specific Prevalence of Serum Antibodies to the Invasion Plasmid and Lipopolysaccharide Antigens of Shigella Species in Chilean and North American Populations (1992)

Shigella species have virulence plasmids that encode outer membrane proteins (invasion plasmid antigens, Ipa) associated with pathogenicity. Western blots were used to detect antibodies to Ipa in sera from 390 Chilean children, and these responses were compared with those of a US population of infants and adults. Antibodies to lipopolysaccharide (LPS) of Plesiomonas shigelloides and Shigella flexneri 2a were measured by ELISA. Among the Chileans, there was an age-related acquisition of Ipa antibodies, with 28% of 1-year-olds and 100% of children greater than or equal to 10 years showing positive responses. In contrast, none of the US infants and only 38% of the adults had antibodies to Ipa. Levels of LPS antibodies were also found to increase in an age-related manner among the Chileans. These results corroborate findings of previous epidemiologic studies which show that Shigella infections are endemic in Chile, as in other developing countries. The measurement of Ipa and LPS antibodies is a useful seroepidemiologic tool for investigating previous exposure to Shigella species in populations.
Molecular characterization of the low-affinity IgE receptor Fc epsilonRII/CD23 expressed by human eosinophils (1998)

CD23/Fc epsilonRII, the low-affinity receptor for IgE, is a pluripotent molecule with pleiotropic effects on cell activation and proliferation, antigen presentation and IgE synthesis. Initial investigations have suggested that CD23 expression was restricted to B lymphocytes and macrophages, but a much wider cell distribution is now acknowledged. Despite experimental evidence suggesting that human eosinophils could express the low-affinity IgE receptor Fc epsilonRII/CD23 with biological functions, no molecular cloning data have been reported until now. Whereas in situ hybridization confirmed the expression of CD23 mRNA in eosinophils, RT-PCR analysis of human eosinophil cDNA derived from a cDNA library revealed the presence of CD23, totally homologous with the CD23 a and b sequences. Eosinophils from different hypereosinophilic patients as well as the eosinophilic leukemia cell line EoL-3, analyzed by RT-PCR, expressed both CD23 a and b isoforms. In situ RT-PCR confirmed that mRNA corresponding to CD23 a and b isoforms was detected in human eosinophils. Finally, immunocytochemistry allowed us to show a differential expression of Fc epsilonRII/CD23 and Fc epsilonRI by subpopulations of eosinophils, with a preferential expression of Fc epsilonRII/CD23 in the hypodense population. These results provide definitive evidence that the low-affinity IgE receptor (Fc epsilonRII) synthesized by human eosinophils is identical to the CD23 molecule expressed on B cells, and that the two CD23 isoforms a and b can be expressed by eosinophils.
Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4 (1994)

Heparin-induced thrombocytopenia (HIT) is an important complication of heparin therapy. Although there is general agreement that platelet activation in vitro by the HIT IgG is mediated by the platelet Fc receptor, the interaction among the antibody, heparin, and platelet membrane components is uncertain and debated. In this report, we describe studies designed to address these interactions. We found, as others have noted, that a variety of other sulfated polysaccharides could substitute for heparin in the reaction. Using polysaccharides selected for both size and charge, we found that reactivity depended on two independent factors: a certain minimum degree of sulfation per saccharide unit and a certain minimum size. Hence, highly sulfated but small (< 1,000 daltons) polysaccharides were not reactive nor were large but poorly sulfated polysaccharides. The ability of HIT IgG to recognize heparin by itself was tested by Ouchterlony gel diffusion, ammonium sulfate and polyethylene glycol precipitation, and equilibrium dialysis. No technique demonstrated reactivity. However, when platelet releasate was added to heparin and HIT IgG, a 50-fold increase in binding of radio-labeled heparin to HIT IgG was observed. The releasate was then depleted of proteins capable of binding to heparin by immunoaffinity chromatography. Only platelet factor 4-immunodepleted releasate lost its reactivity with HIT IgG and heparin. Finally, to determine whether the reaction occurred on the surface of platelets or in the fluid phase, washed platelets were incubated with HIT IgG or heparin and after a wash step, heparin or HIT IgG was added, respectively. Reactivity was only noted when platelets were preincubated with heparin. Consistent with these observations was the demonstration of the presence of PF4 on platelets using flow cytometry. These studies indicate that heparin and other large, highly sulfated polysaccharides bind to PF4 to form a reactive antigen on the platelet surface. HIT IgG then binds to this complex with activation of platelets through the platelet Fc receptors.
Mechanism of Inactivation of Plasminogen Activator Inhibitor-1 by a Small Molecule Inhibitor (2007)

The inactivation of plasminogen activator inhibitor-1 (PAI-1) by the small molecule PAI-1 inhibitor PAI-039 (tiplaxtinin) has been investigated using enzymatic analysis, direct binding studies, site-directed mutagenesis, and molecular modeling studies. Previously PAI-039 has been shown to exhibit in vivo activity in various animal models, but the mechanism of inhibition is unknown. PAI-039 bound specifically to the active conformation of PAI-1 and exhibited reversible inactivation of PAI-1 in vitro. SDS-PAGE indicated that PAI-039 inactivated PAI-1 predominantly through induction of PAI-1 substrate behavior. Preincubation of PAI-1 with vitronectin, but not bovine serum albumin, blocked PAI-039 activity while analysis of the reciprocal experiment demonstrated that preincubation of PAI-1 with PAI-039 blocked the binding of PAI-1 to vitronectin. Together, these data suggest that the site of interaction of the drug on PAI-1 is inaccessible when PAI-1 is bound to vitronectin and may overlap with the PAI-1 vitronectin binding domain. This was confirmed by site-directed mutagenesis and molecular modeling studies, which suggest that the binding epitope for PAI-039 is localized adjacent to the previously identified interaction site for vitronectin. Thus, these studies provide a detailed characterization of the mechanism of inhibition of PAI-1 by PAI-039 against free, but not vitronectin-bound PAI-1, suggesting for the first time a novel pool of PAI-1 exists that is vulnerable to inhibition by inactivators that bind at the vitronectin binding site.
Enhancement of antigen- and mitogen-induced human T lymphocyte proliferation by tumor necrosis factor- alpha . (1988)

The capacity of human recombinant tumor necrosis factor-alpha (rTNF alpha) to modulate human T cell proliferation was examined. To examine the effect of rTNF alpha on the responding T cell directly, T cell activation was studied in the absence of viable accessory cells (AC). Highly purified AC-depleted peripheral blood T4 or T8 cells were stimulated with immobilized monoclonal antibodies to the cluster of differentiation (CD)3 molecular complex, an AC-independent stimulus. rTNF alpha augmented anti-CD3-stimulated T4 and T8 cell proliferation. The capacity of rTNF alpha to enhance T cell proliferation varied inversely with the density of immobilized anti-CD3 and the number of responding cells in each culture. The capacity of rTNF alpha to enhance antigen-induced T4 cell proliferation was also examined. Antigen-bearing paraformaldehyde-fixed antigen-presenting cells induced modest T4 cell proliferation when cultured in flat-bottomed wells; this response was enhanced by rTNF alpha. The results demonstrate that rTNF alpha has direct effects on T cells, facilitating their capacity to proliferate in response to mitogens and antigens. These data indicate that rTNF alpha may play an immunoregulatory role, enhancing the proliferation of T lymphocytes.
Calcium(ii)-catalyzed enantioselective conjugate additions of amines (2018)

The direct enantioselective chiral calcium(ii)·phosphate complex (Ca[CPA]<sub>2</sub>)-catalyzed conjugate addition of unprotected alkyl amines to maleimides was developed. This mild catalytic system represents a significant advance towards the general convergent asymmetric amination of α,β-unsaturated electrophiles, providing medicinally relevant chiral aminosuccinimide products in high yields and enantioselectivities. Furthermore, the catalyst can be reused directly from a previously chromatographed reaction and still maintain both high yield and selectivity.
Superparamagnetic iron oxide nanoparticles functionalized with peptides by electrostatic interactions (2006)

Superparamagnetic iron oxide nanoparticles coated with dextran were functionalized with negatively charged functionalities in order to connect specific peptide labels by electrostatic interactions. Peptide binding on the nanoparticles was indicated by HR-TEM, an electrospray scanning mobility particle sizer, and fluorescence measurements.
Cell aggregation and neurite growth in gels of extracellular matrix molecules (1994)

Components of the extracellular matrix are believed to guide both nerve cells and neurites to their targets during embryogenesis and, therefore, might be useful for controlling regeneration of nervous tissue in adults. To study the influence of extracellular conditions on neurite outgrowth and cell motility, PC12 cells were suspended in three-dimensional gels containing (i) collagen (0.4 to 2 mg/mL), (ii) collagen (1 mg/mL) with added fibronectin or laminin (1 to 100 mug/mL), and (iii) agarose (7 mg/mL) with added collagen (0.001 to 1 mg/mL). Neurite outgrwoth was stimulated with nerve growth factor (NGF) and both the extent of neurite outgrowth ad cell aggregation were quantitated over 10 to 12 days in culture. The extent of neurite outgrowth was greatest at the lowest collagen concentration tested (0.4 mg/mL) and decreased with increasing concentration. The addition of laminin or fibronectin altered the extent of neurite outgrowth in collagen gels, but the differences were small. Although no neurite growth was observed in pure agarose gels, considerable neurite outgrowth occurred with the addition of small amounts (>/=0.01 mg/mL) of collagen. Mean aggregate size increased more quickly in gels with lower concentrations of collagen. For cells in 1.0 mg/mL collagen, a four- to fivefold increase in aggregate volume was seen between days 2 and 10 o the culture period, whereas the increase in DNA content during this same period was less than twofold, suggesting that the cells were aggregating, not multiplying. These results suggest that the composition of the matrix supporting nerve cells has a significant effect on both neurite outgrowth and cell motility. (c) 1994 John Wiley & Sons, Inc.
Interleukin 17, a nitric oxide-producing cytokine with a peroxynitrite-independent inhibitory effect on proteoglycan synthesis. (2002)

These data showed that NO is weakly involved in the IL-17 mediated inhibition of proteoglycan synthesis in rat. NO overload may not be predictive of any inhibitory effect on cartilage anabolism, but instead superoxide is a key regulator of NO contribution to chondrocyte dysfunction. Since IL-17 is a NO-producing cytokine with additive effects when combined with IL-1, it may play a pivotal role in cartilage destruction during rheumatoid arthritis, for which infiltrating cells produce high levels of superoxide and proinflammatory cytokines.
Molecular Diversity of Midbrain Development in Mouse, Human, and Stem Cells (2016)

Understanding human embryonic ventral midbrain is of major interest for Parkinson's disease. However, the cell types, their gene expression dynamics, and their relationship to commonly used rodent models remain to be defined. We performed single-cell RNA sequencing to examine ventral midbrain development in human and mouse. We found 25 molecularly defined human cell types, including five subtypes of radial glia-like cells and four progenitors. In the mouse, two mature fetal dopaminergic neuron subtypes diversified into five adult classes during postnatal development. Cell types and gene expression were generally conserved across species, but with clear differences in cell proliferation, developmental timing, and dopaminergic neuron development. Additionally, we developed a method to quantitatively assess the fidelity of dopaminergic neurons derived from human pluripotent stem cells, at a single-cell level. Thus, our study provides insight into the molecular programs controlling human midbrain development and provides a foundation for the development of cell replacement therapies.
Miniemulsion Polymerization of 2-Ethylhexyl Acrylate. Polymer Architecture Control and Adhesion Properties (2010)

The feasibility of independent control of the gel fraction and sol molecular weight distribution in the miniemulsion polymerization of 2-ethylhexyl acrylate using symmetrical and nonsymmetrical cross-linkers and a chain transfer agent was investigated. It was found that the very reactive symmetrical cross-linker had only a limited effect on polymer architecture, whereas the nonsymmetrical cross-linker and the chain transfer agent had a profound effect allowing decoupling gel and sol molecular weight. Adhesive properties were mainly controlled by the gel content of the polymer.
Decreased hippocampal volume asymmetry on MRIs in nondemented elderly subjects carrying the apolipoprotein E ϵ4 allele (1995)

The APOE ε4 variant and hippocampal atrophy in Alzheimer's disease and Lewy body dementia: a systematic review of magnetic resonance imaging studies and therapeutic relevance ,
Clock skew optimization (1990)

Improving the performance of a synchronous digital system by adjusting the path delays of the clock signal from the central clock source to individual flip-flops is investigated. Using a model to detect clocking hazards, two linear programs are investigated: (1) minimizing the clock period, while avoiding clock hazards, and (2) for a given period, maximizing the minimum safety margin against clock hazard. These programs are solved for a simple example, and circuit simulation is used to contrast the operation of a resulting circuit with the conventionally clocked version. The method is extended to account for clock skew caused by relative variations in the drive capabilities of N-channel versus P-channel transistors in CMOS.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Environmental Contamination Due to Methicillin-Resistant Staphylococcus aureus: Possible Infection Control Implications (1997)

Active surveillance cultures are essential to identify the reservoir for spread of MRSA and VRE infections and make control possible using the CDC's long-recommended contact precautions.
Schizosaccharomyces pombe sxa1+ and sxa2+ encode putative proteases involved in the mating response. (1992)

The Schizosaccharomyces pombe sxa1 and sxa2 mutants showed an exaggerated response to mating pheromones, producing excessively long conjugation tubes and exhibiting mating deficiency. This phenotype was similar to phenotypes of cells bearing an activated allele of ras1, such as ras1Val-17 or ras1Leu-66, and phenotypes of cells defective in gap1. However, genetic evidence suggested that the sxa1 and sxa2 gene products are not directly involved in the Ras1 pathway. The gene products of sxa1 and sxa2, as deduced from their nucleotide sequences, were homologous to aspartyl proteases and serine carboxypeptidases, respectively. The sxa1 gene function was required for efficient mating only in h+ cells, although even disruption of sxa1 did not completely abolish the mating ability. Conversely, the sxa2 gene function was required only in h- cells. Wild-type cells produced a diffusible substance, which may be the sxa2 gene product itself, that could confer fertility to sxa2 mutant cells placed at a distance. These observations are consistent with the possibility that the sxa gene products are involved in degradation or processing of the mating pheromones and that their loss cause a persistent response to the pheromones.
Ultraviolet Radiation-induced Skin Tumors in a South American Opossum (Monodelphis domestica) (1991)

A total of 19 male and 21 female South American opossums (Monodelphis domestica) were exposed to 250 J/m2 ultraviolet radiation from FS-40 sunlamps (280-400 nm) three times weekly for 70 weeks. The backs of the opossums were shaved as necessary to remove hair. In order to prevent photoreactivation of ultraviolet radiation-induced pyrimidine dimers by the light-dependent photolyase enzyme of the opossum, ultraviolet radiation-exposed opossums were housed under red lights (600-800 nm). The opossum photolyase requires light in the 320-450 nm range for its activity. Twenty-nine control opossums (14 males and 15 females) were irradiated by fluorescent lights with emission spectra primarily in the visible light range (320-700 nm); these control opossums were also housed under red lights, and their backs were also shaved to remove hair. No skin tumors were observed in control opossums, while ultraviolet radiation-exposed opossums developed a variety of hyperplastic and neoplastic skin lesions on the backs and on a single ear. Hyperplastic lesions included foci of epithelial hyperplasia, dermal fibroplasia, and focal proliferation of dermal melanocytes. A total of 20 ultraviolet radiation-exposed opossums (50%) developed skin tumors, and 13 opossums (32.5%) had more than a single tumor. Epithelial tumors included 25 papillomas, four keratoacanthomas, seven carcinomas in situ, three microinvasive squamous cell carcinomas, two invasive squamous cell carcinomas, and a single basal cell tumor. Ten dermal spindle cell tumors also occurred; most of these appeared to be fibrosarcomas. Two benign melanomas and one malignant melanoma were observed.
FLT3 inhibitors in acute myeloid leukemia (2008)

The fms-like tyrosine kinase 3 (FLT3) plays an important role in both normal and malignant hematopoiesis. Activating mutations in the FLT3 receptor can be detected in approximately 30% of acute myeloid leukemias (AMLs) and are associated with a distinctly poor clinical outcome for patients. There are now several classes of FLT3 inhibitors in development with varying degrees of potency and selectivity for the target, including several in late-phase clinical trials in combination with chemotherapy. Major clinical responses in AML patients receiving single-agent FLT3 inhibitors have been rare, although transient peripheral blood blast reduction is common. Given such biological suggestion and preclinical activity, FLT3 inhibitors hold promise in improving the outcome of patients with mutant FLT3 AML. This review summarizes the current attempts to target this molecule, with emphasis on the validity of the target, the results of the clinical trials evaluating the FLT3 inhibitors in AML, the optimal use of these compounds and the mechanisms of resistance.
Progesterone receptor expression in human prostate cancer: Correlation with tumor progression (2001)

The progressive emergence of the PR during tumor progression obviously reflects the ability of metastatic and androgen-insensitive tumors to use estrogens through a ERalpha-mediated pathway. The present data provide a theoretical background for studying the efficiency of antiestrogens and antigestagens in the medical treatment of advanced prostate cancer.