gebhart/patrepeval huggingface dataset:
Biology of Langerhans cells: Selective migration of Langerhans cells into allogeneic and xenogeneic grafts on nude mice (1983)

A major question challenging immunobiologists relates to those mechanisms that control the selective movement of cells involved in immune and inflammatory processes at various tissue sites such as the skin. Little is known about those influences that control the selective migration of macrophage-like Langerhans cells (LC) to normal epidermis, where it is uniformly distributed. Mechanistically, this includes the interaction of blood-borne LC precursors with the vascular endothelium of the skin and those factors that control the migration of the LC into the avascular epidermal component of the skin. By using ( i ) monoclonal antibodies specific for I-region associated Ia antigens found on LC from various inbred strains of animals and ( ii ) the congenitally athymic ( nude ) mouse as an immunologically compromised recipient of allografts and selected xenografts, we developed a model system to study the factors that restrict LC migration into the epidermis. Using this model, which excludes the need to lethally x-irradiate graft recipients, we established that: ( i ) the ingress of LC does not show major histocompatibility complex restriction [LC of the nude host are capable of migrating into the epidermis of allogeneic and certain xenogeneic (rat) skin grafts]; ( ii ) host LC are incapable of migrating into the epidermis of guinea pig or human skin grafts; ( iii ) the ingress of host LC into the epidermis of the graft is not accompanied by an overgrowth of the graft by host epidermis; and ( iv ) LC or LC precursors are capable of dividing in the skin or, alternatively, represent an extremely long-lived cell population. The specificity of this model system provides a powerful tool to help understand many aspects of LC biology. Grafting human skin to the nude mouse not only provides a biologic support system for the graft but also is, by design, a system that is devoid of contaminating circulating precursor cell types. Manipulation of the experimental conditions is quite easy and provides a highly specific means to investigate many parameters of LC function.
Generic Method of Preparing Multifunctional Fluorescent Nanoparticles Using Flash NanoPrecipitation (2009)

Abstract There is increased demand for nanoparticles with a high fluorescence yield that have the desired excitation wavelength, surface functionalization, and particle size to act as biological probes. Here, a simple, rapid, and robust method, Flash NanoPrecipitation (FNP), to produce such fluorescent nanoparticles is described. This process involves encapsulation of a hydrophobic fluorophore with an amphiphilic biocompatible diblock copolymer in a kinetically frozen state. FNP is used to produce nanoparticles ranging from 30 to 800 nm with fluorescence emission peaks ranging from, but not limited to, 370 nm to 720 nm. Such fluorescent nanoparticles remain stable in aqueous solutions, and, in contrast to soluble dyes, show no photobleaching. Fluorophores and drugs are incorporated into a single nanoparticle, allowing for simultaneous drug delivery and biological imaging. In addition, functionalization of nanoparticle surfaces with disease‐specific ligands permits precise cell targeting. These features make FNP‐produced fluorescent nanoparticles highly desirable for various biological applications.
Inhibition of human embryonic stem cell differentiation by mechanical strain (2005)

Mechanical forces have been reported to induce proliferation and/or differentiation in many cell types, but the role of mechanotransduction during embryonic stem cell fate decisions is unknown. To ascertain the role of mechanical strain in human embryonic stem cell (hESC) differentiation, we measured the rate of hESC differentiation in the presence and absence of biaxial cyclic strain. Above a threshold of 10% cyclic strain, applied to a deformable elastic substratum upon which the hESC colonies were cultured, hESC differentiation was reduced and self-renewal was promoted without selecting against survival of differentiated or undifferentiated cells. Frequency of mechanical strain application had little effect on extent of differentiation. hESCs cultured under cyclic strain retained pluripotency, evidenced by their ability to differentiate to cell lineages in all three germ layers. Mechanical inhibition of hESC differentiation could not be traced to secretion of chemical factors into the media suggesting that mechanical forces may directly regulate hESC differentiation. Mechanical strain is not sufficient to inhibit differentiation, however, in unconditioned medium, hESCs grown under strain differentiated at the same rate as cells cultured in the absence of strain. Thus, while mechanical forces play a role in regulating hESC self-renewal and differentiation, they must act synergistically with chemical signals. These findings imply that application of mechanical forces may be useful, in combination with chemical and matrix-encoded signals, towards controlling differentiation of hESCs for therapeutic applications.
The toxin component of targeted anti‐tumor toxins determines their efficacy increase by saponins (2012)

Tumor-targeting protein toxins are composed of a toxic enzyme coupled to a specific cell binding domain that targets cancer-associated antigens. The anti-tumor treatment by targeted toxins is accompanied by dose-limiting side effects. The future prospects of targeted toxins for therapeutic use in humans will be determined by reduce side effects. Certain plant secondary metabolites (saponins) were shown to increase the efficacy of a particular epidermal growth factor receptor (EGFR)-targeted toxin, paralleled by a tremendous decrease of side effects. This study was conducted in order to investigate the effects of substituting different toxin moieties fused to an EGF ligand binding domain on the augmentative ability of saponins for each against therapeutic potential of the saponin-mediated efficacy increase for different anti-tumor toxins targeting the EGFR. We designed several EGFR-targeted toxins varying in the toxic moiety. Each targeted toxin was used in combination with a purified saponin (SA1641), isolated from the ornamental plant Gypsophila paniculata L. SA1641 was characterized and the SA1641-mediated efficacy increase was investigated on EGFR-transfected NIH-3T3 cells. We observed a high dependency of the SA1641-mediated efficacy increase on the nature of toxin used for the construction of the targeted toxin, indicating high specificity. Structural alignments revealed a high homology between saporin and dianthin-30, the two toxic moieties that benefit most from the combination with SA1641. We further demonstrate that SA1641 did not influence the plasma membrane permeability, indicating an intracellular interaction of SA1641 and the toxin components of targeted toxins. Surface plasmon resonance measurements point to a transient binding of SA1641 to the toxin components of targeted toxins.
Amylase and 16S rRNA genes from a hyperthermophilic archaebacterium (1999)

A hyperthermophilic and amylolytic prokaryote, designated Rt3, was isolated from a thermal spring near Rotorua, New Zealand. The 16S rRNA gene of Rt3 was cloned and sequenced with the aim of determining its phylogenetic affiliations. The phylogenetic analysis of this sequence, which included a selection of archaebacterial and eubacterial 16S rRNA sequences, indicates that Rt3 most likely belongs to the archaebacterial order Thermococcales. An amylase gene (amyA) from Rt3, encoding a highly thermostable amylase activity, was cloned and its DNA sequence determined. Transcriptional signals typical of archaebacteria were evident in this sequence. The sequence is homologous to a broad range of enzymes from the AMY superfamily and contains a typical N-terminal signal peptide. Phylogenetic analysis and comparison of structural features with other AMY superfamily enzymes reveals that, firstly, the closest homologues of the Rt3 amylase are members of the Bacillus and Plant alpha-amylase groups; and secondly, that the Rt3 amylase is closely related to only one other currently known archaebacterial enzyme, i.e. an (AMY superfamily) alpha-amylase from Natronococcus.
Bupivacaine injection of eye muscles to treat strabismus (2006)

Injection of bupivacaine to induce hypertrophy of the injected muscle and thus alter eye alignment was effective in our patient. This approach can be a useful addition to the treatment of strabismus.
Dynamically-configurable multimode transmitter systems for wireless handsets, cognitive radio and SDR applications (2009)

A unified transmit chain for handsets, SDR, and cognitive radio addresses the need for an efficient low-cost multimode solution. The 65nm CMOS control block contains a small state machine that interprets IQ data inputs and selects settings from memory, which are based on characterization of the modulating device for the operating regime. Nonlinear functions map the desired output into control signals that manipulate a 130nm-SiGe vector-power-amplifier to construct a full-power RF waveform.
Cellulosic ethanol production from AFEX-treated corn stover using Saccharomyces cerevisiae 424A(LNH-ST) (2009)

Current technology using corn stover (CS) as feedstock, Ammonia Fiber Expansion (AFEX) as the pretreatment technology, and Saccharomyces cerevisiae 424A(LNH-ST) as the ethanologenic strain in Separate Hydrolysis and Fermentation was able to achieve 191.5 g EtOH/kg untreated CS, at an ethanol concentration of 40.0 g/L (5.1 vol/vol%) without washing of pretreated biomass, detoxification, or nutrient supplementation. Enzymatic hydrolysis at high solids loading was identified as the primary bottleneck affecting overall ethanol yield and titer. Degradation compounds in AFEX-pretreated biomass were shown to increase metabolic yield and specific ethanol production while decreasing the cell biomass generation. Nutrients inherently present in CS and those resulting from biomass processing are sufficient to support microbial growth during fermentation. This platform offers the potential to improve the economics of cellulosic ethanol production by reducing the costs associated with raw materials, process water, and capital equipment.
The endothelial cell binding site for advanced glycation end products consists of a complex: an integral membrane protein and a lactoferrin-like polypeptide (1994)

Advanced glycation end products (AGEs), formed as the result of the extended interaction of proteins with ketoses, modulate central properties of endothelial cells and mononuclear phagocytes by interacting with a cell surface binding site comprised of a novel integral membrane protein (receptor for AGE = RAGE) and a lactoferrin-like polypeptide (LF-L), the latter having sequence identity to lactoferrin (LF). To further understand this cellular binding site, the interaction of RAGE with LF-L and LF was characterized. By ligand blotting and a solid state competitive binding assay, 125I-LF-L and 125I-LF bound to RAGE immobilized on nitrocellulose membranes or polypropylene tubes in a time-dependent and reversible manner, demonstrating a high affinity component with Kd approximately 100 pM. The interaction of 125I-LF-L and 125I-LF with RAGE was independent of iron in LF and was competed by addition of an excess of unlabeled carboxyl-terminal portion of LF. Cross-linking studies with purified 125I-LF-L and RAGE, in the presence of disuccinimidyl suberate, showed a new, slowly migrating band, corresponding to a complex of RAGE and LF-L, and cross-linking on mouse aortic endothelial cells showed two new slowly migrating bands on immunoblotting visualized with both anti-RAGE IgG and anti-LF-L IgG. These data lead us to propose that the endothelial cell surface binding site for AGEs consists of LF-L bound noncovalently to RAGE anchored in the cell membrane.
Tissue-specific gene silencing monitored in circulating RNA (2013)

Pharmacologic target gene modulation is the primary objective for RNA antagonist strategies and gene therapy. Here we show that mRNAs encoding tissue-specific gene transcripts can be detected in biological fluids and that RNAi-mediated target gene silencing in the liver and brain results in quantitative reductions in serum and cerebrospinal fluid mRNA levels, respectively. Further, administration of an anti-miRNA oligonucleotide resulted in decreased levels of the miRNA in circulation. Moreover, ectopic expression of an adenoviral transgene in the liver was quantified based on measurement of serum mRNA levels. This noninvasive method for monitoring tissue-specific RNA modulation could greatly advance the clinical development of RNA-based therapeutics.
The di- and tripeptide transport protein of Lactococcus lactis. A new type of bacterial peptide transporter (1994)

Lactococcus lactis takes up di- and tripeptides via a proton motive force-dependent carrier protein. The gene (dtpT) encoding the di-tripeptide transport protein of L. lactis was cloned by complementation of a dipeptide transport-deficient and proline auxotrophic Escherichia coli strain. Functional expression of the dipeptide transport gene was demonstrated by uptake studies of alanyl-[14C]glutamate and other peptides in E. coli cells. The di-tripeptide transport protein catalyzes proton motive force-driven peptide uptake and dipeptide exchange activity. The nucleotide sequence of dtpT was determined and the translated sequence corresponds with a protein of 463 amino acid residues. Hydropathy profiling indicates that the protein could form 12 membrane-spanning segments with the amino and carboxyl termini at the outer surface of the membrane. A secondary structure model is presented which is substantiated by analysis of DtpT-PhoA fusion constructs. Amino acid sequence comparisons showed no significant homology with other bacterial peptide transport systems nor with any other known protein. Flanking regions of the di-tripeptide transport gene were used to delete dtpT from the chromosome of L. lactis. Genetic and biochemical characterization of this mutant indicates that DtpT is the only transport protein in L. lactis for hydrophilic di- and tripeptides.
Hepatocellular carcinoma (1998)

Hepatocellular carcinoma is commonly a problem of two diseases, the malignancy itself and cirrhosis. This renders treatment rarely curative, even when surgical resection can be applied in a technically successful sense. Liver transplantation could be a definitive treatment but this is plagued by limited donor resources.
Molecular Engineering of DNA: Molecular Beacons (2008)

Molecular beacons (MBs) are specifically designed DNA hairpin structures that are widely used as fluorescent probes. Applications of MBs range from genetic screening, biosensor development, biochip construction, and the detection of single-nucleotide polymorphisms to mRNA monitoring in living cells. The inherent signal-transduction mechanism of MBs enables the analysis of target oligonucleotides without the separation of unbound probes. The MB stem-loop structure holds the fluorescence-donor and fluorescence-acceptor moieties in close proximity to one another, which results in resonant energy transfer. A spontaneous conformation change occurs upon hybridization to separate the two moieties and restore the fluorescence of the donor. Recent research has focused on the improvement of probe composition, intracellular gene quantitation, protein-DNA interaction studies, and protein recognition.
Whose Human Rights? Suffering and Reconstruction in Postwar Sierra Leone (2005)

This article had its beginnings in my conversations and encounters with refugees in Freetown, Sierra Leone, in the wake of that country’s decade-long civil war. These experiences made me increasingly concerned at the extent to which our Western rhetoric of suffering and human rights ignores the ways in which Sierra Leoneans understand and address their situation. This led me to see the problem of translation not simply as a matter of doing justice to the speech or writing of others, but as a matter of forestalling the unspoken political and ethical judgements that influence every translation, and that so often mean that not only meanings get lost in translation but also lives, livelihoods, languages and land. I therefore offer a critique of the way human rights is currently invoked to give legitimacy to a kind of moral neo-colonialism in West Africa – a reprise of the theme of the white man’s burden that implies that Africans need to be saved from themselves and that we are the ones to do it.
Clinical characteristics predictive of response to pembrolizumab in advanced melanoma. (2015)

9031 Background: Anti-PD-1 therapy has shown significant clinical activity in advanced melanoma and in other cancers. Factors predictive of response remain vaguely defined. We report on clinical characteristics correlated with higher response rates to therapy in a phase I trial of pembrolizumab. Methods: Advanced melanoma patients (n = 110, enrolled Dec 2011 to Oct 2013, data analysis July 2014) received pembrolizumab in 1 of 3 dosing regimens: 2Q3W, 10Q3W, or 10Q2W. Tumor responses were evaluated by RECIST 1.1 criteria. Sites of metastases were determined based on CT imaging, and this analysis was not limited to RECIST target lesions. The overall response rate (ORR) and exact two-sided 95% CI were calculated. Demographic and clinical variables were compared between responders and progressors. Results: In this cohort, ORR to pembrolizumab was 40%. Factors correlated with significantly higher ORR were: LDH ≤ normal (ORR 52.2%), no previous ipilimumab (ORR 48.3%), and presence of lung metastasis (ORR 52.8%). Patients with liver metastasis had worse response (ORR 18.4%), as did those with liver and lung metastases (ORR 31.3%). Data for associations of subgroup variables with ORR in univariate analyses are shown (Table). Conclusions: Normal LDH, no previous ipilimumab, and presence of lung metastasis are correlated with better response to pembrolizumab in advanced melanoma patients. The presence of liver metastasis is correlated with lower response to pembrolizumab, both in the presence and absence of lung metastasis. These correlations were observed regardless of BRAF status, presence of brain metastasis, or site of primary melanoma (cutaneous vs. uveal). Clinical trial information: NCT01295827. Clinical characteristic ORR, % (95% CI) p-value All patients 40 (30.7-49.3) Age <65 36.2 (23.5-49) 0.39 ECOG 0 41.1 (29.5-52.7) 0.741 LDH ≤ normal 52.2 (40-64.5) 0.009 BRAF WT 40.7 (30.1-51.3) 0.416 No previous ipilimumab 48.3 (35.3-61.4) 0.0049 Brain metastasis (met) 38.9 (13.9-63.8) 0.916 Lung met 52.8 (38.9-66.7) 0.008 Liver met 18.4 (5.5-31.3) 0.001 Lung met, no liver met 62.2 (45.8-78.6) 0.001 Lung met and liver met 31.3 (5.7-56.8) 0.001 Liver mets, no lung mets 9.1 (4-22.1) 0.001
Induction of CD4+ T-cell anergy and apoptosis by activated human B cells (2008)

B cells are well-known mediators of humoral immunity and serve as costimulators in the generation of T cell-mediated responses. In several mouse models, however, it was observed that B cells can also down-regulate immune reactions, suggesting a dual role for B cells. Due to this discrepancy and so far limited data, we directly tested the effects of primary human B cells on activated CD4(+) T helper cells in vitro. We found that under optimal costimulation large, activated CD25(+) B cells but not small CD25(-) B cells induced temporary T-cell anergy, determined by cell division arrest and down-regulation of cytokine production. In addition, large CD25(+) B cells directly induced CD95-independent apoptosis in a subpopulation of activated T cells. Suppression required direct B-T-cell contact and was not transferable from T to T cell, excluding potential involvement of regulatory T cells. Moreover, inhibitory effects involved an IL-2-dependent mechanism, since decreasing concentrations of IL-2 led to a shift from inhibitory toward costimulatory effects triggered by B cells. We conclude that activated CD25(+) B cells are able to costimulate or down-regulate T-cell responses, depending on activation status and environmental conditions that might also influence their pathophysiological impact.
An introduction to plant sphingolipids and a review of recent advances in understanding their metabolism and function (2004)

Sphingolipids are ubiquitous constituents of eukaryotic cells, and have been intensively investigated in mammals and yeast for decades. Aspects of sphingolipid biochemistry in plants have been explored only recently. To date, progress has been made in determining the structure and occurrence of sphingolipids in plant tissues; in characterizing the enzymatic steps involved in production and turnover of sphingolipids (and, in some cases, the genes encoding the relevant enzymes); and in identifying a variety of biological functions for sphingolipids in plants. Given that these efforts are far from complete and much remains to be learned, this review represents a status report on the burgeoning field of plant sphingolipid biochemistry. Contents Summary 677 I. Introduction 678 II. Plant sphingolipid structure 678 III. Sphingolipid metabolism in plants 683 IV. Sphingolipid functions in plants 693 V. Conclusions 696 Acknowledgements 696 References 696.
Viral and bacterial diseases of Atlantic cod Gadus morhua, their prophylaxis and treatment: a review (2006)

This review summarises the state of knowledge of both viral and bacterial diseases of Atlantic cod Gadus morhua, and their diagnosis, prophylaxis and treatment. The most important losses have been at the larval and juvenile stages, and vibriosis has long been the most important bacterial disease in cod, with Listonella (Vibrio) anguillarum dominant among pathogenic isolates. Vaccination of cod against pathogens such as L. anguillarum and Aeromonas salmonicida clearly demonstrates that the cod immune system possesses an effective memory and appropriate mechanisms sufficient for protection, at least against some diseases. Well-known viruses such as the nodavirus that causes viral encephalopathy and retinopathy (VER), infectious pancreatic necrosis virus (IPNV) and viral haemorrhagic septicaemia virus (VHSV) have been isolated from Atlantic cod and can be a potential problem under intensive rearing conditions. No commercial vaccines against nodavirus are currently available, whereas vaccines against IPNV infections based upon inactivated virus as well as IPNV recombinant antigens are available. A number of investigations of the pharmacokinetic properties of antibacterial agents in cod and their efficacy in treating bacterial infections have been reviewed.
Investigations into the Mechanisms of Flame Retardation on Wool (1977)

A number of flame-retardant systems have been applied to wool, and their flame-inhibiting efficiencies in atmospheres containing oxygen and nitrous oxide have been compared in order to explore the mechanisms by which they operate. The retardant systems investigated include phosphoric acid, sulfuric acid, sulfamic acid, and their ammonium salts, hexafluorophosphate, borax, boric acid, fluoroborate, antimony oxide/hydrochloric acid, hexafluorozirconate, hexafluorotitanate, hexafluorostannate, and dichromate. Most of the systems apparently operate in the solid phase though by different mechanisms. The antimony-based system inhibits in the gas phase. The chromium system, as well as catalyzing the thermal decomposition of wool, also inhibits gas-phase reactions, probably by a heterogeneous mechanism. Fluorostannate when padded onto wool also exhibits gase-phase inhibition properties, but when exhausted onto wool it appears to inhibit in the solid phase. The fluorotitanate treatment shows a dependence on the nature of the oxidizing atmosphere, but this may be due to the fact that a metal oxide-oxygen species complex is necessary for retardation. Fluorozirconate does not show the same dependence, though it is closely related chemically to the fluorotitanate system. A preliminary investigation has been made into the effectiveness of combinations of the padded fluorozirconate system with the sulfamic acid, fluoroborate, boric acid, and antimony oxide/hydrochloric acid systems.