gebhart/patrepeval huggingface dataset:
Genes involved in forebrain development in the zebrafish, Danio rerio (1996)

We identified four zebrafish mutants with defects in forebrain induction and patterning during embryogenesis. The four mutants define three genes: masterblind (mbl), silberblick (slb), and knollnase (kas). In mbl embryos, the anterior forebrain acquires posterior forebrain characteristics: anterior structures such as the eyes, olfactory placodes and the telencephalon are missing, whereas the epiphysis located in the posterior forebrain is expanded. In slb embryos, the extension of the embryonic axis is initially delayed and eventually followed by a partial fusion of the eyes. Finally, in kas embryos, separation of the telencephalic primordia is incomplete and dorsal midline cells fail to form a differentiated roof plate. Analysis of the mutant phenotypes indicates that we have identified genes essential for the specification of the anterior forebrain (mbl), positioning of the eyes (slb) and differentiation of the roof plate (kas). In an appendix to this study we list mutants showing alterations in the size of the eyes and abnormal differentiation of the lenses.
Controlled expression and purification of human immune interferon from high‐cell‐density fermentations of Saccharomyces cerevisiae (1987)

Conditions for high-cell-density fermentations of Saccharomyces cerevisiae strains producing recombinant-DNA-derived proteins were established. Strains producing human immune interferon (IFN-gamma) from the constitutive PGK promoter failed to grow to high cell densities and exhibited low plasmid stability. Regulated expression of IFN-gamma was obtained in similar strains by employing a hybrid yeast GPD promoter that was subject to carbon source regulation due to the presence of regulatory DNA sequences from the yeast GAL 1,10 intergenic region. IFN-gamma expression programmed by this vector was low during growth on glucose and was induced by galactose. Previously defined fermentation conditions employing glucose as a carbon source were applied to this strain, resulting in high ceil densities with higher plasmid stability. Various methods of galactose induction of IFN-gamma expression in high-cell-density fermentations were investigated. Optimal conditions resulted in a 2000-fold induction and production of 2 g IFN-gamma/L fermentation culture.
Synthesis and Evaluation of Double-Prodrugs against HIV. Conjugation of D4T with 6-Benzyl-1-(ethoxymethyl)-5-isopropyluracil (MKC-442, Emivirine)-Type Reverse Transcriptase Inhibitors via the SATE Prodrug Approach (2005)

This paper reports the synthesis and the antiviral activities of new double-prodrugs against HIV based on the known mixed SATE (S-acyl-2-thioethyl) prodrug approach. The monophosphate of the nucleoside reverse transcriptase inhibitor (NRTI) d4T was masked with one SATE group and one aromatic group through which a nonnucleoside reverse transcriptase inhibitor (NNRTI) was linked. Double-prodrug 1 was a hybrid between d4T monophosphate and the known NNRTI MKC-442, which were linked through a labile p-hydroxybenzoyl protection group in the N-3 position of MKC-442. Double-prodrugs 2 and 3 were conjugates between d4T monophosphate and the new NNRTIs 15 and 19 linked through a stable phenolic linker that was a part of the N-1 substituents of the NNRTIs. The double-prodrugs 1, 2, and 3 all had good activities against wild-type HIV-1, Y181C mutant, and also against a HIV-2 strain that was resistant to NNRTIs.
Requirement for nuclear factor-kappaB activation by a distinct subset of CD40-mediated effector functions in B lymphocytes. (1999)

CD40 stimulation, which is crucial for generating an effective T-dependent humoral response, leads to the activation of transcription factors NF-AT (nuclear factor of activated T cells), AP-1 (activator protein-1), and NF-kappaB (nuclear factor-kappaB). However, which CD40-mediated B cell functions actually require activation of specific transcription factors is unknown. We examined the causal relationship between NF-kappaB activation and CD40 effector functions by evaluating CD40 functions in the presence of an inducible mutant inhibitory kappaBalpha (IkappaBalpha) superrepressor. IkappaBalphaAA inhibited nuclear translocation of multiple NF-kappaB dimers without the complicating effect of depriving cells of NF-kappaB during development. This approach complements studies that use mice genetically deficient in single or multiple NF-kappaB subunits. Interestingly, only a subset of CD40 effector functions was found to require NF-kappaB activation. Both CD40-induced Ab secretion and B7-1 up-regulation were completely abrogated by expression of IkappaBalphaAA. Surprisingly, up-regulation of Fas, CD23, and ICAM-1 was partially independent, and up-regulation of LFA-1 was completely independent, of CD40-induced NF-kappaB activation. For the first time, it is clear that distinct transcription factors are required for the dynamic regulation of CD40 functions.
MTOR Inhibitors Activate the AKT Kinase in Multiple Myeloma Cells by Upregulating the IGF-1/IRS-1/PI-3 Kinase Cascade. (2004)

Abstract MTOR inhibitors, such as rapamycin and CCI-779, have shown pre-clinical potential as therapy for multiple myeloma (MM). By inhibiting expression of cell cycle proteins, these agents induce G1 arrest. However, by also inhibiting an mTOR-dependent phosphorylation of insulin receptor substrate-1 (IRS-1), they may alter its subcellular localization and/or prevent its degradation which could enhance IGF-1 signaling and downstream PI3-kinase/AKT activation. This may be a particular problem in MM where IGF-1-induced activation of AKT is an important anti-apoptotic cascade. We, thus, studied PI3-kinase/AKT activation in MM cells treated with mTOR inhibitors. Rapamycin enhanced basal AKT activity, AKT phosphorylation and PI3-kinase activity in MM cell lines. Both PTEN-null as well as PTEN-wild type myeloma lines were similarly affected. Rapamycin also significantly prolonged activation of AKT induced by exogenous IGF-1. CCI-779, used in a xenograft model, also resulted in MM cell AKT activation in vivo. Blockade of IGF-1 receptor function prevented rapamycin’s activation of AKT. Furthermore, rapamycin prevented serine phosphorylation of IRS-1 and IRS-1 degradation. Though similarly blocking IRS-1 degradation, proteasome inhibitors did not activate MM cell AKT. Although rapamycin sensitized MM cells for dexamethasone-induced apoptosis, it protected against PS-341-induced apoptosis. Thus, mTOR inhibitors activate PI3-K/AKT in MM cells and activation depends on basal IGF-1/IGF-R signaling. As activated AKT may protect against apoptosis, future use of mTOR inhibitors in myeloma patients will have to carefully consider the types of anti-myeloma agents used in combination.
Stromal cell–derived factor-1 and macrophage-derived chemokine: 2 chemokines that activate platelets (2000)

Abstract Platelets play roles in both thrombosis and inflammation, and chemokines that are released at sites of inflammation could potentially activate platelets. Among the chemokine receptors expressed on platelets, the CXCR4 is the receptor for chemokine stromal cell-derived factor-1 (SDF-1), and the CCR4 is the receptor for macrophage-derived chemokine (MDC). Of the chemokines tested, SDF-1 and MDC were the only 2 that activated platelets. Both are weak agonists, but they enhanced response to low-dose adenosine 5′-diphosphate (ADP), epinephrine, or serotonin. When SDF-1 and MDC were added together, full and brisk platelet aggregation occurred. Platelet activation by these 2 chemokines appears to involve distinct pathways: SDF-1 inhibited an increase in cyclic adenosine monophosphate (cAMP) following prostaglandin (PG) I2, while MDC had no effect. In contrast, MDC, but not SDF-1, lead to Ca++mobilization by platelets. Further, second-wave aggregation induced by MDC in platelet-rich plasma was inhibited by aspirin, ADP scavenger creatine phosphate/creative phosphokinase (CP/CPK), and ARL-66096, an antagonist of the ADP P2TAC receptor involved in adenylyl cyclase inhibition. But the aggregation was not affected by A3P5PS, an inhibitor of the ADP P2Y receptor. SDF-1–induced aggregation was inhibited by aspirin, but it was only slightly affected by CP/CPK, ARL-66096, or A3P5PS. Finally, the presence of chemokines in platelets was determined. Reverse transcriptase–polymerase chain reaction studies with platelet RNA did not detect the presence of SDF-1 or MDC. In summary, SDF-1 and MDC are platelet agonists that activate distinct intracellular pathways. Their importance in the development of thrombosis at sites of inflammation needs to be further evaluated.
Review of Genes and Linkage Groups in Cucumber (1990)

The purpose of this review was to summarize all of the cucumber genes in one place, provide information on the lines that carry the published alleles for future checks of allelism, point out possible duplications, and summarize the gene linkages reported so far
Nonclinical Vehicle Use in Studies by Multiple Routes in Multiple Species (2006)

The laboratory toxicologist is frequently faced with the challenge of selecting appropriate vehicles or developing utilitarian formulations for use in in vivo nonclinical safety assessment studies. Although there are many vehicles available that may meet physical and chemical requirements for chemical or pharmaceutical formulation, there are wide differences in species and route of administration specific to tolerances to these vehicles. In current practice, these differences are largely approached on a basis of individual experience as there is only scattered literature on individual vehicles and no comprehensive treatment or information source. This approach leads to excessive animal use and unplanned delays in testing and development. To address this need, a consulting firm and three contract research organizations conducted a rigorous data mining operation of control (vehicle) data from studies dating from 1991 to present. The results identified 65 single component vehicles used in 368 studies across multiple species (dog, primate, rat, mouse, rabbit, guinea pig, minipig, chick embryo, and cat) by multiple routes. Reported here are the results of this effort, including maximum tolerated use levels by species, route, and duration of study, with accompanying dose limiting toxicity. Also included are basic chemical information and a review of available literature on each vehicle, as well as guidance on volume limits and pH by route and some basic guidance on nonclinical formulation development.
Design and fabrication of a cross flow micro heat exchanger (2000)

A cross flow micro heat exchanger was designed to maximize heat transfer from a liquid (water-glycol) to a gas (air) for a given frontal area while holding pressure drop across the heat exchanger of each fluid to values characteristic of conventional scale heat exchangers. The predicted performance for these plastic, ceramic, and aluminum micro heat exchangers are compared with each other and to current innovative car radiators. The cross flow micro heat exchanger can transfer more heat/volume or mass than existing heat exchangers within the context of the design constraints specified. This can be important in a wide range of applications (automotive, home heating, and aerospace). The heat exchanger was fabricated by aligning and then bonding together two identical plastic parts that had been molded using the LIGA process. After the heat exchanger was assembled, liquid was pumped through the heat exchanger, and minimal leakage was observed.
Classifying Depression by Mental State Signs (1990)

The possibility that separation of a categorical depressive disease ('melancholia') from remaining depressive disorders can be improved by assessment of mental state signs was examined in patients treated by representative Sydney psychiatrists and patients referred to a specialised mood disorders unit. A set of signs, principally assessing retardation, was derived within the two samples by principal-components and latent-class analyses. Scores were significantly correlated with clinical, DSM-III, and RDC diagnoses, and appeared independent of severity, suggesting that melancholia can be defined phenomenologically. Scores were also associated with several 'validating' factors. Comparative analyses of a refined list of melancholia symptoms suggested that ratings of defined signs are likely to have greater capacity than symptom ratings to differentiate melancholia from residual depressive disorders.
Electrophysiological Characteristics and Catheter Ablation in Patients with Paroxysmal Supraventricular Tachycardia and Paroxysmal Atrial Fibrillation (2007)

The SVC AF has a close relationship with AVNRT. The effect of atrial vulnerability and remodeling may differ between AVNRT and WPW syndrome.
Insurance Contracts and Judicial Discord Over Whether Liability Insurers Must Defend Insureds' Allegedly Intentional and Immoral Conduct: A Historical and Empirical Review of Federal and State Courts' Declaratory Judgments--1900-1997 (1998)

There is a prevailing view among jurists and practitioners that a declaratory judgment action is an efficient, effective, and equitable method of helping litigants determine legal relations, rights, and obligations, especially under liability insurance contracts. It even has been argued that securing declaratory relief decreases the need to file multiple lawsuits to settle disputes involving legal rights. But does statistical and historical evidence strongly support these assumptions? The short answer is no. Without doubt, a declaratory judgment action is not the most effective or efficient means to resolve disputes under liability insurance contracts, because "filing for declaratory judgment may result in two lawsuits and two jury trials." This Article will present some compelling evidence arguing against the use of the declaratory judgment action to resolve duty-to-defend controversies in state and federal courts.
Reflections on the Graduate Student Experience: An Overview (1998)

Abstract A national survey of doctoral students sought students' reflections on their graduate experiences, their faculty, their department, their academic work, and their prospective careers.
Influence of hormonal contraceptives on the immune cells and thickness of human vaginal epithelium (2003)

Hormonal contraceptives induce hyperplasia of the vaginal epithelium. The significant changes in the intraepithelial leukocyte population in depot-medroxyprogesterone acetate and levonorgestrel implant users most probably reflect altered local immune capacity.
A peptide containing a novel FPGN CD40‐binding sequence enhances adenoviral infection of murine and human dendritic cells (2003)

CD40 is a receptor with numerous functions in the activation of antigen presenting cells (APCs), particularly dendritic cells (DC). Using phage display technology, we identified linear peptides containing a novel FPGN/S consensus sequence that enhances the binding of phage to a purified murine CD40-immunoglobulin (Ig) fusion protein (CD40-Ig), but not to Ig alone. To examine the ability the FPGN/S peptides to enhance adenoviral infection of CD40-positive cells, we used bifunctional peptides consisting of an FPGN-containing peptide covalently linked to an adenoviral knob-binding peptide (KBP). One of these, FPGN2-KBP, was able to enhance adenoviral infection of both murine and human DCs in a dose-dependent manner. FPGN2-KBP also improved infection of murine B cell blasts, a murine B lymphoma cell line (L10A), and immortalized human B cells. To demonstrate that enhancement of adenoviral infection depended on the presence of CD40, we analyzed infection of the breast cancer line, SKBR3, that does not express CD40 or the adenovirus cellular receptor, CAR. Infection of SKBR3 cells was enhanced by FPGN2-KBP following transient transfection with a plasmid vector that expresses murine CD40, but not when the cells were mock-transfected. In conclusion, we have isolated a peptide that binds to murine CD40, and promotes the uptake of adenoviruses into CD40-expressing cells of both murine and human origin, suggesting that it may have potential applications for antigen delivery to CD40-positive antigen-presenting cells.
Reduced Skeletal Muscle Capillarization and Glucose Intolerance (2009)

Hemiparetic muscle capillarization is reduced after stroke, and reduced capillarization is associated with glucose intolerance in stroke and control subjects. Interventions to increase skeletal muscle capillarization may prove beneficial for improving glucose metabolism in chronic stroke patients.
Flexible Graphene Films via the Filtration of Water-Soluble Noncovalent Functionalized Graphene Sheets (2008)

Flexible graphene films were prepared by the filtration of water-soluble noncovalently functionalized graphene sheets with pyrenebutyrate. The work presented here will not only open a new way for preparing water-soluble graphene dispersions but also provide a general route for fabricating conducting films based on graphene.
Immobilised, activated peptides as reagents for cyclic and derivatised peptide libraries (1994)

Cyclic peptides have been synthesised from an immobilised, activated intermediate, where activation of the immobilised peptide is carried out with the Nα-protecting group intact, its subsequent removal leading to cyclisation.
Immunohistochemical identification of cytotoxic lymphocytes using human perforin monoclonal antibody. (1992)

Perforin is a potent cytolytic pore-forming protein expressed in cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells. A new monoclonal antibody raised against human perforin was used to detect both in vitro and in vivo perforin expression in cytotoxic cells. Immunohistochemical analysis of human peripheral blood mononuclear cells cultured in recombinant interleukin-2 (rIL-2) showed strong granular cytoplasmic staining of the IL-2 activated cytotoxic cells. Fresh-frozen tissue sections from patients with heart allograft rejection were also stained. Strong granular cytoplasmic staining of the mononuclear inflammatory infiltrate characteristic for perforin in cardiac allograft rejection was observed. The detection and quantitative analysis of perforin-associated cytotoxic cells by the human anti-perforin monoclonal antibody will help to evaluate the significance of these functionally distinct cytotoxic cells in human tissue.
Direct Measurement of Coupling Between Dendritic Spines and Shafts (1996)

Characterization of the diffusional and electrotonic coupling of spines to the dendritic shaft is crucial to understanding neuronal integration and synaptic plasticity. Two-photon photobleaching and photorelease of fluorescein dextran were used to generate concentration gradients between spines and shafts in rat CA1 pyramidal neurons. Diffusional reequilibration was monitored with two-photon fluorescence imaging. The time course of reequilibration was exponential, with time constants in the range of 20 to 100 milliseconds, demonstrating chemical compartmentalization on such time scales. These values imply that electrical spine neck resistances are unlikely to exceed 150 megohms and more likely range from 4 to 50 megohms.
β‐Peptides: Oligo‐β‐homoalanines – the Amide Analogues of Poly(3‐hydroxybutanoate) (1997)

Abstract The linear oligo‐β‐peptides derived from β‐homoalanine (Hβ‐HAlaOH) have been prepared by Arndt‐Eistert homologation of Boc‐alanine and subsequent peptide coupling procedures. Cyclisation via pentafluorophenyl esters resulted in the formation of the cyclic β‐peptides in remarkably high yields. The X‐ray crystal structure analysis of Boc–(β‐HAla) 2 –OBn is presented. The cyclic derivatives were found to be highly insoluble (m.p. &gt;300°C with decomposition) and the effect of lithium salts on their solubility, particularly with respect to obtaining NMR data, is discussed. The CD spectra of the cyclo‐β‐tetrapeptides are presented and these give an indication that “nanotube‐like” structures may be present.
The “Wired” Laccase Cathode:  High Current Density Electroreduction of O2 to Water at +0.7 V (NHE) at pH 5 (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTThe "Wired" Laccase Cathode: High Current Density Electroreduction of O2 to Water at +0.7 V (NHE) at pH 5Scott Calabrese Barton, Hyug-Han Kim, Gary Binyamin, Yongchao Zhang, and Adam HellerView Author Information Department of Chemical Engineering and the Texas Materials Institute, The University of Texas Austin, Texas 78712 Cite this: J. Am. Chem. Soc. 2001, 123, 24, 5802–5803Publication Date (Web):May 25, 2001Publication History Received15 February 2001Published online25 May 2001Published inissue 1 June 2001https://pubs.acs.org/doi/10.1021/ja010408bhttps://doi.org/10.1021/ja010408brapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views1768Altmetric-Citations186LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Electrical properties,Electrodes,Peptides and proteins,Polymers,Redox reactions Get e-Alerts
The Microfluidic Toolbox for Analyzing Exosome Biomarkers of Aging (2021)

As the fields of aging and neurological disease expand to liquid biopsies, there is a need to identify informative biomarkers for the diagnosis of neurodegeneration and other age-related disorders such as cancers. A means of high-throughput screening of biomolecules relevant to aging can facilitate this discovery in complex biofluids, such as blood. Exosomes, the smallest of extracellular vesicles, are found in many biofluids and, in recent years, have been found to be excellent candidates as liquid biopsy biomarkers due to their participation in intercellular communication and various pathologies such as cancer metastasis. Recently, exosomes have emerged as novel biomarkers for age-related diseases. Hence, the study of exosomes, their protein and genetic cargo can serve as early biomarkers for age-associated pathologies, especially neurodegenerative diseases. However, a disadvantage of exosome studies includes a lack in standardization of isolating, detecting, and profiling exosomes for downstream analysis. In this review, we will address current techniques for high-throughput isolation and detection of exosomes through various microfluidic and biosensing strategies and how they may be adapted for the detection of biomarkers of age-associated disorders.