gebhart/patrepeval huggingface dataset:
Early signaling defects in human T cells anergized by T cell presentation of autoantigen. (1992)

Major histocompatibility complex class II-positive human T cell clones are nontraditional antigen-presenting cells (APCs) that are able to simultaneously present and respond to peptide or degraded antigen, but are unable to process intact protein. Although T cell presentation of peptide antigen resulted in a primary proliferative response, T cells that had been previously stimulated by T cells presenting antigen were completely unresponsive to antigen but not to interleukin 2 (IL-2). In contrast, peptide antigen presented by B cells or DR2+ L cell transfectants resulted in T cell activation and responsiveness to restimulation. The anergy induced by T cell presentation of peptide could not be prevented by the addition of either autologous or allogeneic B cells or B7+ DR2+ L cell transfectants, suggesting that the induction of anergy could occur in the presence of costimulation. T cell anergy was induced within 24 h of T cell presentation of antigen and was long lasting. Anergized T cells expressed normal levels of T cell receptor/CD3 but were defective in their ability to release [Ca2+]i to both alpha CD3 and APCs. Moreover, anergized T cells did not proliferate to alpha CD2 monoclonal antibodies or alpha CD3 plus phorbol myristate acetate (PMA), nor did they synthesize IL-2, IL-4, or interferon gamma mRNA in response to either peptide or peptide plus PMA. In contrast, ionomycin plus PMA induced both normal proliferative responses and synthesis of cytokine mRNA, suggesting that the signaling defect in anergized cells occurs before protein kinase C activation and [Ca2+]i release.
Discovery of Orally Active Prostaglandin D2 Receptor Antagonists. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Oxidized Phospholipids, Lipoprotein(a), Lipoprotein-Associated Phospholipase A2 Activity, and 10-Year Cardiovascular Outcomes (2007)

This study demonstrates that OxPL/apoB levels predict 10-year CVD event rates independently of traditional risk factors, hsCRP, and FRS. Increasing Lp-PLA2 activity further amplifies the risk of CVD mediated by OxPL/apoB.
Bone Morphogenetic Protein-2 Induces Scar Formation and Skin Maturation in the Second Trimester Fetus (1998)

Fetal mammals heal skin wounds through the second trimester of development without evidence of scar. We have investigated the role of bone morphogenetic protein 2 (BMP-2), which is a member of the TGF-beta superfamily, in normal skin development and fetal wound healing. We first used RNA in situ hybridization to demonstrate that BMP-2 was expressed at low levels in the developing hair follicles and in the epidermis of normal human fetal skin. We then created an in vivo model to test how exogenous BMP-2 would affect fetal skin development and wound healing. Fifty micrograms of BMP-2 was implanted into the subcutis of five 70-day-old fetal lambs through a full-thickness linear incision. The BMP-2 was placed beneath the right half of the wound, whereas the left half served as an untreated control. In two of the five animals 1 microgram of TGF-beta was placed into the same position in addition to the 50 micrograms of BMP-2. Twenty days later (90 days gestation, term = 140 days) all the fetal wounds were examined for evidence of cellular hyperproliferation and scar formation. BMP-2 induced massive dermal and epidermal growth when compared with controls. This finding was characterized by marked epidermal thickening and keratinization, a dramatic increase in the number of hair follicles, and more than 50 percent thickening of the dermis. The dermal thickening was the result of both increased cellularity and deposition of large irregular collagen bundles. Wounds treated with both BMP-2 and TGF-beta healed also with an adult-like pattern of scar formation. Surprisingly, the wounds with BMP-2 alone healed with an equal pattern of scar, indicating that there was not an additive effect of combining BMP-2 and TGF-beta. We conclude that BMP-2 is a pleomorphic growth factor that induces cellular growth, maturation, and fibroplasia in both the dermis and epidermis. Further analysis of this growth factor in both fetal and adult wound healing may lead to important discoveries regarding the control of scar formation and fibrosis in many adult tissues.
Role of Platelet-Derived Growth Factor in Renal Injury (1995)

Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and ...Read More
Excitatory amino acids (1991)

This multidisciplinary volume presents findings on excitatory amino acids from some of the world's leading researchers in the field. An overview of recent neurochemical studies on glutamate-mediated neurotransmission is followed by more than 80 studies in the areas of anatomy; molecular biology; electrophysiology, pharmacology, and signal transduction; kynurenate and quinolinate; medicinal chemistry; long-term potentiation and synaptic plasticity; behavioural pharmacology; excitotoxicity; and epilepsy, ischemia and related pathologies.
Chain Length Dependence and Sensing Capabilities of the Localized Surface Plasmon Resonance of Silver Nanoparticles Chemically Modified with Alkanethiol Self-Assembled Monolayers (2001)

In this paper, we explore the optical properties of Ag nanoparticles chemically modified with alkanethiol self-assembled monolayers (SAMs) by measuring the localized surface plasmon resonance (LSPR) spectrum using UV−vis extinction spectroscopy. For all the experiments presented here, the Ag nanoparticles were fabricated using the technique of nanosphere lithography (NSL) and had in-plane widths of 100 nm and out-of-plane heights of 50 nm. We first demonstrate that unmodified nanoparticles are extremely susceptible to slight changes in 3-dimensional structure when exposed to various solvents. These structural effects can have dramatic effects on the extinction maximum, λmax, of the LSPR shifting it to the blue by over 100 nm. The significant discovery reported here is that λmax for NSL fabricated Ag nanoparticles is extremely sensitive to the SAM properties. We will demonstrate the following new features: (1) λmax of the LSPR linearly shifts to the red 3 nm for every carbon atom in the alkane chain; (2) spectral shifts as large as 40 nm are caused by only 60 000 alkanethiol molecules per nanoparticle, which corresponds to only 100 zmol of adsorbate; and (3) the nanoparticles' sensitivity to bulk external environment is only attenuated by 20% when the nanoparticles are modified with the longest chain alkanethiol (1-hexadecanethiol, ∼2 nm). Experimental extinction spectra were modeled by using Mie theory for Ag nanospheres with dielectric shells intended to mimic the self-assembled monolayer (SAM) in thickness and refractive index. We find that the Mie theory qualitatively predicts the experimentally observed trend that λmax linearly shifts to the red with respect to shell thickness, or alkanethiol chain length; however, the theory underestimates the sensitivity by approximately a factor of 4. Excellent correlation between theory and experiment was observed when Mie theory was used to predict the degree of attenuation in LSPR sensitivity to bulk external environment when the nanoparticle is encapsulated in a dielectric shell similar to an alkanethiol SAM. Finally, we demonstrate that Ag nanoparticles modified with functionalized SAMs can be used in sensing applications. Here, we show that the LSPR shifts to the red 5 nm with the adsorption of the polypeptide poly-l-lysine (PL) to Ag nanoparticles modified with deprotonated carboxylate groups from 11-mercaptoundecanoic acid (11-MUA). Furthermore, we will show that this system behaves reversibly and exhibits no detectable nonspecific binding.
Emission Rate of Particulate Matter and Its Removal Efficiency by Precipitators in Under-Fired Charbroiling Restaurants (2011)

In order to explore the potent role of meat cooking processes as the emission sources of particulate matter (PM), emission rates and the associated removal efficiency by precipitators were estimated based on the on-site measurements made at five under-fired charbroiling (UFC) restaurants. The emission patterns of PM for these five restaurants were compared after having been sorted into the main meat types used for cooking: beef (B), chicken (C), intestines (I), and pork (P: two sites). The mass concentrations (μg m -3 ) of three PM fractions (PM 2.5 /PM 10 /TSP) measured from these restaurants were 15,510/15,701/17,175 (C); 8,525/10,760/12,676 (B); 11,027/13,249/13,488 (P); and 22,409/22,412/22,414 (I). Emission factors (g kg -1 ) for those PM fractions were also estimated as 3.23/4.08/4.80 (B), 3.07/3.82/3.87 (P), 8.12/8.22/8.99 (C), and 6.59/6.59/6.59 (I). If the annual emission rate of PM 10 is extrapolated by combining its emission factor, population, activity factor, etc., it is estimated as 500 ton year -1 , which corresponds to 2.4% of the PM 10 budget in Seoul, Korea. Removal efficiencies of PM 10 via precipitators, such as an electrostatic precipitator (ESP), bag filter (BF), and the combination system (ESP + catalyst), installed in those UFC restaurants ranged between 54.76 and 98.98%. The removal efficiency of PM by this control system was the least effective for particles with &lt;0.4 μm, although those in the range of 0.4–10 μm were the most effective.
Inhibition of NF-κB specific transcriptional activation by PNA strand invasion (1995)

Peptide nucleic acid (PNA) strand invasion offers an attractive alternative to DNA oligonucleotide directed triplex formation as a potential tool for gene inhibition. Peptide nucleic acid has been shown to interact with duplex DNA in a process which involves strand invasion of the duplex and binding of one of the DNA strands with two PNA oligomers. By blocking the interaction of a transcription factor with 5' regulatory sequences, PNA might specifically down-regulate gene activity. Here we demonstrate that PNA is capable of specifically blocking interaction of the transcription factor NF-kappa B with the IL2-R alpha NF kappa-B binding site in vitro. We further demonstrate that this interaction is sufficient to prevent transcriptional transactivation both in vitro and when transfected into cells in culture.
Comparison of a Clinic-Based ELISA Test Kit with the Immunofluorescence Test for the Assay ofEhrlichia CanisAntibodies in Dogs (2000)

The "gold standard" for the detection of antibodies to Ehrlichia canis, the cause of canine monocytic ehrlichiosis (CME), is the indirect immunofluorescence antibody (IFA) test. The IFA test however is generally available only in selected laboratories and requires extensive equipment and trained personnel. A double-blind study was conducted to compare the ability of an in-clinic standardized enzyme-linked immunosorbent assay (ELISA) test kit to measure E. canis IgG antibodies in dogs compared with the standard IFA technique. A good correlation was found between the 2 techniques (r2 = 0.8793; P < 0.0001). Evidence for the sensitivity of the ELISA technique for the early detection of E. canis IgG antibodies was demonstrated by comparing the appearance of E. canis antibody titers by the IFA and ELISA techniques after artificial infection of 2 sets of dogs. In both experimental infections, both tests were equally sensitive for the early detection of IgG antibodies against E. canis, and the results correlated well with the appearance of fever and clinical signs. Proposed application of the in-clinic ELISA test is to aid in the diagnosis of CME.
Synthesis, Characterization, and in Vitro Biodegradation of Poly(Ethylene Glycol) Modified Poly[5N-(2-Hydroxyethyl-L-Glutamine] (1996)

The synthesis and in vitro biodegradation of poly(ethylene glycol) modified poly[N-2-hydroxyethyl)L-glutamine] are described. Poly(ethylene glycol) (PEG) with terminal amino endgroup was coupled onto 4-nitrophenyl chloroformate activated poly[N-2-hydroxyethyl-L-glutamineI (PHEG). The influence of the degree of substitution and the molecular weight of PEG side groups on the degradability of the PHEG backbone exposed to isolated rat liver lysosomal enzymes was determined. These data indicate that substitution of PHEG with PEG side-chains only slightly alters the degradability of the carrier. The PEG-grafted polymers showed potential tensioactive properties. DSC analysis demonstrated phase separation of the PEG side-groups in solid state.
Differentiation-state plasticity is a targetable resistance mechanism in basal-like breast cancer (2018)

Intratumoral heterogeneity in cancers arises from genomic instability and epigenomic plasticity and is associated with resistance to cytotoxic and targeted therapies. We show here that cell-state heterogeneity, defined by differentiation-state marker expression, is high in triple-negative and basal-like breast cancer subtypes, and that drug tolerant persister (DTP) cell populations with altered marker expression emerge during treatment with a wide range of pathway-targeted therapeutic compounds. We show that MEK and PI3K/mTOR inhibitor-driven DTP states arise through distinct cell-state transitions rather than by Darwinian selection of preexisting subpopulations, and that these transitions involve dynamic remodeling of open chromatin architecture. Increased activity of many chromatin modifier enzymes, including BRD4, is observed in DTP cells. Co-treatment with the PI3K/mTOR inhibitor BEZ235 and the BET inhibitor JQ1 prevents changes to the open chromatin architecture, inhibits the acquisition of a DTP state, and results in robust cell death in vitro and xenograft regression in vivo.
The Euplotes telomerase subunit p43 stimulates enzymatic activity and processivity in vitro (2004)

Telomerase is a reverse transcriptase that synthesizes telomeric DNA repeats at the ends of eukaryotic chromosomes. Although it is minimally composed of a conserved catalytic protein subunit (TERT) and an RNA component, additional accessory factors present in the holoenzyme play crucial roles in the biogenesis and function of the enzyme complex. Telomerase from the ciliate Tetrahymena can be reconstituted in active form in vitro. Using this system, we show that p43, a telomerase-specific La-motif protein from the ciliate Euplotes, stimulates activity and increases repeat addition processivity of telomerase. Activity enhancement by p43 requires its incorporation into a TERT.RNA.p43 ternary complex but is independent of other dissociable protein factors functioning in telomerase complex assembly. Stimulation is enhanced at elevated temperatures, supporting a role for p43 in structural stabilization of a critical region of the RNA subunit. To our knowledge, this represents the first demonstration that an authentic telomerase accessory protein can directly affect the enzymatic activity of the core enzyme in vitro.
A new velocity model for clay‐sand mixtures1 (1995)

Abstract None of the standard porosity‐velocity models (e.g. the time‐average equation, Raymer's equations) is satisfactory for interpreting well‐logging data over a broad depth range. Clays in the section are the usual source of the difficulty through the bias and scatter that they introduce into the relationship between porosity and P‐wave transit time. Because clays are composed of fine sheet‐like particles, they normally form pores with much smaller aspect ratios than those associated with sand grains. This difference in pore geometry provides the key to obtaining more consistent resistivity and sonic log interpretations. A velocity model for Clay–sand mixtures has been developed in terms of the Kuster and Toksöz, effective medium and Gassmann theories. In this model, the total pore space is assumed to consist of two parts: (1) pores associated with sand grains and (2) pores associated with clays (including bound water). The essential feature of the model is the assumption that the geometry of pores associated with sand grains is significantly different from that associated with clays. Because of this, porosity in shales affects elastic compliance differently from porosity in sand‐Stones. The predictive power of the model is demonstrated by the agreement between its predictions and laboratory measurements and by its ability to predict sonic logs from other logs over large depth intervals where formations vary from unconsolidated to consolidated sandstones and shales.
Distortion Criteria of the Human Viewer (1979)

The ultimate judges of the quality of reproduced pictures are human observers. In many practical situations it is desirable to have objective measures which closely mirror the performance of the human viewer; today we lack accurate measures. To study this problem, a set of five pictures was used in which distortions of different types were introduced. The resulting series of pictures was rated by viewers by means of an impairment rating test. These ratings were then compared with various objective measures of the error. The objective measure is sought which is most closely monotonically related in a smooth manner to the subjective measure. The average spread of the subjective deviations about a polynomial regression of the subjective measure onto the objective measure is used as the criterion. This technique is used to study both linearly filtered error measures and picture dependent nonlinear weightings of the error. The procedure has enabled a crude quantative model of the human viewer to be determined.
Role of the Nuclear Transport Factor p10 in Nuclear Import (1996)

The nuclear import factor p10 was cloned from Saccharomyces cerevisiae and found to be essential. The protein p10 can bind directly to several peptide repeat-containing nucleoporins. It also binds to the guanosine triphosphatase (GTPase) Ran in its guanosine diphosphate (GDP)-bound form and to karyopherin beta. Assembly of the karyopherin heterodimer on immobilized nucleoporin yielded cooperative binding of p10 and Ran-GDP. Addition of GTP to this pentameric complex led to dissociation of karyopherin (chi, presumably via in situ formation of Ran-GTP from Ran-GDP. Thus, p10 appears to coordinate the Ran-dependent association and dissociation reactions underlying nuclear import.
Glyceraldehyde-3-Phosphate Dehydrogenase of Streptococcus oralis Functions as a Coadhesin for Porphyromonas gingivalis Major Fimbriae (2004)

Cohesive interactions between Porphyromonas gingivalis and plaque-forming bacteria, such as Streptococcus oralis, are considered to play an important role in the colonization of P. gingivalis in periodontal sites. Although P. gingivalis fimbriae have been reported to mediate coaggregation with S. oralis, the S. oralis molecule involved has not been identified. We identified the coadhesin of S. oralis ATCC 9811 and purified it by affinity column chromatography. We found that the molecular mass of the purified protein was approximately 40 kDa. Dot blot and Western blot assays showed binding of the 40-kDa protein to P. gingivalis fimbriae. Further, turbidimetric assays showed that the coadhesin inhibited coaggregation between P. gingivalis and S. oralis in a dose-dependent manner. Analyses of the amino-terminal sequences of the protein and its lysyl endopeptidase-cleaved fragments revealed that the coadhesin was identical to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Next, we cloned the gene that encodes S. oralis GAPDH and found that the sequence had a high degree of homology with the sequences of GAPDHs of various bacteria, including Streptococcus gordonii and Fusobacterium nucleatum. To confirm the contribution of S. oralis GAPDH to the interaction with P. gingivalis, a recombinant GAPDH protein was generated in Escherichia coli; this protein bound to P. gingivalis fimbriae and had an inhibitory effect on coaggregation. These results suggest that S. oralis GAPDH functions as a coadhesin for P. gingivalis fimbriae. In addition, considering the high degree of homology of the GAPDHs of various bacteria, those of other plaque-forming bacteria also may contribute to the colonization of P. gingivalis.
Activated T-Cells Inhibit Neurogenesis by Releasing Granzyme B: Rescue by Kv1.3 Blockers (2010)

There is a great need for pharmacological approaches to enhance neural progenitor cell (NPC) function particularly in neuroinflammatory diseases with failed neuroregeneration. In diseases such as multiple sclerosis and stroke, T-cell infiltration occurs in periventricular zones where NPCs are located and is associated with irreversible neuronal loss. We studied the effect of T-cell activation on NPC functions. NPC proliferation and neuronal differentiation were impaired by granzyme B (GrB) released by the T-cells. GrB mediated its effects by the activation of a Gi-protein-coupled receptor leading to decreased intracellular levels of cAMP and subsequent expression of the voltage-dependent potassium channel, Kv1.3. Importantly, blocking channel activity with margatoxin or blocking its expression reversed the inhibitory effects of GrB on NPCs. We have thus identified a novel pathway in neurogenesis. The increased expression of Kv1.3 in pathological conditions makes it a novel target for promoting neurorestoration.
Dexamethasone-cyclodextrin-polymer co-complexes in aqueous eye drops. Aqueous humor pharmacokinetics in humans. (1996)

The cyclodextrin-based drug delivery system enhances both the solubility of dexamethasone in aqueous eye drops and the permeability of the drug into the human eye. Dexamethasone concentration levels in the human aqueous humor exceed those reported with currently available steroid eye drops.
Bruton Tyrosine Kinase Inhibitor Ibrutinib (PCI-32765) Has Significant Activity in Patients With Relapsed/Refractory B-Cell Malignancies (2012)

Ibrutinib, a novel BTK-targeting inhibitor, is well tolerated, with substantial activity across B-cell histologies.
Structurally Distinct, Stage-Specific Ribosomes Occur in Plasmodium (1987)

Two structurally distinct nuclear genes code for cytoplasmic small subunit ribosomal RNA's in the parasite Plasmodium berghei. Stable transcripts from one of the ribosomal RNA genes are found almost exclusively in those stages of the life cycle that develop in the mosquito. When the parasite infects the mammalian host, transcripts from the second gene become the predominant small subunit ribosomal RNA species.
Short synthetic glycopeptides successfully induce antibody responses to carcinoma‐associated Tn antigen (2000)

Glycopeptides containing a tumor-associated carbohydrate antigen (mono-, tri- or hexa-Tn antigen) as a B-cell epitope and a CD4+ T-cell epitope (PV: poliovirus or TT: tetanus toxin) were prepared for immunological studies. Several Tn antigen residues [FmocSer/Thr (alpha-GalNAc)-OH] were successively incorporated into the peptide sequence with unprotected carbohydrate groups. The tri- and hexa-Tn glycopeptides were recognized by MLS128, a Tn-specific monoclonal antibody. The position of the tri-Tn motif in the peptide sequence and the peptide backbone itself do not alter its antigenicity. As demonstrated by both ELISA and FACS analysis, the glycopeptides induced high titers of anti-Tn antibodies in mice, in the absence of a carrier molecule. In addition, the generated antibodies recognized the native Tn antigen on cancer cells. The antibody response obtained with a D-(Tn3)-PV glycopeptide containing three alpha-GalNAc-D-serine residues is similar that obtained with the Tn6-PV glycopeptide. These results demonstrate that short synthetic glycopeptides are able to induce anticancer antibody responses.