gebhart/patrepeval huggingface dataset:
Cannabidiol and (−)Δ 9 -tetrahydrocannabinol are neuroprotective antioxidants (1998)

The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat cortical neuron cultures exposed to toxic levels of the excitatory neurotransmitter glutamate. Glutamate toxicity was reduced by both cannabidiol, a nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (-)Delta9-tetrahydrocannabinol (THC). Cannabinoids protected equally well against neurotoxicity mediated by N-methyl-D-aspartate receptors, 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid receptors, or kainate receptors. N-methyl-D-aspartate receptor-induced toxicity has been shown to be calcium dependent; this study demonstrates that 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid/kainate receptor-type neurotoxicity is also calcium-dependent, partly mediated by voltage sensitive calcium channels. The neuroprotection observed with cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating it to be cannabinoid receptor independent. Previous studies have shown that glutamate toxicity may be prevented by antioxidants. Cannabidiol, THC and several synthetic cannabinoids all were demonstrated to be antioxidants by cyclic voltametry. Cannabidiol and THC also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical (Fenton reaction) system and neuronal cultures. Cannabidiol was more protective against glutamate neurotoxicity than either ascorbate or alpha-tocopherol, indicating it to be a potent antioxidant. These data also suggest that the naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia.
Three-mirror cavity CO/sub 2/ laser for intracavity saturated-absorption spectroscopy (1988)

We report on the results of experimental and theoretical investigations of a CO/sub 2/ laser with a three-mirror cavity, in one of the compartments of which an amplifying medium is placed. It is shown that the transmission function for field intensity in the second compartment and losses of such a cavity depend in a complex manner on the relation of the lengths of the compartments and reflection coefficient of the middle mirror. Dependence of field intensity in the amplifying and hollow compartments when tuning the lasing frequency to the center of the amplifying transition on the reflection coefficient of the middle mirror is studied. It is shown that we can reduce by 10--100 fold the field intensity in the hollow compartment by an appropriate choice of the parameters and geometry of the three-mirror cavity, and achieve values comparable to saturation parameters of mostly widely used absorbing media (SF/sub 6/, OsO/sub 4/) in this spectral range by using a telescopic beam expander.
New Russian Design (1992)

Shows and describes designs for posters, magazines, buildings, products, and furniture, and offers brief profiles of young designers.
[Rectal micropolyps after total colectomy in familial polyposis. Efficacy of sulindac]. (1990)

The aim of this study was to assess the effectiveness of sulindac therapy for eradication of micropolyps in 8 patients with familial polyposis coli. All patients had undergone colectomy and ileoproctostomy 4.5 years (range 3 months-20 years) before and had tubulous adenomas micropolyps in the rectum. Initial sulindac therapy 200 mg or 300 mg daily was started in all patients and was continued in 7 patients. In these 7 patients macroscopic and microscopic eradication of micropolyps was obtained within 3.4 months (1-8). After discontinuation of sulindac therapy, recurrence of micropolyps occurred in 4 patients within 3 to 4 months. Three patients had no recurrence with a follow-up of 1 to 19 months. A new eradication of micropolyps was obtained in these 4 patients with a second sulindac cure within 3 to 6 months. These observations confirm the effectiveness of sulindac therapy for eradication of tubulous adenomas micropolyps in familial polyposis, but after discontinuation of therapy, recurrence is frequent. Continuous or intermittent therapy might reduce recurrence.
Effective analysis for engineering real-time fixed priority schedulers (1995)

There has been considerable activity in recent years in developing analytical techniques for hard real-time systems. Inevitably these techniques make simplifying assumptions so as to reduce the complexity of the problem to be solved. Unfortunately this leads to a gap between theory and engineering practice. The paper presents new analysis that enables the costs of the scheduler (clock overheads, queue manipulations and release delays) to be factored into the standard equations for calculating worst-case response times. As well as predicting the true behavior of realistic systems, the analysis also allows free parameters, such as clock interrupt rate, to be determined.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
New Methods Enabling Efficient Incorporation of Unnatural Amino Acids in Yeast (2008)

New chemical and physical properties can be selectively introduced into proteins directly in live cells by genetically incorporating unnatural amino acids. The incorporation efficiency determines how effective such properties can be exploited and was very low in yeast. We developed a new method for efficient expression of orthogonal bacterial tRNA in yeast using polymerase III promoters that are cleaved from primary transcripts. In addition, a yeast strain deficient in nonsense-mediated mRNA decay was generated to prevent rapid degradation of target mRNA containing premature stop codons, which are the most frequently used to encode unnatural amino acids. These new strategies enabled a significant increase in yield of unnatural amino acid containing proteins from tens of micrograms to tens of milligrams per liter in yeast.
Conservation of structural features reveals the existence of a large family of inhibitory cell surface receptors and noninhibitory/activatory counterparts (1997)

Immunoreceptor tyrosine-based inhibition motifs (ITIMs) consist of a 6-amino acid stretch (ILV)xYxx(LV). ITIMs are expressed in the intracytoplasmic domain of transmembrane receptors, which extinguish cell activation induced by receptors bearing immunoreceptor tyrosine-based activation motifs. The recent identification of new members of the ITIM-bearing receptor family (such as the signal-regulatory proteins) extends the ITIM concept to the negative regulation of growth factor- and oncogene-induced activation in nonhemopoietic cells. In addition, it appears that a feature of the family of ITIM-bearing receptors is the existence of noninhibitory/activatory counterparts devoid of intracytoplasmic ITIMs and characterized by the presence of a charged amino acid residue in their transmembrane domain.
Dielectric thickness dependence of quantum capacitance in graphene varactors with local metal back gates (2012)

The temperature-dependent C-V characteristics for two samples with target HfO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> thicknesses of 20 nm (sample A), and 10 nm (sample B) are shown in Figs. 2 and 3. The results show that the capacitance tuning range increases with decreasing HfO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> thicknesses, as expected. A comparison of the normalized C-V curves for both samples at room temperature is shown in Fig. 4. The capacitance tuning range from V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">g</sub> - V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Dirac</sub> = 0 to +1.5 V is 1.17:1 for sample A and 1.38:1 for sample B. Fig. 5 shows a comparison of the C-V characteristics for the varactors with MIM capacitors fabricated on the same sample. A very consistent trend is observed where the capacitance-per-unit-area for the MIM capacitors is significantly higher than for the varactors. The EOT values extracted from the MIM capacitors are found to be 4.1 nm and 2.7 nm for samples A and B, respectively. In order to understand this behavior in more detail, numerical modeling was performed on the temperature-dependent C-V characteristics where the random potential fluctuations, σ, in the graphene was used as an adjustable fitting parameter [5]. The results are shown in Fig. 6. The fact that the fitted EOT values cannot completely account for the capacitance reduction in Fig. 5 is a strong indicator that the effective device area of the varactors is less than the layout area. However, additional modeling, particularly taking into account the effect of interface traps, and other imperfections between the graphene and HfO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> [6-7] is needed to fully understand the observed behavior. In the future, further scaling of the EOT needs to be investigated, as well as fabrication of the devices on insulating substrates for eventual use in resonator circuits. As a preliminary demonstration (Fig. 7), we have fabricated a single-finger varactor on a quartz substrate, with EOT (as determined by MIM capacitors) of 1.9 nm and tuning range >;1.5:1 at room temperature.
Comparison of Escherichia coli and T3 RNA Polymerases (1973)

The sensitivities of the Escherichia coli and bacteriophage T3 RNA polymerases to various compounds have been investigated in vitro. Neither enzyme is sensitive to the drug α‐amanitin. The E. coli polymerase is inhibited by an exotoxin from Bacillus thuringiensis ; the phage enzyme is not. Although both enzymes are inhibited by actinomycin D and distamycin A, there is a differential effect: the T3 enzyme is more sensitive to distamycin A than the E. coli enzyme, and less sensitive to actinomycin D. While distamycin A preferentially inhibits chain initiation by both enzymes, actinomycin D affects mainly chain elongation. The rifamycin derivative AF/013 was found to selectively inhibit chain initiation by the T3 RNA polymerase and this drug was used to characterize a transient initiation complex observed when the T3 RNA polymerase is incubated with GTP alone as a substrate.
Critical aspects of the Bayesian approach to phase I cancer trials (2008)

The Bayesian approach to finding the maximum-tolerated dose in phase I cancer trials is discussed. The suggested approach relies on a realistic dose-toxicity model, allows one to include prior information, and supports clinical decision making by presenting within-trial information in a transparent way. The modeling and decision-making components are flexible enough to be extendable to more complex settings. Critical aspects are emphasized and a comparison with the continual reassessment method (CRM) is performed with data from an actual trial and a simulation study. The comparison revealed similar operating characteristics while avoiding some of the difficulties encountered in the actual trial when applying the CRM.
Persistent cytokine expression in trigeminal ganglion latently infected with herpes simplex virus type 1 (1996)

Following ocular infection, herpes simplex virus type 1 (HSV-1) establishes latency in trigeminal ganglion (TG) neurons. Using reverse transcription-PCR, cytokine gene expression was analyzed in the TGs of mice infected with HSV-1. IL-2, TNF-alpha, IFN-gamma, IL-10, and RANTES mRNAs were readily detected in TGs taken from mice 7 days postinoculation (PI). Likewise, IL-2, IL-6, IL-10, and IFN-gamma protein were detected by ELISA of TG homogenates. Between 5 and 45 days PI, IL-10, IFN-gamma, TNF-alpha, and RANTES mRNAs were detected in nearly 100% of latently infected TGs (latent infection was confirmed by reverse transcription-PCR detection of HSV-1 latency-associated transcripts). T cell-associated cytokine and chemokine mRNAs (IL-2, IL-10, IFN-gamma, and RANTES) were still detected in the majority of latently infected TG samples taken between 60 and 135 days PI. In contrast, these cytokine mRNA species were rarely detected in uninfected TGs. Measurement of serum Abs to HSV-1 at different times revealed that anti-HSV-1 Ab concentrations approached a plateau in mice by 30 days PI but remained at high levels 67 and 125 days PI. Although there was molecular evidence of an ongoing immune response to HSV-1 in latently infected TG, histologic analysis indicated that very few mononuclear cells remained in the ganglion 60 days PI. Collectively, the results suggest that residual lymphocytes encounter viral Ag during HSV-1 latency with sufficient frequency to remain activated. The paradox of a persistent immune response against a latent infection is discussed.
Targeting of loaded Sendai virus envelopes by covalently attached insulin molecules to virus receptor-depleted cells: fusion-mediated microinjection of ricin A and simian virus 40 DNA. (1985)

Insulin molecules were covalently attached to detergent-solubilized Sendai virus envelope glycoproteins (HN and F polypeptides) by the use of the crosslinking reagent succinimidyl 4-(p-maleimidophenyl)butyrate (SMPB). Reconstitution of modified viral glycoproteins (carrying covalently attached insulin) together with unmodified viral glycoproteins resulted in the formation of "fusogenic" viral envelopes bearing insulin molecules. Reconstitution of such fusogenic viral envelopes in the presence of ricin A or simian virus 40 (SV40) DNA resulted in the formation of viral envelopes bearing insulin molecules and loaded with ricin A or SV40 DNA. Such viral envelopes were able to bind to hepatoma tissue culture cells (HTCC) from which Sendai virus receptors were removed by treatment with neuraminidase. Incubation of viral envelopes loaded with ricin A with virus receptor-depleted HTCC resulted in fusion-mediated injection of the toxin, as inferred from inhibition of protein synthesis and decrease in cell viability of the microinjected cells. Fusion-mediated injection of SV40 DNA was inferred from the appearance of SV40 tumor antigen in microinjected cells. Binding and fusion of the loaded viral envelopes to neuraminidase-treated HTCC was mediated solely by the virus-associated insulin molecules. Addition of free insulin molecules inhibited binding of the viral envelopes and, consequently, the microinjection of ricin A and SV40 DNA.
Technologies for low latency interconnection switches (1989)

This paper presents an engineering design for a low latency high bandwidth interconnection network which will form the switching substrate for a multi-model parallel processing system. The performance is enhanced with a variety of approaches covering interconnection protocols, routing, fault tolerance, advanced packaging, and electrical interconnection techniques. The synergistic application of these technologies leads to a high performance design.
Diverse CD8+ T-Cell Responses to Renal Cell Carcinoma Antigens in Patients Treated with an Autologous Granulocyte-Macrophage Colony-Stimulating Factor Gene-Transduced Renal Tumor Cell Vaccine (2005)

A phase I clinical trial with granulocyte-macrophage colony-stimulating factor tumor cell vaccines in patients with metastatic renal cell carcinoma (RCC) showed immune cell infiltration at vaccine sites and delayed-type hypersensitivity (DTH) responses to autologous tumor cells indicative of T-cell immunity. To further characterize RCC T-cell responses and identify relevant RCC-associated antigens, we did a detailed analysis of CD8+ T-cell responses in two vaccinated RCC patients who generated the greatest magnitude of DTH response and also displayed a strong clinical response to vaccination (>90% reduction in metastatic tumor volume). Three separate CD8+ T-cell lines (and subsequent derived clones) derived from patient 24 recognized distinct RCC-associated antigens. One recognized a shared HLA-A*0201-restricted antigen expressed by both renal cancer cells and normal kidney cells. This recognition pattern correlated with a positive DTH test to normal kidney cells despite no evidence of impairment of renal function by the patient's remaining kidney after vaccination. A second line recognized a shared HLA-C7-restricted antigen that was IFN-gamma inducible. A third line recognized a unique HLA-A*0101-restricted RCC antigen derived from a mutated KIAA1440 gene specific to the tumor. In addition, two independent CTL lines and three clones were also generated from patient 26 and they recognized autologous tumor cells restricted through HLA-A*0205, HLA-A/B/C, and HLA-B/C. These results show that paracrine granulocyte-macrophage colony-stimulating factor tumor vaccines may generate a diverse repertoire of tumor-reactive CD8+ T-cell responses and emphasize the importance of polyvalency in the design of cancer immunotherapies.
CD8+Lymphocytes from Simian Immunodeficiency Virus-Infected Rhesus Macaques Recognize 14 Different Epitopes Bound by the Major Histocompatibility Complex Class I Molecule Mamu-A*01: Implications for Vaccine Design and Testing (2001)

It is becoming increasingly clear that any human immunodeficiency virus (HIV) vaccine should induce a strong CD8(+) response. Additional desirable elements are multispecificity and a focus on conserved epitopes. The use of multiple conserved epitopes arranged in an artificial gene (or EpiGene) is a potential means to achieve these goals. To test this concept in a relevant disease model we sought to identify multiple simian immunodeficiency virus (SIV)-derived CD8(+) epitopes bound by a single nonhuman primate major histocompatibility complex (MHC) class I molecule. We had previously identified the peptide binding motif of Mamu-A*01(2), a common rhesus macaque MHC class I molecule that presents the immunodominant SIV gag-derived cytotoxic T lymphocyte (CTL) epitope Gag_CM9 (CTPYDINQM). Herein, we scanned SIV proteins for the presence of Mamu-A*01 motifs. The binding capacity of 221 motif-positive peptides was determined using purified Mamu-A*01 molecules. Thirty-seven peptides bound with apparent K(d) values of 500 nM or lower, with 21 peptides binding better than the Gag_CM9 peptide. Peripheral blood mononuclear cells from SIV-infected Mamu-A*01(+) macaques recognized 14 of these peptides in ELISPOT, CTL, or tetramer analyses. This study reveals an unprecedented complexity and diversity of anti-SIV CTL responses. Furthermore, it represents an important step toward the design of a multiepitope vaccine for SIV and HIV.
The biology of cancer testis antigens: Putative function, regulation and therapeutic potential (2011)

Cancer testis antigens (CTA) are a large family of tumor-associated antigens expressed in human tumors of different histological origin, but not in normal tissues except for testis and placenta. This tumor-restricted pattern of expression, together with their strong in vivo immunogenicity, identified CTA as ideal targets for tumor-specific immunotherapeutic approaches, and prompted the development of several clinical trials of CTA-based vaccine therapy. Driven by this practical clinical interest, a more detailed characterization of CTA biology has been recently undertaken. So far, at least 70 families of CTA, globally accounting for about 140 members, have been identified. Most of these CTA are expressed during spermatogenesis, but their function is still largely unknown. Epigenetic events, particularly DNA methylation, appear to be the primary mechanism regulating CTA expression in both normal and transformed cells, as well as in cancer stem cells. In view of the growing interest in CTA biology, the aim of this review is to provide the most recent information on their expression, regulation and function, together with a brief summary of the major clinical trials involving CTA as therapeutic agents. The pharmacologic modulation of CTA expression profiles on neoplastic cells by DNA hypomethylating drugs will also be discussed as a feasible approach to design new combination therapies potentially able to improve the clinical efficacy of currently adopted CTA-based immunotherapeutic regimens in cancer patients.
Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma (2014)

This noninvasive classification system is molecularly based on the stem/maturation status of HCCs and can be incorporated into current staging practices to improve management algorithms, especially in the early stage of disease.
Perturbation of sphingolipid metabolism and ceramide production in HIV‐dementia (2004)

Infection by the human immunodeficiency virus type 1 (HIV-1) often results in neurological dysfunction including HIV dementia (HIVD). Alterations in cytokine and redox balance are thought to play important roles in the pathogenesis of HIVD, but the specific mechanisms underlying neuronal dysfunction and death are unknown. Activation of cytokine receptors and oxidative stress can induce the production of ceramide from membrane sphingomyelin, and recent findings suggest that ceramide is an important mediator of a form of programmed cell death called apoptosis. We now report that levels of ceramide, sphingomyelin, and hydroxynonenal (HNE) are significantly increased in brain tissues and cerebrospinal fluid of HIVD patients. Exposure of cultured neurons to the neurotoxic HIV proteins gp120 and Tat resulted in increased cellular levels of sphingomyelin, ceramide, and HNE. The ceramide precursor palmitoyl-CoA sensitized neurons to Tat and gp120 toxicity, whereas an inhibitor of ceramide production reduced Tat and gp120-induced increases of ceramide and HNE and protected the neurons from Tat and gp120-induced death. These results suggest that HIV-1 infection may promote a lipid imbalance in neural cells, resulting in an overproduction of ceramide and consequent cellular dysfunction and death.
Protein−Ligand NOE Matching:  A High-Throughput Method for Binding Pose Evaluation That Does Not Require Protein NMR Resonance Assignments (2006)

Given the three-dimensional (3D) structure of a protein, the binding pose of a ligand can be determined using distance restraints derived from assigned intra-ligand and protein-ligand nuclear Overhauser effects (NOEs). A primary limitation of this approach is the need for resonance assignments of the ligand-bound protein. We have developed an approach that utilizes data from 3D 13C-edited, 13C/15N-filtered HSQC-NOESY spectra for evaluating ligand binding poses without requiring protein NMR resonance assignments. Only the 1H NMR assignments of the bound ligand are essential. Trial ligand binding poses are generated by any suitable method (e.g., computational docking). For each trial binding pose, the 3D 13C-edited, 13C/15N-filtered HSQC-NOESY spectrum is predicted, and the predicted and observed patterns of protein-ligand NOEs are matched and scored using a fast, deterministic bipartite graph matching algorithm. The best scoring (lowest "cost") poses are identified. Our method can incorporate any explicit restraints or protein assignment data that are available, and many extensions of the basic procedure are feasible. Only a single sample is required, and the method can be applied to both slowly and rapidly exchanging ligands. The method was applied to three test cases: one complex involving muscle fatty acid-binding protein (mFABP) and two complexes involving the leukocyte function-associated antigen 1 (LFA-1) I-domain. Without using experimental protein NMR assignments, the method identified the known binding poses with good accuracy. The addition of experimental protein NMR assignments improves the results. Our "NOE matching" approach is expected to be widely applicable; i.e., it does not appear to depend on a fortuitous distribution of binding pocket residues.