gebhart/patrepeval huggingface dataset:
Smooth Muscle Tone Regulation in Rabbit Cavernosal and Spongiosae Tissue by Cyclic AMP- and Cyclic GMP-Dependent Mechanisms (1994)

The relaxing effects of several specific and nonspecific inhibitors of phosphodiesterases (PDE) on rabbit isolated corpus cavernosum (CC) and spongiosum (CS) were investigated. Preparations were mounted in organ baths, and isometric tension was recorded. The results were compared with the effects of direct administration of analogs of the second messenger cyclic nucleotides and the effects of forskolin, a direct stimulator of adenylate cyclase, and the nitric oxide donor 3-morpholinosydnonimine (SIN 1). All drugs relaxed the phenylephrine-induced contractions in CC and CS in a dose-dependent fashion. In CC and CS, type III (SK&F 95654) and type V (zaprinast and dipyramidole) PDE inhibitors, as well as the nonspecific inhibitors papaverine and trequinsin, showed no differences in IC50. The type IV inhibitor rolipram relaxed CC and CS at significantly lower concentrations (p < 0.005) than any other PDE inhibitor, and in CC the type III and IV inhibitor zardaverine was more potent (p < 0.05) than SK&F 95654. SIN 1 stimulates guanylate cyclase and effectively inhibits contractions in CC and CS. Activation of adenylate cyclase by forskolin also was highly effective (p < 0.005). It is concluded that PDE inhibition constitutes an effective relaxing mechanism in rabbit CC and CS. The marked effects of the different types of PDE inhibitors support the importance of cyclic guanosine 3',5'-monophosphate and cyclic adenosine 3',5'-monophosphate in smooth muscle relaxation in erectile tissue.
Increased recurrence and metastasis in patients whose primary head and neck squamous cell carcinomas secreted granulocyte‐macrophage colony‐stimulating factor and contained CD34 natural suppressor cells (1997)

Human head and neck squamous cell carcinomas (HNSCC) that produce high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) have been shown to contain CD34+ natural suppressor cells that inhibit the activity of intratumoral T-cells. The present study evaluated whether GM-CSF production and the presence of CD34+ cells within primary HNSCC would translate into increased recurrence, metastasis or cancer-related death during the 2 years following surgical excision. Freshly excised primary HNSCC of 20 patients that subsequently developed disease, and of 17 patients that remained with no evidence of disease were analyzed for production of GM-CSF and for CD34+ cell content. The cancers of patients that subsequently developed recurrences or metastatic disease produced almost 4-fold the levels of GM-CSF and had approximately 2.5-fold the number of CD34+ cells as did cancers of patients that remained disease-free. In a second method of analysis, the prognostic significance of high vs. low GM-CSF and CD34+ cell values was evaluated. These analyses showed that patients whose cancers produced high GM-CSF levels or had a high CD34+ cell content had a disproportionately high incidence of recurrence or metastatic disease (94% and 100%, respectively), while the majority of patients whose primary cancers produced low levels of GM-CSF or had a low CD34+ cell content remained disease-free (16% and 19%, respectively). Our results indicate that the presence of CD34+ cells in GM-CSF-producing HNSCC is associated with a poorer prognosis for the cancer patients and suggest the utility of these parameters as prognostic indicators of outcome. Mechanistically, our results suggest that the presence of immune suppressive CD34+ cells in GM-CSF-producing HNSCC leads to increased tumor recurrence or metastasis.Int. J. Cancer 74:69–74. © 1997 Wiley-Liss, Inc.
Cell-penetrating peptides in drug development: enabling intracellular targets (2007)

A large body of literature has shown that CPPs (cell-penetrating peptides) are capable of carrying macromolecules across the plasma membrane. CPPs can penetrate a wide variety of tissue types and enable modulation of intracellular targets with molecules that, by themselves, are incapable of penetrating cells. As a result, CPPs are recognized for their potential value in validating intracellular targets that could lead to drug discovery programmes [Dietz and Bahr (2004) Mol. Cell Neurosci. 27, 85-131]. The potential for CPP-drug conjugates to be used as human therapeutic agents has not been extensively explored and there is limited knowledge regarding the characteristics of CPPs which are necessary for drug development. A better understanding of the properties of CPPs relating to in vivo pharmacology, pharmacokinetics, pharmacodynamics and safety will continue to inform and encourage novel drug development efforts using CPPs as therapeutics. Here we will discuss areas of interest for drug development of CPP-conjugated compounds.
Aligning Short Sequencing Reads with Bowtie (2010)

This unit shows how to use the Bowtie package to align short sequencing reads, such as those output by second-generation sequencing instruments. It also includes protocols for building a genome index and calling consensus sequences from Bowtie alignments using SAMtools.
Peptido-Targeting of the Mitochondrial Transition Pore Complex for Therapeutic Apoptosis Induction (2006)

The permeability transition pore (PTPC), a polyprotein complex, participates in the mitochondrial homeostasis as well as in the mitochondrial phase of the intrinsic pathway of apoptosis. It integrates multiple death signals including alterations of the intracellular milieu, translocation of pro-apoptotic members of the Bax/Bcl-2 family, p53, and viral proteins. As a consequence, PTPC can act as a coordinator of the pro-apoptotic mitochondrial membrane permeabilization process and the release of pro-apoptotic intermembrane space proteins into the cytosol. Moreover, the deregulation of PTPC has been involved in several major human pathologies such as cancer, neurodegeneration, ischemia/reperfusion, aging, as well as hepatotoxicity. Therefore, PTPC has emerged as a promising potential therapeutic target. Here, we will review the current knowledge concerning the two opposite functions of the PTPC and its implication in various pathologies. We will discuss the possibility to target this complex with peptides to modulate apoptosis in an innovative therapeutic perspective.
Comparative Analysis of the Magnitude, Quality, Phenotype, and Protective Capacity of Simian Immunodeficiency Virus Gag-Specific CD8+ T Cells following Human-, Simian-, and Chimpanzee-Derived Recombinant Adenoviral Vector Immunization (2013)

Recombinant adenoviral vectors (rAds) are the most potent recombinant vaccines for eliciting CD8(+) T cell-mediated immunity in humans; however, prior exposure from natural adenoviral infection can decrease such responses. In this study we show low seroreactivity in humans against simian- (sAd11, sAd16) or chimpanzee-derived (chAd3, chAd63) compared with human-derived (rAd5, rAd28, rAd35) vectors across multiple geographic regions. We then compared the magnitude, quality, phenotype, and protective capacity of CD8(+) T cell responses in mice vaccinated with rAds encoding SIV Gag. Using a dose range (1 × 10(7)-10(9) particle units), we defined a hierarchy among rAd vectors based on the magnitude and protective capacity of CD8(+) T cell responses, from most to least, as: rAd5 and chAd3, rAd28 and sAd11, chAd63, sAd16, and rAd35. Selection of rAd vector or dose could modulate the proportion and/or frequency of IFN-γ(+)TNF-α(+)IL-2(+) and KLRG1(+)CD127(-)CD8(+) T cells, but strikingly ∼30-80% of memory CD8(+) T cells coexpressed CD127 and KLRG1. To further optimize CD8(+) T cell responses, we assessed rAds as part of prime-boost regimens. Mice primed with rAds and boosted with NYVAC generated Gag-specific responses that approached ∼60% of total CD8(+) T cells at peak. Alternatively, priming with DNA or rAd28 and boosting with rAd5 or chAd3 induced robust and equivalent CD8(+) T cell responses compared with prime or boost alone. Collectively, these data provide the immunologic basis for using specific rAd vectors alone or as part of prime-boost regimens to induce CD8(+) T cells for rapid effector function or robust long-term memory, respectively.
Introduction (1991)

Many techniques described here involve a number of hazards, such as high electrical current and voltage, radioactivity and highly toxic chemicals. It is absolutely essential that the instructions of equipment manufacturers be followed, and that particular attention be paid to the local and federal safety regulations.KeywordsAlpha HelixPlant Molecular Biology ReporterTranscriptional Regulatory ProteinDimerization MotifRecognition HelixThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
The Role of Etiquette in an Automated Medication Reminder (2004)

This paper describes a model of politeness between intentional agents developed from sociolinguistic observations of human-human interactions "Brown and Levinson, 1987" and suggests a method for applying it to human-machine interactions. Applications in the context of a medication reminder system are presented including data which suggest that the Brown and Levinson model provides good predictions for how "polite" alternate reminding utterances will be perceived when delivered by a machine. Additional data from a field test of one such reminding system are presented which indicate that "politeness", and the etiquette behaviors which achieve various levels of politeness, are important to elders-though not that maximal politeness behaviors are either expected, desired or, perhaps, productive. Further, future applications of the Brown and Levinson model in military training are also discussed.
Histone deacetylase inhibitors and paclitaxel cause synergistic effects on apoptosis and microtubule stabilization in papillary serous endometrial cancer cells (2006)

The use of histone deacetylase (HDAC) inhibitors has shown promise for a variety of malignancies. In this investigation, we define the activity of this class of inhibitors in combination with traditional cytotoxic chemotherapy in endometrial cancer cells. Significant reductions in growth were observed in Ark2 and KLE endometrial cancer cells following treatment with paclitaxel, doxorubicin, carboplatin, or the HDAC inhibitor trichostatin A (TSA). However, only combined treatment with TSA/paclitaxel caused synergistic inhibition of cell growth. This combination also resulted in significant changes in cell morphology. Using cell cycle analysis, nuclear staining, and Western blot analysis for poly(ADP-ribose) polymerase and caspase-9 degradation products, TSA/paclitaxel showed the most dramatic activation of the apoptotic cascade. These effects were also observed when the HDAC inhibitors HDAC inhibitor-1 or oxamflatin were substituted for TSA. The anticancer properties of paclitaxel are known to result in part from inhibition of microtubule depolymerization, which results in apoptosis. We show that TSA administration also stabilizes microtubules via alpha-tubulin acetylation. Furthermore, using Western blot and immunohistochemical analysis, treatment with TSA/paclitaxel led to a significant increase in acetylated tubulin and microtubule stabilization. These effects were confirmed in a mouse xenograft model. Moreover, TSA/paclitaxel resulted in a 50% reduction in tumor weight compared with either agent alone. This study provides in vivo evidence of nonhistone protein acetylation as one possible mechanism by which HDAC inhibitors reduce cancer growth. The TSA/paclitaxel combination seems to hold promise for the treatment of serous endometrial carcinoma and other malignancies with limited sensitivity to paclitaxel.
Human T lymphotropic virus type III infection of human alveolar macrophages (1986)

Abstract The human T-cell lymphotropic virus type III (HTLV-III) is the etiologic agent of the acquired immunodeficiency syndrome (AIDS) and preferentially infects T4 lymphocytes. Other cell types, notably B lymphocytes and other nonlymphoid cells, also have been reported to be infected in vitro by HTLV-III. We now report on the susceptibility of human pulmonary macrophages to infection with HTLV-III in vitro. Alveolar macrophages infected with HTLV-III produced low levels of virus that could be transferred to allogeneic human peripheral blood mononuclear leukocytes as long as 2 weeks after initiation of infection. Unlike HTLV-III infection of T lymphocytes, macrophages appeared more resistant to viral-mediated cytopathic effects. Primary cultures of pulmonary macrophages from two of four patients with AIDS spontaneously produced low levels of virus detected as precipitable reverse transcriptase activity, suggesting that these cells were infected in vivo. Because tissue macrophages are long-lived cells, they may act as a reservoir of HTLV-III, capable of transmitting the virus to other susceptible cells such as T lymphocytes, causing periodic low- level viremia. Macrophage infection with HTLV-III may be one mechanism for the establishment of viral persistence in infected hosts.
Failure to Quantify Viral Load with Two of the Three Commercial Methods in a Pregnant Woman Harboring an HIV Type 1 Subtype G Strain (1998)

The level of HIV-1 RNA in plasma has become one of the most important markers in the follow-up of HIV-infected patients. Three techniques are commercially available: both the Amplicor HIV Monitor and the NASBA HIV-1 RNA QT are target amplification methods, whereas the Quantiplex HIV RNA assay is a branched DNA signal amplification technique. Detection in both target amplification techniques is based on a single primer pair and a single probe in the gag region, whereas multiple probes capture the pol region of the viral RNA in the branched DNA assay. We investigated the discrepant observation of an undetectable viral load in an immunodeficient pregnant HIV-1-infected patient of African origin with no prior antiretroviral treatment. Although clinical progression was present in this patient with tuberculosis and a low CD4 cell count, viral load determinations with both the Amplicor Monitor and NASBA assays revealed no detectable RNA levels. The presence of HIV-1 RNA in the plasma of the patient was demonstrated by an in-house RNA-PCR. Subsequent HIV-1 RNA quantification with the branched DNA method revealed a high viremia (460,000 copies/ml). DNA sequence analysis of the gag gene identified a subtype G HIV-1 strain (HIV-1BL). To our knowledge this is the first report of a patient harboring an HIV-1 genotype of the main group with a high viral load as quantified by the branched DNA assay, but undetectable with the two commercial HIV RNA amplification techniques because of genetic divergence. In the case of discrepant low viral loads determined by one amplification technique in patients with advanced clinical stage one should use an alternative quantification technique for confirmation.
Identification of Novel Immunodominant CD4+Th1-Type T-Cell Peptide Epitopes from Herpes Simplex Virus Glycoprotein D That Confer Protective Immunity (2003)

The molecular characterization of the epitope repertoire on herpes simplex virus (HSV) antigens would greatly expand our knowledge of HSV immunity and improve immune interventions against herpesvirus infections. HSV glycoprotein D (gD) is an immunodominant viral coat protein and is considered an excellent vaccine candidate antigen. By using the TEPITOPE prediction algorithm, we have identified and characterized a total of 12 regions within the HSV type 1 (HSV-1) gD bearing potential CD4(+) T-cell epitopes, each 27 to 34 amino acids in length. Immunogenicity studies of the corresponding medium-sized peptides confirmed all previously known gD epitopes and additionally revealed four new immunodominant regions (gD(49-82), gD(146-179), gD(228-257), and gD(332-358)), each containing naturally processed epitopes. These epitopes elicited potent T-cell responses in mice of diverse major histocompatibility complex backgrounds. Each of the four new immunodominant peptide epitopes generated strong CD4(+) Th1 T cells that were biologically active against HSV-1-infected bone marrow-derived dendritic cells. Importantly, immunization of H-2(d) mice with the four newly identified CD4(+) Th1 peptide epitopes but not with four CD4(+) Th2 peptide epitopes induced a robust protective immunity against lethal ocular HSV-1 challenge. These peptide epitopes may prove to be important components of an effective immunoprophylactic strategy against herpes.
Task learning for a real robot by using virtual space (2006)

As a novel learning method, reinforced learning by which a robot acquires control rules through trial and error has gotten a lot of attention. However, it is quite difficult for robots to acquire control rules by reinforcement learning in real space because many learning trials are needed to achieve the control rules; the robot itself may lose control, or there may be safety problems with the control objects. In this paper, we propose a method in which a robot in real space learns the virtual task; then the task is transferred from virtual to real space. The robot eventually acquires the task in a real environment. We show that a real robot can acquire a task in virtual space with an input device by an example of an inverted pendulum. Next, we verify that the acquired task in virtual space can be applied to a real world task. We emphasize the utilization of virtual space to effectively obtain the real world task.
Exfoliative cytology of the human mammary gland and its value in the diagnosis of cancer and other diseases of the breast (1958)

PONTANEOUS nipple discharge, unrelated to S pregnancy or lactation, is usually regarded as a sign of mammary disease or endocrine dysfunction. T h e discharge may be serous, serosanguineous, or sanguineous; however, its macroscopic appearance does not constitute a reliable indicator of its underlying cause. I n view of the fact that spontaneous secretion may occur in the absence of any palpable localized change in the mammary tissue that would pinpoint an area for biopsy or needle aspiration, a microscopic examination of the secretion might be reasonably expected to serve as a valuable aid in diagnosis.
A 900 MHz integrated discrete-time filtering RF front-end (2002)

The authors introduce a radio receiver architecture that avoids external intermediate frequency (IF) filters, while maintaining the selectivity required for narrowband frequency-multiplexed channels. The receiver is based on a subsampling architecture and operates in the 800-900 MHz range. It is a potential candidate for use in applications such as portable mobile data systems, personal communications devices, and cordless telephony. This receiver differs from a superheterodyne architecture in that the mixer is replaced by a sampling circuit and the intermediate frequency filters are replaced by a cascade of downsampling stages employing discrete-time filtering. The process of subsampling, sampling the input signal at a rate lower than the highest frequency components of the input signal, performs a function equivalent to mixing. Because the input is bandlimited by an analog RF filter, the Nyquist criterion is satisfied as long as the sampling rate is more than twice the bandwidth of this filter. The noise filter following the low noise amplifier (LNA) limits the noise bandwidth to prevent wideband noise from aliasing into the signal band and increasing the noise floor.
Evidence of a correlation between process yields and reliability data for a rad-hard SOI technology (2002)

A methodology for wafer level reliability prediction is described. Accelerated lifetests performed on specifically designed test structures allowed us to correlate reliability with elementary process yields. These elementary yields were extracted for each test structure (which characterizes a process step) from data obtained after wafer level tests. The wafer "peripheral" area, on which was detected a significant number of clustered defects at wafer level, presented few failures during the accelerated lifetest, showing that the geographical origin of the devices does not significantly affect the reliability.
Classically Restricted Human CD8+ T Lymphocytes Derived from Mycobacterium tuberculosis -Infected Cells: Definition of Antigenic Specificity (2001)

Previous studies in murine and human models have suggested an important role for HLA Ia-restricted CD8(+) T cells in host defense to Mycobacterium tuberculosis (Mtb). Therefore, understanding the Ags presented via HLA-Ia will be important in understanding the host response to Mtb and in rational vaccine design. We have used monocyte-derived dendritic cells in a limiting dilution analysis to generate Mtb-specific CD8(+) T cells. Two HLA-Ia-restricted CD8(+) T cell clones derived by this method were selected for detailed analysis. One was HLA-B44 restricted, and the other was HLA-B14 restricted. Both were found to react with Mtb-infected, but not bacillus Calmette-Guérin-infected, targets. For both these clones, the Ag was identified as culture filtrate protein 10 (CFP10)/Mtb11, a 10.8-kDa protein not expressed by bacillus Calmette-Guérin. Both clones were inhibited by the anti-class I Ab and anti-HLA-B,C Abs. Using a panel of CFP10/Mtb11-derived 15-aa peptides overlapping by 11 aa, the region containing the epitopes for both clones has been defined. Minimal 10-aa epitopes were defined for both clones. CD8(+) effector cells specific for these two epitopes are present at high frequency in the circulating pool. Moreover, the CD8(+) T cell response to CFP10/Mtb11 can be largely accounted for by the two epitopes defined herein, suggesting that this is the immunodominant response for this purified protein derivative-positive donor. This study represents the first time CD8(+) T cells generated against Mtb-infected APC have been used to elucidate an Mtb-specific CD8(+) T cell Ag.
Comparison of the Hydroxylase Inhibitor Dimethyloxalylglycine and the Iron Chelator Deferoxamine in Diabetic and Aged Wound Healing (2017)

This first direct comparison of deferoxamine and dimethyloxalylglycine in the treatment of impaired wound healing suggests significant therapeutic potential for topical deferoxamine treatment in ischemic and diabetic disease.
Early Diagnosis Key to Epithelial Ovarian Cancer Detection (2003)

Ovarian cancer is the fourth leading cause of cancer death for women and the most fatal of all gynecologic malignancies. Labeled "the whispering disease," ovarian cancer has an insidious onset with vague symptoms such as gastrointestinal upset, abdominal bloating and fatigue. Early diagnosis is often delayed and patients present with advanced disease. This article provides an overview of ovarian cancer, including epidemiology, classification, risk factors, screening and early detection.