gebhart/patrepeval huggingface dataset:
Modulation of glucocorticoid receptor function by protein kinase A. (1992)

Protein kinase A (PKA) has been shown to modulate the pattern of gene expression via transcription factors such as cAMP response element binding protein. However, in F9 embryonal carcinoma cells which lack endogenous functional cAMP response element binding protein, we have found that PKA is still able to control gene transcription through the glucocorticoid receptor (GR) by up-regulating its hormone-dependent trans-activation. Dose-response analysis indicates that PKA does not alter the ligand binding affinity of GR. PKA seems to act through the DNA binding domain of GR, since GR mutants which lack either the amino-terminal or the ligand binding domain are still able to be up-regulated by PKA. In support of this proposal, we demonstrate that PKA can enhance the DNA binding activity of GR. Our results suggest a novel mechanism by which PKA modulates the steroid sensitivity of a target cell by enhancing the DNA binding activity of GR for its cognate hormone response elements.
Delivery of novel macromolecular drugs against HIV-1 (2001)

The development of new low molecular weight drugs against human immunodeficiency virus Type 1 (HIV-1) targets other than reverse transcriptase (RT) and protease, such as the integrase and the envelope glycoprotein, is likely to take many years. Macromolecular drugs, including antisense oligonucleotides, ribozymes, RNA decoys and transdominant mutant proteins, may be able to interfere with a relatively large number of viral targets, thereby decreasing the likelihood of the emergence of drug-resistant strains. It may also be relatively easy to alter the sequence of some of the macromolecular drugs to counter emerging drug-resistant viruses. The delivery of antisense oligonucleotides and ribozymes to HIV-1 infected or potentially infectable cells by antibody-targeted liposomes, certain cationic lipid formulations and pH-sensitive liposomes results in significant anti-HIV-1 activity. These carriers not only facilitate cytoplasmic delivery but also protect the drugs from nuclease digestion. Delivery of therapeutic genes (another form of macromolecular drug) to target cells is an important challenge of gene therapy. Following delivery by a viral vector, sufficient levels of gene expression must be maintained over an extended period of time to have therapeutic activity. Robust expression of therapeutically useful ribozymes, antisense, decoys and aptamers can be achieved by the use of Pol III expression systems. Moloney murine leukaemia virus- (MoMuLV), adeno-associated virus (AAV)-, or HIV-derived vectors expressing a variety of therapeutic genes have been used successfully to inhibit HIV-1 replication in cultured cells.
Correlating Structure and Properties of Super‐Concentrated Electrolyte Solutions: 17O NMR and Electrochemical Characterization (2019)

Abstract Super‐concentrated electrolyte solutions are of increasing interest for safer and more stable lithium and post‐lithium batteries. The combination of 7 Li and 17 O (at natural abundance) nuclear magnetic resonance (NMR) and electrochemical characterization is proposed here as an effective approach to investigate the Li + solvation structures and properties of electrolytes featuring tetraethylene glycol dimethyl ether (TEGDME) and lithium‐bis(trifluoromethane sulfonyl) imide (LiTFSI). Five different formulations from salt‐in‐solvent to solvent‐in‐salt with LiTFSI at different concentrations (0.1 m, 0.5 m, 2 m, 4 m, 5 m) are investigated. The NMR results, also supported by physico‐chemical characterizations such as thermal gravimetric analyses, differential scanning calorimetry, specific conductivity and viscosity, give information about the association of Li + ions with anion and solvent molecules, allowing a deeper knowledge on the relationships among structure and functional properties of super‐concentrated solutions.
An exploratory double‐blind, randomized, placebo‐controlled study to assess the efficacy of CitruSlim on body composition and lipid parameters in obese individuals (2021)

The prevalence of obesity in developing and developed countries has been well recognized, and the worldwide obesity rates have nearly tripled since 1975, according to the World Health Organization. CitruSlim, a standardized product containing a blend of Citrus bergamia and Eurycoma longifolia, can reduce cortisol, cholesterol, triglycerides, and hyperglycemia. These properties can contribute to reduction in body weight or body mass index (BMI) in obese patients. A randomized, double-blind, placebo-controlled clinical study was designed to evaluate the efficacy and tolerability of CitruSlim in body weight management in obese individuals, and the results were compared with that of placebo. A total of 97 participants were allocated, randomized, and treated with CitruSlim high-dose (HD, 400 mg), CitruSlim low-dose (LD, 200 mg), and placebo for 112 days. At the end of the study, CitruSlim HD and CitruSlim LD significantly reduced BMI compared to the placebo group and were well tolerated; however, it did not improve parameters associated with dyslipidemia and metabolic disturbances. The study findings suggested that CitruSlim was effective in reducing body weight in obese patients.
[Characterisitics of Japanese Guidelines for the Management of Hypertension 2009]. (2011)

Revised version of the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2009 (JSH2009) has been delivered in Jan. 2009 (Hypertens Res 32: 3-107, 2009). Followings are the main points of JSH2009 guidelines : (1) CV risk stratification and strategy of hypertension management are revised in consideration with of high-normal BP, metabolic syndrome(risk stratum-2), and CKD(risk stratum-3). (2) Tight control of BP levels < 130/85 mmHg is recommended in general hypertensive patients. More tight control is recommended in patients with DM, CKD, and post MI : BP < 130/80 mmHg. (3) Final target of BP in the elderly is < 140/90 mmHg. However BP should be reduced carefully by setting an intermediate target of < 150/90 mmHg in patients with 75 yrs or over. (4) BP control over 24 hours and usefulness of home BP measurement are stressed. Masked hypertension, morning surge, night-time hypertension, and sleep apnea syndrome are particularly important issues. (5) CCB, ARB, ACE inhibitor, diuretic, and beta-blocker are recommended as initial antihypertensive drugs, combination therapy such as ARB+diuretics or CCB are often necessary to achieve BP target. (6) Tight BP control and specific consideration for choice of drugs such as RA inhibitors are required in hypertension associated with organ damage and hypertension complicated with diabetes, CKD and metabolic syndrome.
Safety of cornea and iris in ocular surgery with 355-nm lasers (2015)

A recent study showed that 355-nm nanosecond lasers cut cornea with similar precision to infrared femtosecond lasers. However, use of ultraviolet wavelength requires precise assessment of ocular safety to determine the range of possible ophthalmic applications. In this study, the 355-nm nanosecond laser was evaluated for corneal and iris damage in rabbit, porcine, and human donor eyes as determined by minimum visible lesion (MVL) observation, live/dead staining of the endothelium, and apoptosis assay. Single-pulse damage to the iris was evaluated on porcine eyes using live/dead staining. In live rabbits, the cumulative median effective dose (ED50) for corneal damage was 231 J/cm2, as seen by lesion observation. Appearance of endothelial damage in live/dead staining or apoptosis occurred at higher radiant exposure of 287 J/cm2. On enucleated rabbit and porcine corneas, ED50 was 87 and 52 J/cm2, respectively, by MVL, and 241 and 160 J/cm2 for endothelial damage. In human eyes, ED50 for MVL was 110 J/cm2 and endothelial damage at 453 J/cm2. Single-pulse iris damage occurred at ED 50 of 208 mJ/cm2. These values determine the energy permitted for surgical patterns and can guide development of ophthalmic laser systems. Lower damage threshold in corneas of enucleated eyes versus live rabbits is noted for future safety evaluation.
Novel silica surface charge density mediated control of the optical properties of embedded optically active materials and its application for fiber optic pH sensing at elevated temperatures (2014)

Silica and silica incorporated nanocomposite materials have been extensively studied for a wide range of applications. Here we demonstrate an intriguing optical effect of silica that, depending on the solution pH, amplifies or attenuates the optical absorption of a variety of embedded optically active materials with very distinct properties, such as plasmonic Au nanoparticles, non-plasmonic Pt nanoparticles, and the organic dye rhodamine B (not a pH indicator), coated on an optical fiber. Interestingly, the observed optical response to varying pH appears to follow the surface charge density of the silica matrix for all the three different optically active materials. To the best of our knowledge, this optical effect has not been previously reported and it appears universal in that it is likely that any optically active material can be incorporated into the silica matrix to respond to solution pH or surface charge density variations. A direct application of this effect is for optical pH sensing which has very attractive features that can enable minimally invasive, remote, real time and continuous distributed pH monitoring. Particularly, as demonstrated here, using highly stable metal nanoparticles embedded in an inorganic silica matrix can significantly improve the capability of pH sensing in extremely harsh environments which is of increasing importance for applications in unconventional oil and gas resource recovery, carbon sequestration, water quality monitoring, etc. Our approach opens a pathway towards possible future development of robust optical pH sensors for the most demanding environmental conditions. The newly discovered optical effect of silica also offers the potential for control of the optical properties of optically active materials for a range of other potential applications such as electrochromic devices.
Suture Fixation of Biodegradable Nanofibrous Poly‐Caprolactone Scaffolds to Bovine Meniscus: A Novel Approach to Repairing Meniscal Tears (SS‐48) (2006)

We have designed a novel biodegradable, aligned nanofibrous scaffold for augmenting the repair of meniscal tears historically considered irreparable. As a first step in this endeavor, scaffold fixation to meniscal tissue was quantified by comparing suture pull-out from scaffolds and fixation strength to the native tissue.
Recent advances in intense laser filamentation (2009)

Recent advances in filamentation nonlinear optics in air will be presented. These include polarization separation effect, THz generation through plasma and four wave mixing, effect of the excitation of rotational wave packet of air molecules and super-excited states excitation.
Independent Control of HVOF Particle Velocity and Temperature (1996)

Abstract In the past, independent control of HVOF spray particle velocity and temperature has not been possible, confusing the effect of either parameter on coating properties. This study describes a method by which velocity and temperature may be varied independently. Commercial HVOF equipment fitted with a special conical supersonic nozzle having three distinct particle injection locations was used. The present results, obtained through experiments and numerical simulations, revealed several pertinent facts. First, particle velocity is principally related to combustion chamber pressure and is relatively unaffected by other design or operating conditions. Second, particle temperature is related to particle residence time within the nozzle, which can be controlled by the choice of particle injection location. In these experiments, the impact velocity and temperature of stainless steel particles were controlled within the ranges 215 to 510 m/s and 1670 to 2160 K, respectively. This range of parameters produced significant variations in splat morphology and coating microstructure. The implications of this study are not limited to the HVOF process, and may be generalized to other thermal spray techniques. From a research perspective, such particle control allows the effects of velocity and temperature on coating properties to be assessed and controlled independently. These results also have commercial application, potentially enabling the user to tailor particle impact velocity and temperature to achieve specific coating properties.
Therapeutic effects of the anti-CD74 mAb, milatuzumab, compared to anti-CD20 antibodies, in B-cell lymphomas (2007)

A58 CD74, an MHC class-II chaperone, is involved in NF-κB signaling pathways implicated in malignant B-cell proliferation and survival. The humanized anti-CD74 monoclonal antibody (mAb), milatuzumab (hLL1, or IMMU-115; Immunomedics, Inc, Morris Plains, NJ), is now in clinical evaluation for therapy of multiple myeloma after preclinical evidence of activity (Stein et al, Blood 2004;104:3705). Here we examine the therapeutic efficacy of milatuzumab in B-cell lymphomas. In vitro and in vivo studies were performed comparing milatuzumab to anti-CD20 mAbs. We observed that the CD74 and CD20 mAbs act through distinct mechanisms and exhibit different expression and sensitivity profiles. Importantly, anti-proliferative activity can be augmented in vitro when anti-CD74 and anti-CD20 mAbs are combined. As with rituximab, in most human lymphoma cell lines, milatuzumab alone does not show a direct cytotoxic effect in vitro, but when crosslinked with goat anti-human IgG does cause inhibition of proliferation and induction of apoptosis. Unlike rituximab, milatuzumab induces little or no ADCC or CDC. Although all B-cell lymphoma cell lines tested (10/10) express both CD74 and CD20, the relative expression of these 2 antigens varies. In Burkitt lines, such as Raji and Daudi, both CD20 and CD74 are expressed at high levels. Greater variability in antigen expression is observed in non-Burkitt NHL cell lines, with Namalwa and WSU-FSCCL expressing less CD20 than the other lines. Milatuzumab efficacy was examined in comparison to and in combination with veltuzumab (hA20 humanized anti-CD20 mAb from Immunomedics) in SCID mice bearing human B-cell lymphoma xenografts. In Raji and Daudi, milatuzumab treatment yielded a small but statistically significant increase in survival. For example, in Raji median survival times (MST) are 15 days (untreated), 21 days with 25 μg milatuzumab (P= 0.0008 vs. untreated), 32 days with 25 μg veltuzumab (P 220 days) in 7/10 mice, while veltuzumab and rituximab were significantly less effective. MST of 96 and 87.5 days were observed with no long-term survivors for veltuzumab and rituximab, respectively (P=0.0013 and P=0.0036 vs. milatuzumab); MST in untreated WSU-FSCCL-bearing SCIDs was 36 days. In a combination therapy study of milatuzumab and veltuzumab, WSU-FSCCL-bearing SCID mice were treated 5 days after injection of cells. Veltuzumab (35 μg) extended MST to 70 days, milatuzumab (35 μg) treatment increased survival further to 90.5 days, and the milatuzumab + veltuzumab combination yielded a MST of 113 days (P=0.0030 vs. veltuzumab and P=0.1478 vs. milatuzumab). Conclusions: Milatuzumab is a promising new therapeutic for B-cell lymphomas as a naked mAb, and shows significantly improved efficacy when combined with anti-CD20 mAbs. (Supported in part by USPHS grants P01CA103985 and R01CA109474 from the NCI and NJDHSS grant 07-1824-FS-N-0.)
Solventless and metal-free regioselective hydrofluorination of functionalized alkynes and allenes: an efficient protocol for the synthesis of gem-difluorides (2019)

A highly acidic fluorination system generated by DMPU-12HF and KHSO<sub>4</sub>-13HF can facilitate exclusive Markovnikov addition of HF to widely functionalized alkynes and allenes to produce <italic>gem</italic>-difluorides with an easy workup.
USP18-Based Negative Feedback Control Is Induced by Type I and Type III Interferons and Specifically Inactivates Interferon α Response (2011)

Type I interferons (IFN) are cytokines that are rapidly secreted upon microbial infections and regulate all aspects of the immune response. In humans 15 type I IFN subtypes exist, of which IFN α2 and IFN β are used in the clinic for treatment of different pathologies. IFN α2 and IFN β are non redundant in their expression and in their potency to exert specific bioactivities. The more recently identified type III IFNs (3 IFN λ or IL-28/IL-29) bind an unrelated cell-type restricted receptor. Downstream of these two receptor complexes is a shared Jak/Stat pathway. Several mechanisms that contribute to the shut down of the IFN-induced signaling have been described at the molecular level. In particular, it has long been known that type I IFN induces the establishment of a desensitized state. In this work we asked how the IFN-induced desensitization integrates into the network built by the multiple type I IFN subtypes and type III IFNs. We show that priming of cells with either type I IFN or type III IFN interferes with the cell's ability to further respond to all IFN α subtypes. Importantly, primed cells are differentially desensitized in that they retain sensitivity to IFN β. We show that USP18 is necessary and sufficient to induce differential desensitization, by impairing the formation of functional binding sites for IFN α2. Our data highlight a new type of differential between IFNs α and IFN β and underline a cross-talk between type I and type III IFN. This cross-talk could shed light on the reported genetic variation in the IFN λ loci, which has been associated with persistence of hepatitis C virus and patient's response to IFN α2 therapy.
Epigenetic silencing of PEG3 gene expression in human glioma cell lines* (2001)

Genomic imprinting, the phenomenon in which alleles of genes are expressed differentially depending on their parental origins, has important consequences for mammalian development, and disturbance of normal imprinting leads to abnormal embryogenesis and some inherited diseases and is also associated with various cancers. In the context of screening for novel imprinted genes on human chromosome 19q13.4 with mouse A9 hybrids, we identified a maternal allele-specific methylated CpG island in exon 1 of paternally expressed imprinted gene 3 (PEG3), a gene that exhibits paternal allele-specific expression. Because PEG3 expression is downregulated in some gliomas and glioma cell lines, despite high-level expression in normal brain tissues, we investigated whether the loss of PEG3 expression is related to epigenetic modifications involving DNA methylation. We found monoallelic expression of PEG3 in all normal brain tissues examined and five of nine glioma cell lines that had both unmethylated and methylated alleles; the remaining four glioma cell lines exhibited gain of imprinting with hypermethylated alleles. In addition, treatment of glioma cell lines with the DNA demethylating agent 5-aza-2'-deoxycytidine reversed the silencing of PEG3 biallelically. In this article, we report that the epigenetic silencing of PEG3 expression in glioma cell lines depends on aberrant DNA methylation of an exonic CpG island, suggesting that PEG3 contributes to glioma carcinogenesis in certain cases.
Magnetism, Ultrasound, and Light-Stimulated Mesoporous Silica Nanocarriers for Theranostics and Beyond (2021)

Stimuli-responsive multifunctional mesoporous silica nanoparticles (MSNs) have been studied intensively during the past decade. A large variety of mesopore capping systems have been designed, initially to show that it could be done and later for biomedical applications such as drug delivery and imaging. On-command release of cargo molecules such as drugs from the pores can be activated by a variety of stimuli. This paper focuses on three noninvasive, biologically usable external stimuli: magnetism, ultrasound, and light. We survey the variety of MSNs that have been and are being used and assess capping designs and the advantages and drawbacks of the nanoplatforms' responses to the various stimuli. We discuss important recent advances, their basic mechanisms, and their requirements for stimulation. On the basis of our survey, we identify fundamental challenges and suggest future directions for research that will unleash the full potential of these fascinating nanosystems for clinical applications.
A study of the structure–activity relationship of GABAA–benzodiazepine receptor bivalent ligands by conformational analysis with low temperature NMR and X-ray analysis (2021)

The stable conformations of GABAA-benzodiazepine receptor bivalent ligands were determined by low temperature NMR spectroscopy and confirmed by single crystal X-ray analysis. The stable conformations in solution correlated well with those in the solid state. The linear conformation was important for these dimers to access the binding site and exhibit potent in vitro affinity and was illustrated for α5 subtype selective ligands. Bivalent ligands with an oxygen-containing linker folded back upon themselves both in solution and the solid state. Dimers which are folded do not bind to Bz receptors.
Disease burden and quality of life of patients with chronic cough in Japan: a population-based cross-sectional survey (2021)

This study showed that patients with CC in Japan experienced significant burden compared with non-cough respondents. Patients with more severe cough and refractory CC experienced worse cough-related QoL. These results highlighted the unmet need for better interventions and treatments to reduce the burden among patients with CC.
Data from Steroid Receptor Coactivator-3 Expression in Lung Cancer and Its Role in the Regulation of Cancer Cell Survival and Proliferation (2023)

&lt;div&gt;Abstract&lt;p&gt;Steroid receptor coactivator-3 (SRC-3) is a histone acetyltransferase and nuclear hormone receptor coactivator, located on 20q12, which is amplified in several epithelial cancers and well studied in breast cancer. However, its possible role in lung cancer pathogenesis is unknown. We found SRC-3 to be overexpressed in 27% of non–small cell lung cancer (NSCLC) patients (&lt;i&gt;n&lt;/i&gt; = 311) by immunohistochemistry, which correlated with poor disease-free (&lt;i&gt;P&lt;/i&gt; = 0.0015) and overall (&lt;i&gt;P&lt;/i&gt; = 0.0008) survival. Twenty-seven percent of NSCLCs exhibited &lt;i&gt;SRC-3&lt;/i&gt; gene amplification, and we found that lung cancer cell lines expressed higher levels of SRC-3 than did immortalized human bronchial epithelial cells (HBEC), which in turn expressed higher levels of SRC-3 than did cultured primary human HBECs. Small interfering RNA–mediated downregulation of SRC-3 in high-expressing, but not in low-expressing, lung cancer cells significantly inhibited tumor cell growth and induced apoptosis. Finally, we found that SRC-3 expression is inversely correlated with gefitinib sensitivity and that SRC-3 knockdown results in epidermal growth factor receptor tyrosine kinase inhibitor–resistant lung cancers becoming more sensitive to gefitinib. Taken together, these data suggest that SRC-3 may be an important oncogene and therapeutic target for lung cancer. Cancer Res; 70(16); 6477–85. ©2010 AACR.&lt;/p&gt;&lt;/div&gt;
Age and morphine analgesia in cancer patients with postoperative pain (1980)

Our objective was to identify age-related differences in analgesia after 8 and 16 mg morphine intramuscularly. Retrospective analyses of controlled relative analgesic potency assays in 947 postoperative cancer patients revealed differences among age groups (18 to 29, 30 to 49, 50 to 69, and 70 to 89 yr) in total pain relief and duration of relief with little differences in peak relief. Weight and initial pain intensity were in the same range among age and dose groups. Aging was associated with enhanced analgesia. The difference in total relief between the extremes of adult age was approximately twice that with twice the dose. While in 50% of the oldest group relief was no longer obtained at 5 hr, in 50% of the youngest group relief was no longer obtained at 3 hr. These observations suggest that age is a factor in morphine analgesia.