gebhart/patrepeval huggingface dataset:
Differential expression of the LYL, SCL and E2A helix-loop-helix genes within the hemopoietic system. (1991)

The helix-loop-helix genes LYL, SCL and E2A are associated with chromosome translocations found in human lymphoid leukemias. To establish their hematopoietic expression patterns, we have isolated murine LYL and SCL cDNA clones and investigated the expression of all three genes by Northern blot analysis of 58 murine hemopoietic cell lines and tissues. The nucleotide sequences of LYL cDNA clones revealed alternative 5' untranslated sequences and differential splicing within the 5' portion of the coding region that may produce a LYL polypeptide lacking an N-terminal segment. The LYL gene was expressed in most myeloid, erythroid and B lymphocyte cell lines and displayed two alternative size classes of transcripts, the smaller size class (1.5-1.8 kb) being typical of the erythroid lineage and the larger class (2.0-2.3 kb) of the B cell lineage. These two size classes were found to differ in the 5' untranslated region. Thus, expression of the LYL gene appears to be differentially regulated in different hemopoietic cell types. In contrast, the E2A gene was expressed throughout the hemopoietic compartment as a single dominant transcript (3.5 kb). SCL expression was restricted to erythroid, mast and early myeloid cell lines, and the level of SCL transcripts (3.0 and 4.7 kb species) increased markedly during DMSO-induced differentiation of erythro-leukemia cells. Hence the SCL gene product may be an important regulatory factor for the erythroid lineage. The low or undetectable expression of both SCL and LYL in most T lymphoid cell sources is consistent with the view that the translocations of these genes in human T cell leukemias alter their normal regulation and may thereby contribute to neoplasia.
Oral Transmucosal Fentanyl Citrate: Overview of Pharmacological and Clinical Characteristics (2006)

Oral transmucosal fentanyl citrate (OTFC; brand name Actiq, Cephalon, UT) is a new opioid formulation that incorporates fentanyl into a lozenge and allows drug delivery through the buccal mucosa. This kind of absorption avoids first-pass metabolism, yielding a bioavailability substantially greater than oral administration. OTFC has a rapid onset of action and a short duration of effect. These characteristics, which resemble the course of a typical breakthrough pain episode, resulted in making OTFC the first opioid analgesic formulation specifically developed and approved for control of breakthrough pain in cancer patients. Apart from that, OTFC has been used in a variety of clinical situations of noncancer pain. This review article presents the synthesis; clinical pharmacology; pharmacokinetic and pharmacodynamic properties, toxicity, and clinical efficacy of this novel agent.
Reductions in corticotropin releasing factor‐like immunoreactivity in cerebral cortex in Alzheimer's disease, Parkinson's disease, and progressive supranuclear palsy (1987)

Dementias occurring in Alzheimer's disease, Parkinson's disease, and progressive supranuclear palsy are associated with dysfunction and death of neurons in a variety of cell populations, including cholinergic, monoaminergic, and peptidergic systems. In the present investigation of these three disorders, we demonstrated decreased levels of corticotropin releasing factor (CRF)-like immunoreactivity in the frontal, temporal, and occipital poles of the neocortex. Moreover, reductions in peptidergic immunoreactivity correlated with reductions in the activity of choline acetyltransferase, the enzyme that catalyzes the formation of acetylcholine. The reduction in cortical CRF levels may be due to abnormalities of intrinsic cortical neurons or to dysfunction in neurons that contain CRF and innervate cortex.
Ferroelectric control of magnetism inBaTiO3∕Feheterostructures via interface strain coupling (2007)

Reversible control of magnetism is reported for a Fe thin film in proximity of a $\mathrm{Ba}\mathrm{Ti}{\mathrm{O}}_{3}$ single crystal. Large magnetization changes emerge in response to ferroelectric switching and structural transitions of $\mathrm{Ba}\mathrm{Ti}{\mathrm{O}}_{3}$ controlled by applied electric fields and temperature, respectively. Interface strain coupling is the primary mechanism altering the induced magnetic anisotropy. As a result, coercivity changes up to 120% occur between the various structural states of $\mathrm{Ba}\mathrm{Ti}{\mathrm{O}}_{3}$. Up to 20% coercivity change is achieved via electrical control at room temperature. Our all solid state ferroelectric-ferromagnetic heterostructures open viable possibilities for technological applications.
A quasi-phase-matching technique for efficient optical mixing and frequency doubling (1976)

A detailed theory is presented of the second-order nonlinear optical interaction in a sequence of crystal lamellae oriented to give quasi-phase-matching. The efficiency of second-harmonic and sum-frequency generation is analyzed with respect to the orientation of the crystal axes, plate thickness, input intensities, transmission coefficients, dispersion in the intervening medium, and number of lamellae. An energy conserving modification of the small-signal approximation is introduced. To overcome the Fresnel reflection losses the use of antireflection coatings, optical contacting, and Brewster-angle incidence is considered with the latter approach emerging as the most promising. A series of experiments are described where 10.6-μ laser radiation is frequency doubled in a sequence of GaAs plates using Brewster-angle incidence. The conversion efficiency is investigated as a function of crystal orientation, intensity, and number of plates, and good agreement is found between theory and experiment.
Immunizing against breast cancer: A new swing for an old sword (2009)

Therapeutic potential of vaccination has been explored in many clinical trials involving patients with breast cancer. A large variety of cancer immunogens have been tested. The majority of clinical vaccination studies have been carried out in patients with metastatic breast cancer, characterized by extremely aggressive malignant tumors, resistant to all standard cytotoxic treatments and with longest-lasting disease. With active specific immunotherapy, tumor-associated antigens coupled to appropriate adjuvant can elicit a powerful antitumor responses. The potential advantages of therapeutic cancer vaccines are that they can augment an established immunogenic response to the tumor (which is generally weak in breast cancer), they target specific tumor antigens (although there are few), they are potentially non-toxic, they can be combined with conventional therapies and/or other immunotherapies, and they elicit immunologic memory to prevent recurrence of the tumor. It is unclear whether therapeutic vaccines for cancer prolong survival. Data of clinical activity have been observed by using vaccines targeting HER-2/neu protein, human telomerase reverse transcriptase, carcinoembryonic antigen (CEA), and carbohydrate antigen given after stem cell rescue. A better understanding of the relation between innate and adaptive immune responses, and of the immune escape mechanisms employed by tumor cells, the discovery of mechanisms underlying immunological tolerance, and acknowledgment of the importance of both cell-mediated and humoral adaptive immunity for the control of tumour growth are necessary for leading to a more comprehensive immunotherapeutic approach in breast cancer.
Novel strategy with potential to identify developmentally competent IVF blastocysts (2008)

The combination of blastocyst biopsy, microarray gene expression profiling and DNA fingerprinting is a powerful tool to identify diagnostic markers of competence to develop to term. This strategy may be used to develop a rapid diagnostic assay or for refining existing criteria for the selection of the single most viable blastocyst among a cohort developing in vitro.
Transdermal progesterone cream as an alternative progestin in hormone therapy. (2006)

Patients preferred transdermal PC over oral MPA. This preliminary data indicate that CEE/PC has a similar effect on the endometrium as standard oral HT over a 6-month period.
Risk of breast cancer and other cancers in heterozygotes for ataxia-telangiectasia (1999)

Mortality from cancer among 178 parents and 236 grandparents of 95 British patients with ataxia-telangiectasia was examined. For neither parents nor grandparents was mortality from all causes or from cancer appreciably elevated over that of the national population. Among mothers, three deaths from breast cancer gave rise to a standardized mortality ratio of 3.37 (95% confidence interval (CI): 0.69–9.84). In contrast, there was no excess of breast cancer in grandmothers, the standardized mortality ratio being 0.89 (95% CI: 0.18–2.59), based on three deaths. This is the largest study of families of ataxia-telangiectasia patients conducted in Britain but, nonetheless, the study is small and CIs are wide. However, taken together with data from other countries, an increased risk of breast cancer among female heterozygotes is still apparent, though lower than previously thought.
Selective Imaging of Malignant Ascites in a Mouse Model of Peritoneal Metastasis Using in Vivo Dynamic Nuclear Polarization-Magnetic Resonance Imaging (2016)

The presence of malignant ascites in advanced cancer patients is associated with both a poor prognosis and quality of life with a risk of abdominal infection and sepsis. Contemporary noninvasive visualization methods such as ultrasound, computed tomography, and magnetic resonance imaging (MRI) often struggle to differentiate malignant ascites from surrounding tissues. This study aimed to determine the utility of selective H2O imaging in the abdominal cavity with a free radical probe and deuterium oxide (D2O) contrast agent using in vivo dynamic nuclear polarization-MRI (DNP-MRI). Phantom imaging experiments established a linear relationship between H2O volume and image intensity using in vivo DNP-MRI. Similar results were obtained when the radical-D2O probe was used to determine selective and spatial information on H2O in vivo, modeled by the injection of saline into the abdominal cavity of mice. To demonstrate the utility of this method for disease, malignant ascites in peritoneal metastasis animal model was selected as one of the typical examples. In vivo DNP-MRI of peritoneal metastasis animal model was performed 7-21 days after intraperitoneal injection of luciferase, stably expressing the human pancreatic carcinoma (SUIT-2). The image intensity with increasing malignant ascites was significantly increased at days 7, 16, and 21. This increase corresponded to in vivo tumor progression, as measured by bioluminescent imaging. These results suggest that H2O signal enhancement in DNP-MRI using radical-D2O contrast is positively associated with the progression of dissemination and could be a useful biomarker for malignant ascites with cancer metastasis.
A novel approach for next‐generation sequencing of circulating tumor cells (2016)

These spiking experiments provide proof of concept of a clinically applicable workflow for real-time monitoring of patient tumor using noninvasive liquid biopsies.
Determination of Petroleum Properties by Fiber-Optic Fourier Transform Raman Spectrometry and Partial Least-Squares Analysis (1995)

The petroleum products unleaded gasoline and reformate have been analyzed by Fourier transform (FT) Raman spectrometry with the use of a fiber optic cable that allows a measurement to be carried out remotely from the spectrometer. Samples were contained in glass cuvettes, and collection of high-quality spectra was simple. Fuel properties such as research octane number (RON), motor octane number (MON), density, benzene content, and flexible volatility index (FVI) were determined by application of the partial least-squares multivariate statistical approach. Analytically useful calibrations ( R 2 &gt; 0.97) were obtained for all of the significant fuel properties studied. Cross-validation results were, as expected, worse than the calibration results but still indicated the usefulness of the method. Standard errors of prediction with the use of cross validation for models that contained 14–28 samples include: MON = 0.12, RON = 0.16, benzene % = 0.09, and density = 0.0018. These results demonstrate that it is feasible to undertake on-line analyses of petroleum fuels by fiber-optic FT-Raman spectrometry.
Levosimendan, a New Inotropic and Vasodilator Agent (2006)

Several clinical studies suggest substantial limitations of currently available positive inotropic substances, including beta1-adrenoceptor agonists and phosphodiesterase III inhibitors in the short- and long-term treatment of heart failure. The reasons for these detrimental effects are related to the mechanism of action of these drugs, including increases in intracellular Ca2+ with subsequent increases in myocardial oxygen demand and arrhythmogenesis. Levosimendan, a myofilament Ca2+ sensitizer with inotropic effects, increases myocardial performance without substantial changes in oxygen consumption and with neutral effects on heart rhythm. In addition, levosimendan has vasodilatory effects that are achieved by stimulation of adenosine triphosphate-dependent potassium channels. This action may be of specific interest in the setting of myocardial ischemia. To date, levosimendan is approved in 31 countries worldwide, and more patients with heart failure have participated in randomized controlled trials with levosimendan than with any other intravenous inotropic agent.
Development of allosteric modulators of GPCRs for treatment of CNS disorders (2013)

The discovery of allosteric modulators of G protein-coupled receptors (GPCRs) provides a promising new strategy with potential for developing novel treatments for a variety of central nervous system (CNS) disorders. Traditional drug discovery efforts targeting GPCRs have focused on developing ligands for orthosteric sites which bind endogenous ligands. Allosteric modulators target a site separate from the orthosteric site to modulate receptor function. These allosteric agents can either potentiate (positive allosteric modulator, PAM) or inhibit (negative allosteric modulator, NAM) the receptor response and often provide much greater subtype selectivity than orthosteric ligands for the same receptors. Experimental evidence has revealed more nuanced pharmacological modes of action of allosteric modulators, with some PAMs showing allosteric agonism in combination with positive allosteric modulation in response to endogenous ligand (ago-potentiators) as well as “bitopic” ligands that interact with both the allosteric and orthosteric sites. Drugs targeting the allosteric site allow for increased drug selectivity and potentially decreased adverse side effects. Promising evidence has demonstrated potential utility of a number of allosteric modulators of GPCRs in multiple CNS disorders, including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, as well as psychiatric or neurobehavioral diseases such as anxiety, schizophrenia, and addiction.
Redundancy, resilience, and host specificity of the ruminal microbiota: implications for engineering improved ruminal fermentations (2015)

The ruminal microbial community is remarkably diverse, containing 100s of different bacterial and archaeal species, plus many species of fungi and protozoa. Molecular studies have identified a "core microbiome" dominated by phyla Firmicutes and Bacteroidetes, but also containing many other taxa. The rumen provides an ideal laboratory for studies on microbial ecology and the demonstration of ecological principles. In particular, the microbial community demonstrates both redundancy (overlap of function among multiple species) and resilience (resistance to, and capacity to recover from, perturbation). These twin properties provide remarkable stability that maintains digestive function for the host across a range of feeding and management conditions, but they also provide a challenge to engineering the rumen for improved function (e.g., improved fiber utilization or decreased methane production). Direct ruminal dosing or feeding of probiotic strains often fails to establish the added strains, due to intensive competition and amensalism from the indigenous residents that are well-adapted to the historical conditions within each rumen. Known exceptions include introduced strains that can fill otherwise unoccupied niches, as in the case of specialist bacteria that degrade phytotoxins such as mimosine or fluoroacetate. An additional complicating factor in manipulating the ruminal fermentation is the individuality or host specificity of the microbiota, in which individual animals contain a particular community whose species composition is capable of reconstituting itself, even following a near-total exchange of ruminal contents from another herd mate maintained on the same diet. Elucidation of the interactions between the microbial community and the individual host that establish and maintain this specificity may provide insights into why individual hosts vary in production metrics (e.g., feed efficiency or milk fat synthesis), and how to improve herd performance.
Oligonucleotides with conjugated dihydropyrroloindole tripeptides: base composition and backbone effects on hybridization (1997)

The ability of conjugated minor groove binding (MGB) residues to stabilize nucleic acid duplexes was investigated by synthesis of oligonucleotides bearing a tethered dihydropyrroloindole tripeptide (CDPI3). Duplexes bearing one or more of these conjugated MGBs were varied by base composition (AT- or GC-rich oligonucleotides), backbone modifications (phosphodiester DNA, 2'-O-methyl phosphodiester RNA or phosphorothioate DNA) and site of attachment of the MGB moiety (5'- or 3'-end of either duplex strand). Melting temperatures of the duplexes were determined. The conjugated CDPI3 residue enhanced the stability of virtually all duplexes studied. The extent of stabilization was backbone and sequence dependent and reached a maximum value of 40-49 degrees C for d(pT)8. d(pA)8. Duplexes with a phosphorothioate DNA backbone responded similarly on CDPI3 conjugation, although they were less stable than analogous phosphodiesters. Modest stabilization was obtained for duplexes with a 2'-O-methyl RNA backbone. The conjugated CDPI3 residue stabilized GC-rich DNA duplexes, albeit to a lesser extent than for AT-rich duplexes of the same length.
Nanoengineering Strong Silica Aerogels (2002)

In the quest for strong lightweight materials, silica aerogels would be very attractive, if they were not fragile. The strength of silica aerogel monoliths has been improved by a factor of over 100 through cross-linking the nanoparticle building blocks of preformed silica hydrogels with poly(hexamethylene diisocyanate). Composite monoliths are much less hygroscopic than native silica, and they do not collapse when in contact with liquids.
Molecular Biology of Steroid Hormone Synthesis* (1988)

STEROID hormones are familiar clinically and physiologically as regulators of physiological processes. Five groups of steroid hormones are generally recognized according to their physiological behavior: mineralocorticoids, which instruct the renal tubules to retain sodium; glucocorticoids, which are named for their carbohydratemobilizing properties but have many other effects as well; estrogens, which induce female secondary sexual characteristics; progestins, which are essential for reproduction; and androgens, which induce male secondary sexual characteristics. These classes of steroid hormones are structurally similar and arise from a common series of pathways. They are distinguished by their actions on one or more specific steroid hormone receptors. The hormone/receptor complexes function as tissue-specific transcriptional regulators of distinct domains of genes and, consequently, exert their broad array of physiological effects. (For reviews, see Refs. 1 and 2.) The pathways by which these steroid hormones are produced from cholesterol were initially studied by studying the structures of the steroids themselves. Over the past 30 yr, studies of enzyme kinetics and of steroidal precursorproduct relationships have led to the widely held belief that a very large number of distinct enzymes are involved in the conversion of cholesterol and its esters to active steroid hormones. The application of modern protein chemistry and molecular biology to these questions has radically changed this view.
Silencing of stat4 gene inhibits cell proliferation and invasion of colorectal cancer cells. (2015)

Signal transducers and activators of transcription (STAT) play critical roles in development, proliferation, and immune defense. However the consequences of STAT hyperactivity can predispose to diseases, including colorectal cancer. In the present study, we aimed to evaluate the function of STAT4 in human colorectal cancer (CRC). The expression of STAT4 was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was carried out to investigate the effects of lentivirus-mediated STAT4 shRNA (Lv-shSTAT4) on cell proliferation and invasive potential indicated by MTT and Transwell assays in CRC cell lines (SW480 and Caco2). As a consequence, it was found that the expression of STAT4 protein was significantly increased in CRC tissues compared with that in adjacent non-cancerous tissues (ANCT) (71.1% vs 44.4%, P=0.015), and was related with the Dukes staging and depth of invasion in CRC patients (P=0.022; P=0.001). Silencing of STAT4 gene suppressed cell proliferation and invasion of CRC cells. Taken together, these findings demonstrate that increased expression of STAT4 is positively correlated with the depth of invasion in CRC patients, and inhibition of STAT4 expression represses the growth and invasion of CRC cells, suggesting that STAT4 may be a promising therapeutic target for the treatment of CRC.
Glutathione selectively modulates the binding of platinum drugs to human copper chaperone Cox17 (2015)

The copper chaperone Cox17 (cytochrome c oxidase copper chaperone) has been shown to facilitate the delivery of cisplatin to mitochondria, which contributes to the overall cytotoxicity of the drug [Zhao et al. (2014) Chem. Commun. 50: , 2667-2669]. Kinetic data indicate that Cox17 has reactivity similar to glutathione (GSH), the most abundant thiol-rich molecule in the cytoplasm. In the present study, we found that GSH significantly modulates the reaction of platinum complexes with Cox17. GSH enhances the reactivity of three anti-cancer drugs (cisplatin, carboplatin and oxaliplatin) to Cox17, but suppresses the reaction of transplatin. Surprisingly, the pre-formed cisplatin-GSH adducts are highly reactive to Cox17; over 90% platinum transfers from GSH to Cox17. On the other hand, transplatin-GSH adducts are inert to Cox17. These different effects are consistent with the drug activity of these platinum complexes. In addition, GSH attenuates the protein aggregation of Cox17 induced by platination. These results indicate that the platinum-protein interactions could be substantially influenced by the cellular environment.