gebhart/patrepeval huggingface dataset:
Effects of antiepileptic drugs on associative LTP‐like plasticity in human motor cortex (2010)

Antiepileptic drugs (AEDs) are used extensively in clinical practice but relatively little is known on their specific effects at the systems level of human cortex. Here we tested, using a double-blind randomized placebo-controlled crossover design in healthy subjects, the effects of a single therapeutic oral dose of seven AEDs with different modes of action (tiagabine, diazepam, gabapentin, lamotrigine, topiramate, levetiracetam and piracetam) on long-term potentiation (LTP)-like motor cortical plasticity induced by paired associative transcranial magnetic stimulation (PAS). PAS-induced LTP-like plasticity was assessed from the increase in motor evoked potential amplitude in a hand muscle contralateral to the stimulated motor cortex. Levetiracetam significantly reduced LTP-like plasticity when compared to the placebo condition. Tiagabine, diazepam, lamotrigine and piracetam resulted in nonsignificant trends towards reduction of LTP-like plasticity while gabapentin and topiramate had no effect. The particularly depressant effect of levetiracetam is probably explained by its unique mode of action through binding at the vesicle membrane protein SV2A. Enhancement of gamma-amino butyric acid-dependent cortical inhibition by tiagabine, diazepam and possibly levetiracetam, and blockage of voltage-gated sodium channels by lamotrigine, may also depress PAS-induced LTP-like plasticity but these mechanisms appear to be less relevant. Findings may inform about AED-related adverse effects on important LTP-dependent central nervous systems processes such as learning or memory formation. The particular depressant effect of levetiracetam on LTP-like plasticity may also relate to the unique properties of this drug to inhibit epileptogenesis, a potentially LTP-associated process.
Telogen skin contains an inhibitor of hair growth (1990)

We have investigated whether C57B1-6 mouse skin with all its follicles in the telogen stage of the hair cycle contains a hair-growth inhibitory activity, as opposed to skin with anagen follicles. Crude aqueous extracts of whole telogen mouse skin (TE), anagen skin (AE) or vehicle alone (V) were injected intraperitoneally into mice in which anagen had previously been induced by plucking of telogen hair follicles. Injection of TE, but not AE or V, significantly retarded the development of anagen follicles, as measured by macroscopic and quantitative microscopic hair growth parameters (skin pigmentation and thickness, appearance of trichohyaline granules) and the incorporation of tritiated thymidine into mouse skin from animals previously treated with either TE or V (skin organ culture). This inhibitory activity seemed to be localized to the epidermis and was also present in rat epidermis. We suggest that this apparently non-species-specific inhibitor present in telogen skin may play a role in regulating the hair cycle in rodents.
Comparative evaluation of seven oligonucleotide analogs as potential antisense agents (1993)

12-Mer analogues, representative of seven different classes of structurally modified oligonucleotides and complementary to the same target, have been compared for their binding affinity for both single-stranded DNA and RNA, resistance to hydrolysis by nucleases in culture medium (RPMI 1640 + 10% inactivated fetal calf serum), and inhibition of HIV-1 replication in de novo infected MT4 T lymphocytes. The viral target was the splice acceptor site of the premessenger coding for the regulatory protein tat. The oligo(2'-O-alkyl)ribonucleotides (beta-2'O-allyl-RNA and beta-2'OMe-RNA) were shown to form the most stable hybrids with complementary RNA strands whereas the alpha-anomeric oligodeoxynucleoside phosphorothioate analogue displayed the highest stability in the culture medium. All the modified oligonucleotides examined in the present study exhibited a sequence-nonspecific inhibitory effect on HIV-1 replication, the phosphorothioate analogues being the most active ones (ED50 < 1 microM).
The Tumor Metastasis Suppressor Gene Drg-1 Down-regulates the Expression of Activating Transcription Factor 3 in Prostate Cancer (2006)

The tumor metastasis suppressor gene Drg-1 has been shown to suppress metastasis without affecting tumorigenicity in immunodeficient mouse models of prostate and colon cancer. Expression of Drg-1 has also been found to have a significant inverse correlation with metastasis or invasiveness in various types of human cancer. However, how Drg-1 exerts its metastasis suppressor function remains unknown. In the present study, to elucidate the mechanism of action of the Drg-1 gene, we did a microarray analysis and found that induction of Drg-1 significantly inhibited the expression of activating transcription factor (ATF) 3, a member of the ATF/cyclic AMP-responsive element binding protein family of transcription factors. We also showed that Drg-1 attenuated the endogenous level of ATF3 mRNA and protein in prostate cancer cells, whereas Drg-1 small interfering RNA up-regulated the ATF3 expression. Furthermore, Drg-1 suppressed the promoter activity of the ATF3 gene, indicating that Drg-1 regulates ATF3 expression at the transcriptional level. Our immunohistochemical analysis on prostate cancer specimens revealed that nuclear expression of ATF3 was inversely correlated to Drg-1 expression and positively correlated to metastases. Consistently, we have found that ATF3 overexpression promoted invasiveness of prostate tumor cells in vitro, whereas Drg-1 suppressed the invasive ability of these cells. More importantly, overexpression of ATF3 in prostate cancer cells significantly enhanced spontaneous lung metastasis of these cells without affecting primary tumorigenicity in a severe combined immunodeficient mouse model. Taken together, our results strongly suggest that Drg-1 suppresses metastasis of prostate tumor cells, at least in part, by inhibiting the invasive ability of the cells via down-regulation of the expression of the ATF3 gene.
The Incidence of Invasive Breast Cancer Among Women Prescribed Testosterone for Low Libido (2009)

In this study, testosterone use was not associated with a significant increase in breast cancer risk.
Fine-grained mobility in the Emerald system (1988)

Emerald is an object-based language and system designed for the construction of distributed programs. An explicit goal of Emerald is support for object mobility; objects in Emerald can freely move within the system to take advantage of distribution and dynamically changing environments. We say that Emerald has fine-grained mobility because Emerald objects can be small data objects as well as process objects. Fine-grained mobility allows us to apply mobility in new ways but presents implementation problems as well. This paper discusses the benefits of tine-grained mobility, the Emerald language and run-time mechanisms that support mobility, and techniques for implementing mobility that do not degrade the performance of local operations. Performance measurements of the current implementation are included.
Mutations of polycomb‐associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia (2009)

The myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal haematological diseases characterized by ineffective haematopoiesis and predisposition to acute myeloid leukaemia (AML). The pathophysiology of MDSs remains unclear. A definition of the molecular biology of MDSs may lead to a better classification, new prognosis indicators and new treatments. We studied a series of 40 MDS/AML samples by high-density array-comparative genome hybridization (aCGH). The genome of MDSs displayed a few alterations that can point to candidate genes, which potentially regulate histone modifications and WNT pathways (e.g. ASXL1, ASXL2, UTX, CXXC4, CXXC5, TET2, TET3). To validate some of these candidates we studied the sequence of ASXL1. We found mutations in the ASXL1 gene in four out of 35 MDS patients (11%). To extend these results we searched for mutations of ASXL1 in a series of chronic myelomonocytic leukaemias, a disease classified as MDS/Myeloproliferative disorder, and found mutations in 17 out of 39 patients (43%). These results show that ASXL1 might play the role of a tumour suppressor in myeloid malignancies.
Influence of ionic association on the nonisothermal crystallization kinetics of sodium sulfonate poly(butylene succinate) ionomers (2008)

Abstract We evaluated the relationship between the ionic substituents and nonisothermal crystallization behavior in poly(butylene succinate) (PBS) ionomers, synthesized by the introduction of sulfonated dimethyl fumarate (SDMF) with sodium sulfonate. In addition, we investigated the effect of sodium ions on the molecular structure of the PBS backbone by solid‐state 23 Na NMR analysis. Sodium ion aggregates (multiplets) was predominately created with the ionic group concentration, and melt rheology and dynamic melt analysis results showed that multiplet formation induced not only remarkable heterogeneity, but also a high degree of clustering in the PBS chains. At low ionic group concentration, well dispersed multiplets behaved as effective nuclei during the crystallization of the PBS ionomer and accelerated the rate of crystallization. As ionic group concentration grew higher, crystallization rates decreased due to hindered chain mobility by clusters consisting of numerous multiplets. A combined Ozawa and Avrami equation proved to be more effective than the Ozawa equation in describing the nonisothermal crystallization kinetics of PBS and its ionomers. The observed nucleation activity indicates that the nonisothermal crystallization rate is not directly proportional to the ionic group concentration. Superior nucleation activity was observed in PBS ionomer containing 1 mol % SDMF. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 925–937, 2008
Classification of human tumors using gene expression profiles obtained after microarray analysis of fine-needle aspiration biopsy samples (2005)

BACKGROUND Gene expression profiling using gene-discovery, high-density microarray technologies is a powerful tool. One potential application is the development of tumor classifiers that predict the site of origin. For this technology to be relevant, however, it must be applicable to tumor biopsy samples, which most often are fine-needle aspiration biopsy (FNAB) samples. METHODS Surgically resected tumors were sampled by FNAB using different gauge needles. A portion of the excised tumor was also collected. RNA samples were extracted using standard techniques and the quality and quantity of the RNA samples were measured for each sample. Thirteen representative FNAB samples and two representative tissue samples were submitted for microarray analysis and then subjected to a tumor classifier. RESULTS Fourteen of 18 samples analyzed for quantity and quality of RNA yielded an adequate amount of RNA (> 1 μg total RNA). Tumor type contributed to the RNA yield because one of the four inadequate samples was retrieved from a patient with lobular carcinoma of the breast and the other three samples were retrieved from patients with retroperitoneal sarcomas. Of the 13 samples submitted for microarray analysis, 9 were classified correctly as to tumor type using a tissue-based tumor classifier. CONCLUSIONS The authors demonstrated that FNABs reproducibly obtained an adequate amount of RNA for microarray analysis when a standardized collection procedure was used. Furthermore, the samples generated interpretable gene expression profiles that could be matched accurately with a tumor classifier established on tissue specimens. The current study showed that FNAB produced adequate material for microarray analysis when utilizing a standardized collection procedure. Cancer (Cancer Cytopathol) 2005. © 2005 American Cancer Society.
Design of a lightweight and wide field-of-view HMD system with free-form-surface prism (2007)

Lightweight head-mounted displays(HMD) with large field-of-views are widely used in fields of virtual reality, augmented reality, defense and anti-terrorism. Eyepieces of the conventional style cannot meet the stringent requirements of HMDs for large field-of-view, compact size and light weight. A novel lightweight, wide field-of-view eyepiece for HMD is achieved using a free-form-surface(FFS) prism. The design method is discussed and the design result is presented.
In Vitro Metronidazole and Tinidazole Activities against Metronidazole- Resistant Strains of Trichomonas vaginalis (2003)

The in vitro activities of tinidazole and metronidazole against Trichomonas vaginalis isolates clinically resistant to metronidazole were compared. Minimal lethal concentrations (MLCs) of tinidazole were significantly lower than MLCs of metronidazole. Increased metronidazole resistance correlated with increased tinidazole resistance. These data support a role for tinidazole in the treatment of trichomoniasis.
The Search for a Better Treatment for RecurrentClostridium difficileDisease: Use of High‐Dose Vancomycin Combined withSaccharomyces boulardii (2000)

Recurrent Clostridium difficile disease (CDD) is a difficult clinical problem because antibiotic therapy often does not prevent further recurrences. In a previous study, the biotherapeutic agent Saccharomyces boulardii was used in combination with standard antibiotics and was found to be effective in reducing subsequent recurrences of CDD. In an effort to further refine a standard regimen, we tested patients receiving a regimen of a standard antibiotic for 10 days and then added either S. boulardii (1 g/day for 28 days) or placebo. A significant decrease in recurrences was observed only in patients treated with high-dose vancomycin (2 g/day) and S. boulardii (16.7%), compared with those who received high-dose vancomycin and placebo (50%; P=.05). No serious adverse reactions were observed in these patients. Comparison of data from this trial with data from previous studies indicates that recurrent CDD may respond to a short course of high-dose vancomycin or to longer courses of low-dose vancomycin when either is combined with S. boulardii.
GVL: a graphical, functional language for the specification of output in programming languages (2002)

The conceptual view model of output is based on the complete separation of the output specification of a program from the program itself, and the use of implicit synchronization to allow the data state of the program to be continuously mapped to a display view. An output specification language called GVL is used to specify the mapping from the program's data state to the display. GVL is a functional language explicitly designed for specifying output. Building from a small number of basic primitives, it provides sufficient power to describe complex graphical output. Examples, including GVL specifications for linked list diagrams, bar charts and an address card file, are given. In keeping with its intended application, GVL is also a graphical language, in which the user draws output specifications directly on the display. How problems often associated with imperative graphical languages are avoided by using the functional paradigm is shown. A prototype implementation of GVL was used to produce examples of graphical output.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Formation and Absence of Intermetallic Compounds during Solid-State Reactions in the Ni−Bi System (1999)

The reactions between Ni and NiBi3 at 330, 370, 410, and 450 °C were studied. The compound NiBi3 was prepared by melting a mixture of 99.9994% Bi shots and 99.996%, −120 mesh Ni powder. It was found that the synthesized NiBi3 is soft and brittle. This is contrary to the characteristics of common intermetallics, which are often hard and brittle. Such inferior mechanical properties make the formation of NiBi3 in solder joints very undesirable. The reaction product was a layer of NiBi that grew parabolically, suggesting diffusion-controlled kinetics. The activation energy for the growth of NiBi is 84 kJ/mol. The fact that NiBi formed here, but not in the reaction between Ni and Bi as reported in the literature, suggests that the reason for absence of NiBi is not due to difficulty in nucleation. The more likely reason is that the interdiffusion coefficient of NiBi is much smaller than that of NiBi3. The dominant diffusing species in NiBi was analyzed by a marker movement experiment. It was found that the Bi flux through NiBi is 3−9 times greater than Ni flux at 370 °C. An expression relating the marker position to the ratio of Bi flux to Ni flux was proposed.
ss-siRNAs allele selectively inhibit ataxin-3 expression: multiple mechanisms for an alternative gene silencing strategy (2013)

Single-stranded silencing RNAs (ss-siRNAs) provide an alternative approach to gene silencing. ss-siRNAs combine the simplicity and favorable biodistribution of antisense oligonucleotides with robust silencing through RNA interference (RNAi). Previous studies reported potent and allele-selective inhibition of human huntingtin expression by ss-siRNAs that target the expanded CAG repeats within the mutant allele. Mutant ataxin-3, the genetic cause of Machado-Joseph Disease, also contains an expanded CAG repeat. We demonstrate here that ss-siRNAs are allele-selective inhibitors of ataxin-3 expression and then redesign ss-siRNAs to optimize their selectivity. We find that both RNAi-related and non-RNAi-related mechanisms affect gene expression by either blocking translation or affecting alternative splicing. These results have four broad implications: (i) ss-siRNAs will not always behave similarly to analogous RNA duplexes; (ii) the sequences surrounding CAG repeats affect allele-selectivity of anti-CAG oligonucleotides; (iii) ss-siRNAs can function through multiple mechanisms and; and (iv) it is possible to use chemical modification to optimize ss-siRNA properties and improve their potential for drug discovery.
Using Salt Cocrystals to Improve the Solubility of Niclosamide (2015)

This Article reports the solvent-free synthesis and characterization of a number of different crystal forms of niclosamide (HNic), which is an API belonging to the Salicilamide class. The synthesized compounds are four new salt cocrystals (KNic·HNic·H2O, KNic·HNic·3H2O, NaNic·HNic·3H2O, NaNic·HNic·2H2O), a classic cocrystal with imidazole (IM) (HNic·IM), and two sodium salts, (NaNic·DMSO·H2O and NaNic·DMSO·2H2O). The peculiarity of these salt cocrystals is the API’s concomitant presence as both a neutral component and as a salt coformer and the fact that they interact via hydrogen bond formation. HNic’s poor aqueous solubility makes the enhancement of its dissolution rate via the modulation of its physical properties extremely important. All samples have been investigated using a combination of solid-state experimental techniques which provide complementary information on powdered samples. These techniques are X-ray powder diffraction, solid-state NMR, IR, and Raman. Single crystals were only obtained for KNic·HNic·H2O and NaNic·DMSO·2H2O. The nature of the adducts (whether salt or cocrystal), their stoichiometry and the presence of independent molecules in the unit cell of the other samples were thus all determined by means of solid-state NMR and the comparative analysis of 13C and 15N CPMAS (Cross-Polarization Magic Angle Spinning) and 1H MAS spectra. Furthermore, differential scanning calorimetry, thermogravimetric analysis and intrinsic dissolution rate measurements completed the characterization and enabled us to evaluate the effects of microscopic changes (molecular packing, weak interactions, conformations, etc.) on the macroscopic properties (thermal stability and bioavailability) of the multicomponent forms. The results obtained indicate that the formation of salt cocrystals provides a reliable method with which to improve the HNic intrinsic dissolution rate.
Neuron-Specific mRNA Complexity Responses during Hippocampal Apoptosis after Traumatic Brain Injury (2004)

In an effort to understand the complexity of genomic responses within selectively vulnerable regions after experimental brain injury, we examined whether single apoptotic neurons from both the CA3 and dentate differed from those in an uninjured brain. The mRNA from individual active caspase 3(+)/terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling [TUNEL(-)] and active caspase 3(+)/TUNEL(+) pyramidal and granule neurons in brain-injured mice were amplified and compared with those from nonlabeled neurons in uninjured brains. Gene analysis revealed that overall expression of mRNAs increased with activation of caspase 3 and decreased to below uninjured levels with TUNEL reactivity. Cell type specificity of the apoptotic response was observed with both regionally distinct expression of mRNAs and differences in those mRNAs that were maximally regulated. Immunohistochemical analysis for two of the most highly differentially expressed genes (prion and Sos2) demonstrated a correlation between the observed differential gene expression after traumatic brain injury and corresponding protein translation.
Several Different Ion Channel Modulators Abrogate Contact Hypersensitivity in Mice (1999)

A major obstacle in transdermal delivery of drugs is the development of adverse skin sensitization reactions. We tested the concept that ion channel modulators as a class of agents suppress contact hypersensitivity in a mouse model. Mice were sensitized to several contact sensitizing chemicals including dinitrochlorobenzene (DNCB) and a sensitizing drug, nadolol. We report our successful use of several ion channel modulators in suppressing contact hypersensitivity, including amiloride, ethacrynic acid (ECA), nifedipine and verapamil. For this purpose, Balb/c female mice were sensitized with DNCB, and abrogation of induction of contact hypersensitivity reaction (CHR) was examined by topical pretreatment of the target-sensitized skin with amiloride, nifedipine and pairwise combinations of these agents with ECA, a potassium ion channel blocker. Abrogation of induction of CHR was observed in all cases. In addition, suppression of contact hypersensitivity was observed in nadolol-sensitized mice pretreated with either verapamil or nifedipine. The results indicate that ion channel inhibitors are broadly effective inhibitors of allergic contact dermatitis and may be useful for facilitating the transdermal delivery of therapeutic drugs that have sensitization potential.