gebhart/patrepeval huggingface dataset:
MER-101–03, a multicenter, phase II study to compare MER-101 20mg tablets to intravenous zoledronic acid 4mg in prostate cancer patients (2009)

5161 Background: The primary objective of this study is to examine the pharmacodynamic effects of two different regimens of zoledronic acid, Orazol 20 mg tablets versus Zometa 4mg IV infusion once-monthly therapy on biomarkers in male bisphosphonate-naïve hormone-refractory prostate cancer patients. Methods: The study is an open-label, multi-center phase II clinical trial to compare oral Orazol 20 mg tablets weekly, to infusions of intravenous Zometa 4mg monthly, in males with hormone-refractory prostate cancer, bone metastases, and no prior bisphosphonate treatment. Patients were assigned into one of three cohorts. The three treatments administered were IV Zometa, 4 mg, 15 minute infusion, Day 0 and Day 28; Orazol po, 20 mg, Days 0, 7, 14, 21, 28, 35, 42, and 49; and Orazol po, 20 mg, Days 0, 1, 2, 3, 28, 35, 42, and 49. The study population consisted of men with hormone refractory prostate cancer as evidenced by history of rising PSA levels (last 2 of 3 PSA levels must be above nadir), who are bisphosphonate-naive, and have radiographically-confirmed bone metastases. Efficacy assessments: The primary endpoints are the assessment of response of four biomarkers, urinary NTX, serum CTX, serum bone specific alkaline phosphatase, and serum calcium on days -7, 0, 7, 14, 21, 28, 35, 42, 49, and 56. Secondary endpoints are assessments of performance and pain scores based on ECOG performance status, BPI, and analgesic use. Safety assessments include physical examinations, vital signs and body weight, hematology panel, urinalysis, and blood chemistry panel. Results: The results demonstrated a rapid decrease for all four biomarkers. This decrease was seen at seven days, and was sustained throughout the study. There were no statistically significant differences between any of the treatments in the primary and secondary endpoints. Conclusions: From the results of MER-101–03, Orazol weekly therapy appears to be as effective as Zometa, based on the biomarkers analyzed. Orazol offers a substantial improvement in therapy over IV infusion for patients, with efficacy that is at least comparable based on the results obtained here. No significant financial relationships to disclose.
Rapid Diagnostic Tests for Malaria Parasites (2002)

Malaria presents a diagnostic challenge to laboratories in most countries. Endemic malaria, population movements, and travelers all contribute to presenting the laboratory with diagnostic problems for which it may have little expertise available. Drug resistance and genetic variation has altered many accepted morphological appearances of malaria species, and new technology has given an opportunity to review available procedures. Concurrently the World Health Organization has opened a dialogue with scientists, clinicians, and manufacturers on the realistic possibilities for developing accurate, sensitive, and cost-effective rapid diagnostic tests for malaria, capable of detecting 100 parasites/microl from all species and with a semiquantitative measurement for monitoring successful drug treatment. New technology has to be compared with an accepted "gold standard" that makes comparisons of sensitivity and specificity between different methods. The majority of malaria is found in countries where cost-effectiveness is an important factor and ease of performance and training is a major consideration. Most new technology for malaria diagnosis incorporates immunochromatographic capture procedures, with conjugated monoclonal antibodies providing the indicator of infection. Preferred targeted antigens are those which are abundant in all asexual and sexual stages of the parasite and are currently centered on detection of HRP-2 from Plasmodium falciparum and parasite-specific lactate dehydrogenase or Plasmodium aldolase from the parasite glycolytic pathway found in all species. Clinical studies allow effective comparisons between different formats, and the reality of nonmicroscopic diagnoses of malaria is considered.
The innervation of the human posterior cricoarytenoid muscle: Evidence for at least two neuromuscular compartments (1994)

Recent work has demonstrated that the dog posterior cricoarytenoid (PCA) muscle is composed of three neuromuscular compartments: a vertical, an oblique, and a horizontal. In this study, the human PCA muscle was examined for evidence of neural compartments. Fifteen human PCA muscles were processed by Sihler's stain, which renders the muscle translucent while counterstaining the nerve supply. The results clearly show that in all specimens the nerve supply of the human PCA muscle is separated into at least two main branches: one supplies the horizontal compartment and a second further subdivides to innervate both the vertical and oblique compartments. In 10 of the specimens, these nerve branches arose as separate branches from the recurrent laryngeal nerve. In all specimens, the nerve branch to the horizontal compartment was either combined or connected with the nerve branch to the interarytenoid muscle. The results suggest that the different compartments of the PCA muscle have distinct functions. In addition, the strong connections with the interarytenoid nerve complicate reinnervation procedures to reanimate a paralyzed or transplanted larynx.
MicroRNA-125b suppresses the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (2014)

The regressive biological function of human bone marrow‑derived mesenchymal stem cells (hBMSCs) is one of the key factors resulting in the decrease of bone mass in senile osteoporosis. MicroRNAs (miRs) are non‑coding small RNAs involved in various gene regulation processes. Whether any miR(s) are involved in the progression of osteoporosis by regulating the biological function of hBMSCs remains to be elucidated. The present study aimed to compare the expression levels of miR‑125b in hBMSCs derived from senile osteoporotic patients with that of control (normal) subjects. A significantly upregulated expression of miR‑125b in osteoporotic hBMSCs was detected. To elucidate the biological function of miR‑125b in senile osteoporosis, the effects of miR‑125b expression on proliferation and osteogenic differentiation of hBMSCs were assessed using gain‑ and loss‑of‑function studies. It was evident that the overexpression of a miR‑125b mimic was able to suppress the proliferative and osteogenic differentiation of senile hBMSCs. In contrast, repression of the function of miR‑125b by transfection of an miR‑125b inhibitor promoted the proliferation and osteogenic differentiation of hBMSCs. Furthermore, the potential target gene of miR‑125b, osterix (Osx), was examined. The results of the present study strongly suggested that miR‑125b may regulate osteogenic differentiation of hBMSCs through the modulation of Osx expression.
Healthy, natural, efficient and tunable lighting: four-package white LEDs for optimizing the circadian effect, color quality and vision performance (2014)

To date, most current reports on the development and optimization of artificial lighting sources have focused on the energy performance levels and limited color qualities of white light-emitting diodes (LEDs). However, these properties are insufficient in terms of representing all performance levels required when adjusting white LEDs for healthy and smart lighting. Here, we introduce essential and advanced figures of merit pertaining to circadian performance as well as vision performance and color quality. We compare all possible properties of commercialized artificial lighting, daylight and four-package white LEDs which consist of long-wavelength pass dichroic filter (LPDF)-capped, phosphor-converted red, amber and green LEDs (pc-LEDs) and a blue LED. We show that these tunable four-package white LEDs produce a tunable circadian effect for melatonin suppression/secretion, a high color quality for color perception/reproduction, high efficiency for energy savings and tunable figures of merit for the smart LED lighting market. Researchers in Korea have discovered that carefully designed white LEDs can help optimize an individual's circadian rhythm. Ji Hye Oh and co-workers from Kookmin University studied four-package white LEDs, which consist of phosphor-converted red, amber and green LEDs, a blue LED and a long-wavelength dichroic filter. They compared these devices with a variety of traditional forms of lighting, and found that such four-package LED designs yield a high luminous efficacy, excellent color rendering and a tunable circadian effect for regulating the secretion of melatonin. The figures of merit suggest that carefully designed white LEDs could play an important role in creating smart lighting systems that help maintain good health, bring energy savings and provide optimal visualization of colors.
Antifungal Activity of the Essential Oils of Callitris neocaledonica and C. sulcata Heartwood (Cupressaceae) (2012)

Mortality due to fungal infections has increased substantially, becoming a worldwide problem in public health. As a contribution to the discovery of new antifungal agents, the properties of the heartwood essential oils of two trees growing in New Caledonia, Callitris neocaledonica and C. sulcata (Cupressaceae) were investigated. The essential oils extracted by hydrodistillation were characterized by GC-FID and GC/MS analyses. From C. neocaledonica oil, 31 constituents were identified, representing 97.0% of the total oil composition, which was mainly constituted by oxygenated sesquiterpenes (88%). Among them, guaiol (1; 30.2%), bulnesol (2; 12.5%), α-eudesmol (3; 10.5%), β-eudesmol (4; 10.5%), γ-eudesmol (10.2%), and elemol (4.9%) predominated. The chemical composition of C. sulcata oil, from which 39 constituents were identified (96.8% of the total oil composition), showed some similarities with that of C. neocaledonica oil. The major constituents were also oxygenated sesquiterpenes, accounting for 78.5% of the oil, amongst them, mainly compounds 1 (16.1%), 3 and 4 (9.7% each), as well as 2 (7.4%). The antifungal activity of the oils against clinical isolates of four dermatophytic fungi (Trichophyton mentagrophytes, T. rubrum, Microsporum canis, and M. gypseum) and six yeasts (Candida albicans, C. parapsilosis, C. glabrata, C. krusei, Cryptococcus neoformans, and Cryptococcus gattii) was tested by determining minimum inhibitory concentrations (MICs) using the microdilution method. The best antifungal activities of the C. neocaledonica and C. sulcata oils were obtained against C. krusei (MICs of 3.9 and 0.975 μg/ml, resp.). These MIC values were similar to those of the reference drugs itraconazole and fluconazole (1.0 and 0.5 mg/ml, resp.). The oils were also subjected to a screening for their possible DPPH(.) (2,2-diphenyl-1-picrylhydrazyl) radical-scavenging activity. C. neocaledonica essential oil was more active than C. sulcata oil (93.3 vs. 32.2% DPPH(.) scavenged at 250 μg/ml).
<title>Using virtual menus in a virtual environment</title> (1992)

Virtual environment interfaces to computer programs in several diverse application areas are currently being developed. The users of virtual environments will require many different methods to interact with the environments and the objects in them. This paper reports on our use of virtual menus as a method of interacting with virtual environments. Several aspects of virtual environments make menu interactions different from interactions with conventional menus. We review the relevant aspects of conventional menus and virtual environments, in order to provide a frame of reference for the design of virtual menus. We discuss the features and interaction methodologies of two different versions of virtual menus which have been developed and used in our lab. We also examine the problems associated with our original version, and the enhancements incorporated into our current version.
Recruitment of CRISPR-Cas systems by Tn7-like transposons (2017)

A survey of bacterial and archaeal genomes shows that many Tn7-like transposons contain minimal type I-F CRISPR-Cas systems that consist of fused <i>cas8f</i> and <i>cas5f</i>, <i>cas7f</i>, and <i>cas6f</i> genes and a short CRISPR array. Several small groups of Tn7-like transposons encompass similarly truncated type I-B CRISPR-Cas. This minimal gene complement of the transposon-associated CRISPR-Cas systems implies that they are competent for pre-CRISPR RNA (precrRNA) processing yielding mature crRNAs and target binding but not target cleavage that is required for interference. Phylogenetic analysis demonstrates that evolution of the CRISPR-Cas-containing transposons included a single, ancestral capture of a type I-F locus and two independent instances of type I-B loci capture. We show that the transposon-associated CRISPR arrays contain spacers homologous to plasmid and temperate phage sequences and, in some cases, chromosomal sequences adjacent to the transposon. We hypothesize that the transposon-encoded CRISPR-Cas systems generate displacement (R-loops) in the cognate DNA sites, targeting the transposon to these sites and thus facilitating their spread via plasmids and phages. These findings suggest the existence of RNA-guided transposition and fit the guns-for-hire concept whereby mobile genetic elements capture host defense systems and repurpose them for different stages in the life cycle of the element.
Distinction of malignant melanoma and epidermis using IR micro-spectroscopy and statistical methods (2008)

Infrared spectroscopy is widely perceived as a future technology for cancer detection and grading. Malignant melanoma, an aggressive skin cancer, is accessible to non-invasive IR radiation based surface probes for its identification and grading. The present work examines the differences in the IR spectra of melanoma tissues and the surrounding epidermis in skin biopsies with the objective of identifying diagnostic parameters and suitable computational/statistical methods of analysis. Melanoma could be differentiated from the epidermis in biopsies of 55 patients, using parameters derived from absorbance bands originating from molecular vibrations of nucleic acids and/or their bases. Additionally, absorbances from tyrosine and phosphate that are abnormally elevated in malignant melanoma could be used as markers. Two-dimensional plots of these parameters in tandem with advanced statistical methods successfully demonstrate the potential of IR spectroscopy to distinguish between epidermal and melanoma regions with a high classification success. The work underlines the importance of developing data analysis methods in FTIR based diagnosis using melanoma as a model system.
Reduction of the steroidal sapogenin spiroketal system (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReduction of the steroidal sapogenin spiroketal systemAnthony H. Albert, George R. Pettit, and Peter BrownCite this: J. Org. Chem. 1973, 38, 12, 2197–2201Publication Date (Print):June 1, 1973Publication History Published online1 May 2002Published inissue 1 June 1973https://pubs.acs.org/doi/10.1021/jo00952a018https://doi.org/10.1021/jo00952a018research-articleACS PublicationsRequest reuse permissionsArticle Views100Altmetric-Citations15LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
CELL SURFACE LOCALIZATION OF THE 60 kDa HEAT SHOCK CHAPERONIN PROTEIN (hsp60) IN MAMMALIAN CELLS (1997)

To investigate whether the 60-kDa heat shock chaperonin protein (hsp60) is present on the surface of mammalian cells, we used immunogold labeling of intact cells and backscattered electron imaging to image gold particles. Chinese hamster ovary cells and the human leukemic CD4-positive T-cell line CEM-SS on glass coverslips were labeled using affinity-purified monoclonal and polyclonal antibodies specific for hsp60 and 30 nm gold markers. Cells were imaged using the scanning mode of the conventional transmission electron microscope. Backscattered electron imaging provided definitive identification of the gold markers while secondary electron imaging gave information on surface architecture. Labeling intensity was 250-800 gold particles per cell in Chinese hamster ovary cells and 600-2000 in CEM-SS human lymphoblasts. The finding of hsp60 on the cell surface of mammalian cells may signify chaperone involvement in surface functions.
YMXM motifs of IRS-1 define substrate specificity of the insulin receptor kinase. (1992)

Of 34 tyrosine residues in insulin receptor substrate 1 (IRS-1), 14 are adjacent to acidic residues, suggesting that they might be phosphorylation sites. Synthetic peptides corresponding to sequences surrounding these tyrosines were used as substrates of the insulin receptor kinase. Surprisingly six of these, each within YMXM motifs, were phosphorylated with greatest efficiency (Km, 24-92 microM; kcat/Km, 0.6-2.1 x 10(4) M-1.sec-1). Substituted YMXM peptides revealed a strong preference of the insulin receptor kinase for methionine at Y + 1 and Y + 3 positions. When phosphorylated, related YMXM sequences are recognition motifs for binding to proteins with src-homology (SH2) domains. The combined hydrophobic and flexible nature of methionine side chains adjacent to the targeted tyrosines provides a versatile contact for recognition by diverse proteins involved in signal transduction.
Synucleins in synaptic plasticity and neurodegenerative disorders (1999)

Synucleins are small highly conserved proteins in vertebrates, especially abundant in neurons and typically enriched at presynaptic terminals. Three genes in humans produce closely related synuclein proteins, all of which share a large amphipathic domain capable of reversible binding to lipid vesicles. Alpha synuclein has been specifically implicated in neurodegenerative disease. Two point mutations are genetically linked to familial Parkinson's disease, and alpha synuclein appears to form the major fibrillary component of Lewy bodies. Alpha synuclein also contributes to the intracellular inclusions of multiple system atrophy, and a fragment has been found in senile plaques in Alzheimer's disease. Although their normal cellular functions are unknown, several observations suggest the synucleins may serve to integrate presynaptic signaling and membrane trafficking. Alpha synuclein has been identified as a potent and selective inhibitor of phospholipase D2, which produces phosphatidic acid (to which synuclein binds) and is believed to function in the partitioning of membranes between the cell surface and intracellular stores. We outline a hypothesis whereby synuclein supports localized, experience-dependent turnover of synaptic membranes. Such a process may be important for lifelong learning and memory functions and may be especially vulnerable to disruption in aging-associated neurodegenerative diseases.
Handling rich turn-taking in spoken dialogue systems (1999)

Telephone based spoken dialogue systems have the potential to automate many routine tasks. Yet, to become widely accepted they must be natural, easy to use, efficient, and robust. We introduce the Conference Room Reservation System (CRRS), a mixed-initiative natural dialogue system used routinely by the employees of our lab. The CRRS allows callers to reserve or cancel rooms by simply stating their constraints in a natural way. The system prompts for missing information and offers alternative solutions if the original constraints cannot be satisfied. Our system uses Nortel Networks’ OpenSpeech continuous speech recognizer with barge-in, a robust natural language parser, and a mixed-initiative discourse manager. We describe the overall system with an emphasis on the discourse manager. We present an analysis of real data collected over several months. We then discuss the issue of defining dialogue performance metrics that are independent of the room occupancy rate.
Common Haplotypes at the Adiponectin Receptor 1 (ADIPOR1) Locus Are Associated With Increased Risk of Coronary Artery Disease in Type 2 Diabetes (2006)

Adiponectin, an adipokine facilitating insulin action, has antiatherogenic effects. This study investigated whether common polymorphisms in the adiponectin receptor 1 (ADIPOR1) gene mediating these effects influence the risk of coronary artery disease (CAD) in type 2 diabetes. Linkage disequilibrium analysis of 28 single nucleotide polymorphisms (SNPs) spanning the entire ADIPOR1 locus revealed two haplotype blocks that could be tagged by six SNPs. These six markers were typed in two populations of CAD-positive and -negative subjects with type 2 diabetes, one from Boston (n = 411) and the other from Italy (n = 533). In the Boston population, the three tags of the more 3' block were all significantly associated with CAD (P = 0.001-0.01). A similar trend, although not significant, was found in Italian subjects. Haplotype analysis of the combined populations revealed different haplotype distributions in case and control subjects (P = 0.0002), with one common haplotype being associated in homozygotes with a greater than threefold increase in cardiovascular risk (odds ratio 3.6 [95% CI 1.8-7.2]). Some of the genotypes associated with increased cardiovascular risk were associated with 30-40% lower ADIPOR1 mRNA levels in blood mononuclear cells (n = 60) and adipose tissue biopsies (n = 28) (P = 0.001-0.014). Our findings point to genetic variability at the ADIPOR1 locus as a strong determinant of CAD susceptibility in type 2 diabetes.
Experimental Realization of an On-Chip All-Optical Analogue to Electromagnetically Induced Transparency (2006)

We provide the first experimental observation of structure tuning of the electromagnetically induced transparency-like spectrum in integrated on-chip optical resonator systems. The system consists of coupled silicon ring resonators with 10 microm diameter on silicon, where the coherent interference between the two coupled resonators is tuned. We measured a transparency-resonance mode with a quality factor of 11,800.
Glutathione Is Required to Regulate the Formation of Native Disulfide Bonds within Proteins Entering the Secretory Pathway (2004)

The formation of native disulfide bonds is an essential event in the folding and maturation of proteins entering the secretory pathway. For native disulfides to form efficiently an oxidative pathway is required for disulfide bond formation and a reductive pathway is required to ensure isomerization of non-native disulfide bonds. The oxidative pathway involves the oxidation of substrate proteins by PDI, which in turn is oxidized by endoplasmic reticulum oxidase (Ero1). Here we demonstrate that overexpression of Ero1 results in the acceleration of disulfide bond formation and correct protein folding. In contrast, lowering the levels of glutathione within the cell resulted in acceleration of disulfide bond formation but did not lead to correct protein folding. These results demonstrate that lowering the level of glutathione in the cell compromises the reductive pathway and prevents disulfide bond isomerization from occurring efficiently, highlighting the crucial role played by glutathione in native disulfide bond formation within the mammalian endoplasmic reticulum.