gebhart/patrepeval huggingface dataset:
Clinical pharmacological properties of mipomersen (Kynamro), a second generation antisense inhibitor of apolipoprotein B (2012)

Mipomersen is a second generation antisense oligonucleotide that targets apolipoprotein B. It has been studied thoroughly in clinical trials (more than 800 subjects), including four randomized double-blind placebo controlled phase 3 studies involving 391 patients, and is in registration for the treatment of severe hypercholesterolaemia. The pharmacokinetic and pharmacodynamic properties of mipomersen are well characterized. Mipomersen is rapidly and extensively absorbed after subcutaneous administration and has an elimination half-life of approximately 30 days across species. It is cleared by nuclease metabolism and renal excretion of the metabolites. Mipomersen reduces all apolipoprotein B containing atherogenic particles and displays dose dependent reductions between 50-400 mg week⁻¹ , both as a single agent and in the presence of maximal lipid lowering therapy. No drug-drug interactions have been identified. Mipomersen is a representative of second generation antisense drugs, all of which have similar properties, and is thus representative of the behaviour of the class of drugs.
IL-4 and IFN (alpha and gamma) exert opposite regulatory effects on the development of cytolytic potential by Th1 or Th2 human T cell clones (1992)

The cytolytic potential of a total number of 118 CD4+ human T cell clones specific for purified protein derivative (PPD) from Mycobacterium tuberculosis, tetanus toxoid, Lolium perenne group I allergen (Lol p I), Poa pratensis group IX allergen (Poa p IX), or Toxocara canis excretory/secretory antigen(s) (TES) was assessed by both a lectin (PHA)-dependent and a MHC-restricted lytic assay and compared with their profile of cytokine secretion. The majority of clones with Th1 or Th0 cytokine profile exhibited cytolytic activity in both assays, whereas Th2 clones usually did not. There was an association between the cytolytic potential of T cell clones and their ability to produce IFN-gamma, even though IFN-gamma produced by T cell clones was not responsible for their cytolytic activity. IL-4 added in bulk culture before cloning inhibited not only the differentiation of PPD-specific T cells into Th1-like cell lines and clones, but also the development of their cytolytic potential. The depressive effect of IL-4 on the development of PPD-specific T cell lines with both Th1 cytokine profile and cytolytic potential was dependent on early addition of IL-4 in bulk cultures. In contrast, the addition in bulk culture of IFN-gamma enhanced both the cytolytic activity of PPD-specific T cell lines, as well as the proportion of PPD-specific T cell clones with cytolytic activity. The addition in bulk cultures before cloning of IFN-gamma or IFN-alpha favored the development of TES-specific and Poa p IX-specific T cells into T cell clones showing a Th0 or even a Th1, rather than a Th2, cytokine profile. Accordingly, most of TES- and Poa p IX-specific T cell clones derived from cultures containing IFN-gamma or IFN-alpha displayed strong cytolytic activity. These data indicate that the majority of human T cell clones that produce IFN-gamma, but not IL-4 (Th1-like), as well as of T cell clones that produce IFN-gamma in combination with IL-4 (Th0-like) are cytolytic. More importantly, they demonstrate that the addition of IFN (alpha and gamma) or IL-4 in bulk cultures before cloning may influence not only the cytokine profile of human CD4+ T cell clones but also their cytolytic potential.
U.S. Parking Policies: An Overview of Management Strategies (2010)

This report identifies core sustainable parking principles and illustrates how smarter parking management can benefit consumers and businesses in time and money savings, while also leading to more livable, attractive communities. Many aspects of current parking management in the United States do not work reliably or efficiently for anyone: Motorists find themselves circling for long periods in search of a place to park; retail employees take choice parking locations away from potential customers; developers are compelled to provide more parking than the market requires; and traffic managers encounter difficulty handling traffic generated by new parking as there is often no link between parking price, supply and the amount of available road space. Finally, the old parking paradigm doesn't work for the environment, as hidden subsidies encourage over reliance on private car use — a major, growing contributor to global warming and air pollution. A few leading local governments around the country have started to chart a different course, earning both economic and political rewards. This report focuses primarily on these success stories and what we can learn from them.
Random Body Movement Cancellation in Doppler Radar Vital Sign Detection (2008)

The complex signal demodulation and the arctangent demodulation are studied for random body movement cancellation in quadrature Doppler radar noncontact vital sign detection. This technique can be used in sleep apnea monitor, lie detector, and baby monitor to eliminate the false alarm caused by random body movement. It is shown that if the dc offset of the baseband signal is accurately calibrated, both demodulation techniques can be used for random body movement cancellation. While the complex signal demodulation is less likely to be affected by a dc offset, the arctangent demodulation has the advantage of eliminating harmonic and intermodulation interference at high carrier frequencies. When the dc offset cannot be accurately calibrated, the complex signal demodulation is more favorable. Ray-tracing model is used to show the effects of constellation deformation and optimum/null detection ambiguity caused by the phase offset due to finite antenna directivity. Experiments have been performed using 4-7 GHz radar to verify the theory.
Antagonistic self-sensing and mate-sensing signaling controls antibiotic-resistance transfer (2013)

Conjugation is one of the most common ways bacteria acquire antibiotic resistance, contributing to the emergence of multidrug-resistant "superbugs." Bacteria of the genus Enterococcus faecalis are highly antibiotic-resistant nosocomial pathogens that use the mechanism of conjugation to spread antibiotic resistance between resistance-bearing donor cells and resistance-deficient recipient cells. Here, we report a unique quorum sensing-based communication system that uses two antagonistic signaling molecules to regulate conjugative transfer of tetracycline-resistance plasmid pCF10 in E. faecalis. A "mate-sensing" peptide sex pheromone produced by recipient cells is detected by donor cells to induce conjugative genetic transfer. Using mathematical modeling and experimentation, we show that a second antagonistic "self-sensing" signaling peptide, previously known to suppress self-induction of donor cells, also serves as a classic quorum-sensing signal for donors that functions to reduce antibiotic-resistance transfer at high donor density. This unique form of quorum sensing may provide a means of limiting the spread of the plasmid and present opportunities to control antibiotic-resistance transfer through manipulation of intercellular signaling, with implications in the clinical setting.
Studies on orally active cephalosporins. I. Synthesis and structure-activity relationships of new 3-substituted carbamoyloxymethyl cephalosporins. (1994)

The synthesis and antibacterial activities of 7 beta-[2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-N,N - dimethylcarbamoyloxymethyl-3-cephem-4-carboxylic acid (E1100) and its analogs are described, as well as oral absorbability and in vivo activities of the 1-(isopropoxycarbonyloxy)ethyl ester (E1101) and its analogous esters. The introduction of acyclic and cyclic lower alkyl groups at the N-position of 3-carbamoyloxymethyl cephems influences antibacterial activities, especially against H. influenzae, and oral absorbability of their prodrug esters. The structure-activity relationships are also discussed.
Dengue hemorrhagic fever and shock syndromes* (2010)

Dengue is no longer confined to the tropics and is a global disease. Treatment is supportive. Outcomes can be optimized by early recognition and cautious titrated fluid replacement, especially in resource-limited environments.
Reversal of NK-Cell Exhaustion in Advanced Melanoma by Tim-3 Blockade (2014)

The immunoregulatory protein T-cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) mediates T-cell exhaustion and contributes to the suppression of immune responses in both viral infections and tumors. Tim-3 blockade reverses the exhausted phenotype of CD4+ and CD8+ T cells in several chronic diseases, including melanoma. Interestingly, natural killer (NK) cells constitutively express Tim-3; however, the role of Tim-3 in modulating the function of these innate effector cells remains unclear, particularly in human diseases. In this study, we compared the function of Tim-3 in NK cells from healthy donors and patients with metastatic melanoma. NK cells from the latter were functionally impaired/exhausted, and Tim-3 blockade reversed this exhausted phenotype. Moreover, Tim-3 expression levels were correlated with the stage of the disease and poor prognostic factors. These data indicate that Tim-3 can function as an NK-cell exhaustion marker in advanced melanoma and support the development of Tim-3-targeted therapies to restore antitumor immunity.
Detection of Conserved N-Linked Glycans and Phase-variable Lipooligosaccharides and Capsules from Campylobacter Cells by Mass Spectrometry and High Resolution Magic Angle Spinning NMR Spectroscopy (2003)

Glycomics, the study of microbial polysaccharides and genes responsible for their formation, requires the continuous development of rapid and sensitive methods for the identification of glycan structures. In this study, methods for the direct analysis of sugars from 108 to 1010 cells are outlined using the human gastrointestinal pathogen, Campylobacter jejuni. Using capillary-electrophoresis coupled with sensitive electrospray mass spectrometry, we demonstrate variability in the lipid A component of C. jejuni lipooligosaccharides (LOSs). In addition, these sensitive methods have permitted the detection of phase-variable LOS core structures that were not observed previously. High resolution magic angle spinning (HR-MAS) NMR was used to examine capsular polysaccharides directly from campylobacter cells and showed profiles similar to those observed for purified polysaccharides analyzed by solution NMR. This method also exhibited the feasibility of campylobacter serotyping, mutant verification, and preliminary sugar analysis. HR-MAS NMR examination of growth from individual colonies of C. jejuni NCTC11168 indicated that the capsular glycan modifications are also phase-variable. These variants show different staining patterns on deoxycholate-PAGE and reactivity with immune sera. One of the identified modifications was a novel -OP=O(NH2)OMe phosphoramide, not observed previously in nature. In addition, HR-MAS NMR detected the N-linked glycan, GalNAc-alpha1,4-GalNAc-alpha1,4-[Glc-beta1,3-]GalNAc-alpha1,4-GalNAc-alpha1,4-GalNAc-alpha1,3-Bac, where Bac is 2,4-diacetamido-2,4,6-trideoxy-d-glucopyranose, in C. jejuni and Campylobacter coli. The presence of this common heptasaccharide in multiple campylobacter isolates demonstrates the conservation of the N-linked protein glycosylation pathway in this organism and describes the first report of HR-MAS NMR detection of N-linked glycans on glycoproteins from intact bacterial cells.
MUC1 and breast cancer. (1999)

The development of an effective immunotherapeutic approach to cancer is now a major focus of research, and despite impressive progress over the last 10 years there are still many hurdles to overcome to elicit an effective immune response which will totally eradicate the cancer. Mucins (MUC1) have attracted interest as potential targets for immunotherapy of cancers of breast, pancreas, ovary and others, and we have demonstrated that mannan, a polymannose carbohydrate is an effective carrier for MUC1 in eliciting a cellular immune response. Several clinical trials are in progress to evaluate the immunogenicity of MUC1 and its suitability as to use for immunotherapy/vaccine for breast cancer.
The characteristics of chemical components in tobacco leaves from Hubei’s main production areas (2010)

Quality parameters of leaf tobacco chemical components in Hubei province were analyzed. Results showed that:(1) the average nicotine contents was 2.80%,slightly higher than desired level. Total sugar,nitrogen and potassium were at proper level,and chlorine content was low. (2) Analysis of variance revealed that all parameters except chlorine showed significant difference leaf tobacco from different positions. Nicotine content showed significant difference (0.05),while the difference between production areas for total sugar,nitrogen,potassium content were highly significant (0.01). (3) Chemical Components Usability Index (CCUI) was about 50.5% at the middle level,and 48.5% at the high level with an average of 78.6,and the coefficient of variation was 0.09. These indicated that chemical components was at the right level. (4) Compared with high quality foreign leaf tobacco,the highest similarity (88.7%) existed in total nitrogen ,nicotine was 69.1%,and others were less than 60.0%,which suggested that tobacco leaves from Hubei province were not as good as those imported in terms of chemical components.
Selective presence of ubiquitin in intracellular inclusions. (1989)

The authors have shown previously that ubiquitin, a protein involved in the degradation of short-lived and abnormal proteins, is present in several cytoplasmic inclusions of neurons. This study used a library of antibodies to ubiquitin and immunohistochemically examined for the presence of ubiquitin in nonviral intracytoplasmic inclusions that form in different cell types under various pathologic conditions. Membrane-bound lysosomal and nonlysosomal inclusions such as those of storage disease, Russell bodies, alpha-1-antitrypsin and alpha-fetoprotein as well as nonmembrane-bound inclusions were examined. Ubiquitin epitopes were detected in some of the nonmembrane-bound inclusions only. The ubiquitin-containing inclusions were the Rosenthal fibers, Mallory bodies, Crooke bodies, Lafora bodies, amyloid bodies, and the giant axons of giant axonal neuropathy. Nemaline bodies and the inclusions of juvenile digital fibromatosis, both of which contain actin and actinbinding proteins, did not show immunoreaction. These findings, as well as those of the previous study, show that the presence of ubiquitin in cellular inclusions is selective. The ubiquitin-containing inclusions are not membrane bound; they are fibrillary and most contain also intermediate filament-related proteins. The role of ubiquitin in the formation of these inclusions remains to be elucidated.
Structural analysis of diols by electrospray mass spectrometry on boric acid complexes (1999)

A method is presented to characterize diols using negative ion electrospray (ES) mass spectrometry in combination with collision-induced dissociation tandem mass spectrometry (MS/MS). The analyte diol is added to a solution containing an ethylene glycol/boric acid [2:1] complex and then subjected to infusion ES. The following boric acid complexes are formed: (i) a complex with two ethylene glycol molecules, (ii) a mixed ethylene glycol/analyte complex, and (iii) a complex with two analyte molecules. The first complex serves as a reference for the assessment of the extent of complex formation with the analyte. The ES mass spectra of acyclic vicinal diols all feature intense mixed complex signals, indicative of efficient complex formation. Chemical fine tuning is achieved by MS/MS experiments. Thus, although the (2R,3R)-(-)-2,3-butanediol and meso-2,3-butanediol stereo-isomers show the same complexation efficiency, MS/MS experiments reveal pronounced structure characteristic differences. By contrast, 1,3- and 1,4-diols are less prone to complex formation as they give only weak signals relative to the reference. For cyclic vicinal diols only the cis isomer produces an intense mixed complex, whose MS/MS spectrum is characteristically different from that of the trans form. The above procedure does not permit an unambiguous differentiation of acyclic polyhydroxy compounds like mannitol and sorbitol. However, structurally related methyl glycosides show characteristic MS/MS spectra. Our findings indicate that the above simple procedure may be useful to probe the presence and structure of diols and other polyols in aqueous solutions. Copyright 1999 John Wiley & Sons, Ltd.
Affine Object Tracking with Kernel-Based Spatial-Color Representation (2005)

This paper presents a new visual tracking method that can achieve accurate estimation of affine transformation and precise spatial-color representation. The estimation of transformation provides more information than translation for better motion understanding and also helps maintain the precise representation; the precise representation enables tracking objects in highly-cluttered environment. The basis of the method is a kernel-based similarity measure called affine matching that describes the relationship between image regions with respect to affine transformation parameters. Based on the similarity measure, a mathematical solution is derived for estimating the transformation parameters for moving objects in videos. Various experiments have yielded positive results.
Nanoparticles – known and unknown health risks (2004)

Abstract Manmade nanoparticles range from the well-established multi-ton production of carbon black and fumed silica for applications in plastic fillers and car tyres to microgram quantities of fluorescent quantum dots used as markers in biological imaging. As nano-sciences are experiencing massive investment worldwide, there will be a further rise in consumer products relying on nanotechnology. While benefits of nanotechnology are widely publicised, the discussion of the potential effects of their widespread use in the consumer and industrial products are just beginning to emerge. This review provides comprehensive analysis of data available on health effects of nanomaterials.
CpG domains downstream of TSSs promote high levels of gene expression (2014)

CpG dinucleotides are known to play a crucial role in regulatory domains, affecting gene expression in their natural context. Here, we demonstrate that intragenic CpG frequency and distribution impacts transgene and genomic gene expression levels in mammalian cells. As shown for the Macrophage Inflammatory Protein 1α, de novo RNA synthesis correlates with the number of CpG dinucleotides, whereas RNA splicing, stability, nuclear export and translation are not affected by the sequence modification. Differences in chromatin accessibility in vivo and altered nucleosome positioning in vitro suggest that increased CpG levels destabilize the chromatin structure. Moreover, enriched CpG levels correlate with increased RNA polymerase II elongation rates in vivo. Interestingly, elevated CpG levels particularly at the 5' end of the gene promote efficient transcription. We show that this is a genome-wide feature of highly expressed genes, by identifying a domain of ∼700 bp with high CpG content downstream of the transcription start site, correlating with high levels of transcription. We suggest that these 5' CpG domains are required to distort the chromatin structure and to increase gene activity.
An International Survey-based Algorithm for the Pharmacologic Treatment of Chorea in Huntington’s Disease (2011)

It is generally believed that treatments are available to manage chorea in Huntington's disease (HD). However, lack of evidence prevents the establishment of treatment guidelines. The HD chorea research literature fails to address the indications for drug treatment, drug selection, drug dosing and side effect profiles, management of inadequate response to a single drug, and preferred drug when behavioral symptoms comorbid to chorea are present. Because there is lack of an evidence base to inform clinical decision-making, we surveyed an international group of experts to address these points. Survey results showed that patient stigma, physical injury, gait instability, work interference, and disturbed sleep were indications for a drug treatment trial. However, the experts did not agree on first choice of chorea drug, with the majority of experts in Europe favoring an antipsychotic drug (APD), and a near equal split in first choice between an APD and tetrabenazine (TBZ) among experts from North America and Australia. All experts chose an APD when comorbid psychotic or aggressive behaviors were present, or when active depression prevented the use of TBZ. However, there was agreement from all geographic regions that both APDs and TBZ were acceptable as monotherapy in other situations. Perceived efficacy and side effect profiles were similar for APDs and TBZ, except for depression as a significant side effect of TBZ. Experts used a combination of an APD and TBZ when treatment required both drugs for control of chorea and a concurrent comorbid symptom, or when severe chorea was inadequately controlled by either drug alone. The benzodiazepines (BZDs) were judged ineffective as monotherapy but useful as adjunctive therapy, particularly when chorea was exacerbated by anxiety. There was broad disagreement about the use of amantadine for chorea. Experts who had used amantadine described its benefit as small and transient. In addition to survey results, this report reviews available chorea studies, and lastly presents an algorithm for the treatment of chorea in HD which is based on expert preferences obtained through this international survey.
Increased DNA methyltransferase expression in rhabdomyosarcomas (1999)

In normal somatic cells, the methylation pattern of DNA is stably maintained by DNA (cytosine-5-)-methyltransferase (DNA methyltransferase). Increased expression of DNA methyltransferase has been detected in many types of human cancer and has been thought to play an important role in tumorigenesis. In our study, we developed a standardized reverse transcription-polymerase chain reaction (RT-PCR) assay to determine the mRNA levels of DNA methyltransferase in rhabdomyosarcoma, the most common soft tissue cancer in children. Using this assay, expression of DNA methyltransferase was analyzed for 32 rhabdomyosarcomas and 12 normal skeletal muscle samples. All tumor samples, of which 18 were embryonal and 14 were alveolar subtype, showed increased expression of DNA methyltransferase after normalization to β-actin. Compared to normal skeletal muscle, the average increase of DNA methyltransferase expression was 6.7-fold (6.7 ±0.96) in the embryonal tumors and 3.7-fold (3.7 ± 0.46) in the alveolar rhabdomyosarcomas. The difference in the average increase of the DNA methyltransferase expression was statistically significant in the 2 rhabdomyosarcoma subtypes, which have distinct etiologies and clinical behaviors. Our results are consistent with previous reports that an increase in DNA methyltransferase activity is associated with neoplastic transformation; however, the role of increased DNA methyltransferase expression in the development and progression of rhabdomyosarcoma needs to be investigated in future studies. Int. J. Cancer 83:10–14, 1999. © 1999 Wiley-Liss, Inc.