gebhart/patrepeval huggingface dataset:
Phase I-II Trials of Poly(ICLC) in Malignant Brain Tumor Patients (1982)

Poly(ICLC) preparation, containing poly-L-lysine and poly(I) . poly(C) at a weight ratio of 1:2, was given intravenously at a dose of 0.05 to 0.2 mg/kg to 7 patients with malignant brain tumor. Poly(ICLC) induced significant serum interferon (more than 100 reference units/ml) in all patients. The highest interferon titer induced was 875 reference units/ml. Severe side effect was not observed except fever. Hypotension, leukopenia and elevation of liver enzyme levels were observed as side effects in a few cases.
The measurement of amino groups in proteins and peptides (1971)

A technique is examined for determining amino groups with 2,4,6-trinitrobenzenesulphonic acid, in which the extinction at 420nm of sulphite complexes of the trinitrophenylated amino groups is measured. The sensitivity of the method is 5-200nmol of amino group. The method is especially suitable for checking the extent of blocking or unblocking of amino groups in proteins and peptides, owing to the short time required for reaction (5min at room temperature). The reaction of the reagent with thiol groups has been studied and was found to proceed 30-50 times faster than with in-amino groups of model compounds. The in(420) of a trinitrophenylated thiol group was found to be 2250m(-1).cm(-1). The reaction with several amino acids, peptides and proteins is presented. The in(420) of a typical alpha-amino group was found to be 22000m(-1).cm(-1) and that of an in-amino group, 19200m(-1).cm(-1). Difficulties inherent in the analysis of constituent amino group reactions in proteins are discussed.
Comprehensive chromosomal analysis of human preimplantation embryos using whole genome amplification and single cell comparative genomic hybridization (2000)

Analysis of small numbers of chromosomes using interphase fluorescent in-situ hybridization (FISH) probes has revealed that 50% of human preimplantation embryos contain abnormal cells. Detection of high levels of mosaicism with so few probes has led some researchers to extrapolate that a full analysis of all 23 pairs of chromosomes would reveal that all human embryos contain a proportion of abnormal cells. However, existing cytogenetic protocols cannot achieve such an analysis due to technical limitations. We have developed a novel technique based on whole genome amplification and comparative genomic hybridization (CGH), which for the first time allows the copy number of every chromosome to be assessed in almost every cell of a cleavage-stage embryo. We have successfully analysed 64 cells (blastomeres) derived from 12 embryos and have detected unusual forms of aneuploidy, high levels of chromosomal mosaicism, non-mosaic aneuploidy and chromosome breakage. This is the first report of a comprehensive assessment of chromosome copy number in human embryos and indicates that, despite high levels of mosaicism, some embryos do have normal chromosome numbers in every cell. Such embryos may have a superior developmental potential, and their low frequency may explain correspondingly low success rates of natural and assisted conception in humans.
Inhibition of Stimulated Bone Resorption by Vanadate* (1983)

We have previously reported that stimulated release of calcium (Ca) from bone is a sodium-dependent process. Partial support for this conclusion came from the observation that ouabain inhibited stimulated bone resorption as a result of inhibition of the Na,K-ATPase in bone. We now present additional supporting evidence from the results of experiments using vanadate, an ion known to inhibit the activity of Na,K-ATPase. Vanadate inhibited stimulated bone resorption in neonatal mouse calvaria. Inhibition occurred in a dose-dependent manner, and ortho-vanadate was 3-fold more potent than meta-vanadate. Ortho-vanadate was equally effective against several different stimulators of resorption, including PTH, prostaglandin E2, and 1,25-dihydroxycholecalciferol. PTH-stimulated bone resorption was inhibited with a Ki of about 9 microM. Stimulated Ca release was completely blocked whether vanadate was added at zero time or 24 h after the addition of a resorption-stimulating agent. Because the responses to vanadate were similar to those observed with ouabain, we conclude that vanadate is probably acting to inhibit stimulated resorption via inhibition of the Na,K-ATPase in bone.
Characterization of HSFY, a novel AZFb gene on the Y chromosome with a possible role in human spermatogenesis (2004)

HSFY (heat shock transcription factor, Y chromosome) has been mapped in the AZFb region of the Y chromosome, whose deletion results in severe male infertility. HSFY belongs to the heat shock factor family that has been shown to be implicated in spermatogenesis both in animals and humans. We report the characterization of the genomic structure, the number of copies on the Y chromosome and the expression of the gene. By comparison of data obtained from expression analysis and from GenBank cDNA sequences, seven exons were identified. Alternative splicing generates three different transcripts and proteins, each containing an HSF domain typical of HSF proteins. Two identical and functional full-length copies of HSFY map in palindrome P4 of AZFb, whereas four similar sequences mapping in two clusters in palindrome P1 of AZFc and P3 seem to represent pseudogenes. Sequences similar to few HSFY exons are also located in the short arm of chromosomes Y, X and 22. Expression analysis revealed that the three HSFY transcripts are differentially expressed, transcript 1 being present in many tissues including testis and ejaculated sperm, and transcripts 2 and 3 being testis-specific. These data suggest that HSFY could have an important role in human spermatogenesis.
The effect of oestrogen on the female cardiovascular system (1992)

The consensus of the published data is that oestrogen conveys a highly protective effect on the cardiovascular system of postmenopausal women. There will be a reduction of up to 50% in myocardial infarction and stroke, a reduction in the incidence of hypertension and an improvement in blood flow. Some of the data suggest that even for women who have suffered from an infarct, their long-term survival is enhanced by oestrogen therapy. The medical myth that oestrogen has a deleterious effect on the cardiovascular system of women is finally laid to rest.
HDAC inhibitors as anti‐inflammatory agents (2007)

Diverse cellular functions including the regulation of inflammatory gene expression, DNA repair and cell proliferation are regulated by changes in the acetylation status of histones and non‐histone proteins. Many human diseases, particularly cancer, have been associated with altered patterns of histone acetylation. Furthermore, abnormal expression and activation of histone acetyltransferases, which act as transcriptional co‐activators, has been reported in inflammatory diseases. Histone deacetylase (HDAC) inhibitors have been developed clinically for malignancies due to their effects on apoptosis. More recently, in vitro and in vivo data indicates that HDAC inhibitors may be anti‐inflammatory due to their effects on cell death acting through acetylation of non‐histone proteins. Although there are concerns over the long‐term safety of these agents, they may prove useful particularly in situations where current anti‐inflammatory therapies are suboptimal. British Journal of Pharmacology (2007) 150, 829–831. doi: 10.1038/sj.bjp.0707166
Pairing the cholinergic agonist carbachol with patterned Schaffer collateral stimulation initiates protein synthesis in hippocampal CA1 pyramidal cell dendrites via a muscarinic, NMDA-dependent mechanism (1993)

Effects of afferent stimulation on local synthesis of protein in CA1 pyramidal cell dendrites were studied using light microscope autoradiography. Tissue was fixed with paraformaldehyde immediately after 3 min exposure to 3H-leucine in order to trap 3H associated with macromolecules. The rate of 3H-leucine incorporation into dendrites of resting hippocampal slices was 10% the rate of incorporation into cell somata. Ninety percent of the incorporation into the somata was inhibited by cycloheximide (300 microM); none of the incorporation into dendrites was blocked by cycloheximide. Thus, there is no measurable extramitochondrial synthesis of protein in the dendrites of the resting slice. Slices were exposed to 50 microM carbachol and the Schaffer collateral afferents to the CA1 pyramidal cells were stimulated intermittently at 10 Hz over a 20 min period. In this case, 3H incorporation into dendrites was increased almost threefold over resting levels, with no effect on label over the cell somata. There was no associated increase in uptake of free 3H-leucine, and the increase in label was completely blocked by cycloheximide. Thus, associating carbachol and afferent stimulation appears to activate de novo protein synthesis in the dendrites. Neither the carbachol alone nor the Schaffer collateral stimulation alone increased synthesis. The activation of dendrite synthesis was completely blocked by 5 microM atropine, and also by 50 microM D-aminophosphonovalerate. It did not occur when carbachol was paired with steady stimulation of the Schaffer collaterals at 1 Hz for 20 min, rather than with the patterned high-frequency stimulation. Thus, associating a cholinergic agonist with a level of neural activity that occurs in CA3 and CA1 pyramidal cells during exploratory behavior (Muller et al., 1987) initiates local protein synthesis in target dendrites. This effect is dependent on muscarinic cholinergic receptors and NMDA-type glutamate receptors. The possible relationship of this phenomenon to mechanisms of learning is discussed.
Free DNA – new potential analyte in clinical laboratory diagnostics? (2012)

The existence of cell free DNA in the human circulatory system has been known since the 1950s, however, intensive research in this area has been conducted for the last ten years. This review paper brings a short overview of the existing literature concerning the cell free DNA research in various clinical fields and pathological states and considers the application possibilities of this new analyte in clinical laboratory diagnostics. At the moment, cell free DNA is most widely used for the purpose of non-invasive prenatal diagnosis of fetal sex or fetal RhD status. The recent discovery of epigenetic changes in placental/fetal DNA and the detection of fetal/placental-specific RNAs have made it possible to use this technology in all pregnancies irrespective of the gender of the fetus. With the application of new techniques such as next generation sequencing, digital PCR and mass spectrometry, it is now possible to detect very small amounts of specific DNA in the presence of excess of other nonspecific nucleic acids. Second most probable application is in oncology, where detection and monitoring of tumors is now possible by the detection of tumor-derived nucleic acids. Third promising field for near future implementation of this analyte is transplantation medicine, where free DNA level could serve as a marker of transplant rejection. Before any further utilization of this new biomarker, pre-analytical and analytical aspects of free DNA analysis remain to be standardized. In the field of noninvasive prenatal diagnosis, important ethical, legal and social questions remain to be discussed.
Reversal of Idiopathic Thrombocytopenic Purpura [ITP] with Fecal Microbiota Transplantation [FMT] (2011)

Purpose: Regarded as an autoimmune disorder, Idiopathic Thrombocytopenic Purpura is characterized by persistent fluctuating thrombocytopenia of unknown cause resulting in platelet destruction. Current treatments include corticosteroids, and other immunosuppressive medications, or splenectomy. The risk of serious morbidity/mortality is substantial, with life-threatening hemorrhagic events and death estimated at being 60 percent above expected mortality rate1. We report an unexpected finding in a patient with long-standing ulcerative colitis (UC) and ITP in whom FMT for UC resulted in a ‘cure' of her concomitant ITP. This response suggests an underlying infection of the gut microbiota as a possible etiology in this disorder. Methods: Case: A 39 year old female presented for opinion and management of her chronic, relapsing UC, diagnosed in 1984. The patient also had concomitant idiopathic thrombocytopenic purpura since 1995. Due to difficult-to-control UC and frequent relapses the patient was offered FMT prior to colectomy. Prior to undergoing FMT in January 1999, the patient's mean platelet levels were consistently beneath the lower limit of normal (mean 96.18, range 62-133). In the months following FMT the patient experienced an abrupt rise in her platelet count with a mean of 127 (range 56-188) which then normalized upwards to lie consistently within the upper limits of the normal range (mean 190, range 153-259) from March 2004 where they remain today. The patient also experienced a marked reduction in UC symptoms, passing 2-3 semi-formed stools daily, without bleeding or urgency. Results: We believe this is the first case of immune-mediated ITP successfully reversed using FMT. Transient thrombocytopenia has been reported secondary to infections with Helicobacter pylori, Campylobacter jejuni, Yersinia enterocolitica and Mycobacterium tuberculosis, all absent in this patient. Success of FMT in this ‘autoimmune' condition, traditionally etiologically unrelated to the gastrointestinal tract, suggests this therapy may be beneficial in other socalled ‘autoimmune' conditions and prompts us to reconsider the mechanisms behind ‘autoimmune disorders'. Conclusion: Our finding that ITP can be reversed by FMT points to an underlying GI infective cause. The success of this procedure in this ‘autoimmune' condition highlights the potential of FMT in other diseases previously thought to be ‘autoimmune'.
Perspectives on Reprograming Cancer-Associated Dendritic Cells for Anti-Tumor Therapies (2014)

In recent years, the relevance of the tumor microenvironment (TME) in the progression of cancer has gained considerable attention. It has been shown that the TME is capable of inactivating various components of the immune system responsible for tumor clearance, thus favoring cancer cell growth and tumor metastasis. In particular, effects of the TME on antigen-presenting cells, such as dendritic cells (DCs) include rendering these cells unable to promote specific immune responses or transform them into suppressive cells capable of inducing regulatory T cells. In addition, under the influence of the TME, DCs can produce growth factors that induce neovascularization, therefore further contributing to tumor development. Interestingly, cancer-associated DCs harbor tumor antigens and thus have the potential to become anti-tumor vaccines in situ if properly reactivated. This perspective article provides an overview of the scientific background and experimental basis for reprograming cancer-associated DCs in situ to generate anti-tumor immune responses.
Signal-signal beat interference cancellation in spectrally-efficient WDM direct-detection Nyquist-pulse-shaped 16-QAM subcarrier modulation (2015)

An experimental demonstration of direct-detection single-sideband Nyquist-pulse-shaped 16-QAM subcarrier modulated (Nyquist-SCM) transmission implementing a receiver-based signal-signal beat interference (SSBI) cancellation technique is described. The performance improvement with SSBI mitigation, which compensates for the nonlinear distortion caused by square-law detection, was quantified by simulations and experiments for a 7 × 25 Gb/s WDM Nyquist-SCM signal with a net optical information spectral density (ISD) of 2.0 (b/s)/Hz. A reduction of 3.6 dB in the back-to-back required OSNR at the HD-FEC threshold was achieved. The resulting reductions in BER in single channel and WDM transmission over distances of up to 800 km of uncompensated standard single-mode fiber (SSMF) achieved are presented.
Nanoscale organization in piperidinium-based room temperature ionic liquids (2009)

Here we report on the complex nature of the phase diagram of N-alkyl-N-methylpiperidinium bis(trifluoromethanesulfonyl)imide ionic liquids using several complementary techniques and on their structural order in the molten state using small-wide angle x-ray scattering. The latter study indicates that the piperidinium aliphatic alkyl chains tend to aggregate, forming alkyl domains embedded into polar regions, similar to what we recently highlighted in the case of other ionic liquids.
Randomized, controlled clinical trials in sepsis: Has methodological quality improved over time? (2002)

The methodological limitations identified in this article can help to target further improvement in trial design to enhance the validity of findings from future randomized clinical trials of sepsis.
Metabolism of the herbicide atrazine by Rhodococcus strains (1993)

Rhodococcus strains were screened for their ability to degrade the herbicide atrazine. Only rhodococci that degrade the herbicide EPTC (s-ethyl-dipropylthiocarbamate) metabolized atrazine. Rhodococcus strain TE1 metabolized atrazine under aerobic conditions to produce deethyl- and deisopropylatrazine, which were not degraded further and which accumulated in the incubation medium. The bacterium also metabolized the other s-triazine herbicides propazine, simazine, and cyanazine. The N dealkylation of triazine herbicides by Rhodococcus strain TE1 was associated with a 77-kb plasmid previously shown to be required for EPTC degradation.
Bilayer resist approach for 193-nm lithography (1996)

Tremendous efforts to extend optical lithography beyond the quarter micrometer boundary, which is currently achievable with KrF-excimer laser lithography, are ongoing. One-hundred- ninety-three nm lithography, using ArF-excimer lasers, is believed to be the technology of choice to approach the ambitious sub-0.2 micrometer resolution target. Single layer, positive tone resist systems, which can be developed with aqueous base, would be preferred. However, it might well turn out that the targeted requirements can only be fulfilled by resist systems which involve some type of dry etch steps. This paper focuses on a positive tone bilayer resist system, which is based on novel silicon containing methacrylate polymers bearing acid labile side groups. Due to a unique combination of monomeric building blocks, polymers with high silicon concentrations and, at the same time, high thermal flow stability are obtained. Hardbaked novolac is used as the planarizing layer. Resists systems based on the new silicon containing polymers demonstrated 0.175 micrometer resolution capability, a thermal flow stability greater than 120 degrees Celsius, and an etch selectivity ratio greater than 20.
Sequence Analysis of the IRES-Loop III Region of Hepatitis C Virus (1998)

Human hepatitis C virus (HCV) causes chronic infection of the liver and has been linked to the development of hepatocellular carcinoma. The viral genome consists of a single-stranded, positivesense RNA approximately 9,500 nucleotides in length with an open reading frame. The 5' noncoding region (5'NCR), which varies in length from 332 to 341 nucleotides, is followed by a long open reading frame encoding a polyprotein of about 3,000 amino acids. The process by which this region initiates translation is controlled by an internal ribosomal entry segment (IRES) that occupies most of the 5'NCR. HCV is classi ed into seven genotypes, and the IRES of HCV genotype 3 is known to reduce translation e ciency. The loop III region of IRES are thought to in uence translation e ciency, but had not yet been compared between genotypes. We therefore analyzed the IRES loop IIIa{IIId region by using principal component analysis (PCA) and multidimensional scaling analysis (MDS) in an attempt to compare the sequences of the region of all genotypes.
Inhibition of replication and expression of human T-cell lymphotropic virus type III in cultured cells by exogenous synthetic oligonucleotides complementary to viral RNA. (1986)

The possibility of using oligodeoxynucleotides complementary to viral RNA or proviral DNA to inhibit the replication of human T-cell lymphotropic virus type III (HTLV-III) [the etiological agent of acquired immunodeficiency syndrome (AIDS)] in cultured human cells was addressed by studying the association of 32P-labeled oligodeoxynucleotides with mammalian cellular components. The results indicated that exogenous oligodeoxynucleotides at 20 microM became associated with the membrane/cytosol fractions of the cell in amounts approximating 1.5 microM. Oligodeoxynucleotides complementary to a region close to the tRNALys primer binding site on HTLV-III RNA and others complementary to HTLV-III mRNA donor or acceptor splice sites inhibited viral replication (assayed as reverse transcriptase) and gene expression (assayed as virus-encoded proteins p15 and p24) by as much as 95%. Use of control (random) oligodeoxynucleotides suggests that the antiviral effects were specific. Although these results pertain to HTLV-III-infected cells in tissue culture, rather than to AIDS patients, they nevertheless point to a therapeutic potential of the complementary oligodeoxynucleotide ("hybridization competition" or "hybridon") approach in the treatment of patients with AIDS and AIDS-related complex.
The Kinetic Mechanism of AAC(3)-IV Aminoglycoside Acetyltransferase from Escherichia coli (2005)

The aminoglycoside 3-N-acetyltransferase AAC(3)-IV from Escherichia coli exhibits a very broad aminoglycoside specificity, causing resistance to a large number of aminoglycosides, including the atypical veterinary antibiotic, apramycin. We report here on the characterization of the substrate specificity and kinetic mechanism of the acetyl transfer reaction catalyzed by AAC(3)-IV. The steady-state kinetic parameters revealed a narrow specificity for the acyl-donor and broad range of activity for aminoglycosides. AAC(3)-IV has the broadest substrate specificity of all AAC(3)'s studied to date. Dead-end inhibition and ITC experiments revealed that AAC(3)-IV follows a sequential, random bi-bi kinetic mechanism. The analysis of the pH dependence of the kinetic parameters revealed acid- and base-assisted catalysis and the existence of three additional ionizable groups involved in substrate binding. The magnitude of the solvent kinetic isotope effects suggests that a chemical step is at least partially rate limiting in the overall reaction.
Targeting colorectal cancer with human anti-EGFR monoclonocal antibodies: focus on panitumumab (2008)

The human anti-epidermal growth factor receptor (EGFR) monoclonal antibody, panitumumab, represents a significant advance in the treatment of colorectal cancer. The strategy to target this receptor is based on sound cancer biology demonstrating its essential role in colorectal carcinogenesis. Panitumumab, unlike its predecessor, cetuximab, is fully human and thus reduces the incidence of hypersensitivity reactions. But, in several clinical trials, unexpected toxicities have become more apparent, raising concerns of how readily panitumumab can succeed cetuximab. This paper reviews the development of this agent and the pivotal clinical trials that help our understanding of its optimal use in colorectal cancer treatment.