gebhart/patrepeval huggingface dataset:
High-Throughput FRET Assay Yields Allosteric SERCA Activators (2012)

Using fluorescence resonance energy transfer (FRET), we performed a high-throughput screen (HTS) in a reconstituted membrane system, seeking compounds that reverse inhibition of sarcoplasmic reticulum Ca-ATPase (SERCA) by its cardiac regulator, phospholamban (PLB). Such compounds have long been sought to correct aberrant Ca(2+) regulation in heart failure. Donor-SERCA was reconstituted in phospholipid membranes with or without acceptor-PLB, and FRET was measured in a steady-state fluorescence microplate reader. A 20 000-compound library was tested in duplicate. Compounds that decreased FRET by more than three standard deviations were considered hits. From 43 hits (0.2%), 31 (72%) were found to be false-positives upon more thorough FRET testing. The remaining 12 hits were tested in assays of Ca-ATPase activity, and six of these activated SERCA significantly, by as much as 60%, and several also enhanced cardiomyocyte contractility. These compounds directly activated SERCA from heart and other tissues. These results validate our FRET approach and set the stage for medicinal chemistry and preclinical testing. We were concerned about the high rate of false-positives, resulting from the low precision of steady-state fluorescence. Preliminary studies with a novel fluorescence lifetime plate reader show 20-fold higher precision. This instrument can dramatically increase the quality of future HTS.
Pure phosphatides and the serodiagnosis of syphilis: relation of chemical structure to reactivity. (1958)

Several pure individual lecithins, all but one of which were synthetic, were used in cardiolipin antigens prepared for the VDRL microflocculation and Kolmer complement-fixation tests for syphilis.A number of compounds lacking one or more radicals of the lecithin molecule were used as substitutes for lecithin in an effort to determine reactive groupings.Several synthetic compounds related to cardiolipin, but simpler in structure, were tested as substitutes for it. Of these, certain fatty-acid derivatives of bis-(L-alpha-glyceryl)-phosphoric acid and of L-alpha-glycerophosphoric acid showed a limited reactivity in the VDRL and Kolmer tests.A number of weakly reactive antigens, in which both cardiolipin and lecithin had been replaced by synthetic compounds, were prepared for the VDRL test. The most reactive of these contained beta-(dioleoyl)-glycerophosphoric acid (sodium salt), dioleoyl lecithin and cholesterol.
Dendritic cells loaded with killed breast cancer cells induce differentiation of tumor-specific cytotoxic T lymphocytes (2004)

Loading DCs with killed breast cancer cells may be considered a novel approach to breast cancer immunotherapy and to identification of shared breast cancer antigens.
Chicago spectrum occupancy measurements & analysis and a long-term studies proposal (2006)

This paper describes spectrum occupancy measurements performed in Chicago, IL in November 2005 and proposes long-term studies in multiple locations. The Chicago project consisted of deploying a high dynamic range spectrum measurement system, a data collection and processing system and conducting spectrum occupancy measurements in all bands between 30 MHz and 3,000 MHz (see Figure 1). These measurements were taken over a two-day period and are added to an existing body of data compiled in other cities and regions including Washington, D.C., and New York City. While these studies are critical in determining what bands have low utilization, longer-term studies are crucial in developing new spectrum access technologies such as cognitive radio algorithms related to Dynamic Spectrum Sharing (DSS). The observed low spectrum occupancy in a business center like Chicago indicates that a DSS radio system could access a huge amount of "prime" spectrum. The unoccupied, large contiguous spectrum blocks show that DSS radios can use conventional contiguous waveforms and that high temporal agility may not be required to significantly expand the data capacity of an accessible section of spectrum. From both short-term and long-term spectrum occupancy studies, candidate bands for spectrum sharing can be readily identified along with unique signal characteristics within these bands. The most important use of the data will be to support senior U.S. (and non-U.S.) government officials in taking action to enhance the use of the currently under utilized RF spectrum resources and to make the R&D investments and policy changes needed to support the development of dynamic spectrum sharing radios.
Pegylated Recombinant Human Arginase (rhArg-peg5,000mw) Inhibits the In vitro and In vivo Proliferation of Human Hepatocellular Carcinoma through Arginine Depletion (2007)

Hepatocellular carcinoma (HCC) is believed to be auxotrophic for arginine through the lack of expression of argininosuccinate synthetase (ASS). The successful use of the arginine-depleting enzyme arginine deiminase (ADI) to treat ASS-deficient tumors has opened up new possibilities for effective cancer therapy. Nevertheless, many ASS-positive HCC cell lines are found to be resistant to ADI treatment, although most require arginine for proliferation. Thus far, an arginine-depleting enzyme for killing ASS-positive tumors has not been reported. Here, we provide direct evidence that recombinant human arginase (rhArg) inhibits ASS-positive HCCs. All the five human HCC cell lines we used were sensitive to rhArg but ADI had virtually no effect on these cells. They all expressed ASS, but not ornithine transcarbamylase (OTC), the enzyme that converts ornithine, the product of degradation of arginine with rhArg, to citrulline, which is converted back to arginine via ASS. Transfection of HCC cells with OTC resulted in resistance to rhArg. Thus, OTC expression alone may be sufficient to induce rhArg resistance in ASS-positive HCC cells. This surprising correlation between the lack of OTC expression and sensitivity of ASS-positive HCC cells shows that OTC-deficient HCCs are sensitive to rhArg-mediated arginine depletion. Therefore, pretreatment tumor gene expression profiling of ASS and OTC could aid in predicting tumor response to arginine depletion with arginine-depleting enzymes. We have also shown that the rhArg native enzyme and the pegylated rhArg (rhArg-peg(5,000mw)) gave similar anticancer efficacy in vitro. Furthermore, the growth of the OTC-deficient Hep3B tumor cells (ASS-positive and ADI-resistant) in mice was inhibited by treatment with rhArg-peg(5,000mw), which is active alone and is synergistic in combination with 5-fluorouracil. Thus, our data suggest that rhArg-peg(5,000mw) is a novel agent for effective cancer therapy.
ChemInform Abstract: STUDIES IN ANTIFERTILITY AGENTS PART 14, SECO‐STEROIDS PART 7, SYNTHESIS OF 2ALPHA‐ AND 2BETA,6BETA‐DIMETHYL‐3BETA‐(P‐HYDROXYPHENYL)‐TRANS‐BICYCLO(4.3.0)NONAN‐7‐ONES AND SOME RELATED COMPOUNDS (1975)

Abstract Das durch Kondensation des Oxobicyclononenols (I) mit dem Li‐Derivat (II) zugängliche Benzhydrol (III) liefert beim Erhitzen in Benzol in Gegenwart katalytischer Mengen Jod das Dienol (IV), dessen Hydrogenolyse ein untrennbares 75 : 25‐Gemisch ( 95% Ausbeute) der Hydroxyäther (V) und (VI) gibt.
A single rat fibronectin gene generates three different mRNAs by alternative splicing of a complex exon. (1984)

Three fibronectin mRNAs exist in rat liver, differing by the presence or absence of segments of 285 or 360 bases at a point within the coding region. We previously proposed that the three mRNAs are encoded by a single gene and arise via alternative splicing of a common transcript. In order to test this hypothesis, we have isolated clones spanning approximately half of the fibronectin gene from a Fisher rat genomic library; blot hybridization analyses reveal the presence of only one fibronectin gene in the haploid rat genome. We determined the sequence of a portion (1221 nucleotides) of this gene. This sequence shows clearly that the three fibronectin mRNAs encoded by this gene are generated by a pattern of alternative splicing in which one 5' splice site can be paired with any one of three 3' splice sites, one at the beginning of, and two within, a single complex exon.
Measurement of mammalian sperm deoxyribonucleic acid by flow cytometry. Problems and approaches. (1977)

Measurement of mammalian sperm deoxyribonucleic acid content is of importance in several areas of biomedical research. When measured in flow systems with orthogonal axes of illumination, flow and detection, an unexpected, distorted distribution consisting of a narrow peak with a lateral extension to the right is observed. Several lines of evidence lead to the conclusion that this effect is an optical-geometric artifact attributable to the flat shape and high index of refraction of mammalian sperm heads. This artifact disappears when an epiillumination flow system is used in which the optic axes for illumination and detection and the flow axis are all coincident. Other approaches also eliminate the artifact. The resulting coefficients of variation observed after acriflavine-Feulgen staining are 4-5%, short of the goal of 1.5% required to distinguish between human sperm bearing X and Y chromosomes and to develop a mutagen test system using mice.
Predicting Gene Expression Level from Relative Codon Usage Bias: An Application to Escherichia coli Genome (2009)

We present an expression measure of a gene, devised to predict the level of gene expression from relative codon bias (RCB). There are a number of measures currently in use that quantify codon usage in genes. Based on the hypothesis that gene expressivity and codon composition is strongly correlated, RCB has been defined to provide an intuitively meaningful measure of an extent of the codon preference in a gene. We outline a simple approach to assess the strength of RCB (RCBS) in genes as a guide to their likely expression levels and illustrate this with an analysis of Escherichia coli (E. coli) genome. Our efforts to quantitatively predict gene expression levels in E. coli met with a high level of success. Surprisingly, we observe a strong correlation between RCBS and protein length indicating natural selection in favour of the shorter genes to be expressed at higher level. The agreement of our result with high protein abundances, microarray data and radioactive data demonstrates that the genomic expression profile available in our method can be applied in a meaningful way to the study of cell physiology and also for more detailed studies of particular genes of interest.
Clinical Trials Using Antisense Oligonucleotides in Duchenne Muscular Dystrophy (2013)

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disorder caused by mutations in the DMD gene, affecting 1 in 3500 newborn males. Complete loss of muscle dystrophin protein causes progressive muscle weakness and heart and respiratory failure, leading to premature death. Antisense oligonucleotides (AONs) that bind to complementary sequences of the dystrophin pre-mRNA to induce skipping of the targeted exon by modulating pre-mRNA splicing are promising therapeutic agents for DMD. Such AONs can restore the open reading frame of the DMD gene and produce internally deleted, yet partially functional dystrophin protein isoforms in skeletal muscle. Within the last few years, clinical trials using AONs have made considerable progress demonstrating the restoration of functional dystrophin protein and acceptable safety profiles following both local and systemic delivery in DMD patients. However, improvement of AON delivery and efficacy, along with the development of multiple AONs to treat as many DMD patients as possible needs to be addressed for this approach to fulfill its potential. Here, we review the recent progress made in clinical trials using AONs to treat DMD and discuss the current challenges to the development of AON-based therapy for DMD.
Insulin-like growth factor-binding protein 2 in tumorigenesis: protector or promoter? (2001)

The IGF[3][1] system is composed of the two peptide ligands (IGF-I and IGF-II), six high-affinity IGF-binding proteins (IGFBP-1 to IGFBP-6), and two IGF receptors (IGF-IR and IGF-IIR), of which IGF-IR confers most of the biological actions of IGFs [(1][2] [, 2)][3] . The actions of IGFs may be
Meningiomas: Role of Vascular Endothelial Growth Factor/Vascular Permeability Factor in Angiogenesis and Peritumoral Edema (1997)

These data suggest that VEGF/VPF may play a role in both meningioma vascularity and peritumoral edema.
High-quality Parametric Spatial Audio Coding at Low Bitrates (2004)

This convention paper has been reproduced from the author’s advance manuscript, without editing, corrections, or consideration by the Review Board. The AES takes no responsibility for the contents. Additional papers may be obtained by sending request and remittance to Audio Engineering Society, 60 East 42nd Street, New York, New York 10165-2520, USA; also see www.aes.org. All rights reserved. Reproduction of this paper, or any portion thereof, is not permitted without direct permission from the Journal of the Audio Engineering Society.
Functional interactions between arginine-133 and aspartate-88 in the human reduced folate carrier: evidence for a charge-pair association (2001)

The human reduced folate carrier (hRFC) is an integral membrane protein that mediates cellular uptake of reduced folates and antifolates. hRFC contains several highly conserved charged residues predicted to lie in the transmembrane domains (TMDs). To explore the possible roles of the conserved arginine-133, located in TMD 4, in hRFC structure and function, this residue was systematically mutagenized to histidine, leucine, lysine and glutamate. When transfected into transport-impaired K562 cells, the mutant hRFC constructs were expressed at high levels; however, only lysine-133hRFC was able to transport methotrexate and (6S)-5-formyl tetrahydrofolate. Substitution of aspartate-453 (in hRFC TMD 12) by valine largely preserved transport activity for both substrates. Although mutagenesis of aspartate-88 (in TMD 2) to leucine completely abolished transport activity in transfected cells, substitution with a glutamate preserved low levels (≈ 12%) of transport. To assess the possibility that arginine-133 and aspartate-88 may form a charge-pair to stabilize hRFC tertiary structure, both charges were neutralized (by substituting leucine and valine, respectively) in the same construct. In contrast to the singly mutated hRFCs, the double mutant exhibited high levels of transport with both methotrexate and 5-formyl tetrahydrofolate. These results strongly suggest that arginine-133 and aspartate-88 form a charge-pair and that TMD 4 lies next to TMD 2 in the hRFC tertiary structure.
Characterization of PLA2G6 as a locus for dystonia‐parkinsonism (2008)

PLA2G6 mutations are associated with infantile neuroaxonal dystrophy and have been reported previously to cause early cerebellar signs, and the syndrome was classified as neurodegeneration with brain iron accumulation (type 2). Our cases have neither of these previously pathognomic features. Thus, mutations in PLA2G6 should additionally be considered in patients with adult-onset dystonia-parkinsonism even with absent iron on brain imaging.
Organotrifluorborate und einfach koordinierte Palladiumkomplexe als Katalysatoren – die perfekte Kombination für die Suzuki‐Miyaura‐Kupplung (2009)

Abstract Einfach koordinierte katalytische Palladiumkomplexe mit sperrigen, elektronenreichen Phosphan‐ oder N‐heterocyclischen Carbenliganden haben die Suzuki‐Miyaura‐Kupplung revolutioniert. Weitere interessante Perspektiven für diese Reaktionen ergaben sich durch die Einführung von Organotrifluorboraten als Organoborkomponenten. Die Kombination dieser beiden Neuerungen führte zu einem außerordentlich leistungsfähigen Kreuzkupplungsverfahren.
A double-blind comparison of acitretin and etretinate in the treatment of severe psoriasis. Results of a Nordic multicentre study. (1989)

Acitretin, the free acid of etretinate, is less lipophilic and has a much shorter terminal half-life than the parent compound. The present double-blind, randomized study compared the therapeutic effectiveness and the tolerability of acitretin (n = 127) and etretinate (n = 41) in psoriasis. Patients were treated with 40 mg daily for the first 4 weeks and with an individually adjusted dose for the subsequent 8 weeks. The average daily doses of acitretin (0.54 mg/kg/day) and etretinate (0.65 mg/kg/day) were similar. The PASI (Psoriasis Area and Severity Index) scores improved in parallel in the 2 treatment groups. At the completion of the study, the PASI score improvement was 75.8% for acitretin and 70.8% for etretinate. Both acitretin and etretinate resulted in mucocutaneous side effects. Assessments of tolerability by investigators and patients showed a statistically significant difference in favour of etretinate. These results demonstrate that acitretin and etretinate have similar therapeutic effectiveness in psoriasis. Although the tolerance to acitretin was lower than to etretinate, acitretin offers the important advantage of a much shorter period of potential teratogenicity and is, therefore, to be preferred in women of childbearing potential.
The influence of long-term administration of Tołpa Peat Preparation on immune reactivity in mice. I. Morphological changes in the thymus. (1993)

In experiment I BALB/c 200 mice were given in drinking water the TPP (Tołpa Peat Preparation) in daily doses of 1, 10 and 50 mg/kg over the period of 3, 5, 7, 9 and 12 weeks. In experiment II before the administration of TPP (as in experiment I) mice were immunized with a single dose i.p. administration of 0.2 cm3 of a 10% suspension of sheep erythrocytes (SRBC), i.e. 4 x 10(8) cells. Histopathological and ultrastructural studies have shown that TPP in all three doses causes morphological changes characteristic of thymus activity stimulation. However, the doses of 10 and 50 mg/kg administered longer than 7 weeks caused retrograde changes that did not occur after administration of 1 mg/kg of TPP. Morphological changes in the thymus of immunized and non-immunized mice simultaneously receiving TPP were similar.
A Refined Calculation of the Solution Dimensions of the Complex Between Gene 32 Protein and Single Stranded DNA Based on Estimates of the Bending Persistence Length (1990)

The rotation diffusion coefficient of a complex of GP32, the single stranded DNA binding protein of the bacteriophage T4, with a single stranded DNA fragment with about 270 bases was determined to obtain further information on the flexibility of this particle. The rotation diffusion of these molecules is used as a sensitive measure of the flexibility of different DNA protein complexes. Using the theory of Hagerman and Zimm (Biopolymers 20, 1481 (1981)) and assuming a bending persistence length of about 35 nanometer it can be shown that the axial increment for GP32 complexes with single stranded DNA is close to 0.5 nm per base. The value for the bending persistence length is in agreement with values found for much larger DNA protein complexes using light scattering experiments. This value for the persistence length also implies that the complex is thin. The radius is estimated to be around 1.7 nm, which shows a moderate degree of hydration. With this set of parameters we can describe all the hydrodynamic experiments on GP32 complexes from 76 to more than 7000 bases obtained using electric birefringence, quasi-elastic light scattering and sedimentation experiments performed in our group over the last few years.
Circulating bone marrow‐derived endothelial progenitor cells: Characterization, mobilization, and therapeutic considerations in malignant disease (2007)

Until recently, tumor vascularization was thought to occur exclusively through angiogenesis. However, recent studies using different animal models of cancer suggested the importance of bone marrow-derived endothelial progenitor cells (EPCs) (i.e. postnatal vasculogenesis) in tumor vascularization and growth. EPCs are present in the peripheral blood, their levels are increased in response to certain signals/cytokines, and they home into the neovascular bed of malignant tissues. Furthermore, at the clinical level, evidence is emerging that changes in EPC levels might predict the efficacy of anticancer drug combinations that include antiangiogenic agents. On the basis of these observations, EPCs have attractive potential diagnostic and therapeutic applications for malignant diseases. In this paper, we review biological features of EPCs and speculate on the utility of these progenitor cells for medical oncology.
Synthesis, in vitro and in vivo activity of novel 9-deoxo-9a-aza-9a-homoerythromycin A derivatives; A new class of macrolide antibiotics, the azalides. (1988)

A series of erythromycin A-derived semisynthetic antibiotics, featuring incorporation of a basic nitrogen atom into a ring expanded (15-membered) macrocyclic lactone, have been prepared and biologically evaluated. Semisynthetic modifications focused upon (1) varied substitution at the macrocyclic ring nitrogen and (2) epimerization or amine substitution at the C-4'' hydroxyl site within the cladinose sugar. In general, the new azalides exhibit improved Gram-negative potency, expanding the spectrum of erythromycin A to fully include Haemophilus influenzae and Neisseria gonorrhoeae. When compared to erythromycin A, the azalides exhibit substantially increased half-life and area-under-the-curve values in all species studied. The overall in vitro/in vivo performance of N-methyl, C-4'' epimers 3a and 9; and C-4'' amine 11 identify these compounds as the most interesting erythromycin A-superior agents. Compound 3a has been advanced to clinical study.
Lipid peroxidation and antioxidant status in patients with periodontitis. (2005)

Our aim was to assess the degree of oxidative stress in patients with periodontitis by measuring their levels of thiobarbituric acid reactive substances (TBARS), enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (GSHPx)), and non-enzymatic antioxidants (vitamins E and C, reduced glutathione (GSH)). This study was conducted on 25 adult chronic periodontitis sufferers who were patients in Rajah Muthiah Dental College and Hospital, Annamalai University. The levels of TBARS and non-enzymatic antioxidants, and the activities of enzymatic antioxidants in the patients' plasma, erythrocytes and gingival tissues were assayed using specific colorimetric methods. The periodontitis sufferers had a significantly higher TBARS level than the healthy subjects. In the plasma, erythrocytes, erythrocyte membranes and gingival tissues of the periodontitis sufferers, enzymatic antioxidant activities were found to be significantly higher, whereas the levels of non-enzymatic antioxidants were significantly lower (except for reduced glutathione in the gingival tissues) relative to the parameters found for healthy subjects. The disturbance in the endogenous antioxidant defense system due to over-production of lipid peroxidation products at inflammatory sites can be related to a higher level of oxidative stress in patients with periodontitis.
Reversal of Postoperative Anuria by Decompressive Celiotomy (1985)

Postoperative oliguria or anuria can rarely be attributed to an increase in intra-abdominal pressure. In this documented case, postoperative anuria responded to reduction in abdominal pressure by celiotomy. Actual abdominal pressure measurements are not available but probably would not be useful. However, hemodynamic measurements that were not consistent with diminished renal blood flow in a middle-aged patient were nevertheless associated with anuria, which responded to release of the abdominal pressure. Because of the association of regional pressure and acute renal decompensation, release of abdominal tension should be considered as a therapeutic option when hemodynamic measurements cannot explain a rapid decline in urine production.