gebhart/patrepeval huggingface dataset:
Dimeric Fragment of the Insulin Receptor α-Subunit Binds Insulin with Full Holoreceptor Affinity (2001)

The insulin receptor (IR) is a dimeric receptor, and its activation is thought to involve cross-linking between monomers initiated by binding of a single insulin molecule to separate epitopes on each monomer. We have previously shown that a minimized insulin receptor consisting of the first three domains of the human IR fused to 16 amino acids from the C-terminal of the alpha-subunit was monomeric and bound insulin with nanomolar affinity (Kristensen, C., Wiberg, F. C., Schäffer, L., and Andersen, A. S. (1998) J. Biol. Chem. 273, 17780-17786). To investigate the insulin binding properties of dimerized alpha-subunits, we have reintroduced the domains containing alpha-alpha disulfide bonds into this minireceptor. When inserting either the first fibronectin type III domain or the full-length sequence of exon 10, the receptor fragments were predominantly secreted as disulfide-linked dimers that both had nanomolar affinity for insulin, similar to the affinity found for the minireceptor. However, when both these domains were included we obtained a soluble dimeric receptor that bound insulin with 1000-fold higher affinity (4-8 pm) similar to what was obtained for the solubilized holoreceptor (14-24 pm). Moreover, dissociation of labeled insulin from this receptor was accelerated in the presence of unlabeled insulin, demonstrating another characteristic feature of the holoreceptor. This is the first direct demonstration showing that the alpha-subunit of IR contains all the epitopes required for binding insulin with full holoreceptor affinity.
Glycogen Storage Disease type 1a – a secondary cause for hyperlipidemia: report of five cases (2013)

Evaluation of health-related quality of life (HRQoL) among people with diabetes has been growing in Iran over the last decade. The main aim of the current study was to systematically review the characteristics of these studies and examine quality of their findings. Persian (SID, Magiran) and English (Pubmed, Medline, Web of Science, CINAHL, Scopus, PsycINFO and ERIC) databases were systematically searched using the search terms: "diabetes" AND "quality of life" AND "Iran". The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A total of 46 studies passed the inclusion criteria and were included in the review. The included studies were conducted in 20 out of 30 provinces of the country. Most studies investigated HRQoL among people with type 2 diabetes. The Short Form Health Survey (SF-36) and WHO quality of life instruments (WHOQOL) were the main instruments used in these studies. Studies showed that people with diabetes had lower HRQoL than people without diabetes. Better socioeconomic status and better control of cardiovascular risk factors were associated with better HRQoL among the patients with diabetes. In general, the predictors of HRQoL among Iranian patients were similar to their international counterparts implying that diabetes patients share many common features. The reviewed studies suffer from major methodological and reporting flaws which limit validity and generalizability of their findings.
Can bio-electrical impedance be used to measure total body water in dialysis patients? (1993)

The measurement of total body water (TBW) by bio-electrical impedance (BEI) in a group of renal patients was evaluated against the tritium dilution method. The effect of haemodialysis and the presence of peritoneal dialysate on the impedance were also investigated. The correlation between the two methods was r = 0.9, with the standard deviation of the differences being 3.66 l (TBW typically 40 l). The BEI method overestimated the actual weight loss after haemodialysis, but underestimated the volume of peritoneal dialysate in situ. The BEI method would not be appropriate for use in assessing total body water and monitoring acute volume changes in patients with renal failure who are on strict fluid restriction.
A Study of Brainwave Entrainment Based on EEG Brain Dynamics (2009)

The brain which is composed of more than 100 billion nerve cells is a sophisticated biochemical factory. For many years, neurologists, psychotherapists, researchers, and other health care professionals have studied the human brain. With the development of computer and information technology, it makes brain complex spectrum analysis to be possible and opens a highlight field for the study of brain science. In the present work, observation and exploring study of the activities of brain under brainwave music stimulus are systemically made by experimental and spectrum analysis technology. From our results, the power of the 10.5Hz brainwave appears in the experimental figures, it was proved that upper alpha band is entrained under the special brainwave music. According to the Mozart effect and the analysis of improving memory performance, the results confirm that upper alpha band is indeed related to the improvement of learning efficiency.
Characterization of unique binding kinetics of follistatin and activin or inhibin in serum. (1994)

Serum binding proteins (BPs) have been identified for several peptide and protein hormones, and their presence has significant implications for the biological action of the hormone. Follistatin (FS) has been identified as an activin- and inhibin-BP in tissues, serum, and follicular fluid of several species, including humans. In this study, the binding kinetics of FS for activin and inhibin were characterized in human serum using gel filtration chromatography and compared to those of pure recombinant hormones using chromatography and a new solid phase assay. When complexed with radiolabeled activin or inhibin, FS eluted at a volume corresponding to a mol wt range of 67,000-150,000, an elution volume identical to the lower mol wt BP peak observed in serum. Furthermore, kinetic analyses of recombinant FS binding to activin using a solid phase assay revealed that 1) the FS-activin interaction is of high affinity, similar to or exceeding that estimated for activin binding to its receptor; 2) binding to activin is essentially irreversible at physiological pH; and 3) the potency of inhibin is approximately 500- to 1000-fold lower than that of activin in the FS binding assay. The lack of FS-[125I]activin complex reversibility observed in the solid phase assay was confirmed using a modified gel filtration chromatography protocol. Thus, preincubation of pure FS or serum with unlabeled activin for 2 h eliminated all binding of subsequently added labeled activin despite a much longer incubation period. However, when labeled activin was incubated with FS for 2 h, subsequent addition of unlabeled activin or inhibin was unable to displace labeled activin from FS, again demonstrating a lack of reversibility. Finally, to map this high affinity interaction, overlapping synthetic peptides were used to compete with labeled activin for FS binding. Two potential contact sites between FS and activin were identified, one near the N-terminus (amino acids 15-29) and the other near the C-terminus (amino acids 99-116). Given its apparently irreversible nature, high affinity, and ability to neutralize activin's biological activity, FS is quite different from the typical hormone-BP. These unique properties of FS undoubtedly attest to the potency of activin in many physiological and developmental settings and, therefore, to the importance of BPs, such as FS for regulating activin's bioactivity, distribution, and/or clearance.
Characterization of R132H Mutation‐specific IDH1 Antibody Binding in Brain Tumors (2009)

Heterozygous point mutations of isocitrate dehydrogenase (IDH)1 codon 132 are frequent in grade II and III gliomas. Recently, we reported an antibody specific for the IDH1R132H mutation. Here we investigate the capability of this antibody to differentiate wild type and mutated IDH1 protein in central nervous system (CNS) tumors by Western blot and immunohistochemistry. Results of protein analysis are correlated to sequencing data. In Western blot, anti-IDH1R132H mouse monoclonal antibody mIDH1R132H detected a specific band only in mutated tumors. Immunohistochemistry of 345 primary brain tumors demonstrated a strong cytoplasmic and weaker nuclear staining in 122 cases. Correlation with direct sequencing of 186 cases resulted in consensus of 177 cases. Genetic retesting of cases with conflicting findings resulted in a match of 186/186 cases, with all discrepancies resolving in favor of immunohistochemistry. Intriguing is the ability of mIDH1R132H to detect single infiltrating tumor cells. The very high frequency and the distribution of this mutation among specific brain tumor entities allow the highly sensitive and specific discrimination of various tumors by immunohistochemistry, such as anaplastic astrocytoma from primary glioblastoma or diffuse astrocytoma World Health Organization (WHO) grade II from pilocytic astrocytoma or ependymoma. Noteworthy is the discrimination of the infiltrating edge of tumors with IDH1 mutation from reactive gliosis.
cDNA isolated from a human T-cell library encodes a member of the protein-tyrosine-phosphatase family. (1989)

A human peripheral T-cell cDNA library was screened with two labeled synthetic oligonucleotides encoding regions of a human placenta protein-tyrosine-phosphatase (protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48). One positive clone was isolated and the nucleotide sequence was determined. It contained 1305 base pairs of open reading frame followed by a TAA stop codon and 978 base pairs of 3' untranslated end, although a poly(A)+ tail was not found. An initiator methionine residue was predicted at position 61, which would result in a protein of 415 amino acid residues (Mr, 48,400). This was supported by the synthesis of a Mr 48,000 protein in an in vitro reticulocyte lysate translation system using RNA transcribed from the cloned cDNA and T7 RNA polymerase. The deduced amino acid sequence was compared to other known proteins revealing 65% identity to the low Mr PTPase 1B isolated from placenta. In view of the high degree of similarity, the T-cell cDNA likely encodes a newly discovered protein-tyrosine-phosphatase, thus expanding this family of genes.
Circuitry-based gene expression profiles in GABA cells of the trisynaptic pathway in schizophrenics versus bipolars (2008)

Significant reductions in GABAergic cell numbers and/or activity have been demonstrated in the hippocampus of subjects with schizophrenia and bipolar disorder. To understand how different subpopulations of interneurons are regulated, laser microdissection and gene expression profiling have been used to "deconstruct" the trisynaptic pathway, so that subtypes of GABA cells could be defined by their location in various layers of CA3/2 and CA1. The results suggest that the cellular endophenotypes for SZ and BD may be determined by multiple factors that include unique susceptibility genes for the respective disorders and altered integration among hippocampal GABA cells with extrinsic and intrinsic afferent fiber systems. The extensive and intricate data that has come from this study has provided insights into how a complex circuit, like the trisynaptic pathway, may be regulated in human hippocampus in both health and disease.
Adenoviral Gene Therapy of the Tay-Sachs Disease in Hexosaminidase A-Deficient Knock-Out Mice (1999)

The severe neurodegenerative disorder, Tays-Sachs disease, is caused by a beta-hexosaminidase alpha-subunit deficiency which prevents the formation of lysosomal heterodimeric alpha-beta enzyme, hexosaminidase A (HexA). No treatment is available for this fatal disease; however, gene therapy could represent a therapeutic approach. We previously have constructed and characterized, in vitro, adenoviral and retroviral vectors coding for alpha- and beta-subunits of the human beta-hexosaminidases. Here, we have determined the in vivo strategy which leads to the highest HexA activity in the maximum number of tissues in hexA -deficient knock-out mice. We demonstrated that intravenous co-administration of adenoviral vectors coding for both alpha- and beta-subunits, resulting in preferential liver transduction, was essential to obtain the most successful results. Only the supply of both subunits allowed for HexA overexpression leading to massive secretion of the enzyme in serum, and full or partial enzymatic activity restoration in all peripheral tissues tested. The enzymatic correction was likely to be due to direct cellular transduction by adenoviral vectors and/or uptake of secreted HexA by different organs. These results confirmed that the liver was the preferential target organ to deliver a large amount of secreted proteins. In addition, the need to overexpress both subunits of heterodimeric proteins in order to obtain a high level of secretion in animals defective in only one subunit is emphasized. The endogenous non-defective subunit is otherwise limiting.
Effect of Ethanol, Temperature, and Gas Flow Rate on Volatile Release from Aqueous Solutions under Dynamic Headspace Dilution Conditions (2008)

On the basis of a mechanistic model, the overall and liquid mass transfer coefficients of aroma compounds were estimated during aroma release when an inert gas diluted the static headspace over simple ethanol/water solutions (ethanol concentration = 120 mL x L(-1)). Studied for a range of 17 compounds, they were both increased in the ethanol/water solution compared to the water solution, showing a better mass transfer due to the presence of ethanol, additively to partition coefficient variation. Thermal imaging results showed differences in convection of the two systems (water and ethanol/water) arguing for ethanol convection enhancement inside the liquid. The effect of ethanol in the solution on mass transfer coefficients at different temperatures was minor. On the contrary, at different headspace dilution rates, the effect of ethanol in the solution helped to maintain the volatile headspace concentration close to equilibrium concentration, when the headspace was replenished 1-3 times per minute.
Discovery of lactoquinomycin and related pyranonaphthoquinones as potent and allosteric inhibitors of AKT/PKB: mechanistic involvement of AKT catalytic activation loop cysteines (2007)

The serine/threonine kinase AKT/PKB plays a critical role in cancer and represents a rational target for therapy. Although efforts in targeting AKT pathway have accelerated in recent years, relatively few small molecule inhibitors of AKT have been reported. The development of selective AKT inhibitors is further challenged by the extensive conservation of the ATP-binding sites of the AGC kinase family. In this report, we have conducted a high-throughput screen for inhibitors of activated AKT1. We have identified lactoquinomycin as a potent inhibitor of AKT kinases (AKT1 IC(50), 0.149 +/- 0.045 micromol/L). Biochemical studies implicated a novel irreversible interaction of the inhibitor and AKT involving a critical cysteine residue(s). To examine the role of conserved cysteines in the activation loop (T-loop), we studied mutant AKT1 harboring C296A, C310A, and C296A/C310A. Whereas the ATP-pocket inhibitor, staurosporine, indiscriminately targeted the wild-type and all three mutant-enzymes, the inhibition by lactoquinomycin was drastically diminished in the single mutants C296A and C310A, and completely abolished in the double mutant C296A/C310A. These data strongly implicate the binding of lactoquinomycin to the T-loop cysteines as critical for abrogation of catalysis, and define an unprecedented mechanism of AKT inhibition by a small molecule. Lactoquinomycin inhibited cellular AKT substrate phosphorylation induced by growth factor, loss of PTEN, and myristoylated AKT. The inhibition was substantially attenuated by coexpression of C296A/C310A. Moreover, lactoquinomycin reduced cellular mammalian target of rapamycin signaling and cap-dependent mRNA translation initiation. Our results highlight T-loop targeting as a new strategy for the generation of selective AKT inhibitors.
Stretching single molecules into novel conformations using the atomic force (2000)

Mechanical stretching in vivo is thought to regulate the function of proteins, polysaccharides and DNA1‐6 . The application of mechanical force to biological polymers produces conformations that are different than those that have been investigated by chemical or thermal denaturation7 and are inaccessible to conventional methods of measurement such as NMR spectroscopy and X-ray crystallography. Force-induced conformational transitions may therefore be physiologically relevant, and may offer novel perspectives on the structure of biomolecules. Recent developments in single molecule force spectroscopy have enabled studies of the mechanical properties of single biological
β-Amyloid Peptide at Sublethal Concentrations Downregulates Brain-Derived Neurotrophic Factor Functions in Cultured Cortical Neurons (2004)

The accumulation of beta-amyloid (Abeta) is one of the etiological factors in Alzheimer's disease (AD). It has been assumed that the underlying mechanism involves a critical role of Abeta-induced neurodegeneration. However, low levels of Abeta, such as will accumulate during the course of the disease, may interfere with neuronal function via mechanisms other than those involving neurodegeneration. We have been testing, therefore, the hypothesis that Abeta at levels insufficient to cause degeneration (sublethal) may interfere with critical signal transduction processes. In cultured cortical neurons Abeta at sublethal concentrations interferes with the brain-derived neurotrophic factor (BDNF)-induced activation of the Ras-mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) and phosphatidylinositol 3-kinase (PI3-K)/Akt pathways. The effect of sublethal Abeta(1-42) on BDNF signaling results in the suppression of the activation of critical transcription factor cAMP response element-binding protein and Elk-1 and cAMP response element-mediated and serum response element-mediated transcription. The site of interference with the Ras/ERK and PI3-K/Akt signaling is downstream of the TrkB receptor and involves docking proteins insulin receptor substrate-1 and Shc, which convey receptor activation to the downstream effectors. The functional consequences of Abeta interference with signaling are robust, causing increased vulnerability of neurons, abrogating BDNF protection against DNA damage- and trophic deprivation-induced apoptosis. These new findings suggest that Abeta engenders a dysfunctional encoding state in neurons and may initiate and/or contribute to cognitive deficit at an early stage of AD before or along with neuronal degeneration.
Cellular reactivity to respiratory syncytial virus in human colostrum and breast milk (1985)

Colostrum and breast-milk samples were taken from 23 mothers between 2 days and 7 weeks postpartum and were examined for the presence of cellular reactivity to respiratory syncytial (RS) virus using a lymphocyte transformation assay. Positive responses were detected in nine of the 23 (39%) samples taken at 2-5 days postpartum, but this reactivity was undetectable at 3 weeks. Positive responses developed in a further three mothers during the 3-7-week period of lactation, suggesting a response to virus infection. Colostral whey was found to suppress the cellular response to RS virus and inhibition was related to the level of specific IgA antibody to RS virus present in the whey. The role of colostral cellular reactivity in protection of breast-fed infants from RS virus bronchiolitis is discussed.
Synthesis of Articulated All-Para Polymers (1981)

Articulated all-para-polymers with 2,6-benzobisoxazole, 2,6- benzobisthiazole, and 2,6-benzobisimidazole units in the backbone were synthesized by copolycondensation in polyphosphoric acid of 4,6-diamino-1,3- benzenediol dihydrochloride, 2,5-diamino-1,4-benzenedithiol dihydrochloride, and 1,2,4,5-tetraaminobenzene tetrahydrochloride, respectively, with terephthalic acid and reactive diphenoxybenzene monomers. Inherent viscosities of up to 12.57 dL/g (CH3SO3H, 25 C, 0.2g/d1) were achieved. The average length of the rod-like all-para segments between the relatively flexible diphenoxybenzene units was controlled by the stoichiometry of the copolycondensation reactions. Films which exhibited optical birefringence under crossed polars could be cast from methanesulfonic acid solutions of the polymers. Modulus and tensile strength values as high as 4696 mPa and 93mPa, respectively, were recorded. Thermooxidative stability of the articulated polymers was evaluated by isothermal aging in air at 316 C. Stability for the articulated polybenzobisoxazoles was found to decrease with increased content of the diphenoxybenzene structure. The articulated polybenzobisoxazole structure was shown to be less stable than the anlogous polybenzobisthiazole structure but more stable than the articulated polybenzobisimidazole structure.
A Formalin-Inactivated Whole SIV Vaccine Confers Protection in Macaques (1989)

A vaccine against human immunodeficiency virus (HIV) would be highly effective in stopping the acquired immunodeficiency syndrome (AIDS) epidemic. A comprehensive evaluation of potential vaccine methodologies can be made by means of the simian model for AIDS, which takes advantage of the similarities in viral composition and disease potential between simian immunodeficiency virus (SIV) infection of rhesus macaques and HIV infection in humans. Immunization with a formalin-inactivated whole SIV vaccine potentiated with either alum and the Syntex adjuvant threonyl muramyl dipeptide (MDP) or MDP alone resulted in the protection of eight of nine rhesus monkeys challenged with ten animal-infectious doses of pathogenic virus. These results demonstrate that a whole virus vaccine is highly effective in inducing immune responses that can protect against lentivirus infection and AIDS-like disease.
Design and implementation of UWB pulse with multiple narrow-band interferences mitigation (2011)

In this paper, a novel ultra-wideband (UWB) pulse shaping method was presented to generate IR-UWB waveforms which can suppress multiple narrow-band interferences. The proposed method includes two steps. First, to completely satisfy and fully utilize the FCC power spectral density mask, an “interim-pulse” was generated by combining several Gaussian derivative pulses with proper combination coefficients. Then, combining two such “interim-pulses” with a certain delay time, a composite UWB waveform which can mitigate multiple narrowband interferences was eventually generated. To verify the accuracy of the proposed method, a simulation setup was conducted by using MATLAB. Moreover, a low-power, low-cost waveform generator was designed and simulated with Spectra-RF 0.13um CMOS technology. The results indicate that the composite waveform generated by the proposed method can suppress multiple narrow-band interferences by introducing inherent notch frequencies in the power spectral density. Furthermore, the notch frequencies and the number of notches can be adjusted by changing the delay time.
Results of Disc Prosthesis After a Minimum Follow-Up Period of 2 Years (1996)

A wrong surgical indication, rather than failure of the prosthesis, appears to be the main cause of unsatisfactory results of disc replacement at medium-term evaluations. Prospective and longer term studies are needed to establish whether disc prosthesis may offer advantages compared with spinal fusion.