gebhart/patrepeval huggingface dataset:
Analogues of VIP, Helodermin, and PACAP Discriminate between Rat and Human VIP1 and VIP2 Receptorsa (1998)

Vasoactive intestinal polypeptide (VIP) acts through interaction with two subclasses of seven transmembrane G protein-coupled receptors named VIP1 and VIP2 receptors. These receptors have been cloned in different species, such as rat and human. Considering the different distribution of both receptor subclasses, there is considerable interest in the development of selective agonists and antagonists. The present study compares the binding properties of VIP, PACAP, GRF, secretin, and helodermin analogues on recombinant rat and human VIP1 and VIP2 receptors. On both rat and human receptors, secretin and GRF had a higher affinity for the VIP1 receptor subtypes. The amino-shortened VIP, and the carboxy terminal-shortened VIP and PACAP analogues also presented a higher affinity for the VIP1 receptor. PHI, PHV, helodermin, and helospectin were selective for the human VIP2 receptor subtypes. These results suggest that the helical structure of the carboxy terminal end is necessary for VIP2 recognition. The differences between species were the following: PHI, PHV, helodermin, and helospectin had a higher affinity for the rat VIP1 receptor than for the human VIP1 receptor. On both rat and human receptors, D-Ala4 VIP and D-Phe4 VIP had a high affinity for the VIP1 receptor and a low affinity for the VIP2 receptor. Thus, three domains of the ligand involved in VIP1/VIP2 receptor discrimination were identified: the amino acid residue in position 4 ([D-Ala4], [D-Phe4]VIP), in positions 8 and 9 (the effects of helodermin and helospectin), and the carboxy terminal end (the effects of the shortened VIP and pituitary adenylate cyclase activating polypeptide analogues).
Tay-Sachs disease-causing mutations and neutral polymorphisms in the Hex A gene (1997)

Tay-Sachs disease is an autosomal recessive disorder affecting the central nervous system. The disorder results from mutations in the gene encoding the alpha-subunit of beta-hexosaminidase A, a lysosomal enzyme composed of alpha and beta polypeptides. Seventy-eight mutations in the Hex A gene have been described and include 65 single base substitutions, one large and 10 small deletions, and two small insertions. Because these mutations cripple the catalytic activity of beta-hexosaminidase to varying degrees, Tay-Sachs disease displays clinical heterogeneity. Forty-five of the single base substitutions cause missense mutations; 39 of these are disease causing, three are benign but cause a change in phenotype, and three are neutral polymorphisms. Six nonsense mutations and 14 splice site lesions result from single base substitutions, and all but one of the splice site lesions cause a severe form of Tay-Sachs disease. Eight frameshift mutations arise from six deletion- and two insertion-type lesions. One of these insertions, consisting of four bases within exon 11, is found in 80% of the carriers of Tay-Sachs disease from the Ashkenazi Jewish population, an ethnic group that has a 10-fold higher gene frequency for a severe form of the disorder than the general population. A very large deletion, 7.5 kilobases, including all of exon 1 and portions of DNA upstream and downstream from that exon, is the major mutation found in Tay-Sachs disease carriers from the French Canadian population, a geographic isolate displaying an elevated carrier frequency. Most of the other mutations are confined to single pedigrees. Identification of these mutations has permitted more accurate carrier information, prenatal diagnosis, and disease prognosis. In conjunction with a precise tertiary structure of the enzyme, these mutations could be used to gain insight into the structure-function relationships of the lysosomal enzyme.
Quantitative Automated Particle-Enhanced Immunonephelometric Assay for the Routinary Measurement of Human Cystatin C (1998)

Human cystatin C is a low molecular mass protein of 13359 Dalton recently proposed as a new very sensitive marker of changes in glomerular filtration rate. Serum cystatin C concentration correlates negatively with glomerular filtration rate as well as or better than creatinine. We evaluated a recently introduced automated nephelometric immunoassay for cystatin C in serum or EDTA-plasma samples on the Behring Nephelometer System. The assay consists of incubating the 100-fold diluted sample for 6 minutes with latex particles covalently coated with anti-human cystatin C antibodies, and then quantifying the change of light-scatter produced. Method reproducibility is satisfactory, the intra- and inter-assay coefficients of variation ranging from 1.58% to 3.77% and from 5.6% to 11.47% respectively. Rheumatoid factor (< or = 1116 IU/ml), bilirubin (< or = 418 micrommol/l), triglycerides (10.47 mmol/), and haemoglobin (12 g/l) do not significantly interfere in the assay. No significant difference was found in cystatin C concentration between serum and EDTA-plasma samples. Cystatin C is stable in serum samples stored under different conditions up to one month. This method correlates well (mean difference=-0.536+/-0.307 mg/l) with another commercially available particle-enhanced turbidimetric immunoassay. Cystatin C offers better clinical sensitivity than creatinine for discriminating patients with normal renal function and those with mild-to-moderate reduction in renal function. This method is suitable for routine cystatin C measurement, including emergencies.
Preoperative Diagnosis of Benign Thyroid Nodules with Indeterminate Cytology (2012)

These data suggest consideration of a more conservative approach for most patients with thyroid nodules that are cytologically indeterminate on fine-needle aspiration and benign according to gene-expression classifier results. (Funded by Veracyte.).
Single-Crystalline Octahedral Au–Ag Nanoframes (2012)

We report the formation of single-crystalline octahedral Au–Ag nanoframes by a modified galvanic replacement reaction. Upon sequential addition of AgNO3, CuCl, and HAuCl4 to octadecylamine solution, truncated polyhedral silver nanoparticles formed first and then changed into octahedral Au–Ag nanoframes, without requiring a conventional Ag removal step with additional oxidation etchant. The nanoframes have 12 sides, and all of the eight {111} faces are empty. The side grows along the [110] direction, and the diameter is less than 10 nm. The selective gold deposition on the high-energy (110) surface, the diffusion, and the selective redeposition of Au and Ag atoms are the key reasons for the formation of octahedral nanoframes.
Glycoprotein 2 is a specific cell surface marker of human pancreatic progenitors (2017)

PDX1<sup>+</sup>/NKX6-1<sup>+</sup> pancreatic progenitors (PPs) give rise to endocrine cells both in vitro and in vivo. This cell population can be successfully differentiated from human pluripotent stem cells (hPSCs) and hold the potential to generate an unlimited supply of β cells for diabetes treatment. However, the efficiency of PP generation in vitro is highly variable, negatively impacting reproducibility and validation of in vitro and in vivo studies, and consequently, translation to the clinic. Here, we report the use of a proteomics approach to phenotypically characterize hPSC-derived PPs and distinguish these cells from non-PP populations during differentiation. Our analysis identifies the pancreatic secretory granule membrane major glycoprotein 2 (GP2) as a PP-specific cell surface marker. Remarkably, GP2 is co-expressed with NKX6-1 and PTF1A in human developing pancreata, indicating that it marks the multipotent pancreatic progenitors in vivo. Finally, we show that isolated hPSC-derived GP2<sup>+</sup> cells generate β-like cells (C-PEPTIDE<sup>+</sup>/NKX6-1<sup>+</sup>) more efficiently compared to GP2<sup>-</sup> and unsorted populations, underlining the potential therapeutic applications of GP2.Pancreatic progenitors (PPs) can be derived from human pluripotent stem cells in vitro but efficiency of differentiation varies, making it hard to sort for insulin-producing cells. Here, the authors use a proteomic approach to identify the secretory granule membrane glycoprotein 2 as a marker for PDX1+/NKX6-1+ PPs.
Differences in cytotoxicity of poly(PEGA)s synthesized by reversible addition–fragmentation chain transfer polymerization (2009)

Toxicity of poly(ethylene glycol acrylate) (poly(PEGA)) synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization using different chain transfer agents (CTA)s is described.
Protocol Conversion (1986)

The difficulty of interconnecting networks or network components when they obey different architectures is an important inhibitor to computer communication growth and flexibility. This paper reviews the state of the protocol conversion art from the architectural point of view. The aim is to state the problem succinctly, propose consistent definitions, review current ad hoc solutions, and speculate about more effective and general methodologies. To do this, we first analyze what happens on an access path between two end users at the discontinuity point where the path passes from a portion of the network obeying one architecture into a portion obeying another. This discontinuity can be designed to occur at a choice of nodes along the access path and at a choice of protocol layer level at each such node. The process of conversion to complete the path at one of these points can range in complexity from the trivial to the impossible. The procedure available today starts by analyzing the set of atomic protocol functions that support the services normally provided at the conversion point by the two architectures in terms of their interface, peer and control protocols (both transient and steady state), and then identifying a usable common subset of the two sets. Known solutions then include defining useful partial resolution of protocol mismatches, complementation of one or both protocols with missing services, and the use of Open System Interconnection as an intermediary in the conversion process.
2-[[(4-Amino-2-pyridyl)methyl]sulfinyl]benzimidazole H+/K+-ATPase inhibitors. The relationship between pyridine basicity, stability, and activity (1989)

The benzimidazole sulfoxide class of antisecretory H+/K+-ATPase inhibitors need to possess high stability under neutral physiological conditions yet rearrange rapidly at low pH to the active sulfenamide 2. Since the initial reaction involves internal nucleophilic attack by the pyridine nitrogen, control of the pyridine pKa is critical. In this paper we show that by utilizing the powerful electron-donating effect of a 4-amino substituent on the pyridine, moderated by the electron-withdrawing effect of a 3- or 5-halogen substituent, a combination of high potency (as inhibitors of histamine-stimulated gastric acid secretion) and good stability under physiological conditions can be obtained. Furthermore, the role of the steric interaction between the 3/5-substituents and the 4-substituent in modifying the electron-donating ability of the 4-amino group is exemplified, and additional factors affecting stability are identified. One compound, in particular, 2-[[(3-chloro-4-morpholino-2- pyridyl)methyl]sulfinyl]-5-methoxy-(1H)-benzimidazole (3a, SK&F 95601), was chosen for further development and evaluation in man.
Asymmetry in Sympathetic and Vagal Activities During Sleep-Wake Transitions (2008)

The parasympathetic activity before falling asleep and the sympathetic activity before waking up change coincidentally with EEG frequency, and may respectively contain the messages of sleeping and waking drives.
Targeting CD73 Enhances the Antitumor Activity of Anti-PD-1 and Anti-CTLA-4 mAbs (2013)

Taken together, our study revealed that targeted blockade of CD73 can enhance the therapeutic activity of anti-PD-1 and anti-CTLA-4 mAbs and may thus potentiate therapeutic strategies targeting immune checkpoint inhibitors in general.
Fluoride-cleavable biotinylation phosphoramidite for 5'-end-labeling and affinity purification of synthetic oligonucleotides (2003)

A fluoride-cleavable phosphoramidite for biotinylation was designed, synthesized and coupled efficiently to the 5'-end of DNA on an automatic synthesizer. The diisopropylsilyl acetal functionality was used to link the biotin moiety through a tertiary hydroxide group to the 5'-end of DNA. This linkage proved to be completely stable under certain post-synthetic DNA cleavage/deprotection conditions [0.05 M K(2)CO(3) in MeOH, room temperature, 24 h and MeNH(2) (approximately 40%)/NH(4)OH (approximately 29%), 1:1 v/v, 65 degrees C, 30 min] while it can be readily broken by fluoride ion, releasing unmodified DNA. To demonstrate the use of this DNA biotinylation method, we applied this method in affinity purification of synthetic DNA. As revealed by HPLC analysis, biotinylated full-length DNA can be efficiently attached to NeutrAvidin coated microspheres, and failure sequences can be readily removed. Subsequent treatment of the microspheres with pyridine/HF released high quality full-length unmodified DNA in good yield.
The clinical importance of a cytokine network in the acute phase of sepsis (2018)

Sepsis remains a major cause of death. Cytokines interact closely with each other and play a crucial role in the progression of sepsis. We focussed on the associations of a cytokine network with prognosis and disease severities in sepsis. This retrospective study included 31 patients with sepsis and 13 healthy controls. Blood samples were collected from patients on days 1, 2, 4, 6, 8, 11 and 15 and from healthy controls. Levels of PAI-1, IFN-α, IFN-γ, IL-1β, IL-6, IL-8, IL-12/IL-23p40, IL-17A, TNF-α, MCP-1, IL-4 and IL-10 were measured. SOFA, JAAM DIC and ISTH DIC scores were evaluated at the same times blood samples were taken. Network analysis revealed a network formed by PAI-1, IL-6, IL-8, MCP-1 and IL-10 on days 1, 2 and 4 throughout the acute phase of sepsis. There were positive correlations of each cytokine and the combined score (IL-6 + IL-8 + IL-10 + MCP-1) with the SOFA, JAAM DIC and ISTH DIC scores throughout the acute phase. A Cox proportional hazards model focussed on the acute phase showed that the above combined score was significantly related with patient prognosis, suggesting that the cytokine network of IL-6, IL-8, MCP-1 and IL-10 could play a pivotal role in the acute phase of sepsis.
Microbial degradation of organophosphorus compounds (2006)

Synthetic organophosphorus compounds are used as pesticides, plasticizers, air fuel ingredients and chemical warfare agents. Organophosphorus compounds are the most widely used insecticides, accounting for an estimated 34% of world-wide insecticide sales. Contamination of soil from pesticides as a result of their bulk handling at the farmyard or following application in the field or accidental release may lead occasionally to contamination of surface and ground water. Several reports suggest that a wide range of water and terrestrial ecosystems may be contaminated with organophosphorus compounds. These compounds possess high mammalian toxicity and it is therefore essential to remove them from the environments. In addition, about 200,000 metric tons of nerve (chemical warfare) agents have to be destroyed world-wide under Chemical Weapons Convention (1993). Bioremediation can offer an efficient and cheap option for decontamination of polluted ecosystems and destruction of nerve agents. The first micro-organism that could degrade organophosphorus compounds was isolated in 1973 and identified as Flavobacterium sp. Since then several bacterial and a few fungal species have been isolated which can degrade a wide range of organophosphorus compounds in liquid cultures and soil systems. The biochemistry of organophosphorus compound degradation by most of the bacteria seems to be identical, in which a structurally similar enzyme called organophosphate hydrolase or phosphotriesterase catalyzes the first step of the degradation. organophosphate hydrolase encoding gene opd (organophosphate degrading) gene has been isolated from geographically different regions and taxonomically different species. This gene has been sequenced, cloned in different organisms, and altered for better activity and stability. Recently, genes with similar function but different sequences have also been isolated and characterized. Engineered microorganisms have been tested for their ability to degrade different organophosphorus pollutants, including nerve agents. In this article, we review and propose pathways for degradation of some organophosphorus compounds by microorganisms. Isolation, characterization, utilization and manipulation of the major detoxifying enzymes and the molecular basis of degradation are discussed. The major achievements and technological advancements towards bioremediation of organophosphorus compounds, limitations of available technologies and future challenge are also discussed.
Promotion of engraftment by donor NK cell infusion and IL-15 in nonmyeloablative allogeneic bone marrow transplantation (145.18) (2010)

Abstract Donor NK cells have been shown to be able to promote engraftment during allogeneic bone marrow transplantation (allo-BMT). The biological activity of NK cells can be significantly enhanced by IL-15. We carried out experiments to determine the effects of combining donor NK cell infusion and IL-15 administration in a murine nonmyeloablative allo-BMT model. Mice infused with donor NK cells and treated with IL-15 during BMT resulted in increased donor engraftment compared with either treatment alone, although single treatment could also significantly promote donor engraftment. The counts of donor derived cell subsets were all increased in the spleens of the recipient mice with combinational treatment compared with either treatment alone. The alloreactivity to donor type antigens was significantly reduced in the recipient mice with combinational treatment, which was manifested by decreased proliferation and IL-2 secretion of splenocytes from recipient mice in response to donor type antigens in mixed lymphocyte responses and decreased capacity of the splenocytes killing donor type tumor targets. In conclusion, the combination of donor NK cell infusion and IL-15 administration could promote donor engraftment and development of all donor derived cell subsets, as well as suppress the host allo-responses in a nonmyeloablative allo-BMT model. The results provide a promising way to promote donor engraftment without involving systemic and nonspecific suppression of the immune system.
Proteomic Patterns in Biological Fluids: Do They Represent the Future of Cancer Diagnostics? (2003)

Writing on the future of cancer diagnostics, this author has predicted that multiparametric biomarker analysis, in combination with artificial neural networks and pattern recognition, will likely represent one of the most promising methodologies for diagnosing and monitoring cancer (1)(2). Over the last few years, we have witnessed publication of many reports dealing with proteomic patterns in biological fluids, and especially serum, by using the so-called “SELDI-TOF” technique (surface-enhanced laser desorption/ionization time-of-flight mass spectrometry), in combination with artificial intelligence (3)(4)(5)(6)(7). The reported sensitivities and specificities of this method for ovarian, prostate, and breast cancer diagnosis are clearly impressive, and they are superior to the sensitivities and specificities obtained with current serologic cancer biomarkers (8)(9)(10)(11)(12). In particular, these techniques appear to detect early as well as advanced disease with similar efficiency, making them candidate tools for cancer screening, an application that is not currently recommended, by utilizing the classical cancer biomarkers, e.g., CA125, carcinoembryonic antigen (CEA), and α-fetoprotein (AFP) (1).

In addition to scientific journals, these reports have also been presented in international news media and have attracted public attention. Despite of some important shortcomings of these methodologies, criticism has been minimal (13)(14). It seems that the impressive bottom line (very high diagnostic sensitivity and specificity) overshadows potential problems. The recent publication of three reports, from two different research groups, on the use of this technology in the diagnosis of prostate cancer allows for comparison of the data and the methodology and for the presentation of some important questions that have not been adequately addressed. In the following paragraphs, I will focus on some critical questions and provide discussion that could form the basis for further investigations. I will concentrate only …
The Blood Exposome and Its Role in Discovering Causes of Disease (2014)

For studies of disease etiology, the complexity of human exposures motivates characterization of the blood exposome, which includes all biologically active chemicals. Because most small molecules in blood are not human metabolites, investigations of causal pathways should expand beyond the endogenous metabolome.
Anomalous Binding Profile of Phenylboronic Acid withN-Acetylneuraminic Acid (Neu5Ac) in Aqueous Solution with Varying pH (2003)

Borates are known to interact with carbohydrate moieties expressed on the surface of biological membranes of a variety of cells, viruses, bacteria, and fungi. This study revealed the anomalous binding profile of borate in aqueous solution with N-acetylneuraminic acid (Neu5Ac, sialic acid) as a potential receptor site on the surfaces of biological membranes using (11)B, (1)H, (13)C, and (15)N nuclear magnetic resonance spectroscopies. 3-(Propionamido)phenylboronic acid (PAPBA) was chosen as the model borate compound. The equilibrium constant (K) for Neu5Ac binding to PAPBA was compared with those for glucose, mannose, and galactose, which are the major carbohydrate constituents of glycoproteins and glycolipids expressed on biological membranes. In the Neu5Ac/PAPBA system, the unusual pH dependency of the K values, a decrease in K with increasing pH, was observed, suggesting the formation of a trigonal-formed complex stabilized by the coordination of an amide group of Neu5Ac at the C-5 position to the boron atom, forming intramolecular B-N or B-O bonding. Furthermore, the anomalously high complexing ability at physiological pH 7.4 was confirmed for this system, with the K value 37.6 which is approximately 7 times higher than that for glucose. This exceptionally high value of K at physiological pH, compared to those of other sugars, strongly suggests that the boronic acid selectively recognizes the Neu5Ac residues of the glycosylated components including glycoproteins and gangliosides existing on the surface of the biological membranes.