gebhart/patrepeval huggingface dataset:
Interchain disulfide bonds and subunit organization in human serum cholinesterase. (1979)

Highly purified “usual” human serum cholinesterase was studied. The enzyme is a tetramer with a molecular weight of approximately 340,000. Its four subunits appear to be identical. On 1% sodium dodecyl sulfate (SDS) gel electrophoresis the enzyme had a molecular weight of about 180,000 when dissolved in 1% SDS, but it had a molecular weight of about 90,000 when dissolved in 1% SDS and 40 mM dithiothreitol. This was evidence that the subunits were arranged as a dimer of dimers ((cw)&, with each (a)~ dimer composed of two identical subunits joined by interchain disulfide bonds. Purified “atypical” cholinesterase had the same dimer of dimers structure and the same molecular weight on SDS-gel electrophoresis as usual cholinesterase. Additional structural experiments were conducted with purified usual choline&erase. The number of interchain disulfide bonds was quantitated by selectively reducing these bonds in the absence of a denaturant, followed by alkylation with [l-‘4C]iodoacetate. One SH per subunit was alkylated. As the enzyme contains no free SH groups, the alkylated residues must previously have been components of disulfide bonds. It was shown that the alkylated -SH groups arose from interchain disulfide bonds, for on SDS-gel electrophoresis of the alkylated enzyme, the labeled product all migrated with the subunit molecular weight of 90,000. It was concluded that each dimer contained only one interchain disulfide bond between two subunits. After reduction and alkylation of the interchain disulfide bonds, the enzyme was still a tetramer and was fully active. Therefore, it was concluded that the interchain disulfides were not necessary for either the tetramerit structure or for activity, and that the four subunits were held together by noncovalent bonds. The interchain disulfide bonds stabilized the enzyme as shown by measurements of rates of heat inactivation. Native enzyme had a half-life of 54 min at 55”C, whereas enzyme that had been selectively reduced and [14C]carboxymethylated, had a half-life of 16 min at 55°C. The interchain disulfide bonds were easily reduced and alkylated, suggesting that these bonds are located near the surface of the molecule. In addition to the single interchain disulfide bond, each subunit contains several (three to five) pairs of intrachain disulfide bonds.
PCR performance of the highly thermostable proof-reading B-type DNA polymerase from Pyrococcus abyssi (2002)

DNA polymerase from the archaeon Pyrococcus abyssi strain Orsay was expressed in Escherichia coli. The recombinant DNA polymerase (Pab) was purified to homogeneity by heat treatment followed by 5 steps of chromatography and characterized for PCR applications. Buffer optimization experiments indicated that Pab PCR performance and fidelity parameters were highest in the presence of 20 mM Tris–HCl, pH 9.0, 1.5 mM MgSO4, 25 mM KCl, 10 mM (NH4)2SO4 and 40 µM of each dNTP. Under these conditions, the error rate was 0.66.10−6 mutations/nucleotide/duplication. Pab DNA polymerase, having a half life of 5 h at 100°C, was demonstrated to be highly thermostable in PCR conditions compared to commercial Taq and Pfu DNA polymerases. These characteristics enable Pab to be one of the most efficient thermostable DNA polymerases described, exhibiting very high accuracy compared to other available commercial DNA polymerases and robust thermostable activity. This new DNA polymerase is currently on the market under the name Isis DNA Polymerase™ (Qbiogene Molecular Biology).
Nanoscale Simulations of Rock and Clay Minerals (2007)

Nanomechanics has huge possibilities in explaining basic materials response such as creep, friction, rate and temperature dependency. Constitutive models based on nanomechanics have distinct advantages over phenomological models in simulating the response of geomaterials under extreme environments. This paper presents a study of the elasticity properties of rock and clay minerals using MD simulations. The interatomic potentials used for these minerals are taken from the published work on the same minerals. Both bonded and non-bonded interatomic contributions and periodic boundary conditions in three dimensions are included in the simulations. The elasticity module of the minerals are calculated from the axial stress versus strain curves. The results show that the elasticity properties of the minerals obtained from the MD simulations agree well with the published data. It is found that the elasticity modulus of kaolinite is even higher than quartz, which is in contrast with their known macroscopic properties. This could be due to the arrangement of the clay particles at the microscopic level, which dominates the macroscopic properties of the clay mass.
BRUCELLA ABORTUSSTRAIN RB51 VACCINATION IN ELK I. EFFICACY OF REDUCED DOSAGE (2002)

Bovine brucellosis is a serious zoonotic disease affecting some populations of Rocky Mountain elk (Cervus elaphus nelsoni) and bison (Bison bison) in the Greater Yellowstone Area, USA. The fear that elk and/or bison may spread Brucella abortus to livestock has prompted efforts to reduce or eliminate the disease in wildlife. Brucella abortus strain RB51 (RB51) vaccine has recently been approved for use in cattle. Unlike strain 19 vaccine, RB51 does not cause false positive reactions on standard brucellosis serologic tests. If effective, it may become the vaccine of choice for wildlife. In February 1995, 45 serologically negative female elk calves were trapped and taken to the Sybille Wildlife Research and Conservation Education Unit near Wheatland, Wyoming, USA. In May 1995, 16 of these elk calves were hand-vaccinated with 1 x 10(9) colony forming units (CFU) of RB51, 16 were vaccinated with 1 x 10(8) CFU RB51 by biobullet, and 13 were given a saline placebo. The elk were bred in fall of 1996 and they were challenged with 1 x 10(7) CFU of B. abortus strain 2308 by intraconjunctival inoculation in March 1997. Thirteen (100%) control elk aborted, 14 (88%) hand-vaccinated elk aborted, and 12 (75%) biobullet vaccinated elk aborted or produced nonviable calves. These results suggest that a single dose of 1 x 10(8) to 1 x 10(9) CFU RB51 does not provide significant protection against B. abortus induced abortion in elk. However, the vaccine appears to be safe at this dose and additional study may reveal a more effective RB51 vaccine regimen for elk.
AFM-IR: Technology and Applications in Nanoscale Infrared Spectroscopy and Chemical Imaging (2016)

Atomic force microscopy-based infrared spectroscopy (AFM-IR) is a rapidly emerging technique that provides chemical analysis and compositional mapping with spatial resolution far below conventional optical diffraction limits. AFM-IR works by using the tip of an AFM probe to locally detect thermal expansion in a sample resulting from absorption of infrared radiation. AFM-IR thus can provide the spatial resolution of AFM in combination with the chemical analysis and compositional imaging capabilities of infrared spectroscopy. This article briefly reviews the development and underlying technology of AFM-IR, including recent advances, and then surveys a wide range of applications and investigations using AFM-IR. AFM-IR applications that will be discussed include those in polymers, life sciences, photonics, solar cells, semiconductors, pharmaceuticals, and cultural heritage. In the Supporting Information , the authors provide a theoretical section that reviews the physics underlying the AFM-IR measurement and detection mechanisms.
Predictive Coding of Speech at Low Bit Rates (1982)

Predictive coding is a promising approach for speech coding. In this paper, we review the recent work on adaptive predictive coding of speech signals, with particular emphasis on achieving high speech quality at low bit rates (less than 10 kbits/s). Efficient prediction of the redundant structure in speech signals is obviously important for proper functioning of a predictive coder. It is equally important to ensure that the distortion in the coded speech signal be perceptually small. The subjective loudness of quantization noise depends both on the short-time spectrum of the noise and its relation to the short-time spectrum of the Speech signal. The noise in the formant regions is partially masked by the speech signal itself. This masking of quantization noise by speech signal allows one to use low bit rates while maintaining high speech quality. This paper will present generalizations of predictive coding for minimizing subjective distortion in the reconstructed speech signal at the receiver. The quantizer in predictive coders quantizes its input on a sample-by-sample basis. Such sample-by-sample (instantaneous) quantization creates difficulty in realizing an arbitrary noise spectrum, particularly at low bit rates. We will describe a new class of speech coders in this paper which could be considered to be a generalization of the predictive coder. These new coders not only allow one to realize the precise optimum noise spectrum which is crucial to achieving very low bit rates, but also represent the important first step in bridging the gap between waveform coders and vocoders without suffering from their limitations.
Pathways to Violence in the Children of Mothers Who Were Depressed Postpartum. (2003)

The impact of postnatal depression on a child's risk for violent behavior was evaluated in an urban British community sample (N=122 families). Mothers were interviewed during pregnancy, at 3 months postpartum, and when the child was 1, 4, and 11 years of age. Mothers, teachers, and children reported on violent symptoms at age 11. Structural equation modeling revealed that the child's violence was predicted by the mother's postnatal depression even when her depression during pregnancy, her later history of depression, and family characteristics were taken into account. Violence was associated with symptoms of attention-deficit/hyperactivity disorder and problems with anger management. Children were most violent if mothers had been depressed at 3 months and at least once thereafter.
Nucleic acid capture assay, a new method for direct quantitation of nucleic acids (2003)

Technologies allowing direct detection of specic RNA/DNA sequences occasionally serve as an alternative to amplication methods for gene expression studies. In these direct methods the hybridization of probes takes place in complex mixtures, thus specicity and sensitivity still limit the use of current technologies. To address these challenges, we developed a new technique called the nucleic acid capture assay, involving a direct multi-capture system. This approach combines a 3-ethylene glycol scaffolding with the incorporation of 2-methoxy deoxyribonucleotides in the capture sequences. In our design, all nucleotides other than those complementary to the target mRNA have been replaced by an inert linker, resulting in signicant reductions in non-specic binding. We also provide a versatile method to detect the presence of captured targets by using specic labeled probes with alkaline phosphatase-conjugated anti-label antibodies. This direct, exible and reliable technique for gene expression analysis is well suited for highthroughput screening and has potential for DNA microarray applications.
Osteogenesis after Bone and Bone Marrow Transplantation (1983)

The ability of four different ceramic materials to support osteogenesis when placed with bone marrow into an intermuscular site was studied. In the search for biodegradable porous ceramic materials that could be used for bone replacement and that would slowly be replaced by bone by means of “creeping substitution,” the authors fabricated porous alumina, calcium aluminate, calcium hydroxyapatite, and tricalcium phosphate. Specially shaped compacts, impregnated with autologous bone marrow, were inserted into intermuscular pouches in rabbits and retrieved after 14-182 days. Newly formed bone was found within the contents of the well after 14 days and was visible at all times up to 182 days. The bone was frequently found to have adhered to the ceramic and to have penetrated the interior if the pore size was greater than 100 µm. Further investigation of the use of synthetic materials in bone replacement is warranted due to the finding that some porous ceramic materials permit bony ingrowth from autologous marrow cells.
[Isolation and characterization of brain tumor stem cells in human medulloblastoma]. (2006)

Tumor stem cells have been isolated from several kinds of solid tumors, including primary brain tumors such as glioma and medulloblastoma. This investigation was to establish a simplified culture system to isolate and passage brain tumor stem cells (BTSCs) from human medulloblastoma, observe their proliferation and differentiation, and determine the expression of normal neural stem cell antigens, CD133 and Nestin, in BTSCs.Eleven specimens of medulloblastoma were acutely dissociated and triturated into single cells without trypsin digestion. The tumor cells were seeded into serum-free DMEM/F12 medium (200,000 viable cells/ml) containing B27 (1:50), basic fibroblast growth factor (bFGF, 20 microg/L), epidermal growth factor (EGF, 20 microg /L), insulin (4 u/L), L-glutamine, and antibiotics. After generation, the primary brain tumor spheres (BTSs) were mechanically dissociated and passaged in the above serum-free medium. The monoclonal formation experiment was performed to determine the proportion of BTSCs in medulloblastoma and to observe the formation of BTSs. The differentiation of BTSCs was induced in mitogen-free DMEM/F12 medium supplemented with 10% fetal bovine serum. The expression of CD133 and Nestin in BTSs was observed with immunofluorescence staining; the distribution of CD133-positive cells in tumor sections was assessed by immunohistochemistry.In each of the 11 specimens, only a minority of medulloblastoma cells showed the capacity of self-renew and proliferation. These BTSCs generated free-floating neurosphere-like BTSs in the simplified serum-free medium. The proportion of BTSCs with monoclonal formation capacity in primary tumor cells was (31.18+/-6.18)%. The BTSCs attached to poly-L-lysine-coated coverslips and differentiated when the serum-supplemented medium was added. The expression of CD133 and Nestin was detected in BTSCs. CD133-positive cells scattered or formed nest-like aggregations in tumor masses, and accounted for (33.06+/-8.57)% of all tumor cells.BTSCs, with the capacity of self-renew and proliferation and express CD133 and Nestin, are exist in human medulloblastoma. They could be isolated and cultured in the simplified serum-free medium, and their differentiation could be induced in serum-supplemented medium.
Genetic diagnosis of progressive familial intrahepatic cholestasis type 2 (2013)

Objectives To investigate the clinical features of progressive familial intrahepatic cholestasis type 2(PFIC2)and to illustrate the importance of genetic diagnosis. Methods The mutations in 27 exons of ABCB11 encoding bile salt export pump(BSEP) were identified using polymerase chain reaction(PCR) and direct DNA sequencing in 6 children with suspected PFIC2. The pathogenicity of the newly identified mutations were predicted by SIFT,PolyPhen-2,SNPsGO software. The clinical features and laboratory examinations were reviewed. Results Four disease-causing mutations,p.R928*,p.E554K,p.R575Q and p.Y337H were identified,and the last three mutations were novel. These three kinds of novel mutations can cause the disease.Two children with genetic diagnosis had such manifestations as onset within a month after birth,jaundice,hepatosplenomegaly,upset,increased levels of total bilirubin and direct bilirubin,GGT100 U/L and high levels of total bile acid. Conclusions Genetic diagnosis is a potent tool for clinical diagnosis of PFIC2.
Intracellular pH, esterase activity, and DNA measurements of human lung carcinomas by flow cytometry (1990)

An important intention of flow cytometric investigations is to obtain biochemical and biophysical information about cells which is suitable for automated tumor diagnosis. In this study, the ploidy status, the intracellular pH value, the intracellular esterase activity, and the cell volume of vital cells and the DNA and cell volume of dead cells were measured in cancerous tissue and normal lung tissue of 30 patients by flow cytometry. The cell samples were simultaneously stained with the pH and esterase indicator dye 1.4-diacetoxy-2,3-dicyanobenzene (ADB) and propidium iodide (PI). The flow cytometric measurements were performed in three-parameter list mode. The data were evaluated on an AT-compatible personal computer with the DIAGNOS1 program system for automated diagnosis of flow cytometric list mode data. Significant differences were found between normal and malignant tissue in DNA ploidy, in the intracellular esterase activity, in the cell, volume and in the percentage of inflammatory cells and parameters of necrosis. DNA-aneuploidy was observed in 38% of the lung carcinomas. The simultaneous detection of DNA-aneuploidy and tumor-associated properties in a multifactorial analysis led to correct automatic tumor diagnosis in 85% of cases. DNA-aneuploidy was found at a significant higher frequency in advanced tumors. Adenocarcinomas displayed DNA-aneuploidy more often (80%) than squamous cell carcinomas (33%).
Structural and Functional Characterization of Disulfide Isoforms of the Human IgG2 Subclass (2008)

In the accompanying report ( Wypych, J., Li, M., Guo, A., Zhang, Z., Martinez, T., Allen, M. J., Fodor, S., Kelner, D. N., Flynn, G. C., Liu, Y. D., Bondarenko, P. V., Ricci, M. S., Dillon, T. M., and Balland, A. (2008) J. Biol. Chem. 283, 16194-16205 ), we have identified that the human IgG2 subclass exists as an ensemble of distinct isoforms, designated IgG2-A, -B, and -A/B, which differ by the disulfide connectivity at the hinge region. In this report, we studied the structural and functional properties of the IgG2 disulfide isoforms and compared them to IgG1. Human monoclonal IgG1 and IgG2 antibodies were designed with identical antigen binding regions, specific to interleukin-1 cell surface receptor type 1. In vitro biological activity measurements showed an increased activity of the IgG1 relative to the IgG2 in blocking interleukin-1beta ligand from binding to the receptor, suggesting that some of the IgG2 isoforms had lower activity. Under reduction-oxidation conditions, the IgG2 disulfide isoforms converted to IgG2-A when 1 m guanidine was used, whereas IgG2-B was enriched in the absence of guanidine. The relative potency of the antibodies in cell-based assays was: IgG1 > IgG2-A > IgG2 >> IgG2-B. This difference correlated with an increased hydrodynamic radius of IgG2-A relative to IgG2-B, as shown by biophysical characterization. The enrichment of disulfide isoforms and activity studies were extended to additional IgG2 monoclonal antibodies with various antigen targets. All IgG2 antibodies displayed the same disulfide conversion, but only a subset showed activity differences between IgG2-A and IgG2-B. Additionally, the distribution of isoforms was influenced by the light chain type, with IgG2lambda composed mostly of IgG2-A. Based on crystal structure analysis, we propose that IgG2 disulfide exchange is caused by the close proximity of several cysteine residues at the hinge and the reactivity of tandem cysteines within the hinge. Furthermore, the IgG2 isoforms were shown to interconvert in whole blood or a "blood-like" environment, thereby suggesting that the in vivo activity of human IgG2 may be dependent on the distribution of isoforms.
Mucus pathophysiology in COPD: differences to asthma, and pharmacotherapy. (2000)

Patients with chronic obstructive pulmonary disease (COPD) exhibit characteristics of airway mucus hypersecretion, including sputum production, increased luminal mucus, goblet cell hyperplasia and submucosal gland hypertrophy. These features are not common to all patients and the impact of hypersecretion on morbidity and mortality is a matter for debate. However, current evidence indicates that airway hypersecretion has pathophysiological and clinical significance in COPD, particularly as patients age or are prone to respiratory tract infection. This suggests that it is important to develop drugs that inhibit mucus hypersecretion in these patients. A number of drugs are currently available that may be of therapeutic benefit in hypersecretory disorders of the airways, e.g. glucocorticosteroids and anticholinergics. Novel compounds are undergoing preclinical research, e.g. inhibitors of epidermal growth factor receptor tyrosine kinase and antisense oligomers. However, preliminary data indicate that the mucus in COPD differs to that in asthma in that: 1) it is less viscous and without marked plasma exudation, 2) the ratio of mucin (MUC) 5AC:MUC5B may be reduced, and 3) there is full release of mucin into the airway lumen rather than "tethering" of mucus as in asthma. Consequently, future research should determine whether there really is an intrinsic abnormality specific to mucus in chronic obstructive pulmonary disease. Based upon this information, appropriate suppressers of mucus hypersecretion in chronic obstructive pulmonary disease can be developed.
Three-step monoclonal antibody tumor targeting in carcinoembryonic antigen-positive patients. (1991)

We describe a method to postlabel, in vivo, biotinylated monoclonal antibodies pretargeted onto tumor deposits when most of the non-tumor-bound antibodies have already been cleared as avidin-bound complexes. The application of this principle to tumor detection by immunoscintigraphy was tested in 20 patients with histologically documented cancer and increased circulating carcinoembryonic antigen levels. One mg of biotinylated anti-carcinoembryonic antigen monoclonal antibody (FO23C5) was administered i.v. (first step). After 3 days, 4-6 mg of cold avidin were injected i.v. (second step), followed 48 h later by 0.2-0.3 mg of a biotin derivative labeled with 111In (2-3 mCi) (third step). No evidence of toxicity was observed. Whole body radioactivity distribution was measured in five patients at various intervals postinjection by the conjugate counting technique. Tumors and metastases were detected in 18 of 19 patients (the remaining patient was a true negative) within 3 h after administration of 111In-biotin by planar or single photon emission tomography imaging. At the time of imaging, tumor/blood pool ratio was 5.5 +/- 3.2, and tumor/liver ratio was 6.7 +/- 3.9. Blood clearance of 111In-biotin was multiexponential, with the fast component having a t1/2 of 5 +/- 3 min. Urinary excretion of radioactivity over 3 h was 63.5 +/- 4.9% of the injected dose. Radioactivity at 3 h was 6.5 +/- 1.8% in blood, 1.6 +/- 0.3% in the kidney, and 2.4 +/- 0.6% in the liver. This approach represents an improvement in immunoscintigraphic techniques for tumor localization. The potential use for radioimmunotherapy is discussed.