gebhart/patrepeval huggingface dataset:
Isolation and physicochemical characterization of the half‐unit membranes of oilseed lipid bodies (1990)

The lipid‐free residue of lipid body membranes was isolated from quiescent peanuts and was physicochemically characterized. The preponderant component of the residue was proteinaceous and consisted of at least two polypeptides according to ultracentrifugation, gel filtration, gel electrophoresis and HPLC. The molecular weight of the principal polypeptide was between 10,000 and 16,000 daltons. Only one antigen, immunochemically unique with respect to other peanut components, was detected. Spectral analyses indicated the presence of a protoheme and revealed conformational modes of β‐sheet and unordered structure but no α‐helix. The amino acid composition was similar to that of an integral membrane polypeptide rather than to those of peripheral membranes or other plant polypeptides. The hydrophobicity, conformation and quantitative content of polypeptides were suitable for the existence of a monolayer at the lipid body‐cytoplasm interface. The results indicated that lipid body coatings physicochemically resemble membranes of intracellular organelles and supported the morphological concept that the coatings are half‐unit biological membranes. Reutilization of lipid body membranes appeared possible after lipid depletion during seed germination.
Radial distortion in low-cost lenses: numerical study (2008)

A few competitive models for lens distortion are presented and their accuracy is considered. Effectiveness of these models is tested comparatively against ray-tracing grid distortion data. Emphasis is made on retrofocus lens design typically occurring in low-cost camera systems. Theoretical conclusions are supported with practical camera calibration data.
Structure of the L1 and L6 core oligosaccharide epitopes of Neisseriameningitidis (1990)

The core oligosaccharides obtained from the lipopolysaccharides of Neisseriameningitidis serotypes 1 and 6 were isolated by mild acid hydrolysis, and their structures elucidated by combined chemical, biochemical, and physical techniques. Use was made of 500 MHz 1 H nuclear magnetic resonance measurements in both one-dimensional and two-dimensional modes as well as of nuclear Overhauser enhancement experiments. To assist in the structural assignments, the purified oligosaccharides were also degraded by chemical and enzymatic procedures to smaller fragments. The L1 oligosaccharide is a biantennary partially O-acetylated heptasaccharide in which the larger antenna terminates in a α-D-Galp1 → 4β-D-Galp1 → 4β-D-Glcp unit, whereas the smallest disaccharide antenna carries phosphorylethanolamine groups at O-3 of its heptosyl moiety. The L6 oligosaccharide is also a biantennary partially O-acetylated heptasaccharide but, unlike the L1 core, is terminated by a β-D-GlcpNAcl → 3β-D-Galp1 → 4β-D-Glcp unit in its larger antenna. The heptosyl moiety in the small disaccharide antenna bears a phosphorylethanolamine group at O-7, unlike O-3 for the L1 determinant. Keywords: lipopolysaccharides, Neisseriameningitidis, oligosaccharide epitopes, structure, NMR spectroscopy.
Lack of Salt-Inducible Kinase 2 (SIK2) Prevents the Development of Cardiac Hypertrophy in Response to Chronic High-Salt Intake (2014)

Cardiac left ventricle hypertrophy (LVH) constitutes a major risk factor for heart failure. Although LVH is most commonly caused by chronic elevation in arterial blood pressure, reduction of blood pressure to normal levels does not always result in regression of LVH, suggesting that additional factors contribute to the development of this pathology. We tested whether genetic preconditions associated with the imbalance in sodium homeostasis could trigger the development of LVH without concomitant increases in blood pressure. The results showed that the presence of a hypertensive variant of α-adducin gene in Milan rats (before they become hypertensive) resulted in elevated expression of genes associated with LVH, and of salt-inducible kinase 2 (SIK2) in the left ventricle (LV). Moreover, the mRNA expression levels of SIK2, α-adducin, and several markers of cardiac hypertrophy were positively correlated in tissue biopsies obtained from human hearts. In addition, we found in cardiac myocytes that α-adducin regulates the expression of SIK2, which in turn mediates the effects of adducin on hypertrophy markers gene activation. Furthermore, evidence that SIK2 is critical for the development of LVH in response to chronic high salt diet (HS) was obtained in mice with ablation of the sik2 gene. Increases in the expression of genes associated with LVH, as well as increases in LV wall thickness upon HS, occurred only in sik2+/+ but not in sik2-/- mice. Thus LVH triggered by HS or the presence of a genetic variant of α-adducin requires SIK2 and is independent of elevated blood pressure. Inhibitors of SIK2 may constitute part of a novel therapeutic regimen aimed at prevention/regression of LVH.
Use of the CRISPR/Cas9 System to Produce Genetically Engineered Pigs from In Vitro-Derived Oocytes and Embryos1 (2014)

Targeted modification of the pig genome can be challenging. Recent applications of the CRISPR/Cas9 system hold promise for improving the efficacy of genome editing. When a designed CRISPR/Cas9 system targeting CD163 or CD1D was introduced into somatic cells, it was highly efficient in inducing mutations. When these mutated cells were used with somatic cell nuclear transfer, offspring with these modifications were created. When the CRISPR/Cas9 system was delivered into in vitro produced presumptive porcine zygotes, the system was effective in creating mutations in eGFP, CD163, and CD1D (100% targeting efficiency in blastocyst stage embryos); however, it also presented some embryo toxicity. We could also induce deletions in CD163 or CD1D by introducing two types of CRISPRs with Cas9. The system could also disrupt two genes, CD163 and eGFP, simultaneously when two CRISPRs targeting two genes with Cas9 were delivered into zygotes. Direct injection of CRISPR/Cas9 targeting CD163 or CD1D into zygotes resulted in piglets that have mutations on both alleles with only one CD1D pig having a mosaic genotype. We show here that the CRISPR/Cas9 system can be used by two methods. The system can be used to modify somatic cells followed by somatic cell nuclear transfer. System components can also be used in in vitro produced zygotes to generate pigs with specific genetic modifications.
Validations of a Portable Home Sleep Study with Twelve-Lead Polysomnography: Comparisons and Insights into a Variable Gold Standard (2006)

There is a convincing correlation between the study-determined AHIs of both PSG and SNAP. This finding supports SNAP as a suitable alternative to PSG in identifying OSA, while accentuating the inherent variation present in a PSG-derived AHI. This test expands the diagnostic and therapeutic prowess of the practicing otolaryngologist by offering an alternative OSA testing modality that is associated with not only less expense, decreased waiting time, and increased convenience, but also statistically proven accuracy.
Searching for a Better Thermal Battery (2012)

Improved materials for storing heat could save energy in applications such as heating and cooling and could enhance generation from solar thermal plants.
143rd Annual Meeting American Neurological Association (2018)

The brain‐computer interface (BCI) uses electrical signals from the brain and uses them as information to control an external device and has the potential to stimulate neuroplasticity in motor impairment. Objective. Implement an immersive virtual reality and BCI system for upper limb rehabilitation and test its safety. Methods: 34 healthy subjects participated. We used an EEG of 16 channels placed on the scalp corresponding to the motor and pre‐motor area, an amplifier (g.USBAmp) and a signal classification method (ANFIS classifier), to detect mu and beta signals related to the intention of movement and used to control an immersive virtual reality representation of an upper limb; and perform 2 movements: flexion and extension, according to the brain signals detected. In addition, the classification percentages and their association with spatial abilities of participants were measured. Results: In this study, the system showed to acquire, amplify and adequately classify the brain signals to control the virtual upper limb, with a success rate of 79.6% and 76.1%, for extension and flexion, respectively. No adverse effect was evidenced. Classifications success show a correlation with spatial abilities, especially mental rotation test (R = 0.56, p &lt; 0.05), block design (R = 0.49, p &lt; 0.05) and matrix reasoning (R = 0, 54, p &lt; 0.05). Conclusions: The implemented system adequately controls the virtual reality software by intention of movement, showing an adequate level of safety.
The role of complement activation in myocardial injury. (1993)

The mechanisms of the complement-mediated myocardial injury associated with ischemia and reperfusion have not been elucidated fully. Complement may directly mediate injury through actions of the anaphylatoxins (C3a, C5a), or generation of the membrane attack complex (C5b-9). An in vitro model was developed to examine the direct effects of complement activation on heart function, assess myocardial tissue damage, and determine which complement components mediate tissue injury. Rabbit isolated hearts were perfused with buffer containing human plasma as a source of complement. Rabbit tissue activates human complement. Perfusion with 6% normal plasma resulted in complement activation as assessed by generation of Bb, C3a, C5a, and SC5b-9. Complement activation caused a number of effects that were onset 7 to 15 minutes following plasma addition, and that developed fully over the next 20 to 30 minutes. The effects were dependent upon the complement titer, and included: (1) an increase in the end diastolic pressure; (2) a decrease in the developed pressure; (3) an increase in the coronary perfusion pressure; and (4) an increase in lymphatic fluid formation. These effects were not elicited when inhibitors of complement activation (FUT-175 or soluble complement receptor type 1) were present, or when heat-inactivated human plasma was used. The effects of complement activation on myocardial function could not be reproduced by treatment with recombinant C5a, zymosan-activated plasma, or plasma selectively depleted of C8. Myocardial tissue accumulated sodium and calcium, and lost potassium, as a result of complement activation. Activation caused the release of creatine kinase from myocytes. The data demonstrate that complement activation caused decrements in the studied physiologic parameters. The effects were not mediated by the anaphylatoxins, but were dependent upon the distal complement component C8, suggesting that the membrane attack complex (C5b-9) was responsible for the physiologic changes. Complement activation directly mediated tissue injury in a manner consistent with plasmalemmal disruption due to C5b-9 formation. Since it has been shown in other models that ischemically injured myocardial tissue can activate complement, the data are compatible with the view that the C5b-9 complex may mediate myocardial injury associated with ischemia and reperfusion.
Carbamoyl Pyridone HIV-1 Integrase Inhibitors 3. A Diastereomeric Approach to Chiral Nonracemic Tricyclic Ring Systems and the Discovery of Dolutegravir (S/GSK1349572) and (S/GSK1265744) (2013)

We report herein the discovery of the human immunodeficiency virus type-1 (HIV-1) integrase inhibitors dolutegravir (S/GSK1349572) (3) and S/GSK1265744 (4). These drugs stem from a series of carbamoyl pyridone analogues designed using a two-metal chelation model of the integrase catalytic active site. Structure-activity studies evolved a tricyclic series of carbamoyl pyridines that demonstrated properties indicative of once-daily dosing and superior potency against resistant viral strains. An inherent hemiaminal ring fusion stereocenter within the tricyclic carbamoyl pyridone scaffold led to a critical substrate controlled diastereoselective synthetic strategy whereby chiral information from small readily available amino alcohols was employed to control relative and absolute stereochemistry of the final drug candidates. Modest to extremely high levels of stereochemical control were observed depending on ring size and position of the stereocenter. This approach resulted in the discovery of 3 and 4, which are currently in clinical development.
Gold content of water, plants, and animals (1970)

Sea water contains from 0.001 to 44 ppb (parts per billion) gold. The amounts of gold in fresh surface waters and ground waters are also within this range. The average amount of gold in sea water as calculated from neutron activation analyses is 0.05 ppb.
Processing of branched DNA intermediates by a complex of human FEN-1 and PCNA (1996)

In eukaryotic cells, a 5' flap DNA endonuclease activity and a ds DNA 5'-exonuclease activity exist within a single enzyme called FEN-1 [flap endo-nuclease and 5(five)'-exo-nuclease]. This 42 kDa endo-/exonuclease, FEN-1, is highly homologous to human XP-G, Saccharomyces cerevisiae RAD2 and S.cerevisiae RTH1. These structure-specific nucleases recognize and cleave a branched DNA structure called a DNA flap, and its derivative called a pseudo Y-structure. FEN-1 is essential for lagging strand DNA synthesis in Okazaki fragment joining. FEN-1 also appears to be important in mismatch repair. Here we find that human PCNA, the processivity factor for eukaryotic polymerases, physically associates with human FEN-1 and stimulates its endonucleolytic activity at branched DNA structures and its exonucleolytic activity at nick and gap structures. Structural requirements for FEN-1 and PCNA loading provide an interesting picture of this stimulation. PCNA loads on to substrates at double-stranded DNA ends. In contrast, FEN-1 requires a free single-stranded 5' terminus and appears to load by tracking along the single-stranded DNA branch. These physical constraints define the range of DNA replication, recombination and repair processes in which this family of structure-specific nucleases participate. A model explaining the exonucleolytic activity of FEN-1 in terms of its endonucleolytic activity is proposed based on these observations.
Retrovirus-mediated expression of a DNA repair protein in bone marrow protects hematopoietic cells from nitrosourea-induced toxicity in vitro and in vivo. (1995)

Severe and delayed myelosuppression is a major side effect encountered with the clinical use of nitrosourea-type chemotherapeutic drugs. The DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) has been shown to repair nitrosourea-induced DNA damage. We therefore investigated the effect of expressing MGMT in hematopoietic cells (via retrovirus-mediated gene transfer) on nitrosourea-induced toxicity. A retroviral vector (N2/ZipPGK-MGMT) expressing the human MGMT cDNA from the phosphoglycerate kinase promoter was constructed. Infection of murine bone marrow with the N2/ZipPGK-MGMT retrovirus significantly increased the survival of murine bone marrow-committed progenitor cells following in vitro exposure to N-N'-bis(2-chloroethyl)-N-nitrosourea (BCNU, carmustine). MGMT gene transfer also protected murine hematopoietic cells in vivo in a murine model of BCNU-induced myelosuppression. The infusion of 4-6 x 10(6) N2/ZipPGK-MGMT-transduced bone marrow cells into mice every 2 weeks significantly increased peripheral leukocyte counts, platelet counts, and hematocrits compared to infusions of mock-infected bone marrow cells. In addition, bone marrow-committed progenitor cells from some recipient animals demonstrated increased resistance to BCNU in vitro when analyzed 2.5 months after initial treatment. The integration of the N2/ZipPGK-MGMT provirus in the spleen DNA from these animals correlated with committed progenitor cell resistance to BCNU. These data suggest that MGMT expression in hematopoietic progenitor and precursor cells protects against nitrosourea-induced toxicity and that gene transfer may prove useful in attempts to reduce nitrosourea-induced myelosuppression in the clinical setting.
Pharmacokinetic interaction of megestrol acetate with zidovudine in human immunodeficiency virus-infected patients (1997)

This nonrandomized, two-period crossover study was performed to assess whether concomitant administration of megestrol acetate influences the steady-state pharmacokinetics of zidovudine and its inactive 5'-O-glucuronide metabolite. Twelve HIV-positive, asymptomatic male volunteers received a 100-mg oral capsule dose of zidovudine at least 30 min before meals five times a day at 0700, 1100, 1500, 1900, and 2300 h on study days 1 to 3 and a single 100-mg dose at 0700 h on day 4. On days 5 to 17, 800 mg of megestrol acetate, as a 40-mg/ml aqueous suspension, was administered orally immediately before the 0700 h dose of zidovudine. On days 5 to 16, zidovudine was also administered at 1100, 1500, 1900, and 2300 h. Serial blood samples were collected for 12 h after the single 100-mg dose of zidovudine on days 4 and 17; trough samples were also obtained just before the 0700 h dose on days 2 to 4 and 15 to 17. Levels of zidovudine and its glucuronide in plasma were assayed by a validated radioimmunoassay. Statistical analysis of trough plasma level data indicated that steady-state levels of zidovudine and its glucuronide in plasma had been attained when pharmacokinetic assessments were made on days 4 and 17. When megestrol acetate and zidovudine were coadministered for 13 days, differences of -14, -6.5, and -4.6% in mean zidovudine peak concentration and areas under the curve at 0 to 4 and 0 to 12 h, respectively, +22.5% in mean trough concentration, +2.6% in mean plasma half-life, and no change in median time to peak were observed compared to conditions when zidovudine was administered alone; for zidovudine 5'-O-glucuronide the respective differences were -9, -7.3, -4.4, +2.3, and +10% and no change. None of the differences were statistically significant (P > 0.05). Concomitant therapy with megestrol acetate, at the dose employed to treat anorexia, cachexia, or an unexplained, significant weight loss in AIDS patients, did not alter the steady-state pharmacokinetics of zidovudine or its 5'-O-glucuronide metabolite.
Universal features of localized eigenstates in disordered systems (2005)

Localization–delocalization transitions occur in problems ranging from semiconductor-device physics to propagation of disease in plants and viruses on the internet. Here, we report calculations of localized electronic and vibrational eigenstates for remarkably different, mostly realistic, disordered systems and point out similar characteristics in the cases studied. We show in each case that the eigenstates may be decomposed into exponentially localized islands which may appear in many different eigenstates. In all cases, the decay length of the islands increases only modestly near the localization–delocalization transition; the eigenstates become extended primarily by proliferation (growth in number) of islands near the transition. Recently, microphotoluminescence experiments (Guillet et al 2003 Phys. Rev. B 68 045319) have imaged exciton states in disordered quantum wires, and these bear a strong qualitative resemblance to the island structure of eigenstates that we have studied theoretically.
Phase I study of BAY 94‐9027, a PEGylated B‐domain‐deleted recombinant factor VIII with an extended half‐life, in subjects with hemophilia A (2014)

This phase I study demonstrates that BAY 94-9027 has an extended half-life in subjects with hemophilia A and, after multiple dosing, was well tolerated with no immunogenicity during the 8-week trial. A phase III study in a larger number of subjects is underway to fully characterize how this prolonged half-life will permit less frequent prophylaxis dosing for patients with hemophilia.
Adenovirus-mediated antisense urokinase-type plasminogen activator receptor gene transfer reduces tumor cell invasion and metastasis in non-small cell lung cancer cell lines. (2001)

The urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an important role in the proteolytic cascade involved in the metastasis of lung and other cancers. We report that the reduction in uPAR levels produced by an antisense strategy using an adenovirus construct (Ad-uPAR) in H1299 cells, an invasive human lung cancer cell line that produces high levels of uPAR, resulted in a decrease of uPAR levels to 80-90% of those seen in cells infected with mock or adenovirus (Ad)-cytomegalovirus vector controls. In addition, increasing the multiplicity of infection from 25 to 200 caused a corresponding decrease in the level of uPAR protein within 5 days of treatment, as shown by Western blot analysis. Furthermore, the in vitro translation of total RNA levels of Ad-uPAR-infected H1299 cells in a rabbit reticulocyte lysate system caused a 50-70% decrease in uPAR immunoprecipitate in Ad-uPAR-infected cells relative to the levels in cells of mock and vector controls. The Matrigel invasion assay showed the invasion of H1299 cells and A549 cells infected with Ad-uPAR to be decreased by 70% relative to mock- and vector-infected controls. Infection of tumor cells with Ad-uPAR before implantation significantly reduced the incidence of lung metastasis by 85% as compared with the control virus-infected cells injected into nude mice through the tail vein. Our collective results show that the uPAR system is a potential target of treatment for lung cancers.
Serum Prostate Specific Antigen Complexed toα1-Antichymotrypsin as an Indicator of Prostate Cancer (1993)

Prostate specific antigen (PSA) in serum has recently been shown to occur in complex with alpha 1-antichymotrypsin and as an approximately 30 kDa. noncomplexed molecular form. We characterized PSA by 3 different assays in samples from 144 patients with benign prostatic hyperplasia (BPH) and 121 with carcinoma of the prostate. One of these noncompetitive assays measured total PSA by detecting PSA complexed to serine proteinase inhibitors and the noncomplexed molecular form, a second measured only PSA in complex with alpha 1-antichymotrypsin, whereas a third detected the noncomplexed form. PSA in complex with alpha 1-antichymotrypsin was the predominant form in all patient sera. Noncomplexed PSA constituted a minor fraction that was significantly smaller in patients with untreated prostate cancer than in those with BPH (p < 0.0001). The proportion of noncomplexed PSA does not correlate to the serum concentration of PSA or that of alpha 1-antichymotrypsin. In men with a serum PSA concentration of less than 10 micrograms./l. the combination of assays measuring total PSA immunoreactivity, the noncomplexed molecular form and PSA in complex with alpha 1-antichymotrypsin may facilitate discrimination between prostate cancer and BPH.