gebhart/patrepeval huggingface dataset:
GSK3B polymorphisms alter transcription and splicing in Parkinson's disease (2005)

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a combination of motor symptoms. We identified two functional single nucleotide polymorphisms in the glycogen synthase kinase-3beta gene (GSK3B). A promoter single nucleotide polymorphism (rs334558) is associated with transcriptional strength in vitro in which the T allele has greater activity. An intronic single nucleotide polymorphism (rs6438552) regulates selection of splice acceptor sites in vitro. The T allele is associated with altered splicing in lymphocytes and increased levels of GSK3B transcripts that lack exons 9 and 11 (GSKDeltaexon9+11). Increased levels of GSKDeltaexon9+11 correlated with enhanced phosphorylation of its substrate, Tau. In a comparison of PD and control brains, there was increased in frequency of T allele (rs6438552) and corresponding increase in GSKDeltaexon9+11 and Tau phosphorylation in PD brains. Conditional logistic regression indicated gene-gene interaction between T/T genotype of rs334558 and H1/H1 haplotype of microtubule-associated protein Tau (MAPT) gene (p = 0.009). There was association between a haplotype (T alleles of both GSK3B polymorphisms) and disease risk after stratification by Tau haplotypes ((H1/H2+H2/H2 individuals: odds ratio, 1.64; p = 0.007; (H1/H1 individuals: odds ratio, 0.68; p < 0.001). Ours results suggest GSK3B polymorphisms alter transcription and splicing and interact with Tau haplotypes to modify disease risk in PD.
Dianthins, ribosome-damaging proteins with anti-viral properties from Dianthus caryophyllus L. (carnation) (1981)

1. Dianthin 30 and dianthin 32, two proteins isolated from the leaves of Diathus caryophyllus (carnation), were purified to homogeneity by chromatography on CM-cellulose. 2. The mol.wt. of dianthin 30 is 29 500 and that of dianthin 32 is 31 700. Both dianthins are glycoproteins containing mannose. 3. Dianthins inhibit protein synthesis in a lysate of rabbit reticulocytes, with an ID50 (concentration giving 50% inhibition) of 9.15 ng/ml (dianthin 30) and 3.6 ng/ml (dianthin 32). They act by damaging ribosomes in a less-than-equimolar ratio. Protein synthesis by intact cells is partially inhibited by dianthins at a concentration of 100 microgram/ml. 4. Dianthins mixed with tobacco-mosaic virus strongly decrease the number of local lesions on leaves of Nicotiana glutinosa.
Safety and Efficacy of Anakinra in Severe Hidradenitis Suppurativa (2015)

clinicaltrials.gov Identifier: NCT01558375.
Electron CrystallographyElectron Microscopy and Electron Diffraction (2011)

This is the first textbook describing crystal structure determination (especially inorganic) from high-resolution transmission electron microscopy (HRTEM) and electron diffraction (ED). The theoretical background and practical procedures are explained with hundreds of figures. The fundamental fact that the crystallographic structure factor phase information is present in EM images is explained by formulas, and HRTEM images and their Fourier transforms.The basics of crystallography are presented in an innovative way compared to standard crystallographic texts, exploiting direct imaging of structures at atomic resolution – impossible with X-ray crystallography. Moving back and forth between real and reciprocal space facilitates a deep understanding of the subject. EM images and ED patterns illustrate the symmetries in crystals.Electron optics and distortion (and how they can be quantified and corrected for) are explained with drawings, formulas and experimental EM images and ED patterns.New developments including precession electron diffraction and 3D reconstruction from HRTEM images and ways of collecting complete 3D ED data are thoroughly covered.We hope this textbook will become the standard for those who investigate crystal structures by EM but want to improve their skills, including going from 2D projections to full 3D structures. It introduces electron crystallography for all crystallographers and materials scientists, who are struggling with crystals, too small or imperfect for single-crystal X-ray diffraction and too complex for X-ray powder diffraction.We believe the easiest way to learn X-ray crystallography is to go via electron crystallography, since you can see both the structure image and the diffraction pattern. We have written this book also with these readers in mind, making reference to X-ray crystallography at every stage. Extensive appendices with worked examples makes the book ideal for courses and self-study.
Reduction of metabotropic glutamate receptor‐mediated heterosynaptic inhibition of developing MNTB‐LSO inhibitory synapses (2007)

The lateral superior olivary nucleus (LSO) is an auditory relay centre within the brain stem that encodes interaural level differences for sound localization by integrating GABA/glycinergic input from the contralateral ear via the medial nucleus of the trapezoid body (MNTB), and glutamatergic input from the ipsilateral ear via the ventral cochlear nucleus (VCN). To study the development of the circuits that contribute to the establishment of sound localization, the heterosynaptic modulation mediated by glutamate released from VCN terminals and group II metabotropic glutamate receptor (mGluR) expressed on MNTB inhibitory terminals was investigated using whole-cell patch-clamp techniques. At postnatal day-4-8 (P4-8), repetitive stimulation of the VCN-LSO excitatory afferents caused significant inhibition of MNTB-LSO inhibitory postsynaptic currents (IPSCs) in amplitude with an increase of its coefficient of variation and changed the paired-pulse ratio. These effects were antagonized by LY341495, an mGluR2/3 antagonist. Thus, the suppression of MNTB-LSO synaptic responses induced by repetitive stimulation applied to the VCN-LSO glutamatergic afferent is presumably due to an activation of mGluR2/3 existing on MNTB-LSO presynaptic terminals. The suppression rate of MNTB-LSO IPSCs by DCG IV, an mGluR2/3 agonist, decreased with development and became negligible by the third week after birth. The immunohistochemical staining of mGluR2/3 in the LSO was also less apparent at P18 compared with that at P4. We suggest that mGluR-mediated heterosynaptic modulation of MNTB-LSO GABAergic/glycinergic transmission might contribute to the development of appropriate adult auditory circuits.
Micropatterning of small molecular weight organic semiconductor thin films using organic vapor phase deposition (2003)

Using both analytical and experimental methods, we show that micron scale patterned growth of small molecular weight organic semiconductor thin films can be achieved by the recently demonstrated process of organic vapor phase deposition (OVPD). In contrast to the conventional process of vacuum thermal evaporation, the background gas pressure during OVPD is typically 0.1–10 Torr, resulting in a molecular mean free path (mfp) of from 100 to 1 μm, respectively. Monte Carlo simulations of film growth through apertures at these gas densities indicate that when the mfp is on the order of the mask-to-substrate separation, deposit edges can become diffuse. The simulations and deposition experiments discussed here indicate that the deposited feature shape is controlled by the mfp, the aperture geometry, and the mask-to-substrate separation. Carefully selected process conditions and mask geometries can result in features as small as 1 μm. Furthermore, based on continuum and stochastic models of molecular transport in confined geometries, we propose the in situ direct patterning growth technique of organic vapor jet printing. The high pattern definition obtained by OVPD makes this process attractive for the growth of a wide range of structures employed in modern organic electronic devices.
Antibody Repertoire Profiling Using Bacterial Display Identifies Reactivity Signatures of Celiac Disease (2012)

A general strategy to identify serum antibody specificities associated with a given disease state and peptide reagents for their detection was developed using bacterial display peptide libraries and multiparameter flow cytometry (MPFC). Using sera from patients with celiac disease (CD) (n = 45) or healthy subjects (n = 40), bacterial display libraries were screened for peptides that react specifically with antibodies from CD patients and not with those from healthy patients. The libraries were screened for peptides that simultaneously cross-react with CD patient antibodies present in two separate patient groups labeled with spectrally distinct fluorophores but do not react with unlabeled non-CD antibodies, thus affording a quantitative separation. A panel of six unique peptide sequences yielded 85% sensitivity and 91% specificity (AUC = 0.91) on a set of 60 samples not used for discovery, using leave-one-out cross-validation. Individual peptides were dissimilar with known CD-specific antigens tissue transglutaminase (tTG) and deamidated gliadin, and the classifier accuracy was independent of anti-tTG antibody titer. These results demonstrate that bacterial display/MPFC provides a highly effective tool for the unbiased discovery of disease-associated antibody specificities and peptide reagents for their detection that may have broad utility for diagnostic development.
Failure of alleles at the Na+, K +-ATPase ??1 locus to cosegregate with blood pressure in Dahl rats (1990)

A previously described Pst I restriction fragment length polymorphism in Dahl rats at the Na+, K(+)-adenosine 5'-triphosphatase (ATPase) alpha 1 isoform locus was tested for cosegregation with blood pressure in segregating populations. Inbred Dahl salt-sensitive (S) and inbred Dahl salt-resistant (R) rats were crossed to produce F1 rats, and three segregating populations, F1 x R, F2 and F1 x S, were produced and raised on a high-salt diet for variable periods to attain the maximal blood pressure response in each population. In no segregating population was there a significant difference in blood pressure among genotypes at the Na+, K(+)-ATPase alpha 1 locus. Power calculations suggest that single-allele dosage effects of less than 7.5 mmHg were unlikely to be detected. It is concluded that either the S and R alleles at the Na+, K(+)-ATPase alpha 1 locus do not influence blood pressure under the conditions of these experiments (high dietary salt, Dahl rat genetic background) or, if they do, their effect is small.
Passive immunization with the anti-HIV-1 human monoclonal antibody (hMAb) 4E10 and the hMAb combination 4E10/2F5/2G12 (2004)

This Phase I trial showed that the hMAb 4E10 can be safely administered, both alone and in combination with 2F5 and 2G12 to HIV-1-infected patients.
Interaction of a Hepatoma-Specific Nuclear Factor with Transcription-Regulatory Sequences of the Human α-Fetoprotein and Albumin Genes (1988)

DNase I footprinting and gel mobility shift analysis showed that an HuH-7 hepatoma nuclear protein, termed AFP1, binds specifically to an AT-rich sequence, TGATTAATAATTACA, in domain B of the human alpha-fetoprotein enhancer. No such binding activity was found in HeLa cell nuclei. Transient transfection studies showed that a 54-base-pair region corresponding to the AFP1-binding site could stimulate the simian virus 40 early promoter to express a linked chloramphenicol acetyltransferase gene in an orientation-independent and cell-specific manner. The correlation between the binding of AFP1 and the stimulation of chloramphenicol acetyltransferase gene expression strongly suggests that specific interaction of AFP1 with the AT motif is important for cell-specific transcriptional enhancement. Competition gel mobility shift analysis revealed that similar AT-rich sequences with high affinities to AFP1 were also present in the promoters of the alpha-fetoprotein and albumin genes. These results suggest that AFP1 may function as a common regulatory factor in the transcription of the alpha-fetoprotein and albumin genes.
Primary and Secondary Isotope Effects on Proton Transfers to Diazocarbonyl Compounds (1980)

Abstract The primary solvent isotope effects on the AS E ‐2 type hydrolyses of α‐diazocarbonyl compounds p ‐XC 6 H 4 CN 2 CH 3 (X = NO 2 , H, OCH 3 and C 6 H 5 CON(CH 3 ) 2 ) are found to be identical despite large differences in their overall hydrolysis rates. The secondary solvent isotope effects diminish considerably with diminishing substrate reactivity, and for two substrates they are smaller than those normally anticipated for a simple proton transfer from the lyonium species. An analysis is presented of these and other abnormal secondary isotope effects found elsewhere, involving consideration of the solvation of the reaction complex.
Factor V Leiden mutation is associated with enhanced arterial thrombotic tendency in lean but not in obese mice (2007)

The homozygous factor V Leiden mutation is associated with enhanced venous thrombotic risk. Obesity is a major risk factor for development of thrombotic cardiovascular disease. It was the objective of this study to investigate whether obesity affects the thrombotic risk associated with the mutation. Male mice with homozygous factor V Leiden mutation (Arg 504 to Gln) (FVQ/Q) and corresponding wild-type (WT) mice were kept on a standard fat diet (SFD) or high fat diet (HFD) for 14 weeks, and femoral artery thrombosis was induced by FeCl3 treatment. As compared to SFD, HFD feeding for 14 weeks resulted in significantly higher body weight and fat mass associated with adipocyte hypertrophy, which were, however, similar for both genotypes. In the FeCl3-induced arterial thrombosis model, FVQ/Q mice kept on SFD had a 40% shorter occlusion time (p = 0.015) and 40% lower blood flow (p = 0.03), as compared to WT mice. However, on HFD the occlusion time and blood flow were not significantly different for both genotypes. This finding could not be explained by differential changes of coagulation factors in either genotype fed on SFD or HFD. In conclusion, on SFD, but not on HFD, the factor V Leiden mutation is associated with enhanced thrombotic tendency after FeCl3 injury of the femoral artery, suggesting that in this model obesity rescues the increased thrombotic risk associated with the factor V Leiden mutation.
Potential Use of Chitosan as a Cell Scaffold Material for Cartilage Tissue Engineering (2002)

One of the most important factors in any tissue-engineering application is the cell substrate. The purpose of this study was the initial evaluation of chitosan, a derivative of the abundant, naturally occurring biopolymer chitin, as a cell scaffold for cartilage tissue engineering. Chitosan scaffolds having an interconnecting porous structure were easily fabricated by simple freezing and lyophilization of a chitosan solution. After rehydration of scaffolds, porcine chondrocytes were seeded onto scaffolds and cultured for up to 28 days in a rotating-wall bioreactor. Chitosan scaffolds supported cell attachment and maintenance of a rounded cell morphology. After 18 days, cells within the scaffolds had synthesized extracellular matrix in which proteoglycan and type II collagen were detected by toluidine blue staining and immunohistochemistry, respectively. Abundant extracellular matrix was found almost exclusively in the periphery of the scaffolds, as scaffold microstructure prevented cells from penetrating to interior regions. Nonetheless, the results suggest that chitosan scaffolds may be a useful alternative to synthetic cell scaffolds for cartilage tissue engineering.
Near-Infrared Fluorescence Imaging in Humans with Indocyanine Green: A Review and Update (2010)

Near-infrared (NIR) fluorescence imaging clinical studies have been reported in the literature with six different devices that employ various doses of indocyanine green (ICG) as a non-specific contrast agent. To date, clinical applications range from (i) angiography, intraoperative assessment of vessel patency, and tumor/metastasis delineation following intravenous administration of ICG, and (ii) imaging lymphatic architecture and function following subcutaneous and intradermal ICG administration. In the latter case, NIR fluorescence imaging may enable new discoveries associated with lymphatic function due to (i) a unique niche that is not met by any other conventional imaging technology and (ii) its exquisite sensitivity enabling high spatial and temporal resolution. Herein, we (i) review the basics of clinical NIR fluorescence imaging, (ii) survey the literature on clinical application of investigational devices using ICG fluorescent contrast, (iii) provide an update of non-invasive dynamic lymphatic imaging conducted with our FDPM device, and finally, (iv) comment on the future NIR fluorescence imaging for non-invasive and intraoperative use given recent demonstrations showing capabilities for imaging following microdose administration of contrast agent.
Effect of Intravenous ω‐3 Fatty Acid Infusion and Hemodialysis on Fatty Acid Composition of Free Fatty Acids and Phospholipids in Patients With End‐Stage Renal Disease (2011)

Intravenous ω-3 PUFAs administered during HD caused a transient selective increase in ω-3 FFA concentration. Furthermore, ω-3 PUFAs were rapidly incorporated into platelets, and the content of ω-3 PUFAs in plasma phospholipids increased after 48 hours.
Active power estimation by averaging of the DFT coefficients (2002)

The paper proposes and discusses an algorithm to improve the estimation of the active power of electrical systems under incoherent sampling. It is based on smoothing sampled data by windowing, prior to their numeric integration, and then averaging the DFT (discrete Fourier transform) coefficients in the frequency domain to reduce the leakage effects. The simulation and experimental results are presented showing that averaging of DFT coefficients provides better estimation of the active power than by windowing. The spectrum of the used window must have a sine function in the kernel. The use of a suitable algorithm depends on a number of observed periods, on positions of the frequency components, and on signal to noise ratio.
Phase II evaluation of DON (6-Diazo-5-Oxo-L-Norleucine) in patients with advanced colorectal carcinoma (1982)

Twenty-three patients with advanced colorectal carcinoma, previously treated with chemotherapy, were entered in a phase II trial of DON (6-Diazo-5-Oxo-l-Norleucine), an antagonist of l-glutamine. One of 14 adequately treated patients had a partial response of 6 weeks duration. The dose-limiting toxicity was nausea and vomiting; 48% of patients originally entered on the study withdrew because of vomiting. Myelosuppression was minimal, with only mild thrombocytopenia noted. The dose and schedule used in this study were beyond the maximally tolerated dose for many patients; future phase II studies of DON will be difficult to complete unless schedules and doses are found which result in less nausea and vomiting.
The Cellular TATA Binding Protein Is Required for Rep-Dependent Replication of a Minimal Adeno-Associated Virus Type 2 p5 Element (2005)

The p5 promoter region of adeno-associated virus type 2 (AAV-2) is a multifunctional element involved in rep gene expression, Rep-dependent replication, and site-specific integration. We initially characterized a 350-bp p5 region by its ability to behave like a cis-acting replication element in the presence of Rep proteins and adenoviral factors. The objective of this study was to define the minimal elements within the p5 region required for Rep-dependent replication. Assays performed in transfected cells (in vivo) indicated that the minimal p5 element was composed by a 55-bp sequence (nucleotides 250 to 304 of wild-type AAV-2) containing the TATA box, the Rep binding site, the terminal resolution site present at the transcription initiation site (trs(+1)), and a downstream 17-bp region that could potentially form a hairpin structure localizing the trs(+1) at the top of the loop. Interestingly, the TATA box was absolutely required for in vivo but dispensable for in vitro, i.e., cell-free, replication. We also demonstrated that Rep binding and nicking at the trs(+1) was enhanced in the presence of the cellular TATA binding protein, and that overexpression of this cellular factor increased in vivo replication of the minimal p5 element. Together, these studies identified the minimal replication origin present within the AAV-2 p5 promoter region and demonstrated for the first time the involvement of the TATA box, in cis, and of the TATA binding protein, in trans, for Rep-dependent replication of this viral element.
Exhaustion of Cytotoxic Effector Systems May Limit Monoclonal Antibody-Based Immunotherapy in Cancer Patients (2012)

The CD20 mAb ofatumumab (OFA) induces complement-mediated lysis of B cells. In an investigator-initiated phase II trial of OFA plus chemotherapy for chronic lymphocytic leukemia (CLL), OFA treatment promoted partial CLL B cell depletion that coincided with reduced complement titers. Remaining CLL B cells circulated with bound OFA and covalently bound complement breakdown product C3d, indicative of ongoing complement activation. Presumably, neither complement- nor effector cell-based mechanisms were sufficiently robust to clear these remaining B cells. Instead, almost all of the bound OFA and CD20 was removed from the cells, in accordance with previous clinical studies that demonstrated comparable loss of CD20 from B cells after treatment of CLL patients with rituximab. In vitro experiments with OFA and rituximab addressing these observations suggest that host effector mechanisms that support mAb-mediated lysis and tumor cell clearance are finite, and they can be saturated or exhausted at high B cell burdens, particularly at high mAb concentrations. Interestingly, only a fraction of available complement was required to kill cells with CD20 mAbs, and killing could be tuned by titrating the mAb concentration. Consequently, maximal B cell killing of an initial and secondary B cell challenge was achieved with intermediate mAb concentrations, whereas high concentrations promoted lower overall killing. Therefore, mAb therapies that rely substantially on effector mechanisms subject to exhaustion, including complement, may benefit from lower, more frequent dosing schemes optimized to sustain and maximize killing by cytotoxic immune effector systems.
Exogenous Ca2+‐ATPase isoform effects on Ca2+ transients of embryonic chicken and neonatal rat cardiac myocytes (2000)

1. Sarco-endoplasmic reticulum Ca2+-ATPase from fast skeletal (SERCA1) or cardiac muscle (SERCA2a) was expressed in embryonic chicken and neonatal rat cardiac myocytes by adenovirus vectors, with c-myc tags on both constructs to compare expression and distinguish exogenous from endogenous SERCA2a in myocytes. 2. Expression of the two isoforms was similar (approximately 3-fold higher than endogenous SERCA). However, SERCA1 activity was 2-fold greater than SERCA2a activity, due to intrinsic differences in turnover rates. Activation of both exogenous SERCA isoforms by Ca2+ was displaced to slightly lower [Ca2+], suggesting that the overexpressed isoforms were independent of phospholamban. In fact, phospholamban and calsequestrin expression were unchanged. 3. Decay time constants of cytosolic Ca2+ transients from cells overexpressing SERCA1 were reduced by 30-40 % and half-widths by 10-15 % compared to controls. SERCA2a overexpression produced much less acceleration of transients in chick than in rat, and less acceleration than SERCA1 overexpression in either species. There was no significant change in resting [Ca2+], peak amplitudes, or in the amount of Ca2+ releasable by caffeine from overexpression of either SERCA isoform. However, the amplitudes of the transients increased with SERCA1 overexpression when pacing frequency limited refilling of the sarcoplasmic reticulum. 4. It is concluded that total SERCA transport velocity has a primary effect on the decay phase of transients. Transport velocity is affected by SERCA isoform turnover rate, temperature, and/or SERCA copy number.