gebhart/patrepeval huggingface dataset:
Prenatal Exclusion of Recessively Inherited Disorders: Should Maternal Plasma Analysis Precede Invasive Techniques? (2002)

Since the presence of large amounts of circulating fetal DNA in maternal plasma and serum samples was first reported by Lo et al. in 1997 (1), a multitude of clinical applications for the noninvasive diagnosis of complications of pregnancy have been reported [reviewed in Ref. (2)]. These applications have largely focused on the quantification of male fetal DNA in maternal plasma/serum samples and its associated increase in conditions such as fetal trisomy 21, maternal hyperemesis gravidarum, preeclampsia, invasive placenta, and preterm labor (3)(4)(5)(6)(7). In addition, qualitative detection of uniquely fetal DNA sequences in maternal plasma/serum has facilitated the noninvasive prenatal diagnosis of Rhesus D genotype, myotonic dystrophy, and achondroplasia (8)(9)(10). Both of these approaches are feasible because fetal and maternal DNA can be distinguished from each other. This same approach, however, will not work in the noninvasive prenatal diagnosis of autosomal recessive disorders, in which a fetus shares a mutant allele with its mother.

In this issue of Clinical Chemistry , Chiu et al. (11) describe a novel strategy to exclude the diagnosis of a recessive condition by identifying polymorphic markers that distinguish the uniquely paternal mutant and wild-type alleles. They amplified cell-free fetal DNA in maternal plasma at 11 and 17 weeks of gestation, and by comparison with DNA from the couple’s first affected child, were able to determine that the current pregnancy was unaffected.

As a model system, these investigators chose the disease congenital adrenal hyperplasia (CAH), but the approach …
High-Resolution NMR Spectroscopy of Membrane Proteins in Aligned Bicelles (2004)

High-resolution solid-state NMR spectra can be obtained from uniformly (15)N-labeled membrane proteins in magnetically aligned bicelles. Fast uniaxial diffusion about the axis of the bilayer normal results in single-line spectra that contain the orientational information necessary for protein structure determination.
A Dipolar Coupling Based Strategy for Simultaneous Resonance Assignment and Structure Determination of Protein Backbones (2001)

A new approach for simultaneous protein backbone resonance assignment and structure determination by NMR is introduced. This approach relies on recent advances in high-resolution NMR spectroscopy that allow observation of anisotropic interactions, such as dipolar couplings, from proteins partially aligned in field ordered media. Residual dipolar couplings are used for both geometric information and a filter in the assembly of residues in a sequential manner. Experimental data were collected in less than one week on a small redox protein, rubredoxin, that was 15N enriched but not enriched above 1% natural abundance in 13C. Given the acceleration possible with partial 13C enrichment, the protocol described should provide a very rapid route to protein structure determination. This is critical for the structural genomics initiative where protein expression and structural determination in a high-throughput manner will be needed.
Effect of N-alkylation on the affinities of analogs of spiperone for dopamine D2 and serotonin 5-HT2 receptors (1992)

Two series of N-substituted spiperone analogues were prepared and evaluated in vitro to measure their affinities for dopamine D2 and serotonin 5-HT2 receptors. Substitution of the amide nitrogen with an alkyl group of five carbon units or less resulted in analogues displaying a low selectivity for D2 compared to 5-HT2 receptors. However, a moderate improvement in selectivity for D2 receptors was observed with N-benzylspiperone. Substitution at either the ortho or para position of the benzyl group resulted in a further reduction in affinity for 5-HT2 receptors and improvement in the selectivity ratio. Examination of N-substituted analogues of spiperone may provide insights into the topography of the antagonist binding region of the 5-HT2 receptor. The results also suggest that an 18F-labeled analogue of N-(4-nitrobenzyl)spiperone (4p) may be a suitable tracer for studying D2 receptors with positron emission tomography since this compound displays a high selectivity for D2 receptors relative to that of spiperone and N-methylspiperone.
Application of Flow-Thru Composite Frac Plugs in Tight-Gas Sand Completions (2003)

Abstract Several major developmental programs in the Rocky Mountain region of the United States are in fields where zones of several hundred to several thousand feet of stacked, tight (&amp;lt;0.05 md) lenticular gas sands exist. In order to be productive, these wells require multiple fracture treatments over the pay interval. Since field development has been ongoing, the drilling programs are extending into more marginal production areas. Infill programs are downsizing spacing, and also, successful refracturing programs are being conducted in some fields. Before 1998, traditional methods were being used to isolate fracture treatments. These methods usually required killing the well between fracture treatments or during cleanout operations. Unfortunately, field studies have determined that the traditional isolation methods have negatively impacted well productivity. In view of the costs involved and the lower productivity experienced with the new drilling programs, it became apparent that either well costs had to be reduced or well productivity had to be improved! This paper will discuss the application of flow-thru composite frac plugs (FTCFP) and how they were capable of addressing the current needs to reduce operational costs and improve productivity. These plugs can be used as an alternative to traditional isolation methods, or induced stress diversion. Through June 2002, there have been over 3,200 FTCFPs run in the Rocky Mountain region. The benefits gained from FTCFP usage are derived from the following: Well drill-out costs are reducedPositive isolation is allowedAll zones can be produced during completion. Their use has now become a "best practice" in stacked-pay completions.
Cyclin-Dependent Kinase 4/6 (Cdk4/6) Inhibitors: Perspectives in Cancer Therapy and Imaging (2010)

Cyclin-dependent kinases 4 and 6 (Cdk4/6) are important components of cell cycle activation and control in early G(1) phase. Both enzymes and their regulators, e.g., cyclins, play critical roles in embryogenesis, homeostasis, and cancerogenesis. Cdk4/6 are attractive targets for cancer treatment. Recently, numerous selective small molecule inhibitors of Cdk4/6 have been developed. The potential of Cdk4/6 inhibitors, particularly, pyrido[2,3-d]pyrimidine derivatives, as both anti-cancer drugs and 124I- and 18F-radiolabeled tracers for cancer imaging using positron emission tomography is discussed.
Trypanocide Diamidine mit vier Ringen in einem oder zwei Ringsystemen (1973)

Abstract Die trypanociden Eigenschaften der Diamidine vom Typ A werden durch Starrheit des Molekülgerüstes und durch seine Flächenvergrößerung beeinträchtigt, wie sich durch die Darstellung von Diamidinen mit folgenden Gerüsten zeigen ließ: 10 H ‐[1]Benzothieno‐[3,2‐ b ]indol ( 1c ); Chrysen ( 4g ); cis ‐4b,5,6,10b,11,12‐Hexahydrochrysen ( 8g ); 2‐(2‐Benzofuranyl)indol ( 10c, 11c ); 2‐Naphthylbenzo[ b ]thiophen ( 12d ); 1‐Phenylnaphtho[2,1‐ b ]thiophen ( 18c ); Bis(2‐benzofuranyl)‐methan ( 24d ), ‐äthylene ( 25c, 28c, 31c ) und ‐äthane ( 29b, 30b ).
Subcutaneous fentanyl and sufentanil infusion substitution for morphine intolerance in cancer pain management (1995)

Eleven patients with cancer pain in a palliative care and chronic pain service required cessation of morphine due to unacceptable opioid side effects. In this retrospective study fentanyl was evaluated as a second-line subcutaneously infused opioid. Starting doses ranged from 100 to 1000 micrograms/24 h, and the duration of fentanyl infusion was 3-70 days. The clinically derived mean relative potency of fentanyl to morphine infusions was 68:1 (SD +/- 23; range: 15-100), and we now recommend cautious dose conversion at an approximate equivalence of 150-200 micrograms fentanyl for 10 mg morphine in non-opioid naive chronic cancer pain patients. All patients demonstrated an improvement in the adverse effect(s) for which the change in opioid was undertaken. Adequate pain relief was achieved in all but 1 patient with mixed nociceptive and neuropathic pelvic pain for whom an epidural infusion of a local anaesthetic/opioid mixture was required. Fentanyl was changed to the more potent synthetic opioid sufentanil in 2 patients for whom the fentanyl dose necessitated too large a volume for the portable syringe driver in use. The clinically derived sufentanil to fentanyl relative potencies were 24:1 and 16:1, respectively. This achieved good analgesia and maintained the favourable side-effect profile seen with fentanyl. Subcutaneous infusion appears to be a safe and viable route of fentanyl delivery, and provided effective analgesia with a low incidence of adverse effects in this small selected group of patients who were intolerant of subcutaneous morphine. We suggest a trial of subcutaneous fentanyl for selected patients who have intractable adverse effects on morphine, and it is now the second-line infusable opioid in our service. Further prospective evaluation of the role of these two synthetic mu opioid agonists in palliative care practice is warranted, as part of an evolving picture of variation in opioid side-effect profile seen with different drugs within the class.
Regulation of KATP Channel Activity by Diazoxide and MgADP (1997)

KATP channels were reconstituted in COSm6 cells by coexpression of the sulfonylurea receptor SUR1 and the inward rectifier potassium channel Kir6.2. The role of the two nucleotide binding folds of SUR1 in regulation of KATP channel activity by nucleotides and diazoxide was investigated. Mutations in the linker region and the Walker B motif (Walker, J.E., M.J. Saraste, M.J. Runswick, and N.J. Gay. 1982. EMBO [Eur. Mol. Biol. Organ.] J. 1:945-951) of the second nucleotide binding fold, including G1479D, G1479R, G1485D, G1485R, Q1486H, and D1506A, all abolished stimulation by MgADP and diazoxide, with the exception of G1479R, which showed a small stimulatory response to diazoxide. Analogous mutations in the first nucleotide binding fold, including G827D, G827R, and Q834H, were still stimulated by diazoxide and MgADP, but with altered kinetics compared with the wild-type channel. None of the mutations altered the sensitivity of the channel to inhibition by ATP4-. We propose a model in which SUR1 sensitizes the KATP channel to ATP inhibition, and nucleotide hydrolysis at the nucleotide binding folds blocks this effect. MgADP and diazoxide are proposed to stabilize this desensitized state of the channel, and mutations at the nucleotide binding folds alter the response of channels to MgADP and diazoxide by altering nucleotide hydrolysis rates or the coupling of hydrolysis to channel activation.
Reverse Transcriptase Polymerase Chain Reaction for Prostate Specific Antigen in the Management of Prostate Cancer (1997)

RT-PCR can detect PSA expressing cells that are otherwise undetectable by other means in patients with localized and metastatic cancers. This assay is highly specific, since PSA expressing cells were consistently undetectable in the peripheral circulation of patients without prostate cancer in most studies. Limited data to date suggest that this test may have a role in the staging of tumors before radical prostatectomy and in the serial followup of patients after treatment. RT-PCR may improve the detectability of lymph node metastasis over immunohistochemistry. Presently this test should remain a powerful research tool in the study of the biology and behavior of prostate cancer, and it should not be used to guide any clinical decision making. The use of this assay as a prognostic and management tool for prostate cancer is in the earliest stages.
Electronic Refrigeration of a Two-Dimensional Electron Gas (2009)

Measurements are presented of a device designed to cool a 6 microm;{2} region of 2D electron gas using quantum dots. Electrostatic effects are found to be significant in the device, and a model that accounts for them is developed. At ambient electron temperatures above 120 mK the results are consistent with the model and the base temperature of the cooled region is estimated. At an ambient electron temperature of 280 mK, the 6 microm;{2} region is found to be cooled below 190 mK. Below 120 mK the results deviate from predictions, which is attributed to reduced electron-electron scattering rates.
Optical tweezers reveal relationship between microstructure and nanoparticle penetration of pulmonary mucus (2012)

In this study, the mobility of nanoparticles in mucus and similar hydrogels as model systems was assessed to elucidate the link between microscopic diffusion behavior and macroscopic penetration of such gels. Differences in particle adhesion to mucus components were strongly dependent on particle coating. Particles coated with 2 kDa PEG exhibited a decreased adhesion to mucus components, whereas chitosan strongly increased the adhesion. Despite such mucoinert properties of PEG, magnetic nanoparticles of both coatings did not penetrate through native respiratory mucus, resisting high magnetic forces (even for several hours). However, model hydrogels were, indeed, penetrated by both particles in dependency of particle coating, obeying the theory of particle mobility in an external force field. Comparison of penetration data with cryogenic scanning EM images of mucus and the applied model systems suggested particularly high rigidity of the mucin scaffold and a broad pore size distribution in mucus as reasons for the observed particle immobilization. Active probing of the rigidity of mucus and model gels with optical tweezers was used in this context to confirm such properties of mucus on the microscale, thus presenting the missing link between micro- and macroscopical observations. Because of high heterogeneity in the size of the voids and pores in mucus, on small scales, particle mobility will depend on adhesive or inert properties. However, particle translocation over distances larger than a few micrometers is restricted by highly rigid structures within the mucus mesh.
A Simple and Uniform Way to Introduce Complimentary Asynchronous Interaction Models in an Existing Document Analysis System (2012)

Extracting and indexing meaningful contents from degraded documents, like historical ones, is a challenging problem. Existing analysis systems usually rely on a manual correction of results during the post-processing stage, and cannot make use of external information to adapt their response. This paper presents how an existing document analysis system can be easily adapted to enable an efficient interaction during the analysis stage, and benefit from external information. We identify the minimal architecture required, and we detail the two complimentary interaction models we propose: a directed interaction model which allows to handle cases where errors can be automatically detected, and a spontaneous interaction model which permits to cope with the other cases. Both models are asynchronous to prevent the human operator or the system from waiting for each other during document processing. They are based on a common foundation which uses standard exception-like mechanisms to implement error detection, correction and recovery aspects. Our system was tested on several tasks. For instance, for the transcription of handwritten words in documents dating from the 18th century, where we were able to diminish the human workload by 28% for an overall recognition rate of 80%.
Truncation of Limonene Synthase Preprotein Provides a Fully Active ‘Pseudomature' Form of This Monoterpene Cyclase and Reveals the Function of the Amino-Terminal Arginine Pair (1998)

The monoterpene cyclase limonene synthase transforms geranyl diphosphate to a monocyclic olefin and constitutes the simplest model for terpenoid cyclase catalysis. (-)-4S-Limonene synthase preprotein from spearmint bears a long plastidial targeting sequence. Difficulty expressing the full-length preprotein in Escherichia coli is encountered because of host codon usage, inclusion body formation, and the tight association of bacterial chaperones with the transit peptide. The purified preprotein is also kinetically impaired relative to the mixture of N-blocked native proteins produced in vivo by proteolytic processing in plastids. Therefore, the targeting sequence, that precedes a tandem pair of arginines (R58R59) which is highly conserved in the monoterpene synthases, was removed. Expression of this truncated protein, from a vector that encodes a tRNA for two rare arginine codons (pSBET), affords a soluble, tractable 'pseudomature' form of the enzyme that is catalytically more efficient than the native species. Truncation up to and including R58, or substitution of R59, yields enzymes that are incapable of converting the natural substrate geranyl diphosphate, via the enzymatically formed tertiary allylic isomer 3S-linalyl diphosphate, to (-)-limonene. However, these enzymes are able to cyclize exogenously supplied 3S-linalyl diphosphate to the olefinic product. This result indicates a role for the tandem arginines in the unique diphosphate migration step accompanying formation of the intermediate 3S-linalyl diphosphate and preceding the final cyclization reaction catalyzed by the monoterpene synthases. The structural basis for this coupled isomerization-cyclization reaction sequence can be inferred by homology modeling of (-)-4S-limonene synthase based on the three-dimensional structure of the sesquiterpene cyclase epi-aristolochene synthase [Starks, C. M., Back, K., Chappell, J., and Noel, J. P. (1997) Science 277, 1815-1820].
Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. (1991)

A human cDNA coding for a protein related to the vascular permeability factor (VPF) was isolated from a term placenta cDNA library; we therefore named its product placenta growth factor (PlGF). PlGF is a 149-amino-acid-long protein and is highly homologous (53% identity) to the platelet-derived growth factor-like region of human VPF. Computer analyses reveal a putative signal peptide and two probable N-glycosylation sites in the PlGF protein, one of which is also conserved in human VPF. By using N-glycosidase F, tunicamycin, and specific antibodies produced in both chicken and rabbit, we demonstrate that PlGF, derived from transfected COS-1 cells, is actually N-glycosylated and secreted into the medium. In addition, PlGF, like VPF, proves to be a dimeric protein. Finally, a conditioned medium from COS-1 cells containing PlGF is capable of stimulating specifically the growth of CPA, a line of endothelial cells, in vitro.
Aldehyde dehydrogenases: Widespread structural and functional diversity within a shared framework (1993)

Sequences of 16 NAD and/or NADP-linked aldehyde oxidoreductases are aligned, including representative examples of all aldehyde dehydrogenase forms with wide substrate preferences as well as additional types with distinct specificities for certain metabolic aldehyde intermediates, particularly semialdehydes, yielding pairwise identities from 15 to 83%. Eleven of 23 invariant residues are glycine and three are proline, indicating evolutionary restraint against alteration of peptide chain-bending points. Additionally, another 66 positions show high conservation of residue type, mostly hydrophobic residues. Ten of these occur in predicted beta-strands, suggesting important interior-packing interactions. A single invariant cysteine residue is found, further supporting its catalytic role. A previously identified essential glutamic acid residue is conserved in all but methyl malonyl semialdehyde dehydrogenase, which may relate to formation by that enzyme of a CoA ester as a product rather than a free carboxylate species. Earlier, similarity to a GXGXXG segment expected in the NAD-binding site was noted from alignments with fewer sequences. The same region continues to be indicated, although now only the first glycine residue is strictly conserved and the second (usually threonine) is not present at all, suggesting greater variance in coenzyme-binding interactions.
Transplants of Fibroblasts Genetically Modified to Express BDNF Promote Regeneration of Adult Rat Rubrospinal Axons and Recovery of Forelimb Function (1999)

Adult mammalian CNS neurons do not normally regenerate their severed axons. This failure has been attributed to scar tissue and inhibitory molecules at the injury site that block the regenerating axons, a lack of trophic support for the axotomized neurons, and intrinsic neuronal changes that follow axotomy, including cell atrophy and death. We studied whether transplants of fibroblasts genetically engineered to produce brain-derived neurotrophic factor (BDNF) would promote rubrospinal tract (RST) regeneration in adult rats. Primary fibroblasts were modified by retroviral-mediated transfer of a DNA construct encoding the human BDNF gene, an internal ribosomal entry site, and a fusion gene of lacZ and neomycin resistance genes. The modified fibroblasts produce biologically active BDNF in vitro. These cells were grafted into a partial cervical hemisection cavity that completely interrupted one RST. One and two months after lesion and transplantation, RST regeneration was demonstrated with retrograde and anterograde tracing techniques. Retrograde tracing with fluorogold showed that approximately 7% of RST neurons regenerated axons at least three to four segments caudal to the transplants. Anterograde tracing with biotinylated dextran amine revealed that the RST axons regenerated through and around the transplants, grew for long distances within white matter caudal to the transplant, and terminated in spinal cord gray matter regions that are the normal targets of RST axons. Transplants of unmodified primary fibroblasts or Gelfoam alone did not elicit regeneration. Behavioral tests demonstrated that recipients of BDNF-producing fibroblasts showed significant recovery of forelimb usage, which was abolished by a second lesion that transected the regenerated axons.
The Chromatographic Determination of Cystine and Cysteine Residues in Proteins as S-β-(4-Pyridylethyl)cysteine (1970)

Abstract Disulfide bonds in proteins and in seed meals were reduced with β-mercaptoethanol to sulfhydryl groups. The generated sulfhydryl groups were then alkylated by treatment with 4-vinylpyridine. The cysteine residues were thus derivatized to S-(4-pyridylethyl)-l-cysteine residues. The cysteine derivative is stable to acid hydrolysis and on amino acid analysis by ion exchange elutes just before arginine. Complete modification of sulfhydryl groups permits quantitative determination of cysteine and cystine content (half-cystine residues) of proteins and of seed meals. The sulfhydryl groups of cysteine are the only groups modified when the alkylation is performed on solutions of reduced proteins at pH 7.5 for 90 to 120 min with an amount of 4-vinylpyridine equivalent to the mercaptoethanol used for reduction. In order to obtain complete modification of the sulfhydryl groups in seed meals, a longer reaction time, 4.5 hours, and a concentration of 4-vinylpyridine equivalent to 3 times the mercaptoethanol concentration were required.
Synthesis and Characterization of a New Efficient Blue-Light-Emitting Copolymer (1995)

In this paper we present the synthesis, the characterization, and the use in light-emitting diodes of a new blue-light-emitting copolymer, poly[2,5,2'',5''-tetraoctyl-p-terphenyl-4,4''-ylenevinylene-p-phenylenevinylene]. This copolymer, obtained by a poly-Heck reaction, has a fully unsaturated backbone consisting of regularly alternating terphenylene and phenylenebisvinylene blocks. The presence of well-defined chromophores, resulting from steric interactions in the polymer chain, gives rise to bright blue fluorescence, both in solution and in thin solid films. Blue-light-emitting diodes were fabricated by using this copolymer as an emitter layer.