gebhart/patrepeval huggingface dataset:
Combined iron chelation therapy (2010)

Patients with thalassemia major accumulate body iron over time as a consequence of continuous red blood cell transfusions which cause hepatic, endocrine, and cardiac complications. Despite the availability of three iron chelators, some patients fail to respond adequately to monotherapy with any of them. Combination therapy, consisting in the use of two chelators on the same day, has been introduced to increase the efficacy and to induce negative iron balance in patients with severe iron overload. Extensive long-term experience has shown that combined chelation with deferiprone and deferoxamine (DFO) rapidly reduces liver iron, serum ferritin, and myocardial siderosis, improves cardiac function, reverses and prevents endocrine complications, reduces cardiac mortality, and improves survival. Side effects, though significant, are manageable if properly monitored. Preliminary promising results have been obtained using combined chelation with deferasirox and DFO. As more drug combination regimes are evaluated, it should be possible to better tailor iron chelation to the needs of the patients, minimizing toxicity and maximizing efficacy throughout life.
Cellular Distribution of Torsin A and Torsin B in Normal Human Brain (2001)

Torsin A and torsin B have similar distribution in the central nervous system, although their subcellular localization is not identical. Strong expression in neuronal processes points to a potential role for torsin proteins in synaptic functioning.
Epitope-tagged ubiquitin. A new probe for analyzing ubiquitin function. (1991)

In the present work, a method based on an epitope-tagged ubiquitin derivative is described that allows for the unambiguous detection of ubiquitin-protein conjugates formed in vivo or in vitro. Expression in the yeast Saccharomyces cerevisiae of ubiquitin that has been tagged at its amino terminus with a peptide epitope results in the formation of tagged ubiquitin-protein conjugates that are detectable by immunoblotting with a monoclonal antibody that recognizes the tag. The expression of tagged ubiquitin has no adverse effect on vegetative growth and, moreover, can suppress the stress-hypersensitive phenotype of yeast lacking the polyubiquitin gene UBI4. We also show that tagged ubiquitin is correctly conjugated in vivo and in vitro to a short-lived test protein and can be covalently extended into the multimeric ubiquitin chain that is normally required for the degradation of this protein. Surprisingly, however, conjugation of tagged ubiquitin inhibits proteolysis. These and related results suggest that the amino-terminal region of ubiquitin is important in protease-substrate recognition and that the multiubiquitin chain is a dynamic transient structure. The potential of tagged ubiquitin for the identification and isolation of ubiquitin-protein conjugates and ubiquitin-related enzymes, and as a tool in mechanistic studies is discussed.
KIDNEY PRESERVATION FOR TRANSPORTATION 5. COMPARISON OF PERFUSATES FOR HYPOTHERMIC STORAGE (1971)

A new perfusate, solution C3, was compared with plasma and a dextran-based plasma substitute in a 24-hour hypothermic kidney storage model. As judged by the rise in serum creatinine level following autografting of the stored kidney and immediate contralateral nephrectomy, solution C3 was significantly better than the other perfusates tested. It is recommended that this perfusate be used in preference to conventional solutions for the preservation of human cadaveric kidneys.
Sucrose-Starch Conversion in Heterotrophic Tissues of Plants (1999)

The historical progress in recent years pertaining to the sucrose-starch conversion in heterotrophic tissues of plants has been described. Special attention has been focused on the enzymatic breakdown of sucrose to produce hexose units that are transported to the amyloplast compartment by means of specific translocator molecules and act as glucose donors for starch biosynthesis. Although the current prevailing view is that variable mechanisms operate in different plant tissues and organs, it is often argued that the following enzymic steps are essential in the overall step of sucrose to starch conversion: sucrose + UDP -> UDPGlc + Fru(sucrose synthase-SS) (UDPGlc UDPGlc + PPi -» G1P + UTPpyrophosphorylase-UGPase) (ADPGlc GlP + ATP -» ADPGlc + PPipyrophosphorylase-AGPase) (starch ADPGlc -> starchsynthase) The presence of an ADPGlc-specific translocator in the amyloplast envelope has been demonstrated in a number of plant sources, which indicates the potential role of ADPGlc-synthesizing machineries located in the cytosol of starch-storing cells. Although it was initially believed that AGPase is present exclusively in the amyloplast compartment, the presence of a cytosolic enzyme has been shown in some cereals. The SS has a potential to produce ADPGlc, but the general belief is that this is not a dominant reaction in the mechanism of starch biosynthesis. Numerous experimental trials have been reported by many scientists employing transgenic plants transformed with cDNAs either in antisense- or sense- orientation encoding enzymes which are presumably involved in the process of sucrose-starch conversion. Although great caution is needed to interpret the data obtained, the general picture is contradictory to the mechanism presented above. It now appears that serious reconsideration is needed for the possible mechanism of SS-catalyzed ADPGlc formation and its subsequent link to starch formation. In the newly proposed mechanistic scheme, which appears to be consistent with the results by other scientists as well, hexokinase, phosphoglucomutase (PGM), and ADPGlc formation by AGPase are components in the cyclic turnover of starch molecules in the amyloplast compartment.
A Controlled Trial of a Two-Component Acellular, a Five-Component Acellular, and a Whole-Cell Pertussis Vaccine (1996)

The five-component acellular pertussis vaccine we evaluated can be recommended for general use, since it has a favorable safety profile and confers sustained protection against pertussis. The two-component acellular vaccine and the whole-cell vaccine were less efficacious.
[Limited proteolysis of human leukocyte interferon-alpha2 and localization of the antigenic determinant binding the monoclonal antibodies]. (1985)

Large peptide fragments of human leucocyte interferon-alpha 2 (INF-alpha 2) were obtained by limited proteolysis with trypsin, pepsin, thermolysine and Bacillus amyloliquefaciens intracellular serine proteinase. The ability of the fragments to bind murine monoclonal antibodies NK2 raised against INF-alpha 2 was studied by the immunoblotting technique. The region of sequence 110-149 is the most sensitive to proteolytic attack, being probably exposed on the surface of the INF-alpha 2 molecule. INF-alpha 2 fragments 1-139, 1-147, 1-149 are capable of binding antibodies, whereas fragments 1-109 and 1-112 do not bind antibodies NK2. A comparison of the primary structure of human leucocyte and murine leucocyte INF families in the region of sequence 110-139 and an analysis of the ability of human INF differing in amino acid sequences to bind antibodies NK2 demonstrated that the antigenic determinant for antibodies NK2 is the sequence Glu114-Asp115-Ser116-Ile117 of the INF-alpha 2 molecule.
A Logic Nanotechnology Featuring Strained-Silicon (2004)

Strained-silicon (Si) is incorporated into a leading edge 90-nm logic technology . Strained-Si increases saturated n-type and p-type metal-oxide-semiconductor field-effect transistors (MOSFETs) drive currents by 10 and 25%, respectively. The process flow consists of selective epitaxial Si/sub 1-x/Ge/sub x/ in the source/drain regions to create longitudinal uniaxial compressive strain in the p-type MOSFET. A tensile Si nitride-capping layer is used to introduce tensile uniaxial strain into the n-type MOSFET and enhance electron mobility. Unlike past strained-Si work: 1) the amount of strain for the n-type and p-type MOSFET can be controlled independently on the same wafer and 2) the hole mobility enhancement in this letter is present at large vertical electric fields, thus, making this flow useful for nanoscale transistors in advanced logic technologies.
Farnesyltransferase inhibitor effects on prostate tumor micro-environment and radiation survival (2004)

FTIs can enhance the killing of prostate tumors with activated H-Ras. Together with the absence of increased acute toxicity to normal bowel, these results imply that FTI treatment should be further studied as a possible adjuvant to radiotherapy in the treatment of abdominal cancers with activated Ras signaling.
Retention and Excretion of Strontium-85 in Mice, Rats and Rabbits-extrapolation to Long-Term Retention in Humans (1965)

The patterns of retention and excretion of 85Sr in mice, rats and rabbits are studied up to 70 ∼ 260 days after a single injection. The results can be fitted with power functions until 100 days, but after that the exponents increase gradually with time. The data on retention in these animals are compared with human results which are known up to 400 days. On the assumption that the patterns of the retention obtained by these small animals are epitomes of that in humans, it is suggested that the long-term retention of Sr in humans will be expressed roughly by 0.80 t−0.30 until 6000 days after injection. The ratios of urine to total excretion are also studied in these animals. The values are compared with human results.
Piezoelectric Field Effect Transistor and Nanoforce Sensor Based on a Single ZnO Nanowire (2006)

Utilizing the coupled piezoelectric and semiconducting dual properties of ZnO, we demonstrate a piezoelectric field effect transistor (PE-FET) that is composed of a ZnO nanowire (NW) (or nanobelt) bridging across two Ohmic contacts, in which the source to drain current is controlled by the bending of the NW. A possible mechanism for the PE-FET is suggested to be associated with the carrier trapping effect and the creation of a charge depletion zone under elastic deformatioin. This PE-FET has been applied as a force/pressure sensor for measuring forces in the nanonewton range and even smaller with the use of smaller NWs. An almost linear relationship between the bending force and the conductance was found at small bending regions, demonstrating the principle of nanowire-based nanoforce and nanopressure sensors.
Styrene polymerization with a macroinitiator having siloxane units (1996)

Block copolymers containing segments of poly(dimethylsiloxane) (PDMS) and polystyrene were synthesized. Dihydroxy terminated PDMS Mn 2500 g/mol, was reacted with an ali-phatic diisocyanate (isophorone diisocyanate) and an aliphatic hydroperxide (t-butyl hy-droperoxide). The resulting polymeric peroxycarbamate having siloxane units (a new mac-roinitiator) was used as free radical initiator for vinyl polymerization of styrene. Formation of block copolymers was illustrated by several characterization methods such as chemical and spectroscopic analysis, fractionation, and GPC. Mechanical and thermal characterization of the copolymers were made by stress–strain tests and DSC. The surface properties and the morphology of the block copolymers were investigated by contact angle measurements and SEM. © 1996 John Wiley & Sons, Inc.
Alterations of the cytokine network in hemodialysis. (2002)

This study focuses on the mechanisms responsible for monocyte activation and enhanced cytokine production in hemodialysis. Particular emphasis is given to recent recognition of a link between cytokine production and chronic inflammation following long-term complications in today's hemodialysis population, namely cardiovascular disease and malnutrition.
Site-specific photochemical RNA editing (2010)

Photo-induced artificial RNA editing was demonstrated using photo-reactive oligonucleotides containing 3-cyanovinylcarbazole nucleoside. This non-enzymatic and sequence-specific methodology will make a major contribution to the elucidation of RNA functions including non-coding RNAs and to the development of drugs based on sequence-specific RNA editing.
Group I metabotropic glutamate receptor‐dependent TRPC channel trafficking in hippocampal neurons (2006)

The group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) elicited two phases of synchronized neuronal (epileptiform) discharges in hippocampal slices: an initial phase of short duration discharges followed by a phase of prolonged discharges. We assessed the involvement of transient receptor potential canonical (TRPC) channels in these responses. Pre-treatment of hippocampal slices with TRPC channel blockers, 1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride (SKF96365) or 2-aminoethoxydiphenyl borate, did not affect the short epileptiform discharges but blocked the prolonged epileptiform discharges. SKF96365 suppressed ongoing DHPG-induced prolonged epileptiform discharges. Western blot analysis showed that the total TRPC4 or TRPC5 proteins in hippocampal slices were unchanged following DHPG. DHPG increased TRPC4 and TRPC5 in the cytoplasmic compartment and decreased these proteins in the plasma membrane. Translocation of TRPC4 and TRPC5 was suppressed when the epileptiform discharges were blocked by ionotropic glutamate receptor blockers. Translocation of TRPC4 and TRPC5 was also prevented in slices from phospholipase C (PLC) beta1 knockout mice, even when synchronized discharges were elicited by the convulsant 4-aminopyridine. The results suggest that TRPC channels are involved in generating DHPG-induced prolonged epileptiform discharges. This function of TRPC channels is associated with a neuronal activity- and PLCbeta1-dependent translocation of TRPC4 and TRPC5 proteins from the plasmalemma to the cytoplasmic compartment.
Human creatine kinase genes on chromosomes 15 and 19, and proximity of the gene for the muscle form to the genes for apolipoprotein C2 and excision repair. (1988)

The human chromosomal assignments of genes of the creatine kinase (CK) family--loci for brain (CKBB), muscle (CKMM), and mitochondrial (CKMT) forms--were studied by Southern filter hybridization analysis of DNAs isolated from a human x rodent somatic cell hybrid clone panel. Probes for the 3'-noncoding sequences of human CKBB and CKMM hybridized concordantly only to DNAs from somatic cell hybrids containing chromosomes 14 and 19, respectively. Thus the earlier assignment of the gene coding for the CKBB isozyme to chromosome 14 was confirmed by molecular means, as was the provisional assignment of CKMM to the long arm of chromosome 19. A probe containing canine sequences for CKMM cross-hybridized with human sequences on chromosomes 14 and 19, a result consistent with the assignments of CKBB and CKMM. A probe containing human sequences for CKMT enabled the provisional assignment of CKMT to human chromosome 15. Independent hybrids with portions of the long arm of chromosome 19 missing indicated the order of genes on the long arm of chromosome 19 as being cen-GPI-(TGFB, CYP1)-[CKMM, (APOC2-ERCC1)]-(CGB, FTL). The unexpectedly more distal location of APOC2 among the genes on the long arm--and APOC2's close association with CKMM--is discussed with respect to the close linkage relationship of APOC2 to myotonic muscular dystrophy.
La pétrectomie combinée: Bases anatomiques, technique chirurgicale et indications (2008)

Abstract Management of large petroclival tumors requires the use of extensive surgical approaches that usually jeopardize the intrapetrous neuro-otologic structures. To confirm the interest of the combined petrosal approach in this indication, we describe the relevant anatomy and the surgical steps of this procedure. After making a periauricular skin incision and muscle elevation, an occipitotemporal bone flap is shaped. Then a retrolabyrinthine exposure is undertaken, with optimal skeletonization of the semicircular canals. Around the internal auditory canal, the retromeatal area and the petrous apex are resected. The retrosigmoid dura is opened followed by the incision of the subtemporal and posterior fossa dura along the superior petrosal sinus. The sinus is coagulated and divided. The tentorium is sectioned transversally toward its free edge behind the porus of the trochlear nerve. The combined petrosal approach is able to provide a wide multidirectional corridor toward the ventral surface of the pons, the basilary trunk and the ipislateral cranial nerves from the oculomotor to the lower cranial nerves. This study confirms that despite a significant extra time needed for proper achievement, the combined petrosal approach is a valuable conservative approach when the petroclival area, ventral brain stem and basilary trunk are targeted. This approach should be included in the panel of the transpetrous routes available by expert skull base teams.
Peroxisomal Proliferator-activated Receptor-γ Coactivator-1α (PGC-1α) Enhances the Thyroid Hormone Induction of Carnitine Palmitoyltransferase I (CPT-Iα) (2004)

Carnitine palmitoyltransferase I (CPT-I) catalyzes the rate-controlling step in the pathway of mitochondrial fatty acid oxidation. Thyroid hormone will stimulate the expression of the liver isoform of CPT-I (CPT-I alpha). This induction of CPT-I alpha gene expression requires the thyroid hormone response element in the promoter and sequences within the first intron. The peroxisomal proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) is a coactivator that promotes mitochondrial biogenesis, mitochondrial fatty acid oxidation, and hepatic gluconeogenesis. In addition, PGC-1 alpha will stimulate the expression of CPT-I alpha in primary rat hepatocytes. Here we report that thyroid hormone will increase PGC-1 alpha mRNA and protein levels in rat hepatocytes. In addition, overexpression of PGC-1 alpha will enhance the thyroid hormone induction of CPT-I alpha indicating that PGC-1 alpha is a coactivator for thyroid hormone. By using chromatin immunoprecipitation assays, we show that PGC-1 alpha is associated with both the thyroid hormone response element in the CPT-I alpha gene promoter and the first intron of the CPT-I alpha gene. Our data demonstrate that PGC-1 alpha participates in the stimulation of CPT-I alpha gene expression by thyroid hormone and suggest that PGC-1 alpha is a coactivator for thyroid hormone.
Metalloporphyrin-catalysed rearrangement of oxaziridines: an efficient and regioselective synthesis of lactams using ring-enlargement of N-phenyl-spirooxaziridines (1994)

K. Suda, M. Sashima, M. Izutsu and F. Hino, J. Chem. Soc., Chem. Commun., 1994, 949 DOI: 10.1039/C39940000949
In Search of Clinical Neuroprotection After Brain Ischemia (2009)

Even when delayed, combined treatment with mild hypothermia and magnesium has broad therapeutic potential as a practical neuroprotective strategy. It warrants further experimental investigation and presents a good case for assessment in clinical trials in treating human patients after brain ischemia.
RETRACTED: Extensive degradation of myelin basic protein isoforms by calpain following traumatic brain injury (2006)

Axonal injury is one of the key features of traumatic brain injury (TBI), yet little is known about the integrity of the myelin sheath. We report that the 21.5 and 18.5-kDa myelin basic protein (MBP) isoforms degrade into N-terminal fragments (of 10 and 8 kDa) in the ipsilateral hippocampus and cortex between 2 h and 3 days after controlled cortical impact (in a rat model of TBI), but exhibit no degradation contralaterally. Using N-terminal microsequencing and mass spectrometry, we identified a novel in vivo MBP cleavage site between Phe114 and Lys115. A MBP C-terminal fragment-specific antibody was then raised and shown to specifically detect MBP fragments in affected brain regions following TBI. In vitro naive brain lysate and purified MBP digestion showed that MBP is sensitive to calpain, producing the characteristic MBP fragments observed in TBI. We hypothesize that TBI-mediated axonal injury causes secondary structural damage to the adjacent myelin membrane, instigating MBP degradation. This could initiate myelin sheath instability and demyelination, which might further promote axonal vulnerability.
Histones and Other Basic Nuclear Proteins (2024)

THE PROTEINS. Human Histone Variants. Histone Occurrence, Isolation, Characterization, and Biosynthesis. Specificity and Distribution of Sperm Basic Proteins. Histone and Basic Nuclear Protein Transitions in Mammalian Spermatogenesis. A Basic Nonhistone Nuclear Protein in Human Myeloid Cells. Posttranslational Modifications of Histones. STRUCTURE, ORGANIZATION, AND REGULATION OF THE GENES. Organization of Histone Genes and Their Variants. Cell Cycle Dependent Human Histone Genes: Their Organization and Regulation. Histone Gene Expression Not Coupled to DNA Synthesis. Structures of Testis-Specific Histones, Spermatid Transition Proteins, and Their Genes in Mammals. Mammalian Protamines and Their Expression. HMG Genes and Their Expression
Functionalized Nanopore-Embedded Electrodes for Rapid DNA Sequencing (2008)

The determination of a patient's DNA sequence can, in principle, reveal an increased risk to fall ill with particular diseases [1,2] and help to design "personalized medicine" [3]. Moreover, statistical studies and comparison of genomes [4] of a large number of individuals are crucial for the analysis of mutations [5] and hereditary diseases, paving the way to preventive medicine [6]. DNA sequencing is, however, currently still a vastly time-consuming and very expensive task [4], consisting of pre-processing steps, the actual sequencing using the Sanger method, and post-processing in the form of data analysis [7]. Here we propose a new approach that relies on functionalized nanopore-embedded electrodes to achieve an unambiguous distinction of the four nucleic acid bases in the DNA sequencing process. This represents a significant improvement over previously studied designs [8,9] which cannot reliably distinguish all four bases of DNA. The transport properties of the setup investigated by us, employing state-of-the-art density functional theory together with the non-equilibrium Green's Function method, leads to current responses that differ by at least one order of magnitude for different bases and can thus provide a much more robust read-out of the base sequence. The implementation of our proposed setup could thus lead to a viable protocol for rapid DNA sequencing with significant consequences for the future of genome related research in particular and health care in general.
Widespread intron retention in mammals functionally tunes transcriptomes (2014)

Alternative splicing (AS) of precursor RNAs is responsible for greatly expanding the regulatory and functional capacity of eukaryotic genomes. Of the different classes of AS, intron retention (IR) is the least well understood. In plants and unicellular eukaryotes, IR is the most common form of AS, whereas in animals, it is thought to represent the least prevalent form. Using high-coverage poly(A)(+) RNA-seq data, we observe that IR is surprisingly frequent in mammals, affecting transcripts from as many as three-quarters of multiexonic genes. A highly correlated set of cis features comprising an "IR code" reliably discriminates retained from constitutively spliced introns. We show that IR acts widely to reduce the levels of transcripts that are less or not required for the physiology of the cell or tissue type in which they are detected. This "transcriptome tuning" function of IR acts through both nonsense-mediated mRNA decay and nuclear sequestration and turnover of IR transcripts. We further show that IR is linked to a cross-talk mechanism involving localized stalling of RNA polymerase II (Pol II) and reduced availability of spliceosomal components. Collectively, the results implicate a global checkpoint-type mechanism whereby reduced recruitment of splicing components coupled to Pol II pausing underlies widespread IR-mediated suppression of inappropriately expressed transcripts.