gebhart/patrepeval huggingface dataset:
Simple Metric For Scaling Motor Threshold Based on Scalp-Cortex Distance: Application to Studies Using Transcranial Magnetic Stimulation (2005)

Transcranial magnetic stimulation (TMS) is a unique method in neuroscience used to stimulate focal regions of the human brain. As TMS gains popularity in experimental and clinical domains, techniques for controlling the extent of brain stimulation are becoming increasingly important. At present, TMS intensity is typically calibrated to the excitability of the human motor cortex, a measure referred to as motor threshold (MT). Although TMS is commonly applied to nonmotor regions, most applications do not consider the effect of changes in distance between the stimulating device and underlying neural tissue. Here we show that for every millimeter from the stimulating coil, an additional 3% of TMS output is required to induce an equivalent level of brain stimulation at the motor cortex. This abrupt spatial gradient will have crucial consequences when TMS is applied to nonmotor regions because of substantial variance in scalp-cortex distances over different regions of the head. Stimulation protocols that do not account for cortical distance therefore risk substantial under- or overstimulation. We describe a simple method for adjusting MT to account for variations in cortical distance, thus providing a more accurate calibration than unadjusted MT for the safe and effective application of TMS in clinical and experimental neuroscience.
Stereocontrolled Photocyclization of 1,2-Diketones: Application of a 1,3-Acetyl Group Transfer Methodology to Carbohydrates (2008)

Photolysis of 1-glycosyl-2,3-butanodione derivatives using visible light is a mild and selective procedure for the synthesis of chiral 1-hydroxy-1-methyl-5-oxaspiro[3.5]nonan-2-one carbohydrate derivatives. The results strongly suggest that stereocontrol of the cyclization is dependent on conformational and stereoelectronic factors. Further oxidative opening of the 1-hydroxy-1-methyl-2-cyclobutanone moiety affords new C-ketoside derivatives either in C- and O-glycoside series. This tandem two-step process could be considered to be a stereocontrolled 1,3-transference of an acetyl group, and it can be applied either to pyranose and furanose models.
ALIVE: A distributed live-link documentation system (1992)

This paper presents the ALIVE project, which has been developed at Italtel to provide the means for automatic management of technical documentation. The main goal of ALIVE is to enable the user of a technical publishing system to establish live-links with data stored on remote databases. Live-links allow for automatic update of a document with database contents: whenever a modification occurs in the database data referenced from the document text, the document is updated accordingly.
Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer (2005)

Disruption of the cell-cell junction with concomitant changes in the expression of junctional proteins is a hallmark of cancer cell invasion and metastasis. The role of adherent junction proteins has been studied extensively in cancer, but the roles of tight junction (TJ) proteins are less well understood. Claudins are recently identified members of the tetraspanin family of proteins, which are integral to the structure and function of TJs. Recent studies show changes in expression/cellular localization of claudins during tumorigenesis; however, a causal relationship between claudin expression/localization and cancer has not been established. Here, we report an increased expression of claudin-1 in human primary colon carcinoma and metastasis and in cell lines derived from primary and metastatic tumors. We also report frequent nuclear localization of claudin-1 in these samples. Genetic manipulations of claudin-1 expression in colon cancer cell lines induced changes in cellular phenotype, with structural and functional changes in markers of epithelial-mesenchymal transition. Furthermore, we demonstrate that changes in claudin-1 expression have significant effects on growth of xenografted tumors and metastasis in athymic mice. We further provide data suggesting that the regulation of E-cadherin expression and beta-catenin/Tcf signaling is a possible mechanism underlying claudin-1-dependent changes.
Targeted delivery of biologic and other antineoplastic agents (1992)

This review summarizes several strategies under investigation for targeted delivery of antineoplastic agents to tumor cells, which avoids normal tissue damage. Monoclonal antibodies remain the molecules of choice for targeted therapy, and several improvements to immunotargeting are discussed. These improvements include the use of novel radioisotopes, cytokines, new linkers for chemotherapeutic drugs, more potent drugs, and improved immunotoxins. Bifunctional antibodies, in which one antigen-binding site recognizes a tumor-associated antigen and the other an antineoplastic agent, have been investigated for radioimmunotherapy and for the activation of cytotoxic cells for targeted immunotherapy. The activation of relatively nontoxic prodrugs by antibody-enzyme conjugates is increasingly being investigated in an effort to reduce the systemic toxicity associated with conventional chemotherapy. Finally, the use of liposomes as carriers of drugs or as activators of macrophages is described.
Induction of tolerance to human factor VIII in mice (2001)

This paper reports loss of human factor VIII (hFVIII) inhibitory antibody in immunocompetent C57BL/6 mice. High-titer anti-hFVIII antibody developed in the mice within 7 to 14 days of intraportal administration of adeno-associated virus (AAV) carrying FVIII that coincided with a reduction in plasma hFVIII antigen. Bethesda titers (> 100 units) persisted relatively unchanged for 9 to 10 months. Unexpectedly, at 10 months after injection of the virus, hFVIII protein (up to 59 ng/mL) was detected in 3 mice at the same time as disappearance of hFVIII inhibitor. The level of hFVIII was similar to that found in immunodeficient mice receiving the same dose of recombinant AAV carrying hFVIII without hFVIII inhibitor. These results suggest that tolerance to hFVIII can be induced by sustained expression of hFVIII in a mouse model. Further elucidation of this observation may affect use of FVIII gene transfer in the treatment of inhibitor-positive patients with hemophilia A.
CpG methylation as a tool to characterize cell-free Epstein-Barr virus DNA (2012)

Figure 1 (A) DNA isolated from purified EBV virions or from latently infected Raji cells were subjected to binding to paramagnetic beads linked to methylCpG binding protein. DNA isolated from the non-captured fraction (NC), washes (300mM and 400mM) and the elution (2000mM) was subjected to real-time PCR with primers that amplify a region in EBV BamW. (B) DNA isolated from the plasma of an AIDS patient and the plasma of a patient with EBV(+) Hodgkin lymphoma was subjected to binding to paramagnetic beads linked to methylCpG binding protein. DNA isolated from the different fractions was amplified as in B.
Exploring development and disease through germ-line genetic engineering in the mouse (1998)

New developments in mouse genetics have transformed the field of genetics from a reactive to a proactive science. Current technologies in transgenesis, chromosome engineering, and saturation mutagenesis are introduced. These approaches permit the creation of new mutations and consequent mutant phenotypes that facilitate both the understanding of functions of existing genes and the search for previously unidentified genes affecting important phenotypes in all mammals.
Pyrrole chemistry. XVII. Alkylation of the pyrrolyl ambident anion (1977)

A series of experiments were carried out to find optimum conditions for C- and N-alkylation of the pyrrolyl ambident anion. While almost total C-alkylation could be obtained, isolation of a single alkylation product was not feasible. However, N-alkylation of pyrrole and several 2-substituted pyrroles was readily achieved by phase transfer catalysis with primary alkyl halides.
Androgen Therapy in Women: An Endocrine Society Clinical Practice Guideline (2006)

We recommend against making a diagnosis of androgen deficiency in women at present because of the lack of a well-defined clinical syndrome and normative data on total or free testosterone levels across the lifespan that can be used to define the disorder. Although there is evidence for short-term efficacy of testosterone in selected populations, such as surgically menopausal women, we recommend against the generalized use of testosterone by women because the indications are inadequate and evidence of safety in long-term studies is lacking. A review of the data currently available is presented, and areas of future research are outlined. To formulate clinical guidelines for use of testosterone in women, additional information will be necessary. This includes defining conditions that, when not treated with androgens, have adverse health consequences to women; defining clinical and laboratory parameters that distinguish those with these conditions; and assessing the efficacy and long-term safety of androgen administration on outcomes that are important to women diagnosed with these conditions. This necessary clinical research cannot occur until the biological, physiological, and psychological underpinnings of the role of androgens in women and candidate disorders are further elucidated.
Random heteropolymers preserve protein function in foreign environments (2018)

The successful incorporation of active proteins into synthetic polymers could lead to a new class of materials with functions found only in living systems. However, proteins rarely function under the conditions suitable for polymer processing. On the basis of an analysis of trends in protein sequences and characteristic chemical patterns on protein surfaces, we designed four-monomer random heteropolymers to mimic intrinsically disordered proteins for protein solubilization and stabilization in non-native environments. The heteropolymers, with optimized composition and statistical monomer distribution, enable cell-free synthesis of membrane proteins with proper protein folding for transport and enzyme-containing plastics for toxin bioremediation. Controlling the statistical monomer distribution in a heteropolymer, rather than the specific monomer sequence, affords a new strategy to interface with biological systems for protein-based biomaterials.
Characterization of G-Protein-Gated K+Channels Composed of Kir3.2 Subunits in Dopaminergic Neurons of the Substantia Nigra (1999)

G-protein-gated K+ (KG) channels generate slow inhibitory postsynaptic potentials in the brain. Current opinion suggests that neuronal KG channels are heterotetramers of Kir3.1 and Kir3.2. In substantia nigra (SN), however, mRNA of Kir3.1 does not express, whereas that of Kir3.2 clearly does. Therefore, we have characterized the KG channels containing Kir3.2 subunits in SN using biochemical and immunological techniques. We found that they were composed of only Kir3.2 subunits and did not contain significant amounts of either Kir3.1 or Kir3.3. Furthermore, at least some of the KG channels in SN were assemblies of the splicing variants Kir3. 2a and Kir3.2c. The channels were localized specifically at the postsynaptic membrane on the dendrites of dopaminergic neurons. Kir3. 2c, but not Kir3.2a, could bind a PDZ domain-containing protein, PSD-95. The heterologously expressed KG channels composed of Kir3.2a plus Kir3.2c or Kir3.2a alone were activated by G-protein stimulation, but expression of Kir3.2c alone was not. This study reveals that the Kir3.2 splicing variants play distinct roles in the control of function and localization of some of the KG channels in dopaminergic neurons of SN.
Modular Structure of Peptide Synthetases Revealed by Dissection of the Multifunctional Enzyme GrsA (1995)

Analysis of the primary structure of peptide synthetases involved in non-ribosomal synthesis of peptide antibiotics revealed a highly conserved and ordered domain structure. These functional units, which are about 1000 amino acids in length, are believed to be essential for amino acid activation and thioester formation. To delineate the minimal extension of such a domain, we have amplified and cloned truncated fragments of the grsA gene, encoding the 1098-amino acid multifunctional gramicidin S synthetase 1, GrsA. The overexpressed His6-tagged GrsA derivatives were affinity-purified, and the catalytic properties of the deletion mutants were examined by biochemical studies including ATP-dependent amino acid activation, carboxyl thioester formation, and the ability to racemize the covalently bound phenylalanine from L- to the D-isomer. These studies revealed a core fragment (PheAT-His) that comprises the first 656 amino acid residues of GrsA, which restored all activities of the native protein, except racemization of phenylalanine. A further deletion of about 100 amino acids at the C-terminal end of the GrsA core fragment (PheAT-His), including the putative thioester binding motif LGGHSL, produced a 556-amino acid fragment (PheA-His) that shows a phenylalanine-dependent aminoacyl adenylation, but almost no thioester formation. A 291-amino acid deletion at the C terminus of the native GrsA, that contains a putative racemization site resulted in complete loss of racemization ability (PheATS-His). However, it retained the functions of specific amino acid activation and thioester formation. The results presented defined biochemically the minimum size of a peptide synthetase domain and revealed the locations of the functional modules involved in substrate recognition and ATP-dependent activation as well as in thioester formation and racemization.
Prospects and problems of gene therapy: an update (2001)

The gene therapy approach can vary from delivering extra copies of a gene, through modifications of a genome using the properties of ribozymes or chimeraplasts, to injection of modified cells. For the treatment of genetic deficits the ultimate goal would be the repair of the mutated gene in the target tissue(s). The techniques required for such an approach are emerging, albeit slowly. Therefore, delivery of an extra copy of a normal gene in a specific vector remains the predominant approach. Moreover, this method finds wider applications in gene therapy relating to disorders other than heritable defects, e.g., malignancies, cardiovascular diseases and infections. The major and most intensive areas of research are: i) vectors and delivery methods, ii) regulation of transgene expression and iii) stability of expression. Targeting of the therapeutic gene is being accomplished by using viral vectors or non-viral delivery systems, either ex vivo or in vivo. The choice of vectors and delivery routes depends on the nature of the target cells and the required levels and stability of expression. Although there have been the first positive clinical results and significant technical achievements over the past 2 years, there are still obstacles to the development of effective clinical products and these remain largely unchanged. The most important barriers are the low levels and stability of expression and immune responses to vectors and/or gene products. The safety aspects of gene therapy have become painfully evident with the first death conclusively linked to gene therapy. The progress in AAV and lentiviral vectors, improved regulation of transgene expression and advances in stem cell technology are among the recent most exciting developments.
One-chain urokinase-type plasminogen activator from human sarcoma cells is a proenzyme with little or no intrinsic activity. (1988)

We have compared the plasminogen activating capacity of one- and two-chain urokinase-type plasminogen activator (u-PA). In a 125I-plasminogen conversion assay in the presence of high amounts of a plasmin inhibitor, one-chain u-PA pretreated with diisopropyl fluorophosphate had no detectable activity, the detection limit corresponding to the activity of a 400-fold lower amount of two-chain u-PA. In coupled assays in which generated plasmin was measured with a synthetic substrate, activity was clearly observed with the one-chain preparation, but the initial rate of plasminogen activation was lower than that of a 250-fold smaller concentration of two-chain u-PA. The coupled assays for one-chain u-PA are self-activating because plasmin catalyzes conversion of one- to two-chain u-PA, and it is not possible to decide whether the low activity of one-chain u-PA observed with this type of assay is intrinsic or due to contaminations. On the basis of these findings and a discussion of previous studies, it is concluded that one-chain u-PA has a variety of properties similar to the one-chain proenzyme forms of other serine proteases and that it should, therefore, be considered as a genuine proenzyme form of u-PA.
Urartian Gardens (2000)

Urartians placed great importance on the establishment of vineyards and gardens. Gardens could be dedicated to kings, nobility, royal consorts or their daughters and gods. Prominence was assigned to the cultivation of fruits and vegetables in their gardens, which were situated in proximity to channels of water. Nonetheless, their overall area was on a fairly small scale. Within the gardens, pavilions were erected upon posts with stone bases. During the hot, summer months, they took on the appearance of arbors. Arbored gardens of this type lay on the south slopes below the citadels of Çavuştepe and Aşağı Anzaf. The Urartians not only dedicated vineyards to the gods, they also offered animal sacrifices to the god Haldi at ritual ceremonies held in vineyards bearing their own names. For this reason, just as in the Near East, their gardens bore a religious significance. This concept of the garden differs both from the early examples of the Assyrian Empire, which were designed for practical purposes only, and those of the Sargonid period, which were showy and served as pleasure haunts.
Translation of open reading frame E5 of bovine papillomavirus is required for its transforming activity. (1986)

A series of mutations in open reading frame (ORF) E5 of bovine papillomavirus type 1 has been constructed to determine whether this putative gene is required for in vitro oncogenic transformation by viral DNA. Frameshift mutations at either of two different positions located exclusively in ORF E5 cause a substantial reduction in the ability of the cloned viral DNA to induce the appearance of transformed foci of mouse C127 cells. A genetic mapping experiment with one of the mutants indicates that this characteristic transformation defect is actually due to the constructed mutation in ORF E5. Analysis of 10 different mutants with sequence changes at a single position in the ORF showed that there is an exact correspondence between transformation-competence and the ability of the 3' half of ORF E5 to be correctly translated. The transformation defect of an ORF E5 frameshift mutant can be suppressed by a second mutation that restores the correct reading frame to most of the ORF, but not by one that restores the reading frame near the 3' end of the ORF. These results constitute strong genetic evidence that translation of ORF E5 is required for efficient transformation of mouse C127 cells by bovine papillomavirus DNA. Wild-type ORF E5 has the potential to encode a short hydrophobic protein or polypeptide domain.
MFCompress: a compression tool for FASTA and multi-FASTA data (2013)

Both source code and binaries for several operating systems are freely available for non-commercial use at http://bioinformatics.ua.pt/software/mfcompress/.
Direct Evidence of GeO Volatilization from GeO2/Ge and Impact of Its Suppression on GeO2/Ge Metal–Insulator–Semiconductor Characteristics (2008)

From the studies on the thermal desorption behaviors of GeO2 film and its impact on the electrical properties of GeO2/Ge metal–insulator–semiconductor (MIS) capacitors, it was clarified that the GeO volatilization is driven by the interface reaction at GeO2/Ge, and that volatilization is the origin of the interface deterioration of the MIS capacitors. We found that a Si cap layer formed on top of the GeO2 film suppresses the GeO desorption very efficiently. Then, a marked improvement of the capacitance–voltage (C–V) characteristics was successfully demonstrated with the GeO2/Ge MIS capacitors fabricated by capped annealing process, where a Ni silicide electrode was used as the cap layer. These results provided us quite an important guide for realizing high-quality Ge/dielectric interfaces.
Protein subunit interfaces: heterodimers versus homodimers (2005)

Protein dimers are either homodimers (complexation of identical monomers) or heterodimers (complexation of non-identical monomers). These dimers are common in catalysis and regulation. However, the molecular principles of protein dimer interactions are difficult to understand mainly due to the geometrical and chemical characteristics of proteins. Nonetheless, the principles of protein dimer interactions are often studied using a dataset of 3D structural complexes determined by X-ray crystallography. A number of physical and chemical properties govern protein dimer interactions. Yet, a handful of such properties are known to dominate protein dimer interfaces. Here, we discuss the differences between homodimer and heterodimer interfaces using a selected set of interface properties.
Activation during preparation of therapeutic platelets affects deterioration during storage: a comparative flow cytometric study of different production methods (1997)

Three different separation methods, all using centrifugation, are routinely used to prepare therapeutic platelet concentrates from human donor blood. Platelet concentrates derived from platelet-rich plasma (PRP-PC), buffy coat (BC-PC) and apheresis (AP-PC) were investigated at the end of production, and over an 8 d storage period. Change in platelet surface markers were measured by flow cytometry, using fluorescein-conjugated antibodies to fibrinogen, P-selectin (CD62P), GPIIb-IIIa (CD41), GPIb alpha (CD42b) and GPV (CD42d), and fluorescein-conjugated Annexin V was used to measure expression of anionic phospholipid. All concentrates showed some changes during preparation but PRP-PC underwent the greatest changes with significantly higher levels of P-selectin (P<0.001) and bound Annexin V (P=0.001) than AP-PC or BC-PC, and lower levels of GPIb alpha (P=0.002) and GPV (P<0.001). These changes were attributable to component separation rather than venesection. These markers all continued to change on storage with a strong positive correlation between the changes seen during production and those after 5 d storage. PRP-PC continued to show the greatest changes whereas BC-PC showed the least. Fibrinogen was bound to 40-50% of platelets in all preparations and this did not alter significantly on storage whereas total expression of GPIIb-IIIa remained unchanged throughout. There was no evidence that the platelet surface changes were thrombin-mediated and leucocyte depletion of BP-PC by filtration had no effect on the changes. It is proposed that the deterioration of platelet concentrates during storage may be related to activation occurring during preparation. 'Whole blood' flow cytometry using a panel of fluorescein-labelled reagents provides an informative method for evaluating platelet concentrates.
SYNTHESIS OF ARYL IODIDES FROM ARYL HALIDES AND POTASSIUM IODIDE BY MEANS OF NICKEL CATALYST (1978)

Abstract Facile synthesis of aryl iodides from aryl halides was reported. NiBr2–Zn catalyzed the halogen exchange reaction of aryl bromides with potassium iodide under mild conditions. At elevated temperatures, NiBr2–PBu3 was an effective catalyst.