gebhart/patrepeval huggingface dataset:
Human DNA Ligase IV and the Ligase IV/XRCC4 Complex:  Analysis of Nick Ligation Fidelity (2007)

In addition to linking nicked/fragmented DNA molecules back into a contiguous duplex, DNA ligases also have the capacity to influence the accuracy of DNA repair pathways via their tolerance/intolerance of nicks containing mismatched base pairs. Although human DNA ligase I (Okazaki fragment processing) and the human DNA ligase III/XRCC1 complex (general DNA repair) have been shown to be relatively intolerant of nicks containing mismatched base pairs, the human DNA ligase IV/XRCC4 complex has not been studied in this regard. Ligase IV/XRCC4 is the sole DNA ligase involved in the repair of double strand breaks (DSBs) via the non-homologous end joining (NHEJ) pathway. During the repair of DSBs generated by chemical/physical damage as well as the repair of the programmed DSB intermediates of V(D)J recombination, there are scenarios where, at least conceptually, a capacity for ligating nicks containing mismatched base pairs would appear to be advantageous. Herein we examine whether ligase IV/XRCC4 can contribute a mismatched nick ligation activity to NHEJ. Toward this end, we (i) describe an E. coli-based coexpression system that provides relatively high yields of the ligase IV/XRCC4 complex, (ii) describe a unique rate-limiting step, which has bearing on how the complex is assayed, (iii) specifically analyze how XRCC4 influences ligase IV catalysis and substrate specificity, and (iv) probe the mismatch tolerance/intolerance of DNA ligase IV/XRCC4 via quantitative in vitro kinetic analyses. Analogous to most other DNA ligases, ligase IV/XRCC4 is shown to be fairly intolerant of nicks containing mismatched base pairs. These results are discussed in light of the biological roles of NHEJ.
Structure-Based Design of Potent, Amidine-Derived Inhibitors of Factor Xa:  Evaluation of Selectivity, Anticoagulant Activity, and Antithrombotic Activity (2000)

To enhance the potency of 1,2-dibenzamidobenzene-derived inhibitors of factor Xa (fXa), an amidine substituent was incorporated on one of the benzoyl side chains to interact with Asp189 in the S1 specificity pocket. Lead molecule 1 was docked into the active site of fXa to facilitate inhibitor design. Subsequently, iterative SAR studies and molecular modeling led to a 1000-fold increase in fXa affinity and a refined model of the new inhibitors in the fXa active site. Strong support for the computational model was achieved through the acquisition of an X-ray crystal structure using thrombin as a surrogate protein. The amidines in this series show high levels of selectivity for the inhibition of fXa relative to other trypsin-like serine proteases. Furthermore, the fXa affinity of compounds in this series (K(ass) = 50-500 x 10(6) L/mol) translates effectively into both anticoagulant activity in vitro and antithrombotic activity in vivo.
Animal breeding and disease (2005)

Single-locus disorders in domesticated animals were among the first Mendelian traits to be documented after the rediscovery of Mendelism, and to be included in early linkage maps. The use of linkage maps and (increasingly) comparative genomics has been central to the identification of the causative gene for single-locus disorders of considerable practical importance. The 'score-card' in domestic animals is now more than 100 disorders for which the molecular lesion has been identified and hence for which a DNA test is available. Because of the limited lifespan of any such test, a cost-effective and hence popular means of protecting the intellectual property inherent in a DNA test is not to publish the discovery. While understandable, this practice creates a disconcerting precedent. For multifactorial disorders that are scored on an all-or-none basis or into many classes, the effectiveness of control schemes could be greatly enhanced by selection on estimated breeding values for liability. Genetic variation for resistance to pathogens and parasites is ubiquitous. Selection for resistance can therefore be successful. Because of the technical and welfare challenges inherent in the requirement to expose animals to pathogens or parasites in order to be able to select for resistance, there is a very active search for DNA markers for resistance. The first practical fruits of this research were seen in 2002, with the launch of a national scrapie control programme in the UK.
Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts (2011)

Hutchinson-Gilford progeria syndrome (HGPS), a devastating premature aging disease, is caused by a point mutation in the lamin A gene (LMNA). This mutation constitutively activates a cryptic splice donor site, resulting in a mutant lamin A protein known as progerin. Recent studies have demonstrated that progerin is also produced at low levels in normal human cells and tissues. However, the cause-and-effect relationship between normal aging and progerin production in normal individuals has not yet been determined. In this study, we have shown in normal human fibroblasts that progressive telomere damage during cellular senescence plays a causative role in activating progerin production. Progressive telomere damage was also found to lead to extensive changes in alternative splicing in multiple other genes. Interestingly, elevated progerin production was not seen during cellular senescence that does not entail telomere shortening. Taken together, our results suggest a synergistic relationship between telomere dysfunction and progerin production during the induction of cell senescence, providing mechanistic insight into how progerin may participate in the normal aging process.
Time-Reversal Wireless Paradigm for Green Internet of Things: An Overview (2014)

In this paper, we present an overview of the time-reversal (TR) wireless paradigm for green Internet of Things (IoT). It is shown that the TR technique is a promising technique that focuses signal waves in both time and space domains. The unique asymmetric architecture significantly reduces the cost of the terminal devices, the total number of which is expected to be very large for IoT. The focusing effect of the TR technique can harvest the energy of all the multi-paths at the receiver, which improves the energy efficiency of the wireless transmission and thus the battery life of terminal devices in IoT. Facilitated by the high-resolution spatial focusing, the TR division multiple access scheme leverages the uniqueness of the multi-path profiles in the rich-scattering environment and maps them into location-specific signatures, so that spatial multiplexing can be achieved for multiple users operating on the same spectrum. In addition, the TR system can easily support heterogeneous terminal devices by providing various quality-of-service (QoS) options through adjusting the waveform and rate backoff factor. Finally, the unique location-specific signature in TR system can provide additional physical-layer security and thus can enhance the privacy and security of customers in IoT. All the advantages show that the TR technique is a promising paradigm for IoT.
Fluorescent-oligonucleotide probing of whole cells for determinative, phylogenetic, and environmental studies in microbiology (1990)

Fluorescent-dye-conjugated oligonucleotides were used to classify 14 Fibrobacter strains by fluorescence microscopy. On the basis of partial 16S rRNA sequences of six Fibrobacter strains, four hybridization probes were designed to discriminate between the species Fibrobacter succinogenes and Fibrobacter intestinalis and to identify F. succinogenes subsp. succinogenes. After in situ hybridization to whole cells of the six sequenced strains, epifluorescence microscopy confirmed probe specificity. The four probes were then used to make presumptive species and subspecies assignments of eight additional Fibrobacter strains not previously characterized by comparative sequencing. These assignments were confirmed by comparative sequencing of the 16S rRNA target regions from the additional organisms. Single-mismatch discrimination between certain probe and nontarget sequences was demonstrated, and fluorescent intensity was shown to be enhanced by hybridization to multiple probes of the same specificity. The direct detection of F. intestinalis in mouse cecum samples demonstrated the application of this technique to the characterization of complex natural samples.
An in‐built proteinase inhibitor system for the protection of recombinant proteins recovered from transgenic plants (2006)

Proteolytic degradation represents a significant barrier to the efficient production of several recombinant proteins in plants, both in vivo during their expression and in vitro during their recovery from source tissues. Here, we describe a strategy to protect recombinant proteins during the recovery process, based on the coexpression of a heterologous proteinase inhibitor acting as a 'mouse trap' against the host proteases during extraction. After confirming the importance of trypsin- and chymotrypsin-like activities in crude protein extracts of potato (Solanum tuberosum L.) leaves, transgenic lines of potato expressing either tomato cathepsin D inhibitor (CDI) or bovine aprotinin, both active against trypsin and chymotrypsin, were generated by Agrobacterium tumefaciens-mediated genetic transformation. Leaf crude protein extracts from CDI-expressing lines, showing decreased levels of cathepsin D-like and ribulose 1,5-bisphosphate carboxylase/oxygenase hydrolysing activities in vitro, conducted decreased turnover rates of the selection marker protein neomycin phosphotransferase II (NPTII) relative to the turnover rates measured for transgenic lines expressing only the marker protein. A similar stabilizing effect on NPTII was observed in leaf protein extracts from plant lines coexpressing bovine aprotinin, confirming the ability of ectopically expressed broad-spectrum serine proteinase inhibitors to reproduce the protein-stabilizing effect of low-molecular-weight proteinase inhibitors generally added to protein extraction media.
Evaluation of gastrointestinal motility by computerized analysis of abdominal auscultation findings (2005)

The results of the present study indicate that the abdominal auscultation test could be used as a new diagnostic method to detect any abnormality in gastrointestinal motility.
Double-Hexahistidine Tag with High-Affinity Binding for Protein Immobilization, Purification, and Detection on Ni−Nitrilotriacetic Acid Surfaces (2006)

There is a particular need in protein analysis and purification for specific, functional, and generic methods of protein immobilization on solid supports. Here we describe a double-hexahistidine (His6) tag sequence, comprising two hexahistidines separated by an 11-amino acid spacer, which shows at least 1 order of magnitude stronger binding to Ni-NTA-modified surfaces than a conventional single-His6 tag or two single-His6 tags at N- and C-termini. Using, as a model, tagged versions of green fluorescent protein (GFP), stable and tight binding of the double-His6 tag/Ni-NTA interaction was demonstrated by competitive elution from Ni-NTA agarose beads, surface plasmon resonance on a Ni-NTA chip, and ELISA in Ni-NTA microwell plates. Protein purification by Ni-NTA chromatography was improved by a 6-8-fold increase in imidazole concentration required for elution, while the dissociation rate of double-His6 GFP from Ni-NTA chips in SPR (BIAcore) was 10 times slower than for single-His6-tagged proteins. ELISA assays and protein microarrays constructed with double-His6 GFP demonstrated greater detection sensitivity with anti-His antibodies and Ni-NTA conjugates. Moreover, the double-His6 tag could serve simultaneously both for protein immobilization and for detection on surfaces. The double-His6 peptide has the potential to be a universal tag for protein immobilization and detection on arrays and single-step purification of proteins from crude mixtures.
Effects of Simvastatin on Plasma Lipids and Apolipoproteins in Familial Hypercholesterolemic Swine (1996)

Familial hypercholesterolemia (FHC) in swine, which resembles human familial combined hyperlipidemia, is a complex lipid and lipoprotein disorder associated with the development of severe coronary lesions similar to those occurring in advanced human coronary disease. The disorder is characterized by elevated plasma total cholesterol (TC), triglycerides (TG), LDL-cholesterol (LDL-C), apolipoproteins (apo) B, C-III, and E, and by decreased levels of HDL-cholesterol (HDL-C), apoA-I, and lecithin:cholesterol acyltransferase (LCAT) activity. A dose-response study with simvastatin, a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was conducted in four treatment groups of FHC animals, exhibiting TC > or = 250 mg/dL. The animals were fed 0, 80, 200, or 400 mg simvastatin daily for 3 weeks. The measured serum parameters included the levels of TC, VLDL-C, LDL-C, HDL-C, TG, lathosterol, apoA-I, B, C-III, and E, as well as LCAT activity. Simvastatin at 200 mg/d significantly decreased the levels of TC (-25%), LDL-C (-27%), lathosterol (-40%), apoB (-22%), apoC-III (-37%), and apoE (-24%) and modestly decreased the levels of HDL-C (-12%) and apoA-I (-11%) (percent relative to the average pretreatment and posttreatment baseline values) but did not affect the levels of TG, VLDL-C, the lathosterol/TC ratio, or LCAT activity. The levels of TC, LDL-C, apoB, and E were also lowered by simvastatin at 80 or 400 mg/d, but to a lesser extent than at 200 mg/d, while the other parameters were not influenced at these doses. The simvastatin-induced decreases of LDL-C, HDL-C, and apoA-I, B, C-III, and E were significantly correlated among each other. These results show that the trend of responses in TC, LDL-C, apoB, apoC-III, and apoE to simvastatin in the FHC swine is similar to that observed in humans, although the drugs is less potent and efficacious in swine, while the results are different from those in humans with regard to the remaining parameters.
Dopamine Dependency of Oscillations between Subthalamic Nucleus and Pallidum in Parkinson's Disease (2001)

The extent of synchronization within and between the nuclei of the basal ganglia is unknown in Parkinson's disease. The question is an important one because synchronization will increase postsynaptic efficacy at subsequent projection targets. We simultaneously recorded local potentials (LPs) from the globus pallidus interna (GPi) and subthalamic nucleus (STN) in four awake patients after neurosurgery for Parkinson's disease. Nuclei from both sides were recorded in two patients so that a total of six ipsilateral GPi-STN LP recordings were made. Without medication, the power within and the coherence between the GPi and STN was dominated by activity with a frequency <30 Hz. Treatment with the dopamine precursor levodopa reduced the low-frequency activity and resulted in a new peak at approximately 70 Hz. This was evident in the power spectrum from STN and GPi and in the coherence between these nuclei. The phase relationship between the nuclei varied in a complex manner according to frequency band and the presence of exogenous dopaminergic stimulation. Synchronization of activity does occur between pallidum and STN, and its pattern is critically dependent on the level of dopaminergic activity.
A Method for Automatic Synthesis of Aged Human Facial Images (2004)

In the attitude of silence the soul finds the path in an clearer light, and what is elusive and deceptive resolves itself into crystal clearness.
Genetic background of different cancer cell lines influences the gene set involved in chromosome 8 mediated breast tumor suppression (2006)

Several lines of evidence suggest that chromosome 8 is likely to harbor tumor-suppressor genes involved in breast cancer. We showed previously that microcell-mediated transfer of human chromosome 8 into breast cancer cell line MDA-MB-231 resulted in reversion of these cells to tumorigenicity and was accompanied by changes in the expression of a breast cancer-relevant gene set. In the present study, we demonstrated that transfer of human chromosome 8 into another breast cancer cell line, CAL51, strongly reduced the tumorigenic potential of these cells. Loss of the transferred chromosome 8 resulted in reappearance of the CAL51 phenotype. Microarray analysis identified 78 probe sets differentially expressed in the hybrids compared with in the CAL51 and the rerevertant cells. This signature was also reflected in a panel of breast tumors, lymph nodes, and distant metastases and was correlated with several prognostic markers including tumor size, grading, metastatic behavior, and estrogen receptor status. The expression patterns of seven genes highly expressed in the hybrids but down-regulated in the tumors and metastases (MYH11, CRYAB, C11ORF8, PDGFRL, PLAGL1, SH3BP5, and KIAA1026) were confirmed by RT-PCR and tissue microarray analyses. Unlike with the corresponding nontumorigenic phenotypes demonstrated for the MDA-MB-231- and CAL51-derived microcell hybrids, the respective differentially expressed genes strongly differed. However, the majority of genes in both gene sets could be integrated into a similar spectrum of biological processes and pathways, suggesting that alterations in gene expression are manifested at the level of functions and pathways rather than in individual genes.
IL-21 Mediates Suppressive Effects via Its Induction of IL-10 (2009)

IL-21 is a pleiotropic cytokine that is required for normal Ig production. We previously showed that IL-21 was elevated in BXSB-Yaa mice with systemic lupus erythematosus. These mice also had elevated IL-10 levels, and we now show that IL-21 induces IL-10 mRNA and protein, suggesting unexpected immunosuppressive activities for IL-21. Indeed, Th1 priming with IL-21 leads to accumulation of cells with immunosuppressive activity, and IL-21 overexpression decreases specific Ab production after immunization in an IL-10-dependent fashion. Moreover, we show that IL-21 signaling is required for maximal induction of IL-10 by IL-6 or IL-27. Overall, our data indicate that IL-21 regulates immune responses at least in part by inducing IL-10 and reveal unanticipated immunosuppressive actions for this cytokine.
Separation of Long DNA Molecules in a Microfabricated Entropic Trap Array (2000)

A nanofluidic channel device, consisting of many entropic traps, was designed and fabricated for the separation of long DNA molecules. The channel comprises narrow constrictions and wider regions that cause size-dependent trapping of DNA at the onset of a constriction. This process creates electrophoretic mobility differences, thus enabling efficient separation without the use of a gel matrix or pulsed electric fields. Samples of long DNA molecules (5000 to approximately 160,000 base pairs) were efficiently separated into bands in 15-millimeter-long channels. Multiple-channel devices operating in parallel were demonstrated. The efficiency, compactness, and ease of fabrication of the device suggest the possibility of more practical integrated DNA analysis systems.
America's trade : markets count more than deficits (1993)

For more about the East-West Center, see <a href="http://www.eastwestcenter.org/">http://www.eastwestcenter.org/</a>
A stretchable strain sensor based on a metal nanoparticle thin film for human motion detection (2014)

Wearable strain sensors for human motion detection are being highlighted in various fields such as medical, entertainment and sports industry. In this paper, we propose a new type of stretchable strain sensor that can detect both tensile and compressive strains and can be fabricated by a very simple process. A silver nanoparticle (Ag NP) thin film patterned on the polydimethylsiloxane (PDMS) stamp by a single-step direct transfer process is used as the strain sensing material. The working principle is the change in the electrical resistance caused by the opening/closure of micro-cracks under mechanical deformation. The fabricated stretchable strain sensor shows highly sensitive and durable sensing performances in various tensile/compressive strains, long-term cyclic loading and relaxation tests. We demonstrate the applications of our stretchable strain sensors such as flexible pressure sensors and wearable human motion detection devices with high sensitivity, response speed and mechanical robustness.
Whole genome amplification and high-throughput allelotyping identified five distinct deletion regions on chromosomes 5 and 6 in microdissected early-stage ovarian tumors. (2001)

Investigation of genetic changes in tumors by loss of heterozygosity is a powerful technique for identifying chromosomal regions that may contain tumor suppressor genes. In this study, we determined allelic loss on chromosomes 5 and 6 in 29 primary early-stage epithelial ovarian carcinomas including 3 microscopically identified adenocarcinomas using a high-throughput PCR-based method combined with laser capture microdissection and whole genome amplification techniques. Twenty microsatellite markers spanning chromosomes 5 and 6 at an average distance of 20 cM were examined. High frequencies of loss on chromosome 5 were identified at loci D5S428 (48%), D5S424 (32%), and D5S630 (32%). Our study also showed that chromosome 6 exhibited high frequencies of loss of heterozygosity at loci D6S1574 (46%), D6S287 (42%), D6S441 (45%), D6S264 (60%), and D6S281 (35%). These results suggest that multiple tumor suppressor genes are located on five distinct regions on chromosomes 5 and 6, i.e., 5p15.2, 5q13-21, 6p24-25, 6q21-23, and 6q25.1-27, and may be involved in the early development of ovarian carcinomas.
Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium. (1997)

Prostate-specific membrane antigen (PSMA), initially defined by monoclonal antibody (mAb) 7E11, is a now well-characterized type 2 integral membrane glycoprotein expressed in a highly restricted manner by prostate epithelial cells. 7E11 has been shown to bind an intracellular epitope of PSMA that, in viable cells, is not available for binding. Herein, we report the initial characterization of the first four reported IgG mAbs that bind the external domain of PSMA. Competitive binding studies indicate these antibodies define two distinct, noncompeting epitopes on the extracellular domain of PSMA. In contrast to 7E11, these mAbs bind to viable LNCaP cells in vitro. In addition, they show strong immunohistochemical reactivity to tissue sections of prostate epithelia, including prostate cancer. These mAbs were also strongly reactive with vascular endothelium within a wide variety of carcinomas (including lung, colon, breast, and others) but not with normal vascular endothelium. These antibodies should prove useful for in vivo targeting to prostate cancer, as well as to the vascular compartment of a wide variety of carcinomas.
[Acoustic investigations in orbital tumor diagnosis (author's transl)]. (1975)

360 patients with unilateral exophthalmos were examined with echoophthalmograph to study the diagnostical possibilities of a method of echography in orbital tumors. The findings of para- and transbulbal methodics were checked in 140 patients. The tonometry of tumors and soft orbital tissues was performed. The methodics of acoustic orbitonometry based on the measurement of retrobulbal neoplasms at the moment of their step-by-step compression was worked out. The echographic symptoms of different orbital neoplasms is described as well as those of pseudotumor and tireotropic exophthalmos. The possibility of acoustic measurement of orbital neoplasms is shown. The dependence between the extent and progress of deformation in the exophthalmed eye on one hand-nature of exophthalmos, character and localization of the tumor on the other was revealed. The quantitative data about the compression of different orbital tumors were obtained. It was shown that the surveying echography, biometry and acoustic orbitonometry facilitate the task of differential diagnosis, allow the localization and size of the tumor to be detected and help to control the results of the treatment.