gebhart/patrepeval huggingface dataset:
Influence of Polyamine Architecture on the Transport and Topoisomerase II Inhibitory Properties of Polyamine DNA−Intercalator Conjugates (2001)

An efficient five-step synthetic method was developed to access a series of spermine derivatives containing appended acridine, anthracene, and 7-chloroquinoline motifs. The derivatives were composed of a spermine fragment covalently tethered at its N4 and N9 positions to an aromatic nucleus via an aliphatic chain (e.g., 8: acridine -[C4 aliphatic tether]-spermine-[C4 aliphatic tether]-acridine). The distance separating the spermine and aromatic nuclei was altered via different tethers composed of four or five methylene units. These bis ligands (8, 9, 12, and 13) were shown to inhibit human DNA topoisomerase II (topo II) activity at 5 microM. Enzymatic activity was assessed as the ability to unknot (decatenate) and cleave kinetoplast DNA (kDNA). Polyamine conjugation did not disrupt the ability of the acridine-spermine conjugates 8 and 9 to inhibit topo II activity as compared with the 9-aminoacridine and 9-(N-butyl)aminoacridine controls (at 5 microM). The parent polyamines, spermine (5 microM) and spermidine (10 microM), had little effect on topo II activity. In general, the bis-substituted spermine derivatives (8, 9, 12, and 13) were more efficient topo II inhibitors at 5 microM than their monosubstituted spermidine counterparts (22-25) at 10 microM. Within the bisintercalator spermine series, insertion of an additional methylene unit (i.e., C5 tethers) increased potency 2-fold (8, bis-C4-acridine, 47 h IC(50) = 40 microM; 9, bis-C5-acridine, IC(50) = 17 microM). Comparison of the bis- and monoacridine spermine motifs (8 and 17) revealed a 4-fold increase in potency for the latter architecture (94 h IC(50) for 8, 74 microM; for 17, 17 microM). In general the bisintercalators (8, 9, 12, and 13) behaved as cytostatic agents, while the monosubstituted acridine and anthracene derivatives (22-25) were cytotoxic. Anthracene-containing conjugates were generally more toxic than their acridine counterparts in an L1210 (murine leukemia) cell assay. Of the conjugates tested the (monointercalator)-spermine motif (e.g., 17) had the highest affinity for the L1210 polyamine transporter as revealed by spermidine protection experiments.
Mutation in a heterochromatin-specific chromosomal protein is associated with suppression of position-effect variegation in Drosophila melanogaster. (1990)

We report here that a point mutation in the gene which encodes the heterochromatin-specific nonhistone chromosomal protein HP-1 in Drosophila melanogaster is associated with dominant suppression of position-effect variegation. The mutation, a G-to-A transition at the first nucleotide of the last intron, causes missplicing of the HP-1 mRNA. This suggests that heterochromatin-specific proteins play a central role in the gene suppression associated with heterochromatic position effects.
Two-Level Trust Federation Model for Cross-Domain Environment (2011)

Under distributed environment, Resources are located in different security domains. The cross-domain network application pattern is formed to access cross-domain resource, which is adapted to industry application and become widely-used network scheme. Therefore, it is necessary to build a loose and scalable dynamic trust federation, which requires the establishment of trust relationship between various entities. Through a study of trust mechanism, this paper divides entity into two parts including inner-domain and inter-domain and presents a two-level trust federation model in a cross-domain environment. And based on this model, this paper realizes the trust establishment and trust management for different security domains. Meanwhile, this paper describes the problem of privacy protection, information security, access control and federation evaluation in the model. The dynamic trust federation model achieves the trust interaction among different entities. It can expand the trust function of SAML components in real application while realizes the two-level trust federation model, which is called trust-based SAML framework (TBSF). At the same time, TBSF achieve cross-domain access in industrial collaborative design and application.
Mannose receptor‐mediated uptake of antigens strongly enhances HLA class II‐restricted antigen presentation by cultured dendritic cells (1997)

Dendritic cells (DC) efficiently take up antigens by macropinocytosis and mannose receptor-mediated endocytosis. Here we show that endocytosis of mannose receptor-antigen complexes takes place via small coated vesicles, while non-mannosylated antigens were mainly present in larger vesicles. Shortly after internalization the mannose receptor and its ligand appeared in the larger vesicles. Within 10 min, the mannosylated and non-mannosylated antigens co-localized with typical markers for major histocompatibility complex class II-enriched compartments and lysosomes. In contrast, the mannose receptor appeared not to reach these compartments, suggesting that it releases its ligand in an earlier endosomal structure. Moreover, we demonstrate that mannosylation of protein antigen and peptides resulted in a 200-10,000-fold enhanced potency to stimulate HLA class II-restricted peptide-specific T cell clones compared to non-mannosylated peptides. Our results indicate that mannosylation of antigen leads to selective targeting and subsequent superior presentation by DC which may be applicable in vaccine design.
Immunization of Man against Falciparum and Vivax Malaria by Use of Attenuated Sporozoites (1975)

With strict adherence to ethical guidelines, a volunteer was immunized against sporozoites of Plasmodium falciparum and P. vivax, the antigen consisting of attenuated sporozoites of each species inoculated through bites of mosquitoes X-irradiated at a minimum dosage of 15,000 rads. On one occasion this dosage did not render all P. vivax sporozoites noninfective. Species specificity of antigen and antibody was demonstrated, but within each species a wide geographical diversity of strains proved interchangeably antigenic and susceptible to the antibody. Once immunized, the volunteer was protected for not more than 3 months and 6 months, respectively, from infective P. falciparum and P. vivax sporozoites, the duration of protection being reflected by a positive species-specific circumsporozoite reaction. Studies in this volunteer, and in two others immunized with P. falciparum sporozoites, did not reveal any increase in serum levels of immunoglobulins G and M.
Idiopathic dystonia among ashkenazi jews: Evidence for autosomal dominant inheritance (1989)

We studied families to clarify the mode of inheritance of idiopathic torsion dystonia among the Ashkenazim. Probands had symptoms before 28 years of age, had at least one Ashkenazi grandparent, and were ascertained independently of family history and not referred by another relative. All available first- and second-degree relatives were examined, and videotapes were made. Examination notes and blinded review of videotapes led to rating of dystonia as definite, probable, possible, or absent. We determined rates of illness for first- and second-degree relatives and calculated age-adjusted lifetime risks. The methods of maximum likelihood and likelihood ratio goodness-of-fit tests were used to estimate parameters and to test dominant and recessive models of inheritance. We studied 43 probands, 146 (90.1%) of 162 living first-degree relatives, and 96 (40.2%) of 239 living second-degree relatives. Nineteen relatives had definite dystonia, and 2 had probable dystonia. Using definite cases only, the age-adjusted risk for all first-degree relatives was 15.5% and for all second-degree relatives 6.5%, with no significant sex differences; parent, offspring, and sibling risks did not differ significantly. The risks were consistent with autosomal dominant inheritance with a penetrance estimated at 29.4% using definite cases only or 32.2% using definite and probable cases. Assuming a disease frequency of 1/15,000, the gene frequency was estimated to be 1/9000.
The Structure of Human DNase I Bound to Magnesium and Phosphate Ions Points to a Catalytic Mechanism Common to Members of the DNase I-like Superfamily (2012)

Recombinant human DNase I (Pulmozyme, dornase alfa) is used for the treatment of cystic fibrosis where it improves lung function and reduces the number of exacerbations. The physiological mechanism of action is thought to involve the reduction of the viscoelasticity of cystic fibrosis sputum by hydrolyzing high concentrations of DNA into low-molecular mass fragments. Here we describe the 1.95 Å resolution crystal structure of recombinant human DNase I (rhDNase I) in complex with magnesium and phosphate ions, both bound in the active site. Complementary mutagenesis data of rhDNase I coupled to a comprehensive structural analysis of the DNase I-like superfamily argue for the key catalytic role of Asn7, which is invariant among mammalian DNase I enzymes and members of this superfamily, through stabilization of the magnesium ion coordination sphere. Overall, our combined structural and mutagenesis data suggest the occurrence of a magnesium-assisted pentavalent phosphate transition state in human DNase I during catalysis, where Asp168 may play a key role as a general catalytic base.
Discrepancies in measuring acetabular coverage: revisiting the anterior and lateral center edge angles (2015)

The lateral center edge angle (LCEA) and the anterior center edge angle (ACEA) are commonly used to assess acetabular coverage of the femoral head. There are two distinct methods found in the literature to obtain these angles, specifically, measuring to the most lateral bone edge versus the sclerotic lateral sourcil edge. A difference between these two methods may contribute to inconsistent estimates of acetabular coverage, and potentially lead to clinical misdiagnosis and treatment mismanagement. The objectives of this study were to quantify the difference between bone edge and sourcil edge measurements and to determine how the difference influences the classification of acetabular coverage in adult patients with suspected hip pathomorphology. Two observers completed the measurements independently using preoperative anteroposterior and false profile radiographs. Bland-Altman plots and paired t-tests were used to compare measurement methods. Bone and sourcil measurements of the LCEA and ACEA were significantly different (both P < 0.001). On average, the bone LCEA was 4° (95% limits of agreement = -2° to 10°) greater than the sourcil LCEA. The bone ACEA was, on average, 10° (95% limit of agreement = -2° to 22°) greater than the sourcil ACEA. The differences often led to different clinical classifications for the same hip. With a statistically and clinically significant difference in the quantification of acetabular coverage using bone edge versus sourcil edge methods for measuring the LCEA and ACEA in adult patients, it should be mandatory to clearly identify which method was used in each study.
Foot Problems in Diabetes: An Overview (2004)

Diabetes is the leading cause of nontraumatic lower-extremity amputations in the United States. Most amputations are preceded by an ulcer, and ulcers are costly in their own right. Most ulcers are neuropathic in etiology and plantar in location. They occur typically at sites of high mechanical loading because of repetitive trauma in people with loss of pain sensation. In an adequately perfused limb, such ulcers are not difficult to heal. When they are properly mechanically off-loaded, approximately 90% of these wounds heal in approximately 6 weeks. The reference standard off-loading device is the total contact cast, but other reasonably efficacious methods exist. Screening and implementation of preventive measures in the high-risk patient are highly recommended and can reduce the incidence of ulceration. All patients with diabetes should be screened annually for loss of protective sensation, with the 10-g Semmes-Weinstein monofilament being the easiest tool to use. Education to prevent complications should be implemented for all patients with loss of protective sensation.
An architectural overview of the programmable multimedia processor, TM-1 (2002)

TM-1 is the first in a family of programmable multimedia processors from the Trimedia product group of Philips Semiconductors. This "C" programmable processor has a high performance VLIW-CPU core with video and audio peripheral units designed to support the popular multimedia applications. TM-1 is designed to concurrently process video, audio, graphics, and communication data. The VLIW-CPU core is capable of executing a maximum of twenty seven operations per cycle, and the sustained execution rate is about five operations per cycle for the tuned applications. The audio unit easily handles different audio formats including the 16-bit stereo data. The video unit is capable of processing different YUV and RGB pixel formats with horizontal and vertical scaling and color space conversion. TM-1 applications can range from low-cost, stand alone systems such as video phones to programmable, multipurpose plug-in cards for traditional computers.
The retinoblastoma gene product protects E2F-1 from degradation by the ubiquitin-proteasome pathway. (1996)

E2F-1 plays a crucial role in the regulation of cell-cycle progression at the G1-S transition. In keeping with the fact that, when overproduced, it is both an oncoprotein and a potent inducer of apoptosis, its transcriptional activity is subject to multiple controls. Among them are binding by the retinoblastoma gene product (pRb), activation by cdk3, and S-phase-dependent down-regulation of DNA-binding capacity by cyclin A-dependent kinase. Here we report that E2F-1 is actively degraded by the ubiquitin-proteasome pathway. Efficient degradation depends on the availability of selected E2F-1 sequences. Unphosphorylated pRb stabilized E2F-1, protecting it from in vivo degradation. pRb-mediated stabilization was not an indirect consequence of G1 arrest, but rather depended on the ability of pRb to interact physically with E2F-1. Thus, in addition to binding E2F-1 and transforming it into a transcriptional repressor, pRb has another function, protection of E2F-1 from efficient degradation during a period when pRb/E2F complex formation is essential to regulating the cell cycle. In addition, there may be a specific mechanism for limiting free E2F-1 levels, failure of which could compromise cell survival and/or homeostasis.
Comparative performance study of several pitch detection algorithms (1975)

A comparative performance study of five pitch detection algorithms was conducted. A speech data base, consisting of eight utterances spoken by three males, three females, and one child was constructed. Both telephone and wideband recordings were made of each of the utterances. For each of the utterances in the data base a “standard” pitch contour was semiautomatically measured using a highly sophistocated interactive pitch detection program. The “standard” pitch contour was then compared with the pitch contour that was obtained from each of the five programmed pitch detectors. The algorithms used in this study were (1) a center clipping, infinite-peak clipping, modified autocorrelation method; (2) the cepstral method; (3) the SIFT method; (4) the parallel processing time domain method; and (5) the data reduction method. A set of measurements were made on the pitch contours to quantify the various types of errors which occur in each of the above methods. Included among the error measurements were the average and standard deviation of the error in pitch period during voiced regions, the number of gross errors in the pitch period, and the average and standard deviation of the error in choosing onset and offset of voicing. By pooling the various error measurements, the individual pitch detectors could be rank ordered as a measure of this relative performance.
Therapeutic Vaccination with Epidermal Growth Factor (EGF) in Advanced Lung Cancer: Analysis of Pooled Data from Three Clinical Trials (2007)

We have undertaken the analysis of pooled data from three pilot clinical trials of vaccination with Epidermal Growth Factor (EGF) in patients with advanced non small cell lung cancer (NSCLC), addressing particularly the issue of the relationship between immunization and survival. Eighty-three patients with advanced disease were included in three pilot clinical trials and vaccinated with the EGF Vaccine. The trials were designed to evaluate the immunogenicity and safety of the vaccine using different adjuvants, cyclophosphamide pretreatment or not, and different dosage levels of the vaccine. The vaccine elicited specific anti-EGF antibody titers in 83% of subjects, and 49% developed a good anti-EGF antibody response. The adjuvant, the vaccine dose, and cyclophosphamide pretreatment significantly influenced immunogenicity. Patients that seroconverted survived significantly longer than patients who did not. Good antibody responders survived significantly longer than poor responders. Pooled results from these trials confirm that vaccination with EGF is safe and immunogenic in advanced NSCLC patients. The association between good antibody responses and survival consistently appeared in every single trial independently of the specific trial designs. Although these were small pilot nonrandomized clinical trials not intended to confirm therapeutic effect, the survival of the pooled patient population was statistically greater compared with 163 control patients receiving standard treatment.
Maximum likelihood tracking algorithms for MIMO-OFDM (2004)

Tracking algorithms for carrier and sampling clock frequency offset are proposed for pilot assisted MIMO-OFDM in frequency selective channels. The methods are based on maximum likelihood estimation theory applied to observations of received pilot subcarriers at the output of the FFTs of the receiver. Simulation results show that larger MIMO configurations benefit from lower estimator variances, providing increased synchronization accuracy at low SNRs, or allowing for a reduction of the number of pilot subcarriers.
A microwave anticipatory crash sensor for activation of automobile passive restraints (1973)

For effective protection of automobile occupants in high-speed collisions, passive restraints (such as airbags) must be actuated prior to impact. A 10-GHz CW homodyne bistatic radar system has been developed to permit exploration of the feasibility of such an application. System design and response to potential real and false-alarm targets and to the automotive environment are delineated. Possible elaborations on the basic system are described.
Lowering the Silver Content in Automotive Conductive Pastes (2017)

The high conductivity of silver and its oxidation resistance make it the metal of choice for automotive applications in defogging and other areas. There is scope to reduce the cost by reducing the content of silver, a costly metal. This article reports the results from testing formulations with reduced silver content. A range of silver-coated and base metal fillers were tested however none of these resulted in performance to match the commercially available silver automotive pastes.
Transactional Memory Architecture and Implementation for IBM System Z (2012)

We present the introduction of transactional memory into the next generation IBM System z CPU. We first describe the instruction-set architecture features, including requirements for enterprise-class software RAS. We then describe the implementation in the IBM zEnterprise EC12 (zEC12) microprocessor generation, focusing on how transactional memory can be embedded into the existing cache design and multiprocessor shared-memory infrastructure. We explain practical reasons behind our choices. The zEC12 system is available since September 2012.
Diamondlike carbon films by rf plasma-assisted chemical vapor deposition from acetylene (1990)

This paper is an overview of studies performed at the IBM Thomas J. Watson Research Center on diamondlike carbon (hydrogenated amorphous carbon) films, including some recent results on their tribological properties. The films were prepared by rf plasma-assisted chemical vapor deposition (PACVD) from acetylene. Their structure and composition were characterized by a variety of methods such as X-ray and TEM diffractometry, XPS, high-resolution <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">13</sup> C NMR spectroscopy, and H( <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">15</sup> Nα,γ)C nuclear-reaction profiling. Their adhesion to various substrates, coefficients of static and dynamic friction, and wear resistance were also characterized. It was found that the films were essentially amorphous, reaching their bulk composition after 40 nm of growth above the initial growth interface. Their bulk composition included about 40% hydrogen. More diamondlike carbon bonding was obtained at the initial growth interface than in the bulk range. The ratio of sp <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> to sp <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> carbon atoms was found to be 1.6, with virtually all sp <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> carbon atoms bound to one or more hydrogen atoms. The diamondlike carbon films (DLC) displayed excellent adhesion to the surface of Si. Furthermore, the films could be bonded to films of otherwise nonbonding metals, provided the metals formed stable silicides. By using an interfacial Si film several atomic layers thick, adhesion to the metal films could be improved to the extent that attempts to detach the DLC films fractured the underlying metal films. The adhesive DLC films were found to have a very high resistance to sliding wear and chemical attack, and are therefore useful in various applications as very thin protective coatings.
Synthesis and Characterization of a Novel Green Cobalt Corrinoid<sup>1</sup> (1996)

Treatment of the c-monocarboxylate of cyanocobalamin with diphenylphosphoryl azide affords the c-NH2 derivative in moderate yield along with a novel green corrinoid. The latter is also obtained when the amine is treated with aqueous base. A single-crystal X-ray diffraction analysis shows that the green corrinoid lacks a c side chain and contains a C7−C8 double bond indicating that the B pyrrole ring has been aromatized.
Nerve Growth Factor Is Mitogenic for Cancerous but Not Normal Human Breast Epithelial Cells (1998)

We show here that nerve growth factor (NGF), the archetypal neurotrophic factor, is able to stimulate the proliferation of breast cancer cells (MCF-7 and MDA-MB-231 cell lines), although it is unable to stimulate growth of normal breast epithelial cells (NBEC). This stimulation induced cells in the G0 phase to reenter the cell cycle, as well as shortening cell cycle duration. Immunoblotting experiments revealed that both the two cancer cell lines and the NBEC express high affinity (p140(trk)) and low affinity (p75) NGF receptors. Inhibition of the NGF growth-promoting effect by the drugs K-252a and PD98059 indicated that activation of Trk-tyrosine kinase activity and the mitogen-activated protein kinase cascade are necessary to obtain the mitogenic effect. Activation of mitogen-activated protein kinase can be detected in breast cancer cells after 10 min of NGF stimulation, whereas no change was detected in NBEC. These results demonstrate that NGF is a mitogenic factor for human breast cancer cells and that it might constitute a new regulator of breast tumor growth.
Passage of Inhaled Particles Into the Blood Circulation in Humans (2002)

We conclude that inhaled (99m)Tc-labeled ultrafine carbon particles pass rapidly into the systemic circulation, and this process could account for the well-established, but poorly understood, extrapulmonary effects of air pollution.