gebhart/patrepeval huggingface dataset:
Synergistic cytotoxic effect of azidothymidine and recombinant interferon alpha on normal human bone marrow progenitor cells (1989)

Azidothymidine (AZT) and interferon alpha (IFN-alpha) are among the drugs showing strong in vitro activity against the human immunodeficiency virus type-1 (HIV-1). Each drug, however, has significant toxicity against normal marrow progenitor cells that frequently proves dose-limiting in patients. In this study, AZT and recombinant IFN-alpha 2a (rIFN-alpha 2a) were tested as single agents and in combination against normal myeloid (CFU-GM) and erythroid (BFU-E) colony forming cells in a standard methylcellulose culture assay. The data were analyzed using a quantitative computerized analysis based on the median-effect principle and the isobologram equation as described by Chou and Talalay (Adv Enz Regul 22:27, 1984). The ED90 for BFU-E and CFU-GM inhibition was then compared with previously measured in vivo plasma levels of each drug and the ED90 for the anti-HIV-1 effect in vitro. We demonstrate that (a) the drugs are strongly synergistic in inhibiting marrow progenitor cell growth and that this synergism occurs at drug levels that are within the range of measured plasma levels in phase I clinical trials, (b) BFU-E are more sensitive than CFU-GM to the inhibiting effects of AZT, rIFN-alpha 2a or both drugs in combination, (c) the drug concentrations in combination that synergistically inhibit bone marrow progenitors are much higher than those required to inhibit HIV-1 replication in vitro, and (d) the anti-HIV-1 effect for the combination of AZT and rIFN-alpha 2a was clearly superior to the effect of AZT or rIFN-alpha 2a alone as indicated by the combination index and the dose-reduction index. These data suggest that substantially lower doses of AZT and rIFN-alpha than those currently being tested in clinical trials might not only maintain a strong synergistic anti-HIV-1 effect but might also avoid significant hematologic toxicity.
The Presence of a Single N-terminal Histidine Residue Enhances the Fusogenic Properties of a Membranotropic Peptide Derived from Herpes Simplex Virus Type 1 Glycoprotein H (2010)

Herpes simplex virus type 1 (HSV-1)-induced membrane fusion remains one of the most elusive mechanisms to be deciphered in viral entry. The structure resolution of glycoprotein gB has revealed the presence of fusogenic domains in this protein and pointed out the key role of gB in the entry mechanism of HSV-1. A second putative fusogenic glycoprotein is represented by the heterodimer comprising the membrane-anchored glycoprotein H (gH) and the small secreted glycoprotein L, which remains on the viral envelope in virtue of its non-covalent interaction with gH. Different domains scattered on the ectodomain of HSV-1 gH have been demonstrated to display membranotropic characteristics. The segment from amino acid 626 to 644 represents the most fusogenic region identified by studies with synthetic peptides and model membranes. Herein we have identified the minimal fusogenic sequence present on gH. An enlongation at the N terminus of a single histidine (His) has proved to profoundly increase the fusogenic activity of the original sequence. Nuclear magnetic resonance (NMR) studies have shown that the addition of the N-terminal His contributes to the formation and stabilization of an alpha-helical domain with high fusion propensity.
Antifungal Agents, Part 11: Biphenyl Analogues of Naftifine: Synthesis and Antifungal Activities (1995)

A series of naftifine analogues having the biphenyl instead of the naphthyl moiety have been synthesized in a search devoted to study bioanalogues of clinically efficacious antifungal agents. The new derivatives were tested against Candida albicans by the direct contact method. They were also assayed against Gram-positive and Gram-negative bacteria and against some isolates of plant pathogenic fungi. Derivatives 8a, 8c, and 9a were found to be active against Candida albicans, derivative 5a was active against E. coli, a very resistant species to antimycotic agents, and derivatives 8a and 8b inhibited the plant pathogenic Rhizoctonia solani.
Testing high speed DRAMs (2002)

If test of high speed DRAMs poses a new challenge for test engineers and test makers, then it would seem that the Rambus DRAMs, which have the fastest pin bandwidth of any DRAM in the world, would present the greatest challenge of all. However, at Rambus we have devised a test strategy that minimizes added test cost by allowing our devices to co-exist with the standard manufacturing flow of conventional pagemode devices. Two features have been added to the DRAM logic to facilitate our test strategy. First, a special test mode is incorporated into the Rambus interface that allows direct access to the core from the device pins. This mode provides a simple RAS/CAS-like access mechanism that can be used by existing equipment to exercise the core. Second, a PLL bypass mechanism is incorporated that allows the protocol logic to be functionally tested at low speed. These features allow the device to be tested with conventional low and medium speed memory testers. The only change to the test flow comes at final test.
Disappearance of the Lymphoid System in Bcl-2 Homozygous Mutant Chimeric Mice (1993)

The bcl-2 proto-oncogene can prevent the death of many cell types. Mice were generated that were chimeric for the homozygous inactivation of bcl-2. Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. In contrast, stimulation of CD3 inhibited the death of these cells. T and B cells with no Bcl-2 disappeared from the bone marrow, thymus, and periphery by 4 weeks of age. Thus, Bcl-2 was dispensable for lymphocyte maturation, but was required for a stable immune system after birth.
Improved blood compatibility and decreased VSMC proliferation of surface-modified metal grafted with sulfonated PEG or heparin (2002)

Although the technique of coronary stenting has remarkably improved long-term results in recent years, (sub)acute thrombosis and late restenosis still remain problems to be solved. Metallic surfaces were regarded as thrombogenic, due to their positive surface charges, and stenosis resulted from the activation and proliferation of vascular smooth muscle cells (VSMCs). In this study, a unique surface modification method for metallic surfaces was studied using a self-assembled monolayer (SAM) technique. The method included the deposition of thin gold layers, the chemisorption of disulfides containing functional groups, and the subsequent coupling of PEG derivatives or heparin utilizing the functional groups of the disulfides. All the reactions were confirmed by ATR-FTIR and XPS. The surface modified with sulfonated PEG (Au-S-PEG-SO3) or heparinized PEG (Au-S-PEG-Hep) exhibited decreased static contact angles and therefore increased hydrophilicity to a great extent, which resulted from the coupling of PEG and the ionic groups attached. In vitro fibrinogen adsorption and platelet adhesion onto the Au-S-PEG-SO3 or Au-S-PEG-Hep surfaces decreased to a great extent, indicating enhanced blood compatibility. This decreased interaction of the modified surfaces should be attributed to the non-adhesive property of PEG and the synergistic effect of sulfonated PEG. The effect of the surface modification on the adhesion and proliferation of VSMCs was also investigated. The modified Au-S-PEG-SO3 or Au-S-PEG-Hep surfaces also exhibited decreased adhesion of VSMCs, while the deposited gold layer itself was effective. The enhanced blood compatibility and the decreased adhesion of VSMCs on the modified metallic surfaces may help to decrease thrombus formation and suppress restenosis. It would therefore be very useful to apply these modified surfaces to stents for improved functions. A long-term in vivo study using animal models is currently under way.
New antifolates in clinical development. (1995)

Numerous new antifolate drugs have been developed in an attempt to overcome the potential mechanisms of tumor cell resistance to methotrexate, which can include decreased drug transport into cells; decreased polyglutamation, leading to increased drug efflux from cells; decreased drug affinity for folate-dependent enzymes; mutations of dihydrofolate reductase (DHFR), a key enzyme required for the maintenance of adequate intracellular reduced folate levels that is inhibited by methotrexate; and increased expression of the DHFR protein. Promising antifolate compounds undergoing clinical testing as anticancer agents include trimetrexate (which was recently approved by the FDA for the treatment of Pneumocystis carinii pneumonia), edatrexate, piritrexim, Tomudex, and lometrexol. The mechanisms of action, dosage, pharmacokinetics, clinical toxicity, and antitumor activity of these drugs are profiled.
Room-temperature exciton transitions in partially intermixed GaAs/AlGaAs superlattices (1988)

Substantial increases are observed in the energies of room-temperature exciton transitions in GaAs/AlGaAs superlattices which have been partially intermixed via the impurity-free vacancy diffusion process. Localized intermixing of the layered structure was accomplished by selective deposition of a SiO2 capping layer followed by rapid thermal annealing at temperatures between 850 and 950 °C for 15 s. In the samples studied, the above process allows continuously variable energy shifts of at least 61 meV while still maintaining clearly resolved excitonic behavior. Shifting and broadening of the exciton transitions are studied using room-temperature photoluminescence and photocurrent spectroscopies. A transmission resonance calculation is used to determine the interdiffusion coefficient as a function of temperature from the measured energy shifts.
Relationships between sequestration, antigenic variation and chronic parasitism in <i>Plasmodium chabaudi chabaudi</i>– a rodent malaria model (1990)

We describe here a rodent malaria model using cloned lines of Plasmodium chabaudi chabaudi in inbred CBA/Ca mice that exhibits both clonal antigenic variation in late stage-specific surface antigens, and deep vascular schizogony in the liver. We show that both these features are modulated by the spleen, and that surface antigen expression is crucially involved in the sequestering phenotype. Surface antigens are variant in chronic infection, and host protective immune responses can distinguish between these variants. Splenectomy abolishes this difference. The acute infection with non-sequestering cloned lines is kinetically indistinguishable from sequestering clones, but parasites unable to express variant sequestration-associated antigen do not form a chronic recrudescing infection. Another clone, able to re-express this antigen in the presence of the spleen, undergoes typical chronic recrudescence. In this model, the biological significance of sequestration-associated variant antigen seems to enable the establishment of chronic infection in the presence of a primed spleen.
Uracil DNA Glycosylase Counteracts APOBEC3G-Induced Hypermutation of Hepatitis B Viral Genomes: Excision Repair of Covalently Closed Circular DNA (2013)

The covalently closed circular DNA (cccDNA) of the hepatitis B virus (HBV) plays an essential role in chronic hepatitis. The cellular repair system is proposed to convert cytoplasmic nucleocapsid (NC) DNA (partially double-stranded DNA) into cccDNA in the nucleus. Recently, antiviral cytidine deaminases, AID/APOBEC proteins, were shown to generate uracil residues in the NC-DNA through deamination, resulting in cytidine-to-uracil (C-to-U) hypermutation of the viral genome. We investigated whether uracil residues in hepadnavirus DNA were excised by uracil-DNA glycosylase (UNG), a host factor for base excision repair (BER). When UNG activity was inhibited by the expression of the UNG inhibitory protein (UGI), hypermutation of NC-DNA induced by either APOBEC3G or interferon treatment was enhanced in a human hepatocyte cell line. To assess the effect of UNG on the cccDNA viral intermediate, we used the duck HBV (DHBV) replication model. Sequence analyses of DHBV DNAs showed that cccDNA accumulated G-to-A or C-to-T mutations in APOBEC3G-expressing cells, and this was extensively enhanced by UNG inhibition. The cccDNA hypermutation generated many premature stop codons in the P gene. UNG inhibition also enhanced the APOBEC3G-mediated suppression of viral replication, including reduction of NC-DNA, pre-C mRNA, and secreted viral particle-associated DNA in prolonged culture. Enhancement of APOBEC3G-mediated suppression by UNG inhibition was not observed when the catalytic site of APOBEC3G was mutated. Transfection experiments of recloned cccDNAs revealed that the combination of UNG inhibition and APOBEC3G expression reduced the replication ability of cccDNA. Taken together, these data indicate that UNG excises uracil residues from the viral genome during or after cccDNA formation in the nucleus and imply that BER pathway activities decrease the antiviral effect of APOBEC3-mediated hypermutation.
Plastics recycling: challenges and opportunities (2009)

Plastics are inexpensive, lightweight and durable materials, which can readily be moulded into a variety of products that find use in a wide range of applications. As a consequence, the production of plastics has increased markedly over the last 60 years. However, current levels of their usage and disposal generate several environmental problems. Around 4 per cent of world oil and gas production, a non-renewable resource, is used as feedstock for plastics and a further 3-4% is expended to provide energy for their manufacture. A major portion of plastic produced each year is used to make disposable items of packaging or other short-lived products that are discarded within a year of manufacture. These two observations alone indicate that our current use of plastics is not sustainable. In addition, because of the durability of the polymers involved, substantial quantities of discarded end-of-life plastics are accumulating as debris in landfills and in natural habitats worldwide. Recycling is one of the most important actions currently available to reduce these impacts and represents one of the most dynamic areas in the plastics industry today. Recycling provides opportunities to reduce oil usage, carbon dioxide emissions and the quantities of waste requiring disposal. Here, we briefly set recycling into context against other waste-reduction strategies, namely reduction in material use through downgauging or product reuse, the use of alternative biodegradable materials and energy recovery as fuel. While plastics have been recycled since the 1970s, the quantities that are recycled vary geographically, according to plastic type and application. Recycling of packaging materials has seen rapid expansion over the last decades in a number of countries. Advances in technologies and systems for the collection, sorting and reprocessing of recyclable plastics are creating new opportunities for recycling, and with the combined actions of the public, industry and governments it may be possible to divert the majority of plastic waste from landfills to recycling over the next decades.
BEHAB (brain enriched hyaluronan binding) is expressed in surgical samples of glioma and in intracranial grafts of invasive glioma cell lines. (1996)

Malignant gliomas aggressively invade the surrounding normal brain, whereas brain metastases of nonglial tumors do not. The invasive behavior of gliomas may be mediated by tissue- or tumor-specific extracellular proteins. mRNA for the brain-specific extracellular brain enriched hyaluronan-binding protein (BEHAB) is not detectable in normal adult human cortex or in any nonglioma tumor examined. BEHAB is consistently expressed in surgical samples of glioma (n = 27). Glioma cell lines maintained under standard cell culture conditions or grown as s.c. tumors do not express BEHAB. When grown as intracranial grafts, glioma cell lines that invade the brain express BEHAB, whereas noninvasive cell lines do not. BEHAB is a unique and selective marker for glioma and may play a role in tumor invasion.
Transgenic potato plants expressing osmotin gene inhibits fungal development in inoculated leaves. (1999)

Osmotin, a 24-KD protein isolated from Nicotiana tabacum 'Xanthi nc' was very toxic to Phytophthora infestans in vitro assay. Transgenic potato plants expressing wild osmotin protein delayed the emergence of symptoms of disease. Two osmotin mutants have been produced by PCR mutagenesis. One mutant, delta C18 osmotin, had a nonsense mutation near the C-terminus that deleted the carboxyl terminal prepropeptide (CTPP) of 18 amino acids. Another mutant, osmotin-P, had amber mutation at 96th amino acid. Both mutant genes driven by CaMV d35S promoter were introduced in potato by Agrobacterium mediated genetic transformation. The expression and osmotin protein accumulation in transgenic potato were detected by Southern, Northern, and Dot-blot ELISA assay. Disease resistance test using P.infestens complex race showed that expression of both osmotin mutants in transgenic potato reduced the lesion growth rate in inoculated leaves. The results showed that accumulation of osmotin protein in intercellular spaces (delta C18osmotin) inhibited the development of fungal disease in inoculated leaves. Based on the results we suggest that antifungal activity was possibly located at N end of osmotin protein (osmotin-P).
Effects of platelet-derived growth factor on endothelial wound healing of human corneas. (1994)

In organ-cultured human corneas, PDGF-BB promotes endothelial wound healing predominantly by cell migration, at least in corneas from senior donors.
Computing the area versus delay trade-off curves in technology mapping (1995)

We examine the problem of mapping a Boolean network using gates from a finite size cell library. The objective is to minimize the total gate area subject to constraints on signal arrival time at the primary outputs. Our approach consists of two steps. In the first step, we compute delay functions (which capture gate area-arrival time tradeoffs) at all nodes in the network, and in the second step we generate the mapping solution based on the computed delay functions and the required times at the primary outputs. For a NAND-decomposed tree, subject to load calculation errors, this two-step approach finds the minimum area mapping satisfying a delay constraint if such solution exists. The algorithm has polynomial run time on a node-balanced tree and is easily extended to mapping a directed acyclic graph (DAG). We also show how to account for the wire delays during the delay function computation step. Our results compare favorably with those of MIS2.2 mapper.
Entangled communities and spatial synchronization lead to criticality in urban traffic (2013)

Understanding the relation between patterns of human mobility and the scaling of dynamical features of urban environments is a great importance for today's society. Although recent advancements have shed light on the characteristics of individual mobility, the role and importance of emerging human collective phenomena across time and space are still unclear. In this Article, we show by using two independent data-analysis techniques that the traffic in London is a combination of intertwined clusters, spanning the whole city and effectively behaving as a single correlated unit. This is due to algebraically decaying spatio-temporal correlations, that are akin to those shown by systems near a critical point. We describe these correlations in terms of Taylor's law for fluctuations and interpret them as the emerging result of an underlying spatial synchronisation. Finally, our results provide the first evidence for a large-scale spatial human system reaching a self-organized critical state.
Single gate 0.15 μm CMOS devices fabricated using RTCVD in-situ boron doped Si/sub 1-x/Ge/sub x/ gates (2002)

Single gate 0.15 CM CMOS devices have been successfully fabricated using in-situ boron doped polycrystalline Si/sub 1-x/Ge/sub x/ (poly-Si/sub 1-x/Ge/sub x/) as the gate material for both surface channel n- and p-MOSFETs. The p/sup +/ poly-Si/sub 1-x/Ge/sub x/ gate electrodes were deposited by rapid thermal chemical vapor deposition using a Si/sub 2/H/sub 6/, GeH/sub 4/, B/sub 2/H/sub 6/ and H/sub 2/ gas mixture. The experimental results showed that the developed single gate process provides a minimized poly-depletion effect and boron penetration. By changing the Ge content in the poly-Si/sub 1-x/Ge/sub x/ films from x=0.3 to 0.76, a threshold voltage (V/sub T/) adjustment of about 0.3 V was achieved with the same channel doping and gate oxide thickness. Computer simulations indicate that an improved current drive and transconductance can be achieved in p/sup +/ poly-Si/sub 1-x/Ge/sub x/ gate devices compared to poly-Si gate devices with a fixed V/sub T/. This work demonstrates a potentially promising approach for deep submicron single gate bulk CMOS technology.
Clinical definition for multiple sclerosis treatment trials (1994)

Clinically, the Schumacher Panel criteria remain the best set of diagnostic criteria. Two subsets therein are definable, i.e., exacerbating-remitting (ER) and chronic progressive (CP), with the latter subdivided into progressive from onset and secondarily progressive. A clinically stable stage can also be recognized. It has been customary in treatment trials to separate ER and CP patients. End point for the latter is a comparison of neurologic status at the end of the trial with that entry. A similar assessment can be made for ER patients. With this criterion both types could be included in a single study. One could also, though, treat the exacerbation in an acute study or assess whether exacerbations can be prevented in a long-term trial. Most clinicians no longer consider monophasic disease as multiple sclerosis (MS). Depending on clinical extent, such patients are divisible into acute disseminated encephalomyelitis, Devic disease, transverse myelopathy, or optic neuritis. Each subgroup could be studied as with an acute exacerbation or in long term as to whether future and different neurologic insults can be prevented. One measure of neurologic status is the Disability Status Scale (DSS), which grades clinical impairment due to MS on a 0 (normal) to 10 (death due to MS) basis. The expanded DSS (EDSS) subdivides each step 1 through 9 into two. Type and severity of neurologic impairment is defined by graded involvement in the following eight functional systems (FS): pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other. Frequency and severity of each FS correlates strongly with DSS scores.(ABSTRACT TRUNCATED AT 250 WORDS)
A 10-bit, 20-MS/s, 35-mW pipeline A/D converter (2002)

This paper describes a 10-bit 20-MS/s pipeline A/D converter implemented in 1.2-/spl mu/m CMOS technology which achieves a power dissipation of 35 mW at full speed operation. Circuit techniques used to achieve this level of power dissipation include operation on a 3.3 V power supply, optimum scaling of capacitor values through the pipeline, and digital correction to allow the use of dynamic comparators. Measured performance includes 0.6 LSB of INL, 59.1 dB of SNDR for 100 kHz input at 20 MS/s. At Nyquist sampling (10 MHz input), SNDR is 55.0 dB.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Potentiation of Nerve Growth Factor-Induced Neurite Outgrowth by Fluvoxamine: Role of Sigma-1 Receptors, IP3 Receptors and Cellular Signaling Pathways (2008)

These findings suggest that stimulation of sigma-1 receptors and subsequent interaction with IP(3) receptors, PLC-gamma, PI3K, p38MAPK, JNK, and the Ras/Raf/MAPK signaling pathways are involved in the mechanisms of action of sigma-1 receptor agonists such as fluvoxamine and SA4503.