gebhart/patrepeval huggingface dataset:
Development of a Melanoma-Specific Adenovirus (2002)

Concerns regarding the hepatotoxicity of adenovirus for cancer gene therapy have led to attempts to engineer viruses for tissue-specific gene expression and tissue-specific replication. The Tyrex2 (a tandem murine melanocyte-specific enhancer) system was used to express luciferase, purine nucleoside phosphorylase (PNP), and the essential adenoviral gene E1A. In nonmelanoma cell lines, the CMV promoter/enhancer (CMV p/e) was 969 times stronger than the Tyrex2 construct, whereas in melanoma cells it was only 2.6 times stronger. An adenovirus with Tyrex2 regulating PNP (Ad2Tyr2-PNP) was tested for cytotoxicity. In melanoma cells, treatment with Ad2Tyr2-PNP plus the prodrug 6-methylpurine deoxyriboside (6-MPDR) resulted in 90% cytotoxicity by day 4. In non-melanoma cell lines, only the CMV p/e resulted in significant cytotoxicity. We compared the intrinsic E1A promoter/enhancer (E1A p/e) system with the melanoma-specific constructs and found that the Tyrex2 system achieved higher levels of luciferase than the E1A p/e in all melanoma lines tested. In non-melanoma cell lines, the E1A p/e is 12.4 times stronger than the Tyrex2 construct. Tyrex2 was then used to regulate adenoviral E1A expression to construct a melanoma-specific replicating adenovirus. We were unable to achieve selective replication. As E1A is a known transactivator of the adenovirus major late promoter (MLP), we studied the ability of the MLP to express a transgene in the context of tissue-selective E1A expression. We were able to demonstrate high levels of luciferase activity with this construct; however, selectivity was lost. Melanoma-specific adenovirus expression was achieved with the Tyrex2 construct, and this led to melanoma-specific cytotoxicity by the potent PNP suicide gene. Selective melanoma-specific replication was not successful. The MLP may be a useful promoter in the context of a tissue-specific replicating adenovirus.
Abnormal Platelet Function in Myelofibrosis (1966)

Journal Article Abnormal Platelet Function in Myelofibrosis Get access Paul Didisheim, M.D., Paul Didisheim, M.D. Department of Medicine, University of Utah College of Medicine, Salt Lake City, Utah Dr. Didisheim's present address is Section of Clinical Pathology, Mayo Clinic, Rochester, Minnesota. Search for other works by this author on: Oxford Academic Google Scholar Dorothy Bunting Dorothy Bunting Department of Medicine, University of Utah College of Medicine, Salt Lake City, Utah Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 45, Issue 5, 1 May 1966, Pages 566–573, https://doi.org/10.1093/ajcp/45.5.566 Published: 01 May 1966 Article history Received: 24 November 1965 Published: 01 May 1966
Twitch-obtaining intramuscular stimulation (TOIMS) in acute partial radial nerve palsy. (1999)

Twitch Obtaining Intramuscular Stimulation (TOIMS) is useful in the management of chronic nerve-related pain. The best understanding of the mechanism of action of TOIMS can occur on treating acute nerve-related symptoms. An opportunity to use TOIMS treatments in an acute, partial left radial palsy within 24 hours of onset did occur. Following treatment to the affected triceps and brachioradialis muscles, there was an immediate improvement in the amplitude, area and conduction velocity of the left radial motor and sensory nerves at the lower arm level. There was also improvement in numbness and all symptoms abolished after four treatments. Serial multiple motor unit action potential (multi-MUAP) analysis performed in the triceps and extensor communis (EDC) showed signs of motor unit enlargement. The triceps MUAPs showed an increase in duration and size index (area/amplitude) by the 3rd month. Both parameters stabilized at 18 months. Phases increased at the 6th month only. In EDC, the size index increased progressively by the 3rd month. The duration increased at the 6th month with stabilization by the 18th month. Phases and turns increased on day 3 examination only. EDC showed reduction in the firing rate with time. By relaxing the muscles through the effects of intramuscular exercise and also by improving local ischemia, TOIMS averted prolonged conduction abnormalities and probably a more serious axonal injury.
PREPARATION OF FOUR NEW ANTIBIOTICS FROM A MUTANT OF <i>Streptomyces fradiae</i> (1969)

A mutant of Streptomyces fradiae 3535 incapable of synthesizing the antibiotic neomycin in the absence of added deoxystreptamine, the aminocyclitol subunit of the antibiotic, has been isolated from a culture treated with N-methyl-N'-nitro-N-nitrosoguanidine. The related aminocyclitols streptamine and 2-epistreptamine, both available by chemical synthesis, were incorporated by the mutant strain into four new antibiotics, for which we suggest the names hybrimycins A (isomers 1 and 2, from streptamine) and hybrimycins B (isomers 1 and 2, from 2-epistreptamine). Structures of the new antibiotics were established from the mass spectral, nuclear magnetic resonance, and optical rotatory properties of appropriate derivatives. This method offers a promising approach to the synthesis of other antibiotics.
THE DESIGN OF A PROXY OF CERTIFICATE VALIDATION BASED ON DISTRIBUTED CROSS-CERTIFICATION (2008)

The design of a proxy of certificate validation for reducing the client's processing burden is introduced,and the overall framework of this proxy is described.Based on the hybrid trust model supporting distributed cross-certification,an optimized method to construct a path is presented,and the detailed algorithms and the main data structures are provided.The process of path validation is described.The application of this proxy separates client from the complicated burdensome cross-certificate validation process.A real thin client is constructed,and the efficiency of the client application is improved.
Quantitative association between electrical potential across the cytoplasmic membrane and early gentamicin uptake and killing in Staphylococcus aureus (1984)

The relationship between the magnitude of the transmembrane electrical potential and the uptake of [14C]gentamicin was examined in wild-type Staphylococcus aureus in the logarithmic phase of growth. The electrical potential (delta psi) and the pH gradient across the cell membrane were determined by measuring the equilibrium distribution of [3H]tetraphenyl-phosphonium and [14C]acetylsalicylic acid, respectively. Incubation in the presence of the H+-ATPase inhibitor N,N'-dicyclohexylcarbodiimide (DCCD) led to an increase in delta psi with no measurable effect on the pH gradient at external pHs ranging from 5.0 to 6.5, and the effect on delta psi was DCCD concentration dependent. In separate experiments, gentamicin uptake and killing were studied in the same cells under identical conditions. At pH 5.0 (delta psi = -140 mV), no gentamicin uptake occurred. In the presence of 40 and 100 microM DCCD, delta psi was increased to -162 and -184 mV, respectively, and gentamicin uptake was observed in a manner that was also dependent on the DCCD concentration. At pH 6.0 (delta psi = -164 mV), gentamicin uptake occurred in the absence of the carbodiimide but was enhanced in a concentration-dependent fashion by 40 and 100 microM DCCD (delta psi = -174 and -216 mV, respectively). In all cases increased gentamicin uptake was associated with an enhanced bactericidal effect. The results indicate that initiation of gentamicin uptake requires a threshold level of delta psi (-155 mV) and that above this level drug uptake is directly dependent on the magnitude of delta psi.
Scintillation screen materials for beam profile measurements of high energy ion beams (2016)

For the application as a transverse ion beam diagnostics device, various scintillation screen materials were analysed. The properties of the materials such as light output, image reproduction and radiation stability were investigated with the ion beams extracted from heavy ion synchrotron SIS-18. The ion species (C, Ne, Ar, Ta and U) were chosen to cover the large range of elements in the periodic table. The ions were accelerated to the kinetic energies of 200 MeV/u and 300 MeV/u extracted with 300 ms pulse duration and applied to the screens. The particle intensity of the ion beam was varied from 1E4 to 1E9 particles per pulse. The screens were irradiated with typically 40 beam pulses and the scintillation light was captured using a CCD camera followed by characterization of the beam spot. The radiation hardness of the screens was estimated with high intensity Uranium ion irradiation. In the study, a linear light output for 5 orders of magnitude of particle intensities was observed from sensitive scintillators and ceramic screens such as Al2O3:Cr and Al2O3. The highest light output was recorded by CsI:Tl and the lowest one by Herasil. At higher beam intensity saturation of light output was noticed from Y and Mg doped ZrO2 screens. The light output from the screen depends not only on the particle intensity but also on the ion species used for irradiation. The light yield (i.e. the light intensity normalised to the energy deposition in the material by the ion) is calculated from the experimental data for each ion beam setting. It is shown that the light yield for light ions is about a factor 2 larger than the one of heavy ions. The image widths recorded exhibit a dependence on the screens material and differences up to 50 % were registered. On radiation stability analysis with high particle intensity of Uranium ions of about 6E8 ppp, a stable performance in light output and image reproduction was documented from Al2O3:Cr screen over 1000 pulses while slight saturation effects was noticed from some other screens. No considerable radiation induced damage for an irradiation by maximal fluence of 1.7×1E11 cm-2 Uranium ions was seen in the samples except the formation of point defects and color centers. Among the investigated screens P43 (Gd2O2S:Tb) powder seems to be a good candidate up to certain energy deposition threshold while for very high intensity measurements Al2O3:Cr screens are recommended.
Simulation through explicit state description and its application to semiconductor fab operation (1992)

A nonstandard methodology in simulator construction is introduced along with its application to on-
Optimization of Cu Low-k bond pad designs to improve mechanical robustness using the Area Release Energy method (2007)

In the development of present and future CMOS-technologies (CMOS065 and beyond) for microelectronic components the combination of state-of-the-art modeling techniques and experimental testing is crucial and provides a challenge to address the thermo-mechanical reliability issues and the demand for shorter time-to-market by the industry. Nowadays these modeling techniques often involve the construction of very detailed Cu low-k IC structures, which is still very time-consuming and computationally demanding. This paper adresses an alternative modeling strategy that intends to gain fundamental insights and understanding of the mechanisms that have an impact on the thermo-mechanical reliability of a Cu low-k device. As an example the relation between the metal densities of the various layers in a typical Cu low-k IC bond pad structure and the area release energy (ARE) criterion has been investigated. The modeling and computational effort have been considerably limited by building a simplified two- dimensional bond pad model. This model is constructed such that it is well capable to reveal the impact on the thermo-mechanical reliability and such that it is still representative for the behaviour of advanced Cu low-k structures. When optimizing the bond pad towards lower ARE levels for better mechanical robustness the impact of the metal density within the BE layers is evident. Furthermore, it shows that the metal density in a single layer does not only affect the ARE level in that specific layer, but it also influences the ARE profile within the entire stack. Clearly, the presented modeling strategy is suitable to identify the design parameters that play an important role when optimizing the thermo-mechanical performance of advanced Cu low-k structures. In combination with experimental tests (e.g. industrial qualification tests, interface strength measurements, etc.) it may provide a robust tool to further improve and ensure the reliability of present and future IC bond pad structures.
Type‐specific associations of human papillomavirus load with risk of developing cervical carcinoma <i>in situ</i> (2004)

We have previously shown that high human papillomavirus (HPV) 16 load in Papanicolaou smears negative for dysplasia is strongly associated with risk for carcinoma in situ (CIS) of the cervix. Here we study the amount of HPV DNA for some of the most frequent high-risk HPV types as determinants of progression to cervical CIS. Real-time PCR is used to estimate the normalized viral load of HPV 16, 18, 31, 33, 35, 39, 45, 52, 58 and 67 in 457 cases of cervical CIS and 552 matched population controls. A total of 2,747 archival Pap smears from gynecologic health examinations, collected over a period of up to 26 years, were analyzed to assess viral load during the infection history. Cervical smear samples differ widely in amount of DNA, underscoring the need for normalization of HPV load to number of cells in the sample. The risk of developing cervical CIS increases with higher viral load for most of the HPV types studied. The range of copy numbers per cell does not differ between HPV types but the odds ratio for CIS in the percentile with highest viral load is substantially higher for HPV 16 (OR = 36.9; 95% CI = 8.9-153.2) than for HPV 31 (OR = 3.2; 95% CI = 1.1-9.1) or HPV 18/45 (OR = 2.6; 95% CI = 1.0-6.4). Therefore, HPV viral load may be predictive of future risk of cervical CIS at a stage when smears are negative for squamous abnormalities, but differences between HPV types need closer attention.
Height Inspection of Wafer Bumps Without Explicit 3-D Reconstruction (2010)

Die bonding in the semiconductor industry requires placement of solder bumps not on PCBs but on wafers. Such wafer bumps, which are much miniaturized from their counterparts on printed circuit boards (PCBs), require their heights meet rigid specifications. Yet the small size, the lack of texture, and the mirror-like nature of the bump surface make the inspection task a challenge. Existing inspection schemes generally reconstruct every bump surface. This work addresses by how much can the task be simplified if merely the bump heights are inspected against the specification. It is assumed that ball bumps are used as the wafer bumps. An imaging setup is described that lets the peaks of the ball bumps be distinguishable in the image data. A measure is also described that reveals how well the ball bumps meet the height specification without going through explicit 3-D reconstruction. The measurement, in the form of a 3 × 3 matrix extractable from the image data, is sensitive to variations in the bump heights, but not to 2-D uncertainties in soldering the bumps onto the wafer substrate, or small variations in the placement of the wafer in 3-D. Experimental results are shown to illustrate the effectiveness of the proposed system.
Phase II clinical trial of intralesional administration of the oncolytic adenovirus ONYX-015 in patients with hepatobiliary tumors with correlative p53 studies. (2003)

Purpose: ONYX-015 is a genetically modified adenovirus with a deletion of the E1B early gene and is therefore designed to replicate preferentially in p53 -mutated cells. A Phase II trial of intralesional ONYX-015 was conducted in patients with hepatobiliary tumors to determine the safety and efficacy of such a treatment. Experimental Design: All patients had biopsy-proven, measurable tumors of the liver, gall bladder, or bile ducts that were beyond the scope of surgical resection. Patients received intralesional injections of ONYX-015 at either 6 × 10 9 or 1 × 10 10 plaque-forming units/lesion up to a total dose of 3 × 10 10 plaque-forming units, and i.p. injections were allowed in patients with malignant ascites. The status of p53 was assessed by immunohistochemistry or Affymetrix GeneChip microarray analysis. Studies were conducted for viral shedding and for the presence of antiadenoviral antibodies before and after the injection of ONYX-015. Patients were assessed for response and toxicity. Results: Twenty patients were enrolled, and 19 patients were eligible. Half of the patients had primary bile duct carcinomas. Serious toxicities (> grade 2) were uncommon and included hepatic toxicity (three patients), anemia (one patient), infection (one patient), and cardiac toxicity (one patient, atrial fibrillation). Sixteen patients were evaluable for response. Among these evaluable patients, 1 of 16 (6.3%) had a partial response, 1 of 16 (6.3%) had prolonged disease stabilization (49 weeks), and 8 of 16 (50%) had a >50% reduction in tumor markers. Of the 19 eligible patients, 18 (94.7%) had specimens available for p53 analysis. Fifteen of these 18 patients (83.3%) had evidence of p53 mutation by one or both methods, although the methods correlated poorly. Viral shedding was confined to bile (two of two patients) and ascites (four of four patients). Pretreatment adenoviral antibodies were present in 14 of 14 patients and increased by 33.2% after ONYX-015 treatment. Conclusions: Intralesional treatment with ONYX-015 in patients with hepatobiliary tumors is safe and well tolerated, and some patients had evidence of an anticancer effect. The high incidence of p53 mutations in these tumors makes this a logical population in which to test this therapy but precludes definitive evaluation about the necessity of a p53 mutation for ONYX-015 clinical activity.
<i>In vivo</i> biocompatibility studies. I. The cage implant system and a biodegradable hydrogel (1983)

A cage implant system has been utilized to examine the in vivo biocompatibility of a biodegradable hydrogel, poly(2-hydroxy-ethyl-L-glutamine) (PHEG). This system permits the quantitative determination of the components of the inflammatory exudate which surrounds the implanted polymer within the cage system. This system permits the serial examination of exudate components without sacrificing the animal. In addition, this system allows the subsequent removal of the polymer for surface and mechanical studies. Following implantation of the biodegradable hydrogel, quantitative and differential white cell counts of the exudates were determined over a 21-day period. In addition, concomitant extracellular enzyme analyses for alkaline phosphatase, acid phosphatase, prostatic acid phosphatase, leucine amino-peptidase, and Cathepsin B1 were determined. Corresponding control samples from exudates of the cage implant without the polymer were also determined. The two-tailed Student's t-test for unpaired samples was used to statistically compare the control and implanted polymer values for these respective analyses at the various time periods. A comparison of the cellular response for the control system and the PHEG system did not show statistically significant differences during the first 7 days following implantation. The acute inflammatory response, polymorphonuclear leukocyte predominant, was followed by a mild chronic inflammatory response, macrophage and lymphocyte predominant, and during this time period, 8-14 days, macrophages were present in significantly larger numbers for the PHEG system when compared to the control values. Enzymic analysis of the exudates revealed statistically significant differences between control and PHEG values at time intervals where no differences were noted in cell density or population. These results are discussed in terms of cell-polymer interactions leading to cellular activation and enhanced enzyme exocytosis by the inflammatory cells. Stress-strain measurements on implanted PHEG samples showed that significant in vivo degradation had occurred during the acute inflammatory phase of the response, i.e., the first 7 days.
Transition from Complete to Partial Wetting within Membrane Compartments (2008)

Wetting and dewetting phenomena are ubiquitous, but wetting transitions have been reported only in a few experimental systems. In this work, we present a wetting transition in a mesoscopic membrane compartment for the first time. A two-phase aqueous polymer solution was encapsulated in a giant vesicle (few tens of micrometers in size). The polymers used are poly(ethyleneglycol) (PEG) and dextran. By increasing the polymer concentration in the vesicle, the PEG-rich phase changed from complete wetting to partial wetting of the membrane.
Individuals Expressing FcγRIIIA-158 V/V and V/F Show Increased NK Cell Surface Expression of FcgRIIIA (CD16), Rituximab Binding, and Demonstrate Higher Levels of ADCC Activity in Response to Rituximab. (2005)

Abstract The homozygous expression of phenylalanine (F/F) at codon 158 of FcγRIIIa (CD16) is associated with inferior clinical responses to the anti-CD20 monoclonal antibody rituximab in patients with indolent non-Hodgkin’s lymphoma, in contrast to higher response rates observed for Waldenstrom’s macroglobulinemia patients expressing at least one valine (V/F, V/V) and follicular NHL patients who are homozygous for valine (V/V). We attempted elucidate the potential basic mechanism(s) behind these clinical observations by analyzing all the potential implications of this polymorphism among the 3 polymorphic subgroups at FcγRIIIA-158 (F/F, V/F, and V/V). We therefore used peripheral blood isolated natural killer (NK) cells from a pool of 52 unrelated healthy donors who were genotyped for FcγRIIIA-158. We evaluated allele-specific differences for FcγRIIIa gene expression by quantitative RT-PCR and demonstrated higher transcript levels among V/V (23.2 ng/mL) versus V/F (6.7 ng/mL) and F/F (6.2 ng/mL) (p&lt;0.0001). We then determined protein levels for CD16 in the same subgroup of donors using quantitative flow cytometry. The number of CD16 receptors per NK cell was 105,947, 94,863, and 69,130 for the V/V, V/F and F/F donors, respectively and was significantly higher among donors who expressed at least one valine (V/V and V/F) versus F/F (p=0.033). We next determined rituximab binding affinity to NK cells from V/V, V/F and F/F donors following incubation at concentrations of 10–200 ug/ml, and use of an indirect competitive assay with the anti-CD16 monoclonal antibody 3G8 (Cancer Research 64:4664). Rituximab binding to NK cells was higher among donors expressing at least one valine at all concentrations evaluated, with mean rituximab binding (defined as % of inhibition of mean fluorescence intensity for 3G8) as follow: V/V (72%); V/F (53%); and FF (37%); (p=0.017). Lastly, we assessed rituximab dependent NK cell mediated cytotoxicity (ADCC) using CD20 expressing ARH-77 B-cells and observed higher levels of ADCC killing among V/V (82%) and V/F (80%) versus F/F (23%) donors at an effector: target cell ratio of 20:1. Taken together, these studies suggest that individuals who express at least one valine at FcγRIIIA-158 might have better clinical outcomes to rituximab therapy on the basis of increased FcγRIIIA-158 receptor expression, rituximab binding and ADCC mediated killing of tumor cells.
Quantitative Evaluation of Side-Channel Security (2009)

There have been enormous research efforts dedicated to new countermeasures against side-channel attacks. However, very few reports were published about how to quantitatively verify their effectiveness. This paper presents statistical approaches of quantitative evaluation in respect of time disarrangement and side-channel magnitude confusion. The statistical mean value of the cross correlation coefficients measures the effectiveness of time disarrangement. The difference between the highest two correlation factors out of the key guesses is assessed to evaluate the effectiveness of side-channel magnitude confusion. Experiment results demonstrate that the proposed evaluation approaches are accurate and feasible. Eliminating requirement of reference makes the evaluations applicable in objective assessment of various devices by any designers or evaluators.