gebhart/patrepeval huggingface dataset:
Java bytecode to native code translation: the caffeine prototype and preliminary results (1996)

The Java bytecode language is emerging as a software distribution standard. With major vendors committed to porting the Java run-time environment to their platforms, programs in Java bytecode are expected to run without modification on multiple platforms. These first generation run-time environments rely on an interpreter to bridge the gap between the bytecode instructions and the native hardware. This interpreter approach is sufficient for specialized applications such as Internet browsers where application performance is often limited by network delays rather than processor speed. It is, however, not sufficient for executing general applications distributed in Java bytecode. This paper presents our initial prototyping experience with Caffeine, an optimizing translator from Java bytecode to native machine code. We discuss the major technical issues involved in stack to register mapping, run-time memory structure mapping, and exception handlers. Encouraging initial results based on our X86 port are presented.
Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy (2016)

Immune-checkpoint blocking antibodies have demonstrated objective antitumor responses in multiple tumor types including melanoma, non-small cell lung cancer (NSCLC), and renal cell cancer (RCC). In melanoma, an increase in overall survival has been demonstrated with anti-CTLA-4 and PD-1 inhibition. However, a plethora of immune-mediated adverse events has been reported with these agents. Immune-mediated cardiotoxicity induced by checkpoint inhibitors has been reported in single cases with variable presentation, including myocarditis and pericarditis. Among six clinical cancer centers with substantial experience in the administration of immune-checkpoint blocking antibodies, eight cases of immune-related cardiotoxicity after ipilimumab and/or nivolumab/pembrolizumab were identified. Diagnostic findings, treatment and follow-up are reported. A large variety of cardiotoxic events with manifestations such as heart failure, cardiomyopathy, heart block, myocardial fibrosis and myocarditis was documented. This is the largest case series to date describing cardiotoxicity of immune-checkpoint blocking antibodies. Awareness, monitoring of patients with pre-existing cardiac disorders and prompt evaluation by the treatment team is essential. Treatment including application of steroids is critical for patient safety.
K-ras gene mutations in early colorectal cancer ... flat elevated vs polyp-forming cancer.... (1995)

K-ras gene mutations in early colorectal cancer were detected by two-step sensitive polymerase chain reaction (PCR) and enzyme digestion method. Early colorectal cancer was classified into flat elevated cancer or polyp-forming cancer according to morphology and presence of adenomatous components. A total of 60 paraffin-embedded tissue specimens from patients with early colorectal cancer were analysed. K-ras codon 12 mutations were detected in 23.3% (7/30) of flat elevated cancer and 63.3% (19/30) of polyp-forming cancer. The incidence of K-ras codon 12 mutations in flat elevated cancer was significantly lower than in polyp-forming cancer (P < 0.01). These data suggested that K-ras gene mutations may be correlated with morphology or clinical features in flat elevated cancer, and that flat elevated cancer may originate from a pathway different from adenoma-carcinoma sequence.
An Introduction to RFID Technology (2006)

In recent years, radio frequency identification technology has moved from obscurity into mainstream applications that help speed the handling of manufactured goods and materials. RFID enables identification from a distance, and unlike earlier bar-code technology, it does so without requiring a line of sight. In this paper, the author introduces the principles of RFID, discusses its primary technologies and applications, and reviews the challenges organizations will face in deploying this technology.
Conditional Suppression of Cellular Genes: Lentivirus Vector-Mediated Drug-Inducible RNA Interference (2003)

RNA interference has emerged as a powerful technique to downregulate the expression of specific genes in cells and in animals, thus opening new perspectives in fields ranging from developmental genetics to molecular therapeutics. Here, we describe a method that significantly expands the potential of RNA interference by permitting the conditional suppression of genes in mammalian cells. Within a lentivirus vector background, we subjected the polymerase III promoter-dependent production of small interfering RNAs to doxycycline-controllable transcriptional repression. The resulting system can achieve the highly efficient and completely drug-inducible knockdown of cellular genes. As lentivirus vectors can stably transduce a wide variety of targets both in vitro and in vivo and can be used to generate transgenic animals, the present system should have broad applications.
Magnetic resonance properties of hydrogen: imaging the posterior fossa (1981)

Posterior fossa scans were performed on five healthy volunteers using a nuclear magnetic resonance (NMR) machine constructed by Thorn-EMI Ltd. Three different NMR scanning sequences were used. In the first, a type of saturation-recovery technique was used to produce images strongly dependent on the density of hydrogen nuclei, but with some dependence on the spin-lattice relaxation time (T1). In the second, an inversion-recovery technique was used to produce images with a stronger dependence on the spin-lattice relaxation time. In the third, a spin-echo technique was used to obtain images with a dependence on the spin-spin relaxation time (T2). All three types of NMR image were unaffected by bone artifact. Visualization of brain adjacent to the skull base was obtained without loss of detail due to partial-volume effect from bone. The saturation-recovery images highlighted arteries and veins that were clearly visible without the use of contrast agents. The inversion-recovery images showed remarkable gray-white matter differentiation enabling internal structure to be seen within the brainstem and cerebellum. The trigeminal nerve and ganglion were also seen outside the brain. Experience with the spin-echo technique is limited, but the images at the base of the brain show considerable soft-tissue detail. The NMR images of the posterior fossa in this study were comparable in quality to those obtained from a new rotate-rotate x-ray computed tomography machine and were superior in several respects.
Chemopreventive property of a soybean peptide (lunasin) that binds to deacetylated histones and inhibits acetylation. (2001)

Lunasin is a unique 43-amino acid soybean peptide that contains at its carboxyl end: (a) nine Asp (D) residues; (b) an Arg-Gly-Asp (RGD) cell adhesion motif; and (c) a predicted helix with structural homology to a conserved region of chromatin-binding proteins. We demonstrated previously that transfection of mammalian cells with the lunasin gene arrests mitosis, leading to cell death. Here we show that exogenous application of the lunasin peptide inhibits chemical carcinogen-induced transformation of murine fibroblast cells to cancerous foci. To elucidate its mechanism of action we show that lunasin: (a) internalizes in the cell through the RGD cell adhesion motif; (b) colocalizes with hypoacetylated chromatin; (c) binds preferentially to deacetylated histone H4 in vitro; and (d) inhibits histone H3 and H4 acetylation in vivo in the presence of a histone deacetylase inhibitor. These results suggest a mechanism whereby lunasin selectively induces apoptosis, mostly in cells undergoing transformation, by preventing histone acetylation. In support of this, lunasin selectively induces apoptosis in E1A-transfected cells but not in nontransformed cells. Finally, in the SENCAR mouse skin cancer model, dermal application of lunasin (250 microg/week) reduces skin tumor incidence by approximately 70%, decreases tumor yield/mouse, and delays the appearance of tumors by 2 weeks relative to the positive control. These results point to the role of lunasin as a new chemopreventive agent that functions possibly via a chromatin modification mechanism.
Effect of cloned gene dosage on cell growth and hepatitis B surface antigen synthesis and secretion in recombinant CHO cells (1992)

The effect of cloned gene copy number on growth and product formation has been studied in sufficient detail using a Chinese hamster ovary (CHO) cell line producing recombinant hepatitis B surface antigen (HbsAg). Batch culture experiments were carried out in T flasks in order to characterize cell growth and HbsAg secretion in various clones carrying different numbers of HbsAg gene copies integrated into CHO cell chromosomes. Specific growth rates were found to decrease with increasing gene copy number. Secreted HbsAg concentration and specific HbsAg secretion rates were found to increase with increase in gene copy number. Gene copy numbers in each clone determined using Southern hybridizations were positively correlated with intracellular dihydrofolate reductase (dhfr) content using a flow cytometric assay. The mRNA levels quantitated using Northern hybridization followed by autoradiography and densitometry also gave the same trends. The flow cytometry experiments show that while parental cells were quite homogeneous with respect to intracellular dhfr content, the amplified clones exhibit a great deal of heterogeneity in dhfr content. Pulse-chase experiments show that the efficiency of HbsAg secretion (defined here as the fraction of initially labeled HbsAg that is secreted into the extracellular medium at the end of a 23.5-h chase) decreases and also that the intracellular HbsAg degradation increases with increasing gene copy number.
Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides (2005)

The transactivator responsive region (TAR) present in the 5'-NTR of the HIV-1 genome represents a potential target for antiretroviral intervention and a model system for the development of specific inhibitors of RNA-protein interaction. Earlier, we have shown that an anti-TAR polyamide nucleotide analog (PNA(TAR)) conjugated to a membrane transducing (MTD) peptide, transportan, is efficiently taken up by the cells and displays potent antiviral and virucidal activity [B. Chaubey, S. Tripathi, S. Ganguly, D. Harris, R. A. Casale and V. N. Pandey (2005) Virology, 331, 418-428]. In the present communication, we have conjugated five different MTD peptides, penetratin, tat peptide, transportan-27, and two of its truncated derivatives, transportan-21 and transportan-22, to a 16mer PNA targeted to the TAR region of the HIV-1 genome. The individual conjugates were examined for their uptake efficiency as judged by FACScan analysis, uptake kinetics using radiolabeled conjugate, virucidal activity and antiviral efficacy assessed by inhibition of HIV-1 infection/replication. While FACScan analysis revealed concentration-dependent cellular uptake of all the PNA(TAR)-peptide conjugates where uptake of the PNA(TAR)-penetratin conjugate was most efficient as >90% MTD was observed within 1 min at a concentration of 200 nM. The conjugates with penetratin, transportan-21 and tat-peptides were most effective as an anti-HIV virucidal agents with IC50 values in the range of 28-37 nM while IC50 for inhibition of HIV-1 replication was lowest with PNA(TAR)-transportan-27 (0.4 microM) followed by PNA(TAR)-tat (0.72 microM) and PNA(TAR)-penetratin (0.8 microM). These results indicate that anti-HIV-1 PNA conjugated with MTD peptides are not only inhibitory to HIV-1 replication in vitro but are also potent virucidal agents which render HIV-1 virions non-infectious upon brief exposure.
Synergistic chemsensitization and inhibition of tumor growth and metastasis by the antisense oligodeoxynucleotide targeting clusterin gene in a human bladder cancer model. (2001)

Clusterin expression is highly up-regulated in several normal and malignant tissues undergoing apoptosis. Although recent studies have demonstrated a protective role of clusterin expression against various kinds of apoptotic stimuli, the functional role of clusterin in the acquisition of a therapy-resistant phenotype in bladder cancer remains unknown. The objectives of this study were to determine whether antisense (AS) oligodeoxynucleotide (ODN) targeting the clusterin gene enhances apoptosis induced by cisplatin and to evaluate the usefulness of combined treatment with AS clusterin ODN and cisplatin in the inhibition of KoTCC-1 tumor growth and metastasis in a human bladder cancer KoTCC-1 model. We initially revealed the dose-dependent and sequence-specific inhibition of clusterin expression by AS clusterin ODN treatment in KoTCC-1 cells at both mRNA and protein levels. Clusterin mRNA was increased in a dose-dependent manner by cisplatin treatment at concentrations < or =10 mg/ml, and clusterin mRNA up-regulation induced by 10 mg/ml cisplatin peaked by 48-h post-treatment and began decreasing by 72-h post-treatment. Although there was no significant effect on growth of KoTCC-1 cells, AS clusterin ODN treatment significantly enhanced cisplatin chemosensitivity of KoTCC-1 cells in a dose-dependent manner, reducing the IC(50) by >50%. Characteristic apoptotic DNA ladder formation and cleavage of poly(ADP-ribose) polymerase protein were detected after combined treatment with AS clusterin ODN and cisplatin but not either agent alone. In vivo systemic administration of AS clusterin and cisplatin significantly decreased the s.c. KoTCC-1 tumor volume compared with mismatch control ODN plus cisplatin. Furthermore, after the orthotopic implantation of KoTCC-1 cells, combined treatment with AS clusterin and cisplatin significantly inhibited the growth of primary KoTCC-1 tumors, as well as the incidence of lymph node metastasis. Collectively, these findings demonstrated that clusterin helps confer a chemoresistant phenotype through inhibition of apoptosis and that combined AS clusterin ODN may be useful in enhancing the effects of cytotoxic chemotherapy in patients with bladder cancer.
Purification, characterization, cloning, and expression of a glutamic acid-specific protease from Bacillus licheniformis ATCC 14580. (1992)

A glutamic acid-specific protease has been purified to homogeneity from Bacillus licheniformis ATCC 14580 utilizing Phe-Leu-D-Glu-OMe-Sepharose affinity chromatography and crystallized. The molecular weight of the protease was estimated to be approximately 25,000 by SDS-polyacrylamide gel electrophoresis. This protease, which we propose to call BLase (glutamic acid-specific protease from B. licheniformis ATCC 14580), was characterized enzymatically. Using human parathyroid hormone (13-34) and p-nitroanilides of peptidyl glutamic acid and aspartic acid, we found a marked difference between BLase and V8 protease, EC 3.4.21.9, although both proteases showed higher reactivity for glutamyl bonds than for aspartyl bonds. Diisopropyl fluorophosphate and benzyloxycarbonyl Leu-Glu chloromethyl ketone completely inhibited BLase, whereas EDTA reversibly inactivated the enzyme. The findings clearly indicate that BLase can be classified as a serine protease. To elucidate the complete primary structure and precursor of BLase, its gene was cloned from the genomic DNA of B. licheniformis ATCC 14580, and the nucleotide sequence was determined. Taking the amino-terminal amino acid sequence of the purified BLase into consideration, the clones encode a mature peptide of 222 amino acids, which follows a prepropeptide of 94 residues. The recombinant BLase was expressed in Bacillus subtilis and purified to homogeneity. Its key physical and chemical characteristics were the same as those of the wild-type enzyme. BLase was confirmed to be a protease specific for glutamic acid, and the primary structure deduced from the cDNA sequence was found to be identical with that of a glutamic acid-specific endopeptidase isolated from Alcalase (Svendsen, I., and Breddam, K. (1992) Eur. J. Biochem. 204, 165-171), being different from V8 protease and the Glu-specific protease of Streptomyces griseus which consist of 268 and 188 amino acids, respectively.
Phosphorylation of transcription factors and control of the cell cycle. (1995)

Protein phosphorylation has evolved as the most versatile posttranslational modification widely used by cells. Signal transduction pathways mediated by activation of MAP kinases and protein kinase C trigger the exit of cells from the quiscence (Go-->G1 transition). Indeed, binding of growth factors at the cell surface triggers their receptors, usually possessing a tyrosine kinase on the cytoplasmic side, to phosphorylate other molecules passing on the information sequentially to GRB2 protein, to p21ras, to c-Raf-1, to MAP kinase kinase, to MAP kinase, to p90rsk, to transcription factors. Activated PKC, MAP kinase, and pp90src can translocate to the nucleus where they phosphorylate a number of protein transcription regulators in a cell cycle-dependent manner or in response to cell stimulation for exit from quiescence. The cell cycle is mainly regulated by p34cdc2 or otherwise called cdc2 in association with cyclins B at G2/M and by Cdk2 in association with cyclins A, D1, and E at G1/S checkpoints; phosphorylation of histone H1 and lamins by cdc2 triggers chromosome assembly and nuclear envelope breakdown, respectively, as a prelude to mitosis. Cdc2 activities functioning as a G2/M regulator are controlled by its phosphorylation and dephosphorylation at Ser/Thr residues. MAP kinases might be the missing link in the chain connecting the Go to G1 transition with the cell cycle regulation, whereas phosphorylation of replication protein factors, retinoblastoma, and p53 might link the G1 to S transition with the control of DNA synthesis. A number of transcription factors are known to stimulate DNA replication, including p53, c-Myc, AP-1, Oct-1, T-antigen; the DNA binding activities of all these proteins and their interaction with other transcription factors are controlled by phosphorylation. The nuclear import of several proteins including NF kappa B, Dorsal, glucocorticoid receptor, ISGF3, rNFIL-6, T antigen, and the kinases PKC, MAP, and p90rsk, are dependent on their phosphorylation at specific sites. Histone phosphorylation stimulated at discrete stages of the cell cycle or in response to cAMP or other stimuli might induce profound changes in chromatin organization.
Interleukin-2 gene transfer into human transitional cell carcinoma of the urinary bladder (1999)

Transitional cell carcinoma of the bladder is one of the human cancers most responsive to immunotherapy, and local interleukin-2 (IL-2) production appears to be an important requirement for immunotherapy to be effective. In this study, we engineered two human bladder cancer cell lines (RT112 and EJ) to constitutively release human IL-2 by retroviral vector-mediated gene transfer. Following infection and selection, stable and consistent production of biologically active IL-2 was demonstrated at both the mRNA and the protein level. Morphology, in vitro growth rate and proliferation, as well as other cytokine gene mRNA or membrane adhesion receptor expression, were not altered in IL-2 transduced cells as compared to their parental or control vector-infected counterparts. Moreover, IL-2 engineered cells lost their tumorigenicity into nu/nu mice and the mechanism of rejection appeared to involve multiple host effector cell populations, among which a prominent role was played by neutrophils and radiosensitive cells. These findings may offer support to the development of an IL-2-based gene therapy approach to human bladder cancer.
Noncontact Tactile Display Based on Radiation Pressure of Airborne Ultrasound (2010)

This paper describes a tactile display which provides unrestricted tactile feedback in air without any mechanical contact. It controls ultrasound and produces a stress field in a 3D space. The principle is based on a nonlinear phenomenon of ultrasound: Acoustic radiation pressure. The fabricated prototype consists of 324 airborne ultrasound transducers, and the phase and intensity of each transducer are controlled individually to generate a focal point. The DC output force at the focal point is 16 mN and the diameter of the focal point is 20 mm. The prototype produces vibrations up to 1 kHz. An interaction system including the prototype is also introduced, which enables users to see and touch virtual objects.
A tale of two cytokines: IL-17 and IL-22 in asthma and infection (2013)

The Th17 pathway has recently been shown to play a critical role in host defense, allergic responses and autoimmune inflammation. Th17 cells predominantly produce IL-17 and IL-22, which are two cytokines with broad effects in the lung and other tissues. This review summarizes not only what is currently known about the molecular regulation of this pathway and Th17-related cytokine signaling, but also the roles of these cytokines in pathogen immunity and asthma. In the last 5 years, the Th17 field has rapidly grown and research has revealed that the Th17 pathway is essential in lung pathogenesis in response to exogenous stimuli. As work in the field continues, it is expected that many exciting therapeutic advances will be made for a broad range of diseases.
Presence of chromosomal elements resembling the composite structure Tn3701 in streptococci (1990)

Tn3701, carried by Streptococcus pyogenes A454, is the first chromosomal composite element to be described; it contains in its central region Tn3703, a transposon similar to Tn916. A comparison by DNA-DNA hybridization of Tn3701 with omega(cat-tet) and Tn3951, carried by Streptococcus pneumoniae BM6001 and by Streptococcus agalactiae B109, respectively, revealed that the two latter structures are also Tn3701-like composite elements. The DNAs of 27 other antibiotic-resistant group A, B, C, and G streptococci and of S. pneumoniae BM4200 showed sequence homologies to Tn3701 (14 strains, including BM4200), to the regions of Tn3701 outside of Tn3703 (5 strains), and to Tn916 alone (8 strains). The DNAs of five strains did not detectably hybridize with any probe. The tetM gene was identified in most chromosomal genetic elements coding for tetracycline-minocycline resistance. Since Tn3701-like elements are widely disseminated among antibiotic-resistant streptococci (47% of the 34 strains studied), we propose that Tn3701 be considered the prototype of chromosomal composite elements.
ARSA: An Attack-Resilient Security Architecture for Multihop Wireless Mesh Networks (2006)

Multihop wireless mesh networks (WMNs) are finding ever-growing acceptance as a viable and effective solution to ubiquitous broadband Internet access. This paper addresses the security of WMNs, which is a key impediment to wide-scale deployment of WMNs, but thus far receives little attention. We first thoroughly identify the unique security requirements of WMNs for the first time in the literature. We then propose ARSA, an attack-resilient security architecture for WMNs. In contrast to a conventional cellular-like solution, ARSA eliminates the need for establishing bilateral roaming agreements and having real-time interactions between potentially numerous WMN operators. With ARSA in place, each user is no longer bound to any specific network operator, as he or she ought to do in current cellular networks. Instead, he or she acquires a universal pass from a third-party broker whereby to realize seamless roaming across WMN domains administrated by different operators. ARSA supports efficient mutual authentication and key agreement both between a user and a serving WMN domain and between users served by the same WMN domain. In addition, ARSA is designed to be resilient to a wide range of attacks. We also discuss other important issues such as incontestable billing