gebhart/patrepeval huggingface dataset:
Peripheral vascular occlusions: mechanical recanalization with a metal laser probe after guide wire dissection. (1990)

Fourteen patients underwent recanalization of occlusions of the iliac or femoral artery. Subintimal passage of the guide wire and catheter occurred and was confirmed on angiograms obtained after administration of contrast medium. Recanalization of the true lumen was impossible, despite repeated attempts. Rather than abandon the procedure, the authors advanced a 2.5-mm laser probe to the occlusion, and the lumen was successfully reentered without the application of laser energy in 12 patients. The authors believe this technique is useful in traversing arterial occlusions after a standard guide wire technique has failed. The development of a wire and catheter with similar properties might allow the more widespread use of this technique.
Why HIV Virions Have Low Numbers of Envelope Spikes: Implications for Vaccine Development (2014)

The major structural proteins of most viruses, including both naked icosahedral and enveloped types, are present in a dense array on the virion surface. This pattern has likely evolved to promote structural integrity, maximize cell binding and entry, and minimize genome size. HIV and related simian lentiviruses are unusual in having a low density of envelope protein spikes on their surfaces (Figure 1) [1]. Why has HIV evolved this exceptional virion structure? We believe that studies of human papillomavirus (HPV) virus-like particles (VLPs), which are the basis of the highly successful HPV vaccine, may provide the conceptual underpinning for answering this question and key insights for developing effective HIV prophylactic vaccines.



Figure 1

What's different about HIV virions?




Why Does HIV Have So Few Virion Spikes?
HIV is notably inefficient at transmission—it has been estimated that 200–2,000 encounters are required per heterosexual transmission event [2]. In large part this may be due to the low number (estimated to be 14, on average) of envelope spikes per virion, especially since increasing the number of envelope spikes per virion increases infectivity, at least in an in vitro simian immunodeficiency virus (SIV) model [1], [3]. It seems unlikely that HIV evolved a low number of envelope spikes to limit its transmission efficiency. Low density of env spikes may have evolved, in part, because it prevents bivalent binding of immunoglobulin G (IgG) antibodies to the virion, thus reducing antibody avidity and impeding neutralization [4]. However, we think that an alternative explanation for the selection for low numbers of envelope spikes is that this feature retards the induction of a broad spectrum antibody response.
Rapid Communication : Somatic Cell Nuclear Transfer in Humans: Pronuclear and Early Embryonic Development (2001)

Human therapeutic cloning requires the reprogramming of a somatic cell by nuclear transfer to generate autologous totipotent stem cells. We have parthenogenetically activated 22 human eggs and also performed nuclear transfer in 17 metaphase II eggs. Cleavage beyond the eight-cell stage was obtained in the parthenogenetic-activated eggs, and blastocoele cavities were observed in six. Three somatic cell-derived embryos developed beyond the pronuclear stage up to the six-cell stage. The ability to create autologous embryos represents the first step towards generating immune-compatible stem cells that could be used to overcome the problem of immune rejection in regenerative medicine.
Loss of methylation at the IFNG promoter and CNS‐1 is associated with the development of functional IFN‐γ memory in human CD4+T lymphocytes (2012)

Cytokine memory for IFN-γ production by effector/memory Th1 cells plays a key role in both protective and pathological immune responses. To understand the epigenetic mechanism determining the ontogeny of effector/memory Th1 cells characterized by stable effector functions, we identified a T-cell-specific methylation pattern at the IFNG promoter and CNS-1 in ex vivo effector/memory Th1 cells, and investigated methylation dynamics of these regions during the development of effector/memory Th1 cells. During Th1 differentiation, demethylation occurred at both the promoter and CNS-1 regions of IFNG as early as 16 h, and this process was independent of cell proliferation and DNA synthesis. Using an IFN-γ capture assay, we found early IFN-γ-producing cells from 2-day differentiating cultures acquired "permissive" levels of demethylation and developed into effector/memory Th1 cells undergoing progressive demethylation at the IFNG promoter and CNS-1 when induced by IL-12. Methylation levels of these regions in effector/memory Th1 cells of peripheral blood from rheumatoid arthritis patients correlated inversely with reduced frequencies of IFN-γ-producers, coincident with recruitment of effector/memory Th1 cells to the site of inflammation. Thus, after termination of TCR stimulation, IL-12 signaling potentiates the stable functional IFN-γ memory in effector/memory Th1 cells characterized by hypomethylation at the IFNG promoter and CNS-1.
Low writing energy and sub nanosecond spin torque transfer switching of in-plane magnetic tunnel junction for spin torque transfer random access memory (2011)

This work investigated in-plane MgO-based magnetic tunnel junctions (MTJs) for the application of spin torque transfer random access memory (STT-RAM). The MTJ in this work had an resistance area product (RA) = 4.3 Ω·μm2, tunneling magnetoresistance ratio ∼135%, thermal stability factor Δ(H)=68 (by field measurement), and Δ(I) = 50 (by current measurement). The optimal writing energy was found to be 0.286 pJ per bit at 1.54 ns for antiparallel (AP) state to parallel (P) state switching, and 0.706 pJ per bit at 0.68 ns for P state to AP state switching. Ultra fast spin torque transfer (STT) switching was also observed in this sample at 580 ps (AP to P) and 560 ps (P to AP). As a result, 0.6–1.3 GHz was determined to be the optimal writing rate from writing energy consumption of view. These results show that in-plane MgO MTJs are still a viable candidate as the fast memory cell for STT-RAM.
Immunogenicity of Ribonucleic Acid Preparations Obtained from Salmonella typhimurium (1970)

Mice immunized with purified whole-cell ribonucleic acid (RNA), RNA from the bacterial "particulate" fraction, and ribosome-associated RNA obtained from Salmonella typhimurium were found to be resistant to subsequent challenge infection with virulent salmonellae. Chemically, the immunogenic nucleic acid fractions contained from 1 to 3% "contaminant" material defined (based on the mean of 19 different preparations) as protein (0.24%), deoxyribonucleic acid (0.43%), methyl pentose (0.64%), hexose (1.58%), and undefined carbohydrate (0.76%). Heptoses and lipoidal material were not detectable in any of the immunogenic preparations examined. Physically, the nucleic acid preparations, after analytical ultracentrifugation, exhibited three boundaries similar to those reported elsewhere in comparable systems: 4 to 5S, 16S, and 23S. An evaluation of the immunity induced by the ribosome-associated RNA established that the immune response was (i) comparable to that induced 15 days postimmunization with live salmonellae and by ribosomal vaccines, but greater at 30 days postimmunization than that in mice immunized with attenuated salmonellae; (ii) dependent on the quantity of immunogen administered; (iii) dependent on the size of the infective inocula; (iv) inhibited at 15 but not at 30 days postimmunization when the immunogenic nucleic acid preparations were incorporated into Freund's incomplete adjuvant, (v) reduced or lost by dialysis in relatively high or low immunizing doses, respectively; and (vi) unaffected by enzymatic treatment of the preparations with trypsin, deoxyribonuclease, Pronase plus pancreatic ribonuclease, or pancreatic ribonuclease alone. The possible mode of action of ribosome-associated RNA in inducing an immune response to subsequent challenge infection with the homologous organism is discussed.
The History and Advances of Reversible Terminators Used in New Generations of Sequencing Technology (2013)

DNA sequencing using reversible terminators, as one sequencing by synthesis strategy, has garnered a great deal of interest due to its popular application in the second-generation high-throughput DNA sequencing technology. In this review, we provided its history of development, classification, and working mechanism of this technology. We also outlined the screening strategies for DNA polymerases to accommodate the reversible terminators as substrates during polymerization; particularly, we introduced the "REAP" method developed by us. At the end of this review, we discussed current limitations of this approach and provided potential solutions to extend its application.
Protection and Security on the Information Superhighway (1995)

A Growing Dependency The Disrupters Are Among Us Asleep at the Switch Protecting Your Information Assets Protection Posture Case Studies Summary and Conclusions Appendices References Glossary Index.
Combination Epigenetic Therapy Has Efficacy in Patients with Refractory Advanced Non–Small Cell Lung Cancer (2011)

This study demonstrates that combined epigenetic therapy with low-dose azacitidine and entinostat results in objective, durable responses in patients with solid tumors and defines a blood-based biomarker that correlates with clinical benefit.
Sucrose Phosphate Synthase, Sucrose Synthase, and Invertase Activities in Developing Fruit of Lycopersicon esculentum Mill. and the Sucrose Accumulating Lycopersicon hirsutum Humb. and Bonpl. (1991)

The green-fruited Lycopersicon hirsutum Humb. and Bonpl. accumulated sucrose to concentrations of about 118 micromoles per gram fresh weight during the final stages of development. In comparison, Lycopersicon esculentum Mill. cultivars contained less than 15 micromoles per gram fresh weight of sucrose at the ripe stage. Glucose and fructose levels remained relatively constant throughout development in L. hirsutum at 22 to 50 micromoles per gram fresh weight each. Starch content was low even at early stages of development, and declined further with development. Soluble acid invertase (EC 3.2. 1.26) activity declined concomitant with the rise in sucrose content. Acid invertase activity, which was solubilized in 1 molar NaCl (presumably cell-wall bound), remained constant throughout development (about 3 micromoles of reducing sugars (per gram fresh weight) per hour. Sucrose phosphate synthase (EC 2.4.1.14) activity was present at about 5 micromoles of sucrose (per gram fresh weight) per hour even at early stages of development, and increased sharply to about 40 micromoles of sucrose (per gram fresh weight) per hour at the final stages of development studied, parallel to the rise in sucrose content. In comparison, sucrose phosphate synthase activity in L. esculentum remained low throughout development. The possible roles of the sucrose metabolizing enzymes in determining sucrose accumulation are discussed.
A Role for the β-Catenin/T-Cell Factor Signaling Cascade in Vascular Remodeling (2002)

Beta-catenin and T cell factor (Tcf) are distal components of the highly conserved Wnt pathway that govern cell fate and proliferation in lower organisms. Thus, we hypothesized that the regulation of beta-catenin and Tcf played a critical role in vascular remodeling. The first objective was to define beta-catenin expression in vascular smooth muscle cells (VSMCs) after balloon injury. Indeed, beta-catenin mRNA and protein were significantly elevated 7 days after balloon injury in the rat carotid artery. We hypothesized that beta-catenin accumulation in response to vascular injury inhibited VSMC apoptosis. In line with our hypothesis, transfection of a degradation-resistant beta-catenin transgene into rat VSMCs significantly inhibited apoptosis. Accumulation of beta-catenin also resulted in a 10-fold increase in the activation of Tcf. To test if Tcf was necessary to confer beta-catenin-induced survival, loss of function studies were carried out with a dominant negative Tcf-4 transgene lacking the beta-catenin binding domain, Tcf4(N31). Indeed, loss of Tcf-4 activity abolished beta-catenin-induced survival. We further postulated that beta-catenin and Tcf promoted cell cycle progression by activating cyclin D1, a target gene of Tcf-4. Beta-catenin activated cyclin D1, and this activation was partially blocked with loss of Tcf-4. In parallel, blockade of Tcf-4 resulted in inhibition of [3H]thymidine incorporation and partial blockade of the G1-S phase transition. In conclusion, beta-catenin and Tcf-4 play a dual role in vascular remodeling by inhibiting VSMC apoptosis and promoting proliferation.
Mouse hepatocytes migrate to liver parenchyma and function indefinitely after intrasplenic transplantation. (1991)

One approach to gene therapy for hepatic diseases is to remove hepatocytes from an affected individual, genetically alter them in vitro, and reimplant them into a receptive locus. Although returning hepatocytes to the liver itself would be advantageous, the feasibility of this approach has never been evaluated due to the inability to distinguish donor from host hepatocytes. To unambiguously identify transplanted hepatocytes after transplantation, and to better quantitate their number and degree of liver function, two transgenic mouse lines were generated in a C57BL/6 background. The first expresses the Escherichia coli beta-galactosidase gene from the relatively liver-specific human alpha 1-antitrypsin (hAAT) promoter and allows transgenic hepatocytes to be readily identified after 5-bromo-4-chloro-3-indolyl beta-D-galactoside staining; the second produces the hAAT protein under control of the same promoter, which enables hepatocyte survival and maintenance of liver function to be quantitated by measuring the serum levels of hAAT. Hepatocytes isolated from transgenic donors were transplanted into nontransgenic C57BL/6 recipients by intrasplenic injection. Surprisingly, a large fraction of these cells were identified within the liver parenchyma but not the spleen at 2 months after transplantation. The high levels of serum hAAT detected in transplant recipients were stable for greater than 6 months, suggesting that established cells will survive indefinitely. These results have important implications for liver organogenesis and hepatic gene therapy.
Frequency of Measles Virus-Specific CD4+and CD8+T Cells in Subjects Seronegative or Highly Seropositive for Measles Vaccine (2003)

The protective effect of measles immunization is due to humoral and cell-mediated immune responses. Little is known about cell-mediated immunity (CMI) to measles vaccine virus, the relative contribution of CD4(+) and CD8(+) T cells to variability in such immune responses, and the immunologic longevity of the CMI after measles vaccination in humans. Our study characterizes cellular immune response in subjects seronegative or highly seropositive for measles vaccine immunoglobulin G-specific antibody, aged 15 to 25 years, previously immunized with two doses of measles-mumps-rubella II vaccine. We evaluated the ability of subjects to respond to measles vaccine virus by measuring measles virus-specific T-cell proliferation. We examined the frequencies of measles virus-specific memory Th1 and Th2 cells by an ELISPOT assay. Our results demonstrated that proliferation of T cells in seronegative subjects was significantly lower than that for highly seropositive subjects (P = 0.003). Gamma interferon (IFN-gamma) secretion predominated over interleukin 4 (IL-4) secretion in response to measles virus in both groups. The median frequency of measles virus-reactive CD8(+) T cells secreting IFN-gamma was 0.09% in seronegative subjects and 0.43% in highly seropositive subjects (P = 0.04). The median frequency of CD4(+) T cells secreting IL-4 in response to measles virus was 0.03% in seronegative subjects and 0.09% in highly seropositive subjects (P = 0.005). These data confirm the presence of measles virus-specific cellular immune responses post-measles vaccine immunization in humans. The detection of measles virus-induced IFN-gamma and IL-4 production by ELISPOT can be used to identify measles virus-specific low-frequency memory T cells in subjects immunized with measles vaccine. These differences agree in directionality with the observed antibody response phenotype.
Ribosome‐independent biosynthesis of biologically active peptides: Application of synthetic biology to generate structural diversity (2012)

Peptide natural products continue to play an important role in modern medicine as last-resort treatments of many life-threatening diseases, as they display many interesting biological activities ranging from antibiotic to antineoplastic. A large fraction of these microbial natural products is assembled by ribosome-independent mechanisms. Progress in sequencing technology and the mechanistic understanding of secondary metabolite pathways has led to the discovery of many formerly cryptic natural products and a molecular understanding of their assembly. Those advances enable us to apply protein and metabolic engineering approaches towards the manipulation of biosynthetic pathways. In this review we discuss the application potential of both templated and non-templated pathways as well as chemoenzymatic strategies for the structural diversification and tailoring of peptide natural products.
[(1-Pyrenylmethyl)amino] alcohols, a new class of antitumor DNA intercalators. Discovery and initial amine side chain structure-activity studies (1990)

In the series of 1-pyrenylmethylamines studied in this work the relationships among structure, interaction with DNA, and murine antitumor activity were examined. Binding studies show that all of these 1-pyrenylmethylamine derivatives bind to some extent to DNA by intercalation. The presence of additional basic amine groups in the side chain enhances DNA binding due to electrostatic interactions. Those compounds containing only a single basic benzylic amine bind similarly to DNA. Only the presence of bulky side chains appears to decrease the DNA interactions in the compounds examined. Although antitumor activity is seen for (1-pyrenylmethyl)amino alcohols, useful antitumor activity in the series is limited to those congeners bearing the 2-amino-1,3-propanediol-type side chain. These derivatives bind moderately to DNA. DNA binding is a necessary but not sufficient criterion for antitumor activity in the series. In addition, the strength of DNA binding does not correlate with the antitumor activity in the group of active compounds. Three related 2-[(arylmethyl)amino]-1,3-propanediol derivatives (AMAPs) [crisnatol (770U82), 773U82, and 502U83] are currently in clinical trials as potential antitumor agents.
A low bending loss multimode fiber transmission system (2012)

This paper presents a high bend tolerant multimode optical fiber transmission system that is compatible with standard 50 im graded index multimode fiber, interms of achievable bandwidth and interconnectivity losses. When the 10 loops of the proposed bend resistive multimode fiber were wrapped around a cylinder of 1.5 mm radius, bend losses below -0.2 dB were achieved in case of experimentally produced fiber. Furthermore, when the section of the proposed bend resistive fiber was inserted between two sections of a standard 50 im graded index multimode fiber, the total experimental measured loss proved to be below -0.15 dB.
The challenge of gene therapy and DNA delivery (2001)

It is 10 years since the first gene therapeutic was administered to patients. Since that time approximately 3500 patients have been treated and although some evidence of gene transfer has been seen it has generally been inadequate for a meaningful clinical response. The major challenges have been delivery of DNA to the target cells and duration of expression. A variety of gene transfer systems have been evaluated and these are summarized with their advantages and disadvantages. Encouraging data have been obtained recently by a number of workers and there is some optimism that the enormous potential of gene therapy will be realized in the second decade of its development.
Programmed death-1 inhibition in renal cell carcinoma: clinical insights and future directions. (2014)

The treatment of metastatic renal cell carcinoma (mRCC) has evolved markedly over the past decade, broaden- ing beyond immune-based strategies (eg, interleukin-2 and interferon-α) to include targeted agents (eg, sunitinib [Sutent, Pfizer] and sorafenib [Nexavar, Bayer]). Recently, there has been a renewed interest in immune-based strategies, with clinical trials underway to assess vaccines and other immunomodulatory agents. Of particular interest are agents that inhibit the interaction between the programmed death-1 (PD-1) receptor and its ligand (PD-L1) at the T-cell/antigen-presenting cell interface. This interaction produces T-cell anergy and therefore stifles the antitumor immune response. Monoclonal antibodies to PD-1 (eg, nivolumab, lambrolizumab, and pidilizumab) and PD-L1 (MPDL3280A and BMS-936559) are in various stages of clinical development. The clinical trajectory of these agents is discussed herein, with specific attention to the potential placement of PD-1/ PD-L1 inhibition in the crowded therapeutic landscape of mRCC.
Efforts To Expand the Genetic Alphabet:  Identification of a Replicable Unnatural DNA Self-Pair (2004)

Six unnatural nucleotides featuring fluorine-substituted phenyl nucleobase analogues have been synthesized, incorporated into DNA, and characterized in terms of the structure and replication properties of the self-pairs they form. Each unnatural self-pair is accommodated in B-form DNA without detectable structural perturbation, and all are thermally stable and selective to roughly the same degree. Furthermore, the efficiency of polymerase-mediated mispair synthesis is similar for each unnatural nucleotide in the template. In contrast, the efficiency of polymerase-mediated self-pair extension is highly dependent on the specific fluorine substitution pattern. The most promising unnatural base pair candidate of this series is the 3-fluorobenzene self-pair, which is replicated with reasonable efficiency and selectivity.
Blotting of RNA onto ion exchange paper allowing subsequent characterization byin situtranslation in addition to blot hybridization (1982)

We present the preparation of an ion exchange paper which can be used as a solid carrier in the transfer of RNA from gels. In addition to detection by blot hybridization to specific probes, transferred RNA can be characterized by cell-free translation in situ. Preparation of the paper is simple, inexpensive and reproducible. Examples of applications are shown and possible other applications are discussed.
A high-speed 8 bit A/D converter based on a Gray-code multiple folding circuit (1979)

An A/D converter is described using a parallel structure to synthesize the multiple folding transfer characteristic for the Gray code. The number of comparators needed equals that of a purely sequential design. The performance is demonstrated by an 8 bit converter for video application, as well as a nonlinear version for PCM speech encoding. In both designs a 4-bit multiple folding circuit is followed by a 4 bit parallel block.