gebhart/patrepeval huggingface dataset:
Translocation Activity of C-terminal Domain of Pestivirus Erns and Ribotoxin L3 Loop (2002)

The pestivirus envelope glycoprotein E(rns) has RNase activity and therefore was suspected to enter cells to cleave RNA. The protein contains an RNase domain with a C-terminal extension, which shows homology with a membrane-active peptide. The modular architecture and the C-terminal homology suggested that the C terminus could be responsible for the presumed translocation. Peptides corresponding to the C-terminal domain of E(rns) and also the homologous L3 loop of ribotoxin II were indeed able to translocate across the eukaryotic cell membrane and were targeted to the nucleoli. The entire E(rns) protein was also able to translocate into the cell. Furthermore, other labeled proteins and even active enzymes could be transported inside the cell when they were attached to the C-terminal E(rns) peptide. Translocation was energy-independent and not mediated by a protein receptor. The peptides showed no specificity for cell type or species.
Peptidomimetics—Tailored Enzyme Inhibitors (1994)

Abstract Peptides and proteins (there is no clear boundary between the two classes of compounds) are absolutely essential components of organisms in many ways. While proteins have biocatalytic functions and are important components of tissues, peptides play an important role in the organism as hormones, neurotransmitters, and neuromodulators. Peptides and their analogues have long been used in medicinal chemistry as therapeutic agents for pathological conditions generally characterized by a disruption of the interplay between messenger molecules or enzyme substrates and their targets, the receptors and enzymes. For various biochemical and biophysical reasons there is an increasing tendency towards the use of chemical “Trojan horses” known as peptidomimetics. The chances that such agents are active generally increase with the magnitude of the “deceptive effect”, in other words in proportion to the degree of conversion of a peptide into a non‐peptide. Rational design has become a catchphrase which is at present applied frequently to the development of peptidomimetics. New computer programs are invaluable tools in such design processes. However, in spite of the many advances already made, we are still far from the final goal, the de novo design of peptidomimetics. Rational design is nonetheless advancing rapidly, and it is already clear that developments in the area of peptidomimetics have given a great boost to peptide chemistry as a whole. This can be expected to continue, so that in future peptide chemistry may be characterized by a type of symbiotic alliance between peptides and non‐peptides.
Genetic alterations in the p53 gene in the blast crisis of chronic myelogenous leukemia: analysis by polymerase chain reaction based techniques. (1993)

Rearrangements of the c-abl protooncogene and the bcr-gene are found in > 90% of patients in chronic phase of chronic myelogenous leukemia (CML). The molecular events leading to blast crisis, however, have not been well characterized. Gross alterations of the p53 gene have been detected in 30% of patients with blast crisis. Since point mutations in the p53 gene appear to be important in the process of transformation in many epithelial tumors, we looked for these mutations in the critical regions of the p53 gene (exons 4, 5, 6, 7, and 8). We used the polymerase chain reaction (PCR), direct sequencing, differential PCR, and single strand conformation polymorphism (SSCP) analysis to detect mutations of the p53 gene in samples from 21 patients with CML blast crisis. Two of 21 patients exhibited an intragenic deletion or rearrangement in p53. In addition, these patients were homozygous for the mutant p53 allele. No mutations were found in the p53 gene of the remaining 19 patients. However, sequencing of the CML blast crisis cell line, K562, revealed an insertion of a C at base position 956 within the fifth exon, causing a frame shift mutation and an early translational stop at codon 148. We conclude that, in contrast to solid tumors, mutations in exons 4-8 of p53 are not frequently seen in primary samples from CML blast crisis. However, deletions and/or rearrangements within the p53 gene do occur and may contribute to the progression from chronic phase to blast crisis in a limited number of patients with CML.
Studies on inflammation and wound healing: angiogenesis and collagen synthesis stimulated in vivo by resident and activated wound macrophages. (1984)

Wound inflammatory cells were harvested by aspiration of fluid from the "dead space" of subcutaneous rabbit wounds and transplanted into the cornea where, compared with suitable controls, they stimulated healing (i.e., angiogenesis, fibroplasia, and new collagen synthesis, which led to formation of visible, vascularized scar tissue). Analysis of the data and the literature supports the conclusions that: (1) inflammatory cells control the continuation of the repair process after the immediate effects of injury subside; (2) macrophages, as opposed to granulocytes, appear to be the major contributors; (3) activated by their presence in the wound, macrophages release substances that stimulate fibroplasia, collagen synthesis, and angiogenesis in vivo; and (4) tissue injury is not a maximum stimulus to repair, since endotoxin-treated macrophages have increased capacity to stimulate collagen synthesis and angiogenesis. A hypothesis is offered to explain the notorious clinical discrepancy between the extent of injury and the extent of repair.
Expression and regulation of neurotrophins in the nondegenerate and degenerate human intervertebral disc (2008)

Our findings show that both the annulus fibrosus and nucleus pulposus cells of the IVD express the neurotrophins NGF and BDNF, factors that may influence and enhance innervation and pain in the degenerate IVD. Expression of Trk-A and Trk-B by cells of the nondegenerate and degenerate IVD suggests an autocrine role for neurotrophins in regulation of disc cell biology. Furthermore, modulation of neurotrophin expression by IL-1beta and modulation of substance P expression by TNFalpha, coupled with their increased expression in the degenerate IVD, highlights novel roles for these cytokines in regulating nerve ingrowth in the degenerate IVD and associated back pain.
Constitutive Activation of the Shaker Kv Channel (2003)

In different types of K+ channels the primary activation gate is thought to reside near the intracellular entrance to the ion conduction pore. In the Shaker Kv channel the gate is closed at negative membrane voltages, but can be opened with membrane depolarization. In a previous study of the S6 activation gate in Shaker (Hackos, D.H., T.H. Chang, and K.J. Swartz. 2002. J. Gen. Physiol. 119:521-532.), we found that mutation of Pro 475 to Asp results in a channel that displays a large macroscopic conductance at negative membrane voltages, with only small increases in conductance with membrane depolarization. In the present study we explore the mechanism underlying this constitutively conducting phenotype using both macroscopic and single-channel recordings, and probes that interact with the voltage sensors or the intracellular entrance to the ion conduction pore. Our results suggest that constitutive conduction results from a dramatic perturbation of the closed-open equilibrium, enabling opening of the activation gate without voltage-sensor activation. This mechanism is discussed in the context of allosteric models for activation of Kv channels and what is known about the structure of this critical region in K+ channels.
Factors limiting adenovirus-mediated gene transfer into human lung and pancreatic cancer cell lines. (1999)

Adenoviral vectors are a widely used means of gene transfer. However, transgene expression after adenoviral administration varies among different carcinoma cell lines. We hypothesized that this variation is attributable, in part, to the presence of cell surface molecules involved in adenoviral infection. To test this, we first assessed adenovirus-mediated transgene expression in four human lung carcinoma cell lines and four human pancreatic carcinoma cell lines in terms of luciferase activities and found it to vary from 4.8 x 10(4) to 6.1 x 10(7) relative light units/microg of protein. Then, to determine whether the molecules involved in the entry of adenovirus into host cells were responsible for this variation, we evaluated the expression of alpha(v)beta5, alpha(v), beta3, alpha5, and beta1 integrins and that of coxsackievirus and adenovirus receptor (CAR) in these cell lines. Statistical analysis revealed that the levels of beta3 were associated with the levels of transgene expression. Blocking analysis showed that adenovirus-mediated gene transfer could be blocked by antibodies against these six molecules but not by the antibodies against alpha2 or alpha3 integrins, thus suggesting that the integrins alphavbeta5, alpha(v), beta3, alpha5, and beta1 and CAR molecules could limit adenovirus-mediated gene transfer when their levels fell below a certain threshold. Furthermore, cells expressing low levels of beta3 and resistant to conventional adenoviral vectors were susceptible to a vector containing the heparin-binding domain in its fiber, thus suggesting that redirecting vectors to receptors other than CAR may bypass the integrin pathway. These findings may have implications for improving the efficiency of adenovirus-mediated gene transfer and developing novel adenoviral vectors.
Listeria monocytogenes: a potent vaccine vector for neoplastic and infectious disease (1997)

Listeria monocytogenes (L. monocytogenes) is a promising candidate vaccine vector that naturally infects antigen-presenting cells, and targets antigen delivery to both the class I MHC pathway of endogenous antigen presentation and the class II pathway of exogenous antigen presentation. At the same time, L. monocytogenes stimulates the innate immune response to produce cytokines that enhance antigen-presenting function and induce a Th1-type cytokine profile associated with cell-mediated immune responses. Immune responses with these features are considered to be particularly important for clearance of viruses, tumors, and intracellular infections. In this review, we describe the development of methods to transform L. monocytogenes to express and secrete foreign antigens and the studies that have demonstrated that genetically engineered L. monocytogenes mutants are highly effective vectors for the induction of potent immune responses against viral antigens and tumor cells. In addition, we discuss the strengths and weaknesses of L. monocytogenes as a vaccine vector.
Establishment and characterization of seven dunning rat prostatic cancer cell lines and their use in developing methods for predicting metastatic abilities of prostatic cancers (1986)

In vitro cell lines were established from seven biologically distinct in vivo Dunning R3327 rat prostatic tumor sublines. Some of these in vitro cell lines (i.e., G, AT-1, AT-2) retain a low metastatic ability when inoculated back into syngeneic Copenhagen male rats, while others (i.e., AT-3, MAT-LyLu, MAT-Lu) retain a very high metastatic ability. A series of genetic (i.e., DNA content per cell, modal chromosomal number), as well as phenotypic parameters (i.e., morphology, 5 alpha-reductase, androgen receptor, estrogen receptor) were used to validate that the in vitro cell lines retained the major characteristics of the parental in vivo tumor sublines used for their respective establishment. A series of additional characteristics (i.e., morphology, growth rate, saturation density in surface culture, anchorage-dependent and -independent clonogenic potential) were compared between the high vs. the low metastatic in vitro cell lines to determine if a discriminatory parameter could be identified which reproducibly predicted the metastatic abilities of the particular prostatic cancer cell line. While the combination of the in vitro cell lines and their parental in vivo tumor subline will be a valuable tool for developing methods for predicting metastatic ability of prostate cancers, no single parameter yet measured is entirely successful in making this important distinction.
ChemInform Abstract: Donor—Acceptor‐Substituted Phenylethenyl Bithiophenes: Highly Efficient and Stable Nonlinear Optical Chromophores. (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Points-to analysis in almost linear time (1996)

We present an interprocedural flow-insensitive points-to analysis based on type inference methods with an almost linear time cost complexity To our knowledge, this is the asymptotically fastest non-trivial interprocedural points-to analysis algorithm yet described The algorithm is based on a non-standard type system. The type inferred for any variable represents a set of locations and includes a type which in turn represents a set of locations possibly pointed to by the variable. The type inferred for a function variable represents a set of functions It may point to and includes a type signature for these functions The results are equivalent to those of a flow-insensitive alias analysis (and control flow analysis) that assumes alias relations are reflexive and transitive.This work makes three contributions. The first is a type system for describing a universally valid storage shape graph for a program in linear space. The second is a constraint system which often leads to better results than the "obvious" constraint system for the given type system The third is an almost linear time algorithm for points-to analysis by solving a constraint system.
Energy consumption in mobile phones (2009)

In this paper, we present a measurement study of the energy consumption characteristics of three widespread mobile networking technologies: 3G, GSM, and WiFi. We find that 3G and GSM incur a high tail energy overhead because of lingering in high power states after completing a transfer. Based on these measurements, we develop a model for the energy consumed by network activity for each technology.Using this model, we develop TailEnder, a protocol that reduces energy consumption of common mobile applications. For applications that can tolerate a small delay such as e-mail, TailEnder schedules transfers so as to minimize the cumulative energy consumed meeting user-specified deadlines. We show that the TailEnder scheduling algorithm is within a factor 2x of the optimal and show that any online algorithm can at best be within a factor 1.62x of the optimal. For applications like web search that can benefit from prefetching, TailEnder aggressively prefetches several times more data and improves user-specified response times while consuming less energy. We evaluate the benefits of TailEnder for three different case study applications - email, news feeds, and web search - based on real user logs and show significant reduction in energy consumption in each case. Experiments conducted on the mobile phone show that TailEnder can download 60% more news feed updates and download search results for more than 50% of web queries, compared to using the default policy.
Identification of novel chemoattractant peptides for human leukocytes (2001)

Superoxide is the most important armory on the primary defense line of monocytes against invading pathogens, and the identification of new stimuli and the characterization of the regulatory mechanism of superoxide generation are of paramount importance. In this study, we identified 3 novel peptides by screening a synthetic hexapeptide combinatorial library and modification of 1 of the peptides. The isolated peptides that can induce superoxide generation in human monocytes are His-Phe-Tyr-Leu-Pro-Met-CONH(2) (HFYLPM), Met-Phe-Tyr-Leu-Pro-Met-CONH(2) (MFYLPM), and His-Phe-Tyr-Leu-Pro-D-Met-CONH(2) (HFYLPm). All 3 peptides also caused intracellular calcium ([Ca(++)](i)) rise. We tested the specificities of the peptides on cells of different origin by looking at [Ca(++)](i) rise. All 3 peptides acted specifically on leukocytes and not on nonimmune cells. Among leukocytes, HL60 and Jurkat T cells were stimulated specifically by MFYLPM or HFYLPM, respectively. As a physiologic characteristic of the peptides, we observed that all 3 peptides induced chemotactic migration of monocytes. Studying receptor specificity, we concluded that the 3 peptides might act on some shared and some distinct receptor(s) on leukocytes. Studying intracellular signaling set in motion by the peptides revealed that HFYLPM, but not MFYLPM or HFYLPm, induced chemotaxis via phosphatidylinositol-3 kinase and protein kinase C. Because HFYLPM, MFYLPM, and HFYLPm not only exhibit different specificities depending on cell type and status of differentiation but also stimulate cells via distinct receptors and signaling, the 3 novel peptides might be useful tools to study leukocyte activation.
THE RIGHT ANSWER TO THE WRONG QUESTION: IDENTIFYING SUPERIOR ACTIVE PORTFOLIO MANAGEMENT (2006)

The debate over the value of active portfolio management has often centered on whether the average active manager is capable of producing returns that exceed expectations. We argue that a more useful way to frame this issue is to focus on identifying those managers who are the most likely to generate superior risk-adjusted returns (i.e., alpha) in the future. Using a style-classified sample of mutual funds, we document several tractable relationships between observable fund characteristics and its future alpha, most notably the tendency for performance to persist over time. While median managers produce positive risk-adjusted performance approximately 45% of the time, we document a selection process that improves an investor’s probability of identifying a superior active manager to almost 60%. We conclude that there is a place in the investor’s portfolio for the properly chosen active manager.
Plasminogen activator inhibitor: a regulator of ancrod-induced fibrin deposition in rabbits (1987)

Plasma levels of a fast-acting plasminogen activator inhibitor (PAI), which neutralizes both tissue plasminogen activator (t-PA) and urokinase, are markedly increased in endotoxin-treated rabbits. The ability of this inhibitor to prevent the fibrinolysis that occurs after a thrombogenic stimulus was investigated in a rabbit model. Normal and endotoxin-treated male New Zealand rabbits were infused with ancrod, an enzyme that causes noncrosslinked fibrin formation in vivo. Ancrod stimulated t-PA activity by 90% in normal rabbits and caused hypofibrinogenemia but did not increase PAI levels or induce fibrin deposition in target organs. Rabbits injected with endotoxin (10 micrograms/kg) showed an increase in PAI from less than 1 to 32 U/mL 4 hours later. When ancrod was infused at this time, 90% of the rabbits developed renal fibrin thrombi. Fibrin deposition was recorded in 40% of the rabbits that received a lower dose of endotoxin (1.0 microgram/kg) and had a PAI level of 14 U/ml at the time of ancrod infusion 4 hours later. Fibrin deposition did not occur in the endotoxin-treated rabbits that received normal saline. These data suggest that high levels of PAI inhibit fibrinolysis in vivo, thereby promoting fibrin clot deposition following a thrombogenic stimulus.
Central pathways of pulmonary and lower airway vagal afferents (2006)

Lung sensory receptors with afferent fibers coursing in the vagus nerves are broadly divided into three groups: slowly (SAR) and rapidly (RAR) adapting stretch receptors and bronchopulmonary C fibers. Central terminations of each group are found in largely nonoverlapping regions of the caudal half of the nucleus of the solitary tract (NTS). Second order neurons in the pathways from these receptors innervate neurons located in respiratory-related regions of the medulla, pons, and spinal cord. The relative ease of selective activation of SARs, and to a lesser extent RARs, has allowed for more complete physiological and morphological characterization of the second and higher order neurons in these pathways than for C fibers. A subset of NTS neurons receiving afferent input from SARs (termed pump or P-cells) mediates the Breuer-Hering reflex and inhibits neurons receiving afferent input from RARs. P-cells and second order neurons in the RAR pathway also provide inputs to regions of the ventrolateral medulla involved in control of respiratory motor pattern, i.e., regions containing a predominance of bulbospinal premotor neurons, as well as regions containing respiratory rhythm-generating neurons. Axon collaterals from both P-cells and RAR interneurons, and likely from NTS interneurons in the C-fiber pathway, project to the parabrachial pontine region where they may contribute to plasticity in respiratory control and integration of respiratory control with other systems, including those that provide for voluntary control of breathing, sleep-wake behavior, and emotions.
Analysis of the cellular mechanism underlying inhibition of EAE after treatment with anti-NKG2A F(ab′) 2 (2010)

Autoimmune encephalomyelitis may be ameliorated experimentally by enhancing NK cell-mediated elimination of activated autoreactive T cells through a mutation that interrupts the interaction between Qa-1(b) and CD94/NKG2A. Here we evaluate the ability of an anti-NKG2A F(ab')(2) Ab to enhance elimination of autoreactive T cells and reduce experimental autoimmune encephalomyelitis (EAE). Anti-NKG2A F(ab')(2) treatment diminishes progression of both myelin oligodendrocyte glycoprotein (MOG)-induced EAE in intact C57BL/6 mice and after adoptive transfer of disease-causing T cells. Analyses of the underlying mechanism revealed that administration of anti-NKG2A F(ab')(2) Ab reduces CD4(+) T recall responses to MOG and skews the proportion of IL-17- and IFNgamma-producing CD4(+) T cells toward the protective IL-4- and IL-10-secreting CD4(+) T cell subpopulations. CD94/NKG2A-dependent inhibition of inflammatory damage to spinal cord is associated with decreased infiltration of T cells and reduced microglia activation in the central nervous system. Because anti-NKG2A F(ab')(2) treatment had no detectable effect on the numbers or activity of T and B lymphocytes and NK cells in peripheral lymphoid tissues, this anti-NKG2A-based approach may represent a safe and effective therapy for this CNS disorder.
Pimelautide or Trimexautide as Built-in Adjuvants Associated with an HIV-1-Derived Peptide: Synthesis and in Vivo Induction of Antibody and Virus-Specific Cytotoxic T-Lymphocyte-Mediated Response (1995)

Covalent association of lipopeptidic immunostimulants is known to improve the immunogenicity of short peptides. In this paper, we describe the synthesis of four analytically pure immunogens, prepared by two different strategies, in which a hexadecameric peptide (V3) derived from the principal neutralizing domain of HIV-1 envelope glycoprotein was associated with two different murein-derived lauroyl-peptides, Pimelautide (RP 44102), or Trimexautide (RP 56142). The in vivo immunogenicity of these compounds was evaluated according to two different criteria: the ability to elicit a cellular-T cytotoxic (CTL response) and the ability to stimulate antibody response. Our studies show that one of our compounds (TrxSucV3) was able to efficiently induce a relevant virus-specific CTL response, while another one (PimSucV3) was able to stimulate a strong antibody response to the linked peptide, or to a co-injected protein. These results suggest that both activities rely on different structure-activity relationships and that such a chemically defined model of peptide vaccines may be used to selectively stimulate subpopulations of immunocompetent cells.