gebhart/patrepeval huggingface dataset:
Cost-Benefit Tradeoffs in Engineered lac Operons (2012)

Cells must balance the cost and benefit of protein expression to optimize organismal fitness. The lac operon of the bacterium Escherichia coli has been a model for quantifying the physiological impact of costly protein production and for elucidating the resulting regulatory mechanisms. We report quantitative fitness measurements in 27 redesigned operons that suggested that protein production is not the primary origin of fitness costs. Instead, we discovered that the lac permease activity, which relates linearly to cost, is the major physiological burden to the cell. These findings explain control points in the lac operon that minimize the cost of lac permease activity, not protein expression. Characterizing similar relationships in other systems will be important to map the impact of cost/benefit tradeoffs on cell physiology and regulation.
Monoclonal antiidiotypic antibodies related to the p97 human melanoma antigen. (1989)

We have made monoclonal antiidiotypic antibodies (Ab2) relating to the p97 antigen of human melanoma. This was accomplished by immunizing BALB/c mice with 96.5, a monoclonal antibody (MAb) specific for epitope p97a, hybridizing their spleen cells with NS-1 myeloma cells, and selecting for hybridomas making antibody binding to Fab fragments prepared from MAb 96.5 (Fab 96.5). The Ab2 were tested for binding to Fab 96.5, as well as for their ability to inhibit the binding between MAb 96.5 and p97. Three monoclonal Ab2 were identified which competitively inhibited the binding between p97 and MAb 96.5 when injected into either BALB/c or C3H/HeN mice; two of them induced Ab3 which expressed the same idiotype as MAb 96.5 and which were specific for p97. These two Ab2 thus appear to functionally mimic p97. They were, however, unable to induce delayed-type hypersensitivity to p97 and to protect mice against transplants of p97-positive mouse melanoma cells, suggesting that the epitope recognized by MAb 96.5 may not be a target for cell-mediated rejection of tumors.
Determination of absolute structure using Bayesian statistics on Bijvoet differences (2008)

A new probabilistic approach is introduced for the determination of the absolute structure of a compound which is known to be enantiopure based on Bijvoet-pair intensity differences. The new method provides relative probabilities for different models of the chiral composition of the structure. The outcome of this type of analysis can also be cast in the form of a new value, along with associated standard uncertainty, that resembles the value of the well known Flack x parameter. The standard uncertainty we obtain is often about half of the standard uncertainty in the value of the Flack x parameter. The proposed formalism is suited in particular to absolute configuration determination from diffraction data of biologically active (pharmaceutical) compounds where the strongest resonant scattering signal often comes from oxygen. It is shown that a reliable absolute configuration assignment in such cases can be made on the basis of Cu Kalpha data, and in some cases even with carefully measured Mo Kalpha data.
MOULD ARTHROPLASTY OF THE KNEE (1969)

1. Stainless steel mould arthroplasty of the knee is described and a ten-year follow-up study of sixty-two operations is reported. Fifty-four were for rheumatoid arthritis and eight for osteoarthritis.

2. Forty-nine of the sixty-two joints retained mobility, six had become ankylosed and five were later arthrodesed ; two limbs were amputated. The forty-nine mobile knees included twenty-seven which were painless at all times, and fourteen in which only an occasional twinge was felt.

3. The range of movement was increased in twenty-two joints as compared with the state before operation, diminished in twelve and unaltered in five. In ten knees measurements before operation were not available.

4. Flexion deformity, swelling, stability and function were improved in a significant number of joints.

5. Patients suffering from active rheumatoid arthritis often found that the joint operated upon no longer took part in generalised flares of the disease.
Electrostrictive Response of Elastomeric Polymers (1993)

It is well known that the electrostrictive response of all materials is small at low applied electric fields. However, the electrostrictive strains (S) are related to the square of the applied field (E). It therefore appeared reasonable to assume that for a soft polymeric material, a large thickness response, d sub T(d sub T = partial derivative of S/partial derivative of E), might be obtained by application of sufficiently high D.C. bias fields (approx. 20MV /m) to a film while driving the film with an A.C. signal. Under such high electric fields, d sub T values greater than 3 A/V were obtained for a low crystallinity poly(vinylidene fluoride) (PVF2) film containing 65% by weight of a plasticizer tricresyl phosphate (TCP). Values of 6 A/V were obtained for certain classes of thermoplastic elastomers, i.e., polyurethanes. These values are considerably greater than those obtained from conventional piezoelectric ceramic materials and an order of magnitude greater than the 0.25 A/V obtained from polarized PVF2. In addition, large elastic strains (&gt;3%) were observed as a function of applied D.C. field.
Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. (2001)

Immunosuppression may contribute to the progression of cancer. In this study we assessed the structural and functional status of T cells from tumor specimens obtained from patients with early stage non-small cell lung cancer and late-stage ovarian cancer. Although some groups have described structural alterations in the TCR in patients with other malignancies, we did not observe decreased expression of the CD3zeta subunit in the tumor-associated T cells. However, increased percentages of CD4(+)CD25(+) T cells were observed in the non-small cell lung cancer tumor-infiltrating lymphocytes and ovarian cancer tumor-associated lymphocytes. Furthermore, these CD4(+)CD25(+) T cells were found to secrete transforming growth factor-beta, consistent with the phenotype of regulatory T cells. Despite a generalized expression of lymphocyte activation markers in the tumor-associated T-cell populations, the CD8(+) T cells expressed low levels of CD25. To determine whether expression of CD25 could be restored on the CD8 cells, tumor-associated T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies. After stimulation, nearly all of the CD8 T cells expressed CD25. Furthermore, despite the low levels of interleukin 2, IFN-gamma, and tumor necrosis factor-alpha secretion by the tumor-associated and peripheral blood T cells at baseline, stimulation with anti-CD3 and anti-CD28 monoclonal antibodies significantly increased the fraction of cells producing these cytokines. Thus, tumor-associated T cells from patients with early and late-stage epithelial tumors contain increased proportions of CD4(+)CD25(+) T cells that secrete the immunosuppressive cytokine transforming growth factor-beta. Furthermore, our results are consistent with previous reports showing impaired expression of CD25 on CD8(+) T cells in cancer patients. Finally, increased lymphocyte costimulation provided by triggering the CD28 receptor is able to increase CD25 expression and cytokine secretion in tumor-associated T cells. These observations provide evidence for the contribution of regulatory T cells to immune dysfunction in cancer patients.
Controlling charge injection in organic electronic devices using self-assembled monolayers (1997)

We demonstrate control and improvement of charge injection in organic electronic devices by utilizing self-assembled monolayers (SAMs) to manipulate the Schottky energy barrier between a metal electrode and the organic electronic material. Hole injection from Cu electrodes into the electroluminescent conjugated polymer poly[2-methoxy,5-(2′-ethyl-hexyloxy)-1,4-phenylene vinylene] was varied by using two conjugated-thiol based SAMs. The chemically modified electrodes were incorporated in organic diode structures and changes in the metal/polymer Schottky energy barriers and current–voltage characteristics were measured. Decreasing (increasing) the Schottky energy barrier improves (degrades) charge injection into the polymer.
Inverted‐Colloidal‐Crystal Hydrogel Matrices as Three‐Dimensional Cell Scaffolds (2005)

Abstract Successful engineering of functional tissues requires the development of three‐dimensional (3D) scaffolds that can provide an optimum microenvironment for tissue growth and regeneration. A new class of 3D scaffolds with a high degree of organization and unique topography is fabricated from polyacrylamide hydrogel. The hydrogel matrix is molded by inverted colloidal crystals made from 104 μm poly(methyl methacrylate) spheres. The topography of the scaffold can be described as hexagonally packed 97 μm spherical cavities interconnected by a network of channels. The scale of the long‐range ordering of the cavities exceeds several millimeters. In contrast to analogous material in the bulk, hydrogel shaped as an inverted opal exhibits much higher swelling ratios; its swelling kinetics is an order of magnitude faster as well. The engineered scaffold possesses desirable mechanical and optical properties that can facilitate tissue regeneration while allowing for continuous high‐resolution optical monitoring of cell proliferation and cell–cell interaction within the scaffold. The scaffold biocompatibility as well as cellular growth and infiltration within the scaffold were observed for two distinct human cell lines which were seeded on the scaffold and were tracked microscopically up to a depth of 250 μm within the scaffold for a duration of up to five weeks. Ease of production, a unique 3D structure, biocompatibility, and optical transparency make this new type of hydrogel scaffold suitable for most challenging tasks in tissue engineering.
Noiseless coding of quantized spectral components in MPEG-2 Advanced Audio Coding (2002)

Advanced Audio Coding (AAC), part of ISO/MPEG-2, issued as an international standard in April, 1997. It supports single or multiple channel audio programs and delivers excellent audio quality at or below 64 kbps/channel by exploiting the compression capabilities of a high-resolution filterbank, backward-adaptive prediction, joint channel coding, nonlinear quantizers and noiseless (Huffman) coding. This paper describes the flexible Huffman coding algorithm used in AAC and discusses the compression provided by this component of the standard.
Biosynthesis and processing of human immunodeficiency virus type 1 envelope glycoproteins: effects of monensin on glycosylation and transport (1989)

When human immunodeficiency virus type 1 envelope glycoproteins were expressed in 293 cells by using a recombinant adenovirus expression vector, the envelope precursor (gp160) was initially glycosylated by cotranslational addition of N-linked high-mannose oligosaccharide units to the protein backbone and then cleaved to gp120 and gp41. The subunits gp120 and gp41 were then further modified by the addition of fucose, galactose, and sialic acid, resulting in glycoproteins containing a mixture of hybrid and complex oligosaccharide side chains. A fraction of glycosylated gp160 that escaped cleavage was further modified by the terminal addition of fucose and galactose, but the addition of sialic acid did not occur, consistent with the notion that it is compartmentalized separately from the gp120 envelope protein. Processing and transport of gp160 were blocked by the monovalent ionophore monensin, which at high concentrations (25 microM and above) was a potent inhibitor of the endoproteolytic cleavage of gp160; at lower concentrations (1 to 10 microM), it selectively blocked the secondary glycosylation steps so that smaller products were produced. Monensin (1 microM) treatment also resulted in a reduction in syncytium formation, which was observed when recombinant infected cells were cocultivated with CD4-bearing HeLa cells. The infectivity of human immunodeficiency virus type 1 was also reduced by monensin treatment, a decrease that may be due to incompletely glycosylated forms of gp120 that have a lower affinity for the CD4 receptor.
Positional Signaling Mediated by a Receptor-like Kinase in Arabidopsis (2004)

The position-dependent specification of root epidermal cells in Arabidopsis provides an elegant paradigm for cell patterning during development. Here, we describe a new gene, SCRAMBLED (SCM), required for cells to appropriately interpret their location within the developing root epidermis. SCM encodes a receptor-like kinase protein with a predicted extracellular domain of six leucine-rich repeats and an intracellular serine-threonine kinase domain. SCM regulates the expression of the GLABRA2, CAPRICE, WEREWOLF, and ENHANCER OF GLABRA3 transcription factor genes that define the cell fates. Further, the SCM gene is expressed throughout the developing root. Therefore, SCM likely enables developing epidermal cells to detect positional cues and establish an appropriate cell-type pattern.
Pathophysiological roles of interleukin-8/CXCL8 in pulmonary diseases (2003)

Fifteen years have passed since the first description of interleukin (IL)-8/CXCL8 as a potent neutrophil chemotactic factor. Accumulating evidence has demonstrated that various types of cells can produce a large amount of IL-8/CXCL8 in response to a wide variety of stimuli, including proinflammatory cytokines, microbes and their products, and environmental changes such as hypoxia, reperfusion, and hyperoxia. Numerous observations have established IL-8/CXCL8 as a key mediator in neutrophil-mediated acute inflammation due to its potent actions on neutrophils. However, several lines of evidence indicate that IL-8/CXCL8 has a wide range of actions on various types of cells, including lymphocytes, monocytes, endothelial cells, and fibroblasts, besides neutrophils. The discovery of these biological functions suggests that IL-8/CXCL8 has crucial roles in various pathological conditions such as chronic inflammation and cancer. Here, an overview of its protein structure, mechanisms of production, and receptor system will be discussed as well as the pathophysiological roles of IL-8/CXCL8 in various types of lung pathologies.
Light-scattering microscope (1999)

We demonstrate a new design for a light-scattering microscope that is convenient to use and that allows simultaneous imaging and light scattering. The design is motivated by the growing use of thermal fluctuations to probe the viscoelastic properties of complex inhomogeneous environments. We demonstrate measurements of an optically nonergodic sample, one of the most challenging light-scattering applications.
Jitters Jeopardize AIDS Vaccine Trials (1993)

AIDS vaccine developers have been planning large-scale tests of experimental vaccines in people at high risk of becoming infected with HIV. The National Institutes of Health (NIH) scheduled plans for tests in December 1993. However discouraging findings were reported in November 1993 at the National Institute of Allergy and Infectious Diseases (NIAID) 6th Annual Conference on Advances in AIDS Vaccine Development in Alexandria Virginia relating to neutralizing antibodies which can prevent the virus from infecting cells. In the toughest laboratory test that mixes blood from a vaccinated person with HIV to assess whether vaccines can raise neutralizing antibodies almost all experimental AIDS vaccines failed to trigger a key immune response against HIV. 3 new students were presented at the meeting. The Duke group analyzed blood from 40 people given 6 different vaccines. While most of the samples neutralized lab-adapted strains of HIV not one could neutralize a field isolate. The Walter Reed Army Institute of Research group also failed to find neutralizing activity against primary isolates when they tested 34 of these blood samples. Californias Chiron Corp. had focused on people who had received a vaccine being jointly developed by Chiron and CIBA-GEIGY and selected the 5 vaccines that had the strongest neutralizing antibodies. They then tested these blood samples against primary isolates and could find no activity. However New Yorks United Biomedica Inc. (UBI) demonstrated that blood from one person injected with UBIs vaccine neutralized a field isolate. NIAID announced at the meeting that it will conduct a thorough review of the field isolate issues and decide whether to launch efficacy trials in the United States by the end of 1994. South San Franciscos Genentech said it had more than 200000 doses of HIV vaccine ready because it thought NIAID had made a commitment and the primary isolate question could not nullify other positive animal and human data from experiments with Genentechs vaccine. WHO already is helping Brazil Uganda Rwanda and Thailand prepare for efficacy trials.
Cancer overdiagnosis and overtreatment (2012)

Reducing overtreatment in patients diagnosed with indolent disease is critical to the success of screening.
Impaired transport of leptin across the blood-brain barrier in obesity is acquired and reversible (2003)

Leptin resistance is a major cause of obesity in humans. A major component of this resistance is likely an impaired transport of leptin across the blood-brain barrier (BBB). The fattest subgroup of otherwise normal 12-mo-old CD-1 mice have severely impaired transport of leptin across the BBB. However, it is unknown whether these mice are born with a BBB impairment or acquire it with aging and obesity. Here, we found within an otherwise normal population of CD-1 mice that the 10% fattest mice gained weight throughout a 12-mo-life span, whereas the 10% thinnest mice gained little weight after 3 mo of age. The fattest mice acquired a progressive impairment in their ability to transport leptin across the BBB, whereas the thinnest mice had a rate of transport that did not change with age. Fasting fat mice for 24 h or treating them with leptin resulted in modest weight reduction and development of transport rates for leptin across the BBB similar to those of thin mice. These results show that, in obese CD-1 mice, the impaired transport of leptin across the BBB develops in tandem with obesity and is reversible with even modest weight reduction.
Preparation of films exhibiting a balanced temperature dependence to permeation by aqueous solutions—a study of lower consolute behavior (1975)

Abstract Temperature dependence of solute transport through aqueously swollen polymeric films and membranes can be altered to show even apparent negative activation energies by the use of polymers exhibiting a lower consolute behavior in solution. The principles by which we constructed a host of such polymers are discussed. A solubility rule is presented which predicts that solutes in water will show a lower critical solution temperature if the proper hydrophilic–hydrophobic balance is achieved.
Communication optimizations for fine-grained UPC applications (2005)

Global address space languages like UPC exhibit high performance and portability on a broad class of shared and distributed memory parallel architectures. The most scalable applications use bulk memory copies rather than individual reads and writes to the shared space, but finer-grained sharing can be useful for scenarios such as dynamic load balancing, event signaling, and distributed hash tables. In this paper we present three optimization techniques for global address space programs with fine-grained communication: redundancy elimination, use of split-phase communication, and communication coalescing. Parallel UPC programs are analyzed using static single assignment form and a dataflow graph, which are extended to handle the various shared and private pointer types that are available in UPC. The optimizations also take advantage of UPC's relaxed memory consistency model, which reduces the need for cross thread analysis. We demonstrate the effectiveness of the analysis and optimizations using several benchmarks, which were chosen to reflect the kinds of finegrained, communication-intensive phases that exist in some larger applications. The optimizations show speedups of up to 70% on three parallel systems, which represent three different types of cluster network technologies.
Immunization with purified N1 and N2 influenza virus neuraminidases demonstrates cross-reactivity without antigenic competition. (1994)

Based on the absence of serologic cross-reactivity, the neuraminidases (NAs) of influenza A viruses are divided into antigenically discrete subtypes, analogous to the hemagglutinin (HA) major antigens with which they share the virion surface. An innovative approach to influenza vaccination takes advantage of the infection-permissive nature of immunization with NA as the minor surface antigen. However, evidence that HA dominates immune response when HA and NA are presented together in the intact virion prompted investigation of possible competing effects during immunization of NA subtype mixtures ultimately required for human vaccination. Immunization of BALB/c mice with purified N1- and N2-subtype NAs demonstrated no antigenic competition in primary or secondary response. However, when homotypic or heterotypic infection followed immunization, cross-reactive antibodies between N1 and N2 were found and "reverse antigen competition" occurred with initial NA priming suppressing response to HA following infection with virus containing homologous NA. These studies of antigen mixtures have implications for the use of combined and chimeric vaccines for diseases other than influenza.
Tight junctions and the modulation of barrier function in disease (2008)

Tight junctions create a paracellular barrier in epithelial and endothelial cells protecting them from the external environment. Two different classes of integral membrane proteins constitute the tight junction strands in epithelial cells and endothelial cells, occludin and members of the claudin protein family. In addition, cytoplasmic scaffolding molecules associated with these junctions regulate diverse physiological processes like proliferation, cell polarity and regulated diffusion. In many diseases, disruption of this regulated barrier occurs. This review will briefly describe the molecular composition of the tight junctions and then present evidence of the link between tight junction dysfunction and disease.
Annexin A5 Increases Survival in Murine Sepsis Model by Inhibiting HMGB1-Mediated Proinflammation and Coagulation (2016)

The identification of HMGB1 as a late-mediator in sepsis has highlighted HMGB1 as a promising therapeutic target for sepsis treatment. Recent studies have revealed that annexin A5, a 35 kDa Ca<sup>2+</sup>-dependent phospholipid binding protein, exerts anti-inflammatory effect by inhibiting LPS binding to TLR4/MD2 complex. Annexin A5 administration has been shown to protect against endotoxin lethality even when the treatment was given after the early cytokine response, which prompted our group to suspect that annexin A5 may inhibit the binding of HMGB1, as well as endotoxin to TLR4. Here we suggest annexin A5 as a new inhibitor of HMGB1-mediated pro-inflammatory cytokine production and coagulation in sepsis. We first confirmed the inhibitory role of annexin A5 in LPS-induced production of pro-inflammatory cytokines both <i>in vitro</i> and <i>in vivo</i>. We observed that annexin A5 protects against tissue damage and organ dysfunction during endotoxemia <i>in vivo</i>. We then assessed the inhibiting role of annexin A5 in HMGB1/TLR4 interaction, and showed that annexin A5 treatment reduces HMGB1-mediated cytokines IL6 and TNFα both <i>in vitro</i> and <i>in vivo</i>. Finally, we confirmed that anticoagulant property of annexin A5 persists in various septic conditions including elevated HMGB1. Overall, we suggest annexin A5 as an alternative therapeutic approach for controlling HMGB1-mediated pro-inflammation and coagulation in patients with sepsis.