gebhart/patrepeval huggingface dataset:
Cooperative and Competitive Binding in Synergistic Mixtures of Thermobifida fusca Cellulases Cel5A, Cel6B, and Cel9A (2002)

Synergism between cellulases facilitates efficient hydrolysis of microcrystalline cellulose. We hypothesize that the effects of synergism, observed as enhanced extents of hydrolysis, are related to cellulase binding to the substrate in mixtures. In this study, direct measurements of bound concentrations of fluorescence-labeled T. fusca Cel5A, Cel6B, and Cel9A on bacterial microcrystalline cellulose were used to study binding behaviors of cellulases in binary component reactions. The accuracy of the determination of fluorescence-labeled cellulase concentrations in binary component mixtures was in the range of 7-9%. Data at 5 degrees C show that binding levels of cellulases in mixture reactions are only 22-70% of the binding levels in single component reactions. At 50 degrees C, however, most of the cellulase components in the same mixtures bound to extents of 40-126% higher than in the corresponding single component reactions. The degrees of synergistic effect (DSE) observed for the reactions at 50 degrees C were greater than 1, indicating that the components in the mixture acted synergistically, whereas DSE < 1 was generally observed for the reactions at 5 degrees C indicating anti-synergistic behavior. Degrees of synergistic binding (DSB) were also calculated, where anti-synergistic mixtures had DSB < 1 and synergistic mixtures had DSB>1. We conclude that the lower extents of binding at 5 degrees C are due to competition for binding sites by the cellulase components in the mixtures and the enhanced binding extents at 50 degrees C are due to increased availability of binding sites on the substrates brought about by the higher extents of hydrolysis.
Critical Role of Conserved Hydrophobic Residues within the Major Homology Region in Mature Retroviral Capsid Assembly (2008)

During retroviral maturation, the CA protein undergoes dramatic structural changes and establishes unique intermolecular interfaces in the mature capsid shell that are different from those that existed in the immature precursor. The most conserved region of CA, the major homology region (MHR), has been implicated in both immature and mature assembly, although the precise contribution of the MHR residues to each event has been largely undefined. To test the roles of specific MHR residues in mature capsid assembly, an in vitro system was developed that allowed for the first-time formation of Rous sarcoma virus CA into structures resembling authentic capsids. The ability of CA to assemble organized structures was destroyed by substitutions of two conserved hydrophobic MHR residues and restored by second-site suppressors, demonstrating that these MHR residues are required for the proper assembly of mature capsids in addition to any role that these amino acids may play in immature particle assembly. The defect caused by the MHR mutations was identified as an early step in the capsid assembly process. The results provide strong evidence for a model in which the hydrophobic residues of the MHR control a conformational reorganization of CA that is needed to initiate capsid assembly and suggest that the formation of an interdomain interaction occurs early during maturation.
Preferred in vivo ubiquitination sites (2004)

http://www.people.fas.harvard.edu/~catic.
Deposition of silicon dioxide films with an atmospheric-pressure plasma jet (1998)

A plasma jet has been developed which deposits silica films at up to at 760 Torr and 115 to C. The jet operates by feeding oxygen and helium gas between two coaxial electrodes that are driven by a 13.56 MHz radio frequency source at 40 to 500 W. Tetraethoxysilane is mixed with the effluent of the plasma jet and directed onto a substrate located 1.7 cm downstream. The properties of the silica films, as determined by infrared spectroscopy and capacitance measurements, are comparable to those of thermally grown silicon dioxide films at C.
Efficient All-Inorganic Colloidal Quantum Dot LEDs (2007)

We present the first all-inorganic QD-LEDs consisting of radio-frequency sputtered metal-oxide charge transport layers and a colloidal quantum dot electroluminescent region. These devices manifest a 100-fold increase in external quantum efficiency over previously reported structures.
Matrix Metalloproteinase Inhibition During the Development of Congestive Heart Failure (1999)

The development of congestive heart failure (CHF) is associated with left ventricle (LV) dilation and myocardial remodeling. The matrix metalloproteinases (MMPs) play a significant role in extracellular remodeling, and recent studies have demonstrated increased MMP expression and activity with CHF. Whether increased MMP activity directly contributes to the LV remodeling with CHF remains unknown. Accordingly, this study examined the effects of chronic MMP inhibition (MMPi) on LV size and function during the progression of CHF. Pigs were assigned to the following groups: (1) CHF, rapid pacing for 3 weeks at 240 bpm (n=12); (2) CHF/MMPi, rapid pacing and concomitant MMPi (PD166793, 20 mg/kg per day [n=10]), and (3) control (n=11). With pacing CHF, LV fractional shortening was reduced (19+/-1 versus 45+/-1%), and end-diastolic dimension increased (5.67+/-0.11 versus 3.55+/-0.05 cm), compared with baseline values (P<0.05). In the CHF/MMPi group, LV endocardial shortening increased (25+/-2%) and the end-diastolic dimension was reduced (4.92+/-0.17 cm) compared with CHF-only values (P<0.05). LV midwall shortening was reduced to a comparable degree in the CHF-only and CHF/MMPi groups. LV peak wall stress increased 3-fold with pacing CHF compared with controls and was significantly reduced in the CHF/MMPi group. LV myocardial stiffness was unchanged with CHF but was increased in the CHF/MMPi group. LV myocyte length was increased with pacing CHF compared with controls (180+/-3 versus 125+/-4 microm, P<0.05) and was reduced in the CHF/MMPi group (169+/-4 microm, P<0.05). Basal-state myocyte shortening velocity was reduced with pacing CHF compared with controls (33+/-2 versus 66+/-1 microm/s, P<0.05) and was unchanged in the CHF/MMPi group (31+/-2 microm/s). Using an ex vivo assay system, myocardial MMP activity was increased with pacing CHF and was reduced with chronic MMPi. In summary, concomitant MMPi with developing CHF limited LV dilation and reduced wall stress. These results suggest that increased myocardial MMP activity contributes to LV myocardial remodeling in developing CHF.
Bandwidth enhancement of PIFA loaded with very high permittivity material using FDTD (2002)

Bandwidth enhancement on a miniature PIFA antenna is demonstrated in this paper. The miniature PIFA antenna consists of multilayers of very high permittivity materials (/spl epsi//sub r/>35). A 75% reduction in size has been accomplished as compared to that of the conventional PIPA. The achieved antenna gain is 7 dBi and the bandwidth is 5.75.
Recombinant endostatin forms amyloid fibrils that bind and are cytotoxic to murine neuroblastoma cells in vitro (2003)

Endostatin is a fragment of collagen XVIII that acts as an endogenous inhibitor of tumor angiogenesis and tumor growth. Anti-tumor effects have been described using both soluble and insoluble recombinant endostatin. However, differences in endostatin structure are likely to cause differences in bioactivity. In the present study we have investigated the structure and cellular effects of insoluble endostatin. We found that insoluble endostatin shows all the hallmarks of amyloid aggregates. Firstly, it binds Congo red and shows the characteristic apple-green birefringe when examined under polarized light. Secondly, electron microscopy shows that endostatin forms short unbranched fibrils. Thirdly, X-ray analysis shows the abundant presence of cross-beta sheets, the tertiary structure that underlies fibrillogenesis. None of these properties was observed when examining soluble endostatin. Soluble endostatin can be triggered to form cross-beta sheets following denaturation, indicating that endostatin is a protein fragment with an inherent propensity to form amyloid deposits. Like beta-amyloid, found in the brains of patients with Alzheimer's disease, amyloid endostatin binds to and is toxic to neuronal cells, whereas soluble endostatin has no effect on cell viability. Our results demonstrate a previously unrecognized functional difference between soluble and insoluble endostatin, only the latter acting as a cytotoxic amyloid substance.
TNFa and IL-2 armed adenoviruses enable complete responses by anti-PD-1 checkpoint blockade (2018)

Releasing the patient's immune system against their own malignancy by the use of checkpoint inhibitors is delivering promising results. However, only a subset of patients currently benefit from them. One major limitation of these therapies relates to the inability of T cells to detect or penetrate into the tumor resulting in unresponsiveness to checkpoint inhibition. Virotherapy is an attractive tool for enabling checkpoint inhibitors as viruses are naturally recognized by innate defense elements which draws the attention of the immune system. Besides their intrinsic immune stimulating properties, the adenoviruses used here are armed to express tumor necrosis factor alpha (TNFa) and interleukin-2 (IL-2). These cytokines result in immunological danger signaling and multiple appealing T-cell effects, including trafficking, activation and propagation. When these viruses were injected into B16.OVA melanoma tumors in animals concomitantly receiving programmed cell-death protein 1 (PD-1) blocking antibodies both tumor growth control (p < 0.0001) and overall survival (p < 0.01) were improved. In this set-up, the addition of adoptive cell therapy with OT-I lymphocytes did not increase efficacy further. When virus injections were initiated before antibody treatment in a prime-boost approach, 100% of tumors regressed completely and all mice survived. Viral expression of IL2 and TNFa altered the cytokine balance in the tumor microenvironment towards Th1 and increased the intratumoral proportion of CD8+ and conventional CD4+ T cells. These preclinical studies provide the rationale and schedule for a clinical trial where oncolytic adenovirus coding for TNFa and IL-2 (TILT-123) is used in melanoma patients receiving an anti-PD-1 antibody.
Prostaglandin E2 enhances hematopoietic stem cell homing, survival, and proliferation (2009)

Adult hematopoietic stem cells (HSCs) are routinely used to reconstitute hematopoiesis after myeloablation; however, transplantation efficacy and multilineage reconstitution can be limited by inadequate HSC number, or poor homing, engraftment, or self-renewal. Here we report that mouse and human HSCs express prostaglandin E2 (PGE2) receptors, and that short-term ex vivo exposure of HSCs to PGE2 enhances their homing, survival, and proliferation, resulting in increased long-term repopulating cell (LTRC) and competitive repopulating unit (CRU) frequency. HSCs pulsed with PGE2 are more competitive, as determined by head-to-head comparison in a competitive transplantation model. Enhanced HSC frequency and competitive advantage is stable and maintained upon serial transplantation, with full multilineage reconstitution. PGE2 increases HSC CXCR4 mRNA and surface expression, enhances their migration to SDF-1 in vitro and homing to bone marrow in vivo, and stimulates HSC entry into and progression through cell cycle. In addition, PGE2 enhances HSC survival, associated with an increase in Survivin mRNA and protein expression and reduction in intracellular active caspase-3. Our results define novel mechanisms of action whereby PGE2 enhances HSC function and supports a strategy to use PGE2 to facilitate hematopoietic transplantation.
Locus control region activity by 5′HS3 requires a functional interaction with β-globin gene regulatory elements: expression of novel β/γ-globin hybrid transgenes (2000)

The human beta-globin locus control region (LCR) contains chromatin opening and transcriptional enhancement activities that are important to include in beta-globin gene therapy vectors. We previously used single-copy transgenic mice to map chromatin opening activity to the 5'HS3 LCR element. Here, we test novel hybrid globin genes to identify beta-globin gene sequences that functionally interact with 5'HS3. First, we show that an 850-base pair (bp) 5'HS3 element activates high-level beta-globin gene expression in fetal livers of 17 of 17 transgenic mice, including 3 single-copy animals, but fails to reproducibly activate Agamma-globin transgenes. To identify the beta-globin gene sequences required for LCR activity by 5'HS3, we linked the 815-bp beta-globin promoter to Agamma-globin coding sequences (BGT34), together with either the beta-globin intron 2 (BGT35), the beta-globin 3' enhancer (BGT54), or both intron 2 and the 3' enhancer (BGT50). Of these transgenes, only BGT50 reproducibly expresses Agamma-globin RNA (including 7 of 7 single-copy animals, averaging 71% per copy). Modifications to BGT50 show that LCR activity is detected after replacing the beta-globin promoter with the 700-bp Agamma-globin promoter, but is abrogated when an AT-rich region is deleted from beta-globin intron 2. We conclude that LCR activity by 5'HS3 on globin promoters requires the simultaneous presence of beta-globin intron 2 sequences and the 260-bp 3' beta-globin enhancer. The BGT50 construct extends the utility of the 5'HS3 element to include erythroid expression of nonadult beta-globin coding sequences in transgenic animals and its ability to express antisickling gamma-globin coding sequences at single copy are ideal characteristics for a gene therapy cassette.
Molecular Evolution of the Wound-Induced Serine Protease Inhibitor wip1 in Zea and Related Genera (2001)

Plant defense mechanisms have been the subject of intensive investigation. However, little is known about their long-term evolutionary dynamics. We investigated the molecular diversity of a wound-induced serine protease inhibitor, wip1, in the genus Zea, as well as the divergence of wip1 among four genera, Zea, Tripsacum, Sorghum, and Oryza, in order to gain insight into the long-term evolution of plant defense. The specific objectives of this study were to determine (1) whether wip1 has a history of positive or balancing selection, as has been shown for genes involved in plant defense against pathogens, and (2) if the evolutionary histories of wip1 inhibitory loops, which come into closest contact with proteases, differ from the evolutionary history of other parts of this gene. The Zea polymorphism data are consistent with a neutral evolutionary history. In contrast, relative-rate tests suggest a nonneutral evolutionary history. This inconsistency may indicate that selection acting on wip1 is episodic or that wip1 evolves in response to selection favoring novel alleles. We also detected significant heterogeneity in the evolutionary rates of the two inhibitory loops of wip1-one inhibitory loop is highly conserved, whereas the second has diverged rapidly. Because these two inhibitory loops are predicted to have very similar biochemical functions, the significantly different evolutionary histories suggest that these loops have different ecological functions.
Use of Annular Apertures to Increase Focal Depth (1960)

A theoretical study is made of the possibilities of using an annular aperture to increase the focal depth of a photographic objective. It is shown that for a given gain in focal depth the loss in speed is the same for both annular apertures and conventional stopping down. For images of isolated point objects, the definition is improved by using an annular stop. The gain in focal depth is less for off-axis points, but it is found that, for example, a factor of 2.7 in focal depth gained by means of an annular aperture is barely affected at a field angle of 30°.
Age and Sex Analyses of Somatic Complaints and Symptom Presentation of Childhood Depression in a Hungarian Clinical Sample (2009)

The symptom presentation of MDD becomes somewhat more neurovegetative as children get older. However, girls display more affective and atypical symptoms across all age groups. Somatic complaints were common regardless of age and should be considered an associated feature of depression in children and adolescents.
Depth assisted compression of full parallax light fields (2015)

Full parallax light field displays require high pixel density and huge amounts of data. Compression is a necessary tool used by 3D display systems to cope with the high bandwidth requirements. One of the formats adopted by MPEG for 3D video coding standards is the use of multiple views with associated depth maps. Depth maps enable the coding of a reduced number of views, and are used by compression and synthesis software to reconstruct the light field. However, most of the developed coding and synthesis tools target linearly arranged cameras with small baselines. Here we propose to use the 3D video coding format for full parallax light field coding. We introduce a view selection method inspired by plenoptic sampling followed by transform-based view coding and view synthesis prediction to code residual views. We determine the minimal requirements for view sub-sampling and present the rate-distortion performance of our proposal. We also compare our method with established video compression techniques, such as H.264/AVC, H.264/MVC, and the new 3D video coding algorithm, 3DV-ATM. Our results show that our method not only has an improved rate-distortion performance, it also preserves the structure of the perceived light fields better.
A 50‐kDa fragment from the NH2‐terminus of the heavy subunit of Clostridium botulinum type A neurotoxin forms channels in lipid vesicles (1987)

1. A 50-kDa fragment representing the NH2-terminus of the heavy subunit of botulinum type A neurotoxin was found, at low pH, to evoke the release of K+ from lipid vesicles loaded with potassium phosphate. Similar K+ release was also observed with the intact neurotoxin, its heavy chain and a fragment consisting of the light subunit linked the 50-kDa NH2-terminal heavy chain fragment. The light subunit alone, however, was inactive. 2. In addition to K+, the channels formed in lipid bilayers by botulinum neurotoxin type A or the NH2-terminal heavy chain fragment were found to be large enough to permit the release of NAD (Mr 665). 3. The optimum pH for the release of K+ was found to be 4.5. Above this value K+ release rapidly decreased and was undetectable above pH 6.0. 4. The binding of radiolabelled botulinum toxin to a variety of phospholipids was assessed. High levels of toxin binding were only observed to lipid vesicles with an overall negative charge; much weaker binding occurred to lipid vesicles composed of electrically neutral phospholipids. 5. A positive correlation between the efficiency of toxin-binding and the efficiency of K+ release from lipid vesicles was not observed. Whereas lipid vesicles containing the lipids cardiolipin or dicetyl phosphate bound the highest levels of neurotoxin, the toxin-evoked release of K+ was low compared to vesicles containing either phosphatidyl glycerol, phosphatidyl serine or phosphatidyl inositol. 6. The implications of these observations to the mechanism by which the toxin molecule is translocated into the nerve ending are discussed.
The interferon-induced 67-kDa guanylate-binding protein (hGBP1) is a GTPase that converts GTP to GMP (1994)

hGBP1 is an interferon-induced 67-kDa protein of human cells that readily binds to agarose-immobilized GTP, GDP, and GMP but not to other nucleotides. We cloned hGBP1 cDNA into a histidine-tagging vector, produced recombinant hGBP1 with 6 extra histidine residues at its N terminus in Escherichia coli, and purified this protein to near homogeneity from bacterial lysates. Purified hGBP1 hydrolyzed radiolabeled GTP but failed to hydrolyze ATP, UTP, or CTP at significant rates. Unexpectedly, the principal product of the GTP hydrolysis reaction was GMP rather than GDP. Although significant amounts of GDP were produced when the reaction was performed at 15 degrees C, GDP could not serve as substrate or as inhibitor of hGBP1. hGBP1 lacked guanylate cyclase and guanylyltransferase activity. Degradation of GTP to GMP most likely occurred via two consecutive cleavages of single phosphate groups, because pyrophosphate was not a reaction product, and because hGBP1 failed to hydrolyze GTP gamma S. In vitro modification assays with radiolabeled mevalonic acid and farnesyl pyrophosphate showed that the CaaX motif at the C terminus of hGBP1 functions as an isoprenylation signal. Thus, hGBP1 is a GTPase with novel biochemical properties that may be membrane-associated in eukaryotic cells.
Material-Specific Recognition Memory Deficits Elicited by Unilateral Hippocampal Electrical Stimulation (2004)

Although the medial temporal lobe is thought to be critical for recognition memory (RM), the specific role of the hippocampus in RM remains uncertain. We investigated the effects of transient unilateral hippocampal electrical stimulation (ES), subthreshold for afterdischarge, on delayed item RM in epilepsy patients implanted with bilateral hippocampal depth electrodes. RM was assessed using a novel computer-controlled test paradigm in which ES to left or right hippocampus was either absent (baseline) or synchronized with item presentation. Subsequent yes-no RM performance revealed a double dissociation between material-specific RM and the lateralization of ES. Left hippocampal ES produced word RM deficits, whereas right hippocampal ES produced face RM deficits. Our findings provide the first demonstration in humans that selective unilateral stimulation-induced hippocampal disruption is sufficient to produce impairments on delayed RM tasks and provide support for the material-specific laterality of hippocampal function with respect to RM.
An ApoA‐I Mimetic Peptide High‐Density‐Lipoprotein‐Based MRI Contrast Agent for Atherosclerotic Plaque Composition Detection (2008)

Cardiovascular disease is one of the prime causes of mortality throughout the world and there is a need for targeted and effective contrast agents to allow noninvasive imaging of the cholesterol-rich atherosclerotic plaques in arteries. A new, fully synthetic, high-density lipoprotein (HDL)-mimicking MRI contrast agent is developed, which enhances macrophage-rich areas of plaque in a mouse model of atherosclerosis by 94%. Confirmation of the targeting of this nanoparticulate agent is achieved using confocal microscopy by tracking a fluorescent lipid incorporated into the nanoparticle.