gebhart/patrepeval huggingface dataset:
Sequence repeats and protein structure (2012)

Repeats are frequently found in known protein sequences. The level of sequence conservation in tandem repeats correlates with their propensities to be intrinsically disordered. We employ a coarse-grained model of a protein with a two-letter amino acid alphabet, hydrophobic (H) and polar (P), to examine the sequence-structure relationship in the realm of repeated sequences. A fraction of repeated sequences comprises a distinct class of bad folders, whose folding temperatures are much lower than those of random sequences. Imperfection in sequence repetition improves the folding properties of the bad folders while deteriorating those of the good folders. Our results may explain why nature has utilized repeated sequences for their versatility and especially to design functional proteins that are intrinsically unstructured at physiological temperatures.
Transparent organic light emitting devices (1996)

We report the demonstration of transparent organic light emitting devices (OLEDs) which are ∼70% transparent throughout the visible spectrum when switched off, and emit light from both sides with a total external quantum efficiency of ∼0.1% when turned on. The devices are Alq3-based single heterostructure OLEDs grown on an ITO-coated glass substrate with a top electrode composed of a very thin layer of Mg–Ag and an overlaying ITO film. The top electrode is both electron injecting and transparent. The transparent OLEDs are expected to be useful in high-resolution full-color displays, as well as for helmet-mounted, windshield-mounted, or other ‘‘head-up’’ display applications.
Biofilm Susceptibility to Antimicrobials (1997)

Microbial biofilms, where organisms are intimately associated with each other and a solid substratum through binding and inclusion within an exopolymer matrix, are widely distributed in nature and disease. In the mouth, multispecies biofilms are associated not only with dental plaque and tooth decay but also with soft tissues of the buccal cavity and with most forms of periodontal disease. Organization of micro-organisms within biofilms confers, on the component species, properties which are not evident with the individual species grown independently or as planktonic populations in liquid media. While many of these properties relate to the establishment of functional, mixed-species consortia within the exopolymeric matrices, others relate to the establishment of physico-chemical gradients, within the biofilm, that modify the metabolism of the component cells. A consequence of biofilm growth that has profound implications for their control in the environment and in medicine is a markedly enhanced resistance to chemical antimicrobial agents and antibiotics. Mechanisms associated with such resistance in biofilms will form the substance of the present review. While some aspects of biofilm resistance are yet only poorly understood, the dominant mechanisms are thought to be related to: (i) modified nutrient environments and suppression of growth rate within the biofilm; (ii) direct interactions between the exopolymer matrices, and their constituents, and antimicrobials, affecting diffusion and availability; and (iii) the development of biofilm/attachment-specific phenotypes.
Efficient Interactive Annotation of Segmentation Datasets with Polygon-RNN++ (2018)

Manually labeling datasets with object masks is extremely time consuming. In this work, we follow the idea of Polygon-RNN [4] to produce polygonal annotations of objects interactively using humans-in-the-loop. We introduce several important improvements to the model: 1) we design a new CNN encoder architecture, 2) show how to effectively train the model with Reinforcement Learning, and 3) significantly increase the output resolution using a Graph Neural Network, allowing the model to accurately annotate high-resolution objects in images. Extensive evaluation on the Cityscapes dataset [8] shows that our model, which we refer to as Polygon-RNN++, significantly outperforms the original model in both automatic (10% absolute and 16% relative improvement in mean IoU) and interactive modes (requiring 50% fewer clicks by annotators). We further analyze the cross-domain scenario in which our model is trained on one dataset, and used out of the box on datasets from varying domains. The results show that Polygon-RNN++ exhibits powerful generalization capabilities, achieving significant improvements over existing pixel-wise methods. Using simple online fine-tuning we further achieve a high reduction in annotation time for new datasets, moving a step closer towards an interactive annotation tool to be used in practice.
Inhibition of Sterol Synthesis in Cultured Mouse Cells by Cholesterol Derivatives Oxygenated in the Side Chain (1974)

Abstract Sterols derived from cholesterol by hydroxylation of the side chain in the 20α, 22α, 22β, or 25 position inhibited sterol synthesis from acetate and depressed the level of 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34) activity in primary cultures of mouse fetal liver cells and in L cell cultures. Rates of acetate metabolism to fatty acids and CO2, and rates of RNA and protein synthesis were not affected. Following the addition of the most potent inhibitors of the group, 25-hydroxycholesterol and 20α-hydroxycholesterol, to l cell cultures the enzyme activity diminished to one-half of the original amount within a period of 1 to 1.3 hours. Inhibitory potency was influenced by the location of the hydroxyl function on the side chain, by the completeness of the side chain, and by the introduction of a third functional group into the molecule.
Transcriptional regulation of the human placental-like alkaline phosphatase gene and mechanisms involved in its induction by sodium butyrate. (1992)

The human alkaline phosphatases constitute a multigene family with at least four members. Placental-like alkaline phosphatase (PLAP) is of particular interest because it is frequently present in tumors, where it serves as a marker of malignant transformation. Moreover, its expression is highly inducible by differentiating agents such as sodium butyrate. In the present study we have examined the PLAP gene promoter in order to better understand the mechanisms involved in its expression and induction. The PLAP promoters from four colon cancer cell lines with widely varied butyrate-inducible alkaline phosphatase activity were thermally amplified and sequenced. The overall sequence similarity of this region was found to be 99% between cell lines; thus, sequence variation of the promoter does not appear to account for the differential expression of this marker. We therefore analyzed the activity of the LS174T cell PLAP promoter using transient transfection experiments. Here, the 5'-flanking region of the gene was found to have positive regulatory elements in nucleotides -1 to -170 and -363 to -512 (relative to the start of transcription). A negative control element was also found to be present in the region between nucleotides -170 and -363. Mobility shift electrophoresis indicated that a nuclear factor bound to the promoter between bases -182 and -341. Furthermore, the activity of the PLAP promoter was found to be inducible by sodium butyrate. In contrast, the closely related placental alkaline phosphatase gene promoter exhibited almost no response to this agent. These results confirm that the activity of the PLAP promoter is stimulated by sodium butyrate and delineate regions that control this induction process.
Build your own glasses-free 3D display (2011)

Driven by the recent resurgence of 3D cinema, depth cameras and stereoscopic displays are becoming commonplace in the consumer market. Introduced last October, Microsoft Kinect has already fostered gesture-based interaction for applications well beyond the intended Xbox 360 platform. Similarly, consumer electronics manufacturers have begun selling stereoscopic displays and inexpensive stereoscopic cameras. Most commercial 3D displays continue to require cumbersome eyewear, but inexpensive, glasses-free 3D displays are imminent with the release of the Nintendo 3DS.
Magnitude of response of histocompatibility-restricted T-cell clones is a function of the product of the concentrations of antigen and Ia molecules. (1983)

The activation of specific T-cell clones by antigens is dependent upon the corecognition of restriction elements expressed on antigen-presenting cells (APC). For clones that respond by proliferation and lymphokine production, the restriction element is usually an Ia (I-region-associated) molecule. We show here that the magnitude of the proliferative response of such clones is a function of the product of antigen concentration and the number of Ia molecules expressed on APC. This conclusion was reached through the study of antigen concentration-response curves of T-cell clones specific for pigeon cytochrome c. These curves are characterized by a peak in thymidine incorporation, followed by a decrease in the magnitude of the response as antigen concentrations are increased. The decline in response at high concentrations was not the consequence of the emergence of suppressor cells in the APC population, as it was observed when cells of a cloned B-cell hybridoma line were used to present pigeon cytochrome c to these T-cell clones. The critical role of both antigen concentration and the number of Ia molecules on the APC in determining the magnitude of proliferation was demonstrated in several ways. (i) An inverse relationship was observed between the antigen concentration required for maximum proliferation and the number of APC present in culture. At high antigen concentrations, which caused responses less than maximum, reducing the number of APC actually increased the magnitude of the antigen-induced proliferation. (ii) Decreasing the number of relevant Ia molecules per APC (i.e., as in F1 hybrids) resulted in the requirement for an increased antigen concentration for maximal response and in enhanced proliferation at high antigen concentrations. (iii) In the presence of anti-Ia antibody, higher concentrations of antigen were required for maximal response; at high antigen concentrations, proliferation was enhanced in the presence of a monoclonal anti-Ia antibody directed against the Ia restriction element.
Numerical model and analysis of an energy-based system using microwaves for vision correction (2009)

A treatment system was developed utilizing a microwave-based procedure capable of treating myopia and offering a less invasive alternative to laser vision correction without cutting the eye. Microwave thermal treatment elevates the temperature of the paracentral stroma of the cornea to create a predictable refractive change while preserving the epithelium and deeper structures of the eye. A pattern of shrinkage outside of the optical zone may be sufficient to flatten the central cornea. A numerical model was set up to investigate both the electromagnetic field and the resultant transient temperature distribution. A finite element model of the eye was created and the axisymmetric distribution of temperature calculated to characterize the combination of controlled power deposition combined with surface cooling to spare the epithelium, yet shrink the cornea, in a circularly symmetric fashion. The model variables included microwave power levels and pulse width, cooling timing, dielectric material and thickness, and electrode configuration and gap. Results showed that power is totally contained within the cornea and no significant temperature rise was found outside the anterior cornea, due to the near-field design of the applicator and limited thermal conduction with the short on-time. Target isothermal regions were plotted as a result of common energy parameters along with a variety of electrode shapes and sizes, which were compared. Dose plots showed the relationship between energy and target isothermic regions.
Photothermal Microscopy of the Core of Dextran-Coated Iron Oxide Nanoparticles During Cell Uptake (2012)

A detailed understanding of cellular interactions with superparamagnetic iron oxide nanoparticles (SPIONs) is critical when their biomedical applications are considered. We demonstrate how photothermal microscopy can be used to follow the cellular uptake of SPIONs by direct imaging of the iron oxide core. This offers two important advantages when compared with current strategies employed to image magnetic cores: first, it is nondestructive and is therefore suitable for studies of live cells and, second, it offers a higher sensitivity and resolution, thus allowing for the identification of low levels of SPIONs within a precise subcellular location. We have shown that this technique may be applied to the imaging of both cell monolayers and cryosections. In the former we have demonstrated the role of temperature on the rate of endocytosis, while in the latter we have been able to identify cells labeled with SPIONs from a mixed population containing predominantly unlabeled cells. Direct imaging of the SPION core is of particular relevance for research involving clinically approved SPIONs, which do not contain fluorescent tags and therefore cannot be detected via fluorescence microscopy.
Analysis of raw microneurographic recordings based on wavelet de-noising technique and classification algorithm: wavelet analysis in microneurography (2003)

We propose a new technique for analyzing the raw neurogram which enables the study of the discharge behavior of individual and group neurons. It utilizes an ideal bandpass filter, a modified wavelet de-noising procedure, an action potential detector, and a waveform classifier. We validated our approach with both simulated data generated from muscle sympathetic neurograms sampled at high rates in five healthy subjects and data recorded from seven healthy subjects during lower body negative pressure suction. The modified wavelet method was superior to the classical discriminator method and the regular wavelet de-noising procedure when applied to simulated neuronal signals. The detected spike rate and spike amplitude rate of the action potentials correlated strongly with number of bursts detected in the integrated neurogram (r = 0.79 and 0.89, respectively, p < 0.001). Eight major action potential waveform classes were found to describe more than 81% of all detected action potentials in all subjects. One class had characteristics similar in shape and in average discharge frequency (27.4 +/- 5.1 spikes/min during resting supine position) to those of reported single vasoconstrictor units. The newly proposed technique allows a precise estimate of sympathetic nerve activity and characterization of individual action potentials in multiunit records.
The biology of airway dendritic cells (1995)

Recent work from our laboratory has identified a network of constitutively class II MHC (Ia) bearing dendritic cells (DC) within the epithelium of the conducting airways of laboratory animal species and in humans. The density of DC within the respiratory tract is highest in those areas exposed to greater amounts of inhaled antigen and further work has identified these DC as being critically important in controlling the induction of immune responses within the airways. The DC population in the airway epithelium is renewed every 48-72 h; this represents a more rapid turnover than DC in other tissues which are exposed to a smaller antigenic load. In addition to these results we will discuss other work which shows that airway DC are a very reactive population, comparable with neutrophils in their response to acute inflammatory stimuli and that their numbers and Ia content can be modulated following exposure to topical and systemic steroids. Finally we will discuss the development of these cells after birth and how this may influence the pathogenesis of immune regulated diseases such as asthma and allergic rhinitis.
Mqo, a Tricarboxylic Acid Cycle Enzyme, Is Required for Virulence of Pseudomonas syringae pv. tomato Strain DC3000 on Arabidopsis thaliana (2009)

Plant pathogenic bacteria, such as Pseudomonas syringae pv. tomato strain DC3000, the causative agent of tomato bacterial speck disease, grow to high levels in the apoplastic space between plant cells. Colonization of plant tissue requires expression of virulence factors that modify the apoplast to make it more suitable for pathogen growth or facilitate adaptation of the bacteria to the apoplastic environment. To identify new virulence factors involved in these processes, DC3000 Tn5 transposon insertion mutants with reduced virulence on Arabidopsis thaliana were identified. In one of these mutants, the Tn5 insertion disrupted the malate:quinone oxidoreductase gene (mqo), which encodes an enzyme of the tricarboxylic acid cycle. mqo mutants do not grow to wild-type levels in plant tissue at early time points during infection. Further, plants infected with mqo mutants develop significantly reduced disease symptoms, even when the growth of the mqo mutant reaches wild-type levels at late stages of infection. Mutants lacking mqo function grow more slowly in culture than wild-type bacteria when dicarboxylates are the only available carbon source. To explore whether dicarboxylates are important for growth of DC3000 in the apoplast, we disrupted the dctA1 dicarboxylate transporter gene. DC3000 mutants lacking dctA1 do not grow to wild-type levels in planta, indicating that transport and utilization of dicarboxylates are important for virulence of DC3000. Thus, mqo may be required by DC3000 to meet nutritional requirements in the apoplast and may provide insight into the mechanisms underlying the important, but poorly understood process of adaptation to the host environment.
Combinatorial immunoglobulin light chain variability creates sufficient B cell diversity to mount protective antibody responses against pathogen infections (2003)

To analyze how combinatorial light (L) chain diversity influences the B cell repertoire, we studied mice with a homozygous immunoglobulin-heavy-chain null mutation (mu MT), in which the B cell developmental block was overridden by the expression of a transgenic immunoglobulin mu heavy (H) chain derived from a vesicular stomatitis virus Indiana serotype (VSV-IND)-neutralizing Ab (T11 mu MT mice). The randomly integrated transgene could not undergo secondary rearrangements and was expressed in combination with endogenous kappa or lambda chains. T11 mu MT mice had a skewed B cell repertoire as evidenced by 30-60% VSV-IND-specific peripheral B cells and spontaneous VSV-IND-neutralizing serum titers. Upon immunization, T11 mu MT mice mounted specific IgM antibody responses against VSV-IND but, interestingly, they also responded against VSV New Jersey serotype (VSV-NJ), lymphocytic choriomeningitis virus, poliovirus and Salmonella typhi porins. Variable-region sequence analysis revealed that VSV-NJ-specific antibodies expressed numerous L chains in combination with the transgenic H chain, which was devoid of hypermutations. Thus, in T11 mu MT mice combinatorial L chain variability alone is able to build up a sufficiently complex B cell repertoire to mount protective immunoglobulin responses against a variety of pathogens.
Human aldolase A natural mutants: relationship between flexibility of the C-terminal region and enzyme function (2004)

We have identified a new mutation in the FBP (fructose 1,6-bisphosphate) aldolase A gene in a child with suspected haemolytic anaemia associated with myopathic symptoms at birth and with a subsequent diagnosis of arthrogryposis multiplex congenita and pituitary ectopia. Sequence analysis of the whole gene, also performed on the patient's full-length cDNA, revealed only a Gly346-->Ser substitution in the heterozygous state. We expressed in a bacterial system the new aldolase A Gly346-->Ser mutant, and the Glu206-->Lys mutant identified by others, in a patient with an aldolase A deficit. Analysis of their functional profiles showed that the Gly346Ser mutant had the same Km as the wild-type enzyme, but a 4-fold lower kcat. The Glu206-->Lys mutant had a Km approx. 2-fold higher than that of both the Gly346-->Ser mutant and the wild-type enzyme, and a kcat value 40% less than the wild-type. The Gly346-->Ser and wild-type enzymes had the same Tm (melting temperature), which was approx. 6-7 degrees C higher than that of the Glu206-->Lys enzyme. An extensive molecular graphic analysis of the mutated enzymes, using human and rabbit aldolase A crystallographic structures, suggests that the Glu206-->Lys mutation destabilizes the aldolase A tetramer at the subunit interface, and highlights the fact that the glycine-to-serine substitution at position 346 limits the flexibility of the C-terminal region. These results also provide the first evidence that Gly346 is crucial for the correct conformation and function of aldolase A, because it governs the entry/release of the substrates into/from the enzyme cleft, and/or allows important C-terminal residues to approach the active site.
Antiviral effect of oryzacystatin, a proteinase inhibitor in rice, against herpes simplex virus type 1 in vitro and in vivo (1995)

Oryzacystatin (OC) is the first-described cystatin originating from rice seed; it consists of two molecular species, OC-I and OC-II, which have antiviral action against poliovirus in vitro (H. Kondo, S. Ijiri, K. Abe, H. Maeda, and S. Arai, FEBS Lett. 299:48-50, 1992). In the experiments reported here, we investigated the effects of OC-I and OC-II on the replication of herpes simplex virus type 1 (HSV-1) in vitro and in vivo. HSV-1 was inoculated onto monolayers of monkey kidney epithelial cells (CV-1 cells) at a multiplicity of infection of 0.1 PFU per cell. After adsorption of the virus onto cells, the cultures were incubated in the presence of either OC-I or OC-II in the concentration range of 1.0 to 300 microM, and the supernatant virus yield was quantitated at 24 h. The effective concentration for 90% inhibition of HSV-1 was 14.8 microM, while a cytotoxic effect on CV-1 cells without infection of HSV-1 was not observed below 500 microM OC-I. Therefore, the apparent in vitro chemotherapeutic index was estimated to be more than 33. In the mouse model of HSV-1-induced keratitis and encephalopathy, topical administration of OC-I to the mouse cornea produced a significant decrease in virus production in the cornea (mean virus yields: 3.11 log10 PFU in the treated group and 4.37 log10 PFU in the control group) and significant improvement in survival rates (P = 0.01). The in vivo antiherpetic effect of OC-I was comparable to that of acyclovir, indicating that topical treatment of HSV-1 infection in humans with OC-I might be possible. Our data also suggest the importance of some thiol proteinases, which may be derived from either the host's cells or HSV-1, during the replication process of HSV-1.
Passive immunization of macaques against SIV infection (1994)

Passive immunization with plasma from an inactivated-whole SIVmac vaccine protected monkey conferred complete or partial protection to rhesus macaques challenged intravenously 4 or 18 hours later with 10 AID50 of homologous cell-free virus. In contrast, passive immunization with inactivated plasma or purified immunoglobulin (Ig) from SIVmac infected asymptomatic monkeys failed to protect any recipients similarly challenged and may have enhanced infection and accelerated disease. Administered 24 hours post challenge, anti-SIV Ig may also have enhanced the infection.
A Click Chemistry Approach to Tetrazoles by Huisgen 1,3-Dipolar Cycloaddition: Synthesis of 5-Acyltetrazoles from Azides and Acyl Cyanides We thank the National Institute of General Medical Sciences, National Institutes of Health (GM-28384), the National Science Foundation (CHE-9985553), the Skaggs Institute for Chemical Biology for a Predoctoral Fellowship (Z.D.), and the W. M. Keck Foundation for financial support. (2002)

Click chemistry: Acyl cyanides react with alkyl azides in high yield by heating at 120–130°C (see scheme). The reactions are run neat, and the workup is simple. When p-nitrophenyl cyanoformate is used as the dipolarophile, the resulting tetrazoles are activated for rapid functionalization as an activated ester.