gebhart/patrepeval huggingface dataset:
Spatially Transformed Adversarial Examples (2018)

Recent studies show that widely used deep neural networks (DNNs) are vulnerable to carefully crafted adversarial examples. Many advanced algorithms have been proposed to generate adversarial examples by leveraging the $\mathcal{L}_p$ distance for penalizing perturbations. Researchers have explored different defense methods to defend against such adversarial attacks. While the effectiveness of $\mathcal{L}_p$ distance as a metric of perceptual quality remains an active research area, in this paper we will instead focus on a different type of perturbation, namely spatial transformation, as opposed to manipulating the pixel values directly as in prior works. Perturbations generated through spatial transformation could result in large $\mathcal{L}_p$ distance measures, but our extensive experiments show that such spatially transformed adversarial examples are perceptually realistic and more difficult to defend against with existing defense systems. This potentially provides a new direction in adversarial example generation and the design of corresponding defenses. We visualize the spatial transformation based perturbation for different examples and show that our technique can produce realistic adversarial examples with smooth image deformation. Finally, we visualize the attention of deep networks with different types of adversarial examples to better understand how these examples are interpreted.
Mechanics of receptor-mediated endocytosis (2005)

Most viruses and bioparticles endocytosed by cells have characteristic sizes in the range of tens to hundreds of nanometers. The process of viruses entering and leaving animal cells is mediated by the binding interaction between ligand molecules on the viral capid and their receptor molecules on the cell membrane. How does the size of a bioparticle affect receptor-mediated endocytosis? Here, we study how a cell membrane containing diffusive mobile receptors wraps around a ligand-coated cylindrical or spherical particle. It is shown that particles in the size range of tens to hundreds of nanometers can enter or exit cells via wrapping even in the absence of clathrin or caveolin coats, and an optimal particles size exists for the smallest wrapping time. This model can also be extended to include the effect of clathrin coat. The results seem to show broad agreement with experimental observations.
Investigation of middle ear anatomy and function with combined video otoscopy-phase sensitive OCT (2016)

We report the development of a novel otoscopy probe for assessing middle ear anatomy and function. Video imaging and phase-sensitive optical coherence tomography are combined within the same optical path. A sound stimuli channel is incorporated as well to study middle ear function. Thus, besides visualizing the morphology of the middle ear, the vibration amplitude and frequency of the eardrum and ossicles are retrieved as well. Preliminary testing on cadaveric human temporal bone models has demonstrated the capability of this instrument for retrieving middle ear anatomy with micron scale resolution, as well as the vibration of the tympanic membrane and ossicles with sub-nm resolution.
A Novel DNA Enzyme Reduces Glycosaminoglycan Chains in the Glial Scar and Allows Microtransplanted Dorsal Root Ganglia Axons to Regenerate beyond Lesions in the Spinal Cord (2004)

CNS lesions induce production of ECM molecules that inhibit axon regeneration. One major inhibitory family is the chondroitin sulfate proteoglycans (CSPGs). Reduction of their glycosaminoglycan (GAG) chains with chondroitinase ABC leads to increased axon regeneration that does not extend well past the lesion. Chondroitinase ABC, however, is unable to completely digest the GAG chains from the protein core, leaving an inhibitory "stub" carbohydrate behind. We used a newly designed DNA enzyme, which targets the mRNA of a critical enzyme that initiates glycosylation of the protein backbone of PGs, xylosyltransferase-1. DNA enzyme administration to TGF-beta-stimulated astrocytes in culture reduced specific GAG chains. The same DNA enzyme applied to the injured spinal cord led to a strong reduction of the GAG chains in the lesion penumbra and allowed axons to regenerate around the core of the lesion. Our experiments demonstrate the critical role of PGs, and particularly those in the penumbra, in causing regeneration failure in the adult spinal cord.
Fluorescent Amplified Fragment Length Polymorphism Analysis of Norwegian Bacillus cereus and Bacillus thuringiensis Soil Isolates (2001)

We examined 154 Norwegian B. cereus and B. thuringiensis soil isolates (collected from five different locations), 8 B. cereus and 2 B. thuringiensis reference strains, and 2 Bacillus anthracis strains by using fluorescent amplified fragment length polymorphism (AFLP). We employed a novel fragment identification approach based on a hierarchical agglomerative clustering routine that identifies fragments in an automated fashion. No method is free of error, and we identified the major sources so that experiments can be designed to minimize its effect. Phylogenetic analysis of the fluorescent AFLP results reveals five genetic groups in these group 1 bacilli. The ATCC reference strains were restricted to two of the genetic groups, clearly not representative of the diversity in these bacteria. Both B. anthracis strains analyzed were closely related and affiliated with a B. cereus milk isolate (ATCC 4342) and a B. cereus human pathogenic strain (periodontitis). Across the entire study, pathogenic strains, including B. anthracis, were more closely related to one another than to the environmental isolates. Eight strains representing the five distinct phylogenetic clusters were further analyzed by comparison of their 16S rRNA gene sequences to confirm the phylogenetic status of these groups. This analysis was consistent with the AFLP analysis, although of much lower resolution. The innovation of automated genotype analysis by using a replicated and statistical approach to fragment identification will allow very large sample analyses in the future.
Half‐Life Extension of Therapeutic Proteins via Genetic Fusion to Recombinant PEG Mimetics (2012)

This chapter contains sections titled: Introduction Mechanisms to Retard Kidney Filtration Using Conjugates of Drugs with Polymers Naturally Occurring Repetitive Amino Acid Sequences Gelatin-Like Protein Polymers Elastin-Like Polypeptides Polyanionic Polymers Genetic Polymers™ XTEN Polypeptides Glycine-Rich Homo-Amino-Acid Polymers PASylation® Technology Conclusions and Outlook References
Skewed Th1 Responses Caused by Excessive Expression of Txk, a Member of the Tec Family of Tyrosine Kinases, in Patients with Behcet's Disease (2006)

Behcet's disease (BD) is characterized by recurrent attacks of uveitis, oral aphtha, genital ulcers and skin lesions. The etiology and pathogenesis of BD are largely unknown. It has been reported that excessive Th1 cell function is involved in the pathogenesis of BD. Previously, we found that Txk, a member of the Tec family of tyrosine kinases, acts as a Th1 cell-specific transcription factor that is involved in the effector function of Th1 cells. Thus, we studied Th1 cytokine production and Txk expression of T-lymphocytes in patients with BD. Peripheral blood lymphocytes produced excessive Th1-associated cytokines including interferon-gamma (IFN-gamma) and interleukin (IL)-12 in patients with BD. Circulating CD3+ and purified CD4+ T cells expressed excessive Txk protein. The extent of IFN-gamma production by the lymphocytes correlated with the expression of Txk protein in the immunoblotting analysis. The majority of cells infiltrating into the skin lesions of patients with BD expressed IFN-gamma. IL-12 and IL-18 were found in the mononuclear cell aggregates in the skin and intestinal lesions of those with BD. Lymphocytes accumulating in the skin and intestinal lesions expressed higher levels of Txk as compared with other Th2-associated diseases. IFN-gamma, IL-18 and IL-12 detected in skin lesions may induce preferential development of Th1 cells in patients with BD. Collectively, Th1 cells expressing Txk and Th1-associated cytokines may play a critical role in the development of skin and intestinal lesions in patients with BD. This review may serve as a reminder of the importance of excessive Th1 cell function in the pathogenesis of BD and may contribute to the discovery of new molecular targets for the development of a specific therapeutic strategy for BD.
Surface‐Enhanced Raman Detection on Metalized Nanostructured Poly(p‐xylylene) Films (2008)

The development of a SERS substrate with high uniformity and sample-to-sample reproducibility is reported. Nanostructured poly(p-xylylene) films are prepared using an oblique-angle polymerization method, and SERS-active metals are deposited onto the nanostructured polymer by using thermal evaporation (see figure). The use of the substrate for a robust and reagentless detection of both Gram-positive and Gram-negative bacteria is demonstrated.
Epidemiologic Features of Chronic Atrial Fibrillation (1982)

In the Framingham Study 2325 men and 2866 women 30 to 62 years old at entry were followed biennially over 22 years for the development of chronic atrial fibrillation in relation to antecedent cardiovascular disease and risk factors. During surveillance, atrial fibrillation developed in 49 men and 49 women. The incidence rose sharply with age but did not differ significantly between the sexes. Overall, there was a 2.0 per cent chance that the disorder would develop in two decades. Atrial fibrillation usually followed the development of overt cardiovascular disease. Only 18 men and 12 women (31 per cent) had chronic atrial fibrillation in the absence of cardiovascular disease. Cardiac failure and rheumatic heart disease were the most powerful predictive precursors, with relative risks in excess of sixfold. Hypertensive cardiovascular disease was the most common antecedent disease, largely because of its frequency in the general population. Among the risk factors for cardiovascular disease, diabetes and electrocardiographic evidence of left ventricular hypertrophy were related to the occurrence of atrial fibrillation. The development of chronic atrial fibrillation was associated with a doubling of overall mortality and of mortality from cardiovascular disease.
Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus (1999)

We report the crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus, a major human pathogen, to 2.8-A resolution. This enzyme is a key target for developing specific antiviral therapy. The structure of the catalytic domain contains 531 residues folded in the characteristic fingers, palm, and thumb subdomains. The fingers subdomain contains a region, the "fingertips," that shares the same fold with reverse transcriptases. Superposition to the available structures of the latter shows that residues from the palm and fingertips are structurally equivalent. In addition, it shows that the hepatitis C virus polymerase was crystallized in a closed fingers conformation, similar to HIV-1 reverse transcriptase in ternary complex with DNA and dTTP [Huang H., Chopra, R., Verdine, G. L. & Harrison, S. C. (1998) Science 282, 1669-1675]. This superposition reveals the majority of the amino acid residues of the hepatitis C virus enzyme that are likely to be implicated in binding to the replicating RNA molecule and to the incoming NTP. It also suggests a rearrangement of the thumb domain as well as a possible concerted movement of thumb and fingertips during translocation of the RNA template-primer in successive polymerization rounds.
Infrared fibers for radiometer thermometry in hypothermia and hyperthermia treatment (1989)

Hypothermia is a condition which results from prolonged exposure to a cold environment. Rapid and efficient heating is needed to rewarm the patient from 32-35 degrees C to normal body temperature. Hyperthermia in cancer treatment involves heating malignant tumors to 42.5-43.0 degrees C for an extended period (e.g., 30 min) in an attempt to obtain remission. Microwave or radio frequency heating is often used for rewarming in hypothermia or for temperature elevation in hyperthermia treatment. One severe problem with such heating is the accurate measurement and control of temperature in the presence of a strong electromagnetic field. For this purpose, we have developed a fiberoptic radiometer system which is based on a nonmetallic, infrared fiber probe, which can operate either in contact or noncontact mode. In preliminary investigations, the radiometer worked well in a strong microwave or radiofrequency field, with an accuracy of +/- 0.5 degrees C. This fiberoptic thermometer was used to control the surface temperature of objects within +/- 2 degrees C.
Plasmacytoid Dendritic Cells Regulate Breach of Self-Tolerance in Autoimmune Arthritis (2009)

Achieving remission in rheumatoid arthritis (RA) remains elusive despite current biological therapeutics. Consequently, interest has increased in strategies to re-establish immune tolerance to provide long-term disease suppression. Although dendritic cells (DC) are prime candidates in initiating autoreactive T cell responses, and their presence within the synovial environment suggests a role in generation and maintenance of autoreactive, synovial T cell responses, their functional importance remains unclear. We investigated the contribution made by plasmacytoid DCs (pDCs) in the spontaneous breach of tolerance to arthritis-related self proteins, including rheumatoid factor, citrullinated peptide, and type II collagen observed in a novel arthritis model. Selective pDC depletion in vivo enhanced the severity of articular pathology and enhanced T and B cell autoimmune responses against type II collagen. pDC may offer a net anti-inflammatory function in the context of articular breach of tolerance. Such data will be vital in informing DC modulatory/therapeutic approaches.
A dynamic balance between gene activation and repression regulates the shade avoidance response in Arabidopsis (2005)

Plants grown under dense canopies perceive through the phytochrome system a reduction in the ratio of red to far-red light as a warning of competition, and this triggers a series of morphological changes to avoid shade. Several phytochrome signaling intermediates acting as positive regulators of accelerated elongation growth and induction of flowering in shade avoidance have been identified. Here we report that a negative regulatory mechanism ensures that in the presence of far-red-rich light an exaggerated plant response does not occur. Strikingly, this unpredicted negative regulatory mechanism is centrally involved in the attenuation of virtually all plant responses to canopy shade.
Na+-Independent Transport (Uniport) of Amino Acids and Glucose in Mammalian Cells (1994)

Recent advances have made possible the isolation of the genes and their cDNAs encoding Na(+)-independent amino acid transporters. Two classes of amino acid 'uniporters' have been isolated. One class contains the mCAT (murine cationic amino acid transporter) gene family that encodes proteins predicted to span the membrane 12-14 times and exhibits structural properties similar to the GLUT (glucose transporter) family and to other well-known transporters. The other class consists of two known genes, rBAT (related to B system amino acid transporters) and 4F2hc, that share amino acid sequence similarity with alpha-amylases and alpha-glucosidases. They are type II glycoproteins predicted to span the membrane only once, yet they mediate the Na(+)-independent transport of cationic and zwitterionic amino acids in Xenopus oocytes. Mutations in the human rBAT gene have been identified by Palacín and his co-workers in several families suffering from a heritable form of cystinuria. This important finding clearly establishes a key role for rBAT in cystine transport. The two classes of amino acid transporters are compared with the well-studied GLUT family of Na(+)-independent glucose transporters.
Isolation of an Active Human Transposable Element (1991)

Two de novo insertions of truncated L1 elements into the factor VIII gene on the X chromosome have been identified that produced hemophilia A. A full-length L1 element that is the likely progenitor of one of these insertions was isolated by its sequence identity to the factor VIII insertion. This L1 element contains two open-reading frames and is one of at least four alleles of a locus on chromosome 22 that has been occupied by an L1 element for at least 6 million years.
Impaired Flow-Mediated Vasodilation in vivo and Reduced Shear-Induced Platelet Reactivity in vitro in Response to Nitric Oxide in Prothrombotic, Stroke-Prone Spontaneously Hypertensive Rats (2002)

Previous investigations using an He-Ne laser-induced thrombosis method have shown that stroke-prone spontaneously hypertensive rats (SHRSP) have an enhanced thrombotic tendency in vivo compared to normotensive, Wistar Kyoto rats (WKY). In addition, studies in the presence of acetylcholine have suggested the presence of endothelial dysfunction in SHRSP. In contrast, shear-induced platelet reactivity in vitro appeared to be depressed in SHRSP. The aim of the present study was to investigate endothelial function in SHRSP using a new physiological in vivo model, and to determine the response of platelets to nitric oxide (NO) in non-anticoagulated blood using a shear-induced platelet function in vitro method (haemostatometry). Endothelial function was estimated by measuring flow-mediated vasodilation (FMV) of the femoral artery. Vessels were exposed and blood flow was arrested using a silicone-coated arterial clamp. Vasodilation was measured by computer-assisted image analysis 3 min after release of stasis. Arterial vasodilation was observed in the femoral artery of WKY, but not in SHRSP. Vasodilation was seen in both WKY and SHRSP; however, in response to the NO donor, 1-hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1-triazene (NOC 5). In contrast, 100 microM NOC 5 did not affect platelet reactivity in SHRSP. The NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide, sodium salt (carboxy-PTIO) and the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester, hydrochloride (L-NAME), did not affect shear-induced platelet reactivity. NOC 5 at 10 microM (final concentration) inhibited shear-induced platelet reactivity in WKY. These results confirm the presence of endothelial dysfunction in SHRSP and indicate that platelets are non-responsive to NO in this hypertensive model. The data suggest that defective endothelial reactions or disturbed thrombogenic mechanisms outweigh the platelet hyporeactivity and contribute to the prothrombotic status in SHRSP.
Highly Conserved Residues Asp-197 and His-250 in Agp1 Phytochrome Control the Proton Affinity of the Chromophore and Pfr Formation (2006)

The mutants H250A and D197A of Agp1 phytochrome from Agrobacterium tumefaciens were prepared and investigated by different spectroscopic and biochemical methods. Asp-197 and His-250 are highly conserved amino acids and are part of the hydrogen-bonding network that involves the chromophore. Both substitutions cause a destabilization of the protonated chromophore in the Pr state as revealed by resonance Raman and UV-visible absorption spectroscopy. Titration experiments demonstrate a lowering of the pK(a) from 11.1 (wild type) to 8.8 in H250A and 7.2 in D197A. Photoconversion of the mutants does not lead to the Pfr state. H250A is arrested in a meta-Rc-like state in which the chromophore is deprotonated. For H250A and the wild-type protein, deprotonation of the chromophore in meta-Rc is coupled to the release of a proton to the external medium, whereas the subsequent proton re-uptake, linked to the formation of the Pfr state in the wild-type protein, is not observed for H250A. No transient proton exchange with the external medium occurs in D197A, suggesting that Asp-197 may be the proton release group. Both mutants do not undergo the photo-induced protein structural changes that in the wild-type protein are detectable by size exclusion chromatography. These conformational changes are, therefore, attributed to the meta-Rc --> Pfr transition and most likely coupled to the transient proton re-uptake. The present results demonstrate that Asp-197 and His-250 are essential for stabilizing the protonated chromophore structure in the parent Pr state, which is required for the primary photochemical process, and for the complete photo-induced conversion to the Pfr state.
Microbiota at Multiple Body Sites during Pregnancy in a Rural Tanzanian Population and Effects of Moringa-Supplemented Probiotic Yogurt (2015)

The nutritional status of pregnant women is vital for healthy outcomes and is a concern for a large proportion of the world's population. The role of the microbiota in pregnancy and nutrition is a promising new area of study with potential health ramifications. In many African countries, maternal and infant death and morbidity are associated with malnutrition. Here, we assess the influence of probiotic yogurt containing Lactobacillus rhamnosus GR-1, supplemented with Moringa plant as a source of micronutrients, on the health and oral, gut, vaginal, and milk microbiotas of 56 pregnant women in Tanzania. In an open-label study design, 26 subjects received yogurt daily, and 30 were untreated during the last two trimesters and for 1 month after birth. Samples were analyzed using 16S rRNA gene sequencing, and dietary recalls were recorded. Women initially categorized as nourished or undernourished consumed similar calories and macronutrients, which may explain why there was no difference in the microbiota at any body site. Consumption of yogurt increased the relative abundance of Bifidobacterium and decreased Enterobacteriaceae in the newborn feces but had no effect on the mother's microbiota at any body site. The microbiota of the oral cavity and GI tract remained stable over pregnancy, but the vaginal microbiota showed a significant increase in diversity leading up to and after birth. In summary, daily micronutrient-supplemented probiotic yogurt provides a safe, affordable food for pregnant women in rural Tanzania, and the resultant improvement in the gut microbial profile of infants is worthy of further study.
Efficient encapsulation with plug-triggered drop formation (2011)

Monodisperse microscale drops formed with microfluidic devices are useful for encapsulating cells, microgel particles, or even additional drops. These techniques are thus useful for applications ranging from high-throughput biology to monodisperse particle and capsule synthesis, which require encapsulation of such objects. However, it is challenging to efficiently encapsulate the objects in all drops; often, the objects are encapsulated inefficiently, resulting in many improperly filled, unusable drops. Here, we describe a phenomenon that allows very efficient encapsulation. We use the inflow of the object to plug the drop maker nozzle; the continued injection of the outer phase pinches off a drop, thereby encapsulating the object; this yields precisely one object encapsulated per drop.
Engineered riboswitches: Expanding researchers' toolbox with synthetic RNA regulators (2012)

Riboswitches are natural RNA-based genetic switches that sense small-molecule metabolites and regulate in response the expression of the corresponding metabolic genes. Within the last years, several engineered riboswitches have been developed that act on various stages of gene expression. These switches can be engineered to respond to any ligand of choice and are therefore of great interest for synthetic biology. In this review, we present an overview of engineered riboswitches and discuss their application in conditional gene expression systems. We will provide structural and mechanistic insights and point out problems and recent trends in the development of engineered riboswitches.