gebhart/patrepeval huggingface dataset:
Self-assembling protein nanoparticles in the design of vaccines (2015)

For over 100 years, vaccines have been one of the most effective medical interventions for reducing infectious disease, and are estimated to save millions of lives globally each year. Nevertheless, many diseases are not yet preventable by vaccination. This large unmet medical need demands further research and the development of novel vaccines with high efficacy and safety. Compared to the 19th and early 20th century vaccines that were made of killed, inactivated, or live-attenuated pathogens, modern vaccines containing isolated, highly purified antigenic protein subunits are safer but tend to induce lower levels of protective immunity. One strategy to overcome the latter is to design antigen nanoparticles: assemblies of polypeptides that present multiple copies of subunit antigens in well-ordered arrays with defined orientations that can potentially mimic the repetitiveness, geometry, size, and shape of the natural host-pathogen surface interactions. Such nanoparticles offer a collective strength of multiple binding sites (avidity) and can provide improved antigen stability and immunogenicity. Several exciting advances have emerged lately, including preclinical evidence that this strategy may be applicable for the development of innovative new vaccines, for example, protecting against influenza, human immunodeficiency virus, and respiratory syncytial virus. Here, we provide a concise review of a critical selection of data that demonstrate the potential of this field. In addition, we highlight how the use of self-assembling protein nanoparticles can be effectively combined with the emerging discipline of structural vaccinology for maximum impact in the rational design of vaccine antigens.
Extracellular matrix dynamics in development and regenerative medicine (2008)

The extracellular matrix (ECM) regulates cell behavior by influencing cell proliferation, survival, shape, migration and differentiation. Far from being a static structure, the ECM is constantly undergoing remodeling--i.e. assembly and degradation--particularly during the normal processes of development, differentiation and wound repair. When misregulated, this can contribute to disease. ECM assembly is regulated by the 3D environment and the cellular tension that is transmitted through integrins. Degradation is controlled by complex proteolytic cascades, and misregulation of these results in ECM damage that is a common component of many diseases. Tissue engineering strives to replace damaged tissues with stem cells seeded on synthetic structures designed to mimic the ECM and thus restore the normal control of cell function. Stem cell self-renewal and differentiation is influenced by the 3D environment within the stem cell niche. For tissue-engineering strategies to be successful, the intimate dynamic relationship between cells and the ECM must be understood to ensure appropriate cell behavior.
Quality Factor in Trench-Refilled Polysilicon Beam Resonators (2006)

In this paper, thermoelastic damping (TED) in trench-refilled (TR) polysilicon microelectromechanical beam resonators is studied as a mechanism for limiting quality factor (Q) at low frequencies. An approximate model based on Zener's theory is developed and verified by numerical simulations in FEMLAB. According to the proposed model a double-dip characteristic is expected for the quality factor versus frequency curve of TR beam resonators. To verify the model experimentally, equal-width TR micro-resonators are fabricated in different length to cover a broad range of frequencies. Frequency response of these devices agrees well with our model. By using the theoretical and numerical models developed in this paper, an upper bound for the quality factor in TR beam resonators or any similar structure such as TR polysilicon gyros can be predicted.
Hyaluronic Acid Hydrogels for Biomedical Applications (2011)

Hyaluronic acid (HA), an immunoneutral polysaccharide that is ubiquitous in the human body, is crucial for many cellular and tissue functions and has been in clinical use for over thirty years. When chemically modified, HA can be transformed into many physical forms-viscoelastic solutions, soft or stiff hydrogels, electrospun fibers, non-woven meshes, macroporous and fibrillar sponges, flexible sheets, and nanoparticulate fluids-for use in a range of preclinical and clinical settings. Many of these forms are derived from the chemical crosslinking of pendant reactive groups by addition/condensation chemistry or by radical polymerization. Clinical products for cell therapy and regenerative medicine require crosslinking chemistry that is compatible with the encapsulation of cells and injection into tissues. Moreover, an injectable clinical biomaterial must meet marketing, regulatory, and financial constraints to provide affordable products that can be approved, deployed to the clinic, and used by physicians. Many HA-derived hydrogels meet these criteria, and can deliver cells and therapeutic agents for tissue repair and regeneration. This progress report covers both basic concepts and recent advances in the development of HA-based hydrogels for biomedical applications.
Expression of a disintegrin‐like protein in cultured human vascular cells and in vivo (1997)

Metalloproteinase-like, disintegrin-like, and cysteine-rich proteins (MDCs) are potential novel regulators of cell-cell and cell-matrix interactions, as well as of matrix degradation. We have asked whether MDCs are expressed in cultured diploid vascular cells, and have identified MDC 15 in human aortic smooth muscle (SMC) and umbilical vein endothelium (HUVEC). MDC 15 mRNA is expressed at higher levels in HUVECs than in SMCs. In cultured SMCs, MDC 15 mRNA levels are not regulated by PDGF or IGF-I or by adherence to different extracellular matrices. Nor is regulation of MDC 15 mRNA levels observed in HUVEC monolayers at different cell densities, after multi-scratch wounding, or after treatment with TNF-alpha, LPS, or thrombin. However, differences in proteolytic processing of MDC 15 are observed in different HUVEC strains. In contrast to cultured arterial cells, MDC 15 protein is not expressed in vivo in normal vessels, but is up-regulated in lesions of atherosclerosis. These findings suggest that MDC 15 may be a potential regulator of vascular cell function and may be involved in the development of lesions of atherosclerosis.
Angle-multiplexed storage of 5000 holograms in lithium niobate (1993)

As many as 5000 holograms of high-resolution images (320 × 220 pixels) have been stored within a single crystal of Fe:LiNbO3. The nominal angle between the reference beam and the object beam was 90°. Fractal-space multiplexing was used to increase the storage bandwidth.
Proteomic and functional characterization of endogenous adiponectin purified from fetal bovine serum (2004)

Adiponectin is a plasma protein exclusively secreted from fat tissue. Many recent pharmacological studies suggest that recombinant adiponectin has multiple therapeutic potentials for obesity-related metabolic disorders, including type 2 diabetes, dyslipidemia, insulin resistance and atherosclerosis. However, the physiological relevance of these findings remains to be further established. In the present study, we have purified endogenous adiponectin from fetal bovine serum and characterized its post-translational modifications and physiological functions in animal models. Endogenous bovine serum adiponectin consists predominantly of full-length proteins that form multiple oligomeric complexes, including trimers, hexamers and higher molecular species. Two-dimensional gel electrophoresis revealed that bovine serum adiponectin exists as multiple post-translationally modified isoforms with distinct molecular weight and isoelectric point. Further analysis using mass spectrometry and Edman degradation sequencing demonstrated that five conserved lysine residues (Lys 28, 60, 63, 72 and 96) within the collagenous domain of bovine adiponectin are hydroxylated and glycosylated by a glucosyl alpha(1-2)galactosyl group. Injection of endogenous bovine adiponectin into C57 mice potently decreased circulating glucose levels and enhanced lipid clearance after a high fat meal. Chronic administration of this protein for a period of two weeks significantly increased insulin sensitivity and glucose tolerance, and depleted hepatic lipid accumulation in high-fat fed mice. These results provide direct evidence that endogenous bovine adiponectin is a physiological hormone that can regulate lipid and glucose metabolism.
Transcriptional analyses of theBacillus licheniformis penPgene (1982)

We report the promoter structure of the Bacillus licheniformis 749/C penicillinase (penP) gene. The transcript encoding the penicillinase gene was identified by in vitro run-off transcription using both E. coli RNA polymerase and B. subtilis RNA polymerase. Utilization of this promoter in linearized DNA by the B. subtilis RNA polymerase showed extreme sensitivity to ionic strength. The 5' sequence of the penP mRNA was determined using enzymatic sequencing (1). Holoenzymes from E. coli and B. subtilis (E sigma 55) initiate penP RNA synthesis at the same site. Alignment of this RNA sequence with the reported DNA sequence of ther penP gene (2,3) revealed the "-35 region" and "Pribnow box" sequences that are recognized as 5'TTGCAT and 5'AATACT, respectively. Potential secondary structure within the promoter exists which may play a role in the expression of the penicillinase gene. The location of the penP promoter was further confirmed by molecular cloning of a DNA fragment containing the expected promoter sequence into a promoter-fishing vector useful for monitoring promoter activities in both E. coli and B. subtilis.
Biodegradable Elastomers for Biomedical Applications and Regenerative Medicine (2014)

Synthetic biodegradable polymers are of great value for the preparation of implants that are required to reside only temporarily in the body. The use of biodegradable polymers obviates the need for a second surgery to remove the implant, which is the case when a nondegradable implant is used. After implantation in the body, biomedical devices may be subjected to degradation and erosion. Understanding the mechanisms of these processes is essential for the development of biomedical devices or implants with a specific function, for example, scaffolds for tissue-engineering applications. For the engineering and regeneration of soft tissues (e.g., blood vessels, cardiac muscle and peripheral nerves), biodegradable polymers are needed that are flexible and elastic. The scaffolds prepared from these polymers should have tuneable degradation properties and should perform well under long-term cyclic deformation conditions. The required polymers, which are either physically or chemically crosslinked biodegradable elastomers, are reviewed in this article.
The Heparin/Heparan Sulfate-binding Site on Apo-serum Amyloid A (1999)

Serum amyloid A isoforms, apoSAA1 and apoSAA2, are apolipoproteins of unknown function that become major components of high density lipoprotein (HDL) during the acute phase of an inflammatory response. ApoSAA is also the precursor of inflammation-associated amyloid, and there is strong evidence that the formation of inflammation-associated and other types of amyloid is promoted by heparan sulfate (HS). Data presented herein demonstrate that both mouse and human apoSAA contain binding sites that are specific for heparin and HS, with no binding for the other major glycosaminoglycans detected. Cyanogen bromide-generated peptides of mouse apoSAA1 and apoSAA2 were screened for heparin binding activity. Two peptides, an apoSAA1-derived 80-mer (residues 24-103) and a smaller carboxyl-terminal 27-mer peptide of apoSAA2 (residues 77-103), were retained by a heparin column. A synthetic peptide corresponding to the CNBr-generated 27-mer also bound heparin, and by substituting or deleting one or more of its six basic residues (Arg-83, His-84, Arg-86, Lys-89, Arg-95, and Lys-102), their relative importance for heparin and HS binding was determined. The Lys-102 residue appeared to be required only for HS binding. The residues Arg-86, Lys-89, Arg-95, and Lys-102 are phylogenetically conserved suggesting that the heparin/HS binding activity may be an important aspect of the function of apoSAA. HS linked by its carboxyl groups to an Affi-Gel column or treated with carbodiimide to block its carboxyl groups lost the ability to bind apoSAA. HDL-apoSAA did not bind to heparin; however, it did bind to HS, an interaction to which apoA-I contributed. Results from binding experiments with Congo Red-Sepharose 4B columns support the conclusions of a recent structural study which found that heparin binding domains have a common spatial distance of about 20 A between their two outer basic residues. Our present work provides direct evidence that apoSAA can associate with HS (and heparin) and that the occupation of its binding site by HS, and HS analogs, likely caused the previously reported increase in amyloidogenic conformation (beta-sheet) of apoSAA2 (McCubbin, W. D., Kay, C. M., Narindrasorasak, S., and Kisilevsky, R. (1988) Biochem. J. 256, 775-783) and their amyloid-suppressing effects in vivo (Kisilevsky, R., Lemieux, L. J., Fraser, P. E., Kong, X., Hultin, P. G., and Szarek, W. A. (1995) Nat. Med. 1, 143-147), respectively.
New Independent Source Extractors with Exponential Improvement. (2012)

We study the problem of constructing explicit extractors for independent general weak random sources. For weak sources on n bits with min-entropy k, perviously the best known extractor needs to use at least log n/log k independent sources [22, 3]. In this paper we give a new extractor that only uses O(log(log n/log k))+O(1) independent sources. Thus, our result improves the previous best result exponentially. We then use our new extractor to give improved network extractor protocols, as defined in [14]. The network extractor protocols also give new results in distributed computing with general weak random sources, which dramatically improve previous results. For example, we can tolerate a nearly optimal fraction of faulty players in synchronous Byzantine agreement and leader election, even if the players only have access to independent n-bit weak random sources with min-entropy as small as k=polylog(n). Our extractor for independent sources is based on a new condenser for somewhere random sources with a special structure. We believe our techniques are interesting in their own right and are promising for further improvement.
Theory and applications of guided-mode resonance filters (1993)

The guided-mode resonance properties of planar dielectric waveguide gratings are presented and explained. It is shown that these structures function as filters that produce complete exchange of energy between forward- and backward-propagating diffracted waves with smooth line shapes and arbitrarily narrow filter linewidths. Simple expressions based on rigorous coupled-wave theory and on classical slab waveguide theory give a clear view and quantification of the inherent TE/TM polarization separation and the free spectral ranges of the filters. Furthermore, the resonance regimes, defining the parametric regions of the guided-mode resonances, can be directly visualized. It is shown that the linewidths of the resonances can be controlled by the grating modulation amplitude and by the degree of mode confinement (refractive-index difference at the boundaries). Examples presented of potential uses for these elements include a narrow-line polarized laser, a tunable polarized laser, a photorefractive tunable filter, and an electro-optic switch. The guided-mode resonance filter represents a basic new optical element with significant potential for practical applications.
High-frequency germ-line transmission of plasmid DNA sequences injected into fertilized zebrafish eggs. (1991)

With the goal of developing techniques for DNA insertional mutagenesis in zebrafish, we established procedures for rapidly obtaining and injecting large numbers of fertilized eggs. Using either of two plasmid constructs, we injected uncut DNA into fertilized eggs at the one- or two-cell stage. Fish hatched from injected eggs were raised to sexual maturity, and the frequency of transgenic founder fish was determined by pair-mating the fish and testing DNA extracted from pools of their 16-hr-old offspring by the polymerase chain reaction (PCR) and then Southern analysis. Eggs injected with one of two different plasmids yielded no transgenic fish, but 7-25% (19 of 115 overall) of the eggs injected with the other plasmid transmitted the injected sequences to their offspring (F1). Of seven lines studied further, all were able to pass the foreign DNA sequences to the next (F2) generation. Inheritance in the F2 generation was Mendelian in the five lines tested. PCR and Southern analysis indicated that the plasmid sequences were present in multiple copies, probably tandemly arranged. Two founder fish carried more than one independent integration of the plasmid sequences. The line studied in more detail was a mosaic carrying two independently segregating copies of the transgene in one germ cell and a third copy in another germ-line precursor cell. The ability to obtain and inject large numbers of zebrafish eggs combined with a high frequency of germ-line integration may be steps toward the goal of being able to perform insertional mutagenesis with this organism.
P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients younger than age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808 (2010)

Cancer and Leukemia Group B 19808 (CALGB 19808) is the only randomized trial of a second-generation P-glycoprotein (Pgp) modulator in untreated patients with acute myeloid leukemia (AML) younger than age 60 years. We randomly assigned 302 patients to receive induction chemotherapy regimens consisting of cytosine arabinoside (Ara-C; A), daunorubicin (D), and etoposide (E), without (ADE) or with (ADEP) PSC-833 (P). The incidence of complete remission was 75% with both regimens. Reversible grade 3 and 4 liver and mucosal toxicities were significantly more common with ADEP. Therapy-related mortality was 7% and did not differ by induction arm. Excess cardiotoxicity was not seen with high doses of D in ADE. The median disease-free survival was 1.34 years in the ADE arm and 1.09 years in the ADEP arm (P = .74, log-rank test); the median overall survival was 1.86 years in the ADE arm and 1.69 years in the ADEP arm (P = .82). There was no evidence of a treatment difference within any identifiable patient subgroup. Inhibition of Pgp-mediated drug efflux by PSC-833 did not improve clinical outcomes in younger patients with untreated AML. This trial was registered at www.clinicaltrials.gov as #NCT00006363.
Assessment of Long-Term Effects of Sports-Related Concussions: Biological Mechanisms and Exosomal Biomarkers (2020)

Concussion or mild traumatic brain injury (mTBI) in athletes can cause persistent symptoms, known as post-concussion syndrome (PCS), and repeated injuries may increase the long-term risk for an athlete to develop neurodegenerative diseases such as chronic traumatic encephalopathy (CTE), and Alzheimer's disease (AD). The Center for Disease Control estimates that up to 3.8 million sport-related mTBI are reported each year in the United States. Despite the magnitude of the phenomenon, there is a current lack of comprehensive prognostic indicators and research has shown that available monitoring tools are moderately sensitive to short-term concussion effects but less sensitive to long-term consequences. The overall aim of this review is to discuss novel, quantitative, and objective measurements that can predict long-term outcomes following repeated sports-related mTBIs. The specific objectives were (1) to provide an overview of the current clinical and biomechanical tools available to health practitioners to ensure recovery after mTBIs, (2) to synthesize potential biological mechanisms in animal models underlying the long-term adverse consequences of mTBIs, (3) to discuss the possible link between repeated mTBI and neurodegenerative diseases, and (4) to discuss the current knowledge about fluid biomarkers for mTBIs with a focus on novel exosomal biomarkers. The conclusions from this review are that current post-concussion clinical tests are not sufficiently sensitive to injury and do not accurately quantify post-concussion alterations associated with repeated mTBIs. In the current review, it is proposed that current practices should be amended to include a repeated symptom inventory, a cognitive assessment of executive function and impulse control, an instrumented assessment of balance, vestibulo-ocular assessments, and an improved panel of blood or exosome biomarkers.
Image based fingerprint verification (2003)

Human fingerprints have been considered as a unique signature certifying one's identity. Fingerprint verification is currently the most popular technique of biometric personal identification. As a biometric proof of identification, an alignment-based minutiae matching algorithm has been widely investigated, however, not many have considered fingerprint identification using image based verification. An image-based approach does not use minutiae features for fingerprint matching. This project investigates fingerprint-scanned image verification via an inverse fast Fourier transform after a thinning process. The technique may be applied directly to a gray-scale fingerprint image without pre-processing. This correlation coefficient approach is capable of finding correspondences between the input fingerprint image and the stored enrolled template with higher computational efficiency than the minutiae-based method. It has the ability of robust fingerprint verification subject to external conditions. In this paper, the design and implementation of a prototype of an automatic verification system is presented. The high matching rate achieved in this project suggests that an efficient small-scale fingerprint verification system is feasible.
A C-terminal alpha-helix plus basic region motif is the major structural determinant of p53 tetramerization. (1992)

The p53 gene product has been implicated in both human and animal tumorigenesis. p53 forms heterologous complexes with the transforming proteins encoded by several different DNA tumor viruses. p53 also assembles into stable homo-oligomers. We demonstrate that the major structural determinant for the tetramerization of p53 is an alpha-helical plus basic region motif near the C-terminus of the protein. A monomeric p53 mutant adopts a conformation distinct from both 'wild-type' and 'mutant' form as defined by PAb1620 and PAb240 monoclonal antibody recognition. Nevertheless, monomeric and dimeric mutant p53 proteins retain the ability to suppress SV40 origin-directed DNA replication in vivo. Thus, p53-p53 interaction and expression of the PAb1620 epitope is not a prerequisite for such activity. We present data suggesting that suppression of replication by p53 may occur by a mechanism that is independent of detectable p53-T antigen association.
Neuropeptide Y-Related Peptides and their Receptors--Are the Receptors Potential Therapeutic Drug Targets? (1993)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More