gebhart/patrepeval huggingface dataset:
Prostate-Specific Membrane Antigen (PSMA) targeted prodrug “smartbombs” as therapy for prostate cancer (2006)

3081 PSMA is a type II membrane carboxypeptidase that possesses a number of characteristics that make it a suitable candidate for targeted cancer therapy. PSMA expression is highly restricted to prostate tissue with strongest expression in both primary and metastatic prostate cancers and is upregulated upon androgen withdrawal. PSMA, however, is also expressed by the neovasculature within most solid tumors, but not by normal tissue vasculature. Functionally, PSMA is both an N-acetylated α-linked acidic dipeptidase (NAALADase) and a pteroyl poly-γ-glutamyl carboxypeptidase (folate hydrolase) whose extracellular domain is accessible to agents in the extracellular peri-tumoral fluid. To develop a prodrug that can be activated selectively within prostate cancer cells or tumor vasculature by PSMA’s enzymatic activity, PSMA selective peptide carriers were identified consisting primarily of α- or γ-carboxyl linked glutamic and or aspartic acids. These peptides were coupled to the amino terminus of 8-O-(12Aminododecanoyl)-8-O debutanoylthapsigargin (12ADT), a potent cytotoxic analog of the natural plant product thapsigargin (TG) that inhibits the ER Ca2+ ATPase pump and induces proliferation independent apoptosis in all cell types. PSMA hydrolysis of the peptide-12ADT prodrug yields Asp- or Glu-12ADT as the final product. Computer modeling demonstrated that these amino acid containing analogs should potently inhibit the Ca2+ pump and these findings were confirmed in vitro with observed IC50 values for Asp- and Glu-12ADT of ∼ 50 nM against prostate cancer cell lines. A series of peptide-12ADT prodrugs were then synthesized and several were identified that were efficiently hydrolyzed by PSMA and stable to hydrolysis in plasma. Dipeptide and pentapeptide prodrugs were identified that were selectively toxic to PSMA expressing prostate cancer cells in vitro but were 10-60 fold less toxic to non-PSMA expressing cells. A lead prodrug (i.e. G202) was identified from these in vitro studies. After identifying a clinically acceptable formulation vehicle (i.e. PEG/Solutol) pharmacokinetic studies were performed. A single dose of 60 mg/kg of G202 produced a Cmax of ∼ 800 μM and a plasma half-life of ∼5hr. Efficacy studies against PSMA-producing CWR22RH xenografts in castrated mice demonstrated tumor regression and significant growth delay following a single 3-day (60 mg/kg/day) or 10-day (18 mg/kg/day) course of G202. On the basis of these results, further preclinical development of G202 is warranted and large scale synthesis and toxicologic studies are in process.
Local Geometric Indexing of High Resolution Data for Facial Reconstruction From Sparse Markers (2023)

When considering sparse motion capture marker data, one typically struggles to balance its overfitting via a high dimensional blendshape system versus underfitting caused by smoothness constraints. With the current trend towards using more and more data, our aim is not to fit the motion capture markers with a parameterized (blendshape) model or to smoothly interpolate a surface through the marker positions, but rather to find an instance in the high resolution dataset that contains local geometry to fit each marker. Just as is true for typical machine learning applications, this approach benefits from a plethora of data, and thus we also consider augmenting the dataset via specially designed physical simulations that target the high resolution dataset such that the simulation output lies on the same so-called manifold as the data targeted.
[P‐006]: Novel multiplexed CSF biomarkers for antemortem Alzheimer's diagnosis (2005)

We are applying a gel-based proteomics strategy to the analysis of antemortem cerebrospinal fluid from Alzheimer’ patients. Our goal is to identify antemortem biomarkers for AD diagnosis. Retrospective samples from definite Alzheimer’ patients as well as appropriate normal and neurological controls have been collected from a number of CSF banks in the United States. Prospective probable and possible AD samples are collected from a well-characterized clinical population in New York. Using protein two-dimensional electrophoresis, fluorescence staining and laser fluorescence scanning, we are able to visualize approximately 1200 protein spots from typical CSF samples. The Random Forest multivariate statistical analysis is applied to spot patterns from 68 samples to segregate AD and nonAD patient samples. A panel of 23 protein spots is most effective at segregating AD and nonAD patient samples. Matrix assisted laser desorption ionization tandem time of flight mass spectrometry has permitted us to characterize and sequence many of these 23 proteins. Based on these identifications, the group of protein biomarkers include three general functions: Abeta transport, inflammation, and proteolytic enzyme inhibitors. These markers have 94% sensitivity, 94% specificity, and a predicted error classification rate of 5.9% for the 68 samples studied. In an ROC type analysis, the AUC is 0.965, which compares favorably to other reported AD biomarkers and suggest the potential for clinical diagnostic applications.
A Population of Thermostable Reverse Transcriptases Evolved from <i>Thermus aquaticus</i> DNA Polymerase I by Phage Display (2006)

Running in reverse: A set of enzymes selected according to their RNA-dependent DNA polymerase activity from a library of more than 107 mutant enzymes has been characterized. The product was specifically bound to catalytically active proteins displayed on filamentous bacteriophage. The selected variants have a catalytic efficiency for reverse transcription that is two orders of magnitude higher. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z601217_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Cervicovaginal peroxidases: markers of the fertile period. (1986)

The specific activity of guaiacol peroxidase was measured daily in human cervical mucus, vaginal fluids, and saliva during 45 cycles in 31 women. Also determined were basal body temperatures and serum hormones (luteinizing hormone [LH], estradiol, progesterone). The guaiacol peroxidase was extracted with 0.5 M CaCl2 and thus may be a different peroxidase from that obtained by noncalcium extraction procedures. The guaiacol peroxidase specific activity did not vary in the saliva during the cycle but fell sharply in the cervical mucus and vaginal fluid four to five days before the ovulation time, estimated by the LH peak, and rose again one to two days after ovulation. Anovulatory cycles did not show the midcycle drop in guaiacol peroxidase. Growth curve analysis gave excellent fitting of the guaiacol peroxidase data to a polynominal model. These data suggest that cervicovaginal guaiacol peroxidase may be clinically useful in detecting the fertile period for population control and for infertility treatment.
Enzymic semisynthesis of a superpotent analog of human growth hormone-releasing factor (1992)

A superpotent analog of human growth hormone-releasing factor, [desNH2Tyr1,D-Ala2,Ala15]-GRF(1-29)-NH2 (4), was prepared from the precursor, [Ala15,29]-GRF(4-29)-OH (1), by a two-step enzymatic semisynthesis. The amidated C-terminus, essential for high biological potency, was obtained via a carboxypeptidase Y-catalyzed exchange of Ala29-OH for Arg29-NH2 to produce [Ala15]-GRF(4-29)-NH2 (2). The N-terminal desNH2Tyr-D-Ala moiety, which greatly increases in vivo duration of action, was then incorporated by V8 protease-catalyzed condensation of segment 2 with desNH2Tyr-D-Ala-Asp(OH)-OR [R = CH3CH2- (3a) or 4-NO2C6H4CH2-(3b)]. The main focus of this report was to develop conditions to use the V8 protease-catalyzed coupling while avoiding a competing cleavage of the proteolytically-sensitive Asp25-Ile26 bond in GRF. Conversion of 2 to 4 in couplings employing the alpha-ethyl ester of the acyl component 3a was limited to about 60% by competing proteolysis at Asp25-Ile26. This system was adequate for preparing, isolating, and fully characterizing the target analog 4 and identifying the side products. The 4-nitrobenzyl ester 3b proved to be a superior substrate, resulting in 90% conversion of 2 to 4 with no detectable loss to proteolysis and requiring significantly lesser amounts of catalyst. These results demonstrate that enzymatic semisynthesis of a biologically-active peptide amide which contains unnatural amino acids at the N-terminus can be achieved from a biosynthetic precursor in good yield and purity.
RBT1, a novel transcriptional co-activator, binds the second subunit of Replication Protein A (2000)

Replication Protein A (RPA) is required for DNA recombination, repair and replication in all eukaryotes. RPA participation in these pathways is mediated by single-stranded DNA binding and protein interactions. We herein identify a novel protein, Replication Protein Binding Trans-Activator (RBT1), in a yeast two-hybrid assay employing the second subunit of human RPA (RPA32) as bait. RBT1-RPA32 binding was confirmed by glutathione S:-transferase pull-down and co-immunoprecipitation. Fluorescence microscopy indicates that green fluorescence protein-tagged RBT1 is localized to the nucleus in vivo. RBT1 mRNA expression, determined by semi-quantitative RT-PCR, is significantly higher in cancer cell lines MCF-7, ZR-75, SaOS-2 and H661, compared to the cell lines normal non-immortalized human mammary epithelial cells and normal non-immortalized human bronchial epithelial cells. Further, yeast and mammalian one-hybrid analysis shows that RBT1 is a strong transcriptional co-activator. Interestingly, mammalian transactivation data is indicative of significant variance between cell lines; the GAL4-RBT1 fusion protein has significantly higher transcriptional activity in human cancer cells compared to human normal primary non-immortalized epithelial cells. We propose that RBT1 is a novel transcriptional co-activator that interacts with RPA, and has significantly higher activity in transformed cells.
Latency of Marek's Disease Virus (MDV) in a Reticuloendotheliosis Virus–Transformed T-Cell Line. II: Expression of the Latent MDV Genome (2009)

Marek's disease virus (MDV) is an alphaherpesvirus of chickens that causes the paralysis and rapid lymphoma formation known as Marek's disease. MDV establishes latent infection in activated CD4+ T-cells, and these cells are also the target for transformation. MDV latency has been studied using MDV lymphoma-derived cell lines and T-cells isolated from infected chickens. Each of these models has limitations because MDV-transformed cell lines require the use of oncogenic viruses; conversely, pools of latently infected cells are in relatively low abundance and invariably contain cells undergoing reactivation to lytic infection. In this study we have examined the spontaneous and induced expression of the MDV genome, the effect of genome uptake on cellular proliferation and apoptosis resistance, and differences in cellular surface antigen expression associated with MDV genome uptake in a reticuloendotheliosis virus (REV)-transformed T-cell model. We report that the MDV genome is highly transcribed during this latent infection, and that the expression of Marek's EcoRI-Q-encoded protein (Meq) transcripts is similar to that of MDV-transformed cells, but is somewhat lower than MDV-transformed cells at the protein level. Uptake of the MDV genome was associated with an increased growth rate and resistance to serum starvation-induced apoptosis. Treatment of cells with bromodeoxyuridine induced the expression of MDV lyric antigens in a manner similar to MDV-transformed cells. Uptake of the MDV genome, however, was not consistently associated with alteration ofT-cell surface antigen expression. Overall, our data show that the REV-transformed cell line model for MDV latency mimics many important aspects of latency also observed in MDV-transformed cells and provides an additional tool for examining MDV latent infection.
A new frequency synthesis method based on "flying-adder" architecture. (2003)

The flying-adder frequency and phase synthesis architecture was presented in papers published by Mair and Xiu in 2000 and Xiu and You in 2002. This architecture contains many excellent features and it can be implemented/integrated easily in a very large scale integration system. However, it has a drawback of inherent jitter on the output frequency, due to the frequency modulation of the output frequency. This brief presents a new frequency synthesis method that eliminates such jitter. The frequency accuracy of this new architecture is studied; subsequently, the frequency error upper bound is found. Furthermore, it leads to the development of a scheme that can be used to derive the frequency error distribution. The comparison to integer-N and fractional-N phase-locked loop (PLL) based frequency synthesis techniques is also presented.
Generalized Recovery From Node Failure in Virtual Network Embedding (2017)

Network virtualization has evolved as a key enabling technology for offering the next generation network services. Recently, it is being rolled out in data center networks as a means to provide bandwidth guarantees to cloud applications. With increasing deployments of virtual networks (VNs) in commercial-grade networks with commodity hardware, VNs need to tackle failures in the underlying substrate network. In this paper, we study the problem of recovering a batch of VNs affected by a substrate node failure. The combinatorial possibilities of alternate embeddings of the failed virtual nodes and links of the VNs make the task of finding the most efficient recovery both non-trivial and intractable. Furthermore, any recovery approach ideally should not cause any service disruption for the unaffected parts of the VNs. We take into account these issues to design a generalized recovery approach that can achieve customized objectives such as fair treatment on the failed VNs, partial treatment based on priority, and so on. We provide integer linear programming (ILP) formulations for two variants of our recovery scheme, namely, fair recovery model and priority-based recovery model. We also propose a fast and scalable heuristic algorithm to tackle the computational complexity of the ILP solution. Evaluation results demonstrate that our heuristic performs close to the optimal solution and outperforms the state-of-the-art algorithm.
Differential effects and transport kinetics of ascorbate derivatives in leukemic cell lines. (1998)

In order to investigate the differential effects of ascorbate derivatives on leukemic cell growth, we examined their stabilities and transmembrane transport efficiencies. The growth of HL-60 and U937 cells was dose-dependently inhibited by ascorbic acid and sodium ascorbate, but not by dehydroascorbic acid and magnesium ascorbyl 2-phosphate up to 200 microM. The growth-suppression by ascorbic acid was dependent on its redox state, showing a complete or partial reversion by ascorbate oxidase or FeCl3 addition, respectively. Three different patterns of intracellular ascorbic acid accumulation were observed by HPLC according to the species of ascorbate derivative applied for the incubation. Compared with the reduced form of ascorbic acid, the oxidized forms (dehydroascorbic acid, ascorbic acid plus ascorbate oxidase or FeCl3) were rapidly transported into cells and readily degraded, while magnesium ascorbyl 2-phosphate, a stable derivative of ascorbic acid, slowly elevated the intracellular level of ascorbic acid, reaching a plateau at 24 hours. We also measured the differential kinetics of ascorbic acid levels In culture supernatants following the addition of ascorbate derivatives. Ascorbic acid at 40, 10, or 1 microM was observed 3 hours following treatment with 100 microM of ascorbic acid, ascorbic acid plus FeCl3, or magnesium ascorbyl 2-phosphate, respectively. No ascorbic acid was found in the culture supernatant treated with dehydroascorbic acid. This order of ascorbic acid concentrations in culture supernatant reflects their growth-inhibitory effects. Thus the growth inhibitory effect of ascorbic acid appears to be dependent on its concentration in culture medium rather than its intracellular concentration. In conclusion, the results in this study indicate that the differential effects of ascorbate derivatives appear to be due to the actual concentration differences of the reduced form of ascorbic acid in culture medium following their addition, which is determined by their stability and efficiency of cellular uptake.
Mimicking Melanosomes: Polydopamine Nanoparticles as Artificial Microparasols (2017)

A primary role of melanin in skin is the prevention of UV-induced nuclear DNA damage to human skin cells, where it serves to screen out harmful UV radiation. Melanin is delivered to keratinocytes in the skin after being excreted as melanosomes from melanocytes. Defects in melanin production in humans can cause diseases, many of which currently lack effective treatments due to their genetic origins (e.g., skin cancer, vitiligo, and albinism). The widespread prevalence of melanin-related diseases and an increasing interest in the performance of various polymeric materials related to melanin necessitates novel synthetic routes for preparing melanin-like materials. In this work, we prepared melanin-like nanoparticles (MelNPs) via spontaneous oxidation of dopamine, as biocompatible, synthetic analogues of naturally occurring melanosomes, and investigated their uptake, transport, distribution, and UV-protective capabilities in human keratinocytes. Critically, we demonstrate that MelNPs are endocytosed, undergo perinuclear aggregation, and form a supranuclear cap, or so-called microparasol in human epidermal keratinocytes (HEKa), mimicking the behavior of natural melananosomes in terms of cellular distribution and the fact that they serve to protect the cells from UV damage.
Enhanced Detection of Single Viruses On-Chip via Hydrodynamic Focusing (2018)

Planar optofluidics provide a powerful tool for facilitating chip-scale light-matter interactions. Silicon-based liquid core waveguides have been shown to offer single molecule sensitivity for efficient detection of bioparticles. Recently, a PDMS based planar optofluidic platform was introduced that opens the way to rapid development and prototyping of unique structures, taking advantage of the positive attributes of silicon dioxide-based optofluidics and PDMS based microfluidics. Here, hydrodynamic focusing is integrated into a PDMS based optofluidic chip to enhance the detection of single H1N1 viruses on-chip. Chip-plane focusing is provided by a system of microfluidic channels to force the particles towards a region of high optical collection efficiency. Focusing is demonstrated and enhanced detection is quantified using fluorescent polystyrene beads where the coefficient of variation is found to decrease by a factor of 4 with the addition of hydrodynamic focusing. The mean signal amplitude of fluorescently tagged single H1N1 viruses is found to increase with the addition of focusing by a factor of 1.64.
X-optogenetics and U-optogenetics: Feasibility and Possibilities (2014)

To address these limitations of optogenetics, here we propose two new methods for optogenetic stimulation. The first is x-optogenetics, which uses visible light-emitting nanophosphors stimulated by focused x-rays. This idea is not new but the application to optogenetics is novel. X-rays can penetrate much more deeply than infrared light and could allow for nerve cell stimulation in any part of the brain. In this paper, we discuss the feasibility and possibilities of such a method by describing the advances in nanomaterials, x-ray focusing, and x-ray sources. Also, we discuss concerns when dealing with x-rays such as radiation dosage. Through the use of quantities and assumptions backed by recent literature, manufacturer specifications, and personal correspondence, a full feasibility analysis of x-optogenetics is completed. The second proposed method we explore is u-optogenetics, which is the application of sonoluminescence to optogenetics. Such a technique uses ultrasound waves instead of x-rays to induce light emission, so there would be no introduction of radiation. However, the penetration depth of ultrasound is less than that of x-ray. The key issues affecting feasibility are laid out for further investigation into both x-optogenetics and u-optogenetics.
Desulfurizing Coal with Alkaline Solutions Containing Dissolved Oxygen (1977)

The extraction of pyritic sulfur from coal by leaching the comminuted material with hot aqueous solutions containing dissolved oxygen has been demonstrated in numerous laboratory experiments (1-6). Although acidic solutions have generally been used for such experiments, basic solutions appear to offer several important advantages. Thus Majima and Peters (7) showed that the rate of extraction of sulfur from relatively pure pyrite is much greater in basic solutions containing dissolved oxygen than in neutral solutions. Moreover it has been shown recently that basic solutions containing ammonium hydroxide and oxygen can extract a significant portion of the organic sulfur as well as most of the inorganic sulfur from coal at relatively moderate temperatures (e.g., 130°C) (4,5) whereas higher temperatures (150°-200°C) seem to be required with acidic solutions to remove organic sulfur (6). Furthermore some types of basic solutions are much less corrosive towards the common materials of construction than acidic solutions.
An Open Source ECG Clock Generator for Visualization of Long-Term Cardiac Monitoring Data (2015)

The collection of long-term health data is accelerating with the advent of portable/wearable medical devices including electrocardiograms (ECGs). This large corpus of data presents great opportunities to improve the quality of cardiac care. However, analyzing the data from these sensors is a challenge; the relevant information from ~120 000 heart beats per patient per day must be condensed into a human-readable form. Our goal is to facilitate the analysis of these unwieldy data sets. We have developed an open source tool for creating easy-to-interpret plots of cardiac information over long periods. We call these plots ECG clocks. The utility of our ECG clock library is demonstrated through multiple examples drawn from a database of 24-h Holter recordings. In these case studies, we focus on the visualization of heart rate and QT dynamics. The ECG clock concept is shown to be relevant for both physicians and researchers, for identifying healthy and abnormal values and patterns in ECG recordings. In this paper, we describe how to use the ECG clock library to analyze 24-h ECG recordings, and how to extend the source code for your own purposes. The tool is applicable to a wide range of cardiac monitoring tasks, such as heart rate variability or ST elevation. This library, which we have made freely available, can help provide new insights into circadian patterns of cardiac function in individuals and groups.