gebhart/patrepeval huggingface dataset:
Artificial Micromotors in the Mouse’s Stomach: A Step toward in Vivo Use of Synthetic Motors (2014)

Artificial micromotors, operating on locally supplied fuels and performing complex tasks, offer great potential for diverse biomedical applications, including autonomous delivery and release of therapeutic payloads and cell manipulation. Various types of synthetic motors, utilizing different propulsion mechanisms, have been fabricated to operate in biological matrices. However, the performance of these man-made motors has been tested exclusively under in vitro conditions (outside the body); their behavior and functionalities in an in vivo environment (inside the body) remain unknown. Herein, we report an in vivo study of artificial micromotors in a living organism using a mouse model. Such in vivo evaluation examines the distribution, retention, cargo delivery, and acute toxicity profile of synthetic motors in mouse stomach via oral administration. Using zinc-based micromotors as a model, we demonstrate that the acid-driven propulsion in the stomach effectively enhances the binding and retention of the motors as well as of cargo payloads on the stomach wall. The body of the motors gradually dissolves in the gastric acid, autonomously releasing their carried payloads, leaving nothing toxic behind. This work is anticipated to significantly advance the emerging field of nano/micromotors and to open the door to in vivo evaluation and clinical applications of these synthetic motors.
Evaluation of desmoglein enzyme‐linked immunosorbent assay (ELISA) in Indian patients with pemphigus vulgaris (2006)

ELISA (dsg1 and dsg3) is an efficient tool for confirming the diagnosis of PV. Specific antibody titers correlate with disease severity; however, desmoglein testing cannot differentiate between the various morphologic subtypes of PV.
Complex Modal Analysis of Non-Self-Adjoint Hybrid Serpentine Belt Drive Systems (2000)

A linear damped hybrid (continuous/discrete components) model is developed in this paper to characterize the dynamic behavior of serpentine belt drive systems. Both internal material damping and external tensioner arm damping are considered. The complex modal analysis method is developed to perform dynamic analysis of linear non-self-adjoint hybrid serpentine belt-drive systems. The adjoint eigenfunctions are acquired in terms of the mode shapes of an auxiliary hybrid system. The closed-form characteristic equation of eigenvalues and the exact closed-form solution for dynamic response of the non-self-adjoint hybrid model are obtained. Numerical simulations are performed to demonstrate the method of analysis. It is shown that there exists an optimum damping value for each vibration mode at which vibration decays the fastest.
Human lymphotoxin. Production by a lymphoblastoid cell line, purification, and initial characterization. (1984)

Human lymphotoxin was purified to homogeneity from a serum-free tissue culture supernatant of a lymphoblastoid 1788 cell line. The purification scheme consisted of DEAE-cellulose chromatography, preparative isoelectric focusing, lentil lectin-Sepharose chromatography, and preparative polyacrylamide gel electrophoresis. The purified glycoprotein was homogeneous by the criteria of high pressure liquid chromatography and polyacrylamide gel electrophoresis run under both nondenaturing and denaturing conditions. The specific activity of the purified lymphotoxin is approximately 40 X 10(6) units/mg. The protein has an apparent molecular weight of approximately 20,000, and RF of 0.33 on 7.5% polyacrylamide gels at pH 8.8 and an isoelectric point of 5.8. A tryptic digest of the purified native material produced two major fragments of approximately 15,000 and 5,000 Da. The amino acid compositions of the intact molecule and of the tryptic fragments are presented.
<title>Multiresolution morphological analysis of document images</title> (1992)

An image-based approach to document image analysis is presented, that uses shape and textural properties interchangeably at multiple scales. Image-based techniques permit a relatively small number of simple and fast operations to be used for a wide variety of analysis problems with document images. The primary binary image operations are morphological and multiresolution. The generalized opening, a morphological operation, allows extraction of image features that have both shape and textural properties, and that are not limited by properties related to image connectivity. Reduction operations are necessary due to the large number of pixels at scanning resolution, and threshold reduction is used for efficient and controllable shape and texture transformations between resolution levels. Aspects of these techniques, which include sequences of threshold reductions, are illustrated by problems such as text/halftone segmentation and word-level extraction. Both the generalized opening and these multiresolution operations are then used to identify italic and bold words in text. These operations are performed without any attempt at identification of individual characters. Their robustness derives from the aggregation of statistical properties over entire words. However, the analysis of the statistical properties is performed implicitly, in large part through nonlinear image processing operations. The approximate computational cost of the basic operations is given, and the importance of operating at the lowest feasable resolution is demonstrated.
Modulation of the hypothalamopituitary axis in Mini rat: Further studies with hypophysiotropic somatostatin and gonadotroph cells. (2010)

In transgenic Mini rat, in which the expression of intrinsic growth hormone (GH) gene is suppressed by the antisense GH transgene are characterized by definite somatic growth retardation at puberty. Compared to age-matched wild-type Wister (non-Mini) rat, Mini rat showed low blood GH levels and GH cell depletion in the anterior pituitary (AP). The AP and periventricular hypothalamic nucleus (PeVN) were processed for immunohistochemical analysis with antisera to Luteinizing hormone (LH) and somatostatin (SOM), respectively. Although LH-immunoreactive (IR) cells showed the decrease in number in Mini rat from 4 to 8 weeks of age, there was the significant increase in non-Mini rat. Interestingly, SOM-IR cells in the PeVN showed the marked increase in number in Mini rat in contrast to the decrease in non-Mini rat during the same periods. The testis weights were not significantly different between Mini and non-Mini rat at 4 weeks of age, whereas at 6 and 8 weeks of age the value of Mini rat was significantly smaller than non-Mini rat. It was concluded that the onset and development of LH-testicular axis need intrinsic GH regulation, which is involved the SOM cell interaction from PeVN, and the SOM plays a crucial role in the development of pituitary-testicular maturation during the puberty.
Delivery of Retinoid-Based Therapies To Target Tissues (2007)

Through its various metabolites, vitamin A controls essential physiological functions. Both naturally occurring metabolites and novel retinoid analogues have shown effectiveness in many clinical settings that include skin diseases and cancer, and in animal models of human conditions affecting vision. In this review, we analyze several potential retinoid-based therapies from the point of view of drug metabolism and transport to target tissues. We focus on the endogenous factors that affect the absorption, transport, and metabolism of retinoids by taking into account data obtained from the analysis of animal models that lack the enzymes or proteins involved in the storage and absorption of retinoids. We also discuss findings of toxicity associated with retinoids in an effort to improve the outcome of retinoid-based therapies. In this context, we review evidence that esterification of retinol and retinol-based drugs within target tissues provides one of the most efficient means to improve the absorption and to reduce the toxicity associated with pharmacological doses of retinoids. Future retinoid-based therapeutic strategies could involve targeted delivery mechanisms leading to lower toxicity and improved effectiveness of retinoids.
Proton nuclear magnetic resonance investigation of the nature of solution conformational equilibriums of monomeric insect deoxyhemoglobins (1981)

The proton nuclear magnetic resonance spectra of the three monomeric deoxyhemoglobins of the insect larva Chironomus thummi thummi have been recorded, assigned, and analyzed. In the two allosteric hemoglobins, the heme methyls and vinyl protons were assigned by specific deuterium labeling. The hyperfine-shifted proximal histidyl imidazole exchangeable protons for the three native and two deuteroheme-reconstituted hemoglobins were assigned by comparison of spectra in H2O and 2H2O. Both native and reconstituted allosteric hemoglobins exhibit two sets of interconvertible resonances indicative of two heme orientations differing by a 180 degrees rotation about the alpha-gamma-meso axis, as previously found for the met-cyano analogues [La Mar, G. N., Smith, K. M., Gersonde, K., Sick, H., & Overkamp, M. (1980) J. Biol. Chem. 255, 66]. The relative pH sensitivities of the heme resonance hyperfine shifts for the two allosteric hemoglobins and the apparent pK approximately 8 indicate that the t in equilibrium r allosteric transition, as modulated by the Bohr proton, is being observed. For the native hemoglobins, the t in equilibrium r conformational transition was found to be centered at the heme periphery, with the proximal histidyl imidazole environment insensitive to both pH and the rotational position of the heme, consistent with the absence of a pH influence on the ligation on-rate. For the deuteroheme-reconstituted allosteric hemoglobins, both the heme and axial imidazole environments sense the t in equilibrium r transition, and the histidine environments for the two components for each hemoglobin can be clearly distinguished, suggesting that the ligation on-rates may depend on both pH and heme orientation.
In vitro and in vivo arterial differentiation of human multipotent adult progenitor cells (2006)

Many stem cell types have been shown to differentiate into endothelial cells (ECs); however, their specification to arterial or venous endothelium remains unexplored. We tested whether a specific arterial or venous EC fate could be induced in human multipotent adult progenitor cells (hMAPCs) and AC133(+) cells (hAC133(+)). In vitro, in the presence of VEGF(165), hAC133(+) cells only adopted a venous and microvascular EC phenotype, while hMAPCs differentiated into both arterial and venous ECs, possibly because hMAPCs expressed significantly more sonic hedgehog (Shh) and its receptors as well as Notch 1 and 3 receptors and some of their ligands. Accordingly, blocking either of those pathways attenuated in vitro arterial EC differentiation from hMAPCs. Complementarily, stimulating these pathways by addition of Delta-like 4 (Dll-4), a Notch ligand, and Shh to VEGF(165) further boosted arterial differentiation in hMAPCs both in vitro and in an in vivo Matrigel model. These results represent the first demonstration of adult stem cells with the potential to be differentiated into different types of ECs in vitro and in vivo and provide a useful human model to study arteriovenous specification.
TGF-β Signaling in Cellular Senescence and Aging-Related Pathology (2019)

Aging is broadly defined as the functional decline that occurs in all body systems. The accumulation of senescent cells is considered a hallmark of aging and thought to contribute to the aging pathologies. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that regulates a myriad of cellular processes and has important roles in embryonic development, physiological tissue homeostasis, and various pathological conditions. TGF-β exerts potent growth inhibitory activities in various cell types, and multiple growth regulatory mechanisms have reportedly been linked to the phenotypes of cellular senescence and stem cell aging in previous studies. In addition, accumulated evidence has indicated a multifaceted association between TGF-β signaling and aging-associated disorders, including Alzheimer's disease, muscle atrophy, and obesity. The findings regarding these diseases suggest that the impairment of TGF-β signaling in certain cell types and the upregulation of TGF-β ligands contribute to cell degeneration, tissue fibrosis, inflammation, decreased regeneration capacity, and metabolic malfunction. While the biological roles of TGF-β depend highly on cell types and cellular contexts, aging-associated changes are an important additional context which warrants further investigation to better understand the involvement in various diseases and develop therapeutic options. The present review summarizes the relationships between TGF-β signaling and cellular senescence, stem cell aging, and aging-related diseases.
Hydrophilic elastomeric biomaterials based on resilin-like polypeptides (2009)

The production of complex, yet well defined materials offers many opportunities in regenerative medicine, in which the mechanical and biological properties of the matrix must meet stringent requirements. Here we report the recombinant production of modular polypeptidic materials, based on the highly resilient protein resilin, which are equipped with multiple biologically active domains. The recombinant materials exhibit useful mechanical and cell adhesion behavior.
Active-site mapping of bovine and human blood coagulation serine proteases using synthetic peptide 4-nitroanilide and thio ester substrates (1984)

A series of 14 tripeptide 4-nitroanilide substrates of the type Z-AA-Gly-Arg-NA and Z-AA-Phe-Arg-NA where AA = Ala, Asn, Glu, Lys, Phe, Pro, or Ser were used to map the S3 subsite of several serine proteases involved in blood coagulation. The enzymes studied included bovine thrombin, factor IXa, factor Xa, factor XIa, human beta-factor XIIa (factor XIIa fragment), and activated bovine and human protein C. Kinetic constants (kcat, KM, and kcat/KM) for the enzymatic hydrolysis of the substrates by each enzyme were determined and used to compare the relative reactivities of the individual enzymes. Most of the enzymes reacted with all the substrates, although a few showed considerable specificity. Human beta-factor XIIa showed the highest reactivity of all the coagulation proteases studied and was also very substrate specific (kcat/KM ranged over 470-fold). The best substrate was Z-Lys-Phe-Arg-NA with kcat/KM = 140 000 M-1 s-1. Activated bovine protein C (best substrate = Z-Ser-Phe-Arg-NA), factor Xa (best substrate = Z-Glu-Gly-Arg-NA), and thrombin (best substrate = Z-Lys-Gly-Arg-NA) were the group of enzymes that showed next highest reactivity toward the substrates. Activated bovine protein C, thrombin, and factor Xa displayed relatively little substrate specificity. Activated human protein C (best substrate = Z-Ser-Phe-Arg-NA) and factor XIa (best substrate = Z-Glu-Gly-Arg-NA) are moderately reactive enzymes. Activated human protein C is an extremely specific enzyme since it has such a large range of kcat/KM values.(ABSTRACT TRUNCATED AT 250 WORDS)
Medium access control protocols using directional antennas in ad hoc networks (2002)

Using directional antennas can be beneficial for wireless ad hoc networks consisting of a collection of wireless hosts. To best utilize directional antennas, a suitable medium access control (MAC) protocol must be designed. Current MAC protocols, such as the IEEE 802.11 standard, do not benefit when using directional antennas, because these protocols have been designed for omnidirectional antennas. In this paper, we attempt to design new MAC protocols suitable for ad hoc networks based on directional antennas.
Adoptive Transfer of CD8 + T Cells Generated from Induced Pluripotent Stem Cells Triggers Regressions of Large Tumors Along with Immunological Memory (2016)

Current approaches to adoptive T cell therapy are limited by the difficulty of obtaining sufficient numbers of T cells against targeted antigens with useful in vivo characteristics. Theoretically, this limitation could be overcome by using induced pluripotent stem cells (iPSCs) that could provide an unlimited source of autologous T cells. However, the therapeutic efficacy of iPSC-derived regenerated T cells remains to be demonstrated. Here we report the first successful reprogramming of T-cell receptor (TCR) transgenic CD8(+) T cells into pluripotency. As part of the work, we established a syngeneic mouse model for evaluating in vitro and in vivo antitumor reactivity of regenerated T cells from iPSCs bearing a rearranged TCR of known antigen specificity. Stably TCR retained T cell-derived iPSCs differentiated into CD4(+)CD8(+) T cells that expressed CD3 and the desired TCR in vitro. Stimulation of iPSC-derived CD4(+)CD8(+) T cells with the cognate antigen in the presence of IL-7 and IL-15 followed by expansion with IL-2, IL-7 and IL-15 generated large numbers of less-differentiated CD8(+) T cells with antigen-specific potent cytokine production and cytolytic capacity. Furthermore, adoptively transferred iPSC-derived CD8(+) T cells escaped immune rejection, mediated effective regression of large tumors, improved survival, and established antigen-specific immunological memory. Our findings illustrate the translational potential of iPSCs to provide an unlimited number of phenotypically defined, functional, and expandable autologous antigen-specific T cells with the characteristics needed to enable in vivo effectiveness.
tRNA-tRNA interactions within cellular ribosomes. (1989)

We describe an assay that converts the effects of tRNA-tRNA contacts at two particular codons into a quantitative effect on beta-galactosidase level. The assay measures the separate and combined efficiency of suppression at adjacent nonsense codons in vivo using a set of specially created homologous messages. In a survey of distal anticodon arm substitutions, we find that particular mutant tRNAs occupying the P-site reduce the apparent efficiency of the suppressor tRNA reading the A-site codon by factors of 2-170. By using measured tRNA-tRNA distances and the crystallographic tRNA structure, we propose a model of the tRNA-tRNA-mRNA complex. In the model, the anticodon loops of the P-site and A-site tRNAs contact one another in a way that is consistent with our combined tRNA efficiency data. These results suggest that tRNA-tRNA interactions that modulate tRNA action are an inevitable feature of translation.
Molecular Pathways: HER3 Targeted Therapy (2014)

The HER family of receptor tyrosine kinases, including EGF receptor (EGFR), HER2, HER3, and HER4, transduce growth-promoting signals in response to ligand binding to their extracellular domains (ECD). This family is deregulated in numerous cancers, with mutations in EGFR and HER2 often serving as "driver" events to activate key growth factor signaling pathways such as the RAS-ERK and PI3K-AKT pathways. Less attention has been paid to the oncogenic functions of HER3 due to its lack of intrinsic kinase activity. Recent work, however, has placed HER3 in the spotlight as a key signaling hub in several clinical contexts. First, HER3 has been shown to play a major role in mediating resistance to HER2 and phosphoinositide 3-kinase (PI3K) pathway-directed therapies due to its feedback regulation via AKT signaling. Second, activating mutations in HER3 have been identified in multiple cancer types, including gastric, colon, bladder, and non-small cell lung cancers. As a result, HER3 is now being examined as a direct therapeutic target. In the absence of a strong enzymatic activity to target, the focus has been on strategies to prevent HER3 activation including blocking its most relevant dimerization partner's kinase activity (erlotinib, gefitinib, and lapatinib), blocking its most relevant dimerization partner's ability to dimerize with HER3 (trastuzumab and pertuzumab), and directly targeting the HER3 ECD (MM-121, U3-1287, and LJM716). Although drugs targeting EGFR and HER2 have proven effective even as single agents, the preclinical and clinical data on the antibodies directly targeting HER3 suggest more limited potential for single-agent activity. Possible reasons for this include the lack of a suitable biomarker for activated HER3, the lack of potency of the antibodies, and the lack of relevance of HER3 for growth of some of the cancer types analyzed. Nevertheless, clear improvements in activity are being observed for many of these compounds when they are given in combination. In this snapshot, we will highlight the basis for HER3 activation in cancer, the different pharmacologic strategies being used, and opportunities for further development.
Cat-Transmitted Fatal Pneumonic Plague in a Person who Traveled from Colorado to Arizona (1994)

Plague, primarily a disease of rodents and their infected fleas, is fatal in 50% of infected humans if untreated. In the United States, human cases have been concentrated in the southwest. The most common modes of plague transmission are through flea bites or through contact with infected blood or tissues; however, primary pneumonic plague acquired from cats has become increasingly recognized. We report on the case investigation of a patient, presumably exposed to a plague-infected cat in Colorado, who presented with gastrointestinal symptoms, and subsequently died of primary pneumonic plague. Public health officials should be vigilant for plague activity in rodent populations, veterinarians should suspect feline plague in ill or deceased cats, and physicians should have a high index of suspicion for plague in any person who has traveled to plague enzootic areas.
Effects of L-arginine on forearm vessels and responses to acetylcholine. (1992)

This study was designed to investigate the effects of L-arginine (the substrate of endothelium-derived nitric oxide) in human forearm vessels. We examined whether intra-arterial infusion of L-arginine dilated forearm vessels and augmented vasodilatory responses to acetylcholine in young, healthy humans. The left brachial artery was cannulated for drug infusions and direct measurement of arterial pressure. Forearm blood flow was measured by a strain gauge plethysmograph. Intra-arterial infusions of L-arginine at 10, 20, 40, and 60 mg/min increased forearm blood flow from 4.7 +/- 0.6 to 4.9 +/- 0.5, 5.7 +/- 0.5, 7.2 +/- 0.8, and 8.2 +/- 0.9 ml.min-1.100 ml-1, respectively (n = 8, p less than 0.01), whereas D-arginine at the same doses did not alter forearm blood flow (n = 7). Intra-arterial infusions of acetylcholine (n = 7) (4, 8, 16, and 24 micrograms/min) and sodium nitroprusside (n = 5) (0.2, 0.4, 0.8, and 1.2 micrograms/min) increased forearm blood flow dose dependently (p less than 0.01 for both). Arterial pressure was not altered with infusions of these drugs. Responses to acetylcholine were augmented with simultaneous intra-arterial infusion of L-arginine at 10 mg/ml (p less than 0.01) but not with D-arginine. Responses to sodium nitroprusside were not altered by L-arginine. These results in human forearm resistance vessels support the notion that vasodilation induced by acetylcholine is a result of the conversion from L-arginine to endothelium-derived nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)