gebhart/patrepeval huggingface dataset:
Helix propensities of the amino acids measured in alanine‐based peptides without helix‐stabilizing side‐chain interactions (1994)

Helix propensities of the amino acids have been measured in alanine-based peptides in the absence of helix-stabilizing side-chain interactions. Fifty-eight peptides have been studied. A modified form of the Lifson-Roig theory for the helix-coil transition, which includes helix capping (Doig AJ, Chakrabartty A, Klingler TM, Baldwin RL, 1994, Biochemistry 33:3396-3403), was used to analyze the results. Substitutions were made at various positions of homologous helical peptides. Helix-capping interactions were found to contribute to helix stability, even when the substitution site was not at the end of the peptide. Analysis of our data with the original Lifson-Roig theory, which neglects capping effects, does not produce as good a fit to the experimental data as does analysis with the modified Lifson-Roig theory. At 0 degrees C, Ala is a strong helix former, Leu and Arg are helix-indifferent, and all other amino acids are helix breakers of varying severity. Because Ala has a small side chain that cannot interact significantly with other side chains, helix formation by Ala is stabilized predominantly by the backbone ("peptide H-bonds"). The implication for protein folding is that formation of peptide H-bonds can largely offset the unfavorable entropy change caused by fixing the peptide backbone. The helix propensities of most amino acids oppose folding; consequently, the majority of isolated helices derived from proteins are unstable, unless specific side-chain interactions stabilize them.
PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum (1996)

It has been proposed that the Xenopus homeobox gene, XlHbox8, is involved in endodermal differentiation during pancreatic and duodenal development (Wright, C.V.E., Schnegelsberg, P. and De Robertis, E.M. (1988). Development 105, 787-794). To test this hypothesis directly, gene targeting was used to make two different null mutations in the mouse XlHbox8 homolog, pdx-1. In the first, the second pdx-1 exon, including the homeobox, was replaced by a neomycin resistance cassette. In the second, a lacZ reporter was fused in-frame with the N terminus of PDX-1, replacing most of the homeodomain. Neonatal pdx-1 -/- mice are apancreatic, in confirmation of previous reports (Jonsson, J., Carlsson, L., Edlund, T. and Edlund, H. (1994). Nature 371, 606-609). However, the pancreatic buds do form in homozygous mutants, and the dorsal bud undergoes limited proliferation and outgrowth to form a small, irregularly branched, ductular tree. This outgrowth does not contain insulin or amylase-positive cells, but glucagon-expressing cells are found. The rostral duodenum shows a local absence of the normal columnar epithelial lining, villi, and Brunner's glands, which are replaced by a GLUT2-positive cuboidal epithelium resembling the bile duct lining. Just distal of the abnormal epithelium, the numbers of enteroendocrine cells in the villi are greatly reduced. The PDX-1/beta-galactosidase fusion allele is expressed in pancreatic and duodenal cells in the absence of functional PDX-1, with expression continuing into perinatal stages with similar boundaries and expression levels. These results offer additional insight into the role of pdx-1 in the determination and differentiation of the posterior foregut, particularly regarding the proliferation and differentiation of the pancreatic progenitors.
Adjunctive use of the non‐ionic surfactant Poloxamer  188 improves fetal dopaminergic cell survival and reinnervation in a neural transplantation strategy for Parkinson's disease (2007)

Although neural transplantation of fetal dopaminergic cells is a promising therapy for Parkinson's disease, poor transplanted cell survival limits its efficacy. In the present study it was hypothesized that the use of Poloxamer 188 (P188), a non-ionic surfactant, during cell preparation and transplantation may protect cells from associated mechanical injury and thus improve transplanted cell survival in a rat model of Parkinson's disease. Fetal rat dopaminergic tissue was dissociated in media with or without P188 and then cultured for 1 week or transplanted into the striatum of rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal dopaminergic pathway. Fetal dopaminergic cell survival and reinnervation of the host brain were examined using tyrosine hydroxylase immunohistochemistry and stereological quantification. The number of surviving tyrosine hydroxylase-immunoreactive cells in vitro and in vivo was significantly increased by 2.2-fold by incubating fetal dopaminergic cells with P188 during tissue dissociation. Furthermore, the striatal reinnervation in parkinsonian rats that received intrastriatal transplants of P188-exposed dopaminergic cells was significantly enhanced (1.8-fold increase) compared with rats that received non-P188-treated cells. In conclusion, P188 protects fetal dopaminergic cells from mechanical injury by increasing cell survival and enhances dopaminergic fibre outgrowth into the transplanted striatum. Use of P188 may thus be an important adjunct to improve the clinical efficacy of neural transplantation for Parkinson's disease.
Targeting Notch to Target Cancer Stem Cells (2010)

The cellular heterogeneity of neoplasms has been at the center of considerable interest since the "cancer stem cell hypothesis", originally formulated for hematologic malignancies, was extended to solid tumors. The origins of cancer "stem" cells (CSC) or tumor-initiating cells (TIC; henceforth referred to as CSCs) and the methods to identify them are hotly debated topics. Nevertheless, the existence of subpopulations of tumor cells with stem-like characteristics has significant therapeutic implications. The stem-like phenotype includes indefinite self-replication, pluripotency, and, importantly, resistance to chemotherapeutics. Thus, it is plausible that CSCs, regardless of their origin, may escape standard therapies and cause disease recurrences and/or metastasis after apparently complete remissions. Consequently, the idea of selectively targeting CSCs with novel therapeutics is gaining considerable interest. The Notch pathway is one of the most intensively studied putative therapeutic targets in CSC, and several investigational Notch inhibitors are being developed. However, successful targeting of Notch signaling in CSC will require a thorough understanding of Notch regulation and the context-dependent interactions between Notch and other therapeutically relevant pathways. Understanding these interactions will increase our ability to design rational combination regimens that are more likely to prove safe and effective. Additionally, to determine which patients are most likely to benefit from treatment with Notch-targeting therapeutics, reliable biomarkers to measure pathway activity in CSC from specific tumors will have to be identified and validated. This article summarizes the most recent developments in the field of Notch-targeted cancer therapeutics, with emphasis on CSC.
Measuring the Effectiveness of Downtown Revitalization Strategies (2003)

Downtowns, the traditional business centers of our communities, have survived many changes throughout the last century. Once thriving retail and civic centers, they were adversely affected by changes in mobility, retail patterns and shopping habits. Since the 1960's downtowns have seen serious competition from suburban shopping centers, malls, strip commercial areas, major discount centers and on-line and catalogue sales. Despite these changes, downtowns still play a central role in our cities today. They are the centers of our urbanized areas and still reflect the economic core and image of our cities. A healthy downtown is often synonymous wit a healthy community.
The Theory and Applications of Homomorphic Cryptography (2008)

Homomorphic cryptography provides a third party with the ability to perform simple computations on encrypted data without revealing any information about the data itself. Typically, a third party can calculate one of the encrypted sum or the encrypted product of two encrypted messages. This is possible due to the fact that the encryption function is a group homomorphism, and thus preserves group operations. This makes homomorphic cryptosystems useful in a wide variety of privacy preserving protocols.&#13;\n&#13;\nA comprehensive survey of known homomorphic cryptosystems is provided, including formal definitions, security assumptions, and outlines of security proofs for each cryptosystem presented. Threshold variants of several homomorphic cryptosystems are also considered, with the first construction of a threshold Boneh-Goh-Nissim cryptosystem given, along with a complete proof of security under the threshold semantic security game of Fouque, Poupard, and Stern. This approach is based on Shoup's approach to threshold RSA signatures, which has been previously applied to the Paillier and Damg\\aa rd-Jurik cryptosystems. The question of whether or not this approach is suitable for other homomorphic cryptosystems is investigated, with results suggesting that a different approach is required when decryption requires a reduction modulo a secret value.&#13;\n&#13;\nThe wide variety of protocols utilizing homomorphic cryptography makes it difficult to provide a comprehensive survey, and while an overview of applications is given, it is limited in scope and intended to provide an introduction to the various ways in which homomorphic cryptography is used beyond simple addition or multiplication of encrypted messages. In the case of strong conditional oblivious tranfser, a new protocol implementing the greater than predicate is presented, utilizing some special properties of the Boneh-Goh-Nissim cryptosystem to achieve security against a malicious receiver.
The effect of an inhibitor of matrix metalloproteinases on colonic inflammation in a trinitrobenzenesulphonic acid rat model of inflammatory bowel disease (1999)

Dosing rats with TNBS-induced colitis using sulphasalazine or marimastat produced a significant reduction in tissue injury and inflammation.
Squamous cell carcinoma of the head and neck in nonsmokers: clinical and biologic characteristics and implications for management (2001)

Squamous cell carcinoma of the head and neck has been strongly linked to chronic tobacco and alcohol abuse. However, we are increasingly recognizing subgroups of patients without traditional risk factors. Recent clinical and molecular investigations suggest that there are distinctive clinical entities, particularly affecting young patients with cancers of the oral tongue and oropharynx. We review data from clinical observations and current biologic inquiries and consider therapeutic implications for these important patient subgroups.
M protein and protein F act as important determinants of cell-specific tropism of Streptococcus pyogenes in skin tissue. (1994)

The pathogenic gram-positive bacterium Streptococcus pyogenes (group A streptococcus) causes numerous diseases of cutaneous tissue, each of which is initiated after the interaction of the bacterium with the cells of the epidermis. In this study, we show that different surface proteins of S. pyogenes play important roles in determining the cell-specific tropism of the bacterium in skin. Using streptococcal strains with defined mutations in the genes which encode surface proteins in combination with primary cultures of human skin and an in situ adherence assay which uses histological sections of human skin, we show that the M protein of S. pyogenes mediates the binding of the bacterium to keratinocytes, while a second streptococcal surface protein, protein F, directs the adherence of the organism to Langerhans' cells. Characterization of binding revealed that adherence was inhibited by purified streptococcal proteins and pretreatment of both host cells with the protease trypsin. Adherence was only slightly affected by the state of keratinocyte differentiation in vitro, but was considerably modulated in response to environmental conditions known to regulate expression of M protein and protein F, suggesting that the interaction between these bacterial cell-surface structures/adhesins and keratinocytes and Langerhans' cells may play an important role in streptococcal skin disease.
Introducing the Clusterin Gene Into Human Renal Cell Carcinoma Cells Enhances Their Metastatic Potential (2002)

These findings suggest that, if clusterin is over expressed, it prolongs cell survival under unfavorable conditions in the metastatic process, resulting in the enhanced metastatic potential of renal cell carcinoma.
Prostate cancer: comparison of transrectal US and digital rectal examination for screening. (1988)

The authors examined 784 self-referred men over age 60 years to compare clinical usefulness of transrectal ultrasound (US) and digital rectal examination in a screening program for prostate cancer. Biopsy was performed in 77 cases, 83% (64 of 77) for abnormalities detected with transrectal US and 38% (29 of 77) because of findings at digital examination. Twenty-two cancers were detected, 20 with transrectal US and ten at digital examination. Overall detection rate for prostate cancer with transrectal US was two times higher than that with digital examination (2.6% vs 1.3%). Sensitivity, specificity, and negative predictive value for transrectal US and digital examination were calculated for a range of prevalences (0.028-0.1543). Sensitivity was two times higher for transrectal US than for digital examination. Transrectal US demonstrated 100% (17 of 17) of tumors with the most favorable prognosis (less than or equal to 1.5 cm in diameter) compared with 41% (seven of 17) for digital examination. The authors conclude that transrectal US is more sensitive than digital examination in the detection of prostate cancer, and they advocate broader implementation and evaluation of transrectal US as a tool for early detection.
Electrical Connectivity in Single-Walled Carbon Nanotube Networks (2009)

Transport in single-walled carbon nanotubes (SWCNTs) networks is shown to be dominated by resistance at network junctions which scale with the size of the interconnecting bundles. Acid treatment, known to dope individual tubes, actually produces a dramatic reduction in junction resistances, whereas annealing significantly increases this resistance. Measured junction resistances for pristine, acid-treated and annealed SWCNT bundles correlate with conductivities of the corresponding films, in excellent agreement with a model in which junctions control the overall network performance.
Hyperfractionated radiation therapy with or without concurrent low-dose daily carboplatin/etoposide for stage III non-small-cell lung cancer: a randomized study. (1996)

The combination of HFX RT and low-dose daily CBDCA plus VP-16 was tolerable and improved the survival of patients with stage III NSCLC as a result of improved local control.
Small molecule antagonists for CXCR1 and CXCR2 inhibit human colon cancer metastasis by decreasing angiogenesis and enhancing apoptosis (2007)

5632 Our previous reports suggest the important role of the CXCR1 and CXCR2 ligands, interleukin-8 and growth regulated oncogene (gro)-α in colon cancer growth and metastasis. The objective of this study was to determine whether inhibition of CXCR1 and CXCR2 activity by using a small molecule antagonist(s) inhibits colon cancer growth and metastasis. KM12L4, a highly metastatic colon carcinoma cell line was implanted intrasplenically into nude mice and SCH527123 (which blocks both CXCR1 and CXCR2) or SCH479833 (which preferentially blocks CXCR2) were given orally at 0, 25, 50 or 100 MPK twice daily for three weeks. Primary splenic tumors and liver metastases were examined in treated and control groups. SCH57213 and SCH479833 were well tolerated with no toxicity. We did not observe significant differences in the primary spleen tumor weight. We observed significant inhibition of liver metastases in CXCR antagonist treated groups as compared to the control group; however, the effect was not dose-dependent. The levels of neovascularization in SCH57213 and SCH479833 treated groups were lower in primary tumors and liver metastases. The number of apoptotic tumor cells in SCH57213, SCH479833 and control treated splenic tumors were similar. However, we observed significantly higher levels of apoptotic tumor cells in liver metastases from SCH57213 and SCH479833 treated groups as compared to control. We did not observe any significant differences between SCH57213 and SCH479833 treated groups. Together, these studies demonstrate the important role of CXCR1 and CXCR2 in colon cancer growth and metastasis. In addition, inhibition of CXCR1 and CXCR2 using a small molecule antagonist provides a novel therapeutic strategy for metastatic colon cancer.
The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization. (1993)

The predominant brain cholecystokinin receptor (CCK-B/gastrin) has been implicated in mediating many of the central effects of cholecystokinin, including anxiety, panic attacks, satiety, and analgesia, suggesting it is an important pharmacologic target. We now report the cloning and characterization of the cDNA encoding the human brain CCK-B/gastrin receptor. The cDNA was isolated from a human brain library by low stringency screening using the canine "gastrin" receptor cDNA as a hybridization probe. Nucleotide sequence analysis revealed an open reading frame encoding a 447-amino-acid protein with seven putative hydrophobic transmembrane domains and significant homology with other known members of the gastrin/cholecystokinin receptor family. Agonist and antagonist affinities of the recombinant human brain receptor expressed in COS-7 cells are consistent with a classical "CCK-B" receptor as defined by the literature. In COS-7 cells expressing the cloned receptor, CCK-8-stimulated phosphatidylinositol hydrolysis and intracellular Ca2+ mobilization suggesting second messenger signaling through phospholipase C. CCK-B/gastrin receptor transcripts were identified in human brain, stomach, and pancreas using high stringency Northern blot analysis. Southern blot hybridization analysis of human genomic DNA indicates that a single gene encodes both the brain and the stomach CCK-B/gastrin receptors. Our data suggest that the CCK-B and gastrin receptors are identical and that the long standing distinction between them may no longer apply.
Clinical Implications of the Osteoprotegerin/RANKL/RANK System for Bone and Vascular Diseases (2004)

Bone resorption by osteoclasts is coupled with bone formation by osteoblasts, and this balanced process continuously remodels and adapts the skeleton. The receptor activator of nuclear factor kappaB ligand (RANKL) has been identified as an essential cytokine for the formation and activation of osteoclasts. The effects of RANKL are physiologically counterbalanced by the decoy receptor osteoprotegerin (OPG). Estrogen deficiency, glucocorticoid exposure, T-cell activation (eg, rheumatoid arthritis), and skeletal malignancies (eg, myeloma, metastases) enhance the ratio of RANKL to OPG and, thus, promote osteoclastogenesis, accelerate bone resorption, and induce bone loss. Moreover, alterations of the OPG/RANKL/RANK system have been implicated in vascular diseases. RANKL blockade (using OPG or RANK fusion proteins or RANKL antibodies) has prevented bone loss caused by osteoporosis, chronic inflammatory disorders, and malignant tumors in animal models and may emerge as a therapy in humans based on studies in postmenopausal osteoporosis, myeloma bone disease, and osteolytic metastases. This review summarizes the clinical implications of the OPG/RANKL/RANK system for bone and vascular diseases.
Polychotomous Regression (1997)

Abstract An automatic procedure that uses linear splines and their tensor products is proposed for fitting a regression model to data involving a polychotomous response variable and one or more predictors. The fitted model can be used for multiple classification. The automatic fitting procedure involves maximum likelihood estimation, stepwise addition, stepwise deletion, and model selection by the Akaike information criterion, cross-validation, or an independent test set. A modified version of the algorithm has been constructed that is applicable to large datasets, and it is illustrated using a phoneme recognition dataset with 250,000 cases, 45 classes, and 63 predictors.
The Great and Marvelous Change: An Alternate Interpretation (2010)

Research Article| January 01 2010 The Great and Marvelous Change: An Alternate Interpretation Clifford P. Jones Clifford P. Jones Clifford P. Jones earned a BS in accounting from Brigham Young University and a JD with honors from J. Reuben Clark Law School. He is president of AvidLaw, LLC, a software development firm. His understanding of and love for the scriptures have come primarily through personal and family scripture study. He and his wife, Sharon, have four children and three grandchildren. Search for other works by this author on: This Site Google Journal of the Book of Mormon and Other Restoration Scripture (2010) 19 (2): 50–63. https://doi.org/10.5406/jbookmormotheres.19.2.0050 Cite Icon Cite Share Icon Share Facebook Twitter LinkedIn MailTo Permissions Search Site Citation Clifford P. Jones; The Great and Marvelous Change: An Alternate Interpretation. Journal of the Book of Mormon and Other Restoration Scripture 1 January 2010; 19 (2): 50–63. doi: https://doi.org/10.5406/jbookmormotheres.19.2.0050 Download citation file: Zotero Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All Scholarly Publishing CollectiveUniversity of Illinois PressJournal of Book of Mormon Studies Search Advanced Search The text of this article is only available as a PDF. Copyright 2010 by the Board of Trustees of the University of Illinois2010 Article PDF first page preview Close Modal You do not currently have access to this content.
Reduced lysyl oxidase messenger RNA levels in experimental and human prostate cancer. (1998)

To identify genes associated with prostate cancer progression, we developed a strategy involving the use of differential display PCR and a panel of genetically matched primary tumor- and metastasis-derived mouse prostate cancer cell lines. We analyzed sequences that were differentially stimulated by transforming growth factor-beta1 in primary tumor-versus metastasis-derived cell lines, based on our previous studies indicating that acquisition of differential responses to this growth factor could result in phenotypic traits that facilitate tumor metastasis from specific cell clones within the primary tumor. Using this system, we isolated and sequenced a cDNA fragment that encoded mouse lysyl oxidase (LO) and was induced by transforming growth factor-beta1 in primary tumor but not in metastasis-derived cells. Northern blotting analysis revealed increased LO expression in a panel of primary tumor cell lines but significantly reduced or nondetectable expression in their matched metastatic counterparts. Further in situ hybridization analysis revealed LO expression in normal mouse prostate epithelium but, in most cases, progressive loss of expression in primary prostate cancer and associated metastatic lesions. Importantly, in situ hybridization studies of normal human prostate and prostate malignancies revealed a similar loss of expression during progression to metastasis. The progressive loss of LO expression during prostate cancer progression provides information that may increase our understanding of the mechanisms that underlie this disease. In addition, LO may provide a useful molecular marker and/or establish a novel therapeutic target for prostate cancer.