gebhart/patrepeval huggingface dataset:
Effects of intralesional versus ip administration of cisplatin on squamous cell carcinoma of mice. (1987)

The effects of intralesional versus ip administration of cisplatin (total, 24 mg/kg) given on different schedules were studied using transplantable squamous cell carcinoma of mice. The size of the tumor in the control group increased approximately 60 times at the end of the experiments, whereas it decreased to 0.04 of the initial volume following a single intralesional injection of cisplatin. The ratio of treated/control mice was 0%. The comparable values in the groups with intralesional cisplatin at 3- and 1-week intervals were 7% and 20%, respectively. The responses of the tumor to cisplatin in the ip groups were lower than those of the intralesional groups and were not dependent on the schedule of administration. Toxic deaths were less frequently encountered in the intralesional groups of animals. Platinum concentration in tumors of the intralesional group was two to five times higher than that of the ip group 15 minutes to 96 hours after injection of 12 mg/kg of cisplatin, whereas the concentration in sera of the intralesional group remained lower than that of the ip group until 48 hours after the injection. The results indicate that the intralesional route produces a good response of tumor to cisplatin by maintaining high levels of the non-protein-bound form of the agent in the tumor tissue that cannot be provided by other routes of administration.
Phylogeny and taxonomy of the food-borne pathogen Clostridium botulinum and its neurotoxins (1998)

Until recently, all clostridia producing neurotoxins able to cause paralysis symptomatic of botulism were deemed to be Clostridium botulinum. Defining Cl. botulinum on the basis of this single phenotypic trait has resulted in the species encompassing metabolically very diverse organisms, and four distinct phenotypic groups are recognized within this taxon (designated groups I-IV). Nucleic acid hybridization and 16S ribosomal RNA sequencing studies have revealed the presence of four phylogenetically distinct lineages within the species, which correlate with these phenotypic divisions. In addition to marked phenotypic and genotypic heterogeneity between groups, the taxonomy of the species is further complicated by the existence of strains which are closely related, if not genetically identifiable, to members of each Cl. botulinum group, but are non-toxigenic. Furthermore, strains of species other than Cl. botulinum (viz. Cl. baratii, Cl. butyricum) have been found which express botulinum neurotoxin (BoNT). Great advances have been made in recent years in elucidating the nucleotide sequences of genes encoding the various BoNT antigenic types (A through to G). Genealogical trees derived from BoNTs show marked discordance with those depicting 'natural' relationships inferred from 16S rRNA and phenotypic clusters, and strong evidence exists for BoNT gene transfer between some groups of Cl. botulinum (e.g. groups I and II), and with non-botulinum species. Botulinum neurotoxin is produced by Cl. botulinum as a non-covalently bound progenitor toxin complex of two or more protein components. Information on the evolutionary histories of the various non-toxic progenitor proteins is currently limited, although there is evidence of gene recombination. In particular, chimera-like or mosaic non-toxic-non-haemagglutinins (NTNH) genes in group I Cl. botulinum have been described, and it is now apparent that the phylogeny of the NTNHs is not going to 'mirror' that of botulinal neurotoxins, although their genes are physically contiguous. In this article, the current state of knowledge of the phylogenetics of the species Cl. botulinum and its neurotoxins is reviewed, and a view is presented that a nomenclature based rigidly on BoNT production is no longer tenable.
Sales promotions on the internet (1998)

Our results suggest that the presentation of hypothyroidism is altered in the elderly in comparison with young patients in that there are (1) fewer signs or symptoms and (2) diminished frequency of some classical signs. Our results underline the importance of TSH measurement in the elderly.
Expression of viral and cellular cycle proteins and proteinases in cervical carcinoma cell lines as possible immunocytochemical markers of malignant phenotype (2007)

Background Cervical cytology has been used extensively as a screening procedure for cervical cancer. Recent molecular developments increase its sensitivity and sensibility including HPV assessment, and the use of molecular biomarkers such as p16 protein. The aim of this study was to explore the pattern of expression of proteins from HPV, cell cycle and proteinases in various cell lines to determine the best candidates to serve as cytological biomarkers of malignancy.
Data lifetime is a systems problem (2004)

As sensitive data lifetime (i.e. propagation and duration in memory) increases, so does the risk of exposure. Unfortunately, this issue has been largely overlooked in the design of most of today's operating systems, libraries, languages, etc. As a result, applications are likely to leave the sensitive data they handle (passwords, financial and military information, etc.) scattered widely over memory, leaked to disk, etc. and left there for an indeterminate period of time. This greatly increases the impact of a system compromise.Dealing with data lifetime issues is currently left to application developers, who largely overlook them. Security-aware developers who attempt to address them (e.g. cryptographic library writers) are stymied by the limitations of the operating systems, languages, etc. they rely on. We argue that data lifetime is a systems issue which must be recognized and addressed at all layers of the software stack.
Toward an Understanding of Public Purchaser and Salesperson Interaction Activities: (1997)

Despite the magnitude of the public sector as a market segment and the growing trend of governmental purchasers' reliance on suppliers to meet their needs, relatively little research has been conducted regarding the public purchaser--salesperson interaction. Past descriptions of the public purchasing function have focused on the bidding transactional nature, neglecting the relevance of public purchaser relational activities with internal customers and external vendors. This empirical study demonstrates the importance of various public purchasing relational roles and the corresponding activities for sellers in this domain. Implications are drawn for this significant context.
Synthesis and evaluation of some water-soluble prodrugs and derivatives of taxol with antitumor activity (1992)

The synthesis and evaluation of some 2'- and 7-amino acid derivatives of taxol (1) are reported. Reaction of taxol with N-protected amino acids gave 2'-N-protected amino acid esters of taxol. However, deprotection of the amino group and subsequent isolation of products were complex and only successful when formic acid was used to deprotect a t-BOC protecting group. Esterification of taxol using N,N-dialkylated amino acids gave 2'-amino acid esters of taxol, 2'-(N,N-dimethylglycyl)taxol (4) and 2'-[3-(N,N-diethylamino)propionyl]taxol as its methanesulfonic acid salt (5b), in good yield. The 7-derivatives, 7-(N,N-dimethylglycyl)taxol (9) and 7-L-alanyltaxol (12), were prepared by two alternate methods. In the first approach, the 2'-hydroxyl group was protected using the [(2,2,2-trichloro-ethyl)oxy]carbonyl, or troc, protecting group followed by the esterification of the 7-hydroxyl and subsequent deprotection of the amino and troc groups. In the second approach, taxol was allowed to react with more than 2 molar equiv of the N-protected amino acids or N,N-dialkylated amino acids to give 2',7-diamino acid esters of taxol. For the protected amino acids, the deprotection of the amino group followed by removal of the 2'-substituent gave the 7-amino acid esters of taxol. The methanesulfonic acid salts of both 2'- and 7-amino acid esters showed improved solubility ranging from 2 to greater than 10 mg/mL. The 7-derivatives were effective in promoting microtubule assembly in vitro while 2'-derivatives showed little in vitro activity. The derivatives 2'-(N,N-dimethylglycyl)taxol (4) and 2'-[3-(N,N-diethylamino)propionyl]taxol (5) inhibited proliferation of B16 melanoma cells to an extent similar to that of taxol, while the other derivatives were about 50% as cytotoxic. In a mammary tumor screen, 2'-[3-(N,N-diethylamino)propionyl]taxol showed the greatest antitumor activity compared to the other analogues. The lower activities of the 7-derivatives in inhibiting tumor growth and melanoma cell proliferation (although they were almost as active as taxol in inducing microtubule assembly in vitro) may be due to differences in drug uptake by the cells. The similar cytotoxic and antitumor activities of the 2'-analogues and taxol can be explained by their conversion to taxol or an active taxol metabolite. Therefore, the 2'-analogues appear to behave as prodrugs and have the potential to be developed as chemotherapeutic agents.
Identification by antibody to a synthetic peptide of a protein specified by a diploid gene located in the terminal repeats of the L component of herpes simplex virus genome (1986)

In the course of studies on the a sequences located at the termini of and at the junction between the L and S components of herpes simplex virus 1 DNA, J. Chou and B. Roizman (J. Virol. 57:629-637, 1986) noted that the a sequence acted as a gamma 1 promoter when fused to the structural sequence of the thymidine kinase gene, the b inverted repeat sequences located in the L component next to the a sequences contained an open reading frame predicted to encode the protein of 358 amino acids with a molecular weight of 37,054, and the transcription of an RNA homologous to the open reading frame initiated within the a sequence. The nucleotide sequence of the open reading frame predicted the presence of the triplet Ala-Thr-Pro repeated 10 times. To verify the existence of the predicted gene, designated gamma 134.5, a synthetic peptide consisting of the triplet Ala-Thr-Pro repeated 10 times was synthesized and used to raise antibodies in rabbits. The results were as follows. The antiserum to the peptide reacted with a 43,500-apparent-molecular-weight protein present in lysates of cells infected with herpes simplex virus 1 but not present in mock-infected or herpes simplex virus 2-infected cells. We genetically engineered a recombinant virus containing a single copy of a truncated gene. Concordant with predictions, the antibody reacted with a faster-migrating protein in cells infected with this recombinant. The gamma 134.5 gene product was soluble, and it accumulated primarily in the cytoplasm late in infection. The overlap of the domain of the gamma 134.5 gene with the a sequence raises the possibility that it acts in trans on the a sequence and is associated with one of the functions currently ascribed to the a sequences.
Light emission by magnetic and electric dipoles close to a plane dielectric interface III Radiation patterns of dipoles with arbitrary orientation (1979)

We have derived analytic expressions for the angular distribution of light emitted by an atomic system, e.g., a fluorescent molecule, located in a dielectric medium 1 at distance z0 from the interface to a different dielectric medium 2. The theory is rigorously valid for electric and magnetic dipole transitions with arbitrary orientation of the dipole transition moment. (In Paper II [ J. Opt. Soc. Am.57, 1615– 1619 ( 1977)], only the special case of dipoles oriented perpendicular to the interface had been treated.) The radiation patterns of dipoles located on the interface (z0 = 0) and oriented parallel to it, and ensembles of such dipoles radiating incoherently with randomly oriented dipole moments were examined in particular. They differ greatly from the corresponding well-known dipole radiation patterns in an unbounded medium 1, due to the wide-angle interferences of emitted plane waves, and radiation from evanescent waves in the dipole’s near field into medium 2, if this is denser than medium 1.
Current Understanding of Dysbiosis in Disease in Human and Animal Models (2016)

Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects more than 2 million people in the United States. Although the etiology and pathogenesis of IBD are still largely unknown, dysregulated host/enteric microbial interactions are requisite for the development of IBD. So far, many researchers have tried to identify a precise relationship between IBD and an imbalance of the intestinal microbiota, termed "dysbiosis." Despite extensive efforts, it is still largely unknown about the interplay among microbes, their hosts, and their environments, and whether dysbiosis is a causal factor or an effect of IBD. Recently, deep-sequencing analyses of the microbiota in patients with IBD patients have been instrumental in characterizing the strong association between dysbiosis and IBD development, although it is still unable to identify specific-associated species level changes in most cases. Based on many recent reports, dysbiosis of the commensal microbiota is implicated in the pathogenesis of several diseases, including IBD, obesity, and allergic disorders, in both human and animal models. In this review article, the authors have focused on explaining the multiple types of dysbiosis, as well as dysbiosis-related diseases and potential treatments to apply this knowledge to understand a possible cause and potentially find therapeutic strategies for IBD as well as the other dysbiosis-related diseases.
A propensity score case‐control comparison of aprotinin and tranexamic acid in high‐transfusion‐risk cardiac surgery (2006)

Aprotinin and tranexamic acid have similar hemostatic effectiveness in high-transfusion-risk cardiac surgery. Within the confines of propensity score matching, our results suggest that aprotinin may be associated with renal dysfunction.
The Integrin-linked Kinase Regulates the Cyclin D1 Gene through Glycogen Synthase Kinase 3β and cAMP-responsive Element-binding Protein-dependent Pathways (2000)

The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the pRB tumor suppressor protein. Cyclin D1 is overexpressed in 20-30% of human breast tumors and is induced both by oncogenes including those for Ras, Neu, and Src, and by the beta-catenin/lymphoid enhancer factor (LEF)/T cell factor (TCF) pathway. The ankyrin repeat containing serine-threonine protein kinase, integrin-linked kinase (ILK), binds to the cytoplasmic domain of beta(1) and beta(3) integrin subunits and promotes anchorage-independent growth. We show here that ILK overexpression elevates cyclin D1 protein levels and directly induces the cyclin D1 gene in mammary epithelial cells. ILK activation of the cyclin D1 promoter was abolished by point mutation of a cAMP-responsive element-binding protein (CREB)/ATF-2 binding site at nucleotide -54 in the cyclin D1 promoter, and by overexpression of either glycogen synthase kinase-3beta (GSK-3beta) or dominant negative mutants of CREB or ATF-2. Inhibition of the PI 3-kinase and AKT/protein kinase B, but not of the p38, ERK, or JNK signaling pathways, reduced ILK induction of cyclin D1 expression. ILK induced CREB transactivation and CREB binding to the cyclin D1 promoter CRE. Wnt-1 overexpression in mammary epithelial cells induced cyclin D1 mRNA and targeted overexpression of Wnt-1 in the mammary gland of transgenic mice increased both ILK activity and cyclin D1 levels. We conclude that the cyclin D1 gene is regulated by the Wnt-1 and ILK signaling pathways and that ILK induction of cyclin D1 involves the CREB signaling pathway in mammary epithelial cells.
Lyme arthritis synovial gamma delta T cells respond to Borrelia burgdorferi lipoproteins and lipidated hexapeptides. (1998)

Lyme arthritis synovial fluid contains a large proportion of gamma delta T cells that proliferates upon stimulation with the causative spirochete, Borrelia burgdorferi. A panel of Borrelia-reactive gamma delta T cell clones was derived from synovial fluid of two patients with Lyme arthritis. Each of six gamma delta clones from one patient used the V delta 1 TCR segment but had otherwise unique CDR3 sequences and diverse V gamma segment usage. Stimulation of the V delta 1 clones was optimal in the presence of Borrelia, dendritic cells, and exogenous IL-2, which was reflected by proliferation, TCR down-modulation, as well as induction of CD25 and Fas ligand expression. Stimulation by B. burgdorferi-pulsed dendritic cells withstood chemical fixation and was not restricted to class I or class II MHC, CD1a, CD1b, or CD1c. In contrast, anti-gamma delta antibody potently inhibited proliferation. Extraction of B. burgdorferi lipoproteins with Triton X-114 enriched for the stimulatory component. This was confirmed using lipidated vs nonlipidated hexapeptides of Borrelia outer surface proteins. These observations suggest that synovial V delta 1 T cells may mediate an innate immune response to common lipoprotein products of spirochetes.
A mouse model for the renal salt-wasting syndrome pseudohypoaldosteronism (1997)

Aldosterone-dependent epithelial sodium transport in the distal nephron is mediated by the absorption of sodium through the highly selective, amiloride-sensitive epithelial sodium channel (ENaC) made of three homologous subunits (alpha, beta, and gamma). In human, autosomal recessive mutations of alpha, beta, or gammaENaC subunits cause pseudohypoaldosteronism type 1 (PHA-1), a renal salt-wasting syndrome characterized by severe hypovolemia, high plasma aldosterone, hyponatremia, life-threatening hyperkaliemia, and metabolic acidosis. In the mouse, inactivation of alphaENaC results in failure to clear fetal lung liquid at birth and in early neonatal death, preventing the observation of a PHA-1 renal phenotype. Transgenic expression of alphaENaC driven by a cytomegalovirus promoter in alphaENaC(-/-) knockout mice [alphaENaC(-/-)Tg] rescued the perinatal lethal pulmonary phenotype and partially restored Na+ transport in renal, colonic, and pulmonary epithelia. At days 5-9, however, alphaENaC(-/-)Tg mice showed clinical features of severe PHA-1 with metabolic acidosis, urinary salt-wasting, growth retardation, and 50% mortality. Adult alphaENaC(-/-)Tg survivors exhibited a compensated PHA-1 with normal acid/base and electrolyte values but 6-fold elevation of plasma aldosterone compared with wild-type littermate controls. We conclude that partial restoration of ENaC-mediated Na+ absorption in this transgenic mouse results in a mouse model for PHA-1.
Complement Is Activated by IgG Hexamers Assembled at the Cell Surface (2014)

Complement activation by antibodies bound to pathogens, tumors, and self antigens is a critical feature of natural immune defense, a number of disease processes, and immunotherapies. How antibodies activate the complement cascade, however, is poorly understood. We found that specific noncovalent interactions between Fc segments of immunoglobulin G (IgG) antibodies resulted in the formation of ordered antibody hexamers after antigen binding on cells. These hexamers recruited and activated C1, the first component of complement, thereby triggering the complement cascade. The interactions between neighboring Fc segments could be manipulated to block, reconstitute, and enhance complement activation and killing of target cells, using all four human IgG subclasses. We offer a general model for understanding antibody-mediated complement activation and the design of antibody therapeutics with enhanced efficacy.
Effort-Related Motivational Effects of the VMAT-2 Inhibitor Tetrabenazine: Implications for Animal Models of the Motivational Symptoms of Depression (2013)

Motivated behaviors are often characterized by a high degree of behavioral activation, and work output and organisms frequently make effort-related decisions based upon cost/benefit analyses. Moreover, people with major depression and other disorders often show effort-related motivational symptoms such as anergia, psychomotor retardation, and fatigue. It has been suggested that tasks measuring effort-related choice behavior could be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT) inhibitor tetrabenazine. Tetrabenazine produces depressive symptoms in humans and, because of its selective inhibition of VMAT-2, it preferentially depletes dopamine (DA). Rats were assessed using a concurrent fixed-ratio 5/chow feeding choice task that is known to be sensitive to dopaminergic manipulations. Tetrabenazine shifted response choice in rats, producing a dose-related decrease in lever pressing and a concomitant increase in chow intake. However, it did not alter food intake or preference in parallel free-feeding choice studies. The effects of tetrabenazine on effort-related choice were reversed by the adenosine A2A antagonist MSX-3 and the antidepressant bupropion. A behaviorally active dose of tetrabenazine decreased extracellular DA in nucleus accumbens and increased expression of DARPP-32 in accumbens medium spiny neurons in a pattern indicative of reduced transmission at both D1 and D2 DA receptors. These experiments demonstrate that tetrabenazine, which is used in animal models to produce depression-like effects, can alter effort-related choice behavior. These studies have implications for the development of animal models of the motivational symptoms of depression and related disorders.
EFFICIENTIN SITUESTERIFICATION OF CARBOXYLIC ACIDS USING CESIUM CARBONATE (1996)

(1996). EFFICIENT IN SITU ESTERIFICATION OF CARBOXYLIC ACIDS USING CESIUM CARBONATE. Organic Preparations and Procedures International: Vol. 28, No. 4, pp. 480-483.
Discriminating Molecular Length of Chemically Adsorbed Molecules Using an Atomic Force Microscope Having a Tip Covered with Sensor Molecules (An Atomic Force Microscope Having Chemical Sensing Function) (1993)

A novel atomic force microscope (AFM) having a chemical sensing function has been proposed. Using an AFM having a tip on which surface sensor molecules were immobilized, the molecular lengths of chemically adsorbed molecules on the solid surface were discriminated for the first time.
Bacterial Community Structure Associated With Elective Cesarean Section Versus Vaginal Delivery in Chinese Newborns (2014)

These results demonstrate that delivery method has a profound influence on the structure of the intestinal microbiota in Chinese newborn infants. This is in accordance with data reported in other regions.