Miracle-dz/UniFAR-FTUs huggingface dataset:
The absorption, distribution, excretion, and biotransformation of the carcinostatic 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in animals.

Summary The physiological disposition of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, a highly active agent against intraperitoneal and intracranial mouse leukemia L1210, was studied in mice, rats, dogs, and monkeys with the 14C label in each of 3 positions of the molecule, the ethylene, carbonyl, and cyclohexyl moieties. 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea is lipid soluble and, after parenteral dosage, rapidly degraded in mouse and dog plasma with 2 exponential phases. The half-life of the initial phase is about 5 min, while the 2nd phase extends over 1 hr. During the 6 hr after i.v. injection of ethylene-labeled 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in dogs, radioactivity in the cerebrospinal fluid exceeded that of plasma 3-fold. With the label in the cyclohexyl moiety, plasma radioactivity was about 50% of cerebrospinal fluid 14C levels. The drug following biotransformation is primarily excreted by the kidneys with excretion being essentially complete during the first 24 hr in rodents and monkeys, but more protracted in dogs. Biliary secretion and reabsorption from the gastrointestinal tract have been demonstrated. The cyclohexyl portion of the molecule was bound extensively (40 to 60%), while the ethylene moiety was not bound to plasma proteins of dogs. In mice, 10 to 20% of the carbonyl and 4 to 6% of ethylene carbon atoms were recovered in expired CO2 1 day after parenteral or oral dosage. The detection of cyclohexylamine, N, N′-dicyclohexylurea, among other predominant unidentified molecular species, supports the hypothesis of intermediate hydroxydiazoalkane and isocyanate formation during the degradation of nitrosoureas in vivo. However, the identified catabolites and cyclohexyl isocyanate were found to be inactive against the mouse leukemia L1210.
Pit Cell‐Hepatocyte Contact in Autoimmune Hepatitis

This is the first report to document pit cells in the human liver. These cells were identified by characteristic electron‐dense granules and rod‐cored vesicles. The granules of human pit cells were smaller in number and size than those of the rat. In the present case of autoimmune hepatitis, pit cells and conventional agranular lymphocytes migrated into hepatic parenchyma and contacted degenerating and immature hepatocytes. Pit cells show natural killer activity (Kaneda et al., 1983), and may participate in development of lesions and cellular damage.
Expression of Vascular Endothelial Growth Factor and Angiogenesis in Gastrointestinal Stromal Tumor of the Stomach

Vascular endothelial growth factor (VEGF) is associated with the malignant potential of several types of carcinoma. The aim of this study was to elucidate the clinical significance of VEGF expression in gastrointestinal stromal tumor (GIST). Methods: Specimens obtained from 53 patients who had underwent surgical resection for GIST of the stomach were used in this study. Specimens were examined immunohistochemically for VEGF expression and Ki-67 expression. Tumor microvessel density (MVD) was determined immunohistochemically with anti-CD31 antibody, and was estimated by averaging the counts from three high-power fields in the area showing the greatest neovascularization. Results: VEGF expression was detected in 14 (26.4%) of the 53 lesions and correlated significantly with tumor size, liver metastasis, Ki-67 labeling index, and MVD. Prognosis was significantly poorer than in patients with tumors expressing VEGF than in patients with tumors lacking VEGF expression. Multiple logistic regression analysis for 10-year survival showed VEGF expression and high mitotic rate to be independent predictor of a poor outcome. Conclusions: Angiogenesis associated with VEGF may play an important role in the progression of GIST. VEGF expression may serve as an indicator of a poor prognosis.
Effects of adenine arabinoside and coformycin on the kinetics of G2 chromatid aberrations in X-irradiated human lymphocytes.

The kinetics of chromatid aberrations have been studied in human lymphocytes exposed to X-rays in the G2 phase of the cell cycle and incubated with or without the nucleoside analogue 9-beta-D-arabinofuranosyladenine (ara A), known to inhibit the repair of DNA double-strand breaks. In the absence of ara A an exponential decrease in frequencies of chromatid breaks occurred which we interpret as repair. Few breaks were observed if samples were harvested immediately following irradiation. The frequency of chromatid breaks at 1 h after X-irradiation (442 per 100 cells/Gy) was similar to that previously observed in Chinese hamster ovary (CHO) K1 cells. However, the exponential decrease of chromatid breaks between X-irradiation and sampling occurred with a t1/2 of 0.87 h, a faster rate than we have previously observed in CHO K1 cells and was not inhibited by 200 microM ara A alone, in contrast with our previous findings in a human fibroblast line. However, in the presence of the ADA inhibitor coformycin, inhibition of break repair was already observed at an ara A concentration of 100 microM indicating that the apparent unresponsiveness to ara A of lymphocyte chromatid break rejoining results from the deamination of this nucleoside analogue. This deamination effect was confirmed by measurements of DNA synthesis which showed stable inhibition of synthesis by ara A only when coformycin was present. Frequencies of chromatid exchanges in irradiated cells remained constant except at the sampling time directly after irradiation, consistent with the view that chromosomal radiosensitivity remained constant throughout the G2 phase, except for the period immediately prior to mitosis. (ABSTRACT TRUNCATED AT 250 WORDS)
The Integrity of the Periplasmic Domain of the VirA Sensor Kinase Is Critical for Optimal Coordination of the Virulence Signal Response in Agrobacterium tumefaciens

ABSTRACT The plant pathogen Agrobacterium tumefaciens responds to three main signals at the plant-bacterium interface: phenolics, such as acetosyringone (AS), monosaccharides, and acidic pH (∼5.5). These signals are transduced via the chromosomally encoded sugar binding protein ChvE and the Ti plasmid-encoded VirA/VirG two-component regulatory system, resulting in the transcriptional activation of the Ti plasmid virulence genes. Here, we present genetic and physical evidence that the periplasmic domain of VirA dimerizes independently of other parts of the protein, and we examine the effects of several engineered mutations in the periplasmic and transmembrane regions of VirA on vir-inducing capacity as indicated by AS sensitivity and maximal level of vir-inducing activity at saturating AS levels. The data indicate that helix-breaking mutations throughout the periplasmic domain of VirA or mutations that reposition the second transmembrane domain (TM2) of VirA relieve the periplasmic domain's repressive effects on the maximal activity of this kinase in response to phenolics, effects normally relieved only when ChvE, sugars, and low pH are also present. Such relief, however, does not sensitize VirA to low concentrations of phenolics, the other major effect of the ChvE-sugar and low pH signals. We further demonstrate that amino acid residues in a small Trg-like motif in the periplasmic domain of VirA are crucial for transmission of the ChvE-sugar signal to the cytoplasmic domain. These experiments provide evidence that small perturbations in the periplasmic domain of VirA can uncouple sugar-mediated changes in AS sensitivity from the sugar-mediated effects on maximal activity.
The afferent and efferent connections of the feline nucleus tegmenti pedunculopontinus, pars compacta

The fiber connections of the nucleus tegmenti pedunculopontinus, pars compacta (TPc) were studied by means of the anterograde autoradiographic and retrograde horseradish peroxidase tracer methods. The limits of TPc, which is not a cytoarchitecturally distinct cell group in the cat, were estimated on the basis of autoradiographic experiments in which we plotted the distribution of afferent connections from the entopeduncular nucleus, motor cortex, substantia nigra, and subthalamic nucleus. We concluded that in the cat, TPc can most readily be identified by the terminal distribution of fibers originating in the substantia nigra. Deposits of radiolabel in the motor‐pre‐motor cortex, the entopeduncular nucleus, and subthalamic nucleus weakly labeled the same tegmental region. Parallel horseradish peroxidase experiments suggested that neurons near the entopeduncular nucleus, especially in the lateral hypothalamus and subthalamus, contribute to the pallido‐TPc pathway; that entopeduncular neurons projecting to TPc are most numerous in the ventral part of the nucleus; and that of the neocortical motor fields, both areas 4 and 6 project to TPc.
Massive Destruction of Malaria-Parasitized Red Blood Cells despite Spleen Closure

ABSTRACT It is currently accepted that malaria-parasitized red blood cells (pRBC) are eliminated, like senescent erythrocytes, phagocytically by macrophages in the red pulp of the spleen. Here, however, we show that self-healing Plasmodium chabaudi malaria activates spleen closure in C57BL/6 mice. Confocal laser scanning microscopy revealed that spleen closing was manifested by elimination of entry into the red pulp of 3-μm polystyrol particles, pRBC, and nonparasitized red blood cells but not of bovine serum albumin. This spleen closure did not reflect a reduction in the number of phagocytic cells, as shown by flow cytometry, whereas marginal zone macrophages (MZM) were lost and red pulp macrophages entered the white pulp. Splenic trapping of pBRC was strongly reduced in the absence of MZM and marginal metallophilic macrophages (MMM), as it is in noninfected mice with a disrupted lymphotoxin β receptor (LTβR−/−), and it was still significantly reduced when the number of MZM and MMM was diminished, as in tumor necrosis factor alpha-deficient (TNF-α−/−) mice. Moreover, mice deficient in TNF-α, tumor necrosis factor receptor I (TNFRI−/−), and LTβR exhibited progressive impairment in malaria-induced spleen closing. Treatment of C57BL/6 mice with TNF-α induced loss of MZM and spleen closing by about 20%. Our data indicate that TNF/TNFRI signaling is involved in regulating malaria-induced spleen closure, which is maximal during crisis, when parasitemia declines more than 100-fold. Consequently, the vast majority of pRBC cannot be destroyed by the spleen during crisis, suggesting that the known sophisticated sequestration system of Plasmodium parasites did not evolve to avoid splenic clearance.
Korean Prehistory: Current Perspectives

This volume dedicated to Korean prehistory is a synthesis of current research by Korean scholars working in the areas of palaeoanthropology and Palaeolithic, Neolithic, Bronze Age, and Iron Age archaeology. Here we introduce this special volume by helping to place each of the contributions in broader perspective. One of the key contributions we anticipate resulting from this volume is that interested readers (both students and senior researchers alike) will now be able to go to one place to learn about recent research avenues in Korean prehistoric studies.
Effect of Urease Injection on Body Weights of Growing Rats and Chicks. ∗

Summary Experiments with 40-day-old chicks and 60 weanling Sprague Dawley rats were conducted. The experimental subjects were immunized with jackbean urease injected during the first 4 weeks of experiments lasting 8. weeks. During the 4-8 week or post injection period, the immunized chicks gained 905 g vs. 777 g for their controls and were more efficient in converting feed to weight gain. In 2 successive experiments immunized rats grew slightly faster and showed a difference in feed efficiency which was statistically significant. In both chicks and rats there were no differences in body weight during the 0-4 week injection period. Antibodies to urease were demonstrable in sera of immunized rats by in vivo methods with C-14 urea and by in vitro tests. Soybean diets were fed.
Changing the Image of Scientists among College Students in Israel

With this study, we sought to address some deficiencies in the image of scientists held by pre-service teachers in Israel. These include a few concerns for women scientists, as well as a lack of understanding about fieldwork and contemporary scientific equipment. The study was carried out with two groups of pre-service science students, mostly women. It was done through interference: following the web, meeting with experts and constructing leaning materials for pupils by the participants. Research was in the form of one strand research using qualitative methods. During the research, the image of women scientists changed considerably. Pre interference views were: there are no women scientists and physics and astrophysics are not for women. Women scientists were described as torn between family and work. In the post interference stage, a high appreciation for women scientists and their work in all domains was observed, woman scientist were portrayed as relaxed, taking part in team work, doing field work, and using specialized sophisticated equipment.
On Lactobacillus plantarum 299v, bacterial translocation and intestinal permeability.

The gastrointestinal tract harbours a huge load of bacteria which exerts important biological functions to maintain health. In certain conditions the relation between commensal bacteria and pathogens may be set off balance, with an increase in number of pathogens and risk of bacterial translocation (BT). Disease and trauma may also render the intestinal barrier dysfunctional, inducing BT and increased permeability. Probiotic bacteria, i.e. living bacteria which, when ingested, exerts beneficial effects on the host, have been found to stabilize the intestinal mucosa and affect the intestinal microflora. The aim of this thesis was to study the effects of Lactobacillus plantarum 299v in relation to intestinal permeability and BT. In study I L. plantarum 299v normalized E. coli-induced permeability in distal ileum of rats. This effect was achieved with a more continuous supply of L. plantarum 299v, rather than intermittent or acute pretreatment. Study II showed that pretreatment with L. plantarum 299v prevented BT in rats rendered septic with LPS. The protective effect seemed to be dependent on the ability of L. plantarum 299v to adhere to intestinal mucosa, indicating competitive inhibition as a possible mechanism behind prevention of translocation. Moreover, treatment with prebiotics, without a probioticum, did not prevent translocation. In study III LPS-induced intestinal barrier dysfunction on rats was found to be regulated by P-selectin-dependent leukocyte recruitment. With anti-P-selectin antibody intestinal permeability was attenuated, as well as leukocyte rolling and adhesion. This indicates anti-P-selectin treatment as a mean of ameliorating barrier dysfunction in sepsis. Finally, in study IV, it was found that high doses of L. plantarum 299v given to patients undergoing colon surgery were not able to reduce translocation of selected enteric bacteria but seemed to have a stimulatory effect on bacterial load in the colon. Further, L. plantarum 299v could be given to patients with malignancy without risk of tumour proliferation. Taken together, the findings herein indicates a potential of L. plantarum 299v pretreatment in reducing BT and intestinal permeability and warrants further studies in the clinical setting.
Ler, compartilhar e interagir: blogs como ferramentas de mediação de leitura Read, share and interaction: blogs as reading mediation tools

com o objetivo principal de compreender os blogs literarios como possivel ferramenta de mediacao de leitura e investigar o perfil dos atores envolvidos nesses ambientes bem como suas interacoes, este trabalho inicia-se com uma breve incursao conceitual acerca dos blogs como fonte e canal de compartilhamento de informacao com atencao especial aos blogs literarios. Discorre sobre a leitura e a escrita na web e o seus processos de mediacao. Apresenta os resultados de uma pesquisa exploratoria com aplicacao de questionarios direcionados a blogueiros literarios (17) e seus respectivos leitores (265) no periodo de 16 a 23 de junho de 2014. Ha semelhanca entre os perfis (no que se refere ao genero, idade, preferencias de aquisicao de livros e indices de leitura) e compatibilidade de opinioes entre os dois publicos (constante mencao as resenhas de livros como elo entre eles para escolha de obras a ler), bem como indicativos relevantes de interacao mutua. Pode-se concluir que os respondentes referem-se aos blogs literarios como um mecanismo de mediacao e incentivo a leitura
Specific Changes in Human Brain Following Reperfusion After Cardiac Arrest

Very few reports are available on serial changes in human brain after cardiac arrest. The pri-mary objective of this study is to investigate sequential neuro-radiological changes in patients remaining in a persistent vegetative state following resuscitation after cardiac arrest. Methods We repeatedly studied eight vegetative patients resuscitated from unexpected out-of-hospital cardiac arrest using computed tomographic (CT) scanning and high-field magnetic resonance (MR) imaging at 1.5 T. Results In seven of the eight patients, CT scans obtained between days 2 and 6 featured symmetrical low-density lesions in the bilateral caudate, lenticular, and/or thalamic nuclei. These ischemic lesions were persistently of low density on serial CT scans. In these seven patients, MR images demon-strated what were thought to be hemoglobin degradation products derived from minor hemorrhages localized in the bilateral basal ganglia, thalami, and/or substantia nigra. Dif-fuse brain edema in the acute stage and diffuse brain atrophy in the chronic stage were consistent neuroradiological findings. No abnormal enhanced lesions were demonstrated by CT scans. Conclusions The most characteristic findings on high-field MR images were symmetrical lesions in the bilateral basal ganglia, thalami, and/or substantia nigra with specific changes suggestive of minor hemorrhages that were not evident on CT scans. We speculate that these minor hemorrhages result from diapedesis of red blood cells in these regions during the reperfusion period through the endothelium disrupted by ischemia-reperfusion insult.
[Injuries due to domestic violence against women: sites on the body, types of injury and the methods of infliction].

OBJECTIVE To obtain insight into the characteristics of intentional injuries in adult women, such as the sites, types, methods of infliction and the inflictors. DESIGN Descriptive. METHOD 11 trained and experienced forensic physicians collected data from 450 adult women who had reported domestic violence to the police in Amsterdam, the Netherlands, during the period from 1 April 2001 through 31 March 2005. RESULTS In 42% of the cases of domestic abuse, the partner was named as the inflictor; in 26% this was the ex-partner. Of the injuries inflicted, 85% were found on more than one area of the body. The most common sites of injury were the eye, the side of the face, the throat or neck, the upper and lower arms and the upper and lower legs; injury to the mouth, the outside of the hand, the back, the scalp, the shoulder and the thorax was somewhat less common. In 76% of the victims there was more than one type of injury. In 64% of the cases the injury had been inflicted in more than one way. In 79% of the victims the injury was at a site that was visible to the outside world, such as the head or the back of the hand. CONCLUSION In women with injuries due to domestic violence, there was a recognisable pattern with regard to the multiplicity of the injuries, the types of injury, the preferred sites of injury and the visibility of these sites to the outside world.
Tolbutamide as a model drug for the study of enzyme induction and enzyme inhibition in the rat

1 The effects of various drugs on the pharmacokinetics of tolbutamide have been examined in the rat. 2 Phenobarbitone pretreatment caused a significant decrease in half life and area under the curve (AUC) and a significant increase in clearance and volume of distribution (Vd). 3 Acute administration of primaquine significantly increased half life and AUC and decreased clearance. In contrast, the related animoquinolone chloroquine, was without effect. 4 Acute administration of cimetidine produced similar changes to primaquine but of lesser magnitude. 5 Formation of the major metabolite hydroxytolbutamide, was markedly enhanced by phenobarbitone and reduced by primaquine and cimetidine. 6 We conclude that due to its single pathway of metabolism, tolbutamide is a good substrate to use when examining pharmacokinetic interactions involving hepatic enzyme induction and inhibition.
Enzymatic degradation of lignin‐carbohydrate complexes (LCCs): Model studies using a fungal glucuronoyl esterase from Cerrena unicolor

Lignin‐carbohydrate complexes (LCCs) are believed to influence the recalcitrance of lignocellulosic plant material preventing optimal utilization of biomass in e.g. forestry, feed and biofuel applications. The recently emerged carbohydrate esterase (CE) 15 family of glucuronoyl esterases (GEs) has been proposed to degrade ester LCC bonds between glucuronic acids in xylans and lignin alcohols thereby potentially improving delignification of lignocellulosic biomass when applied in conjunction with other cellulases, hemicellulases and oxidoreductases. Herein, we report the synthesis of four new GE model substrates comprising α‐ and ɣ‐arylalkyl esters representative of the lignin part of naturally occurring ester LCCs as well as the cloning and purification of a novel GE from Cerrena unicolor (CuGE). Together with a known GE from Schizophyllum commune (ScGE), CuGE was biochemically characterized by means of Michaelis–Menten kinetics with respect to substrate specificity using the synthesized compounds. For both enzymes, a strong preference for 4‐O‐methyl glucuronoyl esters rather than unsubstituted glucuronoyl esters was observed. Moreover, we found that α‐arylalkyl esters of methyl α‐D‐glucuronic acid are more easily cleaved by GEs than their corresponding ɣ‐arylalkyl esters. Furthermore, our results suggest a preference of CuGE for glucuronoyl esters of bulky alcohols supporting the suggested biological action of GEs on LCCs. The synthesis of relevant GE model substrates presented here may provide a valuable tool for the screening, selection and development of industrially relevant GEs for delignification of biomass. Biotechnol. Bioeng. 2015;112: 914–922. © 2014 Wiley Periodicals, Inc.
Recurrent deletions and duplications of chromosome 2q11.2 and 2q13 are associated with variable outcomes

Copy number variation (CNV) in the long arm of chromosome 2 has been implicated in developmental delay (DD), intellectual disability (ID), autism spectrum disorder (ASD), congenital anomalies, and psychiatric disorders. Here we describe 14 new subjects with recurrent deletions and duplications of chromosome 2q11.2, 2q13, and 2q11.2–2q13. Though diverse phenotypes are associated with these CNVs, some common features have emerged. Subjects with 2q11.2 deletions often exhibit DD, speech delay, and attention deficit hyperactivity disorder (ADHD), whereas those with 2q11.2 duplications have DD, gastroesophageal reflux, and short stature. Congenital heart defects (CHDs), hypotonia, dysmorphic features, and abnormal head size are common in those with 2q13 deletions. In the 2q13 duplication cohort, we report dysmorphic features, DD, and abnormal head size. Two individuals with large duplications spanning 2q11.2–2q13 have dysmorphic features, hypotonia, and DD. This compilation of clinical features associated with 2q CNVs provides information that will be useful for healthcare providers and for families of affected children. However, the reduced penetrance and variable expressivity associated with these recurrent CNVs makes genetic counseling and prediction of outcomes challenging. © 2015 Wiley Periodicals, Inc.