Miracle-dz/UniFAR-FTUs huggingface dataset:
Stx2-Specific Human Monoclonal Antibodies Protect Mice against Lethal Infection with Escherichia coli Expressing Stx2 Variants

ABSTRACT Shiga toxin-producing Escherichia coli (STEC) strains are responsible for causing hemolytic-uremic syndrome (HUS), and systemic administration of Shiga toxin (Stx)-specific human monoclonal antibodies (HuMAbs) is considered a promising approach for prevention or treatment of the disease in children. The goal of the present study was to investigate the ability of Stx2-specific HuMAbs to protect against infections with STEC strains that produce Stx2 variants. Dose-response studies on five HuMAbs, using the mouse toxicity model, revealed that only the three directed against the A subunit were protective against Stx2 variants, and 5C12 was the most effective among the three tested. Two HuMAbs directed against the B subunit, while highly effective against Stx2, were ineffective against Stx2 variants. In a streptomycin-treated mouse model, parenteral administration of 5C12 significantly protected mice up to 48 h after oral bacterial challenge. We conclude that 5C12, reactive against the Stx2 A subunit, is an excellent candidate for immunotherapy against HUS and that antibodies directed against the A subunit of Stx2 have broad-spectrum activity that includes Stx2 variants, compared with those directed against the B subunit.
Psychiatric lessons from World War II.

When the final history of World War II is written and like all history is entombed in large volumes, to the student who reads it carefully it will reveal the same lessons which are learned so painfully and at such great cost in all wars. Each successive war necessarily brings with it new problems, but the old ones crop up repeatedly and as we encounter them again and again we wonder why man is so slow to profit by experience and history. Perhaps the cynic expressed it best of all when he said, “Men learn from history only that men learn nothing from history. ” Simple as it may seem, one of the most important basic principles to remember is that wars are fought by people. They were in the days of triremes, they are today and they will continue to be even in an atomic age unless the nations of the world decide to settle their problems in a peaceful fashion. In the last analysis then the outcome of a battle, the final result of a war, and even the peace time negotiations which follow are dependent upon what men do and how they react, and these phenomena are of paramount interest to psychiatrists. In this regard the psychiatrists follow literally the dictum of the sage that “the proper study of manldnd is man. ” It has been said that “experience is the best teacher. ” Certainly it is the best teacher of the reactions of men subjected to stress. If it can also be said to be the best teacher of psychiatry, then present day psychiatry has had experiences from which it can profit for many years to come. These papers today deal with experiences garnered the hard way and, inasmuch as the process of gaining psychiatric knowledge at the expense of world catastrophe is too high a purchase price, it is imperative that we at least expect to use
Formal Analysis of MAC in IEEE 802.11p with Probabilistic Model Checking

In vehicular ad-hoc network, Media AccessControl (MAC) is one of the technologies which determinewhether the information is transferred reliably and timely or not. It is also a key to the quality of service of self organizationnetworks. Some behaviors of the MAC protocol can be estimatedby experiment and simulation. But the main drawback of thesemethods is that the estimation can not be accurate to support theenough confidence. In this paper, we complete the preciseanalysis of the MAC protocol by probabilistic model checking. First, based on the nature of MAC, its dynamic behavior isabstracted into a probabilistic timed automata which candescribe non-deterministic, continuous time and the probabilityselection of MAC. Then we calculate the probability of the datasent successfully and the probability of the backoff counterreaching the maximum value. The analysis result shows that theprobability of conflict in 802.11p is much smaller than the 802.11standard. Therefore the waiting time in 802.11p is significantlyreduced and in the case of fast-moving, the data can be senttimely. Further we calculate the maximum expect conflictnumber under the different values of maximum backoff and thelongest time to complete the data transmission. The result showsthat when the value of maximum backoff increases, the numberof collisions that occurred in 802.11p tends to be stable, which isless than the 802.11 standard's collisions, and the average speedof the data transmission in 802.11p is as four times faster as the802.11 standard.
Elevated Plasma Immunoreactive Concentrations and Its Increased Patients with Advanced Diabetic Neuropeptide Y Urinary Excretion in Nephropathy

Neuropeptide Y (NPY) is a potent vasoconstrictor peptide that is abundant in the brain and the peripheral sympathetic nervous system. In the present study we investigated possible changes in plasma immunoreactive (IR)-NPY concentrations and urinary IR-NPY excretion in patients with noninsulin dependent diabetes mellitus (NIDDM) and the relationship to diabetic complications, such as nephropathy and neuropathy. IR-NPY in plasma and urine was measured by radioimmunoassay in 69 patients with NIDDM. Plasma IR-NPY concentrations in patients with advanced nephropathy (creatinine clearance <30 ml/min) (100.5 ± 10.3 pmol/l, n=9, mean ± SEM) were higher than in the control subjects (55.0 ± 6.8 pmol/l, n=15) (P<0.02). Urinary excretion of IR-NPY and fractional excretion of NPY were also increased in the patients with advanced nephropathy. Sephadex G-50 column chromatography of the urine extracts obtained from healthy subjects, diabetic patients with renal failure and non-diabetic patients with renal failure showed an immunoreactive peak eluting in the NPY position. On the other hand, neither plasma nor urinary IR-NPY was high in patients with retinopathy, or in patients with peripheral neuropathy. The present study has, for the first time, shown high plasma IR-NPY concentrations and urinary IR-NPY excretion in NIDDM patients with advanced nephropathy.
UV‐A Fingerprint Mutations in Human Skin Cancer ¶

This review of our work, presented at the Photocarcinogenesis Symposium of the 14th International Congress on Photobiology, shows that UV‐A causes a similar number of gene mutations as UV‐B in human skin cancer. Areas of about 20 keratinocytes from solar keratoses and squamous cell carcinomas, which are benign and malignant skin cancers, respectively, were sampled by laser capture microdissection. Automated sequencing of the p53 gene was used to detect mutations in these tumor areas, and the cause of the mutations was attributed on the basis of previously published studies. UV‐A and UV‐B caused similar numbers of p53 gene mutations in both benign and malignant human skin tumors, with UV‐B–induced mutations being restricted to the upper areas of the tumors and UV‐A–induced mutations predominating at the basal layer. Furthermore, each microdissected region within a tumor had distinct mutations showing that the skin tumors consisted of different clones of cells. This is not consistent with how human skin carcinogenesis is currently understood, and hypotheses to explain our data are presented. We propose that the UV‐A waveband of sunlight is as important as UV‐B in causing skin cancer in humans.
Uncontrolled Hypertension in Type 1 Diabetes: Assessment of Patients' Desires about Treatment and Improvement of Blood Pressure Control by a Structured Treatment and Teaching Programme

Control of arterial blood pressure at near‐normal levels is of importance for the prognosis of patients with Type 1 (insulin‐dependent) diabetes mellitus. In non‐diabetic populations patient compliance to antihypertensive therapy is frequently poor, especially in young people. Thirty‐seven consecutive eligible patients with longstanding Type 1 diabetes and persistently uncontrolled hypertension were questioned about their preferences regarding hypertension treatment. Throughout they expressed a strong desire for more information about hypertension and for active participation in monitoring of blood pressure and therapeutic decision‐making. In addition, they showed considerable reluctance to accept a pharmacological intervention. Therefore, in order to improve blood pressure control, the patients participated in a structured outpatient hypertension treatment and teaching programme for groups of about 6 patients consisting of four teaching sessions at weekly intervals. The programme comprised home‐monitoring of blood pressure and involvement of the patients in treatment decision‐making. In 34 patients who had a complete follow‐up examination after an average of 16 months, mean sitting arterial pressure had decreased from 111 to 101 mmHg (p < 0.001) and 53 % of the patients were below 140/90 mmHg. The number and dosage of prescribed antihypertensive agents remained unchanged by the intervention. Sodium intake was not reduced during the study, but pulse rate decreased significantly in patients treated with β‐adrenergic blockers and serum uric acid rose in patients on diuretic therapy, suggesting increased adherence of the patients to prescribed antihypertensive drug therapy. In 34 comparable Type 1 diabetic patients who were not subjected to a hypertension treatment and teaching programme mean arterial blood pressure remained unchanged during a 12‐month period.
The Making of Britain's First Urban Landscapes: The Case of Late Iron Age and Roman Essex

ABSTRACT This paper presents preliminary research into the social and economic impact of early urban settlement in Britain, focusing on the case-study area of Late Iron Age to Roman Essex. Through fresh analysis of ceramic assemblages from Colchester and Heybridge, we describe hitherto unrecognised socio-cultural groupings and identities through subtle differences in the deposition of pottery in the generations before and after conquest. The concluding discussion concentrates on problems that we still have to address in describing the economic basis of early urban society in Britain.
Genetic variation of CACNA1H in idiopathic generalized epilepsy

In a recent report, Chen and colleagues described 12 putative mutations in the T-type calcium channel gene CACNA1H in 14 of 118 patients with childhood absence epilepsy (CAE), and concluded that missense mutations in this gene may predispose to CAE. To investigate variation of CACNA1H in our patient population, we screened exons 9 to 11, in which 75% of the putative mutations described by Chen and colleagues are located, in 192 patients (134 unrelated) with idiopathic generalized epilepsies or generalized epilepsy with febrile seizures plus. This group included 34 CAE and 15 juvenile absence epilepsy patients. The study was approved by the ethics committees of the Women’s and Children’s Hospital and Austin Health. Informed consent was obtained from participants. DNA was amplified by polymerase chain reaction and screened for variation by single-stranded conformation analysis. Sequencing was performed using ABI BigDye v3.0 on the ABI 3700 instrument. Ninety-six control samples were screened for variants identified in patients. When a variant was present in a patient and not in controls, available members of the patient’s family were tested for the variant. Four variants were present only in patients. These were c.1438G3A (A480T); c.1853C3T (P618L); c.18571858del (V621fsX654), and c.2264G3A (G755D). The inheritance of these changes in the families is shown in the Figure. None of these variants was found in CAE or juvenile absence epilepsy patients. None of the four variants segregate with a specific epilepsy phenotype in each family, nor is their presence associated with any one phenotype. There are two instances in which siblings with the same phenotype are discordant for a variant, and all four variants are present in unaffected individuals. Our failure to replicate the findings of Chen and colleagues in absence phenotypes in our patient population suggests that the significance of CACNA1H variants in the cause of human epilepsy remains unclear. Moreover, functional data are required for all CACNA1H variants before their role in epilepsy is established. Generalized epilepsies are likely to be polygenic in origin, with variations in multiple ion-channel subunits or other genes interacting to cause epileptogenesis. For example, a mutation of GABRG2 has been found previously in three members of Family E and it is probable that several genes
Morphological plasticity in scleractinian corals

When describing coral shape and form the term phenotypic plasticity, i.e. environment‐induced changes in morphology, is often used synonymously with intraspecific variation. Variation, however, may simply be due to genetic differentiation (polymorphism). Of the 1314 extant scleractinian coral species, less than 20 have been tested for plastic responses. Morphological plasticity has important implications for coral identification, as skeletal features used in coral systematics are directly affected by environment. Furthermore, plastic changes can indicate how corals acclimatise to environmental change. The studies that have examined phenotypic plasticity in corals experimentally can be divided into two groups, i.e. ‘non‐clonal’—those that have transplanted whole colonies or fragments of colonies (but not treated the fragments as clones) to new environments, and ‘clonal’—those that have transplanted colony fragments and used them as clone‐mates. The use of clone‐mates is preferable as it facilitates the identification of among‐genotype variation for plasticity. The heterogeneous nature of the reef environment makes identifying the parameters that affect coral morphology difficult in the field, but there are also many problems conducting suitable aquarium experiments. Nevertheless, evidence to date suggests light and water movement are the most important variables inducing change. As these factors are known to be axiomatic to coral growth, it is possible that associated plastic changes in corals are adaptive; however, this hypothesis is yet to be tested rigorously.
Vision-Based Toddler Tracking at Home

This paper presents a vision-based toddler tracking system for detecting risk factors of a toddler's fall within the home environment. The risk factors have environmental and behavioral aspects and the research in this paper focuses on the behavioral aspects. Apart from common image processing tasks such as background subtraction, the vision-based toddler tracking involves human classification, acquisition of motion and position information, and handling of regional merges and splits. The human classification is based on dynamic motion vectors of the human body. The center of mass of each contour is detected and connected with the closest center of mass in the next frame to obtain position, speed, and directional information. This tracking system is further enhanced by dealing with regional merges and splits due to multiple object occlusions. In order to identify the merges and splits, two directional detections of closest region centers are conducted between every two successive frames. Merges and splits of a single object due to errors in the background subtraction are also handled. The tracking algorithms have been developed, implemented and tested.
Ultra low-level tritium measurement using electrolytic enrichment and LSC

We describe an advanced methodology for low-level tritium measurement in regard to calibration, electrolytic tritium enrichment, liquid scintillation counting (LSC) measurement, and prevention of sample contamination. Details are given on enrichment parameters and electrode processes for optimisation of enrichment reproducibility and on optimisation of LSC stability. Intercomparison results demonstrate high accuracy of the tritium measurement system. The use of accurate tritium data for groundwater dating in the southern hemisphere is demonstrated with data from several groundwater systems of New Zealand. †Updated paper: originally presented on the IAEA International Symposium “Quality Assurance for Analytical Methods in Isotope Hydrology” (August 2004, Vienna).
Application of the topological gradient method to tomography

A new method for parallel beam tomography is proposed. This method is based on the topological gradient approach. The use of the topological asymptotic analysis for detecting the main edges of the data allows us to ﬁlter the noise while inverting the Radon transform. Experimental results obtained on noisy data illustrate the efﬁciency of this promising approach in the case of Magnetic Resonance Imaging. We also study the sensitivity of the algorithm with respect to several regularization and weight parameters. RÉSUMÉ. Une nouvelle méthode de reconstruction pour la tomographie par faisceaux parallèles est proposée. Cette méthode est basée sur l’approche du gradient topologique. En détectant les contours sur les données grâce à l’analyse asymptotique topologique, il est possible de ﬁltrer le bruit dans le processus d’inversion de la transformée de Radon. Des résultats expérimentaux obtenus sur des données bruitées illustrent les possibilités de cette approche prometteuse dans le domaine de traitement d’images IRM. Nous étudions également la sensibilité de l’algorithme par rapport aux différents paramètres de régularisation et pondération.
SIRT1 Deacetylation and Repression of p300 Involves Lysine Residues 1020/1024 within the Cell Cycle Regulatory Domain 1*

The SIR2 family of nicotinamide adenosine dinucleotide (NAD)-dependent deacetylases modulates diverse biological functions in different species, including longevity, apoptosis, cell cycle exit, and cellular differentiation. SIRT1, the closest mammalian ortholog of the yeast SIR2 (silent information regulator 2) gene, represses several transcription factors, including p53, NFκB and forkhead proteins. The p300 protein serves as a rate-limiting transcriptional cointegrator of diverse transcription factors either to activate or to repress transcription through modular subdomains. Herein, SIRT1 physically interacted with and repressed p300 transactivation, requiring the NAD-dependent deacetylase activity of SIRT1. SIRT1 repression involved the CRD1 transcriptional repression domain of p300. Two residues within the CRD1 domain (Lys-1020 and Lys-1024) were required for SIRT1 repression and served as substrates for SIRT1 deacetylation. These residues also serve as acceptor lysines for modification by the ubiquitin-like SUMO protein. The SUMO-specific protease SSP3 relieved SIRT1 repression of p300. SSP3 antagonism of SIRT1 required the SUMO-deconjugating function of SSP3. Thus, p300 serves as a deacetylase substrate for SIRT1 through a conserved SUMO consensus motif. Because p300 is a limiting transcriptional cofactor, deacetylation and repression of p300 by SIRT1 may serve an important integration point during metabolism and cellular differentiation.
A general clustering approach with application to the Miyazawa–Jernigan potentials for amino acids

In this article, we address the problem of classification of amino acids. Starting from the Miyazawa–Jernigan matrix obtained from the relative positions of amino acids in the crystal structure of globular proteins, we develop a fully unsupervised method of classification for the amino acids. The method is based in the subdominant ultrametric associated to the distance induced by the Miyazawa–Jernigan matrix and the maximum likelihood principle to determine the cluster structure. We obtain a classification consistent with the five groups used in the literature, although with some peculiarities. We also show the stability of our results against changes of the method used to classify the amino acids. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Distribution of hippocampal mossy fibers in the rat. An experimental study with silver impregnation methods

The paper deals with the distribution of the axons that arise in the fascia dentata and go to the hippocampus proper. lesions were placed in the fascia dentata and degenerating mossy fibers were mapped by silver impregnation, mostly according to the method of Fink and Heimer ('67). The fascia dentata and the layer of mossy fibers in the rat form a curved and twisted structure extending from the level of the posterior aspect of the septum to the temporal tip. The horizontal serial sections used for this study were, therefore, in part interpreted by means of three‐dimensional reconstructions.
Brain natriuretic peptide administered to man: actions and metabolism.

To investigate the effects and metabolism of brain natriuretic peptide (BNP) in man, eight normal subjects received 3-h infusions of synthetic porcine BNP (2 pmol/kg.min) in a placebo-controlled study. The MCR and plasma half-life of BNP were 2.69 L/min and 3.1 min, respectively. BNP clearly suppressed PRA to less than 50% of placebo values (P less than 0.001). Plasma aldosterone concentrations were also significantly reduced by 30% (P less than 0.05). Urinary sodium excretion tended to rise (P = 0.054), and urinary cGMP excretion was clearly enhanced (P less than 0.01). Systemic and renal hemodynamics, hematocrit, plasma protein concentrations, plasma ACTH, arginine vasopressin, PRL, and catecholamines were unchanged. Porcine BNP has a similar range of effects and is similarly metabolized in man as human ANP. Further elucidation of the possible role of BNP as a circulating hormone in man awaits measurement of tissue and plasma concentrations of human BNP in health and disease and provision of fuller dose-response data for human as well as porcine BNP.
Transfer RNA modifications: nature's combinatorial chemistry playground

Following synthesis, tRNAs are peppered by numerous chemical modifications which may differentially affect a tRNA's structure and function. Although modifications affecting the business ends of a tRNA are predictably important for cell viability, a majority of modifications play more subtle structural roles that can affect tRNA stability and folding. The current trend is that modifications act in concert and it is in the context of the specific sequence of a given tRNA that they impart their differing effects. Recent developments in the modification field have highlighted the diversity of modifications in tRNA. From these, the combinatorial nature of modifications in explaining previously described phenotypes derived from their absence has emerged as a growing theme. WIREs RNA 2013, 4:35–48. doi: 10.1002/wrna.1144
Oncogenes and growth factors in gliomas.

The activation of cellular proto-oncogenes is related to the genesis and progression of neoplasias. Protein growth factors and their cellular receptors have been identified as products of some proto-oncogenes. The role of epidermal growth factor receptor (EGFr) in gliomas is presented. The expression of mRNA for platelet-derived growth factor (PDGF) and PDGF B-type receptor (PDGF-rec-B) in gliomas is analyzed. Gliomas express "in vivo" PDGF.B and PDGF-rec-B mRNAs. PDGF.B mRNA levels correlate with GFAP mRNA and does not correlate with the degree of malignancy. This is in agreement with the hypothesis of an autocrine growth stimulation in gliomas. However some findings seem to indicate that in these tumors the PDGF-rec-B is preferentially expressed by vascular elements. Thus, also a paracrine loop for endothelial cell growth stimulation may be suggested in malignant gliomas.