Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of efficacy and toxicity in two different hypofractionated 3 D-conformal external beam radiotherapy schedules in localised muscle invasive bladder cancer

Purpose: To evaluate the efficacy as well as acute and late toxicity of two different accelerated hypofractionated 3D-conformal radiotherapy (Hypo-3DCRT) schedules in patients with bladder cancer. Methods: Between February 2006 and June 2011, 50 elderly patients with cT1-2N0 bladder carcinoma were treated with Hypo-3DCRT. Mean age was 75 years. All patients were medically inoperable, with poor performance status, who couldn’t tolerate either cystectomy or radical external beam irradiation on a daily basis. A dose of 36 Gy in 6 weekly fractions (arm A, N=39) or 39.96 Gy of 3.33 Gy twice daily, once a week, for 6 weeks (arm B, N=11) were prescribed. The primary study endpoints were the evaluation of acute/late gastrointestinal (GI) toxicity according to the EORTC/RTOG scale together with the visual analogue bladder-related pain score (VAS). Results: The GI acute toxicities were: grade 1: arm A 24/39 (61.5%), arm B 9/11 (81.8%); grade 2: arm A 14/39 (35.9%), arm B 1/11 (9.1%); grade 3: arm A 1/39 (9.1%) (x2, p=0.29). Only grade 1 late GI toxicity was seen and was significantly higher in arm A: arm A 17/39 (43.6%) and arm B 1/11 (9.1%) (x2, p=0.037). The reduction of VAS score was similar in both arms (p=0.065). The median relapse free survival (RFS) was 15 and 16 months for arm A and B, respectively (log rank, p=0.71). Conclusions: Beyond the non-randomized design of the trial, the Hypo-3DCRT schedules used appear to be an acceptable alternative to the traditional longer radiotherapy (RT) schedules for elderly patients unfit for daily irradiation.
Fine structure of the chemoreceptor cell in the amphibian carotid labyrinth.

The cephalic end of the common carotid artery in amphibia carries a swelling, the so-called carotid gland or the carotid labyrinth. This has been investigated histologically and embryologically by many workers for more than 100 years (Adams, 1958). Karasik (1934) failed to find any evidence for reflex action due to the chemoreceptor of the carotid labyrinth; and section of the glossopharyngeal nerve did not prevent the dyspnoeic response to the administration of cyanide. On the other hand, Smyth (1939) denervated the carotid glands of frogs by painting with phenol and reported that such denervation abolished the usual dyspnoeic reaction on the exposure to a nitrogen atmosphere. Anichkov & Belen'kii (1963) repeated Smyth's work, and concluded that the carotid labyrinth did not have a chemosensory function. Furthermore, Palme (1934) stated that the carotid labyrinth contained no cell elements similar to the specific cells in mammalian carotid body; but the presence of such cells has been described recently (Rogers, 1963; Laurent & Krieger, 1965). Thus Rogers in an electron microscopic study noted two distinctive types of the cells, one similar to the receptor cell and the second type to the sustentacular cell of mammalian carotid bodies. Using light microscopy, Rogers (1966) also studied the histological and histochemical composition of the carotid labyrinth, and claimed that it is comparable to the mammalian carotid body. Ishii, Honda & Ishii (1966) found that in the toad the carotid labyrinth responds to oxygen lack with increase of the afferent impulse discharge of the carotid nerve, as does the mammalian carotid body, and they also confirmed by light microscopy the presence of specific cells. These findings indicate the existence of a chemosensory apparatus in the carotid labyrinth. The present paper offers information concerning ultrastructural features of this chemosensory apparatus in the toad, with special reference to the innervation of receptor cells. A preliminary report of the results has been published elsewhere (Ishii & Oosaki, 1966).
Principles of S-C-R Compatibility with Spatial and Verbal Tasks: The Role of Display-Control Location and Voice-Interactive Display-Control Interfacing

A pilot's tasks may be categorized into those that demand predominantly verbal operations and those that are spatial. We describe two experiments that define two principles of compatibility of interfacing such tasks with displays and controls. The first, based upon hemispheric laterality effects, defines compatibility according 10 the display location and the response hand; the second defines compatibility according to the modality of display (auditory and visual) and response (manual and speech). Verbal tasks are best served by auditory inputs and speech response, whereas spatial tasks are best served by visual-manual channels. In both experiments, these principles of compatibility are confirmed under dual-task conditions. We describe their implications for cockpit design.
MMP‐2 mediates ethanol‐induced invasion of mammary epithelial cells over‐expressing ErbB2

Ethanol is a tumor promoter and may enhance the metastasis of breast cancer. We have previously demonstrated that over‐expression of ErbB2 promoted ethanol‐mediated invasion of mammary epithelial cells and breast cancer cells. However, the underlying cellular/molecular mechanisms remain unknown. By gelatin zymography, we showed that over‐expression of ErbB2 increased the production of matrix metalloproteinase‐2 (MMP‐2) and MMP‐9 in human mammary epithelial cells (HB2). Transient or stable transfection of ErbB2 cDNA to HB2 cells upregulated the transcripts and the activity of the MMP‐2/‐9 gene promoter; the upregulation of MMP‐2/‐9 expression was mediated by p38 mitogen‐activated protein kinase (p38 MAPK) and phosphatidylinositol 3‐kinase (PI3K). Although ethanol, at physiologically relevant concentrations (100–400 mg/dl), did not affect the production of MMP‐2/‐9, it activated MMP‐2 in HB2 cells over‐expressing ErbB2 (HB2ErbB2), but not HB2 cells; it enhanced the cleavage of proform MMP‐2 (72 kDa) to an active form (62 kDa). The activation was dependent on c‐jun N‐terminal kinases (JNKs) and reactive oxygen species (ROS). On the other hand, ethanol affected neither the expression nor the activation of MMP‐9. Selective inhibitors of MMP‐2 (SB‐3CT and OA‐Hy) and antioxidants significantly inhibited ethanol‐stimulated invasion of HB2ErbB2 cells. Furthermore, knocking down MMP‐2 by small interference RNA also induced a partial blockage on ethanol‐promoted invasion of HB2ErbB2 cells. Thus, ethanol‐stimulated invasion of cells over‐expressing ErbB2 was mediated, at least partially, by MMP‐2 activation. © 2006 Wiley‐Liss, Inc.
Early onset cerebellar ataxia with retained tendon reflexes: prevalence and gene frequency in an Italian population

A genetic epidemiologic analysis of early onset cerebellar ataxias (EOCA) with retained tendon reflexes was performed in a defined area of Northwestern Italy. Forty cases diagnosed from 1940 to 1990 were ascertained. The ascertainment probability was 85.7%. The segregation analysis (Weinberg's proband method and ‘singles” method under incomplete ascertainment) is compatible with autosomal recessive inheritance. The point prevalence ratio was 1.0/100000 population. The birth incidence rate was 1/48000 live births. Gene frequency was estimated to be 1/218. The ratio of first‐cousin marriages among parents of EOCA (4.5%) was lower than expected using Dahlberg's formula (8.9%).
Francisella Tularensis Genomics and Proteomics

Abstract: The availability of the genome sequences of different strains of Francisella tularensis is having a major impact on a wide range of research projects, from understanding the biology of this organism to devising vaccines and diagnostics. Comparative genomics and molecular typing methods suggest that the four different subspecies of F. tularensis are genetically distinct groups. Although there is a high degree of nucleotide identity between strains, there are numerous DNA rearrangements. IS elements appear to have played a major role in these chromosomal rearrangements. The different subspecies of F. tularensis appear to have evolved by vertical descent from a common ancestor, probably F. tularensis subspecies novicida. Comparative genomic and proteomic studies have revealed possible reasons for the different virulence of different strains and a range of candidate virulence genes have been identified including those located on the Francisella pathogenicity island. Proteomic studies have identified proteins which are produced at elevated levels in vivo, and proteins which are recognized by immune or convalescent sera. These proteins might be exploited as components of vaccines or diagnostic systems.
A work in progress: The clinical development of histone deacetylase inhibitor

It has been widely recognized that histone deacetylases (HDAC) are promising targets in the field of oncology. An impressive body of preclinical research points to the ability of HDAC inhibitors (HDACIs) to modulate a wide variety of cellular functions, including cell differentiation, cell cycle progression, apoptosis, cytoskeletal modifications, and angiogenesis. Originally developed as epigenetic drugs because of their ability to inhibit histones deacetylation, HDACIs are now being considered also because of their effects on other acetylation-regulated proteins with pivotal roles in transformed cells. This review will highlight the clinical development of HDACIs in oncology and will try to discuss the several major open clinical issues challenging the successful clinical development of HDACIs, with a particular emphasis on the spectrum of activity of these agents, the best development strategy in solid tumours, the cardiac side effects and bio-markers to be used in clinical trials.
Behaviour of cells mutant for an EGF receptor homologue of Drosophila in genetic mosaics

The Drosophila homologue of the epidermal growth factor receptor (DEGFr or DER, also called torpedo or top) has many mutant alleles that cause either embryonic lethality (both early and late), pupal lethality or female sterility, possibly corresponding to degrees of hypomorphism. We have studied the clonal behaviour of some lethal alleles in genetic mosaics in the imaginal development of thorax, head and tergite epidermis. These alleles cause reduced cell viability to different degrees (measured in frequency and size of clones), smaller cell sizes, abnormal patterning of sensory-organ differentiation and lack of differentiation of macro-chaetae and veins. These effects are cellautonomous but also cause abnormal differentiation in wild-type cells surrounding the clones. In addition, we have studied the phenotypes of double mutant combinations of viable top alleles with wingpattern mutants, some related to other Drosophila proto-oncogenes, to reveal gene interactions in the role(s) of DER in cell proliferation and differentiation. We discuss how those complex cell-behaviour phenotypes and genetic interactions are related to the molecular nature of the DER.
Embryonic cardiomyocytes beat best on a matrix with heart-like elasticity: scar-like rigidity inhibits beating

Fibrotic rigidification following a myocardial infarct is known to impair cardiac output, and it is also known that cardiomyocytes on rigid culture substrates show a progressive loss of rhythmic beating. Here, isolated embryonic cardiomyocytes cultured on a series of flexible substrates show that matrices that mimic the elasticity of the developing myocardial microenvironment are optimal for transmitting contractile work to the matrix and for promoting actomyosin striation and 1-Hz beating. On hard matrices that mechanically mimic a post-infarct fibrotic scar, cells overstrain themselves, lack striated myofibrils and stop beating; on very soft matrices, cells preserve contractile beating for days in culture but do very little work. Optimal matrix leads to a strain match between cell and matrix, and suggests dynamic differences in intracellular protein structures. A `cysteine shotgun' method of labeling the in situ proteome reveals differences in assembly or conformation of several abundant cytoskeletal proteins, including vimentin, filamin and myosin. Combined with recent results, which show that stem cell differentiation is also highly sensitive to matrix elasticity, the methods and analyses might be useful in the culture and assessment of cardiogenesis of both embryonic stem cells and induced pluripotent stem cells. The results described here also highlight the need for greater attention to fibrosis and mechanical microenvironments in cell therapy and development.
Free Word Associations Correspond to Contiguities Between Words in Texts*

A free associative response is the first word a person comes up with after perceiving another word, the so-called associative stimulus. People commonly associate hot to cold, church to priest, and hard to work. According to traditional association theory this behaviour is the result of learning by contiguity: “Objects once experienced together tend to become associated in the imagination, so that when any one of them is thought of, the others are likely to be thought of also, in the same order of sequence or coexistence as before” (James, 1890). This explanation has been rejected by cognitive psychologists who explain the production of associations as the result of symbolic processes which make use of complex semantic structures (Clark, 1970). We will show, however, that human associative responses can be predicted from contiguities between words in language use. This finding supports the hypothesis that the behaviour of participants in the free association task can be explained by associative learning.
Peptides derived from HIV‐1 Rev inhibit HIV‐1 integrase in a shiftide mechanism

The HIV‐1 Integrase protein (IN) mediates the integration of the viral cDNA into the host genome. IN is an emerging target for anti‐HIV drug design, and the first IN‐inhibitor was recently approved by the FDA. We have developed a new approach for inhibiting IN by “shiftides”: peptides derived from its cellular binding protein LEDGF/p75 that inhibit IN by shifting its oligomerization equilibrium from the active dimer to an inactive tetramer. In addition, we described two peptides derived from the HIV‐1 Rev protein that interact with IN and inhibit its activity in vitro and in cells. In the current study, we show that the Rev‐derived peptides also act as shiftides. Analytical gel filtration and cross‐linking experiments showed that IN was dimeric when bound to the viral DNA, but tetrameric in the presence of the Rev‐derived peptides. Fluorescence anisotropy studies revealed that the Rev‐derived peptides inhibited the DNA binding of IN. The Rev‐derived peptides inhibited IN catalytic activity in vitro in a concentration‐dependent manner. Inhibition was much more significant when the peptides were added to free IN before it bound the viral DNA than when the peptides were added to a preformed IN‐DNA complex. This confirms that the inhibition is due to the ability of the peptides to shift the oligomerization equilibrium of the free IN toward a tetramer that binds much weaker to the viral DNA. We conclude that protein–protein interactions of IN may serve as a general valuable source for shiftide design. © 2008 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 481–487, 2008.
Treatment of ACTH-dependent Cushing ’ s syndrome : a consensus statement

Neuroendocrine Clinical Center, Massachusetts General Hospital (B.M.K.B., A.K., B.S.), Boston, USA; Department of Endocrinology (A.B.G.), St Bartholomew’s Hospital, London, UK; Division of Medical Sciences (P.M.S.), University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK; Department of Medicine (S.M.), Cedars Sinai Medical Center, Los Angeles, California, USA; Endocrinology Department (X.B., J.B.), Hôpital Cochin, AP-HP, Faculté de Médecine Paris Descartes, Paris, France; Neurochirurgische Klinik (M.B.), Universität Erlangen, Nürnberg, Germany; Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica (A.C.), Università degli Studi di Napoli Federico II, Napoli, Italy; Department of Endocrinology (A.R.H.), University Medical Center Nijmegen, The Netherlands; Department of Internal Medicine (L.J.H.), Division of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands; Division of Endocrinology (A.L.), Department of Medicine, Centre Hospitalier de l’Université de Montréal, Montréal, Quebec, Canada; Altnagelvin Area Hospital (J.R.L), Londonderry, UK; The Medical School (J.N-P.), University of Sheffield, Sheffield, UK; Reproductive Biology and Medicine Branch (L.K.N.), National Institutes of Health, Bethesda, Maryland, USA; Division of Endocrinology (S.P.), University of Essen, Essen, Germany; Department of Statistical Sciences (N.S.), University of Padova, Padova, Italy; Department of Endocrinology (G.K.S.), Max Planck Institute of Psychiatry, Munich, Germany; University of Virginia Health System (M.L.V.), Charlottesville, Virginia, USA; Department of Endocrinology (J.A.H.W.), Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK; Division of Endocrinology (M.B), Institute of Internal Medicine, Polytechnic University of Marche, Ancona, Italy
The Arabidopsis eukaryotic translation initiation factor 3, subunit F (AteIF3f), is required for pollen germination and embryogenesis

Summary Previous studies have shown that subunits E (eIF3e), F (eIF3f) and H (elF3h) of eukaryotic translation initiation factor 3 play important roles in cell development in humans and yeast. eIF3e and eIF3h have also been reported to be important for normal cell growth in Arabidopsis. However, the functions of subunit eIF3f remain largely unknown in plant species. Here we report characterization of mutants for the Arabidopsis eIF3f (AteIF3f) gene. AteIF3f encodes a protein that is highly expressed in pollen grains, developing embryos and root tips, and interacts with Arabidopsis eIF3e and eIF3h proteins. A Ds insertional mutation in AteIF3f disrupted pollen germination and embryo development. Expression of some of the genes that are essential for pollen tube growth and embryogenesis is down‐regulated in ateif3f‐1 homozygous seedlings obtained by pollen rescue. These results suggested that AteIF3f might play important roles in Arabidopsis cell growth and differentiation in combination with eIF3e and eIF3h.
Domains of BclA, the major surface glycoprotein of the B. cereus exosporium: glycosylation patterns and role in spore surface properties

The role of the BclA domains of B. cereus ATCC 14579 was investigated in order to understand the phenomena involved in the interfacial processes occurring between spores and inert surfaces. This was done by (i) creating deletions in the collagen-like region (CLR) and the C-terminal domain (CTD) of BclA, (ii) building BclA proteins with various lengths in the CLR and (iii) modifying the hydrophobic upper surface in the CTD. First, it was demonstrated that the CLR was substituted by three residues already reported in the CLR of B. anthracis, viz. rhamnose, 3-O-methyl-rhamnose, and GalNH2 residues, while the CTD was also substituted by two additional glycosyl residues, viz. 2-O-methyl-rhamnose and 2,4-O-methyl-rhamnose. Regarding the properties of the spores, both CLR and CTD contributed to the adhesion of the spores, which was estimated by measuring the resistance to detachment of spores adhered to stainless steel plates). CLR and CTD also impacted the hydrophobic character and isoelectric point of the spores. It was then shown that the resistance to detachment of the spores was not affected by the physicochemical properties, but by the CLR length and the presence of hydrophobic amino acids on the CTD.
Index of productive syntax for children who speak African American English.

PURPOSE The validity of the Index of Productive Syntax (IPSyn; Scarborough, 1990) for children who speak African American English (AAE) was evaluated by conducting an item analysis and a comparison of the children's scores as a function of their maternal education level, nonmainstream dialect density, age, and clinical status. METHOD The data were language samples from 62 children; 52 of the children were between the ages of 4 and 6 years and were classified as developing typically, and 10 were 6 years old with specific language impairment (SLI). RESULTS All IPSyn items were produced by at least 1 child, and 88% of the items were produced by 50% or more of the children. The children's IPSyn scores were unrelated to maternal education level and dialect density and were visually comparable to IPSyn scores reported for children who speak mainstream English. Nevertheless, IPSyn could not be used to detect differences between the 4- to 6-year-olds based on age, nor could it be used to detect differences between the 6-year-olds with and without SLI. CONCLUSION IPSyn is a valid measure for AAE speakers, but it can be insensitive to age and clinical differences between children who are over the age of 48 months.
Causes of death at different ages, by sex, and by season, in a rural population of the Punjab, 1957-1959: A field study.

To identify the leading causes of death in the rural Ludhiana District of the Punjab 615 deaths out of a popultion of 12022 occurring between January 1 1957 and December 31 1959 were investigated at the time of occurrence using case study methods in order to contribute to the effective use of health services. (To utilize reported findings knowledge of the particular disease processes most active in the stated epidemiological situations is required.) Death rates for females exceeded those for males at all ages except for persons past 65 years with the majority occurring in the age range 1-4; tetanus accounted for almost one-third of the deaths in the neonatal period; birth injuries and diseases peculiar to newborns were unusually high in this population. No outstanding epidemics occurred during the specified time. The great variations in death rates by season suggest intensified efforts during the hot season of the year against diarrheal disease and typhoid fever; the emphasis in control is on nutrition and environmental sanitation. It is concluded that fundamental preventive measures and improved medical care primarily through augmented maternal and child health services would do much to lower the high death rates.
Dispersion and Attenuation of Small Artificial Pressure Waves in the Canine Aorta

A method was developed to determine the elastic behavior of large blood vessels in terms of their transmission characteristics for small sinusoidal pressure signals. The method is new insofar as it utilizes transient signals of the form of finite trains of sine waves that are superimposed on the naturally occurring pressure fluctuations and are generated by an electrically driven impactor or by a pump. Its application to the thoracic aortas of 18 mature mongrel dogs anesthetized with pentobarbital has shown that dispersion and attenuation data for frequencies between 40 and 200 cps can be obtained without requiring either Fourier transform computations or resolution of reflection interference. For the frequency range considered, the descending aorta is only mildly dispersive but exhibits strong attenuation that must be attributed primarily to dissipative mechanisms in the vessel wall. At normal blood pressure levels, the wave speed during diastole can have a value between 4 and 6 m/sec. For all frequencies tested the amplitude ratio of the waves exhibits the same exponential decay pattern with distance measured in wavelengths. A marked increase in wave speed observed from diastole to systole can be associated with an increase in mean flow and with a stiffening of the aortic wall due to the rise in pressure. This phenomenon implies that the aortas of anesthetized dogs should exhibit nonlinear properties with respect to large amplitude pulse waves such as those generated by the heart.