Mechanism of T-Cell Lymphomagenesis: Transformation of Growth-Factor-Dependent T-Lymphoblastoma Cells to Growth-Factor-Independent T-Lymphoma Cells

In a previous paper we described the induction by x-irradiation or radiation-induced leukemia virus-in-oculation of two classes of lymphoid T-cell neoplasms: The first class, designated T-cell lymphoblastoma (TCLB), consists of growth-factor-dependent eudiploid cells that home to the spleen and give rise to splenic tumors on injection into syngeneic mice; the second class, designated T-cell lymphoma (TCL), consists of growth-factor-independent aneuploid or pseudodiploid cells that give rise to local tumors at the site of subcutaneous injection. This paper describes the generation of a family of growth-factor-independent aneuploid or pseudodiploid TCL cells after the injection into the thymus of growth-factor-dependent diploid TCLB cells. In contrast to the donor TCLB cells, the resulting TCL cells could be cloned in semisolid medium, produced local tumors at the site of subcutaneous injection, and proliferated in a growth-factor-independent fashion in vitro. The induced growth-factor-independent TCL cells were chromosomally and phenotypically unstable and continued to evolve both in vivo and in vitro. After propagation in the thymus, the cells often showed stable translocations in addition to the evolving aneuploidy. We propose that the chromosome abnormalities induced during the proliferation of growth-factor-dependent TCLB cells in the thymus constitute a general mechanism by which neoplastic cells progress from growth-factor dependency to independency

Interactive Augmentation of Voice Quality and Reduction of Breath Airflow in the Soprano Voice

SummaryIn 1985, at a conference sponsored by the National Institutes of Health, Martin Rothenberg first described a form of nonlinear source-tract acoustic interaction mechanism by which some sopranos, singing in their high range, can use to reduce the total airflow, to allow holding the note longer, and simultaneously enrich the quality of the voice, without straining the voice. (M. Rothenberg, “Source-Tract Acoustic Interaction in the Soprano Voice and Implications for Vocal Efficiency,” Fourth International Conference on Vocal Fold Physiology, New Haven, Connecticut, June 3–6, 1985.) In this paper, we describe additional evidence for this type of nonlinear source-tract interaction in some soprano singing and describe an analogous interaction phenomenon in communication engineering. We also present some implications for voice research and pedagogy

The Voice Foundation

I would like to discuss the physical factors that differentiate the strong or well-carrying singing voice from the weak or average voice. In this discussion I will be most concerned with the voice of a male singer singing open vowels, such as the vowel /a/, in modal or chest register; however, the principles discussed undoubtedly extend beyond these limitations. It has been long recognized that in this situation a strong voice invariably contains a higher than normal amount of energy near the third highest vocal tract resonance ("formant"), or at roughly 3000 Hz (Bartholemew, 1934). Besides helping to give the voice an aesthetic quality usually desired in operatic-style singing, this energy permits the voice to carry well over the sound of the orchestra, since most instruments have little energy at that high a frequency. To see where this added energy can come from, let us examine the common source-tract model for voice production in The air flow pulses from the glottis then passes through the pharynx, and the oral and nasal cavities, where they are "resonated" at the natural or resonant frequencies of this system of chambers. In other words, the energy distribution in the pulses is modified so that the energy near the resonant frequencies of the vocal tract is increased, and the energy between these frequencies is generally decreased. From the diagrammatic representation i

Disaggregating Health Inequalities Within Rio de Janeiro, Brazil, 2002-2010, by Applying an Urban Health Inequality Index

An urban health index (UHI) was used to quantify health inequalities within Rio de Janeiro, Brazil, for the years 2002-2010. Eight main health indicators were generated at the ward level using mortality data. The indicators were combined to form the index. The distribution of the rank ordered UHI-values provides information on inequality among wards, using the ratio of the extremes and the gradient of the middle values. Over the decade the ratio of extremes in 2010 declined relative to 2002 (1.57 vs. 1.32) as did the slope of the middle values (0.23 vs. 0.16). A spatial division between the affluent south and the deprived north and east is still visible. The UHI correlated on an ecological ward-level with socioeconomic and urban environment indicators like square meter price of apartments (0.54, p \u3c 0.01), low education of mother (-0.61, p \u3c 0.01), low income (-0.62, p \u3c 0.01) and proportion of black ethnicity (-0.55, p \u3c 0.01). The results suggest that population health and equity have improved in Rio de Janeiro in the last decade though some familiar patterns of spatial inequality remain

Reconstruction of Phonated Speech from Whispers Using Formant-Derived Plausible Pitch Modulation

Whispering is a natural, unphonated, secondary aspect of speech communications for most people. However, it is the primary mechanism of communications for some speakers who have impaired voice production mechanisms, such as partial laryngectomees, as well as for those prescribed voice rest, which often follows surgery or damage to the larynx. Unlike most people, who choose when to whisper and when not to, these speakers may have little choice but to rely on whispers for much of their daily vocal interaction. Even though most speakers will whisper at times, and some speakers can only whisper, the majority of today’s computational speech technology systems assume or require phonated speech. This article considers conversion of whispers into natural-sounding phonated speech as a noninvasive prosthetic aid for people with voice impairments who can only whisper. As a by-product, the technique is also useful for unimpaired speakers who choose to whisper. Speech reconstruction systems can be classified into those requiring training and those that do not. Among the latter, a recent parametric reconstruction framework is explored and then enhanced through a refined estimation of plausible pitch from weighted formant differences. The improved reconstruction framework, with proposed formant-derived artificial pitch modulation, is validated through subjective and objective comparison tests alongside state-of-the-art alternatives

Quality Incentives for Federally Qualified Health Centers, Rural Health Clinics and Free Clinics: A Report to Congress

This report to Congress is submitted pursuant to Section 13113(b) of the American Recovery and Reinvestment Act of 2009 (hereafter, the Recovery Act), under Title XIII, also known as the Health Information Technology for Economic and Clinical Health Act or the HITECH Act. The Section requires the Secretary of Health and Human Services to provide a study that examines methods to create efficient reimbursement incentives for improving health care quality in federally qualified health centers, rural health clinics, and free clinics. The report discusses current initiatives and incentives that apply to these categories of primary care clinics and the current knowledge regarding quality of care and the use of health information technology in this sector. Insofar as the report was authorized under the HITECH Act, it particularly addresses issues related to the use of health information technology by these clinics

La plata de la cultura de El Argar del sur de la Península Ibérica: Una primera aproximación a su producción y distribución

More than 700 silver objects are known from the Middle Bronze Age El Argar culture, which contrasts significantly with the rest of Bronze Age Europe, where silver is mostly rare. This has traditionally been explained by the difficulties of extracting silver from complex ores by cupellation and the relative abundance of easily accessible occurrences of native silver and silver chlorides in the south of the Iberian peninsula. However, until now in the Iberian Bronze Age the use of native silver has only been inferred by the absence of evidence of cupellation. The results of trace element analysis of a series of silver objects from several Argaric settlements reveal for the first time positive evidence for the use of native silver. Lead isotope analyses show that hardly any of the objects were made of silver from known and characterised mining districts.Se han documentado más de 700 objetos de plata de la cultura argárica del Bronce Medio. Esta cifra contrasta con la realidad del II milenio AC europeo, donde la plata es muy escasa. Esto se ha explicado tradicionalmente por la dificultad de extraer plata de minerales complejos mediante la técnica de copelación y la relativa abundancia de plata nativa y cloruros de plata fácilmente accesibles en el sur de la Península Ibérica. Sin embargo, hasta ahora, el uso de plata nativa en la Edad del Bronce ibérica se había deducido principalmente por la falta de evidencias de copelación. Los resultados de los análisis de elementos traza de una serie de objetos de plata de varios yacimientos argáricos suministran por primera vez una evidencia positiva del uso de plata nativa. Los análisis de isótopos de plomo demuestran que la mayoría de los objetos no procede de ninguno de los distritos mineros conocidos y caracterizados

Newly Developed and Validated Eosinophilic Esophagitis Histology Scoring System and Evidence that it Outperforms Peak Eosinophil Count for Disease Diagnosis and Monitoring

Eosinophilic esophagitis is diagnosed by symptoms, and at least 15 intraepithelial eosinophils per high power field in an esophageal biopsy. Other pathologic features have not been emphasized. We developed a histology scoring system for esophageal biopsies that evaluates eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells and lamina propria fibrosis. Severity (grade) and extent (stage) of abnormalities were scored using a 4 point scale (0 normal; 3 maximum change). Reliability was demonstrated by strong to moderate agreement among 3 pathologists who scored biopsies independently (p≤0.008). Several features were often abnormal in 201 biopsies (101 distal, 100 proximal) from 104 subjects (34 untreated, 167 treated). Median grade and stage scores were significantly higher in untreated compared to treated subjects (p≤0.0062). Grade scores for features independent of eosinophil counts were significantly higher in biopsies from untreated compared to treated subjects (basal zone hyperplasia p≤0.024 and dilated intercellular spaces p≤0.005), and were strongly correlated (r-square\u3e0.67). Principal components analysis identified 3 principal components that explained 78.2% of the variation in the features. In logistic regression models, 2 principal components more closely associated with treatment status than log distal peak eosinophil count (r-square 17, area under the curve 77.8 vs r-square 9, area under the curve 69.8). In summary, the eosinophilic esophagitis histology scoring system provides a method to objectively assess histologic changes in the esophagus beyond eosinophil number. Importantly, it discriminates treated from untreated patients, uses features commonly found in such biopsies, and is utilizable by pathologists after minimal training. These data provide rationales and a method to evaluate esophageal biopsies for features in addition to peak eosinophil count