Miracle-dz/UniFAR-FTUs huggingface dataset:
A Study of the Relation of Factors of a Sanitary Character to Pellagra Incidence in Seven Cotton-Mill Villages of South Carolina in 1916.

In the spring of 1916 a study was begun of the relation of various factors to pellagra incidence in some representative textile-mill tommunities in South Carolina. On a varying scale the study was continued through 1917 and 1918. The results of ,the first year's (1916) study with respect-to diet2 have already been reported as have also the data relating. to the general incidence3 of the disease'in the population . of the selected mill village& In the present paper we.wish to record the results of the part of this study dealing #ith the relationof sanitation to the incidence' of the disease.
Imaging lifetime and anisotropy spectra in the frequency domain

We report the development of a system combining the capabilities of fluorescence imaging spectroscopy (x, λ, I), fluorescence lifetime (τ) and static and dynamic fluorescence anisotropy (r), enabling the wide‐field measurement of the spectroscopic parameters of fluorophores: (x, λ, I, τ, r). The system employs a frequency domain data collection strategy with a modulated light emitting diode as the light source. A polarization rotator placed in the excitation path after a polarizer allows alternating parallel and perpendicular images to be collected without moving parts. A second polarizer on the emission side serves as the analyzer, leading to estimations of the wavelength‐dependent dynamic anisotropies. The spectrograph has a nominal range of 365–920 nm; however, the light‐emitting diodes and filter sets used in this study restricted the usable range from about 510 to 700 nm. The system was tested on rhodamine 6G (R6G) solutions containing 0, 15, 37, 45, 59, 74 and 91 glycerol. These experiments gave rotational diffusion results comparing favourably with literature values while also demonstrating a trend towards shorter measured lifetimes at high refractive index. The ability of the system to resolve mixtures was tested on mixtures of anti‐human IgG‐FITC (γ‐chain‐specific) and R6G. These fluorophores have similar lifetimes but could be separated using anisotropy parameters. The imaging capabilities of the system were tested on mixtures of fluorescent beads with glycerol solutions of R6G.
Effects of Recombinant α-Interferon-Gelatin Conjugate on in Vivo Murine Tumor Cell Growth

A recombinant human α-interferon A/D (IFN), also known to be effective in mice, was conjugated to gelatin with a water-soluble carbodiimide. The IFN-gelatin conjugate was much more efficient than free IFN in activating mouse peritoneal macrophages (Mφ) in an in vitro experiment to inhibit the growth of IFN-resistant subline cells (RR1) of murine fibrosarcoma. A single i.p. injection of the conjugate administered to normal mice was also more effective than one of free IFN in activating peritoneal Mϕ and natural killer cells in peritoneal exudate cell and spleen cell populations. In the investigation on body distribution of the IFN-gelatin conjugate, an enhanced affinity to Mφ as well as a prolonged retention were observed in comparison with free IFN. An injection of the IFN-gelatin conjugate i.p. was more effective than one of free IFN in suppressing the in vivo growth of not only IFN-sensitive SS2 cells but also RR1 cells in the peritoneal cavity of mice, although RR1 cells were only susceptible to the indirect effect of IFN via host cells, in contrast to SS2 cells. In addition to an increased recruitment of Mφ to the peritoneal cavity in RR1-bearing mice receiving i.p. injection of the IFN-gelatin conjugate, these Mφ were activated to inhibit the in vitro growth of RR1 cells. These results indicate that the IFN-gelatin conjugate is a promising antitumor agent that is much more effective than free IFN. The dose of IFN in the conjugate required for exerting the antitumor effects is much lower than that of free IFN, which leads to a reduction of adverse effects of IFN.
A Mechanism for the Auto-inhibition of Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) Channel Opening and Its Relief by cAMP*

Background: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control electrical activity through tetramerization of an intracellular linker. Results: NMR shows that the apo-cAMP-binding domain (CBD) of HCN4 destabilizes the tetramer through steric clashes. Conclusion: The apo-HCN4 CBD structure is compatible with monomeric and dimeric but not with tetrameric HCN4. Significance: The proposed mechanism explains HCN auto-inhibition and its relaxation by cAMP. Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels control neuronal and cardiac electrical rhythmicity. There are four homologous isoforms (HCN1–4) sharing a common multidomain architecture that includes an N-terminal transmembrane tetrameric ion channel followed by a cytoplasmic “C-linker,” which connects a more distal cAMP-binding domain (CBD) to the inner pore. Channel opening is primarily stimulated by transmembrane elements that sense membrane hyperpolarization, although cAMP reduces the voltage required for HCN activation by promoting tetramerization of the intracellular C-linker, which in turn relieves auto-inhibition of the inner pore gate. Although binding of cAMP has been proposed to relieve auto-inhibition by affecting the structure of the C-linker and CBD, the nature and extent of these cAMP-dependent changes remain limitedly explored. Here, we used NMR to probe the changes caused by the binding of cAMP and of cCMP, a partial agonist, to the apo-CBD of HCN4. Our data indicate that the CBD exists in a dynamic two-state equilibrium, whose position as gauged by NMR chemical shifts correlates with the V½ voltage measured through electrophysiology. In the absence of cAMP, the most populated CBD state leads to steric clashes with the activated or “tetrameric” C-linker, which becomes energetically unfavored. The steric clashes of the apo tetramer are eliminated either by cAMP binding, which selects for a CBD state devoid of steric clashes with the tetrameric C-linker and facilitates channel opening, or by a transition of apo-HCN to monomers or dimer of dimers, in which the C-linker becomes less structured, and channel opening is not facilitated.
Physician-Patient Communication and Physician Satisfaction: Analysis of Physician and Patient Behavioral Characteristics in the Medical Visit

The objective of this dissertation study was to develop a reliable and valid scale, called the Physician Patient Behavioral Characteristics Scale (PPBCS), to assess physician and patient behavioral characteristics that are expressed during the primary care medical visit. Relationships were assessed between PPBCS composite ratings, physician characteristics, visit satisfaction as expressed by both patients and physicians, and rated global affect in audio recordings of the medical visit. The degree to which physician gender and ethnicity was related to physician satisfaction was also examined across levels of patient income/socioeconomic status (SES). Four judges used the PPBCS to objectively rate 298 physician-patient audio recordings from a study originally fielded by the Bayer Institute for Health Care Communication. The PPBCS was shown to have good interrater reliability. Principal components analyses yielded two physician factors, enthusiasm and frustration, and three patient factors, demanding, enjoyable, and nonadherent. Scale composites formed from these factors had good internal consistency. The PPBCS demonstrated empirical validity in correlations of physician and patient factors with patient satisfaction. As expected, physicians who were rated highly on enthusiasm had patients’ who perceived better opportunities for decision-making, better choice in their care, and had more positive perceptions of their physicians’ ability to provide information. Further evidence of validity was revealed from correlations: Enjoyable patients and enthusiastic physicians (as rated on the PPBCS) perceived there to be more effective communication, more patient involvement, and more healthy collaboration in the medical interaction. The PPBCS was also shown to have good convergent validity due to correlations with the zBGRS, another observer-rated measure of patient and physician behavioral characteristics in the medical visit. In general, there were few significant relationships between physician characteristics and PPBCS composites, PSQ, and zBGRS measures. Physicians’ reported level of stress, however, was negatively correlated with assessments of their satisfaction with: the medical visits, the use of time, and with the patient. Analysis of the relationships between physician gender and patient and physician behavioral characteristics revealed female physicians to be more enthusiastic compared to male physicians. Female physicians were also found to be more effective communicators and more engaged in healthy collaboration compared to male physicians. There were no relationships between physicians’ gender-ethnicity group membership and physicians’ satisfaction with patients of different SES, however. Strengths, limitations, and clinical implications of this study were also discussed.
Examination of the Dimerization States of the Single-stranded RNA Recognition Protein Pentatricopeptide Repeat 10 (PPR10)*

Background: PPR (pentatricopeptide repeat) proteins in dimer state can specifically recognize single-stranded RNA. Results: The different amino-terminal lengths and critical point mutations in PPR protein lead to distinct dimerization state of PPR protein. Conclusion: PPR proteins are regulated to adopt different dimerization state. Significance: The biochemical studies advanced our understanding of PPR protein regulations and can facilitate the biotechnological applications of PPR proteins. Pentatricopeptide repeat (PPR) proteins, particularly abundant in plastids and mitochrondria of angiosperms, include a large number of sequence-specific RNA binding proteins that are involved in diverse aspects of organelle RNA metabolisms. PPR proteins contain multiple tandom repeats, and each repeat can specifically recognize a RNA base through residues 2, 5, and 35 in a modular fashion. The crystal structure of PPR10 from maize chloroplast exhibits dimeric existence both in the absence and presence of the 18-nucleotide psaJ RNA element. However, previous biochemical analysis suggested a monomeric shift of PPR10 upon RNA binding. In this report, we show that the amino-terminal segments of PPR10 determine the dimerization state of PPR10. A single amino acid alteration of cysteine to serine within repeat 10 of PPR10 further drives dimerization of PPR10. The biochemical elucidation of the determinants for PPR10 dimerization may provide an important foundation to understand the working mechanisms of PPR proteins underlying their diverse physiological functions.
Confocal bi‐protocol: a new strategy for isotropic 3D live cell imaging

The conventional approach for microscopic 3D cellular imaging is based on axial through‐stack image series which has some significant limitations such as anisotropic resolution and axial aberration. To overcome these drawbacks, we have recently introduced an alternative approach based on micro‐rotation image series. Unfortunately, this new technique suffers from a huge burden of computation that makes its use quite difficult for current applications. To address these problems we propose a new imaging strategy called bi‐protocol, which consists of coupling micro‐rotation acquisition and conventional z‐stack acquisition. We experimentally prove bi‐protocol 3D reconstruction produces similar quality to that of pure micro‐rotation, but offers the advantage of reduced computation burden because it uses the z‐stack volume to accelerate the registration of the micro‐rotation images.
An automatic segmentation algorithm for 3D cell cluster splitting using volumetric confocal images

With the rapid advance of three‐dimensional (3D) confocal imaging technology, more and more 3D cellular images will be available. Segmentation of intact cells is a critical task in automated image analysis and quantification of cellular microscopic images. One of the major complications in the automatic segmentation of cellular images arises due to the fact that cells are often closely clustered. Several algorithms are proposed for segmenting cell clusters but most of them are 2D based. In other words, these algorithms are designed to segment 2D cell clusters from a single image. Given 2D segmentation methods developed, they can certainly be applied to each image slice with the 3D cellular volume to obtain the segmented cell clusters. Apparently, in such case, the 3D depth information with the volumetric images is not really used. Often, 3D reconstruction is conducted after the individualized segmentation to build the 3D cellular models from segmented 2D cellular contours. Such 2D native process is not appropriate as stacking of individually segmented 2D cells or nuclei do not necessarily form the correct and complete 3D cells or nuclei in 3D. This paper proposes a novel and efficient 3D cluster splitting algorithm based on concavity analysis and interslice spatial coherence. We have taken the advantage of using the 3D boundary points detected using higher order statistics as an input contour for performing the 3D cluster splitting algorithm. The idea is to separate the touching or overlapping cells or nuclei in a 3D native way. Experimental results show the efficiency of our algorithm for 3D microscopic cellular images.
EXPERIMENTAL DETERMINATION OF THE INFLUENCE OF ABNORMAL CARDIAC RHYTHMS ON THE MECHANICAL EFFICIENCY OF THE HEART

INTRODUCTION The occurrence of an abnormal cardiac rhythm clinically involves two important and essentially different considerations. First, the information it may give as to the general pathologic condition of the heart and the prognosis of the disease, and second, the mechanical influence it exerts on the pumping action of the heart. The normal heart beat, in which there is a regular succession of auricular systoles within certain rates, each of which is followed after a definite interval by contraction of the two ventricles, is best adapted to the function of the heart as a pump. Anything which seriously interferes with the normal rate or coordination of beats, interferes, to a certain extent, with the mechanical efficiency of the heart. An excessive rate of contraction, even though the regularity and coordination of beats is maintained, reduces the amount of blood pumped by the heart by shortening and rendering insufficient the period
Freeze substitution in 3 hours or less

Freeze substitution is a process for low temperature dehydration and fixation of rapidly frozen cells that usually takes days to complete. New methods for freeze substitution have been developed that require only basic laboratory tools: a platform shaker, liquid nitrogen, a metal block with holes for cryotubes and an insulated container such as an ice bucket. With this equipment, excellent freeze substitution results can be obtained in as little as 90 min for cells of small volume such as bacteria and tissue culture cells. For cells of greater volume or that have significant diffusion barriers such as cuticles or thick cell walls, one can extend the time to 3 h or more with dry ice. The 3‐h method works well for all manner of specimens, including plants and Caenorhabditis elegans as well as smaller samples. Here, we present the basics of the techniques and some results from Nicotiana leaves, C. elegans adult worms, Escherichia coli and baby hamster kidney tissue culture cells.
Long‐term monitoring of live cell proliferation in presence of PVP‐Hypericin: a new strategy using ms pulses of LED and the fluorescent dye CFSE

During fluorescent live cell imaging it is critical to keep excitation light dose as low as possible, especially in the presence of photosensitizer drugs, which generate free radicals upon photobleaching. During fluorescent imaging, stress by excitation and free radicals induces serious cell damages that may arrest the cell cycle. This limits the usefulness of the technique for drug discovery, when prolonged live cell imaging is necessary. This paper presents a strategy to provide gentle experimental conditions for dynamic monitoring of the proliferation of human lung epithelial carcinoma cells (A549) in the presence of the photosensitizer Polyvinylpyrrolidone‐Hypericin. The distinctive strategy of this paper is based on the stringent environmental control and optimizing the excitation light dose by (i) using a low‐power pulsed blue light‐emitting diode with short pulse duration of 1.29 ms and (ii) adding a nontoxic fluorescent dye called carboxyfluorescein‐diacetate‐succinimidyl‐ester (CFSE) to improve the fluorescence signals. To demonstrate the usefulness of the strategy, fluorescence signals and proliferation of dual‐marked cells, during 5‐h fluorescence imaging under pulsed excitation, were compared with those kept under continuous excitation and nonmarked reference cells. The results demonstrated 3% cell division and 2% apoptosis due to pulsed excitation compared to no division and 85% apoptosis under the continuous irradiation. Therefore, our strategy allows live cell imaging to be performed over longer time scales than with conventional continuous excitation.
Juvenile Hormone Prevents 20-Hydroxyecdysone-induced Metamorphosis by Regulating the Phosphorylation of a Newly Identified Broad Protein*

Background: JH antagonizes the 20E pathway. Results: JH induces Broad protein BrZ7 phosphorylation in the lepidopteran insect Helicoverpa armigera. Conclusion: JH induces the phosphorylation of BrZ7 to inhibit 20E-mediated metamorphosis. Significance: Our study reveals a mechanism of JH antagonizing 20E-activating metamorphosis. The steroid hormone 20-hydroxyecdysone (20E) initiates insect molting and metamorphosis. By contrast, juvenile hormone (JH) prevents metamorphosis. However, the mechanism by which JH inhibits metamorphosis remains unclear. In this study, we propose that JH induces the phosphorylation of Broad isoform Z7 (BrZ7), a newly identified protein, to inhibit 20E-mediated metamorphosis in the lepidopteran insect Helicoverpa armigera. The knockdown of BrZ7 in larvae inhibited metamorphosis by repressing the expression of the 20E response gene. BrZ7 was weakly expressed and phosphorylated during larval growth but highly expressed and non-phosphorylated during metamorphosis. JH regulated the rapid phosphorylation of BrZ7 via a G-protein-coupled receptor-, phospholipase C-, and protein kinase C-triggered pathway. The phosphorylated BrZ7 bound to the 5′-regulatory region of calponin to regulate its expression in the JH pathway. Exogenous JH induced BrZ7 phosphorylation to prevent metamorphosis by suppressing 20E-related gene transcription. JH promoted non-phosphorylated calponin interacting with ultraspiracle protein to activate the JH pathway and antagonize the 20E pathway. This study reveals one of the possible mechanisms by which JH counteracts 20E-regulated metamorphosis by inducing the phosphorylation of BrZ7.
Pushing the resolution limits in cryo electron tomography of biological structures

Cryo electron tomography is a three‐dimensional imaging technique that is suitable for imaging snapshots of the structural arrangements of biomolecular complexes and macromolecules, both in vitro and in the context of the cell. In terms of attainable resolution, cryo electron tomographic reconstructions now show resolvable details in the 5–10 nm range, connecting optical microscopy with molecular imaging techniques. In view of the current developments in super‐resolution light microscopy and correlative light and electron microscopy, cryo electron tomography will be increasingly important in structural biology as a tool to bridge light microscopy with molecular imaging techniques like NMR, X‐ray diffraction and single particle electron microscopy. In cell biology, one goal, often referred to as visual proteomics, is the molecular mapping of whole cells. To achieve this goal and link cryo electron tomography to these high‐resolution techniques, increasing the attainable resolution to 2–5 nm is vital. Here, we provide an overview of technical factors that limit the resolution in cryo electron tomography and discuss how during data acquisition and image processing these can be optimized to attain the highest possible resolution. Also, existing resolution measurement approaches and current technological developments that potentially increase the resolution in cryo electron tomography are discussed.
The prevalence of obesity as indicated by body mass index among apparently healthy adults living in Aba, Abia State, Nigeria

The aim of this study is to determine the prevalence of obesity using BMI and to assess the relative associations with some cardiovascular risk factors (CVD). Subjects for this study were apparently healthy volunteers who willingly granted their informed consent. They reported at the various study zones of the town after an over-night fast where their weights (in Kg), heights (in Metres), and blood pressures (mm Hg) were measured and recorded. Blood samples were also collected via venipuncture for serum lipid profile studies. The data obtained were analysed using the Statistical Package for Social Sciences (SPSS). The student t-test was used and p ≤ 0.05 was considered as statistically significant. The results showed that the prevalence of obesity as determined by BMI ≥ 30kg/m 2 was 16.56%. Obesity was more prevalent among the subjects older than 40 years and among females than males (p<0.05). BMI appeared to be significantly associated with CVD risks factors. Thus, healthier eating and increase physical activities are strongly encouraged to reduce the increasing prevalence of obesity and the associated CVD risk burden. Key words: Prevalence, BMI, Obesity, Aba, Nigerians
Magnetic resonance imaging pattern in natalizumab‐associated progressive multifocal leukoencephalopathy

Natalizumab is an effective treatment for patients with multiple sclerosis (MS) that is associated with a risk of progressive multifocal leukoencephalopathy (PML). Recommendations were published in 2006 to improve early diagnosis of PML using magnetic resonance imaging (MRI). However, due to the small number of MS patients initially diagnosed with PML, the imaging criteria could only be derived from PML lesions in patients with human immunodeficiency virus. Therefore, there is an urgent need to assess the MRI characteristics of PML in MS patients to update the existing recommendations.