Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunohistochemical evaluation of HER-2/neu expression in infiltrating breast carcinoma: a study of reproducibility.

OBJECTIVE To determine interobserver and intraobserver reproducibility in the assessment of the HercepTest- and TAB250-immunostained slides. STUDY DESIGN Three independent expert pathologists (two with and one without training in HercepTest assessment) evaluated the HercepTest and TAB250-immunostained slides of 108 infiltrating breast carcinomas with a triple-blind method. The evaluation was repeated, with the same method and sequence of view, after 60 days. RESULTS Expert pathologists, after adequate training in HercepTest evaluation, could reach excellent interobserver (K=.911, P<.001) and intraobserver reproducibility (K of .863-.926; P <.001 for all). The percentage of disagreement in intraobserver reproducibility ranged from 0.9% to 3.7%. Interobserver and intraobserver reproducibility in the evaluation of TAB250-immunostained slides was good (K = .658, P < .001) and from good to excellent (K of .600-.895, P < .001 for all), respectively. CONCLUSION Optimization of the level of accuracy in HercepTest evaluation is mandatory because the decision to initiate therapy with Herceptin depends on the result. Moreover, considering that the percentage of disagreement in intraobserver reproducibility ranges from 0.9% to 3.7%, it is advisable that two expert pathologists evaluate all HercepTest slides with a double-blind method. If there are discordant results, they must be discussed by the same pathologists.
A peptide vaccine that prevents experimental autoimmune myasthenia gravis by specifically blocking T cell help

Myasthenia gravis (MG) and its animal model, experimental autoimmune (EA) MG, are caused by T cell‐dependent autoantibodies that react with the nicotinic acetylcholine receptor (AChR) on muscle and interfere with neuromuscular transmission. Thus, selective inactivation of CD4+ AChR‐specific T helper cells should lower AChR Ab levels and ameliorate disease. In the Lewis rat model of EAMG, a chain residues 100–116 of the AChR represent the dominant T cell epitope, which is important in helping Ab responses to this autoantigen. In the present report, we have applied a new design technique that requires no knowledge of Ag receptor sequences on errant T cells in order to develop a synthetic peptide vaccine against T cells reactive with the aforementioned T cell epitope. Immunization with the peptide 1) induced polyclonal and monoclonal Ab, which inhibited AChR 100–116 stimulation of AChR‐sensitized lymphocytes and recognized Vβ15 containing T cell receptors on AChR 100–116‐specific T cell lines and clones; 2) lowered AChR Ab levels; 3) reduced the loss of muscle AChR; and 4) lessened the incidence and severity of EAMG. These findings suggest a new strategy for the functional abrogation of epitope‐specific T cells that could have potential application to human autoimmune diseases. —Araga, S. , Xu, L. , Nakashima, K. , Villain, M. , Blalock, J. E. A peptide vaccine that prevents experimental autoimmune myasthenia gravis by specifically blocking T cell help. FASEB J. 14, 185–196(2000)
Comment on “Drought-Induced Reduction in Global Terrestrial Net Primary Production from 2000 Through 2009”

Zhao and Running (Reports, 20 August 2010, p. 940) reported a reduction in global terrestrial net primary production (NPP) from 2000 through 2009. We argue that the small trends, regional patterns, and interannual variations that they describe are artifacts of their NPP model. Satellite observations of vegetation activity show no statistically significant changes in more than 85% of the vegetated lands south of 70°N during the same 2000 to 2009 period.
Harnessing Human Dendritic Cell Subsets to Design Novel Vaccines

Dendritic cells (DCs) orchestrate a repertoire of immune responses that endow resistance to infection and tolerance to self. DC plasticity and subsets are prominent determinants of the quality of elicited immune responses. Different DC subsets display different receptors and surface molecules and express different sets of cytokines/chemokines, all of which lead to distinct immunological outcomes. Recent findings on human DC subsets and their functional specialization have provided insights for the design of novel human vaccines.
Analysis of the factors influencing the private cost of teacher education in South-South Nigeria

The study analyzed the factors that influence private cost of teacher education in public tertiary institutions in South-South Nigeria in 2014/2015 academic session. The aim was to determine the actual private unit cost of teacher education as well as the factors influencing it and their level of impact on private cost. The ex-post-facto research design was adopted for the study. The population consisted of all federal and state tertiary institutions offering teacher education programme. The sample was 2030 respondents drawn from twelve out of the twenty such institutions in the South-South Nigeria using the purposive and proportional stratified random sampling techniques. The instrument used was an inventory titled (PCTEI) which was duly validated. The research questions were analyzed using descriptive statistics, while the hypotheses were analyzed using the z-test for independent samples and multiple regression statistics at 0.05 level of significance. It was discovered that private cost of teacher education was higher in state tertiary institutions than their federal counterparts, while the private cost of university students was higher than the college of education counterparts. The study also revealed that factors such as type of institutions, gender, programme of study, level of study, place of students’ residence and ownership status of institutions influence private cost. The study further revealed that the type of programme had a greater influence on the private cost than the other factors, while the programme of study made the least impact. Consequently, it was recommended among others that bursary awards, increased accommodation facilities and functional libraries be provided for students especially in state owned institutions to ameliorate their private cost burden.
A Feature-Based Knowledge Transfer Framework for Cross-Environment Activity Recognition Toward Smart Home Applications

Building contextual models for new “smart” environments is not considered cost effective if data for model training must be collected from scratch. It is more practical to transfer as much learned knowledge as possible from an existing environment to the new target environment in order to reduce the data collection effort. In order to reuse learned knowledge from an original environment, this study proposed a feature-based knowledge transfer framework. The framework makes use of transfer learning, which relaxes the constraint requiring model training and testing datasets to be highly similar in distribution. Experimental results show that this framework can successfully help extract and transfer knowledge between two different smart-home environments. Models trained via the proposed framework can even outperform nontransfer-learning models by up to 8% in accuracy. Finally, the flexibility of the proposed framework enables used as a test bed for evaluating different methods and models in order to improve the service quality of human-centric context-aware applications.
The Abilities Of Very Low‐Birthweight Children And Their Classroom Controls

Forty‐three children born in the Nottingham area in 1981 and weighing >1501g who had received treatment in the neonatal intensive care unit were followed up on entry to primary school at the age of five years. All were apparently normal, with no observable handicap or need for special educational provision. Their results on the McCarthy Scales of Children's Abilities were compared with those of closely matched classmates and significant differences were found between the two groups on all six scales, most markedly on the General Cognitive Index.
Differential Effects of Fetal Number and Maternal Nutrition in Late Gestation on Prolactin Receptor Abundance and Adipose Tissue Development in the Neonatal Lamb

The present study examined the extent to which abundance of the prolactin receptor (PRLR) and a range of primary mitochondrial proteins are influenced by either maternal nutrition and/or fetal number in adipose tissue. Pregnant sheep were control fed [consuming 100% of total metabolizable energy (ME) requirements (taking into account requirements for both ewe maintenance and growth of the conceptus to produce a 4.5-kg lamb at term) for that stage of gestation] or were nutrient restricted (consuming 60% of total ME requirements). All ewes lambed normally at term and both perirenal adipose and hepatic tissues were sampled within 6 h of birth. Plasma membranes and mitochondria were prepared and analyzed using immunoblotting for abundance of PRLR and/or cytochrome c, voltage-dependent anion channel (VDAC), and uncoupling protein-1 (UCP1). Irrespective of maternal nutrition, abundance of specific isoforms of PRLR were significantly higher in adipose tissue sampled from twins compared with singletons and total UCP1 concentration per milligram of tissue was increased (p < 0.05). There was no effect of fetal number on PRLR abundance in the liver. Maternal nutrient restriction resulted in an increased abundance of both cytochrome c (p < 0.001) and VDAC in adipose tissue of twins but not singletons. This occurred despite maternal nutrition having no effect on either lamb body or adipose tissue weights, although both were lower (p < 0.05) in twins compared with singletons. In conclusion, fetal adipose tissue development is highly sensitive to nutritionally mediated changes in late gestation. An increase in fetal number results in greater PRLR abundance, which, in conjunction with a decrease in maternal nutrition, results in up-regulation of specific mitochondrial proteins.
Anatomical variations of the right coronary artery may be a source of difficult block and conduction recurrence in catheter ablation of common-type atrial flutter.

AIMS Although Eustachian valves and recesses have been related to resistance to block, the effect of convective cooling by the right coronary artery (RCA) has not been evaluated in the clinical setting. METHODS AND RESULTS The distance and course of the RCA in relation to the cavotricuspid isthmus (CTI) in addition to variants of CTI anatomy and the presence of Eustachian valves were analysed from computed tomography scans of 54 patients. Ablation power was titrated using a step-up protocol. Invasive follow-up was available for 34 patients. The RCA came closest to the CTI inferiorly separated by a mean of 5.3 ± 2.5 mm compared with 7.3 ± 3.3 mm septally and 5.7 ± 2.3 mm anteriorly (P < 0.01). The maximum power required for CTI block correlated inversely with the distance of the RCA to the CTI, whereas the cumulative energy was highest in the presence of recesses. Neither failure of acute block nor a higher rate of conduction recurrence could be attributed to variants of CTI anatomy or the presence of a Eustachian valve. Using multivariate analysis, a position of the RCA underneath the central part of the CTI was the only significant predictor for late conduction recurrence. These patients showed a 2.7 mm larger distance of the RCA to the tricuspid valve plane (P = 0.05). CONCLUSION The RCA affects CTI ablation as higher power settings are required at closer distances to the ablation site. Late conduction recurrences were observed in patients with a variation of the RCA, leaving the atrioventricular groove towards the atrial aspect.
Directional shape complementarity at the protein–DNA interface

Nature utilizes various styles of architecture for DNA‐binding proteins to recognize diverse DNA sequences, a process facilitated by a complementary surface between protein and DNA. However, the extent and ways this ‘shape complementarity’ occurs at the protein–DNA interface have yet to be characterized. Here, by analyzing a set of diverse protein–DNA complexes of known three‐dimensional structures, we investigated whether the normal vectors of a protein surface at the interface exhibited any relationship with DNA conformation. Generally, the normal vectors of a DNA‐contacting protein surface distinctly preferred certain angles, enabling them to align with certain axes characterizing the conformation of DNA. Thus, a new geometric property of DNA‐binding protein is demonstrated, i.e. the ‘shape complementarity’ of protein–DNA recognition clearly bears the property of ‘directionality’. Copyright © 2003 John Wiley & Sons, Ltd.
Overcoming resistance to existing therapies in HIV‐infected patients: The role of new antiretroviral drugs

Resistance to available antiretroviral (ARV) agents is of increasing concern, and development of novel agents that address this problem has been identified as a major public health priority. As ARV resistance becomes more prevalent with extended use of existing agents, individuals with HIV infection resistant to all three traditional classes of ARVs, nucleoside reverse transcriptase inhibitors (NRTIs), non‐nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), find themselves increasingly limited with regard to effective treatment options. The need for tolerable new drug regimens that effectively suppress viral replication while being simple to adhere to is increasingly pressing. This article reviews the epidemiology of antiretroviral drug resistance, the factors that contribute to the emergence of resistance, and presents data that support the need for early detection of resistance and maximal virologic suppression in order to delay treatment failure and reduce mortality. Healthcare providers are encouraged to optimize therapy through the use of new agents from existing drug classes, which can minimize cross‐resistance, as well as agents with novel mechanisms of action, in order to realize the potential for greater viral containment and to forestall development of resistance mutations. This article evaluates several emerging therapies that are in late‐stage clinical development and promise to expand treatment options for highly treatment‐experienced patients with the goal of improving outcomes for HIV‐infected individuals whose options for sustained antiviral efficacy are increasingly limited. J. Med. Virol. 80:565–576, 2008. © 2008 Wiley‐Liss, Inc.
Structure, spectroscopic, and redox properties of Rhodobacter sphaeroides reaction centers bearing point mutations near the primary electron donor.

Single mutations of three amino acid residues in the vicinity of the primary electron donor, P, in the reaction center (RC) from Rhodobacter (Rb.) sphaeroides were constructed and characterized in order to study the effects of hydrogen-bonding on the physical properties of P. The mutations, Phe M197-->Tyr, Met L248-->Thr, and Ser L244-->Gly, represent single amino acid changes near P designed to introduce residues found in Rhodopseudomonas (Rps.) viridis and to, thus, probe the effects of nonconserved residues. The mutations were designed to change the nonconserved H-bonding interactions of P in Rb. sphaeroides, at the level of a C2 acetyl, a C9 keto, and a C10 ester carbonyl of P, respectively, to those present in Rps. viridis. The Fourier transform (pre)resonance Raman (FTRR) spectra of P, in its reduced and oxidized states, from reaction centers of these mutants were studied to determine modifications of H-bond interactions of the pi-conjugated C2 acetyl and C9 keto carbonyl groups and the C10 carbomethoxy ester carbonyl groups of P. The vibrational spectra of reduced P in the Met L248-->Thr and Ser L244-->Gly mutants reveal no evidence for changes in the H-bonding pattern of P; this suggests that for Rb. sphaeroides wild type, Ser L244 is not H-bonded to the C10 ester carbonyl of PL. The vibrational spectrum of reduced P from the Phe M197-->Tyr mutant compared to that of wild type can unambiguously be interpreted in terms of the formation of a new H-bond with an acetyl carbonyl of P, specifically PM. Correlating with the new H-bond, the Phe M197-->Tyr mutant exhibits an electronic absorption spectrum where the P absorption band is significantly perturbed. Intact cell and chromatophore photobleaching spectra of the same mutant indicate that the P absorption band has red-shifted by ca. 10 nm; no such behavior is observed for the other mutants. As well, the P-->BPheL electron transfer rate does not seem to strongly depend on the H-bonding of the C2 acetyl carbonyl of PM to a tyrosine residue. The EPR zero-field splitting parameters, E and D, of the primary donor triplet are only slightly modified in the mutant reaction centers, on the order of 1%. (ABSTRACT TRUNCATED AT 400 WORDS)
Evidence of a Monosynaptic Pathway Between Cells of the Ventromedial Medulla and the Motoneuron Pool of the Thoracic Spinal Cord in Rat: Electron Microscopic Analysis of Synaptic Contacts

Previous electrophysiological and anatomical data have suggested the existence of a descending pathway from the ventromedial medulla into the thoracic motoneuron pool. However, systematic light and electron microscopic analysis have not yet been done to reveal such a projection. In the present study, the anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA‐L) was injected into several discrete regions of the medioventral medulla and descending PHA‐L‐labelled axons were investigated in the thoracic ventral horn using both light and electron microscopy. Light microscopic analysis of descending projections from 20 distinct areas of the medioventral medulla showed that neurons that project predominantly to the intermediate and ventral regions of the thoracic spinal grey matter are located caudal to the facial nucleus. Monosynaptic contacts were found between axons originating from five distinct regions of the medioventral medulla (containing raphé and/or gigantocellular reticular neurons) and cells in the thoracic motoneuron pool. PHA‐L‐labelled boutons formed synaptic contacts with large calibre dendrites and with somata. Seventy‐two per cent of the investigated 32 boutons appeared to have symmetrical synaptic membrane specializations. The majority of the boutons contained only small, pleomorphic vesicles. Our findings show the existence of a direct monosynaptic pathway between the neurons of the ventromedial medulla and thoracic motor nuclei, providing anatomical support for previous physiological data.
Cause of death in men diagnosed with prostate carcinoma

Prostate carcinoma is one of the leading causes of death in men. Although the mortality rate is high, it still may underestimate the number of deaths associated with the disease. This study was conducted to compare causes of death among men previously diagnosed with prostate carcinoma and to examine the extent to which differences in cause of death (death from prostate carcinoma vs. death from other causes) varied by age, race, clinical factors, and comorbid conditions.
[Effects of BNP preconditioning on myocardial cell apoptosis and expressions of bcl-2 and Bax during myocardial ischemia-reperfusion injury in rats].

OBJECTIVE To study the effects of B-type natriuretic peptide (BNP) preconditioning on the apoptosis and expressions of Bcl-2 and Bax in rat cardiomyocytes during myocardial ischemia-reperfusion. METHODS Twenty-one male Sprague-Dawley rats weighing (250 ± 50) g were randomly divided into 3 groups of sham operation (SHAM), ischemia-reperfusion (I/R) and B-type natriuretic peptide (BNP). A rat model of in vivo myocardial ischemia-reperfusion injury was established by ligating the left anterior descending coronary artery for 35 minutes and then reperfusing for 240 minutes. The apoptosis of myocardial cell was determined by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end-labeling (TUNEL) method. Real-time polymerase chain reaction and Western blot were used to detect the expression changes of Bcl-2 and Bax in rat ischemia myocardium. RESULTS The apoptotic indices of SHAM, BNP and I/R groups were 5.4% ± 4.2%, 22.5% ± 9.5% and 45.2% ± 13.0% respectively (P < 0.05). The Bcl-2 protein expression of SHAM, BNP and I/R groups were 0.87 ± 0.09, 0.70 ± 0.07 and 0.38 ± 0.09 respectively (P < 0.05). The Bax protein expression of SHAM, BNP and I/R groups were 0.08 ± 0.04, 0.39 ± 0.09 and 0.71 ± 0.18 respectively (P < 0.01). The Bcl-2/Bax mRNA ratio of SHAN, BNP and I/R groups were 0.763 ± 0.154, 0.099 ± 0.025 and 0.022 ± 0.024 respectively (P < 0.05). CONCLUSION The BNP preconditioning can decrease the myocardial apoptosis induced by ischemia-reperfusion injury. The mechanisms may be associated with an elevated expression of Bcl-2, an increased ratio of Bcl-2/Bax and a lowered expression of Bax.
Outcome of a web-based mindfulness intervention for families living with mental illness – A feasibility study

ABSTRACT Background: Families living with a person with mental illness can experience distress requiring therapeutic interventions. Web-based mindfulness interventions have shown beneficial health outcomes for both clinical and healthy populations, and may help families cope and overcome barriers that can otherwise hinder a help-seeking process. Aims: To develop and assess outcomes of a web-based mindfulness intervention for families living with a person with mental illness. Methods: A pilot study investigating an 8-week web-based mindfulness intervention with a pre–post design and follow-up after 3 months, with mindfulness as the primary outcome and perceived stress, caregiver burden and self-compassion as secondary outcomes. The study included a sample of 97 persons approached by advertisement in newspapers, newsletters, and online. Results: The study showed significant improvements in levels of mindfulness post-intervention and at follow-up as well as significant improvements in levels of perceived stress, caregiver burden, and self-compassion both post-intervention and at follow-up. Discussion: Acceptability and feasibility of the intervention were high, outcomes were relevant, and the intervention showed positive and significant results supporting the hypothesis that the intervention may help families cope with a stressful situation. Conclusion: Further randomized controlled studies of the intervention are needed to investigate the intervention’s effectiveness, including dose-effect studies.