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To describe effects of season on milk production in Holstein dairy cows and to determine the location and effectiveness of fans and sprinklers in the management of stress attributable to season.Longitudinal observational study.141 dairy herds for which owners used the Dairy Herd Improvement Association's database for production and reproduction record keeping.Owners were interviewed to identify location of fans, shade structures, and sprinklers. Production and reproduction data were retrieved from the database, and a mixed model ANOVA was used to estimate effects of season, parity, and use of sprinklers, and fans on milk production.Daily peak milk production decreased for all parity groups in the summer, but the effect decreased with increasing days in lactation. Use of sprinklers increased peak milk production in parity-1 and -3 or higher cows, but use of fans did not significantly alter effects of season. After calving in the summer, 305-day milk production decreased in parity-2 and -3 cows. This decrease was not significantly modified by the presence of sprinklers or fans.Use of sprinklers may increase peak milk production in high-producing cows and could be recommended for reducing heat and total stress during this time. Production-oriented veterinarians should be cautious when recommending use of sprinklers and fans to increase production because of the wide confidence intervals describing their effectiveness. Management of parity-2 or higher cows so that they calve from October to June could increase 305-day milk production.

In this paper we present a novel scheme for modelling and tracking complex real life objects. The scheme uses multiple models based on a variation of the point distribution model known as the vector distribution model. Inter and intra-class variation is separated using a variation on linear discriminant analysis known as `Delta Analysis'. The tracking scheme is stochastic and is based on modelling model characteristics by a set of discrete probability distributions, which are updated in an iterative manner. Initialisation is performed using low level processing and a predictor is used to initialise characteristic probabilities on subsequent frames. This scheme has been applied to the task of tracking livestock in a realistic farmyard situation. (7 pages)

Tumour necrosis factor (TNF) is a cytokine with multiple biological activities which plays a pivotal role in the response of the body to infection. TNF is secreted in the the monomeric form and associates to yield a biologically active oligomeric molecule. Bioactive TNF can be measured in plasma using cytotoxic assays which employ the murine cell-lines L929 or WEHI 164 clone 13. However, it has become clear that inactive TNF also circulates in vivo, which is not detected by bioassay. These inactive forms may play an important role in the regulation of TNF activity. The rat is often used as a model for the study of acute infection and its systemic effects. Our aim was to develop an ELISA for rat TNF which would provide a convenient and cost effective method of assay. The assay employs two commercially available antibodies raised against recombinant murine TNF (rMuTNF) which exhibit cross-reactivity with rat TNF. The lower limit of detection for this assay was determined to be 39.0 pg/ml rMuTNF. The inter and intra-assay coefficients of variation were12.0%. Specificity of the assay was shown by the high degree of parallelism obtained between rMuTNF and commercially available rRatTNF. The assay described measures rat TNF in both plasma and tissue culture supernatant. The measurement of plasma concentrations of TNF using both the ELISA and bioassay may help elucidate more fully the biological importance of TNF.

Validation of evaluation methods is necessary in order to appropriately monitor Patellofemoral Pain Syndrome (PFPS) patients and to determine the effectiveness of treatment and prevention programs. The goal of this study was to investigate the psychometric properties of five evaluation methods: a functional index questionnaire (FIQ), visual analogue scales (VAS) for pain, a patellofemoral function scale (PFS), a step test and a subjective report of functional limitations. Measurements for each of the six components were taken on 56 PFPS patients participating in a randomized clinical trial, prior to and at one month following treatment. Modest test-retest reliability for the FIQ, VAS and step test were found. High internal consistency for the FIQ and modest internal consistency for the PFS were demonstrated. The VAS and FIQ were found to be good discriminators for measuring clinical change, while the step test was found to be reliable but poor at detecting clinical change. The PFS, which combines a number of evaluation areas into an index, demonstrated potential to detect clinical change, however, conclusions are limited as reliability testing was not performed.

Mutation hotspots have been a staple of mutation spectra since the introduction of fine structure mutation mapping almost 40 years ago. It has been well established that sequence context is an important determinant of mutational activity at mutagen induced hotspots and coldspots. However, our understanding of the sequence effectors of base substitution hotspots is quite limited. This is because manipulation of the sequence about a hotspot site in a marker gene is restricted by the need to maintain a functional marker. In this work, we describe a generalizable system for studying sequence context effects on mutagenesis. We have prepared a variant of the supF tRNA gene (a marker used by us in previous studies) in which an eight-base palindrome, the site of two UV hotspots in the interior of the gene, was copied into the acceptor stem and pre-tRNA region. The variant tRNA was active. The UV mutation spectrum of this variant showed that the new copy of the palindrome generated two hotspots which were as intense as the original sites in the interior of the gene. Variant genes were constructed with all possible bases at the first position in the palindrome in the pre-tRNA sequence, which does not affect tRNA function. The mutation analysis showed that activity at one of the hotspots could be reduced or enhanced by the changes, while activity at the other site was not significantly affected. The base changes did not influence the frequency of cyclobutane dimer or (6-4) photoproduct formation at the two hotspot sites. Thus, the changes in mutational activity were due to the influence of sequence context on the efficiency of mutation formation at the sites of UV lesions.

Background Naive CD4+ T cells can differentiate into different subsets. Whereas transcriptional regulation of CD4+ T cells is well studied, posttranscriptional control by RNA binding proteins (RBPs) and microRNAs is poorly understood. CD4+ Th2 mediated diseases such as allergen-induced asthma, are driven by GATA-3, IL-4 and IL-13. The RBP, HuR, has been shown to posttranscriptionally regulate many early response genes, including IL-4 and IL-13. GATA-3 contains AU-rich elements (ARE) in its 3’ untranslated region (UTR) which are binding sites for HuR. We first identified GATA-3, IL-4 and IL-13 as HuR targets using RIP-Chip (RNA immunoprecipitation applied to microarrays). We hypothesized that HuR may be coordinately regulating Th2 differentiation.

Changes in scrotal sonograms and semen quality were monitored in 26 bulls with idiopathic scrotal hydrocele over a 4-month period. After 120 days, scrotal hydrocele had resolved (ultrasonographically, fluid was not detectable within the vaginal process) in 85% (22/26) of the bulls. Percentage of bulls with unilateral scrotal hydrocele that resolved was higher than that for bulls with bilateral hydrocele (94 vs 62.5% or 17/18 bulls vs 5/8 bulls, respectively). After 120 days, 77% (20/26) of the bulls passed a breeding soundness evaluation. At 90 days, semen quality was satisfactory in more of the bulls with unilateral disease (9/18) than with bilateral disease (1/8). The finding of multifocal echodensities in the testicular parenchyma was not correlated with a poor breeding soundness score or with a high number of spermatozoal abnormalities. The prognosis for full recovery in bulls with scrotal hydrocele likely depends on the severity and duration of the condition.

The evaluation of different design criteria to improve the performance of a rural distribution network requires a broad approach to be taken in comparing technical improvements that could be implemented, with the corresponding benefits obtained. This paper describes the examination of an existing rural 11 kV network in Northern Ireland in need of improvement in performance. The basic improvement aims are to halve (i.e. improve) the reported overall security and availability indices and to ensure that the security and availability on any particular circuit are maintained within a specified upper limit. The approach adopted was to model the performance of selected circuits, compare predicted performance with actual historical performance and provide a quantitative assessment of individual and combined improvement measures. >

Breast cancer is one of the most prevalent cancers worldwide. Distance metastasis is responsible for patient mortality. Therefore, understanding the mechanisms underlying tumor pathogenesis and metastasis is crucial for the development of novel therapies as well as preventive strategies for those who are prone to breast cancer. In contrast to transcriptional gene regulation, posttranscriptional control mechanisms of gene expression are poorly understood. Yet, many metastasis genes are regulated by RNA binding proteins (RBPs) at the levels of mRNA stability and translation. The paraneoplastic antigen, HuR, is an RBP shown to regulate multiple genes that are significantly related to breast cancer metastasis by stabilizing target mRNAs and facilitating translation into proteins. Using novel techniques developed in our lab of RNA immunoprecipitation applied to microarrays (RIP-Chip) we identified novel discrete HuR-associated mRNAs in triple negative breast cancer and estrogen receptor positive breast cancer. Many of these HuR-associated mRNA transcripts were metastasis related. We investigated the role of HuR in an aggressive triple-negative breast cancer metastatic cell line, LM2. The LM2 cells were retrovirally transduced with triple fusion reporter construct encoding thymidine kinase1, GFP and firefly luciferase to obtain in vivo and in vitro tracking capabilities. The cells were further transfected with plasmid containing HA-HuR or empty vector control to demonstrate the function of HuR in LM2. HuR over-expressing clones showed greater metastatic capability by in vitro matrigel invasion assay. Furthermore, athymic mice that were intravenously injected with HuR over-expressing LM2 cells had greater (335-fold more) tumor metastasis to the lungs than empty vector control injected group as measured by IVIS imaging. Mice injected with HuR over-expressing LM2 cells were more moribund and had greater mortality as compared with mice injected with empty vector control cells. These results suggest that HuR may play a role in breast cancer metastasis by stabilizing various pro-metastatic genes. The implications of this work are twofold. First, HuR RIP-Chip can be used to identify novel cancer relevant genes and second, interference with HuR function may ameliorate distant metastasis in breast cancer, potentially providing new therapeutic approaches for treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A27.

e21071 Background: Accurate stratification of patients prior to treatment with combination chemotherapy would allow non-responders to receive an alternative treatment in a timely manner and potenti...

Breast cancer is the second most common cancer among women worldwide. It is estimated that approximately one million women are diagnosed with breast cancer annually. Furthermore, more than 410,000 women will die each year from the disease primarily due to tumor metastasis. Currently, even the most effective treatments often result in recurrence and metastasis, in part due to genetic factors. Therefore, understanding the mechanism of breast cancer related gene regulation is crucial for the development of novel treatments and preventive strategies to those who are predisposed to developing breast cancer. Previously, we have shown that the RNA-binding protein HuR posttranscriptionally regulates various proto-oncogenes by stabilizing their mRNAs and facilitating their translation into proteins. Additionally, HuR upregulation and cytoplasmic localization has been associated with invasive cancer progression and poor prognosis. HuR has been described to control genes in multiple areas of the acquired capabilities model of cancer and has been hypothesized to be a tumor-maintenance gene, allowing for cancers to proliferate once they are established. HuR regulates genes involved in angiogenesis, cell growth and cell cycle regulation including VEGFα, TSP1, HIF1α, CDKN1A(p21) and β-catenin. In this study, we investigated the role of HuR in an aggressive triple-negative (estrogen receptor ER-, human epidermal growth factor receptor 2 (HER2)- and progesterone receptor (PR)-) breast cancer cell subline LM-2. The LM-2 cells were derived from triple-negative breast cancer cells MDA-MB-231 which were isolated from two rounds of in vivo selection of the cancer cells which metastasized to the lungs. The LM-2 cells were retrovirally transduced with triple-fusion protein reporter construct encoding thymidine kinase1, green fluorescent protein (GFP) and firefly luciferase in order to obtain nuclear imaging, fluorescent and bioluminescent properties for in vivo and in vitro tracking. LM2 cells were further transfected with a plasmid containing HA-HuR or empty vector control to investigate the function of HuR in LM2 cells. Two clones of HuR overexpressing LM2 cells were shown to grow faster in vitro compared to the empty vector control. Also, HuR overexpression significantly facilitates tumor invasion in vitro by matrigel invasion assay. Further analysis of HuR overexpressing LM2 cells using in vivo imaging system (IVIS) will reveal the role of HuR in breast cancer growth and metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3084. doi:10.1158/1538-7445.AM2011-3084

Traditional microarray analysis has uncovered a variety of genes involved in diseases such as asthma. However, it may potentially miss important genes due to the discordance between steady state mRNA levels and protein products. Posttranscriptional events conferred by RNA binding proteins (RBPs) contribute to this phenomenon. We have developed novel techniques known as RIP-on-Chip (microchip) which allow for the immunoprecipitation and identification of in vivo mRNA targets bound to RBPs. We study the RBP HuR, which regulates many early response genes including cytokines and chemokines. Using RIP-on-Chip, HuR has been demonstrated to associate and regulate many asthma relevant genes including recently identified genes IL-4 and IL-13. We have extended this assay to solid organ tissues. Employing the standard ovalbumin model of allergic airway inflammation, coupled to genome-wide arrays (47,000 genes) we have identified in vivo HuR targets in lungs of naïve, alum only or ova challenged mice. Remarkably, there are only 12 HuR targets (2 fold or greater) up regulated in ova and alum immunized over alum alone mice. Some are known HuR target genes such as TLR4 and IL-13; others are potentially novel asthma genes. Furthermore, we have created a transgenic mouse which over expresses HuR in CD4+ T cells. In the allergic airway inflammation model these mice have an increase in lung lymphocyte infiltration when compared to wild-type littermates, further implicating coordinate posttranscriptional gene regulation and HuR in allergic airway inflammation.

Previous studies strongly suggest that adenosine receptors on juxtaglomerular cells function to restrain the secretion of renin induced by a variety of stimuli. The clinical significance of this is that caffeine, a widely consumed adenosine receptor antagonist, could augment renin release responses to diseases such as renovascular hypertension, liver cirrhosis and heart failure and to therapeutic maneuvers such as salt restriction, diuretics and vasodilators. Caffeine may be particularly troublesome in this regard because this methylxanthine has central nervous system effects and intracellular actions that also might contribute to the overall ability of caffeine to potentiate renin secretion. The purpose of this study was to document the effects of caffeine on renin release responses to a vasodilator and to investigate what mechanisms were responsible for any augmentation of vasodilator-induced renin secretion. Accordingly, we compared the effects of caffeine vs. 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX; a xanthine that we documented in this study not to significantly enter the brain or penetrate cell membranes) on base-line and hydralazine-induced renin release in both normal and beta adrenoceptor-blocked (propranolol, 15 mg/kg) rats. Both xanthines (at a dose of 10 mg/kg plus 150 micrograms/min) attenuated adenosine-mediated hypotension and bradycardia, and DPSPX was at least as effective as caffeine in antagonizing peripheral adenosine receptors. Caffeine and DPSPX increased base-line plasma renin activity to a similar extent regardless of whether the animals were pretreated with propranolol. In rats with an intact beta adrenergic system, caffeine, but not DPSPX, increased the renin release response to low-dose hydralazine (1 mg/kg). Although both xanthines augmented the renin release response to high-dose hydralazine (10 mg/kg), caffeine was more efficacious in this regard. In beta adrenoceptor-blocked rats, neither caffeine nor DPSPX augmented the renin release response to low-dose hydralazine, whereas both xanthines equally potentiated the renin release response to high-dose hydralazine. These data demonstrate that caffeine increases base-line renin release primarily by blocking peripheral (most likely renal), cell-surface adenosine receptors; however, caffeine potentiates vasodilator-induced renin secretion in part by blocking peripheral (most likely renal), cell-surface adenosine receptors and in part by additional central nervous system and/or intracellular mechanism(s) that involve the beta adrenergic system.

This paper describes an efficient algorithm for finding the minimal cut-sets for the output nodes of any network. The advantages over previously published algorithms are that it can be used on a desktop computer, and it requires simpler input data preparation hence providing for rapid testing of the effect of network changes.

Three successive fields of 136 eyes (86 patients) were extracted from our data base containing over 3000 visual fields performed on the Humphrey visual field analyser with program 30-2. Series of fields in which the second field was depressed relative to the first were selected for analysis to determine how much change between the first two fields was required to predict a downward trend as confirmed by the third field in the series. The data were stratified with respect to initial field damage. Seven regions of the visual field were analysed including the upper and lower temporal and nasal quadrants, the superior and inferior Bjerrum regions, and the whole field. Minimally damaged regions required between 4.7 and 5.6 dB change in mean sensitivity, whereas more damaged regions required between 5.5 and 7.2 dB change in mean sensitivity to have 95% confidence that the negative trend would be confirmed by the third field. The superior Bjerrum region was the most sensitive for the detection of change, and the lower temporal region was the least sensitive. We conclude from this series of data that large changes between two successive fields are required to be sure that the changes are due to disease rather than chance fluctuation. Where any doubt exists, the field should be repeated to confirm the reality of change.

A retrospective, longitudinal study of 129 eyes in 65 patients with pigmentary dispersion syndrome and either ocular hypertension of glaucoma was undertaken. The mean follow-up period was 17 years (range, 5-35 years). Visual acuity, intraocular pressure (IOP), visual field loss, pigment grade, Krukenberg spindle, iris transillumination, medications, and surgeries were analyzed for each patient at 5-year intervals from 1960 through 1983. Disc and field changes developed in 35% of patients with pigment dispersion syndrome and ocular hypertension during the study period. The long-term prognosis of the medical and surgical management of pigmentary glaucoma is discussed.

The role of mucus in protecting the underlying gastric epithelium is unknown. We investigated the pH gradient and thickness of the mucus gel layer in in vitro gastric fundic mucosa mounted in a special chamber using an antimony microelectrode, a slit lamp, and a dissecting microscope (× 40). This system allowed visualization of the tip of the electrode as it entered the mucus gel and as it reached the mucosa. With luminal pH maintained at 3.0-3.5, the maximum pH at interface between mucus and cells was 6.50 ± 0.10 (n = 9). At luminal pH 3.0-3.5, an increase in nutrient [HCO3-] from 17.8 to 47.8 δM resulted in an increase in maximum pH within the mucus from 6.80 ± 0.20 to 7.60 ± 0.20 (p

Informed male volunteers completed maximal isometric knee extension efforts under each of three contraction conditions: 1) voluntary, 2) electrical stimulation (ES) only, and 3) superimposed (ES superimposed onto voluntary). Ten subjects completed the three contraction conditions using each of the following current formats: 1) asymmetrical biphasic rectangular wave, 2) asymmetrical biphasic spike wave, and 3) symmetrical monophasic square wave. Under the voluntary and the superimposed contraction conditions no significant differences in mean torque were observed between the three current formats. However, under the ES contraction condition, the torque associated with the symmetrical monophasic square wave was significantly less than that associated with the other two current formats. As well, the torque associated with the asymmetrical biphasic spike wave was significantly less than that associated with the asymmetrical biphasic rectangular wave format. No significant difference was observed between the maximum voluntary contraction (MVC) and the superimposed contraction conditions for the groups receiving the asymmetrical biphasic spike and the symmetrical monophasic square wave current formats, or between all three contraction conditions for the group receiving the asymmetrical biphasic rectangular wave format. However, the ES condition was associated with significantly less torque than were the MVC and the superimposed conditions for the asymmetrical biphasic spike and the symmetrical monophasic square wave formats. In response to a posttest questionnaire, 18 of 30 subjects felt that the ES contraction produced greater torque than did MVC, and 26 subjects selected the superimposed condition as having produced greater torque than the ES condition. The different current formats, resulting in different levels of sensation and preception, and the different output capabilities of each electrical stimulator are considered to have been jointly responsible for the ES only torque discrepancies. It is suggested that ES does not recruit more motor units, resulting in a greater force of contraction, than are recruited under MVC.J Orthop Sports Phys Ther 1984;5(6):324-331.

The dielectric absorption and dispersions of several solutions of phenol in p-xylene have been measured at four microwave frequencies and at 2 MHz at a temperature of 25 °C. The data have been analyzed in terms of a mean relaxation time, a distribution parameter, and an apparent dipole moment which are useful empirical parameters for assessing the state of aggregation of the phenol molecules. The relaxation time at the lowest practicable concentration (0.02 mole fraction) is long for a molecule expected to relax predominantly by an intramolecular process. This and the behavior of the relaxation time and apparent dipole moment with increasing concentration are considered in terms of a model based on progressive association into an extended series of multimers, the trimer having a zero (or low) dipole moment and higher multimers becoming increasingly flexible.

The accuracy of the determination of e∞ from the Cole–Cole equations for systems which really relax by two Debye mechanisms is considered. The estimated value of e∞ is shown to be too low but an empirical equation helps to formulate limits within which the true value is likely to lie. Errors incurred in e∞ obtained by this method probably do not seriously influence relaxation time parameters obtained by a subsequent Budo analysis but approximations to e∞ (such as nD2) which are likely to be low may give very misleading results. Relationships between the Cole–Cole distribution parameter (α) and mean relaxation time (τ0) and the Budo parameters (τ1, τ2, and C1) are presented and discussed.

An assessment is made of the errors in the dielectric constant Iµ′ and loss Iµ″ determined at five microwave frequencies by a bridge technique for dilute solutions of polar substances. Analysis of these data into relaxation parameters τ1, τ2 and C1 is discussed for systems which are characterized by two relaxation processes of the Debye type. Sources of error are considered and estimates have been made of the accuracy of analysis. The dielectric data from two mixtures have been analyzed and each yields τ1, τ2 and C1 values in reasonable agreement with the known values.

The dielectric absorption of some intramolecularly hydrogen-bonded phenols in dilute p-xylene solution has been determined at four or five microwave frequencies and the static dielectric constant at 1 Mc/sec. The dielectric data have been analyzed to yield relaxation times and dipole moments. Strongly intramolecularly hydrogen-bonded phenols such as salicylaldehyde are characterized by one relaxation time whereas weakly intramolecularly hydrogen bonded compounds such as o-chloro-phenol yield a molecular relaxation time and one for hydroxyl re-orientation. Although the cis and trans forms of the o-substituted phenols have different energies of activation for hydroxyl re-orientation, the data have been interpreted in terms of one hydroxyl relaxation time. Theories by Garton and by Hoffman and Pfeiffer appear to offer a satisfactory explanation for only one intramolecular relaxation time.

The dielectric constant (ε′) and loss factor (ε″) of solutions of (i) 8-hydroxyquinoline in cyclohexane, carbon tetrachloride, p-xylene and 1,4-dioxan, (ii) o-nitrophenol in n-heptane, cyclohexane, carbon tetrachloride, and 1,4-dioxan, (iii) 2,4-dinitrophenol in 1,4-dioxan, and (iv) 2,6-dinitrophenol also in 1,4-dioxan have been recorded at four microwave frequencies and at 25 °C. A comparison of the relaxation time data of 1-nitro-naphthalene with that of 8-hydroxyquinoline in a number of solvents indicates that a strong specific interaction occurs between the latter solute and the solvent 1,4-dioxan which leads to the formation of a complex. In addition, a comparative study of nitrobenzene and o-nitrophenol indicates a similar phenomenon. Strong interaction of the 1,4-dioxan with an atom or atoms in the chelated ring system appears to take place which produces a larger reorienting species than the solute molecule itself and appreciably lengthens the relaxation time, although the data do not establish the point of attachment of the 1,4-dioxan to the chelated ring. The complex formation is accompanied by an additional component to the dipole moment. For the dinitrophenols significant interaction with the solvent p-xylene complicates the interpretation of the relaxation time data, although in the 2,4-dinitrophenol the formation of a complex is indicated in 1,4-dioxan.