Using the delocalization
and charge transfer descriptors, we obtain all couplings between these three states. Our results are important in the context of DNA photophysics, since the calculated couplings can be used to parametrize effective Hamiltonians to model extended DNA stacks. Our calculations Bioactive Compound Library screening also suggest that the 5′-purine-pyrimidine-3′ sequence favors the formation of charge transfer excited states. (C) 2014 AIP Publishing LLC.”
“Human detection is a significant and challenging task with applications in various domains. In real-time systems, the speed of detection is crucial to the performance of system, while the accuracy is also taken into consideration. In this work, a human detection approach based on Histograms of Oriented Gradients (HOG) feature and differential evolution (DE), termed as HOG-SVM-DE, is proposed to achieve both fast and accurate detection. The proposed method considers the problem of locating an objective detection window as a search problem, and speeds up the detection stage by solving the search problem with DE. DE is chosen as the optimizer as it is characterized by fast and global convergence. The proposed system trains only one linear-SVM, and allows tradeoffs between the detection rate and the detection
time to satisfy different applications by simply tuning one parameter. Experiments are conducted on a set of images from the INRIA Person Dataset, and the results validate that the proposed HOG-SVM-DE is promising in terms of both speed and accuracy. (C) 2014 Elsevier B.V. All rights reserved.”
“Background IgE binds to mast cells and basophils via
its high-affinity GSK1120212 supplier receptor, GM6001 concentration Fc epsilon RI, and cross-linking of Fc epsilon RI-bound IgE molecules by allergen leads to the release of allergic mediators characteristic of type I hypersensitivity reactions. Previous work has shown that cross-linking of Fc epsilon RI with Fc gamma RIIb, an ITIM-containing IgG receptor, leads to inhibition of basophil triggering. 2G10, a chimeric human IgG1 anti-idiotype, has broad reactivity with human IgE and as such has the potential to bind simultaneously to Fc epsilon RI-bound IgE, via its Fab regions, and the negative regulatory receptor, Fc gamma RIIb, via its Fc region.\n\nObjective To assess the ability of human 2G10 to inhibit anti-IgE and allergen-driven basophil degranulation through cross-linking of Fc epsilon RI-bound IgE with Fc gamma RIIb.\n\nMethods 2G10 was assessed for its ability to bind to Fc gamma RIIb on transfected cells and on purified basophils. In the basophil degranulation assay, basophils were purified from peripheral blood of atopic individuals and activated with either anti-IgE or the house dust mite allergen Der p 1, in the presence or absence of human 2G10. Basophil activation was quantified by analysis of CD63 and CD203c expression on the cell surface, and IL-4 expression intracellularly, using flow cytometery.
“Background\n\nAssisted reproduction techniques (ART) such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) can help subfertile couples to create a family. It is necessary to induce multiple follicles; this is achieved by follicle stimulating hormone (FSH) injections. Current
treatment regimens prescribe daily injections of FSH (urinary FSH with or without luteinizing hormone (LH) injections or recombinant FSH (rFSH)).\n\nRecombinant DNA technologies have produced a new recombinant molecule which is a long-acting FSH, named corifollitropin alfa (Elonva) or FSH-CTP. Birinapant chemical structure A single dose of long-acting FSH is able to keep the circulating FSH level above the threshold necessary to support multi-follicular growth for an entire week. The optimal dose of long-acting FSH is still being determined. A single injection of long-acting FSH can replace seven daily FSH injections during the first week of controlled selleck compound ovarian stimulation (COS) and can make assisted reproduction
more patient friendly.\n\nObjectives\n\nTo compare the effectiveness of long-acting FSH versus daily FSH in terms of pregnancy and safety outcomes in women undergoing IVF or ICSI treatment cycles.\n\nSearch methods\n\nWe searched the following electronic databases, trial registers and websites: the Cochrane Central Register of Controlled Trials (CENTRAL), the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, MEDLINE, EMBASE, PsycINFO, CINAHL, electronic trial registers for ongoing and registered trials, citation indexes, conference abstracts in the ISI Web of Knowledge, LILACS, Clinical Study Results (for clinical trial results of marketed pharmaceuticals), PubMed and OpenSIGLE (10 October 2011). We also carried
out handsearches.\n\nSelection criteria\n\nAll randomised controlled trials (RCTs) comparing long-acting FSH versus daily FSH in women who were part of a couple with subfertility and undertaking IVF or ICSI treatment cycles with a GnRH antagonist or agonist protocol were included.\n\nData collection and analysis\n\nData extraction and assessment of risk of bias was independently done by two review authors. Original trial authors were contacted in the case of missing data. We calculated Peto odds ratios for each outcome; our primary outcomes were live Selleck JNK inhibitor birth rate and ovarian hyperstimulation syndrome (OHSS) rate.\n\nMain results\n\nWe included four RCTs with a total of 2335 participants. A comparison of long-acting FSH versus daily FSH did not show evidence of difference in effect on overall live birth rate (Peto OR 0.92; 95% CI 0.76 to 1.10, 4 RCTs, 2335 women) or OHSS (Peto OR 1.12; 95% CI 0.79 to 1.60, 4 RCTs, 2335 women). We compared subgroups by dose of long-acting FSH. There was evidence of reduced live birth rate in women who received lower doses (60 to 120 mu g) of long-acting FSH compared to daily FSH (Peto OR 0.60; 95% CI 0.40 to 0.91, 3 RCTs, 645 women).
Direct tests of the effects of egg load on glassy-winged sharpshooter oviposition behavior found that females were more likely to deposit eggs as egg load increased. Similarly, acceptance of a low-ranked oviposition plant species
by female glassy-winged sharpshooters increased with egg load and time since last oviposition. The results indicate that adult feeding affected glassy-winged sharpshooter egg maturation, plant species varied CBL0137 cell line in quality for providing nutrients for egg maturation, and egg load affected oviposition behavior. Thus, the quantity and quality of available feeding plant species may affect glassy-winged sharpshooter egg maturation rates, which in turn may affect the plant species female glassy-winged sharpshooters select for oviposition.”
“AimTo investigate hormonal dynamics in a group
of non-obese polycystic ovary syndrome (PCOS) patients under myo-inositol (MYO) administration. MethodsHormonal profiles, insulin response to oral glucose tolerance test (OGTT) and luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH) stimulation test Nepicastat cell line before and after the administration of a preparation of MYO (3g p.o. daily) mixed with lactoferrin and bromelin, in a group (n=24) of normal weight PCOS patients. ResultsAfter the treatment interval, body mass index (BMI) did not change while LH, LH/follicle-stimulating hormone, 17-hydroxy-progesterone and androstenedione decreased significantly. Insulin response to OGTT was significantly reduced after the treatment interval (P smaller than 0.05) as well as GnRH-induced LH response (P smaller than 0.05). High-sensitivity C-reactive protein decreased significantly after the treatment interval. ConclusionMYO administration positively modulates insulin sensitivity in non-obese PCOS patients
Selleck Luminespib without compensatory hyperinsulinemia, improving hormonal parameters. The presence of bromelin in the formulation modulated the pro-inflammatory state that characterizes PCOS, independently of BMI.”
“BACKGROUND CONTEXT: Bone morphogenetic protein-2 (BMP-2) has been used to successfully promote spine fusion, but side-effects including nerve inflammation have been observed. PURPOSE: To investigate the direct neurotoxic effects of BMP-2 and test the hypotheses that the use of BMP binding proteins, such as secreted phosphoprotein 24 kD (Spp24), can reduce or eliminate these effects. STUDY DESIGN: In vitro experiments and in vivo analysis in a rodent model. METHODS: In vitro, dorsal root ganglion cells were cultured in the presence of BMP-2 with and without Spp24 and calcitonin gene-related peptide and Substance P, markers of neuroinflammation, were measured by immunohistochemistry.
Methods: This cross-sectional study included 88 PD patients and 90 controls. RVC and RVH were assessed with a visual symptom questionnaire and the North-East-Visual-Hallucinations-Interview (NEVHI). Results: Double vision (PD vs. Controls: 18.2% vs. 1.3%; p smaller than 0.001), misjudging objects when walking (PD vs. Controls: 12.5% vs. 13%; PF-00299804 mouse p smaller than 0.01), words moving whilst reading (PD vs. Controls: 17.0% vs. 1.3%; p smaller than 0.001) and freezing in narrow spaces (PD vs. Controls: 30.7% vs. 0%; p smaller than 0.001) were almost exclusively found in PD patients. The same was true for recurrent
complex visual hallucinations and illusions (PD vs. Controls: both 17.0% vs. 0%; p smaller than 0.001). Multiple RVC (43.2% vs. 15.8%) and multiple RVH (29.5% vs. 5.6%) were also more common in PD patients (both p smaller than 0.001). Autophagy Compound Library manufacturer RVC did not predict recurrent complex visual hallucinations; but double vision (p = 0.018, R-2 = 0.302) and misjudging objects (p = 0.002, R-2 = 0.302) predicted passage hallucinations. Misjudging objects also predicted the feeling of presence (p = 0.010, R-2 = 0.321). Conclusions: Multiple and recurrent visual symptoms are common in PD. RVC emerged as risk factors predictive of the minor forms of hallucinations,
but not recurrent complex visual hallucinations. (C) 2013 Elsevier Ltd. All rights reserved.”
“Objective: To describe and compare onset and intensity of thoracic duct (TD) coloration after injection o Study Design: Experimental study. Animals: Adult dogs (n = 18). Methods: Methylene blue ( smaller than = 0.5 mg/kg 1% solution) was injected into the left (n = 9) or right (n
= 9) diaphragmatic crus via right 10th intercostal thoracotomy. TD coloration was graded over 10 minutes. A right paracostal laparotomy was then performed in all dogs, and an equal volume of methylene blue injected into a mesenteric lymph node (n = 18). TD color grading was repeated. Statistical analysis was performed on subject weight, volume of contrast agent injected between left and right crus, and number of successful outcomes between diaphragmatic crus injection and mesenteric lymph node injection. Results: TD coloration occurred in 6 dogs with left crus injection and 4 dogs with right crus injection Nutlin-3 purchase with obvious staining present in 2 and 3 dogs, respectively. Successful outcome was noted in all dogs with mesenteric lymph node injection. The number of successful outcomes was significantly greater after mesenteric lymph node injection compared with diaphragmatic crus injection (P smaller than .001). Conclusions: Methylene blue injected into the diaphragmatic crura and mesenteric lymph node was successful in coloring the TD; however, mean thoracic duct color grade and number of successful outcomes were significantly higher after mesenteric injection.
Binding enthalpy and entropy
changes do not correlate with structural features such as buried surface area or the number of hydrogen bonds within TCR-pMHC interfaces, possibly reflecting the myriad of contributors to binding thermodynamics, but likely also reflecting a reliance on van’t Hoff over calorimetric measurements and the unaccounted influence of equilibria linked to binding. TCR-pMHC binding heat capacity changes likewise vary considerably. In some cases, the heat capacity changes are consistent with conformational Dinaciclib supplier differences between bound and free receptors, but there is little data indicating these conformational differences represent the need to organize disordered CDR loops. In this regard, we discuss how thermodynamics may provide additional insight into conformational changes STA-9090 clinical trial occurring upon TCR binding. Finally, we highlight opportunities for the further use of thermodynamic measurements in the study of TCR-pMHC interactions, not only for understanding TCR binding in general, but also for understanding specifics of individual interactions and the engineering of TCRs with desired molecular recognition properties. Copyright (C) 2008 John Wiley &
“Full quantitative analysis of brain PET data requires knowledge of the arterial input function into the brain. Such data are normally acquired by arterial sampling with corrections for delay and dispersion to account for the distant sampling site. Several attempts have been made to extract an image-derived input function (IDIF) directly from the internal carotid arteries that supply the brain and are often visible in brain PET images. We have devised a method of delineating the internal carotids in co-registered magnetic resonance (MR) images using the level-set method and applying the segmentations to PET images using a novel centerline approach. Centerlines of the segmented carotids were modeled as cubic splines and re-registered in PET images summed over the early portion of the scan. Using information
from the anatomical center of the vessel should minimize partial volume and spillover effects. Centerline time-activity curves were taken as the mean of the values for points along the centerline interpolated from neighboring learn more voxels. A scale factor correction was derived from calculation of cerebral blood flow (CBF) using gold standard arterial blood measurements. We have applied the method to human subject data from multiple injections of [O-15] water on the HRRT. The method was assessed by calculating the area under the curve (AUC) of the IDIF and the CBF, and comparing these to values computed using the gold standard arterial input curve. The average ratio of IDIF to arterial AUC (apparent recovery coefficient: aRC) across 9 subjects with multiple (n = 69) injections was 0.49 +/- 0.
The impact of such dependence on the empirical cumulative distribution function (c.d.f.) is studied. An asymptotic framework and weak conditions on the informative selection mechanism are developed under which the (unweighted) empirical c.d.f. converges uniformly, in L-2 and almost surely, to a weighted version of the superpopulation c.d.f. This yields an analogue of the Glivenko-Cantelli theorem. A series of examples, motivated by real problems in surveys and other observational studies, shows that the conditions are verifiable for specified designs.”
“New signal processing techniques have enabled selleck chemicals the
use of the vectorcardiogram (VCG) for the detection of cardiac ischemia. Thus, we studied this signal during ventricular depolarization in 80 ischemic patients, before undergoing angioplasty, and 52 healthy subjects with the objective of evaluating the vectorcardiographic difference between both groups so leading to their subsequent classification. For that matter, seven QRS-loop parameters were analyzed, i.e.: (a) Maximum Vector Magnitude; (b) Volume; (c) Planar Area;
(d) Maximum Distance between Centroid and Loop; (e) Angle between XY and Optimum Plane; (f) Perimeter and, (g)Area-Perimeter Ratio. For comparison, the conventional ST-Vector Magnitude (STVM) was also calculated. Results indicate that several vectorcardiographic parameters show significant differences between healthy and ischemic subjects. The identification of ischemic patients via discriminant analysis using STVM produced 73.2% Sensitivity (Sens) and 73.9% Specificity (Spec). In our study, the QRS-loop parameter with BV-6 in vivo the best global performance Selleck Wnt inhibitor was Volume, which achieved Sens = 64.5% and Spec = 74.6%. However, when all QRS-loop parameters and STVM were combined, we obtained Sens = 88.5% and Spec = 92.1%. In conclusion,
QRS loop parameters can be accepted as a complement to conventional STVM analysis in the identification of ischemic patients. (c) 2012 IPEM. Published by Elsevier Ltd. All rights reserved.”
“The authors propose and test a simple model of the time course of visual identification of briefly presented. mutually confusable single stimuli in pure accuracy tasks. The model implies that during stimulus analysis, tentative categorizations that stimulus i belongs to category j are made at a constant Poisson rate, v(i, j). The analysis is continued until the stimulus disappears, and the overt response is based on the categorization made the greatest number of times. The model was evaluated by Monte Carlo tests of goodness of fit against observed probability distributions of responses in two extensive experiments and also by quantifications of the information loss of the model compared with the observed data by use of information theoretic measures. The model provided a close fit to individual data on identification of digits and an apparently perfect fit to data on identification of Landolt rings.
“Objective: The aim of this study was to assess vasomotor and other menopausal symptoms before starting estrogens or placebo, 1 year later, again at trial closure, and after stopping estrogens
or placebo. The role of baseline symptoms and age was examined, as was the frequency and determinants of hormone use and symptom management strategies after discontinuing conjugated equine estrogens (CEE) or placebo.\n\nMethods: Intent-to-treat analyses of 10,739 postmenopausal women before and 1 year after randomization to CEE or placebo at 40 clinical centers and a cohort analysis of participants (n = 3,496) who continued taking assigned study pills up to trial closure and completed symptom surveys shortly before (mean, 7.4 +/- MI-503 inhibitor 1.1 y from baseline) and after (mean, 306 +/- 55 d after trial closure) stopping
pills were performed. Generalized linear regression modeled vasomotor symptoms, vaginal dryness, breast tenderness, pain/stiffness, and mood swings as a function of treatment assignment and baseline symptoms, before and after stopping study pills.\n\nResults: Approximately one third of participants reported at least one moderate to severe symptom at baseline. Fewer symptoms were reported with increasing age, except joint pain/stiffness, which was similar among age groups. At 1 year, hot flashes, night sweats, and vaginal dryness were reduced by CEE, whereas breast signaling pathway tenderness was increased. Breast tenderness was also significantly higher in the CEE group at trial selleck products closure. After stopping, vasomotor symptoms were reported by significantly more women who had reported symptoms at baseline, compared with those who had not, and by significantly more participants assigned to CEE (9.8%) versus placebo (3.2%); however, among women with no moderate or severe symptoms at baseline, more than five times as many reported hot flashes after stopping CEE (7.2%) versus placebo (1.5%).\n\nConclusions:
CEE significantly reduced vasomotor symptoms and vaginal dryness in women with baseline symptoms but increased breast tenderness. The likelihood of experiencing symptoms was significantly higher after stopping CEE than placebo regardless of baseline symptom status. These potential effects should be considered before initiating CEE to relieve menopausal symptoms.”
“The interactions between herbivores and their host plants determine, to a great extent, the formation, structure and sustainability of terrestrial communities. The selection pressures that herbivores exert on plants and vice versa might vary geographically, leading eventually to population differentiation and local adaptation.
Poignantly we show that acute starvation which is detrimental to wild-type animals is beneficial in terms of metabolism and muscle function in the myostatin null mice by normalising tension production.”
“PURPOSE. To investigate the cause of the syndrome characterized by endothelial
dystrophy, iris hypoplasia, congenital cataract, and stromal thinning (EDICT).\n\nMETHODS. Previously a multigenerational family was reported that comprised 10 individuals affected by syndromal anterior segment dysgenesis. Blood samples were re-collected from eight affected and two unaffected individuals, and genomic DNA was extracted. A total of 24 candidate genes XMU-MP-1 supplier and 4 microRNAs residing within the critical interval were sequenced bidirectionally. In silico analyses were performed to examine the effect of the causal variant on the stability of the pre-microRNA structure.\n\nRESULTS. Bidirectional sequencing identified the single-base substitution +57C > T in miR-184. This variation segregated with the disease phenotype and was absent in the 1000 Genomes project, 1130 control chromosomes, and 28 nonhuman vertebrates.\n\nCONCLUSIONS. The single-base-pair substitution in the seed region of miR-184 is responsible for the disease phenotype observed in EDICT syndrome. (Invest Ophthalmol Vis Sci. 2012;
53: 348-353) DOI:10.1167/iovs.11-8783″
“Purpose. To investigate the depth of field of pseudophakic eye implanted Histone Methyltransf inhibitor with translating optics accommodating Liproxstatin-1 solubility dmso intraocular lenses (AIOLs).\n\nMethods. Theoretical analyses using paraxial optics equations were used. The crystalline lens in the Navarro eye model was replaced with an AIOL modeled as a thin-lens
system with either a single lens element (1E-AIOL) or two element (2E-AIOL). To quantify the depth of field, a reference limit for retinal blur circle diameter was adopted from typical values of depth of field of the normal eye. Effect of various factors including AIOL type, lens element power, implant position, and pseudophakic accommodation on depth of field were analyzed.\n\nResults. Depth of field increased with more posterior positioning of the AIOL and decreased with pseudophakic accommodation by translation of optics. However, the changes did not exceed 0.02 D over the range of factors tested. Effective depth of field, defined as the magnification adjusted depth of field, is relatively independent of the implant position and power combination of AIOL. Effects of varying design factors on the depth of field of AIOL are too small to be clinically observable.\n\nConclusions. Although depth of field extends the range of near vision with AIOL, varying design and surgical factors such as depth of implantation and optical power of lens element(s) within clinically practical limits modifies depth of field by an insignificant amount.
81; 95% CI, 2.11 to 3.75; P=0.001).\n\nConclusions-For the treatment of multivessel coronary artery disease, percutaneous coronary intervention with DES implantation showed equivalent long-term mortality as CABG.”
“CD47, a receptor for thrombospondin-1, limits two important regulatory axes: nitric oxide-cGMP signaling and cAMP signaling, both of which can promote mitochondrial biogenesis. Electron microscopy revealed increased mitochondria( Mizoribine densities in skeletal muscle from both CD47 null and thrombospondin-1 null mice. We further assessed the mitochondria status of CD47-null vs WT mice. Quantitative RT-PCR of RNA extracted from tissues of 3 month old mice revealed dramatically
elevated expression of mRNAs encoding mitochondrial proteins and PGC-1 alpha in both fast and slow-twitch skeletal muscle from CD47-null mice, but modest to no elevation in other tissues. These observations were confirmed by Western blotting of mitochondria! proteins. Relative amounts of electron transport enzymes and ATP/O-2 ratios of isolated mitochondria were not different between mitochondria CT99021 from CD47-null and WT cells. Young CD47-null mice displayed enhanced treadmill endurance relative to WTs and CD47-null gastrocnemius had undergone fiber type switching to a slow-twitch pattern of myoglobin and myosin heavy chain expression. In 12 month old mice, both skeletal muscle mitochondrial volume density and
endurance had decreased to wild type levels. Expression of myosin heavy chain isoforms and myoglobin also reverted to a fast twitch pattern in gastrocnemius. Both CD47 and TSP1 null mice are leaner than WTs, use Selleck JQ-EZ-05 less oxygen and produce less heat than WT mice. CD47-null cells produce substantially less reactive oxygen species than WT cells. These data indicate that loss of signaling from the TSP1-CD47 system promotes accumulation of normally functioning mitochondria in a tissue-specific and age-dependent fashion leading to enhanced physical performance, lower reactive oxygen species production and more efficient metabolism. (C) 2011 Elsevier
B.V. All rights reserved.”
“Some epidemiological studies suggest that vitamin A (retinol), vitamin E, and vitamin D (total 25-hydroxyvitamin D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)(2)D) are protective against prostate cancer. However, the evidence is not conclusive, with positive and null associations reported for all three vitamins. Limitations of previous studies include small sample size, lack of population controls, and reliance on self-reported dietary intake. Few studies have explored the interactions of circulating 25(OH)D with 1,25(OH)(2)D or retinol, which are biologically plausible interactions.\n\nWe investigated the associations of circulating retinol, vitamin E, and 1,25(OH)(2)D with PSA-detected prostate cancer risk, stage, and grade in a case-control study nested within the Prostate Testing for Cancer and Treatment (ProtecT) trial.
Annual influenza vaccination is therefore commonly recommended for people with cystic fibrosis. Objectives To assess the effectiveness of influenza vaccination for people with cystic fibrosis. Search methods We searched
the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also contacted the companies which market the influenza vaccines used in the trials to obtain further information about randomised controlled trials. Date of the most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Cystic Fibrosis Trials Register: 08 July 2013. Selection criteria All randomised and quasi-randomised trials (published GSK621 solubility dmso or unpublished) comparing any influenza vaccine with a placebo or with another type of influenza vaccine. Data collection and analysis Two authors independently assessed study quality and extracted data. Additional information was obtained by contacting the investigators when it was indicated. Main results Four studies enrolling a total of 179 participants with cystic fibrosis (143 (80%) were children aged 1 to 16 years) were included in this review.
There was no study comparing a vaccine to a placebo or a whole virus vaccine to a subunit or split virus vaccine. Two studies compared an intranasal applied live NVP-BSK805 vaccine to an intramuscular inactivated vaccine and the other two studies compared a split virus to a subunit vaccine and a virosome to a subunit vaccine (all intramuscular). The incidence of all reported adverse events was high depending on the type of
influenza vaccine. The total adverse event rate ranged from 48 out of 201 participants (24%) for the intranasal live vaccine Nocodazole cell line to 13 out of 30 participants (43%) for the split virus vaccine. With the limitation of a statistical low power there was no significant difference between the study vaccinations. None of the events were severe. All study influenza vaccinations generated a satisfactory serological antibody response. No study reported other clinically important benefits. Authors’ conclusions There is currently no evidence from randomised studies that influenza vaccine given to people with cystic fibrosis is of benefit to them. There remains a need for a well-constructed clinical study, that assesses the effectiveness of influenza vaccination on important clinical outcome measures.”
“Mathematics is beautiful and precise and often necessary to understand complex biological phenomena. And yet biologists cannot always hope to fully understand the mathematical foundations of the theory they are using or testing. How then should biologists behave when mathematicians themselves are in dispute? Using the on-going controversy over Hamilton’s rule as an example, I argue that biologists should be free to treat mathematical theory with a healthy dose of agnosticism.