Centrifugal Detachment of Compound Droplets from Fibers.

This article presents the first experimental-computational study on the centrifugal detachment of a compound droplet (e.g., a primary water droplet cloaked by an immiscible oil) from a fiber. The work was intended to establish a method for quantifying the force needed to detach compound droplets of different compositions from a fiber. More importantly, our study was aimed at improving the understanding of the interplay between interfacial and external forces acting on a compound droplet during forceful detachment. The experiments were conducted using DI water, for the primary droplet, and silicone or mineral oil, for the cloaking fluid. It was observed from the experiments that the silicone-oil-cloaked droplets behave differently from the mineral-oil-cloaked droplets. It was also observed that detachment force decreases with increasing the oil-to-water volume ratio. The simulations were performed using the Surface Evolver (SE) finite element code programmed for the complicated four-phase (air, water, oil, and solid) interfacial problem at hand. Our simulations revealed the evolution of the interfacial forces between the interacting phases under an increasing external body force on the droplet. The simulations also allowed us to define effective interfacial tensions and contact angles for detaching compound droplets, for the first time. Reasonable agreement was observed between the experimental measurements and computational results.

Quantum error correction in a solid-state hybrid spin register.

Error correction is important in classical and quantum computation. Decoherence caused by the inevitable interaction of quantum bits with their environment leads to dephasing or even relaxation. Correction of the concomitant errors is therefore a fundamental requirement for scalable quantum computation. Although algorithms for error correction have been known for some time, experimental realizations are scarce. Here we show quantum error correction in a heterogeneous, solid-state spin system. We demonstrate that joint initialization, projective readout and fast local and non-local gate operations can all be achieved in diamond spin systems, even under ambient conditions. High-fidelity initialization of a whole spin register (99 per cent) and single-shot readout of multiple individual nuclear spins are achieved by using the ancillary electron spin of a nitrogen-vacancy defect. Implementation of a novel non-local gate generic to our electron-nuclear quantum register allows the preparation of entangled states of three nuclear spins, with fidelities exceeding 85 per cent. With these techniques, we demonstrate three-qubit phase-flip error correction. Using optimal control, all of the above operations achieve fidelities approaching those needed for fault-tolerant quantum operation, thus paving the way to large-scale quantum computation. Besides their use with diamond spin systems, our techniques can be used to improve scaling of quantum networks relying on phosphorus in silicon, quantum dots, silicon carbide or rare-earth ions in solids.

Evaluation of the effect of endoscopic partial middleturbinectomy surgery on the quality of life of patients with chronic rhinosinusitis and nasal polyps.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease. Endoscopic sinus surgery is recommended as a standard method when medical treatment fails. The effectiveness of various complementary surgical methods such as endoscopic partial middle-turbinectomy is controversial in the improvement of CRS symptoms in these patients. This study aimed to investigate the effect of endoscopic partial middle-turbinectomy on the quality of life (QOL) of patients with chronic rhinosinusitis and nasal polyps (CRSwNP) in Iran. METHOD: Ninety patients with CRSwNP of grades 3 and 4 were randomly assigned to either an intervention (45 patients) or control group (45 patients). In the control group, endoscopic sinus surgery without middle turbinectomy was performed and in the intervention group, endoscopic partial middle-turbinectomy was performed in addition to endoscopic sinus surgery. To evaluate the outcomes, the SNOT-22 QOL questionnaire was used, and the results were analyzed using SPSS version 24. RESULTS: Most of the patients were male and had a mean age of 39 years. The mean SNOT-22 QOL questionnaire scores were 49.13 ± 16.72 and 52.51 ± 16.95 before surgery in the control and intervention groups respectively, which did not show any significant difference. In contrast, after endoscopic surgery these scores changed to 28.46 ± 12.38 and 11.13 ± 5.55 in the control and intervention groups, respectively and there was a significant difference between both groups. Although there was a significant improvement in both groups, the patients in the intervention group experienced more improvement than the control group (41.4 (± 16.46)) vs 30.7 (±18.27), respectively CONCLUSION: According to this study, it appears that the use of endoscopic partial middle-turbinectomy in addition to endoscopic sinus surgery improves CRS symptoms and the QOL of patients compared with endoscopic sinus surgery alone.

Droplet Mobility on Hydrophobic Fibrous Coatings Comprising Orthogonal Fibers.

Water droplet mobility on a hydrophobic surface cannot be guaranteed even when the droplet exhibits a high contact angle (CA) with the surface. In fact, droplet mobility on a surface, especially a fibrous surface, has remained an unsolved empirical problem. This paper is a combined experimental-computational study focused on droplet mobility on a fibrous surface. Electrospun polystyrene (PS) coatings were used in this work for their ability to exhibit high CAs simultaneously with low droplet mobility. To simplify this otherwise complicated problem and better isolate droplet-fiber interactions, the orientation of the fibers in the coatings was limited to the x and y directions. As the earth gravity was not strong enough to mobilize small droplets on PS coatings, experiments were conducted using ferrofluid droplets, and a magnet was used to make them move on the surface. Experimentally validated numerical simulations were used to enhance our understanding of the forces acting on a droplet before moving on the surface. Effects of Young-Laplace CA and fiber-fiber spacing on droplet mobility were investigated. In particular, it was found that droplet mobility depends strongly on the balance of forces exerted on the droplet by the fibers on the receding and advancing sides.

Targeting focal adhesion turnover in invasive breast cancer cells by the purine derivative reversine.

BACKGROUND: The dynamics of focal adhesion (FA) turnover is a key determinant for the regulation of cancer cell migration. Here we investigated FA turnover in a panel of breast cancer models with distinct invasive properties and evaluated the impact of reversine on this turnover in relation to cancer cell invasion in in vitro and in vivo conditions. METHODS: Live imaging and immunofluorescence assays were used to investigate FA turnover in breast cancer cells. Biochemical studies were used to investigate the impact of reversine on FA signalling and turnover. In vivo activity was investigated using orthotopic breast cancer mouse models. RESULTS: Accelerated FA disassembly from plasma membrane protrusions was observed in invasive compared with non-invasive breast cancer cells or non-immortalised mammary epithelial cells. Reversine significantly inhibited FA disassembly leading to stable FAs, which was associated with reduced cell motility and invasion. The inhibitory effect of reversine on FA turnover accounted for a large part on its capacity to interfere with FAK function on regulating its downstream targets. In orthotopic breast cancer mouse models, reversine revealed a potent inhibitory activity on tumour progression to metastasis. CONCLUSION: These results support the utility of targeting FA turnover as a therapeutic approach for invasive breast cancer.

Quality improvement of prerigor salted ground chicken breast with basic amino acids at low NaCl level.

The prerigor salting effect is known to provide superior meat processing quality. Based on the urgent need for low salt meat products, the present study was undertaken to evaluate the prerigor salting effect when basic amino acids were introduced at 1% NaCl level. Ground chicken breast meat was salted with NaCl and basic amino acids at 30 min, 60 min, and 90 min postmortem for prerigor treatments. Compared to the 1% NaCl (w/w) treatment, the introduction of 0.06% basic amino acids (w/w) in the prerigor significantly led to an increase in myofibril fragmentation, myofibrillar protein solubility, emulsion activity, storage modulus change rate, gel water-holding capacity and hardness (P < 0.05). Furthermore, smaller and more uniformly sized droplets were produced in emulsion by basic amino acids. Individual basic amino acids had different prerigor salting effects, and it was indicated that basic amino acids could play a positive role in the prerigor salting effect when NaCl was reduced.

Halothermal and hydrothermal time models describe germination responses of canola seeds to ageing.

Hydrothermal time (HTT) and halothermal time (HaloTT) models were used to quantitatively characterize the combined effects of temperature (T), water potential (ψ) and NaCl concentration on seed germination of canola after different accelerated ageing periods (AAP) at 42 °C and 100% humidity. Seed germination time courses were observed and electrical conductivities of seed leachates were measured in all experiments. The cardinal temperatures estimated by both models were 4.6, 28 and 35 °C for the base (Tb ), optimum (To ) and ceiling (Tc ) temperatures in water (0 MPa), respectively, when the seeds were not aged. The Tb increased with AAP, while the Tc decreased and the To remained constant at all AAP. Below To , the median base water potentials (ψb (50)) were -1.07, -0.73, -0.48 and -0.39 MPa for the AAP levels of 0, 24, 36 and 48 h, respectively. These values were more negative when germination occurred in salt solutions (the base NaCl concentrations converted to ψ were -1.25, -0.81, -0.51 and -0.41 MPa, respectively), due to uptake of salt ions. Thresholds became more positive above To and reached zero at Tc in all AAP. Seed osmotic adjustment capacity declined linearly with increasing AAP while the conductivity of seed leachates increased in association with the loss of seed vigour. Significant correlations between conductivity results and the parameters of HTT and HaloTT models suggest that they could be considered as effective descriptors of canola seed vigour.

Does maxillary advancement alter vocal acoustic parameters in class III skeletal patients?

Any change in the maxillary position can affect the length of the vocal tract. This cross-sectional study aimed to assess the vocal acoustic parameters in 24 class III skeletal patients who underwent Le Fort I osteotomy for maxillary advancement. The vocal acoustic parameters (fundamental frequency, and jitter and shimmer perturbation indexes) were studied before, and at three, seven, and 10 months after maxillary advancement. The age and gender of the patients were the variables of the study. The amount of maxillary advancement was the predictive factor, and the changes in vocal acoustic parameters the study outcomes. Repeated-measures ANOVA were used to analyse the vocal acoustic parameters at different time points. Mean (SD) maxillary advancement was 3.5 (0.59) mm (range 3 - 6 mm). Data analysis did not demonstrate any significant correlation between the mean amount of maxillary advancement and changes in vocal acoustic parameters except for frequency of the 'i' sound. The results did not show a substantial change in the vocal acoustic parameters at 10 months after orthognathic surgery compared with baseline. These changed at three and seven months, but had returned to their baseline preoperative state 10 months after surgery.

Characterization of a xenograft model for anti-CD19 CAR T cell studies.

PURPOSE: Chimeric antigen receptor (CAR) T cell development for B cell malignancies treatment has triggered a paradigm shift in oncology. The development of anti-CD19 CAR T cells relies primarily on a panel of cell line-derived xenograft models, including Raji cells; however, the behavior of this model is under debate. We attempted to characterize this lymphoma model and propose outcome measures for CAR T cell studies METHODS: Raji cell line was inoculated into NOG mice via intra-venous (IV), intra-peritoneal (IP), and subcutaneous (SC) routes with different inoculum sizes, and consequent clinical and histopathological outcomes were assessed. RESULTS: Inoculum sizes of 105-106 resulted in a complete take rate. The mice with IV and SC-inoculated Raji cells presented the shortest and longest survival among lymphoma-bearing mice, respectively (P < 0.01). The IP group had the highest number of both infiltrated organs (P < 0.05; compared to SC) and involvement of lymphatic sites (P < 0.05; compared to IV). The number of lymphoma lesions on the liver was higher in the IV compared to IP (P < 0.001) and SC (P < 0.05). CONCLUSION: We demonstrate that the Raji cell line inoculation route could determine the xenograft model system behavior in terms of survival, tumor burden, and dissemination pattern and gives the model the specific features suitable for testing the specific hypothesis in CAR T cell therapy. We also conclude outcome measures for CAR T cell studies that do not require imaging techniques.

The active form of quinol-dependent nitric oxide reductase from Neisseria meningitidis is a dimer.

Neisseria meningitidis is carried by nearly a billion humans, causing developmental impairment and over 100 000 deaths a year. A quinol-dependent nitric oxide reductase (qNOR) plays a critical role in the survival of the bacterium in the human host. X-ray crystallographic analyses of qNOR, including that from N. meningitidis (NmqNOR) reported here at 3.15 Šresolution, show monomeric assemblies, despite the more active dimeric sample being used for crystallization. Cryo-electron microscopic analysis of the same chromatographic fraction of NmqNOR, however, revealed a dimeric assembly at 3.06 Šresolution. It is shown that zinc (which is used in crystallization) binding near the dimer-stabilizing TMII region contributes to the disruption of the dimer. A similar destabilization is observed in the monomeric (∼85 kDa) cryo-EM structure of a mutant (Glu494Ala) qNOR from the opportunistic pathogen Alcaligenes (Achromobacter) xylosoxidans, which primarily migrates as a monomer. The monomer-dimer transition of qNORs seen in the cryo-EM and crystallographic structures has wider implications for structural studies of multimeric membrane proteins. X-ray crystallographic and cryo-EM structural analyses have been performed on the same chromatographic fraction of NmqNOR to high resolution. This represents one of the first examples in which the two approaches have been used to reveal a monomeric assembly in crystallo and a dimeric assembly in vitrified cryo-EM grids. A number of factors have been identified that may trigger the destabilization of helices that are necessary to preserve the integrity of the dimer. These include zinc binding near the entry of the putative proton-transfer channel and the preservation of the conformational integrity of the active site. The mutation near the active site results in disruption of the active site, causing an additional destabilization of helices (TMIX and TMX) that flank the proton-transfer channel helices, creating an inert monomeric enzyme.

Regulation of focal adhesion turnover by ErbB signalling in invasive breast cancer cells.

A crucial early event by which cancer cells switch from localised to invasive phenotype is initiated by the acquisition of autonomous motile properties; a process driven by dynamic assembly and disassembly of multiple focal adhesion (FA) proteins, which mediate cell-matrix attachments, extracellular matrix degradation, and serve as traction sites for cell motility. We have reported previously that cancer cell invasion induced by overexpression of members of the ErbB tyrosine kinase receptors, including ErbB2, is dependent on FA signalling through FA kinase (FAK). Here, we show that ErbB2 receptor signalling regulates FA turnover, and cell migration and invasion through the Src-FAK pathway. Inhibition of the Src-FAK signalling in ErbB2-positive cells by Herceptin or RNA interference selectively regulates FA turnover, leading to enhanced number and size of peripherally localised adhesions and inhibition of cell invasion. Inhibition of ErbB2 signalling failed to regulate FA and cell migration and invasion in cells lacking FAK or Src but gains this activity after restoration of these proteins. Taken together, our results show a regulation of FA turnover by ErbB2 signalling.

Assessment of water quality of polluted lake using multivariate statistical techniques: a case study.

Multivariate statistical techniques, cluster analysis (CA) and principal component analysis (PCA) were applied to the data on water quality of Manchar Lake (Pakistan), generated during 2005-06, with monitoring at five different sites for 36 parameters. This study evaluated and interpreted complex water quality data sets and apportioned of pollution sources to get better information about water quality and to design a monitoring network. The chemical correlations were observed by PCA, which were used to classify the samples by CA, based on the PCA scores. Three significant sampling locations--(sites 1 and 2), (site 4) and (sites 3 and 5)--were detected on the basis of similarity of their water quality. The results revealed that the major causes of water quality deterioration were related to inflow of effluent from industrial, domestic, agricultural and saline seeps into the lake at site 1 and also resulting from people living in boats and fishing at sites 2 and 3.

Toxic metals distribution in different components of Pakistani and imported cigarettes by electrothermal atomic absorption spectrometer.

It was extensively investigated that a significant flux of toxic metals, along with other toxins, reaches the lungs through smoking. In present study toxic metals (TMs) (Al, Cd, Ni and Pb) were determined in different components of Pakistani local branded and imported cigarettes, including filler tobacco (FT), filter (before and after normal smoking by a single volunteer) and ash by electrothermal atomic absorption spectrometer (ETAAS). Microwave-assisted digestion method was employed. The validity and accuracy of methodology were checked by using certified sample of Virginia tobacco leaves (ICHTJ-cta-VTL-2). The percentages (%) of TMs in different components of cigarette were calculated with respect to their total contents in FT of all branded cigarettes before smoking, while smoke concentration has been calculated by subtracting the filter and ash contents from the filler tobacco content of each branded cigarette. The highest percentage (%) of Al was observed in ash of all cigarettes, with range 97.3-99.0%, while in the case of Cd, a reverse behaviour was observed, as a range of 15.0-31.3% of total contents were left in the ash of all branded cigarettes understudy.

Molecular genetic diagnosis of Glanzmann syndrome in Iranian population; reporting novel and recurrent mutations.

BACKGROUND: Glanzmann thrombasthenia (GT) is a rare autosomal recessive abnormality of platelet aggregation with quantitative and/or qualitative abnormality of αIIbß3 integrin. The αIIbß3 is a platelet fibrinogen receptor, which is required for platelet aggregation, firm adhesion, and also spreading. The disease is more prevalent in the populations with a higher rate of consanguineous marriages as in some Middle Eastern populations including Iraq, Jordan, and Iran. Different types of mutations in ITGA2B and ITGB3 genes have been previously reported to cause the disease. RESULT: In this study, 16 patients with the clinical diagnosis of GT were studied. Direct sequencing of the exons and exon-intron boundaries of the above genes revealed mutations in 14 patients (detection rate: 87.5%). Briefly, out of fifteen types of identified mutations, 14 were novel. Seven mutations in the ITGB3 gene included 4 missense [c.2T > C, c.155 G > T, c. 538 G > A, c.1990 G > T], one nonsense mutation [c.1303 G > T], a small deletion [c.1656_1658delCTC] and a deletion of one nucleotide [c.401delA]. Mutations in the ITGA2B were 8 different mutations consisting 2 missense [c.286 T > A, c.842 C > T], 2 deletions [c.1899 del T, c.189-319_236del], an insertion [c.1071_1072insG] and one splice site mutations [c.409-3 C > G], one synonymous mutation that might alter the normal splicing process [c.1392 A > G] and a nonsense mutation [c.1555 C > T]. The causative mutation in 2 patients remained unknown. Using long-range PCR and sequencing, we found a rather large deletion. The break point of this deletion covers 319 nt from the last part of the first intron and 48 nt from the beginning of the second exon of ITGA2B gene. The deletion was also detected in two unrelated patients with the same ethnicity. In addition, in silico analyses of novel mutations were performed. CONCLUSION: There was no recurrent mutation in the studied population. This may be due to either small sample size or the heterogeneity of the studied population.

Overexpression of SERTAD3, a putative oncogene located within the 19q13 amplicon, induces E2F activity and promotes tumor growth.

The amplified region of chromosome 19q13.1-13.2 has been associated with several cancers. The well-characterized oncogene AKT2 is located in this amplicon. Two members of the same gene family (SERTAD1 and SERTAD3) are also located within this region. We report herein the genomic structure and potential functions of SERTAD3. SERTAD3 has two transcript variants with short mRNA half-lives, and one of the variants is tightly regulated throughout G1 and S phases of the cell cycle. Overexpression of SERTAD3 induces cell transformation in vitro and tumor formation in mice, whereas inhibition of SERTAD3 by small interfering RNA (siRNA) results in a reduction in cell growth rate. Furthermore, luciferase assays based on E2F-1 binding indicate that SERTAD3 increases the activity of E2F, which is reduced by inhibition of SERTAD3 by siRNA. Together, our data support that SERTAD3 contributes to oncogenesis, at least in part, via an E2F-dependent mechanism.

Spoligotyping of Mycobacterium tuberculosis in anthracotic bronchitis.

BACKGROUND: Mycobacterium tuberculosis infection has been shown to be associated with anthracotic bronchitis. However, the typical manifestation of infection is not usually present in infected patients, which raises the question of whether a particular strain of M. tuberculosis is associated with this group of patients. OBJECTIVE: To determine whether a particular strain of M. tuberculosis is associated with anthracotic bronchitis. DESIGN: We assessed the predominant space oligonucleotide (spoligotype) patterns of M. tuberculosis complex isolated from patients with anthracotic bronchitis and compared the results with tuberculosis (TB) subtype patterns in Iran and other countries. RESULTS: During a 7-month period (April--October 2006), we enrolled 87 patients (30 men and 57 women) with anthracotic bronchitis, 26% (n = 23) of whom had TB. Spoligotyping of M. tuberculosis among these 23 patients showed four distinct patterns: East-African-Indian (11, 47.8%) and Central-Asian (7, 30.4%), Haarlem I (4, 17.4%) and T-1 (1, 4.3%). When compared with spoligotype patterns of M. tuberculosis in Middle Eastern countries, including Iran, anthracotic bronchitis had similar patterns. CONCLUSION: Our results indicate that the atypical manifestations of TB in anthracotic patients are not caused by any particular subtypes of M. tuberculosis. We conclude that anthracotic bronchitis is actually an atypical presentation of tuberculous infection with common subtypes inside the bronchial mucosa.

Determination of cadmium in whole blood and scalp hair samples of Pakistani male lung cancer patients by electrothermal atomic absorption spectrometer.

A large number of epidemiologic studies have been undertaken to identify potential risk factors for cancer, amongst which the association with cadmium has received considerable attention. There is compelling evidence in support of positive associations between cadmium and risk of lung cancer. In present study we measured the concentration of Cd in whole blood and scalp hair samples of 120 male lung cancer patients (smokers) and 150 controls or referents (smokers and nonsmokers) from different cities of Pakistan. Both referents and patients were of same age group (ranged 40-70 years), socio-economic status, localities and dietary habits. The scalp hair and whole blood samples were oxidized by 65% nitric acid: 30% hydrogen peroxide (2:1) ratio in microwave oven. To check the validity of the proposed method, a conventional wet acid digestion method was used to obtain total Cd concentration in certified samples of human hair BCR 397 and Clincheck control-lyophilized human whole blood. All digests were analyzed for Cd concentration by electrothermal atomic absorption spectrometer (ETAAS). The results of this study showed that the average Cd concentration was higher in the blood and scalp hair of lung cancer patients at different stages as compared to controls (p<001). The smoker referents have high level of Cd in both biological samples as compared to nonsmoker subjects. These results illustrate that the patients who continued smoking after confirmed diagnosis of lung cancer have 34.2-67.26 and 22.4-57.3% more Cd in blood samples and scalp hair than lung cancer patients who cease smoking. This study is compelling evidence in support of positive associations between cadmium, cigarette smoking and lung cancer risk.

Total dissolved and bioavailable elements in water and sediment samples and their accumulation in Oreochromis mossambicus of polluted Manchar Lake.

The concentrations of 15 elements were determined in water, sediment and tissues of fish (Oreochromis mossambicus) collected from five sampling stations of Manchar Lake in 2005 for two successive seasons, winter (WS) and summer (SS). Elements analysis was performed by atomic absorption spectrometry with flame (FAAS) and electrothermal (ETAAS) modes, using multielement standard solution. The obtained results show that, the trace and toxic elements (As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn) and macronutrients (Al, Ca, K, Mg and Na) concentrations in lake water were above the recommended drinking water standards by WHO. Concentrations of Na detected in lake water in WS and SS, were in the range of 445.5-562.7 and 420.6-643.5 mgl(-1), respectively. While among toxic elements As concentration in both seasons, have been found in the range of 60.4-88.9 and 64.9-101.8 microgl(-1) respectively, these values are 6-10 times higher than the permissible limit of WHO. The mean concentrations of elements understudy in muscles of fish were found as 2.35, 1.39, 0.46, 2.3, 1517.9, 2.2, 2.4 and 188.9 mgkg(-1) for As, Cd, Cr, Cu, Fe, Ni, Pb and Zn, respectively. High accumulation of toxic elements in fish tissues is indicating that some of the metal contaminants are entering the food chain. Correlations among the variables were identified by multivariate analysis. The extraction of elements from sediments with EDTA, to predict the bioavailability of trace and toxic elements, has shown that among them As, Cd and Zn were the most bioavailable elements in lake sediment.

Time saving modified BCR sequential extraction procedure for the fraction of Cd, Cr, Cu, Ni, Pb and Zn in sediment samples of polluted lake.

The mobility, availability and persistence of heavy metals (Cd, Cr, Cu, Ni, Pb and Zn) in contaminated lake sediment samples were evaluated by means of sequential extraction scheme, proposed by the Community Bureau of Reference protocol (BCR). The metal content in the extracts was measured by atomic absorption spectrometry. The precision and accuracy of the proposed procedure were evaluated by using a certified reference material BCR 701. The maximum recoveries for heavy metals (HMs) were observed for all three steps of BCR protocol at 32h total shaking period instead of previously reported 51h, with p>0.05. The lixiviation tests (DIN 38414-S4) were used to evaluate the leaching of HMs from sediment samples and it was observed that levels of water extractable HMs were low as compared to those values obtained by acid-soluble fraction of the BCR protocol.

Protein tyrosine kinase signaling diversity and susceptibility to targeted kinase inhibitors.

Protein kinases, including tyrosine kinases, are one of the largest classes of proteins implicated in cancer development and progression. Recent discovery of selective therapies targeting tyrosine kinase receptor signaling has provided encouraging clinical results. Clinical trials with anti-EGFR, anti-ErbB2/Her2, anti-Bcr-Abl and others have demonstrated the clinical utility of tyrosine kinases as therapeutic targets and as surrogate markers to guide the selection of patients susceptible to respond to treatment. This success has been tempered in part because resistance to targeted therapies is now documented to occur in experimental models and in patients, which hampers therapeutic efficacy. Mechanisms of resistance include cell heterogeneity in target expression, mutations in target's encoding genes, and compensatory signaling mechanisms. This paper provides a brief overview on the diversity of tyrosine kinase signaling and the impact on cancer cell response to targeted tyrosine kinase inhibitors.