A K+-sensitive AND-gate dual-mode probe for simultaneous tumor imaging and malignancy identification

Although molecular imaging probes have the potential to non-invasively diagnose a tumor, imaging probes that can detect a tumor and simultaneously identify tumor malignancy remain elusive. Here, we demonstrate a potassium ion (K⁺) sensitive dual-mode nanoprobe (KDMN) for non-invasive tumor imaging and malignancy identification, which operates via a cascaded ‘AND’ logic gate controlled by inputs of magnetic resonance imaging (MRI) and fluorescence imaging (FI) signals. We encapsulate commercial K⁺ indicators into the hollow cavities of magnetic mesoporous silica nanoparticles, which are subsequently coated with a K⁺-selective membrane that exclusively permits the passage of K⁺ while excluding other cations. The KDMN can readily accumulate in tumors and enhance the MRI contrast after systemic administration. Spatial information of the tumor lesion is thus accessible via MRI and forms the first layer of the ‘AND’ gate. Meanwhile, the KDMN selectively captures K⁺ and prevents interference from other cations, triggering a K⁺-activated FI signal as the second layer of the ‘AND’ gate in the case of a malignant tumor with a high extracellular K⁺ level. This dual-mode imaging approach effectively eliminates false positive or negative diagnostic results and allows for non-invasive imaging of tumor malignancy with high sensitivity and accuracy.     

The microfluidics of the eccrine sweat gland,including biomarker partitioning,transport, and biosensing implications

Non-invasive and accurate access of biomarkers remains a holy grail of the biomedical community. Human eccrine sweat is a surprisingly biomarker-rich fluid which is gaining increasing attention. This is especially true in applications of continuous bio-monitoring where other biofluids prove more challenging, if not impossible. However, much confusion on the topic exists as the microfluidics of the eccrine sweat gland has never been comprehensively presented and models of biomarker partitioning into sweat are either underdeveloped and/or highly scattered across literature. Reported here are microfluidic models for eccrine sweat generation and flow which are coupled with review of blood-to-sweat biomarker partition pathways, therefore providing insights such as how biomarker concentration changes with sweat flow rate. Additionally, it is shown that both flow rate and biomarker diffusion determine the effective sampling rate of biomarkers at the skin surface (chronological resolution). The discussion covers a broad class of biomarkers including ions (Na⁺, Cl⁻, K⁺, NH₄⁺), small molecules (ethanol, cortisol, urea, and lactate), and even peptides or small proteins (neuropeptides and cytokines). The models are not meant to be exhaustive for all biomarkers, yet collectively serve as a foundational guide for further development of sweat-based diagnostics and for those beginning exploration of new biomarker opportunities in sweat.     

Role of prostaglandin in the regulation of gastric H+—Transporting system

Prostaglandins and (PG) have been reported to be an important gastric acid suppressive factor. However, the mechanism underlying is yet to be clearly established. In vitro study with gastric microsomes in presence of both PGE₂ and PGI₂ shows a stimulation of gastric H⁺ K⁺-ATPase activity below 1X10⁻⁶M and 2.5X10⁻⁷M concentrations respectively. However, with further increase in concentrations of both PGE₂ and PGI₂, H⁺, K⁺-ATPase activity shows an inhibition but PGI₂ completely obliterates the K⁺ stimulated part of H⁺, K⁺-ATPase activity at higher concentration. The H⁺-ion transport study using chambered frog gastric mucosa shows that both PGE₂ and PGI₂ inhibit H⁺-ion transport at 5X10⁻⁶ M and 10X10⁻⁶M concentrations respectively but the effect of PGI₂ is reversible. These differential effects of PGE₂ and PGI₂ on microsomal H⁺, K⁺-ATPase and on H⁺ transport my be caused by the differential effects of these phospholipid mediators with the gastric mucosal cell membrane. This in vitro investigation shows the role of prostaglandin (s) as a physiological switch/regulator of gastric H⁺ ion transport leading to the cessation of gastric acid secretion.     

Effect of corticosteroids on elevated intracellular sodium, plasma lipid peroxide levels and reduced Na+, K+-ATPase activity in patients of bronchial asthma

In view of several reports that there is a lack of balance in free radicals in case of bronchial asthma (1) the effect of free radicals on cell membrane was studied by estimating the membrane bound protein Na⁺, K⁺-ATPase activity and the intracellular sodium level in patients of bronchial asthma before and after a short course (one week) of oral corticosteroid (prednisolone 0.75–1mg/kg body weight) therapy. Results showed that there is a definite statistically significant rise in free radical level and intracellular sodium level and a significant lowering of Na⁺, K⁺-ATPase activity in case of untreated bronchial asthma. After short course of therapy with oral corticosteroids, the free radical level and intracellular sodium level decreased significantly, together with a significant rise of the Na⁺, K⁺-ATPase activity. Also, a significant negative correlation (r=−0.74) between the lipid peroxide level and the Na⁺,-K⁺-ATPase activity was found in these cases.     

Evaluation of alkali and thermotolerant lipase from an indigenous isolated Bacillus strain for detergent formulation

BackgroundLipases are used in detergent industries to minimise the use of phosphate-based chemicals in detergent formulations. The use of lipase in household laundry reduces environmental pollution and enhances the ability of detergent to remove tough oil or grease stains.ResultsA lipase-producing indigenous Bacillus subtilis strain [accession no. KT985358] was isolated from the foothills of Trikuta mountain in Jammu and Kashmir, India. The lipase (BSK-L) produced by this strain expressed alkali and thermotolerance. Lipase has an optimal activity at pH 8.0 and temperature 37°C, whereas it is stable at pH 6.0–9.0 and showed active lipolytic activity at temperatures 30 to 60°C. Furthermore, lipase activity was found to be stimulated in the presence of the metal ions Mn^2 +, K⁺, Zn^2 +, Fe^2 + and Ca^2 +. This lipase was resistant to surfactants, oxidising agents and commercial detergents, suggesting it as a potential candidate for detergent formulation. BSK-L displayed noticeable capability to remove oil stains when used in different washing solutions containing buffer, lipase and commercial detergent. The maximum olive oil removal percentage obtained was 68% when the optimum detergent concentration (Fena) was 0.3%. The oil removal percentage from olive oil-soiled cotton fabric increased with 40 U/mL of lipase.ConclusionsThis BSK-L enzyme has the potential for removing oil stains by developing a pre-soaked solution for detergent formulation and was compatible with surfactants, oxidising agents and commercial detergents.     

Increasing Glucose Concentrations Interfere with Estimation of Electrolytes by Indirect Ion Selective Electrode Method

The estimation of electrolytes like sodium (Na⁺), potassium (K⁺) and chloride (Cl⁻) using direct and indirect ion-selective electrodes (ISE) is a routine laboratory practice. Interferents like proteins, triglycerides, drugs etc. are known to affect the results. The present study was designed to look into the effect of increasing glucose concentrations on estimation of Na⁺, K⁺ and Cl⁻ by direct and indirect ISE. Pooled sera was mixed with glucose stock solution (20 g/dL) prepared in normal saline to obtain glucose concentrations ranging from ~100 to ~5000 mg/dL. Na⁺, K⁺ and Cl⁻ levels were estimated by direct and indirect ISE analyzers and results were statistically analysed using ANOVA and Pearson’s correlation. Similar experiment was also performed in 24 h urine sample from healthy subjects. Significant difference was observed between Na⁺ and Cl⁻ measurements by direct and indirect ISE, with indirect ISE values being consistently higher than direct ISE. Besides this, significant difference was observed amongst Na⁺ and Cl⁻ values from baseline values obtained by indirect ISE at glucose concentrations ≥2486 mg/dL. However, no such difference was observed with direct ISE. Na⁺ and Cl⁻ estimation by indirect ISE showed significant negative correlation with glucose concentration, more so, above ~2000 mg/dL. K⁺, however, showed no significant difference with varying glucose. Similar results were observed in 24 h urine samples with a significant difference observed amongst Na⁺ and Cl⁻ values at ≥2104 mg/dL glucose. Thus we conclude that high glucose concentrations interfere significantly in estimation of Na⁺ and Cl⁻ by indirect ISE in serum as well as urine.

Electronic supplementary material

The online version of this article (doi:10.1007/s12291-015-0522-0) contains supplementary material, which is available to authorized users.     

Insulin or sulfonylurea treatments of the diabetics differentially affect erythrocyte membrane and serum enzymes and extent of protein glycosylation

Erythrocyte membrane protein glycosylation increase by 3.4 fold in diabetes. Insulin or sulfonylurea treatment did not reduce the extent of glycosylation. The serum protein glycosylation was comparable in all the groups including control. Erythrocyte membrane Na⁺,K⁺-ATPase activity decreased in the diabetics; only insulin treatment partly restored the activity. Erythrocyte membrane acetylcholinesterase activity decreased only in the sulfonylurea treated group. Serum butyrylcholinesterase activity was relatively low in the diabetic and insulin treated diabetic groups. The Km and Vmax of the two components of Na⁺,K⁺-ATPase from erythrocyte membranes were differently affected in the diabetic and the two treatment groups. The Vmax of acetylcholinesterase decreased only in the sulfonylurea treated group. Diabetic states resulted in decreased Vmax of components I and II of serum butyrylcholinesterase. In insulin-treated diabetics, component II was absent. Sulfonylurea group resembled diabetics.In vitro incubation with insulin differentially affected the Na⁺,K⁺-ATPase and serum butyrylcholinesterase activities.     

The effects of different syringe volume, needle size and sample volume on blood gas analysis in syringes washed with heparin

Introductıon:

We evaluated the effect of different syringe volume, needle size and sample volume on blood gas analysis in syringes washed with heparin.

Materials and methods:

In this multi-step experimental study, percent dilution ratios (PDRs) and final heparin concentrations (FHCs) were calculated by gravimetric method for determining the effect of syringe volume (1, 2, 5 and 10 mL), needle size (20, 21, 22, 25 and 26 G) and sample volume (0.5, 1, 2, 5 and 10 mL). The effect of different PDRs and FHCs on blood gas and electrolyte parameters were determined. The erroneous results from nonstandardized sampling were evaluated according to RiliBAK’s TEa.

Results:

The increase of PDRs and FHCs was associated with the decrease of syringe volume, the increase of needle size and the decrease of sample volume: from 2.0% and 100 IU/mL in 10 mL-syringe to 7.0% and 351 IU/mL in 1 mL-syringe; from 4.9% and 245 IU/mL in 26G to 7.6% and 380 IU/mL in 20 G with combined 1 mL syringe; from 2.0% and 100 IU/mL in full-filled sample to 34% and 1675 IU/mL in 0.5 mL suctioned sample into 10 mL-syringe. There was no statistical difference in pH; but the percent decreasing in pCO₂, K⁺, iCa²⁺, iMg²⁺; the percent increasing in pO₂ and Na⁺ were statistical significance compared to samples full-filled in syringes. The all changes in pH and pO₂ were acceptable; but the changes in pCO₂, Na⁺, K⁺ and iCa²⁺ were unacceptable according to TEa limits except fullfilled-syringes.

Conclusions:

The changes in PDRs and FHCs due nonstandardized sampling in syringe washed with liquid heparin give rise to erroneous test results for pCO₂ and electrolytes.     

伊犁谷地灰钙土和风沙土剖面特性及生态建设意义

西部的生态环境安全关系到国家的生态安全。研究土壤特性及其垂直分布,能对区域生态环境建设和可持续发展提供重要的理论基础和指导。灰钙土与风沙土是新疆伊犁谷地的两种主要土壤类型。本文在对新疆伊犁谷地实地考察基础上,运用42个灰钙土剖面和12个风沙土剖面自然发生层各层的土壤样品测试数据—土壤有机质、pH值、电导率、总盐、八大阴阳离子,研究了灰钙土和风沙土土壤特性的垂直分布,并进行了比较;在此基础上提出区域生态建设中土壤利用和保护的建议。研究表明,伊犁河谷的不同土壤,其土壤特性的垂直分布和变化具有一致性和差异性。一致性体现在有机质和K＋的含量随土壤深度增加而减少,pH值、CO32-、Mg2＋和Na＋的含量随土壤深度增加而增加。差异性体现在两类土壤的有机质、pH值、电导率和总盐在数量上不同。此外,两类土壤的电导率、总盐及SO42-,Cl-,HCO3-,Ca2＋的含量随土壤深度发生变化的趋势不同。     

天山乌鲁木齐河源区径流水化学特征及影响因素分析

在乌鲁木齐河源区采集两年的大气降水和1号冰川、空冰斗、总控3个水文点逐日定时径流样品,对主要离子、pH、电导率EC和总溶解固体TDS进行了分析。结果表明,大气降水离子类型为Ca^2＋-Na^＋-HCO3--SO4^2-,接近中性;径流离子类型为Ca^2＋-Na^＋-HCO3--SO4^2-,呈弱碱性。径流中EC和TDS均值总控〉1号冰川〉空冰斗,其中1号冰川径流的峰值远高于其它两个水文点。受不同下垫面的影响,1号冰川水文点TDS变化受日径流量影响显著,而空冰斗水文点基本不受影响。径流中离子组成主要受岩石风化作用影响,离子比值和Piper图分析说明控制径流离子的主要过程是碳酸盐、黄铁矿和长石类矿物风化。海盐校正分析得出,大气降水对1号冰川、空冰斗、总控径流离子贡献率分别为4.91％,9．10％和5．42％。通过阳离子通量计算,2006年、2007年1号冰川径流的化学风化侵蚀率分别为18．1t／（km^2·a）和12．3t／（km^2·a）。     

Estimation of mRNA levels of interleukin (IL)-10, tumor necrosis factor (TNF)-α, IL-4 and interferon (IFN)-γ in HIV infected children in Mumbai

Cytokines, viral load and opportunistic infections play an important role in HIV-disease progression. Hundred children vertically infected with HIV were enrolled to determine mRNA levels of TNF-α, IL-10, IL-4 and IFN-γ. These levels were estimated by amplifying cytokine mRNA from peripheral blood mononuclear cells. Severity of HIV was staged by the reduction in CD₄ ⁺ T cells and the onset of opportunistic infections. IL-10 mRNA levels were observed to increase with the severity. Despite the rising IL-10 mRNA levels, TNF-α mRNA levels increased with severity of HIV and decrease in CD₄ ⁺ T cell counts. IL-4 mRNA levels increased with the reduction in CD₄ ⁺ T cell numbers. Depleting mRNA levels of IFN-γ contributed to the worsening of HIV disease. Increase in TNF-α and IL-4 levels appended to the disease severity by upregulation of the viral replication. Increased IL-10 levels and decreased IFN-γ levels predisposed the children to HIV associated opportunistic infections, which in return contributed to cytokine disarray.     

Effect ofCrataeva nurvala bark decoction on enzymatic changes in liver of normal and stone forming rats

The influence of Crataeva nurvala bark decoction was studied in calcium oxalate stone forming rats, in relation to oxalate metabolism in liver. The activities of the major oxalate synthesizing enzymes in liver namely, glycollate oxidase (GAO) and lactate dehydrogenase (LDH) were significantly increased in the calculogenic group. Bark decoction treatment lowered the liver GAO activity considerably. Transport ATPases (Na⁺, K⁺ and Ca²⁺-ATPases) and alkaline phosphatase were enhanced in rats fed calculi producing diet, while the activities of acid phosphatase, inorganic pyrophosphatase and aminotransferases were slightly reduced. Bark decoction administration produced a marginal decrease in Na⁺, K⁺-ATPase and increase in aspartate aminotransferase activities, without significantly altering other enzyme activities. The decrease in liver GAO activity seen during bark decoction treatment, with concomitant decrease in kidney oxalate level, may prove beneficial as a prophylactic measure in preventing stone recurrence.     

Diffraction-limited ultrasensitive molecular nano-arrays with singular nano-cone scattering

Large-library fluorescent molecular arrays remain limited in sensitivity (1 × 10⁶ molecules) and dynamic range due to background auto-fluorescence and scattering noise within a large (20–100 μm) fluorescent spot. We report an easily fabricated silica nano-cone array platform, with a detection limit of 100 molecules and a dynamic range that spans 6 decades, due to point (10 nm to 1 μm) illumination of preferentially absorbed tagged targets by singular scattering off wedged cones. Its fluorescent spot reaches diffraction-limited submicron dimensions, which are 10⁴ times smaller in area than conventional microarrays, with comparable reduction in detection limit and amplification of dynamic range.Commercially available fluorescent micro-arrays based on target labeling, northern blot, or enzyme-linked immunosorbent assay (ELISA) are limited to a detection threshold of 1 to 10 × 10⁶ molecules per fluorescent spot,^{1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23} thus requiring cell culturing or Polymerase Chain Reaction (PCR) amplification for many applications. The low sensitivity is often due to broad illumination, which creates auto-fluorescence noise. Even if point illumination and pin-hole filtering of non-focal plane noise are implemented in a confocal setup, the large and non-uniform fluorescent spots create scattering noise over each 20–100 μm element, which degrades the detection limit.⁴ Smaller spots can, in theory, be introduced by nano-sprays and nano-imprinting. However, directing the targets to such small areas then becomes problematic. Real-time PCR is, in principle, capable of detecting a single molecule but is limited in its target number⁵ and is hence slow/expensive for large-library assays. A large-library platform with much better detection limit than the current fluorescent microarrays would transform many screening assays. Ideally, this platform would not use the confocal configuration. Instead, it would direct the target molecules to a submicron spot and illuminate them with a nearby point source that does not require scanning.A promising platform is the optical fiber bundle array,⁶ with more than 10⁴ fibers and targets, in principle. With its endoscopic configuration, these fiber bundles are most convenient for in situ and real-time biosensing modalities in microfluidic biochips and microfluidic 3-D cell cultures. Consequently, the optical sensing is typically carried out in the transmission mode, with the optical signals transmitted through the optical fibers to a detector. Microwell arrays at the distal end of imaging fiber, with molecular targets captured and transported to the microwells by microbeads, are the most popular among these optical fiber arrays. Although detection limit better than 1 × 10⁶ molecules per bead has been reported, the bar-coded beads limit the target number of this platform.^{7, 8}Our previous work^{9, 10} has shown that plasmonics at nanotips can enhance local electric field by three orders of magnitude. However, conduction loss and quenching of fluorescence^{11, 12} by the metal substrates limit the use of plasmonic enhanced fluorescence for large-library assays. Only nano-molar sensitivity has been demonstrated using plasmonics from metal coated nanocone tips.^{13, 14} In this paper, we will extend the conical fiber array platform not by tip plasmonics but by another optical phenomenon with induced dipoles: singular scattering off dielectric wedges and tips.¹⁵ Instead of the surface plasmon resonance on metallic nanostructures,¹⁶ field focusing at the cone tip by the dielectric media (the silica fiber) is used to produce a localized and singularly large scattering intensity at the tip. Singular scattering from a wedge or a cone has been known for decades.^{17, 18} It is only recently that numerical simulation¹⁹ has revealed that field focusing by this singular scattering can effect a five-order intensity enhancement that is frequency independent. This intense tip scattering produces a local light source at the tip that does not suffer from conduction loss. Unlike plasmonic metal nanostructures, the dielectric tip would also not quench the fluorescent reporters excited by the light source. In fact, it will help scatter the fluorescent signal, with Rayleigh scattering intensity scaling with respect to wavelength. We hence utilize this phenomenon for diffraction-limit fluorescent sensing/imaging for the first time here.The local light source due to tip scattering minimizes background auto-fluorescence and scattering noise, provided the target molecules preferentially diffuse towards the dielectric vertices. If the targets do not preferentially hybridize with probes at the vertices, there would be significant target loss, with a concomitant loss in sensitivity, because the vertex regions are just a small fraction of the total area. Fortunately, like electromagnetic radiation at the electrostatic limit of the Maxwell equations for sharp (sub-wavelength) vertices,²⁰ the steady-state diffusion of molecules also obey the Laplace equation and so do the DC or AC electric potentials that drive electrophoresis and dielectrophoresis of the molecules.²¹ Hence, the diffusive, electrophoretic, and dielectrophoretic fluxes of target molecules are also singularly large at the vertices and there will be preferential hybridization there until the tip is saturated. Previously, we have demonstrated preferential diffusive transport of colloids to channel corners²² and dieletrophoretic trapping of bacteria²³ and DNA molecules²⁴ around sharp nanostructures like carbon nanotubes. Hence, dielectric nanotips fabricated by low-cost techniques can potentially provide the smallest fluorescent spot, which can preferentially capture target molecules and whose fluorescent image is limited in size only by the diffraction limit, without a confocal configuration.Although the scattering singularity is stronger at the conic tip, the total increase in scattering area of this singularity of measure zero is not as high as that of a sharp wedge, thus rendering the signal relatively weak. We hence employ a well-defined multi-wedged silica cone fabricated by wet-etching, with the wedges introduced by non-uniform stress formed during the fiber assembly process, to produce maximum scattering at the tip where three to four wedges converge (see inset of Fig. ​Fig.1A).1A). Using the reflection mode to fully exploit this singular scattering to excite fluorescent reporters at the tip and transmit the resulting signal, we report a nanocone array that can detect down to 100 molecules per cone tip with a large dynamic range from femtomolar to nanomolar concentrations. Although quantification for a single target is reported in this preliminary report, multi-target assays can readily be developed.Open in a separate windowFigure 1(A) A SEM image of the silica cone array where the single cone inset image shows three wedges converging into a 10 nm junction at the tip. (B) The optical setup of measurement. (C) The diffraction-limited fluorescent spot images.Amine-modified 35-base oligo-probes were functionalized onto both unetched silica fibers (as a control) and etched conic silica tips. The sample of 35-base ssDNA targets (corresponding to a primer for a segment of the Serotype 2 dengue genome) with a 5′ tagged Cy3 fluorophore was inserted into a microfluidic chip housing the fiber bundle (Fig. ​(Fig.1B)1B) and left overnight (see the supplementary material²⁵ for exact sequence). After a standard rinsing protocol, fluorescent images were taken with an Olympus IX-71 fluorescent microscope for target concentrations ranging from 1 fM to 1 nM. A typical fluorescent image after hybridization is shown in Fig. ​Fig.1c,1c, where each micron-sized bright spot corresponds to a single tip in the cone array. The intensity profile shown in the supplementary material²⁵ indicates a fluorescent spot smaller than 1 μm, indicating that the fluorescent light source is sub-wavelength and the resolution is close to diffraction limit. The size of this bright spot at the conic tip does not vary much with respect to the concentration but its intensity does, as shown in Fig. ​Fig.2A.2A. It was found that for flat fibers, only concentrations higher than 1 nM produced significant signals above the background. However, for etched conic fibers, 10 fM is clearly distinguishable from the background, which indicates that an improvement of sensitivity up to five orders can be realized by simply etching the flat surface into cone arrays. It also suggests very little target loss due to preferential hybridization onto the cone at sub-nM concentrations. We estimated the number of molecules per cone from the total number of molecules in target solution divided by the number of pixels on each fiber (10⁴), which suggests less than 100 molecules per cone for a 10 fM bulk concentration, four orders better than any existing technology.Open in a separate windowFigure 2(A) Fluorescent intensity of etched conic fiber and unetched fiber for different concentrations of target molecules from 1 fM to 1 nM. (B) Fluorescent intensity increases linearly with exposure time. Non-target molecules with 1 μM concentration do not produce significant signal compared to lower concentrations of target molecules such as 1 nM and 10 nM (see the supplementary material²⁵ for details of image analysis).Selectivity of the platform was also examined. Fig. ​Fig.2B2B presents the fluorescent intensity of the tips for non-target (1 μM) and target (1 nM and 10 nM) at different exposure times, which shows that fluorescent intensity increases linearly with exposure time. Beyond 5 s, saturation of images prevents further increase in the signal. For non-target, the intensity is much lower than 1 nM Target and 10 nM Target, which means non-target do not bind to the probes at the wedged tip as effectively as target molecules. Non-specific binding can be further removed by using more stringent buffers and higher flow rates.²⁶ This platform can be extended to detect 70 000 targets, in theory, by functionalizing different probes onto each cones using localized photochemistry via masking, micro-mirror directed illumination, or direct laser writing. Extension to ELISA type protein assays is also straight forward. Integration of a transmission-mode optical fiber endoscope into a microfluidic biochip and into a 3-D cell culture for real-time monitoring of multiple molecular targets at near-single molecule resolution is currently underway.     

Cl-指示的石羊河流域地下水演化

化学示踪剂是研究干旱区地下水化学演化和补给来源追踪的有效手段之一。本文以Cl-为示踪剂,通过其他离子与Cl-的相互关系对石羊河流域地下水演化特征及影响因子进行分析:Br-/Cl-、Na+/Cl-、S042-/Cl-、HCO3-/Cl-、Ca2+/Cl-、Mg2+/Cl-相互关系指示了流域中游地区地下水与地表水补给关系密切,水质较好,水化学作用以溶滤为主,蒸发也起到一定作用,下游盆地地下水矿化度较高,不完全是现代降水的补给,石膏、方解石溶解和阳离子交换作用使得地下水富镁。总体而言,石羊河流域地下水演化在多种地球化学作用下进行,在以蒸发为主导动力的条件下,水岩相互作用和阳离子交换过程促使地下水演化为现代特征。     

Role of pump prime in the etiology of cardio-pulmonary bypass associated acidosis

The development of metabolic acidosis during cardio-pulmonary bypass (CPB) is a well recognized but poorly explained phenomenon. It has been hypothesized that it is purely a development after the delivery of pump prime. A retrospective study was conducted at our hospital on 68 patients who underwent elective coronary artery bypass grafting (CABG). Sampling of arterial blood was performed at three time intervals: (T₁) Baseline, prior to induction; (T₂) 5 minutes after initiation of CPB and prior to administration of cardioplegia solution; (T3) during rewarming prior to weaning the patient off CPB. Measurements of Na⁺, K⁺, Cl⁻, pH, pCO₂, HCO₃ ⁻, Base excess, Anion gap, Strong ion difference at each collection point were performed. Results were analyzed in a quantitative manner. On delivery of pump prime, all patients' developed metabolic acidosis. However, it is very important to distinguish the metabolic acidosis as their management varies. Anion gap has been found to be useful in managing peri-operative metabolic acidosis.     

Effect of a dual inlet channel on cell loading in microfluidics

Unwanted sedimentation and attachment of a number of cells onto the bottom channel often occur on relatively large-scale inlets of conventional microfluidic channels as a result of gravity and fluid shear. Phenomena such as sedimentation have become recognized problems that can be overcome by performing microfluidic experiments properly, such as by calculating a meaningful output efficiency with respect to real input. Here, we present a dual-inlet design method for reducing cell loss at the inlet of channels by adding a new “ upstream inlet ” to a single main inlet design. The simple addition of an upstream inlet can create a vertically layered sheath flow prior to the main inlet for cell loading. The bottom layer flow plays a critical role in preventing the cells from attaching to the bottom of the channel entrance, resulting in a low possibility of cell sedimentation at the main channel entrance. To provide proof-of-concept validation, we applied our design to a microfabricated flow cytometer system (μFCS) and compared the cell counting efficiency of the proposed μFCS with that of the previous single-inlet μFCS and conventional FCS. We used human white blood cells and fluorescent microspheres to quantitatively evaluate the rate of cell sedimentation in the main inlet and to measure fluorescence sensitivity at the detection zone of the flow cytometer microchip. Generating a sheath flow as the bottom layer was meaningfully used to reduce the depth of field as well as the relative deviation of targets in the z-direction (compared to the x-y flow plane), leading to an increased counting sensitivity of fluorescent detection signals. Counting results using fluorescent microspheres showed both a 40% reduction in the rate of sedimentation and a 2-fold higher sensitivity in comparison with the single-inlet μFCS. The results of CD4⁺ T-cell counting also showed that the proposed design results in a 25% decrease in the rate of cell sedimentation and a 28% increase in sensitivity when compared to the single-inlet μFCS. This method is simple and easy to use in design, yet requires no additional time or cost in fabrication. Furthermore, we expect that this approach could potentially be helpful for calculating exact cell loading and counting efficiency for a small input number of cells, such as primary cells and rare cells, in microfluidic channel applications.     

Serum Cytokine Profile in Psoriasis-A Case–Control Study in a Tertiary Care Hospital from Northern India

Psoriasis is chronic autoimmune hyperproliferative skin disease with a population prevalence of 1.5–3%. The cause of psoriasis is still not fully understood. It has been hypothesized to be an immune-mediated disorder in which the excessive reproduction of keratinocytes is due to cytokines such as interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha, secreted by infiltrating CD4⁺ and CD8⁺ T cells and natural killer cells. The aim of our study was to determine the serum levels of TNF-α, IL-4, IL-6 & IL-10 in psoriasis patients and compare it with healthy controls. 30 clinically diagnosed psoriasis patients and 30 age and sex matched healthy controls were included in the study. The serum cytokine levels were measured by solid phase sandwich ELISA (DIACLONE Research, France). TNF-α and IL-6 levels were significantly raised in patients and the results were statistically significant (P < 0.001). IL-4 levels were higher in patients than in controls (1.91 ± 4.7 pg/ml in cases & 0.9 ± 0.3 pg/ml in controls) but were not statistically significant. Interestingly, IL-10 levels were found to be higher in controls than in patients but again, it was not statistically significant. Pro-inflammatory cytokines play a pivotal role in the pathogenesis of psoriasis and it is the type 1(TH1) cytokine pattern, i.e., IL-6 & TNF-α, which predominate in the psoriatic T cell response. Further studies on IL-10 levels in psoriasis are recommended to establish their exact role in the pathogenesis of the disease.     

Hyperlipidemia, increased lipid peroxidation and changes in antioxidant enzymes, Na+−K+-ATPase in erythrocytes of type 2 diabetic patients in andhra pradesh

Plasma levels of lipids, lipoproteins and lipid peroxides and erythrocyte Na⁺−K⁺ ATPase, Mg²⁺ATPase and antioxidant enzymes were measured in type-2 diabetic patients. A significant decrease in Na⁺-K⁺-ATPase activity was observed in diabetic patients which was negatively correlated with blood glucose and lipid peroxides, while the Mg²⁺-ATPase activity was increased. In the diabetic subjects the plasma concentrations of Na⁺ and K⁺ were increased where as erythrocyte levels of Na⁺ were increased and K⁺ were decreased. Hyperlipidaemia and increased levels of lipid peroxides were observed in the diabetic subjects. There was a significant increase in erythrocyte catalase activity in diabetics which positively correlated with their lipid peroxides. There was no change in GPx activities between controls and diabetics.     

A portable lab-on-a-chip system for gold-nanoparticle-based colorimetric detection of metal ions in water

Heavy metal ions released into various water systems have a severe impact on the environment and human beings, and excess exposure to toxic metal ions through drinking water poses high risks to human health and causes life-threatening diseases. Thus, there is high demand for the development of a rapid, low-cost, and sensitive method for detection of metal ions in water. We present a portable analytical system for colorimetric detection of lead (Pb²⁺) and aluminum (Al³⁺) ions in water based on gold nanoparticle probes and lab-on-a-chip instrumentation. The colorimetric detection of metal ions is conducted via single-step assays with low limits of detection (LODs) and high selectivity. We design a custom-made microwell plate and a handheld colorimetric reader for implementing the assays and quantifying the signal readout. The calibration experiments demonstrate that this portable system provides LODs of 30 ppb for Pb²⁺ and 89 ppb for Al³⁺, both comparable to bench-top analytical spectrometers. It promises an effective platform for metal ion analysis in a more economical and convenient way, which is particularly useful for water quality monitoring in field and resource-poor settings.     

Some properties of a class of biased regression estimators

For the linear statistical model y = Xb + e, X of full column rank estimates of b of the form (C + X′X)⁺X′y are studied, where C commutes with X′X and Q⁺ is the Moore-Penrose inverse of Q. Such estimators may have smaller mean square error, component by component than does the least squares estimator. It is shown that this class of estimators is equivalent to two apparently different classes considered by other authors. It is also shown that there is no C such that (C + X′X)⁺X′Y = My, in which My has the smallest mean square error, component by component. Two criteria, other than tmse, are suggested for selecting C. Each leads to an estimator independent of the unknown b and σ². Subsequently, comparisons are made between estimators in which the C matrices are functions of a parameter k. Finally, it is shown for the no intercept model that standardizing, using a biased estimate for the transformed parameter vector, and retransforming to the original units yields an estimator with larger tmse than the least squares estimator.