A rapid and reliable determination of doxycycline hyclate by HPLC with UV detection in pharmaceutical samples

An accurate, sensitive and reproducible high performance liquid chromatographic (HPLC) method for the quantification of doxycycline hyclate in pharmaceutical samples has been developed and validated. The drug and the standard were eluted from a Lichrosorb RP-8 (250 mm´4.6 mm, 10 mm particle size) at 20 °C with a mobile phase consisting of methanol, acetonitrile and 0.010 M aqueous solution of oxalic acid (2:3:5, v/v/v). The flow rate was 1.25 ml min-1. A UV detector set at 350 nm was used to monitor the effluent. Each analysis required no longer than 4 min. The limits of detection and quantification were 1.15 and 3.84 μg ml-1, respectively. Recoveries for different concentrations ranged from 99.58 to 101.93 %

Vav1/2/3-null mice define an essential role for vav family proteins in lymphocyte development and activation but a differential requirement in MAPK signaling in T and B cells

The Vav family of Rho guanine nucleotide exchange factors is thought to orchestrate signaling events downstream of lymphocyte antigen receptors. Elucidation of Vav function has been obscured thus far by the expression of three highly related family members. We generated mice lacking all Vav family proteins and show that Vav-null mice produce no functional T or B cells and completely fail to mount both T-dependent and T-independent humoral responses. Whereas T cell development is blocked at an early stage in the thymus, immature B lineage cells accumulate in the periphery but arrest at a late “transitional” stage. Mechanistically, we show that the Vav family is crucial for both TCR and B cell receptor (BCR)–induced Ca(2+) signaling and, surprisingly, is only required for mitogen-activated protein kinase (MAPK) activation in developing and mature T cells but not in B cells. Thus, the abundance of immature B cells generated in Vav-null mice may be due to intact Ras/MAPK signaling in this lineage. Although the expression of Vav1 alone is sufficient for normal lymphocyte development, our data also reveal lineage-specific roles for Vav2 and Vav3, with the first demonstration that Vav3 plays a critical compensatory function in T cells. Together, we define an essential role for the entire Vav protein family in lymphocyte development and activation and establish the limits of functional redundancy both within this family and between Vav and other Rho–guanine nucleotide exchange factors

LOVING YOUR LIVER: the complete guide to liver detox

Loving Your Liver. The Complete Guide to Liver Detox is a comprehensive guide to liver “maintenance”. Written in a simple and intuitive way, it helps understand what the liver is, what it does, how it works, how it is affected by our lifestyle, the most common diseases that can affect it and most importantly, how to take care of it. Of course, the key to a good liver detox lies in nutrition and for this very reason the learning journey with Hrvoje Miletic and Simon Taylor-Robinson ends with a section entirely dedicated to a number of delicious recipes that are good for the liver without sacrificing taste. Hrvoje Miletic is a noted food expert in Croatia and across Europe. He holds international diplomas in culinary affairs and in management. Hrvoje’s experience in the United Kingdom and across Europe has moulded his culinary experience and flair. He is currently a food researcher and entrepreneur, using his skills to help people lead a healthy lifestyle. His considerable expertise is reflected in the book. Simon Taylor-Robinson is a medical doctor. He trained as a gastroenterologist and hepatologist. He has conducted medical research on liver disease with projects around the world. During his career, he has combined being a clinical doctor with liver expertise with being a medical researcher and a teacher at the undergraduate and postgraduate level. He also holds several honorary Professorial appointments at institutions in sub-Saharan Africa and in Asia

Measurement of the 8B Solar Neutrino Flux with the KamLAND Liquid Scintillator Detector

We report a measurement of the neutrino-electron elastic scattering rate from 8B solar neutrinos based on a 123 kton-day exposure of KamLAND. The background-subtracted electron recoil rate, above a 5.5 MeV analysis threshold is 1.49+/-0.14(stat)+/-0.17(syst) events per kton-day. Interpreted as due to a pure electron flavor flux with a 8B neutrino spectrum, this corresponds to a spectrum integrated flux of 2.77+/-0.26(stat)+/-0.32(syst) x 10^6 cm^-2s^-1. The analysis threshold is driven by 208Tl present in the liquid scintillator, and the main source of systematic uncertainty is due to background from cosmogenic 11Be. The measured rate is consistent with existing measurements and with Standard Solar Model predictions which include matter enhanced neutrino oscillation.Comment: 6 pages, 3 figure

A compact ultra-clean system for deploying radioactive sources inside the KamLAND detector

We describe a compact, ultra-clean device used to deploy radioactive sources along the vertical axis of the KamLAND liquid-scintillator neutrino detector for purposes of calibration. The device worked by paying out and reeling in precise lengths of a hanging, small-gauge wire rope (cable); an assortment of interchangeable radioactive sources could be attached to a weight at the end of the cable. All components exposed to the radiopure liquid scintillator were made of chemically compatible UHV-cleaned materials, primarily stainless steel, in order to avoid contaminating or degrading the scintillator. To prevent radon intrusion, the apparatus was enclosed in a hermetically sealed housing inside a glove box, and both volumes were regularly flushed with purified nitrogen gas. An infrared camera attached to the side of the housing permitted real-time visual monitoring of the cable's motion, and the system was controlled via a graphical user interface.Comment: Revised author affiliations, corrected typos, made minor improvements to text, and revised reference

Glutamine synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restriced glioblastoma

L-Glutamine (Gln) functions physiologically to balance the carbon and nitrogen requirements of tissues. It has been proposed that in cancer cells undergoing aerobic glycolysis, accelerated anabolism is sustained by Gln-derived carbons, which replenish the tricarboxylic acid (TCA) cycle (anaplerosis). However, it is shown here that in glioblastoma (GBM) cells, almost half of the Gln-derived glutamate (Glu) is secreted and does not enter the TCA cycle, and that inhibiting glutaminolysis does not affect cell proliferation. Moreover, Gln-starved cells are not rescued by TCA cycle replenishment. Instead, the conversion of Glu to Gln by glutamine synthetase (GS; cataplerosis) confers Gln prototrophy, and fuels de novo purine biosynthesis. In both orthotopic GBM models and in patients, (13)C-glucose tracing showed that GS produces Gln from TCA-cycle-derived carbons. Finally, the Gln required for the growth of GBM tumours is contributed only marginally by the circulation, and is mainly either autonomously synthesized by GS-positive glioma cells, or supplied by astrocytes

7Be Solar Neutrino Measurement with KamLAND

We report a measurement of the neutrino-electron elastic scattering rate of 862 keV 7Be solar neutrinos based on a 165.4 kton-day exposure of KamLAND. The observed rate is 582 +/- 90 (kton-day)^-1, which corresponds to a 862 keV 7Be solar neutrino flux of (3.26 +/- 0.50) x 10^9 cm^-2s^-1, assuming a pure electron flavor flux. Comparing this flux with the standard solar model prediction and further assuming three flavor mixing, a nu_e survival probability of 0.66 +/- 0.14 is determined from the KamLAND data. Utilizing a global three flavor oscillation analysis, we obtain a total 7Be solar neutrino flux of (5.82 +/- 0.98) x 10^9 cm^-2s^-1, which is consistent with the standard solar model predictions.Comment: 8 pages, 6 figures, submitted to Phys. Rev.

Search for extraterrestrial antineutrino sources with the KamLAND detector

We present the results of a search for extraterrestrial electron antineutrinos ($\bar{\nu}_{e}$'s) in the energy range $8.3 MeV < E_{\bar{\nu}_{e}} < 31.8 MeV$ using the KamLAND detector. In an exposure of 4.53 kton-year, we identify 25 candidate events. All of the candidate events can be attributed to background, most importantly neutral current atmospheric neutrino interactions, setting an upper limit on the probability of $^{8}$B solar $\nu_{e}$'s converting into $\bar{\nu}_{e}$'s at $5.3 \times 10^{-5}$ (90% C.L.), if we assume an undistorted $\bar{\nu}_{e}$ shape. This limit corresponds to a solar $\bar{\nu}_{e}$ flux of $93 cm^{-2} s^{-1}$ or an event rate of $1.6 events (kton-year)^{-1}$ above the energy threshold $(E_{\bar{\nu}_{e}} > 8.3 MeV)$. The present data also allows us to set more stringent limits on the diffuse supernova neutrino flux and on the annihilation rates for light dark matter particles.Comment: 22 pages, 6 figure