Health, Wealth, and the 21st Century Cures Act

Americans are increasingly apprehensive about our future, so it is inspiring when Congress produces legislation intended to both enhance our health and expand our economy. The 21st Century Cures Act,1 recently passed by the House with an impressive bipartisan majority vote of 344 to 77, intends to accelerate the many-step process of drug discovery and development, from basic scientific research to clinical development to delivery, distribution, and ongoing monitoring. Among other things, the legislation boosts National Institute of Health funding, dramatically speeds up the US Food and Drug Administration (FDA) approval process, and aims to make use of new information technology to better monitor the performance of medical products after they reach the market. This landmark bill now awaits a comparable piece of legislation being developed by the Senate Health Education, Labor, and Pensions Committee. Together, they will transform the biomedical ecosystem and provide the foundation for the next several decades of innovative life-saving and health-enhancing solutions for our nation and the world

SPIN-MIMS simplifying the SPIN-MAS instrumentation for online measurement of 15N-abundances of ammonium, nitrite and nitrate in aqueous solutions

Common methods for measuring selectively the 15N abundances in individual N-species such as NH4+, NO2- and NO3- in samples with multiple N-species are laborious and time consuming. The SPIN-MAS technique (Stange et al. 2007) offers an automated, rapid and selective determination of 15N abundances in NH4+, NO2- and NO3- in aqueous samples. During a SPIN-MAS measurement one of three different reaction solutions is mixed with the aqueous sample in a Sample Preparation unit for Inorganic N-species (SPIN). The reaction solution is chosen in dependence on the N-species of interest. The gaseous reaction products (N2 or NO) are then conducted to a quadrupole mass spectrometer (MAS) in a helium stream. This measurement technique is not commonly used due to its complex instrumentation. The instrumentation can be significantly simplified by the use of a membrane inlet mass spectrometer (MIMS). The presented SPIN-MIMS approach relies on the use of a reaction capillary in which the sample containing the N-species of interest is mixed with the corresponding reaction solution. The mixture of reaction solution and sample is pumped from the reaction capillary directly to the membrane inlet of the mass spectrometer. The reaction products (N2 or NO) formed during the reaction of NH4+, NO2- and NO3- with the reaction solutions are passed through the gas-permeable membrane of the inlet directly into the ion source of the mass spectrometer. 15N standards with different at% 15N (NH4+, NO2- and NO3- respectively in dist. Water) were used to assess the performance of the system. Overall, SPIN-MIMS measurements showed a good agreement between measured and expected 15N abundances (range 0.36 – 10 at% 15N deviations: <0.5 at% 15N for NH4+-, <0.23 for NO2-- and <0.15 at% 15N for NO3-- standards)

crystal and solution structures of the multidomain cochaperone DnaJ

Hsp70 chaperones assist in a large variety of protein-folding processes in the cell. Crucial for these activities is the regulation of Hsp70 by Hsp40 cochaperones. DnaJ, the bacterial homologue of Hsp40, stimulates ATP hydrolysis by DnaK (Hsp70) and thus mediates capture of substrate protein, but is also known to possess chaperone activity of its own. The first structure of a complete functional dimeric DnaJ was determined and the mobility of its individual domains in solution was investigated. Crystal structures of the complete molecular cochaperone DnaJ from Thermus thermophilus comprising the J, GF and C-terminal domains and of the J and GF domains alone showed an ordered GF domain interacting with the J domain. Structure-based EPR spin- labelling studies as well as cross-linking results showed the existence of multiple states of DnaJ in solution with different arrangements of the various domains, which has implications for the function of DnaJ.1\. Auflag

CaGrid Workflow Toolkit: A taverna based workflow tool for cancer grid

SOFTWAR

Inhibition of Vaginal Lactobacilli by a Bacteriocin-Like Inhibitor Produced by Enterococcus faecium 62-6: Potential Significance for Bacterial Vaginosis

Objective: Bacterial vaginosis (BV) is characterized by a shift in vaginal tract ecology, which includes a decrease in the concentration and/or prevalence of facultative lactobacilli. Currently, mechanisms which could account for the disappearance of lactobacilli are not well understood. The objective of this study was to determine whether vaginal streptococci/enterococci can produce bacteriocin-like inhibitors antagonistic to vaginal lactobacilli. Methods: Seventy strains of vaginal streptococci or enterococci were tested for antagonistic activities against vaginal lactobacilli using the deferred antagonism technique. Results: One strain, Enterococcus faecium 62-6, which strongly inhibited growth of lactobacilli was selected for further characterization. The spectrum of inhibitory activity of strain 62-6 included Gram-positive organisms from the vaginal environment, although native lactobacilli from the same host were resistant to inhibitor action. Following growth inMRSbroth the strain 62-6 inhibitor was shown to be heat- (100℃, 30 minutes), cold- (4℃, less than 114 days) and pH- (4–7) stable. The sensitivity of inhibitor-containing supernatants to pepsin and α-chymotrypsin suggested an essential proteinaceous component. The inhibitor was sensitive to lipase but resistant to lysozyme. Dialysis of inhibitor-containing culture supernatants suggested a molecular mass greater than 12 000 Da. All physicochemical properties were consistent with its classification as a bacteriocin-like inhibitor. Kinetic assays demonstrated a sharp onset of inhibitor production coinciding with a concentration of 62-6 of 10(7) cfu/ml, suggesting that production may be regulated by quorum sensing. Conclusions: These results may have clinical significance as a novel mechanism to account for the decline of vaginal Lactobacillus populations and contribute to both the establishment and recurrence of BV

The Structure of Spatial Localization

Material objects, such as tables and chairs, have an intimate relationship with space. They have to be somewhere. They must possess an address at which they are found. Under this aspect, they are in good company. Events, too, such as Caesar’s death and John’s buttering of the toast, and more elusive entities, such as the surface of the table, have an address, difficult as it may be to specify. A stronger notion presents itself, though. Some entities may not only be located at an address; they may also own (as it were) the place at which they are located, so as to exclude other entities from being located at the same address. Thus, for certain kinds of entities, no two tokens of the same kind can be located at the same place at the same time. This is typically the case with material objects. Likewise, no two particularized properties of the same level or degree of determinacy can be located at the same place at the same time (although particularized properties of different degree, such as the red of this table and the color of this table, can). Other entities seem to evade the restriction. Two events can be perfectly co-located without competing for their address. Or, to use a different terminology, events do not occupy the spatial region at which they are located, and can therefore share it with other events. The rotation of the Earth and the cooling down of the Earth take place at exactly the same regio

Improving Appropriate Use of Antifungal Medications: The Role of an Over-the-Counter Vaginal pH Self-Test Device

Objectives: To determine whether patients can understand and use the vaginal pH device in the diagnosis of vaginitis. To compare whether vaginal pH readings determined by patients and healthcare providers are similar. To determine whether vaginalpHcan reduce inappropriate over-the-counter (OTC) antifungal medication use and improve the correct diagnosis of vaginitis. Methods: One hundred and fifty-one women indicated their belief about the cause of their vaginal infection, read the instructions of the vaginal pH device package insert, used the device and interpreted the findings. The patient interpretations were compared with results obtained by healthcare providers, blinded to patient findings. Results: Over 96% of patients stated that they could easily read the instructions, use the vaginal pH device and interpret the readings. They obtained the same readings as healthcare professionals (Kappa = 0.9). Restricting the use of OTC antifungal medications to those individuals with vaginitis symptoms and vaginal pH ≤ 4.5 significantly reduced inappropriate use by approximately 50%, Fisher's exact test,p-value = 0.018. Conversely, seeking healthcare provider assessment with vaginal pH > 4.5, leads to correct diagnosis of vaginitis. Conclusions: The vaginal pH device can be used as an OTC diagnostic tool by consumers when a vaginal infection is suspected. Vaginal pH readings would direct patients whether to purchase an antifungal medication or seek professional diagnosis from a healthcare provider. Understanding and use of this vaginal pH device could reduce inappropriate use of OTC antifungal medications by approximately 50% and improve the correct diagnosis of vaginitis