Solid-State Laser Source of Tunable Narrow-Bandwidth Ultraviolet Radiation

A solid-state laser source of tunable and narrow-bandwidth UV light is disclosed. The system relies on light from a diode laser that preferably generates light at infrared frequencies. The light from the seed diode laser is pulse amplified in a light amplifier, and converted into the ultraviolet by frequency tripling, quadrupling, or quintupling the infrared light. The narrow bandwidth, or relatively pure light, of the seed laser is preserved, and the pulse amplifier generates high peak light powers to increase the efficiency of the nonlinear crystals in the frequency conversion stage. Higher output powers may be obtained by adding a fiber amplifier to power amplify the pulsed laser light prior to conversion

Conventional metaphors elicit greater real-time engagement than literal paraphrases or concrete sentences

Conventional metaphors (e.g., a firm grasp on an idea) are extremely common. A possible explanation for their ubiquity is that they are more engaging, evoking more focused attention, than their literal paraphrases (e.g., a good understanding of an idea). To evaluate whether, when, and why this may be true, we created a new database of 180 English sentences consisting of conventional metaphors, literal paraphrases, and concrete descriptions (e.g., a firm grip on a doorknob). Extensive norming matched differences across sentence types in complexity, plausibility, emotional valence, intensity, and familiarity of the key phrases. Then, using pupillometry to study the time course of metaphor processing, we predicted that metaphors would elicit greater event-evoked pupil dilation compared to other sentence types. Results confirmed the predicted increase beginning at the onset of the key phrase and lasting seconds beyond the end of the sentence. When metaphorical and literal sentences were compared directly in survey data, participants judged metaphorical sentences to convey “richer meaning,” but not more information. We conclude that conventional metaphors are more engaging than literal paraphrases or concrete sentences in a way that is irreducible to difficulty or ease, amount of information, short-term lexical access, or downstream inferences

The Mre11-Rad50-Nbs1 complex mediates activation of TopBP1 by ATM

The activation of ATR-ATRIP in response to double-stranded DNA breaks (DSBs) depends upon ATM in human cells and Xenopus egg extracts. One important aspect of this dependency involves regulation of TopBP1 by ATM. In Xenopus egg extracts, ATM associates with TopBP1 and thereupon phosphorylates it on S1131. This phosphorylation enhances the capacity of TopBP1 to activate the ATR-ATRIP complex. We show that TopBP1 also interacts with the Mre11-Rad50-Nbs1 (MRN) complex in egg extracts in a checkpoint-regulated manner. This interaction involves the Nbs1 subunit of the complex. ATM can no longer interact with TopBP1 in Nbs1-depleted egg extracts, which suggests that the MRN complex helps to bridge ATM and TopBP1 together. The association between TopBP1 and Nbs1 involves the first pair of BRCT repeats in TopBP1. In addition, the two tandem BRCT repeats of Nbs1 are required for this binding. Functional studies with mutated forms of TopBP1 and Nbs1 suggested that the BRCT-dependent association of these proteins is critical for a normal checkpoint response to DSBs. These findings suggest that the MRN complex is a crucial mediator in the process whereby ATM promotes the TopBP1-dependent activation of ATR-ATRIP in response to DSBs

The m18 aspartyl aminopeptidase of the human malaria parasite Plasmodium falciparum

A member of the M18 family of aspartyl aminopeptidases is expressed by all intra-erythrocytic stages of the human malaria parasite Plasmodium falciparum ( PfM18AAP), with highest expression levels in rings. Functionally active recombinant enzyme, rPfM18AAP, and native enzyme in cytosolic extracts of malaria parasites are 560-kDa octomers that exhibit optimal activity at neutral pH and require the presence of metal ions to maintain enzymatic activity and stability. Like the human aspartyl aminopeptidase, the exopeptidase activity of PfM18AAP is exclusive to N-terminal acidic amino acids, glutamate and aspartate, making this enzyme of particular interest and suggesting that it may function alongside the malaria cytosolic neutral aminopeptidases in the release of amino acids from host hemoglobin-derived peptides. Whereas immunocytochemical studies using transgenic P. falciparum parasites show that PfM18AAP is expressed in the cytosol, immunoblotting experiments revealed that the enzyme is also trafficked out of the parasite into the surrounding parasitophorous vacuole. Antisense-mediated knockdown of PfM18AAP results in a lethal phenotype as a result of significant intracellular damage and validates this enzyme as a target at which novel antimalarial drugs could be directed. Novel phosphinic derivatives of aspartate and glutamate showed modest inhibition of rPfM18AAP but did not inhibit malaria growth in culture. However, we were able to draw valuable observations concerning the structure-activity relationship of these inhibitors that can be employed in future inhibitor optimization studies

Evidence-Based Guidelines for Empirical Therapy of Neutropenic Fever in Korea

Neutrophils play an important role in immunological function. Neutropenic patients are vulnerable to infection, and except fever is present, inflammatory reactions are scarce in many cases. Additionally, because infections can worsen rapidly, early evaluation and treatments are especially important in febrile neutropenic patients. In cases in which febrile neutropenia is anticipated due to anticancer chemotherapy, antibiotic prophylaxis can be used, based on the risk of infection. Antifungal prophylaxis may also be considered if long-term neutropenia or mucosal damage is expected. When fever is observed in patients suspected to have neutropenia, an adequate physical examination and blood and sputum cultures should be performed. Initial antibiotics should be chosen by considering the risk of complications following the infection; if the risk is low, oral antibiotics can be used. For initial intravenous antibiotics, monotherapy with a broad-spectrum antibiotic or combination therapy with two antibiotics is recommended. At 3-5 days after beginning the initial antibiotic therapy, the condition of the patient is assessed again to determine whether the fever has subsided or symptoms have worsened. If the patient's condition has improved, intravenous antibiotics can be replaced with oral antibiotics; if the condition has deteriorated, a change of antibiotics or addition of antifungal agents should be considered. If the causative microorganism is identified, initial antimicrobial or antifungal agents should be changed accordingly. When the cause is not detected, the initial agents should continue to be used until the neutrophil count recovers

Reperfusion therapy of acute myocardial infarction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27516/1/0000560.pd

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