A Computational-Experimental Approach Identifies Mutations That Enhance Surface Expression of an Oseltamivir-Resistant Influenza Neuraminidase

The His274 → Tyr (H274Y) oseltamivir (Tamiflu) resistance mutation causes a substantial decrease in the total levels of surface-expressed neuraminidase protein and activity in early isolates of human seasonal H1N1 influenza, and in the swine-origin pandemic H1N1. In seasonal H1N1, H274Y only became widespread after the occurrence of secondary mutations that counteracted this decrease. H274Y is currently rare in pandemic H1N1, and it remains unclear whether secondary mutations exist that might similarly counteract the decreased neuraminidase surface expression associated with this resistance mutation in pandemic H1N1. Here we investigate the possibility of predicting such secondary mutations. We first test the ability of several computational approaches to retrospectively identify the secondary mutations that enhanced levels of surface-expressed neuraminidase protein and activity in seasonal H1N1 shortly before the emergence of oseltamivir resistance. We then use the most successful computational approach to predict a set of candidate secondary mutations to the pandemic H1N1 neuraminidase. We experimentally screen these mutations, and find that several of them do indeed partially counteract the decrease in neuraminidase surface expression caused by H274Y. Two of the secondary mutations together restore surface-expressed neuraminidase activity to wildtype levels, and also eliminate the very slight decrease in viral growth in tissue-culture caused by H274Y. Our work therefore demonstrates a combined computational-experimental approach for identifying mutations that enhance neuraminidase surface expression, and describes several specific mutations with the potential to be of relevance to the spread of oseltamivir resistance in pandemic H1N1

A Multiwavelength Investigation of Unidentified EGRET Sources

Statistical studies indicate that the 271 point sources of high-energy gamma rays belong to two groups: a Galactic population and an isotropic extragalactic population. Many unidentified extragalactic sources are certainly blazars, and it is the intention of this work to uncover gamma-ray blazars missed by previous attempts. Until recently, searches for blazar counterparts to unidentified EGRET sources have focused on finding AGN that have 5-GHz radio flux densities S_5 near or above 1 Jy. However, the recent blazar identification of 3EG J2006-2321 (S_5 = 260 mJy) and other work suggest that careful studies of weaker flat-spectrum sources may be fruitful. In this spirit, error circles of 4 high-latitude unidentified EGRET sources have been searched for 5-GHz sources. The gamma-ray sources are 3EG J1133+0033, 3EG J1212+2304, 3EG J1222+2315, and 3EG J1227+4302. Within the error contours of each of the four sources are found 6 radio candidates; by observing the positions of the radio sources with the 0.81-m Tenagra II telescope it is determined that 14 of these 24 radio sources have optical counterparts with R < 22. Eight of these from two different EGRET sources have been observed in the B, V, and R bands in more than one epoch and the analysis of these data is ongoing. Any sources that are found to be variable will be the objects of multi-epoch polarimetry studies.Comment: 6 pages, 2 tables. To appear in Astrophysics & Space Scienc

The impact of health on professionally active people's incomes in Poland. Microeconometric analysis

The outcome of the research confirms the occurrence of positive interaction between professionally active people's incomes and the self-assessed state of health. People declaring a bad state of health have incomes by 20% on average lower than people who enjoy good health (assuming that the remaining characteristics of the surveyed person are the same). In case of men, the impact of health state on incomes is slightly greater than in case of women.Wyniki badań potwierdzają istnienie pozytywnej zależności dochodów osób aktywnych zawodowo od stanu zdrowia mierzonego jego samooceną. Osoby deklarujące zły stan zdrowia osiągają dochody przeciętnie o 20% niższe niż osoby, które cieszą się dobrym stanem zdrowia (przy założeniu, że pozostałe charakterystyki badanej osoby są takie same). W przypadku mężczyzn zależność dochodów od stanu zdrowia jest nieznacznie silniejsza niż w przypadku kobiet

Expected characteristics of the subclass of Supernova Gamma-ray Bursts (S-GRBs)

The spatial and temporal coincidence between the gamma-ray burst (GRB) 980425 and supernova (SN) 1998bw has prompted speculation that there exists a class of GRBs produced by SNe (``S-GRBs''). Robust arguments for the existence of a relativistic shock have been presented on the basis of radio observations. A physical model based on the radio observations lead us to propose the following characteristics of supernovae GRBs (S-GRBs): 1) prompt radio emission and implied brightness temperature near or below the inverse Compton limit, 2) high expansion velocity of the optical photosphere as derived from lines widths and energy release larger than usual, 3) no long-lived X-ray afterglow, and 4) a single pulse (SP) GRB profile. Radio studies of previous SNe show that only type Ib and Ic potentially satisfy the first condition. Accordingly we have investigated proposed associations of GRBs and SNe finding no convincing evidence (mainly to paucity of data) to confirm any single connection of a SN with a GRB. If there is a more constraining physical basis for the burst time-history of S-GRBs beyond that of the SP requirement, we suggest the 1% of light curves in the BATSE catalogue similar to that of GRB 980425 may constitute the subclass. Future optical follow-up of bursts with similar profiles should confirm if such GRBs originate from some fraction of SN type Ib/Ic.Comment: 11 pages of LaTeX with 1 figure. Submitted to the Astrophysical Journal Letter

The Rapidly Fading Afterglow from the Gamma-Ray Burst of 1999 May 6

We report on the discovery of the radio afterglow from the gamma-ray burst (GRB) of 1999 May 6 (GRB 990506) using the Very Large Array (VLA). The radio afterglow was detected at early times (1.5 days), but began to fade rapidly sometime between 1 and 5 days after the burst. If we attribute the radio emission to the forward shock from an expanding fireball, then this rapid onset of the decay in the radio predicts that the corresponding optical transient began to decay between 1 and 5 minutes after the burst. This could explain why no optical transient for GRB 990506 was detected in spite of numerous searches. The cause of the unusually rapid onset of the decay for the afterglow is probably the result of an isotropically energetic fireball expanding into a low density circumburst environment. At the location of the radio afterglow we find a faint (R ~ 24 mag) host galaxy with a double morphology.Comment: in press at ApJ Letters, 13 page LaTeX document includes 2 postscript figure

The Discovery of Vibrationally-Excited H_2 in the Molecular Cloud near GRB 080607

GRB 080607 has provided the first strong observational signatures of molecular absorption bands toward any galaxy hosting a gamma-ray burst. Despite the identification of dozens of features as belonging to various atomic and molecular (H_2 and CO) carriers, many more absorption features remained unidentified. Here we report on a search among these features for absorption from vibrationally-excited H_2, a species that was predicted to be produced by the UV flash of a GRB impinging on a molecular cloud. Following a detailed comparison between our spectroscopy and static, as well as dynamic, models of H_2* absorption, we conclude that a column density of 10^{17.5+-0.2} cm^{-2} of H_2* was produced along the line of sight toward GRB 080607. Depending on the assumed amount of dust extinction between the molecular cloud and the GRB, the model distance between the two is found to be in the range 230--940 pc. Such a range is consistent with a conservative lower limit of 100 pc estimated from the presence of Mg I in the same data. These distances show that substantial molecular material is found within hundreds of pc from GRB 080607, part of the distribution of clouds within the GRB host galaxy.Comment: Submitted to ApJL, 6 pages emulate