Improving gene annotation using peptide mass spectrometry

Annotation of protein-coding genes is a key goal of genome sequencing projects. In spite of tremendous recent advances in computational gene finding, comprehensive annotation remains a challenge. Peptide mass spectrometry is a powerful tool for researching the dynamic proteome and suggests an attractive approach to discover and validate protein-coding genes. We present algorithms to construct and efficiently search spectra against a genomic database, with no prior knowledge of encoded proteins. By searching a corpus of 18.5 million tandem mass spectra (MS/MS) from human proteomic samples, we validate 39,000 exons and 11,000 introns at the level of translation. We present translation-level evidence for novel or extended exons in 16 genes, confirm translation of 224 hypothetical proteins, and discover or confirm over 40 alternative splicing events. Polymorphisms are efficiently encoded in our database, allowing us to observe variant alleles for 308 coding SNPs. Finally, we demonstrate the use of mass spectrometry to improve automated gene prediction, adding 800 correct exons to our predictions using a simple rescoring strategy. Our results demonstrate that proteomic profiling should play a role in any genome sequencing project.

Survival and Sensemaking: Organizational Resilience in a Wall Street Trading Room After 9/11

How do organizations cope with extreme uncertainty? The existing literature is divided on this issue: some argue that organizations deal best with uncertainty in the environment by reproducing it in the organization, whereas others contend that the orga nization should be protected from the environment. In this paper we study the case of a Wall Street investment bank that lost its entire office and trading technology in the terrorist attack of September 11 th. The traders survived, but were forced to relocate to a makeshift trading room in New Jersey. During the six months the traders spent outside New York City, they had to deal with fears and insecurities inside the company as well as outside it: anxiety about additional attacks, questions of professional identity, doubts about the future of the firm, and ambiguities about the future re-location of the trading room. The firm overcame these uncertainties by protecting the traders' identities and their ability to engage in sensemaking. The organization held together through a leadership style that managed ambiguities and created the conditions for new solutions to emerge.

Ecologies of Value in a Wall Street Trading Room

Our task in this paper is to analyze the organization of trading in the era of quantitative finance. To do so, we conduct an ethnography of arbitrage, the trading strategy that best exemplifies finance in the wake of the quantitative revolution. In contrast to value and momentum investing, we argue, arbitrage involves an art of association-the construction of equivalence (comparability) of properties across different assets. In place of essential or relational characteristics, the peculiar valuation that takes place in arbitrage is based on an operation that makes something the measure of something else-associating securities to each other. The process of recognizing opportunities and the practices of making novel associations are shaped by the specific socio-spatial and socio-technical configurations of the trading room. Calculation is distributed across persons and instruments as the trading room organizes interaction among diverse principles of valuation.

An economic theory of church strictness

This paper makes several contributions to the growing literatureon the economics of religion. First, we explicitly introduce spatial-location models into the economics of religion. Second, we offer a newexplanation for the observed tendency of state (monopoly) churches tolocate toward the "low-tension" end of the "strictness continuum" (ina one-dimensional product space): This result is obtained through theconjunction of "benevolent preferences" (denominations care about theaggregate utility of members) and asymmetric costs of going to a moreor less strict church than one prefers.We also derive implications regarding the relationship between religiousstrictness and membership. The driving forces of our analysis, religiousmarket interactions and asymmetric costs of membership, high-light newexplanations for some well-established stylized facts. The analysis opensthe way to new empirical tests, aimed at confronting the implications ofour model against more traditional explanations.

Specialization and rent-seeking in moral enforcement: The case of confession

Moral codes are produced and enforced by more or less specialized means and are subject to standard economic forces. This paper argues that the intermediary role played by the Catholic Church between God and Christians, a key difference from Protestantism, faces the standard trade-off of specialization benefits and agency costs. It applies this trade-off hypothesis to confession of sins to priests, an institution that epitomizes such intermediation, showing that this hypothesis fits cognitive, historical and econometric evidence better than a simpler rent-seeking story. In particular, Catholics who confess more often are observed to comply more with the moral code; however, no relationship is observed between mass attendance and moral compliance. The data also links the current decline in confession to the rise in education, which makes moral self-enforcement less costly, and to the productivity gap suffered by confession services, given its necessarily interpersonal nature.

How to recognize opportunities: Heterarchical search in a Wall Street trading room

Our task in this paper is to analyze the organization of trading in the era of quantitativefinance. To do so, we conduct an ethnography of arbitrage, the trading strategy that bestexemplifies finance in the wake of the quantitative revolution. In contrast to value andmomentum investing, we argue, arbitrage involves an art of association - the constructionof equivalence (comparability) of properties across different assets. In place of essentialor relationa l characteristics, the peculiar valuation that takes place in arbitrage is based on an operation that makes something the measure of something else - associating securities to each other. The process of recognizing opportunities and the practices of making novel associations are shaped by the specific socio-spatial and socio-technical configurations of the trading room. Calculation is distributed across persons and instruments as the trading room organizes interaction among diverse principles of valuation.

Income and body mass index in Europe

The problem of obesity is alarming public health authorities around the world. Therefore, it is important to study its determinants. In this paper we explore the empirical relationship between household income and body mass index (BMI) in nine European Union countries. Our findings suggest that the association is negative for women, but we find no statistically significant relationship for men. However, we show that the different relationship for men and women appears to be driven by the negative relationship for women between BMI and individual income from work. We tentatively conclude that the negative relationship between household income and BMI for women may simply be capturing the wage penalty that obese women suffer in the labor market.

The Coordinated Radio and Infrared Survey for High-Mass Star Formation (The CORNISH Survey). I. Survey Design

We describe the motivation, design, and implementation of the CORNISH survey, an arcsecondresolution radio continuum survey of the inner galactic plane at 5 GHz using the Very Large Array (VLA). It is a blind survey coordinated with the northern SpitzerGLIMPSE I region covering 10° massive star formation. A sensitivity around 2 mJy will allow the automatic distinction between radio-loud and radio-quiet midIR sources found in the Spitzersurveys. This survey has many legacy applications beyond star formation, including evolved stars, active stars and binaries, and extragalactic sources. The CORNISH survey for compact ionized sources complements other Galactic plane surveys that target diffuse and nonthermal sources, as well as atomic and molecular phases to build up a complete picture of the interstellar medium in the Galaxy.

Beta cell mass and growth after syngeneic islet cell transplantation in normal and streptozocin diabetic C57BL/6 mice

In islet transplantation, nonimmunological factors such as limited growth capacity or increased death rate could reduce the beta cell mass in the graft and lead to failure of the transplant. We studied the evolution of beta cell replication and mass after transplantation of insufficient, minimally sufficient, or excessive islet tissue. Streptozocin diabetic C57BL/6 mice received 150 or 300 syngeneic islets under the kidney capsule and normal mice received 300 islets. In streptozocin diabetic mice 300 islets restored normoglycemia; beta cell replication in transplanted islets was similar to replication in normal pancreas and beta cell mass in the graft remained constant. In contrast, 150 islets were insufficient to achieve normoglycemia; beta cell replication was increased initially but not by 18 or 30 d despite persistent hyperglycemia, and beta cell mass fell progressively. When islets were transplanted into normal recipients, beta cell replication remained normal but beta cells underwent atrophy and mass in the graft was substantially reduced. Therefore, with a successful islet transplant, in diabetic mice beta cell replication and mass remain constant. In contrast, when insufficient islet tissue is transplanted an initial increase in beta cell replication can not compensate for a decline in beta cell mass. When excessive islet tissue is transplanted, beta cell mass is reduced despite normal beta cell replication.

Transplanted beta cell response to increased metabolic demand. Changes in beta cell replication and mass

We determined the capacity of transplanted beta cells to modify their replication and mass when stimulated by changes in metabolic demand. Five groups of Lewis rats were studied: group 1 (Tx-Px) had a 95% pancreatectomy 14 d after transplantation of 500 islets; group 2 (Px-Tx) had a 95% pancreatectomy 14 d before transplantation of 500 islets; group 3 (Tx) was transplanted with 500 islets; group 4 (Px) had a 95% pancreatectomy; and group 5 (normal) was neither transplanted nor pancreatectomized. Blood glucose was normal in Tx-Px and Tx groups at all times. Px-Tx and Px groups developed severe hyperglycemia after pancreatectomy that was corrected in Px-Tx group in 83% of rats 28 d after transplantation. Replication of transplanted beta cells increased in Tx-Px (1.15 +/- 0.12%) and Px-Tx (0.85 +/- 0.12%) groups, but not in Tx group (0.64 +/- 0.07%) compared with normal pancreatic beta cells (0.38 +/- 0.05%) (P < 0.001). Mean beta cell size increased in Tx-Px (311 +/- 14 microns2) and Px-Tx (328 +/- 13 microns2) groups compared with Tx (252 +/- 12 microns2) and normal (239 +/- 9 microns2) groups (P < 0.001). Transplanted beta cell mass increased in Tx-Px (1.87 +/- 0.51 mg) and Px-Tx (1.55 +/- 0.21 mg) groups compared with Tx group (0.78 +/- 0.17 mg) (P < 0.05). In summary, changes in transplanted beta cells prevented the development of hyperglycemia in Tx-Px rats. Transplanted beta cells responded to increased metabolic demand increasing their beta cell mass.

Effective mass and dielectric constant mismatch effects in spherical multishell quantum dots

The role of effective mass and dielectric mismatches on chemical potentials and addition energies of many-electron multishell quantum dots (QDs) is explored within the framework of a recent extension of the spin density functional theory. It is shown that although the gross electronic density is located in the wells of these multishell QDs, taking position-dependent effective mass and dielectric constant into account can lead to the appearance of relevant differences in chemical potential and addition energies as compared to standard calculations in which the effective mass and the dielectric constant of the well is assumed for the whole multishell structure.

Maximum mass of neutron stars

We determine the structure of neutron stars within a Brueckner-Hartree-Fock approach based on realistic nucleon-nucleon, nucleon-hyperon, and hyperon-hyperon interactions. Our results indicate rather low maximum masses below 1.4 solar masses. This feature is insensitive to the nucleonic part of the EOS due to a strong compensation mechanism caused by the appearance of hyperons and represents thus strong evidence for the presence of nonbaryonic "quark" matter in the interior of heavy stars.

Constraints on additional Z' gauge bosons from a precise measurement of the Z mass

We analyze the constraints on the mass and mixing of a superstring-inspired E6 Z' neutral gauge boson that follow from the recent precise Z mass measurements and show that they depend very sensitively on the assumed value of the W mass and also, to a lesser extent, on the top-quark mass.