A Field Experiment on Search Costs and the Formation of Scientific Collaborations
Scientists typically self-organize into teams, matching with others to collaborate in the production of new knowledge. We present the results of a field experiment conducted at Harvard Medical School to understand the extent to which search costs affect matching among scientific collaborators. We generated exogenous variation in search costs for pairs of potential collaborators by randomly assigning individuals to 90-minute structured information-sharing sessions as part of a grant funding opportunity for biomedical researchers. We estimate that the treatment increases the baseline probability of grant co-application of a given pair of researchers by 75% (increasing the likelihood of a pair collaborating from 0.16 percent to 0.28 percent), with effects higher among those in the same specialization. The findings indicate that matching between scientists is subject to considerable frictions, even in the case of geographically-proximate scientists working in the same institutional context with ample access to common information and funding opportunities.
Acyldepsipeptide Antibiotics Kill Mycobacteria by Preventing the Physiological Functions of the ClpP1P2 Protease
The Clp protease complex in Mycobacterium tuberculosis is unusual in its composition, functional importance and activation mechanism. Whilst most bacterial species contain a single ClpP protein that is dispensable for normal growth, mycobacteria have two ClpPs, ClpP1 and ClpP2, which are essential for viability and together form the ClpP1P2 tetradecamer. Acyldepsipeptide antibiotics of the ADEP class inhibit the growth of Gram-positive firmicutes by activating ClpP and causing unregulated protein degradation. Here we show that, in contrast, mycobacteria are killed by ADEP through inhibition of ClpP function. Although ADEPs can stimulate purified M. tuberculosis ClpP1P2 to degrade larger peptides and unstructured proteins, this effect is weaker than for ClpP from other bacteria and depends on the presence of an additional activating factor (e.g. the dipeptide benzyloxycarbonyl-leucyl-leucine in vitro) to form the active ClpP1P2 tetradecamer. The cell division protein FtsZ, which is a particularly sensitive target for ADEP-activated ClpP in firmicutes, is not degraded in mycobacteria. Depletion of the ClpP1P2 level in a conditional Mycobacterium bovis BCG mutant enhanced killing by ADEP unlike in other bacteria. In summary, ADEPs kill mycobacteria by preventing interaction of ClpP1P2 with the regulatory ATPases, ClpX or ClpC1, thus inhibiting essential ATP-dependent protein degradation.
Analysis of Normal Retinal Nerve Fiber Layer Thickness by Age, Sex, and Race Using Spectral Domain Optical Coherence Tomography
Purpose: To determine the effects of age, sex, and race on the retinal nerve fiber layer (RNFL) in the normal human eye as measured by the spectral domain optical coherence tomography (SD-OCT) Spectralis machine (Heidelberg Engineering).
Methods: Peripapillary SD-OCT RNFL thickness measurements were determined in normal subjects seen at a university-based clinic. One randomly selected eye per subject was used for analysis in this cross-sectional study. Multiple regression analysis was applied to assess the effects of age, sex, ethnicity, and mean refractive error on peripapillary RNFL thickness. Results are expressed as means±SD wherever applicable.
Results: The study population consisted of 190 healthy participants from 9 to 86 years of age. Of the 190 participants, 62 (33%) were men, 125 (66%) Caucasians, 26 (14%) African Americans, 14 (7%) Hispanics, 16 (8%) Asians, and 9 (5%) other races. The mean RNFL thickness for the normal population studied was 97.3±9.6 µm. Normal RNFL thickness values follow the ISNT rule with decreasing RNFL thickness values starting from the thickest quadrant inferiorly to the thinnest quadrant temporally: inferior quadrant (126±15.8), superior quadrant (117.2±16.13), nasal quadrant (75±13.9), and temporal quadrant (70.6±10.8 µm). Thinner RNFL measurements were associated with older age (P<0.001); being Caucasian, versus being either Hispanic or Asian (P=0.02 and 0.009, respectively); or being more myopic (P<0.001). For every decade of increased age, mean RNFL thickness measured thinner by approximately 1.5 µm (95% confidence interval, 0.24-0.07). Comparisons between ethnic groups revealed that Caucasians had mean RNFL values (96±9.2 µm) slightly thinner than those of Hispanics (102.9±11 µm; P=0.02) or Asians (100.7±8.5 µm; P=0.009). African Americans RNFL values (99.2±10.2 µm) were not significantly different when compared with Caucasians. There was no relationship between RNFL thickness and sex.
Conclusions: The thickest RNFL measurements were found in the inferior quadrant, followed by the superior, nasal, and temporal quadrants (ISNT rule applied to the RNFL). Thinner RNFL measurements were associated with older age and increasing myopia. Caucasians tend to have thinner RNFL values when compared with Hispanics and Asians. SD-OCT analysis of the normal RNFL showed results similar to time domain OCT studies.