Students Choosing Colleges: Understanding the Matriculation Decision at a Highly Selective Private Institution

The college choice process can be reduced to three questions: 1) Where does a student apply? 2) Which schools accept the students? 3) Which offer of admission does the student accept? This paper addresses question three. Specifically, we offer an econometric analysis of the matriculation decisions made by students accepted to Williams College, one of the nation’s most highly selective colleges and universities. We use data for the Williams classes of 2008 through 2012 to estimate a yield model. We find that—conditional on the student applying to and being accepted by Williams—applicant quality as measured by standardized tests, high school GPA and the like, the net price a particular student faces (the sticker price minus institutional financial aid), the applicant’s race and geographic origin, plus the student’s artistic, athletic and academic interests, are strong predictors of whether or not the student will matriculate.

Educational “Goodwill”: Measuring the Intangible Assets at Highly Selective Private Colleges and Universities

In this paper we utilize data on the head-to-head loss rate for students accepted at Williams College, but who opt to enroll elsewhere. For example, we employ data that measure the fraction of students admitted to Williams and to Amherst (or Harvard or Yale, etc.) but who opt to attend Amherst (or Harvard or Yale, etc.) instead of Williams. We then model this head-to-head loss rate using data from a variety of sources. A better understanding of the head-to-head loss rate can assist an institution in the competition for high quality students. Importantly, it can also shed light on the degree to which some part of the loss rate might be due to “intangible” differences between the schools being compared. These intangibles (positive or negative) might grant a school greater success (or failure) in the market for students than an objective accounting of its characteristics might suggest. Such an advantage (or disadvantage) is closely aligned with the business concept of “goodwill.” We present preliminary evidence on how a quantitative measure of educational goodwill can be computed.

Atomistic Insight into the Role of Threonine 127 in the Functional Mechanism of Channelrhodopsin-2

Channelrhodopsins (ChRs) belong to the unique class of light-gated ion channels. The structure of channelrhodopsin-2 from Chlamydomonas reinhardtii (CrChR2) has been resolved, but the mechanistic link between light-induced isomerization of the chromophore retinal and channel gating remains elusive. Replacements of residues C128 and D156 (DC gate) resulted in drastic effects in channel closure. T127 is localized close to the retinal Schiff base and links the DC gate to the Schiff base. The homologous residue in bacteriorhodopsin (T89) has been shown to be crucial for the visible absorption maximum and dark–light adaptation, suggesting an interaction with the retinylidene chromophore, but the replacement had little effect on photocycle kinetics and proton pumping activity. Here, we show that the T127A and T127S variants of CrChR2 leave the visible absorption maximum unaffected. We inferred from hybrid quantum mechanics/molecular mechanics (QM/MM) calculations and resonance Raman spectroscopy that the hydroxylic side chain of T127 is hydrogen-bonded to E123 and the latter is hydrogen-bonded to the retinal Schiff base. The C=N–H vibration of the Schiff base in the T127A variant was 1674 cm−1, the highest among all rhodopsins reported to date. We also found heterogeneity in the Schiff base ground state vibrational properties due to different rotamer conformations of E123. The photoreaction of T127A is characterized by a long-lived P2380 state during which the Schiff base is deprotonated. The conservative replacement of T127S hardly affected the photocycle kinetics. Thus, we inferred that the hydroxyl group at position 127 is part of the proton transfer pathway from D156 to the Schiff base during rise of the P3530 intermediate. This finding provides molecular reasons for the evolutionary conservation of the chemically homologous residues threonine, serine, and cysteine at this position in all channelrhodopsins known so far

Transient 2D IR spectroscopy and multiscale simulations reveal vibrational couplings in the Cyanobacteriochrome Slr1393-g3

Cyanobacteriochromes are bi-stable photoreceptor proteins with desirable photochemical properties for biotechnological applications such as optogenetics or fluorescence microscopy. Here, we investigated Slr1393-g3, a cyanobacteriochrome that reversibly photo-switches between a red-absorbing (Pr) and green-absorbing (Pg) form. We applied advanced IR spectroscopic methods to track the sequence of intermediates during the photocycle over many orders in magnitude in time. In the conversion from Pg to Pr, we have revealed a new intermediate which precedes the Pr formation by using transient IR spectroscopy. In addition, stationary and transient 2D~IR experiments measured the vibrational couplings between different groups of the chromophore and the protein during these intermediate states. Anharmonic QM/MM calculations predict spectra in close-to-quantitative agreement with experimental 2D~IR spectra of the initial and the final state of the photocycle. They facilitate the assignment of the IR spectra and provide an atomistic insight into the coupling mechanism. This serves as a basis for the interpretation of the spectroscopic results and suggests structural changes of the intermediates along the photocycle

Distal communication by chimpanzees (Pan troglodytes): evidence for common ground?

van der Goot et al. (2014) proposed that distal, deictic communication indexed the appreciation of the psychological state of a common ground between a signaler and a receiver. In their study, great apes did not signal distally, which they construed as evidence for the human uniqueness of a sense of common ground. This study exposed 166 chimpanzees to food and an experimenter, at an angular displacement, to ask, “Do chimpanzees display distal communication?” Apes were categorized as (a) proximal or (b) distal signalers on each of four trials. The number of chimpanzees who communicated proximally did not statistically differ from the number who signaled distally. Therefore, contrary to the claim by van der Goot et al., apes do communicate distally

Multiplexed Immunoassay Panel Identifies Novel CSF Biomarkers for Alzheimer's Disease Diagnosis and Prognosis

Clinicopathological studies suggest that Alzheimer's disease (AD) pathology begins ∼10-15 years before the resulting cognitive impairment draws medical attention. Biomarkers that can detect AD pathology in its early stages and predict dementia onset would, therefore, be invaluable for patient care and efficient clinical trial design. We utilized a targeted proteomics approach to discover novel cerebrospinal fluid (CSF) biomarkers that can augment the diagnostic and prognostic accuracy of current leading CSF biomarkers (Aβ42, tau, p-tau181).Using a multiplexed Luminex platform, 190 analytes were measured in 333 CSF samples from cognitively normal (Clinical Dementia Rating [CDR] 0), very mildly demented (CDR 0.5), and mildly demented (CDR 1) individuals. Mean levels of 37 analytes (12 after Bonferroni correction) were found to differ between CDR 0 and CDR>0 groups. Receiver-operating characteristic curve analyses revealed that small combinations of a subset of these markers (cystatin C, VEGF, TRAIL-R3, PAI-1, PP, NT-proBNP, MMP-10, MIF, GRO-α, fibrinogen, FAS, eotaxin-3) enhanced the ability of the best-performing established CSF biomarker, the tau/Aβ42 ratio, to discriminate CDR>0 from CDR 0 individuals. Multiple machine learning algorithms likewise showed that the novel biomarker panels improved the diagnostic performance of the current leading biomarkers. Importantly, most of the markers that best discriminated CDR 0 from CDR>0 individuals in the more targeted ROC analyses were also identified as top predictors in the machine learning models, reconfirming their potential as biomarkers for early-stage AD. Cox proportional hazards models demonstrated that an optimal panel of markers for predicting risk of developing cognitive impairment (CDR 0 to CDR>0 conversion) consisted of calbindin, Aβ42, and age.Using a targeted proteomic screen, we identified novel candidate biomarkers that complement the best current CSF biomarkers for distinguishing very mildly/mildly demented from cognitively normal individuals. Additionally, we identified a novel biomarker (calbindin) with significant prognostic potential

Abnormal cognition, sleep, EEG and brain metabolism in a novel knock-in Alzheimer mouse, PLB1

Peer reviewedPublisher PD

Acute multi-sgRNA knockdown of KEOPS complex genes reproduces the microcephaly phenotype of the stable knockout zebrafish model

Until recently, morpholino oligonucleotides have been widely employed in zebrafish as an acute and efficient loss-of-function assay. However, off-target effects and reproducibility issues when compared to stable knockout lines have compromised their further use. Here we employed an acute CRISPR/Cas approach using multiple single guide RNAs targeting simultaneously different positions in two exemplar genes (osgep or tprkb) to increase the likelihood of generating mutations on both alleles in the injected F0 generation and to achieve a similar effect as morpholinos but with the reproducibility of stable lines. This multi single guide RNA approach resulted in median likelihoods for at least one mutation on each allele of >99% and sgRNA specific insertion/deletion profiles as revealed by deep-sequencing. Immunoblot showed a significant reduction for Osgep and Tprkb proteins. For both genes, the acute multi-sgRNA knockout recapitulated the microcephaly phenotype and reduction in survival that we observed previously in stable knockout lines, though milder in the acute multi-sgRNA knockout. Finally, we quantify the degree of mutagenesis by deep sequencing, and provide a mathematical model to quantitate the chance for a biallelic loss-of-function mutation. Our findings can be generalized to acute and stable CRISPR/Cas targeting for any zebrafish gene of interest