Regional abnormalities of brain connectivity may be an important substrate for the expression of schizophrenia, a severe form of mental illness. Brain imaging and postmortem morphometric studies indicate hippocampal structure is abnormal in schizophrenia. To study molecular components of hippocampal connectivity the presynaptic proteins SNAP-25 and synaptophysin were assayed in postmortem samples. Immunocytochemical studies indicated reduced SNAP-25 immunoreactivity in schizophrenia compared to controls, particularly in the terminal fields of entorhinal cortex projections. Although there were no overall changes in synaptophysin immunoreactivity, in the granule cell layer of the dentate gyrus synaptophysin immunoreactivity was increased in schizophrenia. These results indicate that disconnection of a subset of hippocampal circuitry from the entorhinal cortex, as well as intrinsic changes in hippocampal connectivity, may contribute to the mechanism of illness in schizophrenia.

When consequential decisions are informed by algorithmic input, individuals may feel compelled to alter their behavior in order to gain a system's approval. Models of agent responsiveness, termed "strategic manipulation," analyze the interaction between a learner and agents in a world where all agents are equally able to manipulate their features in an attempt to "trick" a published classifier. In cases of real world classification, however, an agent's ability to adapt to an algorithm is not simply a function of her personal interest in receiving a positive classification, but is bound up in a complex web of social factors that affect her ability to pursue certain action responses. In this paper, we adapt models of strategic manipulation to capture dynamics that may arise in a setting of social inequality wherein candidate groups face different costs to manipulation. We find that whenever one group's costs are higher than the other's, the learner's equilibrium strategy exhibits an inequality-reinforcing phenomenon wherein the learner erroneously admits some members of the advantaged group, while erroneously excluding some members of the disadvantaged group. We also consider the effects of interventions in which a learner subsidizes members of the disadvantaged group, lowering their costs in order to improve her own classification performance. Here we encounter a paradoxical result: there exist cases in which providing a subsidy improves only the learner's utility while actually making both candidate groups worse-off-even the group receiving the subsidy. Our results reveal the potentially adverse social ramifications of deploying tools that attempt to evaluate an individual's "quality" when agents' capacities to adaptively respond differ.

The persistence of racial inequality in the U.S. labor market against a general backdrop of formal equality of opportunity is a troubling phenomenon that has significant ramifications on the design of hiring policies. In this paper, we show that current group disparate outcomes may be immovable even when hiring decisions are bound by an input-output notion of "individual fairness." Instead, we construct a dynamic reputational model of the labor market that illustrates the reinforcing nature of asymmetric outcomes resulting from groups' divergent accesses to resources and as a result, investment choices. To address these disparities, we adopt a dual labor market composed of a Temporary Labor Market (TLM), in which firms' hiring strategies are constrained to ensure statistical parity of workers granted entry into the pipeline, and a Permanent Labor Market (PLM), in which firms hire top performers as desired. Individual worker reputations produce externalities for their group; the corresponding feedback loop raises the collective reputation of the initially disadvantaged group via a TLM fairness intervention that need not be permanent. We show that such a restriction on hiring practices induces an equilibrium that, under particular market conditions, Pareto-dominates those arising from strategies that statistically discriminate or employ a "group-blind" criterion. The enduring nature of equilibria that are both inequitable and Pareto suboptimal suggests that fairness interventions beyond procedural checks of hiring decisions will be of critical importance in a world where machines play a greater role in the employment process.

A fundamental molecular component of neural connectivity is the SNARE (SNAP receptor) protein complex, which consists of three proteins, syntaxin, SNAP-25 and VAMP. Under appropriate conditions, the SNARE complex can be formed in vitro. To investigate the hypothesis that dysregulation of SNARE proteins or their interactions could be abnormal in severe mental disorders, the three SNARE proteins and the complex were studied in post-mortem anterior frontal cortex homogenates. An ELISA was used to quantify SNARE protein immunoreactivities in cortical homogenates from four groups: patients with schizophrenia who died of causes other than suicide (n = 6), patients with schizophrenia and suicide (n = 7), patients with depression and suicide (n = 11), and controls (n = 11). Differences between groups in patterns of SNARE protein immuno-reactivities were demonstrated [Wilks' Lambda F(9,68) = 3.57, P = 0.001]. Protein-by-protein analyses indicated a significant reduction in SNAP-25 immunoreactivity in the schizophrenia non-suicide group [28% decrease relative to controls, F(3,31) = 6.45, P = 0.002, Student-Newman-Keuls test, P < 0.01]. The intercorrelations between SNARE protein and synaptophysin immunoreactivities were high in controls, but lower in the other groups, further indicating disturbances in relationships between these proteins. The extent of SNARE complex formation in vitro was studied using immuno-blotting. Significant differences related to group membership were observed for the SNARE complexes identified by SNAP-25 [Wilks' Lambda F(3,31) = 4.76, P = 0.008] and by syntaxin immunostaining [Wilks' Lambda F(3,31) = 9.16, P = 0.0002]. In both groups with suicide as a cause of death, relatively more SNAP-25 and syntaxin was present in the heterotrimeric SNARE complex than in other molecular forms. These abnormalities in the SNARE complex could represent a molecular substrate for abnormalities of neural connectivity in severe mental disorders.

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The presence of hypoxic cells in human brain tumors is an important factor leading to resistance to radiation therapy. However, this physiological difference between normal tissues and tumors also provides the potential for designing cancer-specific gene therapy. We compared the increase of gene expression under anoxia (<0.01% oxygen) produced by 3, 6, and 9 copies of hypoxia-responsive elements (HRE) from the erythropoietin gene (Epo), which are activated through the transcriptional complex hypoxia-inducible factor 1 (HIF-1). Under anoxic conditions, nine copies of HRE (9XHRE) yielded 27- to 37-fold of increased gene expression in U-251 MG and U-87 MG human brain tumor cell lines. Under the less hypoxic conditions of 0.3% and 1% oxygen, gene activation by 9XHRE increased expression 11- to 18-fold in these cell lines. To generate a recombinant adeno-associated virus (rAAV) in which the transgene can be regulated by hypoxia, we inserted the DNA fragment containing 9XHRE and the LacZ reporter gene into an AAV vector. Under anoxic conditions, this vector produced 79- to 110-fold increase in gene expression. We believe this hypoxia-regulated rAAV vector will provide a useful delivery vehicle for cancer-specific gene therapy.

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