Neural Decision Boundaries for Maximal Information Transmission

We consider here how to separate multidimensional signals into two categories, such that the binary decision transmits the maximum possible information transmitted about those signals. Our motivation comes from the nervous system, where neurons process multidimensional signals into a binary sequence of responses (spikes). In a small noise limit, we derive a general equation for the decision boundary that locally relates its curvature to the probability distribution of inputs. We show that for Gaussian inputs the optimal boundaries are planar, but for non-Gaussian inputs the curvature is nonzero. As an example, we consider exponentially distributed inputs, which are known to approximate a variety of signals from natural environment.Comment: 5 pages, 3 figure

Fractionated 131I anti-CEA radioimmunotherapy: effects on xenograft tumour growth and haematological toxicity in mice

Dose fractionation has been proposed as a method to improve the therapeutic ratio of radioimmunotherapy (RIT). This study compared a single administration of 7.4 MBq 131I-anti-CEA antibody given on day 1 with the same total activity given as fractionated treatment: 3.7 MBq (days 1 and 3), 2.4 MBq (days 1, 3, and 5) or 1.8 MBq (days 1, 3, 5, and 8). Studies in nude mice, bearing the human colorectal xenograft LS174T, showed that increasing the fractionation significantly reduced the efficacy of therapy. Fractionation was associated with a decrease in systemic toxicity as assessed by weight, but did not lead to any significant decrease in acute haematological toxicity. Similarly, no significant decrease in marrow toxicity, as assessed by colony-forming unit assays for granulocytes and macrophages (CFUgm), was seen. However, there was a significant depression of CFUgm counts when all treated animals were compared with untreated controls, suggesting that treatment did suppress marrow function. In conclusion, in this tumour model system, fractionated RIT causes less systemic toxicity, but is also less effective at treating tumours

Effects of regular salt marsh haying on marsh plants, algae, invertebrates and birds at Plum Island Sound, Massachusetts

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Wetlands Ecology and Management 17 (2009): 469-487, doi: 10.1007/s11273-008-9125-3.The haying of salt marshes, a traditional activity since colonial times in New England, still occurs in about 400 ha of marsh in the Plum Island Sound estuary in northeastern Massachusetts. We took advantage of this haying activity to investigate how the periodic large-scale removal of aboveground biomass affects a number of marsh processes. Hayed marshes were no different from adjacent reference marshes in plant species density (species per area) and end-of-year aboveground biomass, but did differ in vegetation composition. Spartina patens was more abundant in hayed marshes than S. alterniflora, and the reverse was true in reference marshes. The differences in relative covers of these plant species were not associated with any differences between hayed and reference marshes in the elevations of the marsh platform. Instead it suggested that S. patens was more tolerant of haying than S. alterniflora. S. patens had higher stem densities in hayed marshes than it did in reference marshes, suggesting that periodic cutting stimulated tillering of this species. Although we predicted that haying would stimulate benthic chlorophyll production by opening up the canopy, we found differences to be inconsistent, possibly due to the relatively rapid regrowth of S. patens and to grazing by invertebrates on the algae. The pulmonate snail, Melampus bidendatus was depleted in its δ13C content in the hayed marsh compared to the reference, suggesting a diet shift to benthic algae in hayed marshes. The stable isotope ratios of a number of other consumer species were not affected by haying activity. Migratory shorebirds cue in to recently hayed marshes and may contribute to short term declines in some invertebrate species, however the number of taxa per unit area of marsh surface invertebrates and their overall abundances were unaffected by haying over the long term. Haying had no impact on nutrient concentrations in creeks just downstream from hayed plots, but the sediments of hayed marshes were lower in total N and P compared to references. In sum, haying appeared to affect plant species composition but had only short-term affects on consumer organisms. This contrasts with many grassland ecosystems, where an intermediate level of disturbance, such as by grazing, increases species diversity and may stimulate productivity. From a management perspective, periodic mowing could be a way to maintain S. patens habitats and the suite of species with which they are associated.This research was supported by the Plum Island Ecosystem Long Term Ecological Research program (OCE-972692 and OCE 0423565) of the National Science Foundation (NSF). J. Horowitz and J. Ludlam were supported by NSF Research Experience for Undergraduate (REU) grants when they were students at Hampshire College and Gordon College respectively

Long-term complete responses after 131I-tositumomab therapy for relapsed or refractory indolent non-Hodgkin's lymphoma

We present the long-term results of 18 chemotherapy relapsed indolent (N=12) or transformed (N=6) NHL patients of a phase II anti-CD20 131I-tositumomab (Bexxar®) therapy study. The biphasic therapy included two injections of 450 mg unlabelled antibody combined with 131I-tositumomab once as dosimetric and once as therapeutic activity delivering 75 or 65 cGy whole-body radiation dose to patients with normal or reduced platelet counts, respectively. Two patients were not treated due to disease progression during dosimetry. The overall response rate was 81% in the 16 patients treated, including 50% CR/CRu and 31% PR. Median progression free survival of the 16 patients was 22.5 months. Median overall survival has not been reached after a median observation of 48 months. Median PFS of complete responders (CR/CRu) has not been reached and will be greater than 51 months. Short-term side effects were mainly haematological and transient. Among the relevant long-term side effects, one patient previously treated with CHOP chemotherapy died from secondary myelodysplasia. Four patients developed HAMA. In conclusion, 131I-tositumomab RIT demonstrated durable responses especially in those patients who achieved a complete response. Six of eight CR/CRu are ongoing after 46–70 months

The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development

BACKGROUND: Int-6 (integration site 6) was identified as an oncogene in a screen of tumorigenic mouse mammary tumor virus (MMTV) insertions. INT6 expression is altered in human cancers, but the precise role of disrupted INT6 in tumorigenesis remains unclear, and an animal model to study Int-6 physiological function has been lacking. PRINCIPAL FINDINGS: Here, we create an in vivo model of Int6 function in zebrafish, and through genetic and chemical-genetic approaches implicate Int6 as a tissue-specific modulator of MEK-ERK signaling. We find that Int6 is required for normal expression of MEK1 protein in human cells, and for Erk signaling in zebrafish embryos. Loss of either Int6 or Mek signaling causes defects in craniofacial development, and Int6 and Erk-signaling have overlapping domains of tissue expression. SIGNIFICANCE: Our results provide new insight into the physiological role of vertebrate Int6, and have implications for the treatment of human tumors displaying altered INT6 expression

Neural Correlates of Ongoing Conscious Experience: Both Task-Unrelatedness and Stimulus-Independence Are Related to Default Network Activity

The default mode network (DMN) is a set of brain regions that consistently shows higher activity at rest compared to tasks requiring sustained focused attention toward externally presented stimuli. The cognitive processes that the DMN possibly underlies remain a matter of debate. It has alternately been proposed that DMN activity reflects unfocused attention toward external stimuli or the occurrence of internally generated thoughts. The present study aimed at clarifying this issue by investigating the neural correlates of the various kinds of conscious experiences that can occur during task performance. Four classes of conscious experiences (i.e., being fully focused on the task, distractions by irrelevant sensations/perceptions, interfering thoughts related to the appraisal of the task, and mind-wandering) that varied along two dimensions (“task-relatedness” and “stimulus-dependency”) were sampled using thought-probes while the participants performed a go/no-go task. Analyses performed on the intervals preceding each probe according to the reported subjective experience revealed that both dimensions are relevant to explain activity in several regions of the DMN, namely the medial prefrontal cortex, posterior cingulate cortex/precuneus, and posterior inferior parietal lobe. Notably, an additive effect of the two dimensions was demonstrated for midline DMN regions. On the other hand, lateral temporal regions (also part of the DMN) were specifically related to stimulus-independent reports. These results suggest that midline DMN regions underlie cognitive processes that are active during both internal thoughts and external unfocused attention. They also strengthen the view that the DMN can be fractionated into different subcomponents and reveal the necessity to consider both the stimulus-dependent and the task-related dimensions of conscious experiences when studying the possible functional roles of the DMN

Order recall in verbal short-term memory: The role of semantic networks

In their recent article, Acheson, MacDonald, and Postle (Journal of Experimental Psychology: Learning, Memory, and Cognition 37:44-59, 2011) made an important but controversial suggestion: They hypothesized that (a) semantic information has an effect on order information in short-term memory (STM) and (b) order recall in STM is based on the level of activation of items within the relevant lexico-semantic long-term memory (LTM) network. However, verbal STM research has typically led to the conclusion that factors such as semantic category have a large effect on the number of correctly recalled items, but little or no impact on order recall (Poirier & Saint-Aubin, Quarterly Journal of Experimental Psychology 48A:384-404, 1995; Saint-Aubin, Ouellette, & Poirier, Psychonomic Bulletin & Review 12:171-177, 2005; Tse, Memory 17:874-891, 2009). Moreover, most formal models of short-term order memory currently suggest a separate mechanism for order coding-that is, one that is separate from item representation and not associated with LTM lexico-semantic networks. Both of the experiments reported here tested the predictions that we derived from Acheson et al. The findings show that, as predicted, manipulations aiming to affect the activation of item representations significantly impacted order memory