Bewitched by the Word "Know�

You ask me if our friend is in town, I say yes; you ask, "Are you sure?,� I reply, "I know it – I just installed him in our guest room!�—What if you're mistaken?—One can't be making a mistake about something like that!---So you"re claiming infallibility?—Saying "I can't be making a mistake" was just a way of saying "I know ...�; I wasn"t alleging a ridiculous "justification� for my claim!---But only the infallible possession of truth really justifies a claim to knowledge.— The "I know ...� is just an instrument with a limited, practical purpose -- a purpose which the following expansion of the "builder's language" helps to bring out: The number [of building stones] is sometimes estimated, sometimes established by counting. Then the question arises "Do you believe there are as many stones as that?,� and the answer "I know there are – I"ve just counted them.� But then the "I know� could be dropped. If, however, there are several ways of finding something out for sure, like counting, weighing, measuring the stack, then the statement "I know� can take the place of mentioning how I know. [Wittgenstein 1969, sec. 564

Relationships between correlated spikes, oxygen and LFP in the resting-state primate

Resting-state functional MRI (rsfMRI) provides a view of human brain organization based on correlation patterns of blood oxygen level dependent (BOLD) signals recorded across the whole brain. The neural basis of resting-state BOLD fluctuations and their correlation remains poorly understood. We simultaneously recorded oxygen level, spikes, and local field potential (LFP) at multiple sites in awake, resting monkeys. Following a spike, the average local oxygen and LFP voltage responses each resemble a task-driven BOLD response, with LFP preceding oxygen by 0.5 s. Between sites, features of the long-range correlation patterns of oxygen, LFP, and spikes are similar to features seen in rsfMRI. Most of the variance shared between sites lies in the infraslow frequency band (0.01-0.1 Hz) and in the infraslow envelope of higher-frequency bands (e.g. gamma LFP). While gamma LFP and infraslow LFP are both strong correlates of local oxygen, infraslow LFP explains significantly more of the variance shared between correlated oxygen signals than any other electrophysiological signal. Together these findings are consistent with a causal relationship between infraslow LFP and long-range oxygen correlations in the resting state

Wittgenstein's Thought Experiments and Relativity Theory

In this paper, I discuss the similarity between Wittgenstein’s use of thought experiments and Relativity Theory. I begin with introducing Wittgenstein’s idea of “thought experiments” and a tentative classification of different kinds of thought experiments in Wittgenstein’s work. Then, after presenting a short recap of some remarks on the analogy between Wittgenstein’s point of view and Einstein’s, I suggest three analogies between the status of Wittgenstein’s mental experiments and Relativity theory: the topics of time dilation, the search for invariants, and the role of measuring tools in Special Relativity. This last point will help to better define Wittgenstein’s idea of description as the core of his philosophical enterprise

Entropy and information in neural spike trains: Progress on the sampling problem

The major problem in information theoretic analysis of neural responses and other biological data is the reliable estimation of entropy--like quantities from small samples. We apply a recently introduced Bayesian entropy estimator to synthetic data inspired by experiments, and to real experimental spike trains. The estimator performs admirably even very deep in the undersampled regime, where other techniques fail. This opens new possibilities for the information theoretic analysis of experiments, and may be of general interest as an example of learning from limited data.Comment: 7 pages, 4 figures; referee suggested changes, accepted versio

Universal Statistical Behavior of Neural Spike Trains

We construct a model that predicts the statistical properties of spike trains generated by a sensory neuron. The model describes the combined effects of the neuron's intrinsic properties, the noise in the surrounding, and the external driving stimulus. We show that the spike trains exhibit universal statistical behavior over short times, modulated by a strongly stimulus-dependent behavior over long times. These predictions are confirmed in experiments on H1, a motion-sensitive neuron in the fly visual system.Comment: 7 pages, 4 figure

Cyclical browning in a subtropical lake inferred from diatom records

Changing climate and land use activity are altering inputs of colored dissolved organic carbon (cDOC) into lakes. Increased cDOC reduces water transparency (browning) and changes lake physicochemistry, with biological consequences. Identifying the drivers and effects of changing cDOC inputs is critical for mitigating the consequences of climate change on lake ecosystems through adaptive watershed management. This study focused on determining the drivers of lake browning by evaluating shifts in diatom assemblages in subtropical, oligotrophic Lake Annie (FL, United States), which is known to experience climate-driven oscillations in transparency associated with watershed inputs of cDOC. We combined long-term limnological monitoring data and paleolimnological techniques to determine how diatoms respond to changes in cDOC and to infer past cDOC fluctuations relative to records of past climate and land use changes in the watershed. Diatom assemblage composition in a 14-year phytoplankton dataset was strongly correlated with cDOC-driven transparency fluctuations. Likewise, diatom assemblages in the upper 35 cm of the sediment core, which corresponded to a 35-year lake monitoring record, were also strongly related to past water transparency, yielding a strong transfer function (paleo model, R2 = 0.72). When the model was applied to the diatom record from a 166-cm sediment core, diatom-inferred transparency and rates of nutrient input showed that localized ditching in the 1930s enhanced the effect of climate oscillations on water transparency, intensifying cyclical browning thereafter. Integration of long-term monitoring and paleoecological data provided valuable insights into the history of the aquatic ecosystem, enabling implementation of adaptive management strategies to contend with a changing climate

The immune cell landscape in kidneys of patients with lupus nephritis.

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies

Unequal allelic expression of wild-type and mutated β-myosin in familial hypertrophic cardiomyopathy

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease, which in about 30% of the patients is caused by missense mutations in one allele of the β-myosin heavy chain (β-MHC) gene (MYH7). To address potential molecular mechanisms underlying the family-specific prognosis, we determined the relative expression of mutant versus wild-type MYH7-mRNA. We found a hitherto unknown mutation-dependent unequal expression of mutant to wild-type MYH7-mRNA, which is paralleled by similar unequal expression of β-MHC at the protein level. Relative abundance of mutated versus wild-type MYH7-mRNA was determined by a specific restriction digest approach and by real-time PCR (RT-qPCR). Fourteen samples from M. soleus and myocardium of 12 genotyped and clinically well-characterized FHC patients were analyzed. The fraction of mutated MYH7-mRNA in five patients with mutation R723G averaged to 66 and 68% of total MYH7-mRNA in soleus and myocardium, respectively. For mutations I736T, R719W and V606M, fractions of mutated MYH7-mRNA in M. soleus were 39, 57 and 29%, respectively. For all mutations, unequal abundance was similar at the protein level. Importantly, fractions of mutated transcripts were comparable among siblings, in younger relatives and unrelated carriers of the same mutation. Hence, the extent of unequal expression of mutated versus wild-type transcript and protein is characteristic for each mutation, implying cis-acting regulatory mechanisms. Bioinformatics suggest mRNA stability or splicing effectors to be affected by certain mutations. Intriguingly, we observed a correlation between disease expression and fraction of mutated mRNA and protein. This strongly suggests that mutation-specific allelic imbalance represents a new pathogenic factor for FHC