Mixed Signals: Why investors may misjudge first time high technology founders

This paper seeks to explain an unexpected result of a previous quantitative study which suggested sub-optimal evaluation by investors of the human capital of first time high tech venture founders. A literature review revealed two possible reasons for this finding: biases/heuristics and signaling. Six investors across three countries (one venture capitalist and one business angel each from the US, UK and Israel) with experience in investing in early stage high technology ventures were interviewed using an identical semi-structured interview protocol. This research design is appropriate for research that seeks to reflect back unexpected findings of previous quantitative research on the subjects of research. Interviewees were first asked to state their own investment criteria, and then presented with the results of the quantitative study and asked for their views. Previous research suggesting a gap between in-use and espoused criteria, and extensive use of gut feeling in decision-making, was supported. Interviewees focused on harvest potential and de-emphasised measures of founder technology capability that predicted early survival and growth in the earlier study. The paper concludes by suggesting how investors might improve funding decisions in high tech ventures led by first-time entrepreneurs, noting the study's limitations and making recommendations for further research

Gravitational duality near de Sitter space

Gravitational instantons ''Lambda-instantons'' are defined here for any given value Lambda of the cosmological constant. A multiple of the Euler characteristic appears as an upper bound for the de Sitter action and as a lower bound for a family of quadratic actions. The de Sitter action itself is found to be equivalent to a simple and natural quadratic action. In this paper we also describe explicitly the reparameterization and duality invariances of gravity (in 4 dimensions) linearized about de Sitter space. A noncovariant doubling of the fields using the Hamiltonian formalism leads to first order time evolution with manifest duality symmetry. As a special case we recover the linear flat space result of Henneaux and Teitelboim by a smooth limiting process.Comment: 13 pages, no figure - v2 contains only small redactional changes (one reference added) and is essentially the published versio

GluN2A NMDA Receptor Enhancement Improves Brain Oscillations, Synchrony, and Cognitive Functions in Dravet Syndrome and Alzheimer's Disease Models.

NMDA receptors (NMDARs) play subunit-specific roles in synaptic function and are implicated in neuropsychiatric and neurodegenerative disorders. However, the in vivo consequences and therapeutic potential of pharmacologically enhancing NMDAR function via allosteric modulation are largely unknown. We examine the in vivo effects of GNE-0723, a positive allosteric modulator of GluN2A-subunit-containing NMDARs, on brain network and cognitive functions in mouse models of Dravet syndrome (DS) and Alzheimer's disease (AD). GNE-0723 use dependently potentiates synaptic NMDA receptor currents and reduces brain oscillation power with a predominant effect on low-frequency (12-20 Hz) oscillations. Interestingly, DS and AD mouse models display aberrant low-frequency oscillatory power that is tightly correlated with network hypersynchrony. GNE-0723 treatment reduces aberrant low-frequency oscillations and epileptiform discharges and improves cognitive functions in DS and AD mouse models. GluN2A-subunit-containing NMDAR enhancers may have therapeutic benefits in brain disorders with network hypersynchrony and cognitive impairments

Modification of Al Current Collector/Active Material Interface for Power Improvement of Electrochemical Capacitor Electrodes

This paper presents results about carbon nanofibers (CNFs) synthesis and their use as surface treatments for Al current collector for carbon electrochemical capacitors in organic electrolyte. CNFs have been successfully synthesized on a pretreated Al substrate; the pretreatment of Al consists of an etching followed by a carbonaceous sol-gel deposit. Performances of cells assembled with pretreated Al and pretreated Al coated by CNFs have been compared by using galvanostatic cycling measurements. Internal resistances as low as 0.4 Omega cm2 are obtained for cells using CNF-treated Al. The increase of the surface contact and interface conductivity between the Al and the active material are responsible for this internal resistance decrease. The capacitance obtained for the two cells is the same (95 F g–1 of activated carbon). Performances [both equivalent series resistance (ESR) and capacitance] are stable over 10 000 cycles, proving the great efficiency of surface treatments

SAHA Enhances Synaptic Function and Plasticity In Vitro but Has Limited Brain Availability In Vivo and Does Not Impact Cognition

Suberoylanilide hydroxamic acid (SAHA) is an inhibitor of histone deacetylases (HDACs) used for the treatment of cutaneous T cell lymphoma (CTCL) and under consideration for other indications. In vivo studies suggest reducing HDAC function can enhance synaptic function and memory, raising the possibility that SAHA treatment could have neurological benefits. We first examined the impacts of SAHA on synaptic function in vitro using rat organotypic hippocampal brain slices. Following several days of SAHA treatment, basal excitatory but not inhibitory synaptic function was enhanced. Presynaptic release probability and intrinsic neuronal excitability were unaffected suggesting SAHA treatment selectively enhanced postsynaptic excitatory function. In addition, long-term potentiation (LTP) of excitatory synapses was augmented, while long-term depression (LTD) was impaired in SAHA treated slices. Despite the in vitro synaptic enhancements, in vivo SAHA treatment did not rescue memory deficits in the Tg2576 mouse model of Alzheimer’s disease (AD). Along with the lack of behavioral impact, pharmacokinetic analysis indicated poor brain availability of SAHA. Broader assessment of in vivo SAHA treatment using high-content phenotypic characterization of C57Bl6 mice failed to demonstrate significant behavioral effects of up to 150 mg/kg SAHA following either acute or chronic injections. Potentially explaining the low brain exposure and lack of behavioral impacts, SAHA was found to be a substrate of the blood brain barrier (BBB) efflux transporters Pgp and Bcrp1. Thus while our in vitro data show that HDAC inhibition can enhance excitatory synaptic strength and potentiation, our in vivo data suggests limited brain availability may contribute to the lack of behavioral impact of SAHA following peripheral delivery. These results do not predict CNS effects of SAHA during clinical use and also emphasize the importance of analyzing brain drug levels when interpreting preclinical behavioral pharmacology

The practices of apartheid as a war crime: a critical analysis

The human suffering caused by the political ideology of apartheid in South Africa during the Apartheid era (1948-1994) prompted worldwide condemnation and a variety of diplomatic and legal responses. Amongst these responses was the attempt to have apartheid recognised both as a crime against humanity in the 1973 Apartheid Convention as well as a war crime in Article 85(4)(c) of Additional Protocol I. This article examines the origins, nature and current status of the practices of apartheid as a war crime and its possible application to the Israeli-Palestinian conflict

Maternal Iodine Status During Pregnancy Is Not Consistently Associated with Attention-Deficit Hyperactivity Disorder or Autistic Traits in Children

BACKGROUND: Severe iodine deficiency during pregnancy can cause intellectual disability, presumably through inadequate placental transfer of maternal thyroid hormone to the fetus. The association between mild-to-moderate iodine deficiency and child neurodevelopmental problems is not well understood. OBJECTIVES: We investigated the association of maternal iodine status during pregnancy with child attention-deficit hyperactivity disorder (ADHD) and autistic traits. METHODS: This was a collaborative study of 3 population-based birth cohorts: Generation R (n = 1634), INfancia y Medio Ambiente (n = 1293), and the Avon Longitudinal Study of Parents and Children (n = 2619). Exclusion criteria were multiple fetuses, fertility treatment, thyroid-interfering medication use, and pre-existing thyroid disease. The mean age of assessment in the cohorts was between 4.4 and 7.7 y for ADHD symptoms and 4.5 and 7.6 y for autistic traits. We studied the association of the urinary iodine-to-creatinine ratio (UI/Creat) <150 μg/g-in all mother-child pairs, and in those with a urinary-iodine measurement at ≤18 weeks and ≤14 weeks of gestation-with the risk of ADHD or a high autistic-trait score (≥93rd percentile cutoff), using logistic regression. The cohort-specific effect estimates were combined by random-effects meta-analyses. We also investigated whether UI/Creat modified the associations of maternal free thyroxine (FT4) or thyroid-stimulating hormone concentrations with ADHD or autistic traits. RESULTS: UI/Creat <150 μg/g was not associated with ADHD (OR: 1.2; 95% CI: 0.7, 2.2; P = 0.56) or with a high autistic-trait score (OR: 0.8; 95% CI: 0.6, 1.1; P = 0.22). UI/Creat <150 μg/g in early pregnancy (i.e., ≤18 weeks or ≤14 weeks of gestation) was not associated with a higher risk of behavioral problems. The association between a higher FT4 and a greater risk of ADHD (OR: 1.3; 95% CI: 1.0, 1.6; P = 0.017) was not modified by iodine status. CONCLUSIONS: There is no consistent evidence to support an association of mild-to-moderate iodine deficiency during pregnancy with child ADHD or autistic traits

Amplifier spurious input current components in electrode-electrolyte interface impedance measurements

BACKGROUND: In Impedance Microbiology, the time during which the measuring equipment is connected to the bipolar cells is rather long, usually between 6 to 24 hrs for microorganisms with duplication times in the order of less than one hour and concentrations ranging from 10(1 )to 10(7 )[CFU/ml]. Under these conditions, the electrode-electrolyte interface impedance may show a slow drift of about 2%/hr. By and large, growth curves superimposed on such drift do not stabilize, are less reproducible, and keep on distorting all over the measurement of the temporal reactive or resistive records due to interface changes, in turn originated in bacterial activity. This problem has been found when growth curves were obtained by means of impedance analyzers or with impedance bridges using different types of operational amplifiers. METHODS: Suspecting that the input circuitry was the culprit of the deleterious effect, we used for that matter (a) ultra-low bias current amplifiers, (b) isolating relays for the selection of cells, and (c) a shorter connection time, so that the relays were maintained opened after the readings, to bring down such spurious drift to a negligible value. Bacterial growth curves were obtained in order to test their quality. RESULTS: It was demonstrated that the drift decreases ten fold when the circuit remained connected to the cell for a short time between measurements, so that the distortion became truly negligible. Improvement due to better-input amplifiers was not as good as by reducing the connection time. Moreover, temperature effects were insignificant with a regulation of ± 0.2 [°C]. Frequency did not influence either. CONCLUSION: The drift originated either at the dc input bias offset current (I(os)) of the integrated circuits, or in discrete transistors connected directly to the electrodes immersed in the cells, depending on the particular circuit arrangement. Reduction of the connection time was the best countermeasure

TLR9 ligation in pancreatic stellate cells promotes tumorigenesis

Modulation of Toll-like receptor (TLR) signaling can have protective or protumorigenic effects on oncogenesis depending on the cancer subtype and on specific inflammatory elements within the tumor milieu. We found that TLR9 is widely expressed early during the course of pancreatic transformation and that TLR9 ligands are ubiquitous within the tumor microenvironment. TLR9 ligation markedly accelerates oncogenesis, whereas TLR9 deletion is protective. We show that TLR9 activation has distinct effects on the epithelial, inflammatory, and fibrogenic cellular subsets in pancreatic carcinoma and plays a central role in cross talk between these compartments. Specifically, TLR9 activation can induce proinflammatory signaling in transformed epithelial cells, but does not elicit oncogene expression or cancer cell proliferation. Conversely, TLR9 ligation induces pancreatic stellate cells (PSCs) to become fibrogenic and secrete chemokines that promote epithelial cell proliferation. TLR9-activated PSCs mediate their protumorigenic effects on the epithelial compartment via CCL11. Additionally, TLR9 has immune-suppressive effects in the tumor microenvironment (TME) via induction of regulatory T cell recruitment and myeloid-derived suppressor cell proliferation. Collectively, our work shows that TLR9 has protumorigenic effects in pancreatic carcinoma which are distinct from its influence in extrapancreatic malignancies and from the mechanistic effects of other TLRs on pancreatic oncogenesis

Where Nothing Happened: The Experience of War Captivity and Levinas’s Concept of the ‘There Is’

This article takes as its subject matter the juridico-political space of the prisoner of war (POW) camp. It sets out to determine the nature of this space by looking at the experience of war captivity by Jewish members of the Western forces in World War II, focusing on the experience of Emmanuel Levinas, who spent 5 years in German war captivity. On the basis of a historical analysis of the conditions in which Levinas spent his time in captivity, it argues that the POW camp was a space of indifference that was determined by the legal exclusion of prisoners from both war and persecution. Held behind the stage of world events, prisoners were neither able to exercise their legal agency nor released from law into a realm of extra-legal violence. Through a close reading of Levinas’s early concept of the ‘there is’ [il y a], the article seeks to establish the impact on prisoners of prolonged confinement in such a space. It sets out how prisoners’ subjectivity dissolved in the absence of meaningful relations with others and identifies the POW camp as a space in which existence was reduced to indeterminate, impersonal being