Jack of All Trades vs Master of Some: Searching Ideal Knowledge Portfolio for Tech Start-Ups

17 pagesSenior leadership is indisputably central to firm performance. Numerous studies have delved into various attributes of firm leadership as predictors of performance, primarily focusing on educational background and prior tenure in other organizations. Surprisingly, the role of technical skills within firm leaders remains an under-researched area. Given that these leaders often serve as chief decision-makers in technology-centric firms, managing numerous engineers, their technical skills likely play a crucial role in ensuring seamless operations and fostering productive teams. This study addresses this gap by examining the influence of leaders' technical skills, specifically evaluating the diversity of these skills, and their depth and breadth within each technical domain on firm performance. Using data from Angel.co and LinkedIn, we constructed technical profiles for 100 firms based on the technical skills of their founders. Our analysis focused on the relationship between the Euclidean distance of technical profiles, their breadth and depth, and firm performance was measured in terms of the capital raised. Our findings suggest that the diversity and depth of technical profiles affect firm performance. We further discuss the broader implications of our results for both research and practical application

Fluid effects in model granular flows

Pore fluid plays a crucial role in many granular flows, especially those in geophysical settings. However, the transition in behaviour between dry flows and fully saturated flows and the underlying physics that relate to this are poorly understood. In this paper, we report the results of small-scale flume experiments using monodisperse granular particles with varying water content and volume in which the basal pore pressure, total pressure, flow height and velocity profile were measured at a section. We compare the results with theoretical profiles for granular flow and with flow regimes based on dimensional analysis. The runout and the centre of mass were also calculated from the deposit surface profiles. As the initial water content by mass was increased from zero to around 10%, we first observed a drop in mobility by approximately 50%, as surface tension caused cohesive behaviour due to matric suction. As the water content was further increased up to 45%, the mobility also increased dramatically, with increased flow velocity up to 50%, increased runout distance up to 240% and reduced travel angle by up to 10° compared to the dry case. These effects can be directly related to the basal pore pressure, with both negative pressures and positive pore pressures being measured relative to atmospheric during the unsteady flow. We find that the initial flow volume plays a role in the development of relative pore pressure, such that, at a fixed relative water content, larger flows exhibit greater positive pore pressures, greater velocities and greater relative runout distances. This aligns with many other granular experiments and field observations. Our findings suggest that the fundamental role of the pore fluid is to reduce frictional contact forces between grains thus increasing flow velocity and bulk mobility. While this can occur by the development of excess pore pressure, it can also occur where the positive pore pressure is not in excess of hydrostatic, as shown here, since buoyancy and lubrication alone will reduce frictional forces. Graphical abstract

Deployable Optical Receiver Array Cubesat

Small satellites and cubesats often have low data transmission rates due to the use of low-gain radio links in UHF and S bands. These links typically provide up to only 1 Mbps for communication between the ground and LEO, limiting the applications and mission operations of small satellites. Optical communication technology can enable much higher data rates and is rapidly gaining hold for larger satellites, including for crosslinks within SpaceX’s Starlink constellation and upcoming NASA deep space missions. However, it has been difficult to implement on small satellites and cubesats due to the need for precision pointing on the order of arcseconds to align the narrow optical laser beam between terminals--a laser transmitter in LEO may yield a footprint less than 100 meters wide at its receiving ground station. We report the development of a 3U cubesat to demonstrate new optical communication technology that eliminates precision pointing accuracy requirements on the host spacecraft. The deployable optical receiver aperture (DORA) aims to demonstrate 1 Gbps data rates over distances of thousands of kilometers. DORA requires an easily accommodated host pointing accuracy of only 10 degrees with minimal stability, allowing the primary mission to continue without reorienting to communicate and/or enabling small satellite missions using low-cost off-the-shelf ADCS systems. To achieve this performance, DORA replaces the traditional receiving telescope on the spacecraft with a collection of wide-angle photodiodes that can identify the angle of arrival for incoming communication lasers and steer the onboard transmitting laser in the corresponding direction. This work is motivated by NASA’s plans for a lunar communications and navigation network and supported by NASA’s Space Technology Program (STP). It is ideally suited for crosslink communications among small spacecraft, especially for those forming a swarm and/or a constellation, and for surface to orbit communications. We will implement the deployable optical receiver aperture and miniature transmission telescope as a 1U payload in the 3U cubesat and conduct the demonstration flight in LEO. Future implementations of the DORA technology are expected to further enable omnidirectional receiving of multiple optical communications simultaneously and accommodate multiple transmitting modules on a single cubesat

Reciprocity and the Hyperlocal Journalist

Increased interest in hyperlocal news has led to growing evidence of its economic value, its ability to play traditional democratic roles associated with news, and its merits and deficiencies in comparison with the outputs a declining established commercial news industry. Given many hyperlocal producers cite the desire to play a role in producing better communities, this paper breaks new ground in examining the social and cultural dimensions of hyperlocal journalism’s news-making, community-building, and place-making roles. We examine this emergent cultural form’s affinity with telling stories, and enabling conversations, about civic and political concerns, but also its affinity with, and celebration of, the banal everyday. Employing the novel theoretical concept of reciprocal journalism we provide new evidence about the mutually reinforcing online, and offline, practices that underpin relationships between producers and the communities they inhabit and represent. Drawing on evidence from the most extensive multi-method study of UK hyperlocal news to date, it demonstrates the different kinds of direct and indirect reciprocal exchange practices common in community news, and shows how such work, often composed of journalistic and community-activist practices, can enable and foster relationships of sustained reciprocity which improve and strengthen both hyperlocal news and the communities it serves

Language Models (Mostly) Know What They Know

We study whether language models can evaluate the validity of their own claims and predict which questions they will be able to answer correctly. We first show that larger models are well-calibrated on diverse multiple choice and true/false questions when they are provided in the right format. Thus we can approach self-evaluation on open-ended sampling tasks by asking models to first propose answers, and then to evaluate the probability "P(True)" that their answers are correct. We find encouraging performance, calibration, and scaling for P(True) on a diverse array of tasks. Performance at self-evaluation further improves when we allow models to consider many of their own samples before predicting the validity of one specific possibility. Next, we investigate whether models can be trained to predict "P(IK)", the probability that "I know" the answer to a question, without reference to any particular proposed answer. Models perform well at predicting P(IK) and partially generalize across tasks, though they struggle with calibration of P(IK) on new tasks. The predicted P(IK) probabilities also increase appropriately in the presence of relevant source materials in the context, and in the presence of hints towards the solution of mathematical word problems. We hope these observations lay the groundwork for training more honest models, and for investigating how honesty generalizes to cases where models are trained on objectives other than the imitation of human writing.Comment: 23+17 pages; refs added, typos fixe

Red Teaming Language Models to Reduce Harms: Methods, Scaling Behaviors, and Lessons Learned

We describe our early efforts to red team language models in order to simultaneously discover, measure, and attempt to reduce their potentially harmful outputs. We make three main contributions. First, we investigate scaling behaviors for red teaming across 3 model sizes (2.7B, 13B, and 52B parameters) and 4 model types: a plain language model (LM); an LM prompted to be helpful, honest, and harmless; an LM with rejection sampling; and a model trained to be helpful and harmless using reinforcement learning from human feedback (RLHF). We find that the RLHF models are increasingly difficult to red team as they scale, and we find a flat trend with scale for the other model types. Second, we release our dataset of 38,961 red team attacks for others to analyze and learn from. We provide our own analysis of the data and find a variety of harmful outputs, which range from offensive language to more subtly harmful non-violent unethical outputs. Third, we exhaustively describe our instructions, processes, statistical methodologies, and uncertainty about red teaming. We hope that this transparency accelerates our ability to work together as a community in order to develop shared norms, practices, and technical standards for how to red team language models

Simultaneous siRNA Targeting of Src and Downstream Signaling Molecules Inhibit Tumor Formation and Metastasis of a Human Model Breast Cancer Cell Line

Src and signaling molecules downstream of Src, including signal transducer and activator of transcription 3 (Stat3) and cMyc, have been implicated in the development, maintenance and/or progression of several types of human cancers, including breast cancer. Here we report the ability of siRNA-mediated Src knock-down alone, and simultaneous knock-down of Src and Stat3 and/or cMyc to inhibit the neoplastic phenotype of a highly metastatic human model breast cancer cell line, MDA-MB-435S, a widely used model for breast cancer research.Src and its downstream signaling partners were specifically targeted and knocked-down using siRNA. Changes in the growth properties of the cultured cancer cells/tumors were documented using assays that included anchorage-dependent and -independent (in soft agar) cell growth, apoptosis, and both primary and metastatic tumor growth in the mouse tumor model. siRNA-mediated Src knock-down alone, and simultaneous knock-down of Src and Stat3 and/or cMyc inhibited the neoplastic phenotype of a highly metastatic human model breast cancer cell line, MDA-MB-435S. This knock-down resulted in reduced growth in monolayer and soft agar cultures, and a reduced ability to form primary tumors in NOD/SCID mice. In addition, direct intra-tumoral injection of siRNAs targeting these signaling molecules resulted in a substantial inhibition of tumor metastases as well as of primary tumor growth. Simultaneous knock-down of Src and Stat3, and/or Myc exhibited the greatest effects resulting in substantial inhibition of primary tumor growth and metastasis.These findings demonstrate the effectiveness of simultaneous targeting of Src and the downstream signaling partners Stat3 and/or cMyc to inhibit the growth and oncogenic properties of a human cancer cell line. This knowledge may be very useful in the development of future therapeutic approaches involving targeting of specific genes products involved in tumor growth and metastasis

Oral abstracts 3: RA Treatment and outcomesO13. Validation of jadas in all subtypes of juvenile idiopathic arthritis in a clinical setting

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR. Disclosure statement: All authors have declared no conflicts of interest. Table 1Spearman's correlation between JADAS 71 and single markers DA by ILAR subtype ILAR Subtype Systemic onset JIA Persistent oligo JIA Extended oligo JIA Rheumatoid factor neg JIA Rheumatoid factor pos JIA Enthesitis related JIA Psoriatic JIA Undifferentiated JIA Unknown subtype Total cohort Number of children 23 111 12 57 7 9 19 7 17 262 AJC 0.54 0.67 0.53 0.75 0.53 0.34 0.59 0.81 0.37 0.59 PGA 0.63 0.69 0.25 0.73 0.14 0.05 0.50 0.83 0.56 0.64 PGE 0.51 0.68 0.83 0.61 0.41 0.69 0.71 0.9 0.48 0.61 ESR 0.28 0.31 0.35 0.4 0.6 0.85 0.43 0.7 0.5 0.53 Limited 71 JC 0.29 0.51 0.23 0.37 0.14 -0.12 0.4 0.81 0.45 0.41 Parental pain 0.23 0.62 0.03 0.57 0.41 0.69 0.7 0.79 0.42 0.53 Childhood health assessment questionnaire 0.25 0.57 -0.07 0.36 -0.47 0.84 0.37 0.8 0.66 0.4

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies