cssi/SciSciGPT-SciSciNet huggingface dataset:
Point: Combination Versus Single-Agent Chemotherapy: The Argument for Sequential Single Agents

Metastatic breast cancer is a heterogeneous disease, and treatment decisions depend on several individualized patient and tumor characteristics. Although combination therapy often shows improved response rates in metastatic breast cancer, few studies have shown superiority in overall survival. The choice of combination versus sequential single-agent treatment, therefore, must consider many factors, with no one strategy right for all patients. This article reviews several important clinical trials that address this issue, and argues for single-agent sequential therapy for most patients with metastatic breast cancer.
120 CARDIOTROPHIN 1 EXPRESSION IN THE NEONATAL BRAIN FOLLOWING FOCAL CEREBRAL ISCHEMIA.

Background Cardiotrophin 1 (CT-1), a gp130 ligand and an inflammation mediator, was initially found to induce hypertrophy of neonatal cardiac myocytes in vitro. Subsequent studies have shown that CT-1 also protects neonatal ventricular myocytes and isolated rat cardiac myocytes against apoptosis caused by serumdeprivation or stress stimuli when added before simulated ischemia or during reoxygenation in vitro. Recent studies demonstrate that CT-1 acts as a neuroprotectant for motor, sensory, and sympathetic neurons in the peripheral nervous system. To date, however, a role for CT-1 neuroprotection within the central nervous system (CNS) has not been clearly demonstrated. In addition, it is unknown if there is CT-1 expression within the CNS after stroke. Objective To determine if there is CT-1 expression within the brain after focal cerebral ischemia (FCI) in the postnatal day 7 (P7) rat. Methods FCI was induced by an intraluminal catheter technique causing middle cerebral artery occlusion in P7 rats, as we have previously described. The rat pups were sacrificed at 1, 3, 6, 12, 24, and 72 h after FCI, and then their brains were collected and prepared for Western blot and immunohistochemistry analyses with an antimouse CT-1 antibody. Recombinant human CT-1 was used as a positive control for Western blot analysis. Results Western blot analysis showed a single weak band corresponding to CT-1 in the nonischemic right cortex. The intensity of CT-1-positive bands began to increase in the ischemic left cortex from 3 h after FCI. Densitometric analysis showed that CT-1 protein was significantly increased in the ischemic left cortex from 6 to 24 h after FCI compared with the corresponding nonischemic right cortex (p Conclusion This study is the first demonstration that FCI induces a rapid increase in the expression of CT-1 protein within the ischemic cortex of the P7 rat brain. Future work will need to examine if this increased CT-1 expression is associated with a neuroprotective effect within the CNS.
Field Marshal Erwin Rommel: the head injury that may have prolonged the Second World War.

War-related head injury, indeed neurological injury in general, has been a part of the history of humankind for as long as there has been warfare. Such injuries can result in the removal of the individual from combat, thus eliminating any subsequent contribution that he or she might have made to the battle. However, at times, the injuries can have more wide-reaching effects. In the case of commanders or leaders, the impact of their injuries may include the loss of their influence, planning, and leadership, and thus have a disproportionate effect on the battle, or indeed the war. Field Marshal Erwin Rommel was a talented military strategist and leader who was respected by friends and foes alike. He held an honored reputation by the German people and the military leadership. His head injury on July 17, 1944, resulted in his being removed from the field of battle in northern France, but also meant that he was not able to lend his stature to the assassination attempt of Adolph Hitler on July 20. It is possibl...
The Problem of Social Cost

If a psychologist were to play a word association game with economists, the most frequent response to the word ‘Coase’ would undoubtedly be ‘the Coase theorem’. The Coase theorem, and the ideas embodied therein, have captured the imagination of economists as have few other ideas. Indeed, Robert Cooter (1987, p.457) has remarked that ‘Anyone who has taught the Coase Theorem to fresh minds has experienced first hand the wonder and admiration which it inspires’. This by itself merits some analysis, and will be discussed below. What is most important here, however, is the development of an entire movement within economics — that of neoclassical law and economics — largely around a single article, Coase’s ‘The Problem of Social Cost’ (1960).1
Markets of English: Linguistic Capital and Language Policy in a Globalizing World, by Park, J. S. Y. & Wee, L.

In a previous book, Joseph Sung-Yul Park (2009) wrote that his purpose for examining English in South Korea was to free South Koreans from the oppressive ideologies of English that they were subjec...
Microwave modeling of vegetation: A historical prospective

This paper traces the development vegetation modeling during the 1980's. In this time period, discrete random media methods were applied to model vegetation. The distorted Born approximation and transport theory were successfully employed to understand the different contributions to the backscattering cross section from a layer of vegetation. Leaves were modeled by thin dielectric discs and stems, trunks and branches by dielectric cylinders. The discussion will emphasize active modeling but many of the methods apply to the passive case. In addition, most of the references refer to US authors. Contributions form researchers in other countries have not been considered at this time.
Tremor, Essential (Syndromes)

Essential tremor (ET), formerly known as benign ET, is the most common movement disorder. It is now recognized as progressive, and often disabling rather than benign. Growing clinical, genetic, and pathological data suggest that ET is a family of disorders with a range of features. Treatment can provide symptom relief, but disease-modifying therapies await the understanding of underlying pathophysiology.
Abstract 5107: Divergent behaviors and underlying mechanisms of cell migration and invasion in non-metastatic T24 and its metastatic derivative T24T bladder cancer cell lines

Previous studies on cancer cell invasion were primarily focused on its migration because these two events were often considered biologically equivalent. Here we found that T24T cells exhibited higher invasion but lower migration abilities than T24 cells. Expression of Rho-GDPases was much lower and expression of SOD2 was much higher in T24T cells than in T24 cells. Indeed, knockdown of SOD2 in T24T cells can reverse the cell migration but without affecting cell invasion. We also found that SOD2 inhibited the JNK/C-Jun cascade, and the inhibition of c-Jun activation by ectopic expression of TAM67 impaired Rho-GDPases expression and cell migration in T24T shSOD2 cells. Further, we found that Sp1 can upregulate SOD2 transcription in T24T cells. Importantly, matrix metalloproteinase-2 (MMP-2) was overexpressed in T24T and participated in increasing its invasion, and MMP-2 overexpression was mediated by increasing nuclear transport of nucleolin, which enhanced mmp-2 mRNA stability. Taken together, our study unravels an inverse relationship between cell migration and invasion in human bladder cancer T24T cells and suggests a novel mechanism underlying the divergent roles of SOD2 and MMP-2 in regulating metastatic behaviors of human bladder T24T in cell migration and invasion. Citation Format: Honglei Jin, Jingxia Li, Chuanshu Huang. Divergent behaviors and underlying mechanisms of cell migration and invasion in non-metastatic T24 and its metastatic derivative T24T bladder cancer cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5107. doi:10.1158/1538-7445.AM2015-5107
Supporting the development of empathy: The role of theory of mind and fantasy orientation

Theory of mind (ToM) and empathy are separate, but related components of social understanding. However, research has not clearly defined the distinctions between them. Similarly, related constructs, such as fantasy orientation (FO), are associated with better ToM understanding; however, little is known about how FO may provide a context in which both ToM and affective empathy develop. Children between the ages of 3 and 5 (N = 82) completed a battery of ToM, empathy, and FO measures. Results demonstrated a developmental progression from ToM to affective empathy: 3-year-olds were likely to have neither, 4-year-olds were likely to have ToM only, and 5-year-olds were likely to have both. Additionally, results indicated that FO predicted affective empathy above and beyond ToM ability, suggesting that children whose play is high in fantasy are more practiced than their peers in sharing emotions. These findings are discussed in terms of how children's propensity toward fantasy play may contribute to their social development.
Lanthanum fluoride upconverting nanoparticles for photo-biomodulation of cell function

Inorganic fluorescent nanoprobes have been widely used as passive agents for intracellular imaging for decades. An emerging field of research is the development of these contrast agents and using them actively in a way that they respond to external stimulation by inducing photo-chemical, thermal or mechanical actions that enable control and modulation over cell function. To achieve such control, methods which are remote, non-invasive and with low-thermal means of stimulation is preferable. Among a large variety of candidates, lanthanide doped upconverting nanoparticles (UCNPs) are one of the most interesting class of fluorescent materials. Non-scattering, low energy near infrared (NIR) light can be used for excitation of UCNPs as on-demand light sources resulting in emission peaks throughout the near-UV and visible wavelengths. Towards this goal, we developed nano-size, hydrophilic, non-toxic and biocompatible core-shell nanoparticles with enhanced upconversion intensity for photo-biomodulation studies. Under this approach, un-doped LaF3 (inert) shell and Yb3+ doped LaF3 (active) shell are grown on core LaF3:20% Yb, 2% Tm upconverting nanoparticles for enhanced luminescence for the first time with rapid microwave-assisted synthesis method that employs Polyvinylpyrrolidone (PVP) as biocompatible surfactant. The as-synthesized high efficiency UCNPs are analyzed through XRD, TEM, HRTEM, and Photoluminescence spectrum that is acquired under 980 nm laser excitation. Confocal microscopy is used to visualize nanoparticles in cells. The cellular response to NIR irradiation and upconverted light are visualized by luminescence microscopy.
Haploinsufficiency for Mutations in Type I Collagen Genes: Mechanisms and Clinical Effects

The most common class of mutation that results in dominant forms of osteogenesis imperfecta (OI) is haploinsufficiency. Haploinsufficiency describes a state in which the protein products of one allele of a gene are not available for use. The most common mechanism is the introduction of a premature termination codon that results in mRNA instability and loss of ability to produce protein. The most common mechanisms by which these changes occur are as a consequence of nonsense mutation, frameshifts and splice site mutation that lead to frameshifts. Virtually all these mutations occur in COL1A1 and lead to OI type I. The same class of mutations is very rare in COL1A2, probably because they do not bring the individual to clinical attention.
Smart Pedagogy for Smart Universities

The performed analysis of innovative technology-based learning and teaching strategies for smart classrooms clearly shows that in the near future smart pedagogy will be actively deployed by leading academic institutions in the world for teaching of local and remote students in one class. The research project is focused on in-depth analysis of innovative learning strategies, including (1) learning-by-doing, (2) flipped classroom, (3) games-based learning, (4) adaptive teaching, (5) context-based learning, (6) collaborative learning, (7) learning analytics, (8) “bring your own device” (BYOD) strategy, (9) personal enquiry based learning, (10) crossover learning, (11) robotics-based learning, and other advanced technology-based approaches to teaching and learning. The obtained outcomes of this performed research, analysis, and testing of implemented smart pedagogy components undoubtedly prove that those learning and teaching strategies support identified “smartness” levels and smart features of smart classrooms such as (1) adaptivity, (2) sensing, (3) inferring, (4) anticipation, (5) self-learning, and (6) self-organization. The obtained student feedback undoubtedly demonstrates students’ strong interest in smart pedagogy – the approach that will be an essential topic of multiple research, design, and development projects in the next 5–10 years.
Control of Crop Growth in Advanced Life Support Systems

Abstract An elementary method for controlling crop growth in Advanced Life Support Systems is presented. Two models for crop growth are considered, one developed by the agricultural industry and used by the Ames Research Center, and a mechanistic model. termed the Energy Cascade model. The controller is applied to both models using wheat as the crop. A variety of circumstances are considered, such as model errors, measurement errors, and the incapability of applying the desired control input. It is shown that the proposed approach is a potentially viable way of controlling crop growth.
A sequential, multiple-treatment, targeted approach to reduce wound healing and failure of glaucoma filtration surgery in a rabbit model (an American Ophthalmological Society thesis).

PURPOSE The purpose of this study was to evaluate the concept of targeting mediators of the scarring process at multiple points across the course of bleb failure, in order to prolong bleb survival. METHODS There were three linked parts to the experiment. In the first part, a cannula glaucoma filtration surgery (GFS) was performed on 32 New Zealand White (NZW) rabbits, and bleb survival was assessed for six different regimens plus controls by grading bleb height and width. For the second part of the study, the same GFS surgery was performed on an additional 10 NZW rabbits. Two additional filtering blebs were treated with balanced saline solution (BSS), two received mitomycin-C (MMC) (0.4 mg/mL), and for the remaining six, a sequential regimen was given consisting of 200 mmol/L mannose-6-phosphate (M-6-P) solution at the time of surgery, followed by subconjunctival injections of antibody to connective tissue growth factor at days 2 and 4, and Ilomastat, a broad-spectrum matrix metalloproteinase inhibitor, at days 7, 12, and 20 postoperatively. Bleb survival was again assessed. In the final part of the experiment, blebs treated with either BSS, MMC, or the above sequential multitreatment regimen were examined histologically at 14 days postoperatively in three additional NZW rabbits. RESULTS All six individual therapies selected resulted in some improvement of bleb survival compared to BSS control. Blebs treated with the new sequential, multitreatment protocol survived an average of 29 days (regression slope, P < .0001 compared to control), those receiving BSS an average of 17 days, and those treated with MMC (0.4 mg/mL) an average of 36 days. The sequential, multitreatment regimen was significantly superior to any of the six monotherapies for time to zero analysis (flattening) of the bleb (P < .002). Histologic examination of the bleb tissues showed a markedly less epithelial thinning, subepithelial collagen thinning, and goblet cell loss in the multitreatment group, when compared with the MMC blebs. CONCLUSIONS In a rabbit model of GFS, a sequential, targeted, multitreatment approach prolonged bleb survival compared to BSS controls and decreased bleb tissue morphological changes when compared to those treated with MMC. It is not known whether these findings can be reproduced in humans, and further work is needed to determine an optimum regimen and timing of therapeutic delivery.
Effects of Size of Variable Ratio Schedule on Disinhibition

Rats were trained to press a bar for food on a CRF, VR5, or VR20 reinforcement schedule. After meeting an extinction criterion of 30 sec. without a response, a 4 sec. buzzer was presented to most Ss. Disinhibition was a function of size of variable ratio. A non-disinhibited VR20 group gave significantly fewer responses than an equivalently trained disinhibited group, ruling out an explanation of these effects in terms of short-term spontaneous recovery. This variable-ratio disinhibition effect is held to have considerable generality, i.e., from rat to retardate.
Efficient swimming using flexible fins with tapered thickness

Three-dimensional computer simulations reveal that tapering the thickness of a fin enhances propulsion efficiency and enables high thrust and swimming velocity for a wide range of actuation frequencies.
Input-Output Distance Properties of Good Linear Codes

Consider a linear code defined as a mapping between vector spaces of dimensions $k$ and $n$ . Let $\beta^{\ast}$ denote the minimal (relative) weight among all images of input vectors of full Hamming weight $k$ . Operationally, $\beta^{\ast}$ characterizes the threshold for adversarial (erasure) noise beyond which decoder is guaranteed to produce estimate of k-input with 100% symbol error rate (SER). This paper studies the relation between $\beta^{\ast}$ and $\delta$ , the minimum distance of the code, which gives the threshold for 0 % SER. An optimal tradeoff between $\beta^{\ast}$ and $\delta$ is obtained (over large alphabets) and all linear codes achieving $\beta^{\ast}=1$ are classified: they are repetition-like. More generally, a design criteria is proposed for codes with favorable graceful degradation properties. As an example, it is shown that in an overdetermined system of $n$ homogeneous linear equations in $k$ variables (over a field) it is always possible to satisfy some $k-1$ equations with non-zero assignments to every unknown, provided that any subset of $k$ equations is linearly independent. This statement is true if and only if $n\geq 2k-1$ .
Extending OpenMP to Facilitate Loop Optimization

OpenMP provides several mechanisms to specify parallel source-code transformations. Unfortunately, many compilers perform these transformations early in the translation process, often before performing traditional sequential optimizations, which can limit the effectiveness of those optimizations. Further, OpenMP semantics preclude performing those transformations in some cases prior to the parallel transformations, which can limit overall application performance.
Conflict-related medial frontal theta as an endophenotype for alcohol use disorder.

Abstract Diminished cognitive control in alcohol use disorder (AUD) is thought to be mediated by prefrontal cortex circuitry dysregulation. Research testing the relationship between AUD and specific cognitive control psychophysiological correlates, such as medial frontal (MF) theta-band EEG power, is scarce, and the etiology of this relationship is largely unknown. The current report tested relationship between pathological alcohol use through young adulthood and reduced conflict-related theta at age 29 in a large prospective population-based twin sample. Greater lifetime AUD symptomatology was associated with reduced MF theta power during response conflict, but not alpha-band visual attention processing. Follow-up analyses using cotwin control analysis and biometric modeling suggested that genetic influences, and not the consequences of sustained AUD symptomatology, explained the theta-AUD association. Results provide strong evidence that AUD is genetically related to diminished conflict-related MF theta, and advance MF theta as a promising electrophysiological correlate of AUD-related dysfunctional frontal circuitry.
Hedgehog Signaling in Carcinogenesis

The Hedgehog (Hh) pathway mediates normal patterning during embryogenesis and contributes to tissue homeostasis after development is complete. Aberrant activation of Hh signaling has been implicated in a wide variety of malignancies and is involved in multiple cellular processes important in carcinogenesis and tumor progression. Strikingly, mutations that constitutively activate the Hh pathway cause the nevoid basal cell carcinoma (BCC) syndrome (NBCCS), which is a heritable cancer predisposition syndrome that greatly increases the risk of developing BCCs and medulloblastomas. Preclinical data have demonstrated that Hh inhibition is an attractive target in cancer, but the translation of this research to the clinic has been a challenge. Despite a number of negative clinical trials, Hh-directed therapies are proven to be effective in cancers reliant on this pathway, and future trials must be designed to properly select for patients with Hh-driven tumors to increase the likelihood of a positive result. Here, we review the mechanisms underlying the pathway and different strategies used to inhibit Hh signaling. We also discuss the role that the Hh pathway plays in carcinogenesis and carefully examine available trial data to understand why clinical applications have lagged behind preclinical successes. Finally, we address the future of Hh-directed therapies and factors that will be critical to effectively expanding their use for the treatment of cancer patients.
Theory of SAR Signature Defocus Morphology for Arbitrary 3-D Target Motion Over Terrain Relief

This paper generates analytic equations for predicting the 2-D defocus morphology of the signature smears within spotlight synthetic aperture radar imagery, which are induced by targets having arbitrary 3-D motion. One primary application of such 3-D target motion is to enable the inclusion of terrain relief in the signatures smears due to surface targets. These mathematical techniques can predict the detailed imagery shapes of such induced signature smears, including width and interference effects. These methods provide an accurate and effective tool in predicting the shape, extent, and location of the defocused smears due to surface targets that are subject to terrain relief.
Reviewing and repurposing: the next iteration of ROC

Progress is enchanting. I felt its charms when I learned that I would be the next editor of this journal, news that I took as proof of personal and professional growth. I have embraced its aspirati...
Afterword: The Consolations of Ruins—From the Acropolis to Epidaurus

I draw on my sensory experiences of the Acropolis ruin (and the Acropolis archaeological museum) followed by a visit to the Epidaurus complex (especially the theatre) to explore the themes of destruction, melancholy, preservation, hospitality (and intimacy), among others, as they evoke both the ruins of cultures and global preoccupations with the cultures of ruin. In a “presentist” theoretical move, this essay reflects on the affective and imaginative impact of these classical ruins during the immediacy of my contact with them. The centre of “gravity” of my musings on the monuments is “now, rather than then”: evoking their materiality, I consider how they produce affective consolations by re-imagining the past.
Pre-surgical stress and social support predict post-surgical percent excess weight loss in a population of bariatric surgery patients.

Although bariatric surgery is an effective treatment of morbid obesity, many patients fail to lose significant weight or regain weight over time. This study examined pre-surgical psychosocial predi...
QUANTITATIVE FREEZE-FRACTURE ANALYSIS OF THE FROG NEUROMUSCULAR JUNCTION SYNAPSE : I. NATURALLY OCCURRING VARIABILITY IN ACTIVE ZONE STRUCTURE

The orderly arrays of intramembranous particles (IMPs) found in the p-face of freeze-fracture replicas of the frog neuromuscular junction (‘active zones’) are believed to be involved in transmitter release. Some or all of the particles represent voltage-dependent Ca2+ channels. Since there is a great heterogeneity in the amount of transmitter released by different frog motor nerve terminals we sought to determine whether active zone (AZ) structure displayed a similar heterogeneity by using a novel freeze-fracture procedure providing large, intact replicas containing significant portions of motor nerve terminals from the cutaneous pectoris muscle of the frog, Rana pipiens. Using only junctions in which more than 50 AZs or more than 50 μm of nerve terminal were included in the fractures, we measured AZ length, AZ intramembranous particle density, terminal width at each AZ, space between AZs, the angle of AZ orientation with respect to the longitudinal axis of the nerve terminal, exposed pre-synaptic nerve terminal surface area and a calculated value for mean AZ length per unit terminal length. The analysis led to the following conclusions. There is an approximate 5-fold range in mean AZ length/micrometre terminal length. Terminal width is a good predictor of AZ length. Particle density does not vary significantly within a given AZ, nor between AZs from the same or different junctions. The distance between AZs is not related to AZ length, i.e. shorter AZs are no more or less likely to be closer to the adjacent AZ. The probability of release from any AZ on action potential invasion is small. If most of the IMPs are Ca2+ channels, either the probability of channel opening or the efficacy of triggering release is very low or both. That the variability in release efficacy in different terminals is much greater than ultrastructural variability in terminals suggests that regulation of release is dominated by physiological processes that do not have obvious ultrastructural correlates. On the other hand, the apparent excess of AZ relative to the number of vesicles released indicates that the amount and variability in amount of AZ is important in ways that need to be elucidated.
A variable X-ray chopper system for phase-sensitive detection in synchrotron X-ray scanning tunneling microscopy.

An ultra-high-vacuum compatible X-ray chopper system has been designed, constructed and integrated into the XTIP beamline at the Advanced Photon Source at Argonne National Laboratory. The XTIP beamline can operate at soft X-ray energies from 400 eV to 1900 eV while providing a focused beam down to about 10 µm × 10 µm into the synchrotron X-ray scanning tunneling microscopy (SX-STM) endstation instrument. The X-ray chopper is a critical component for separating topographic information from chemical information in SX-STM through phase-sensitive current detection. Depending on the experimental needs, the modulation frequency can be controlled from 100 Hz to 10 kHz. In addition, the chopper system is fully bakeable and can achieve a base pressure of 10−10 mbar. Facilities for active water cooling have been designed, but passive cooling through copper braids has been shown to be sufficient at standard chopping frequencies. Using an Fe/Al2O3/CoAl(111) sample, the separation of the SX-STM current into a chemical component and a stable feedback signal is demonstrated.
COVID-19-Associated Acute Kidney Injury: An Evolving Picture

Over the past 7 months, severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) has afflicted over 21 million patients and resulted in over 760,000 deaths. Rapid recognition of the extrapulmonary manifestations of infection has prompted an unprecedented rate of reports
Aesthetic Judgments of Live and Recorded Music: Effects of Congruence Between Musical Artist and Piece

The COVID-19 pandemic has brought the live music industry to an abrupt halt; subsequently, musicians are looking for ways to replicate the live concert experience virtually. The present study sought to investigate differences in aesthetic judgments of a live concert vs. a recorded concert, and whether these responses vary based on congruence between musical artist and piece. Participants (N = 32) made continuous ratings of their felt pleasure either during a live concert or while viewing an audiovisual recorded version of the same joint concert given by a university band and a United States Army band. Each band played two pieces: a United States patriotic piece (congruent with the army band) and a non-patriotic piece (congruent with the university band). Results indicate that, on average, participants reported more pleasure while listening to pieces that were congruent, which did not vary based on live vs. lab listening context: listeners preferred patriotic music when played by the army band and non-patriotic music when played by the university band. Overall, these results indicate that felt pleasure in response to music may vary based on listener expectations of the musical artist, such that listeners prefer musical pieces that "fit" with the particular artist. When considering implications for concerts during the COVID-19 pandemic, our results indicate that listeners may experience similar degrees of pleasure even while viewing a recorded concert, suggesting that virtual concerts are a reasonable way to elicit pleasure from audiences when live performances are not possible.
Milk Quality Premiums Received by Wisconsin Dairy Farms Participating in Veterinary-directed Milk Quality Programs

High quality milk is generally defined as adulterant free milk that meets specific quality criteria relating to the level of somatic cells (SCC) and bacteria. In the U.S., production of high quality milk is encouraged by legislating maximum limits of SCC and bacteria, and by financial rewards offered by processors (premiums). This study describes the relationship between measures of milk quality, dairy management practices and financial incentives offered by milk processors on selected Wisconsin dairy farms.
Mail, Rail, and Legwork: State and Nation Building through Postal Service in France and Great Britain, 1830–1914

A comparative spatial history using GIS, this article examines the similar and differing effects of railway expansion on the growth of postal communications in Great Britain and France from 1830 to the eve of the Great War. It argues that the modern Postal Age in Great Britain and France began in the 1830s. In Britain in 1839, the Parliament obligated private railway companies to convey the Royal Mail throughout the kingdom at reasonable rates. Thereafter, the expansion of postal services and railway networks went hand in hand. Over the years, thousands of new post offices were established and were closer to rail stations than before. As the years wore on the geography of postal communication expanded greatly and by 1914 the majority of rural districts became part of the system of regular, daily mail. In France, a country four or five times larger than England and Wales with a relatively vast rural population, the task of modernizing postal service was a greater challenge. The inauguration of a “rural service” in 1829 employed some 5,000 men as postal carriers to deliver and collect mail throughout the countryside. Thereafter, their numbers grew as new post offices were established to serve villages and small towns with mail deliveries every other day. In the 1880s, under the Third Republic, the state greatly expanded the postal service, deeming it a national mission. It was then that the growing rail network came to shape the national geography of postal service. Hence, at the turn of the century the patterns British and French postal expansions converged.
Lessons Learned From the Implementation of a Participant-Collected, Mail-Based SARS-CoV-2 Serological Survey in Massachusetts, USA

Abstract The rapid spread of SARS-CoV-2 is largely driven by pre-symptomatic or mildly symptomatic individuals who transmit the virus. Serological tests to identify antibodies against SARS-CoV-2 are an important tool to characterize subclinical infection exposure, which is critical in determining transmission trajectories and consequent population immunity. During the summer of 2020, a mail-based serological survey with self-collected dried blood spot (DBS) samples was implemented among university affiliates and their household members in Massachusetts, USA. Described here are some of the challenges faced and novel procedures used during the implementation of this study to assess the prevalence of SARS-CoV-2 antibodies amid the global pandemic. Important challenges included remote and contact-minimized participant recruitment, limited availability of commodities and laboratory capacity, a potentially biased sample population, and policy changes impacting the distribution of clinical results to study participants. Methods used to surmount these challenges and lessons learned are presented to inform similar studies. Key lessons relate to the acceptability and feasibility of DBS sampling, supply requirements, the logistics of packing and shipping packages, data linkages to enrolled household members, and the utility of having an on-call nurse available for participant concerns during sample collection. Future studies might consider additional recruitment techniques such as conducting studies during academic semesters when recruiting in a university setting, partnerships with supply and shipping specialists, and using a stratified sampling approach to minimize potential biases in recruitment. This study design highlights the feasibility and acceptability of self-collected bio-samples and has broad applicability for other serological surveys for a range of pathogens.
Blood in the Water (Transcript of Discussion)

A couple of years ago when we were analysing voting machines we came across a question for which we didn’t have an answer, namely if these machines are so bad why aren’t they being attacked left and right? These machines were full of vulnerabilities, they were trivial to exploit, and yet it strikes me now there’s been no documented case of an attack on any voting system by exploiting a software or a hardware vulnerability.
Double-Strand Break Recognition and its Repair by Non-Homologous End-Joining

Publisher Summary Double-strand breaks (DSBs) are the most challenging type of DNA damage to repair in cells, and efficient repair mechanisms are critical. In mammalian cells, the error-free homologous recombination (HR), and the error prone non-homologous end-joining (NHEJ) are the two major pathways for repair of DSBs. The HR pathway, in general, repairs the damaged strand by using an intact sister chromatid. In contrast, the NHEJ pathway includes steps involving editing of DNA ends by deleting or adding nucleotides at the ends. NHEJ is the primary DSB repair pathway used in mammalian cells. DSBs can be induced both physiologically and pathologically. In simplest terms, repair of DSBs is focused on joining the two ends back together. However, it is a much more complicated procedure than just simple ligation. The NHEJ repair pathway involves several proteins that are involved in its various steps. The largest protein in the NHEJ pathway, DNA dependent protein kinase or DNA-PKcs, is 469 kDa. Cells lacking DNA-PKcs are sensitive to ionizing irradiation as well as chemical compounds that induce double-strand breaks. Using purified proteins, biochemical assays are able to detect DNA-PKcs kinase activity initiated via binding to DNA and autophosphorylation of itself or substrate proteins. Autophosphorylation of DNA-PKcs correlates with loss of DNA-PK activity and dissociates from DNA, which might also be an indication of completion of the repair process.
Timesharing without synchronization

The capacity region of a multiple-access channel has recently been identified as the convex hull (barred K) of a certain set (K) of points in the first quadrant of the (R1,R2) plane. For a pair of rates in K, a more or less standard random-coding argument can be used to show the existence of a good pair of codes. But for points in barred K-K, it is apparently necessary for the two senders to use some form of time sharing to achieve the desired rates. However, in order to share time, at least one of the senders must have knowledge of the other's phase; and in many practical situations this knowledge does not exist. This paper investigates the problems which arise in coding for multiple-access channels when the senders cannot synchronize with each other.
Teaching Patrons to Fish: The Educational Value of Cancelling Requests for Locally Available Materials

Expansive document delivery service for locally available materials is becoming increasingly popular, but is a learning component lost with the implementation of this service? In this study, the authors compare data from two institutions, one that provides an unadvertised document delivery service without instruction, and another that cancels requests for locally available materials with an instructional component. The behavior of each institution's patrons over a 4-year period is analyzed and found to differ at statistically significant levels. These findings will be useful for interlibrary loan policy makers who are considering whether to implement document delivery for locally available items.
Immunopotentiation by SGP and Quil A. II. Identification of responding cell populations.

Abstract The adjuvants SGP (a starch-acrylamide polymer) and Quil A (purified saponin) were shown to markedly augment antibody responses to T-independent (TI) antigens, suggesting that their adjuvant effects may be at least partially mediated through B cells. The ability of both adjuvants to augment primary responses to trinitrophenyl (TNP)-Ficoll (TI-2 antigen) in athymic nude mice further suggested these adjuvants affect B cells. SGP, however, did not induce a response to the T-dependent (TD) antigen dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH) in athymic nude mice, indicating it was unable to replace the requirement for T-helper cells for responses to TD antigens. Responses to TNP-lipopolysaccharide (LPS) were augmented by SGP in CBA/N X Balb/c immune defective (xid) mice. However, SGP was unable to induce a response to TNP-Ficoll in xid mice. The SGP and Quil A augmented responses to TNP-Ficoll were completely inhibited by the mitotic inhibitor, Velban, indicating that SGP and Quil A increased the plaque-forming cell (PFC) response primarily by stimulating cell proliferation, and not by recruitment of antigen-reactive cells. The effects of the adjuvants on secondary responses were investigated using adoptive transfer experiments. SGP and Al(OH)3 both increased the induction of haptenspecific memory B cells in mice primed with DNP-KLH. SGP, Quil A, and Al(OH)3 also increased priming of carrier specific T cells. Priming of memory B cells with DNP-KLH and either Al(OH)3 or SGP was prevented when T cells were depleted with anti-lymphocyte serum (ALS) at the time of antigen priming, indicating that the augmentation of memory B-cell priming by SGP and Al(OH)3 was dependent on the presence of functional T cells. SGP and Quil A were both unable to augment memory cell induction to the TI antigen, TNP-Ficoll, even though both adjuvants markedly augmented primary IgM and IgG responses to this antigen. Based on these results, it is suggested that SGP and Quil A can mediate their adjuvant effects primarily by a direct or indirect effect on B cells although the adjuvants may also affect T cells to some extent.
Race-Based Perceptual Asymmetry in Face Processing Is Evident Early in Life.

Adults' processing of own-race faces differs from that of other-race faces. The presence of an "other-race" feature (ORF) has been proposed as a mechanism underlying this specialization. We examined whether this mechanism, which was previously identified in adults and in 9-month-olds, is evident at 3.5 months. Caucasian 3.5-month-olds looked longer at a pattern containing a single Asian face among seven Caucasian faces than at a pattern containing a single Caucasian face among seven Asian faces. Homogenous and inverted face control conditions indicated that infants' preference was not driven by the majority of faces in arrays or by low-level features. Thus, 3.5-month-olds found the presence of an other-race face among own-race faces to be more salient than the reverse configuration. This asymmetry suggests sensitivity to an ORF at 3.5 months. Thus, a key mechanism of race-based processing in adults has an early onset, indicating rapid development of specialization early in life.
Biochemical Effects of Novobiocin on Staphylococcus aureus

Wishnow, Rodney M. (Washington University School of Medicine, St. Louis, Mo.), Jack L. Strominger, Claire H. Birge, and Robert H. Threnn. Biochemical effects of novobiocin on Staphylococcus aureus. J. Bacteriol. 89:1117-1123. 1965.-Novobiocin induced accumulation in Staphylococcus aureus of uridine nucleotide precursors of the cell-wall glycopeptide, of a cytidine nucleotide precursor of the teichoic acid in the cell wall, and of a large number of other ultraviolet-absorbing materials. These substances accumulated promptly on addition of the antibiotic at levels near the growth-inhibitory concentration. Isotopic experiments showed that, in addition to inhibiting cell-wall synthesis, novobiocin also inhibited both protein and nucleic acid synthesis. The lack of selectivity in the action of novobiocin is similar to that previously observed with gentian violet, and is quite different from the selective inhibition of cell-wall synthesis observed with penicillin or with d-cycloserine. Although inhibition of cell-wall synthesis is not excluded as one of the primary lethal effects of novobiocin, it is also possible that all of the observed phenomena are secondary to some other primary metabolic lesion.
Synthesis and characterization of a lubricin mimic (mLub) to reduce friction and adhesion on the articular cartilage surface.

The lubricating proteoglycan, lubricin, facilitates the remarkable low friction and wear properties of articular cartilage in the synovial joints of the body. Lubricin lines the joint surfaces and plays a protective role as a boundary lubricant in sliding contact; decreased expression of lubricin is associated with cartilage degradation and the pathogenesis of osteoarthritis. An unmet need for early osteoarthritis treatment is the development of therapeutic molecules that mimic lubricin function and yet are also resistant to enzymatic degradation common in the damaged joint. Here, we engineered a lubricin mimic (mLub) that is less susceptible to enzymatic degradation and binds to the articular surface to reduce friction. mLub was synthesized using a chondroitin sulfate backbone with type II collagen and hyaluronic acid (HA) binding peptides to promote interaction with the articular surface and synovial fluid constituents. In vitro and in vivo characterization confirmed the binding ability of mLub to isolated type II collagen and HA, and to the cartilage surface. Following trypsin treatment to the cartilage surface, application of mLub, in combination with purified or commercially available hyaluronan, reduced the coefficient of friction, and adhesion, to control levels as assessed over macro-to micro-scales by rheometry and atomic force microscopy. In vivo studies demonstrate an mLub residency time of less than 1 week. Enhanced lubrication by mLub reduces surface friction and adhesion, which may suppress the progression of degradation and cartilage loss in the joint. mLub therefore shows potential for treatment in early osteoarthritis following injury.
Mechanism of Action of Calcitonin Gene-Related Peptide in Inhibiting Pancreatic Enzyme Secretion in Rats

Abstract Background: Recently, calcitonin gene-related peptide (CGRP) receptors have been identified in the central nervous system. Therefore whether CGRP inhibits pancreatic enzyme secretion at a central site was investigated. Methods: In vivo studies were performed on rats to examine the effect of CGRP on pancreatic enzyme secretion evoked by stimulants that act on different sites: (1) 2-Deoxy-d-glucose (2DG), a central vagal stimulant; (2) cholecystokinin, which acts via vagal afferent pathways under physiologic conditions; (3) electric vagal nerve stimulation, which stimulates vagal release of acetylcholine in the pancreas; and (4) bethanechol, which directly activates pancreatic muscarinic receptors. Results: CGRP produced a dose related inhibition of pancreatic secretion evoked by 2DG. Complete inhibition was observed at a dose of 25 μg · kg −1 · h −1 . Similarly, CGRP at a dose of 50 μg · kg −1 · h −1 completely inhibited pancreatic protein secretion in response to a physiological concentration of cholecystokinin octapeptide (CCK-8). In contrast, pancreatic protein secretion evoked by bethanechol or electrical stimulation of the vagal trunk were unaffected by CGRP. It was also shown that perivagal capsaicin treatment impaired pancreatic responses to CCK-8 but not to 2DG ruling out an effect of CGRP on vagal afferent pathway. Conclusions: Our data indicates that CGRP inhibits pancreatic enzyme secretion evoked by 2DG or CCK-8 via vagal pathways. CGRP exerts its inhibitory action at a central vagal site.
Long-Term Oestradiol Treatment Enhances Hippocampal Synaptic Plasticity that is Dependent on Muscarinic Acetylcholine Receptors in Ovariectomised Female Rats

Short-term oestradiol treatment modulates hippocampus-dependent memory and synaptic plasticity in the hippocampus. Long-term oestradiol treatment can also enhance hippocampus- dependent memory, although the effects of long-term oestradiol treatment on synaptic plasticity are unknown. We investigated the effects of long-term oestradiol treatment on synaptic plasticity at the Schaeffer Collateral/CA1 synapse in 8-month-old female rats. In addition, we determined the role of endogenous activation of muscarinic acetylcholine receptors (mAChRs) in synaptic transmission and plasticity using scopolamine (1 μm), an antagonist of mAChRs. Hippocampus slices from ovariectomised rats that were treated with oestradiol-containing capsules for 5 months were compared with slices from ovariectomised rats that received cholesterol-containing capsules. Unexpectedly, scopolamine application significantly increased the baseline field excitatory postsynaptic potentials (fEPSP) and decreased paired pulse facilitation (PPF) in slices from cholesterol-treated rats. Baseline fEPSPs and PPF were not significantly modulated in slices from oestradiol-treated rats by scopolamine. Slices from oestradiol-treated rats showed enhanced long-term potentiation relative to slices from cholesterol-treated rats. Scopolamine significantly reduced the magnitude of plasticity in slices from oestradiol-treated rats. Taken together, these results suggest that mAChRs have a significant effect on baseline synaptic transmission through a decrease in the probability of glutamate release in slices from cholesterol-treated rats. Long-term oestradiol treatment blocks this effect and enhances theta-burst stimulation-induced synaptic plasticity in the middle-aged female rat, and this effect is mediated by activation of mAChRs.
Dimensions of Suicide: Perceptions of Lethality, Time, and Agony

Two hundred ninety-one lay persons and 10 forensic pathologists rated the lethality, time, and agony for 28 methods of suicide for 4117 cases of completed suicide in Los Angeles County in the period 1988-1991. Whereas pathologists provided consistent ratings, lay persons demonstrated extreme variability and a tendency to inflate ratings of all three dimensions. Significant gender differences emerged, with females rating frequently used suicide methods more similarly to pathologists than the males did. Males who suicided used the most lethal and quickest methods whereas females selected methods varying in lethality, duration, and agony. African Americans were overrepresented in the use of the most lethal and quickest methods.