cssi/SciSciGPT-SciSciNet huggingface dataset:
An innate immune response and altered nuclear receptor activation defines the spinal cord transcriptome during alpha-tocopherol deficiency in Ttpa-null mice

Mice with deficiency in tocopherol (alpha) transfer protein gene develop peripheral tocopherol deficiency and sensory neurodegeneration. Ttpa-/- mice maintained on diets with deficient α-tocopherol (α-TOH) had proprioceptive deficits by six months of age, axonal degeneration and neuronal chromatolysis within the dorsal column of the spinal cord and its projections into the medulla. Transmission electron microscopy revealed degeneration of dorsal column axons. We addressed the potential pathomechanism of α-TOH deficient neurodegeneration by global transcriptome sequencing within the spinal cord and cerebellum. RNA-sequencing of the spinal cord in Ttpa-/- mice revealed upregulation of genes associated with the innate immune response, indicating a molecular signature of microglial activation as a result of tocopherol deficiency. For the first time, low level Ttpa expression was identified in the murine spinal cord. Further, the transcription factor liver X receptor (LXR) was strongly activated by α-TOH deficiency, triggering dysregulation of cholesterol biosynthesis. The aberrant activation of transcription factor LXR suppressed the normal induction of the transcription factor retinoic-related orphan receptor-α (RORA), which is required for neural homeostasis. Thus we find that α-TOH deficiency induces LXR, which may lead to a molecular signature of microglial activation and contribute to sensory neurodegeneration.
An Initial Evaluation of Trial-Based Functional Analyses of Inappropriate Mealtime Behavior

Treatment of inappropriate mealtime behavior (IMB) should involve a functional analysis to determine variables maintaining the target behaviors. The purpose of the present study was to evaluate the trial-based functional analysis of IMB and assess correspondence of the results with a traditional functional analysis. The participants were two boys, ages 3 and 5 years old, diagnosed with developmental disabilities. A trial-based functional analysis and traditional analogue functional analysis of IMB were conducted with each participant, with the order of functional analyses counterbalanced across participants. The trial-based functional analysis resulted in differentially higher levels of IMB in one or more test conditions, indicating a social function of IMB for both participants. In addition, the results of the trial-based and traditional functional analysis corresponded for both participants. The subsequent function-based intervention, developed based on the results of the trial-based functional analysis, was associated with a decrease in IMB and an increase in appropriate feeding behaviors for both participants. The results of this study provide initial support for the use of trial-based functional analysis to assess the function of IMB.
Risk/Benefit Trade-off Analysis in Water Resources Planning

This little ditty contains the basic characteristics of value associated with any resource. For the most part, resources are of little value, perhaps even negative value, until they are put to beneficial use. By definition they are means to accomplish ends and are seldom, if ever, ends in themselves. To be put to beneficial use, a resource must be available when and where needed, in the appropriate amounts and in an appropriate form or “quality.”
Responses of seasonally anovulatory mares to daily administration of thyrotropin-releasing hormone and(or) gonadotropin-releasing hormone analog.

Seventeen seasonally anovulatory light horse mares were treated daily, starting January 5 (d 1), for 28 d with GnRH analog (GnRH-A; 50 ng/kg BW) and(or) thyrotropin-releasing hormone (TRH; 5 microg/kg BW) in a 2 x 2 factorial arrangement of treatments to test the hypothesis that combined treatment may stimulate follicular growth and development. Ovaries were examined via ultrasonography and jugular blood samples were collected every 3 d. Frequent blood samples were collected after treatment injections on d 1, 2, 4, 7, 11, 16, and 22; on d 29, all mares received an i.v. mixture of GnRH, TRH, sulpiride, and EP51389 (a growth hormone secretagogue) to assess pituitary responsiveness. No consistent effects (P > 0.1) of treatment were observed for plasma LH, FSH, prolactin, or thyroxine concentrations in samples collected every 3 d. The only effect on ovarian follicle numbers was a reduction in number of follicles 11 to 19 mm in diameter due to TRH treatment (P = 0.029). No mare ovulated during treatment. On the days of frequent sampling, mean LH (P = 0.0001) and FSH (P = 0.001) concentrations were higher in mares receiving GnRH-A and tended to increase from d 1 through 7. In contrast, mean prolactin (P = 0.001) and thyroid-stimulating hormone (P = 0.0001) concentrations were high in mares receiving TRH on d 1 but rapidly decreased thereafter. When mares were administered the secretagogue mixture on d 29, the LH response was greater (P = 0.0002) in mares that had previously received GnRH-A but the FSH response was not affected (P > 0.1); the prolactin response was greater (P = 0.014) and the TSH response was smaller (P = 0.0005) in mares that had previously received TRH. Surprisingly, an immediate growth hormone response to EP51389 was absent in all mares. In conclusion, daily GnRH-A treatment stimulated plasma LH and FSH concentrations immediately after injection; although no long-term elevation in preinjection concentrations was achieved, the responses gradually increased over time, indicating a stimulation of gonadotropin production and storage. Daily treatment with TRH stimulated plasma TSH and prolactin concentrations, but the response diminished rapidly and was minimal within a few days, indicating a depletion of pituitary stores and little or no stimulation of production. There was no beneficial effect of adding TRH treatment to the daily GnRH-A regimen.
Role-Playing Activity to Demonstrate Diffusion Across a Cell Membrane.

Transport of molecules across the cell plasma membrane can be a difficult concept for introductory biology students to understand and visualize. Role-playing activities provide a simple, cost-effective method for enhancing student understanding of various challenging biological concepts. This cell membrane role-playing activity was designed to teach introductory biology students how small nonpolar and polar molecules cross the cell membrane as well as the importance of diffusion, osmosis, and tonicity.
Relationships among Child Eating Behaviors and Household Food Insecurity in Youth with Obesity.

Background: Food insecurity may trigger eating behaviors that contribute to pediatric obesity. The aim of this study is to identify eating behaviors among a pediatric population with obesity and household food insecurity. Methods: A cross-sectional study analyzed Child Eating Behavior Questionnaire (CEBQ) and household food insecurity screener responses, and BMI measurements from pediatric participants with obesity (BMI ≥95th percentile) from a weight management clinic between 2013 and 2017. Multivariate linear regression was performed to evaluate associations between CEBQ eating domains [Food Responsiveness, Emotional Overeating, Enjoyment of Food, Desire to Drink (DD), Satiety Responsiveness, Slowness in Eating, Emotional Undereating (EUE), and Food Fussiness] and household food insecurity, adjusting for age, sex, race/ethnicity, SNAP participation, and BMI percentile. A sub-group analysis was performed on participants from food insecure (FI) households to evaluate the associations between SNAP participation and eating domains. Results: Eight hundred twenty-two participants were included in the final analysis. Participants from FI households had significantly higher BMI percentiles even after adjustment for age, sex, race/ethnicity, and SNAP status (p = 0.000). Household food insecurity was associated with increased DD beverages (p = 0.000). Among participants from FI households, SNAP participation was significantly positively associated with the EUE (p = 0.009). Conclusions: Youth from FI households have higher BMIs even among a population with obesity. DD is positively associated with household food insecurity and may contribute to obesity in this population. Results suggest that providers treating pediatric patients with obesity should consider regularly screening for household food insecurity and associated eating behaviors as part of their medical management of obesity.
Crude Protein, Amino Acid, and Iron Content of Tenebrio molitor (Coleoptera, Tenebrionidae) Reared on an Agricultural Byproduct from Maize Production: An Exploratory Study

Edible insects offer environmental and nutritional benefits, as they are characteristically nutrient-dense, are efficient biotransformers of organic material, and emit fewer greenhouse gasses than traditional livestock. Cultivating Tenebrio molitor (yellow mealworm) as ‘minilivestock’ is one possible means of increasing access to insect protein for food insecure populations. Tenebrio molitor growth and nutrient content varies with diet and rearing conditions, but little is known about the precise impact of poor quality feedstocks, such as maize crop residue (stover). Stover is widely available across sub-Saharan Africa where maize is a common dietary staple. Early instar larvae were reared under controlled conditions on three feed substrates: a standard control; a mixed soy, maize grain, and stover diet; and a 100% stover diet. Larvae reared for 32 d were analyzed for total amino acid profile, crude protein, and iron content. Larvae fed the three diets contained all essential amino acids for human nutrition and compared favorably to other traditional protein sources.The mixed diet contained 40% stover by weight and yielded amino acid values similar to the control diet, suggesting that some grain feedstock could be replaced with stover without hampering nutrient content. A second experiment demonstrated that T. molitor were able to complete metamorphosis and survive on a 100% stover diet for multiple generations. These results suggest that stover could be a suitable dietary component for T. molitor, which could facilitate the development of low-cost insect farming systems in low-resource settings that stand to benefit from increased access nutrient-dense edible insects.
Nonalcoholic Fatty Liver Disease and Alcoholic Liver Disease are Major Drivers of Liver Mortality in the United States.

In the United States, chronic viral hepatitis B and C (CHB and CHC), nonalcoholic fatty liver disease (NAFLD), and alcohol-related liver disease (ALD) are the main causes of liver deaths attributable to hepatocellular carcinoma (HCC) and cirrhosis. Our aim was to assess the changes in the rates of mortality and years of potential life lost (YLL) for HCC and cirrhosis due to different liver diseases. We used multiple-cause mortality data (2007-2017) from the National Center for Health Statistics. Annual percentage change (APC) in age-standardized death rate per 100,000 (ASDR) and age-standardized years of life lost per 100,000 (ASYLLR) were calculated. In the United States in 2017, there were 2,797,265 deaths with 73,424 liver deaths, contributing to 1,467,742 of YLL. Of the liver deaths, HCC was noted in 12,169 (16.6%) and cirrhosis in 60,111 (82.0%). CHC was responsible for 50.4% of HCC deaths; NAFLD, 35.4%; HBV, 6.0%; ALD, 5.4%; and others, 2.8%. NAFLD was responsible for 48.9% of cirrhosis deaths; ALD, 34.7%; CHC, 12.3%; CHB, 0.9%; and others, 3.2%. Between 2007 and 2017, the increase in ASDR for HCC due to ALD and NAFLD accelerated after 2014 (APC, 11.38% and 6.55%, respectively) whereas CHC stabilized (APC, 0.63%; P = 0.272) after 2011. The increase in ASYLLR of HCC escalated after 2014 for ALD and NAFLD (APC, 12.12% and 6.15%, respectively) and leveled out for CHC after 2012 (APC, -1.05%; P = 0.056). Furthermore, the highest annual increase in ASDR and ASYLLR for cirrhosis was due to ALD (APC, 3.24% and 3.34%, respectively) followed by NAFLD (APC, 1.23% and 0.49%, respectively). Conclusion: Over the past decade, ASDR and ASYLLR due to ALD and NAFLD have been increasing in the United States. The rising burden of HCC and cirrhosis are primarily driven by NAFLD and ALD.
Phase control of coherent acoustic phonons in gold bipyramids for optical memory and manipulating plasmon–exciton coupling

Recent efforts have targeted manipulation of nanomaterial vibrational modes in applications such as chemical/mass sensing, optical switching, and phonon-driven photochemistry. While impulsive photoexcitation can generate coherent phonons, multiple excitation pulses offer the prospect of control and manipulation of coherent phonon modes for functions of optical memory and logic. Here, we use such an approach to inject an arbitrary coherent phonon phase into a colloidal ensemble of highly monodisperse gold bipyramids. We then demonstrate that this technique can be applied to a system that exhibits plasmon–exciton coupling to further manipulate the hybridization of the system. This ability to manipulate acoustic phonons and hybridization can enable optical logic applications of acoustic phonons in addition to optical memory.
“It Takes Time for Language to Change”: Challenging Classroom Heteronormativity through Teaching Proficiency through Reading and Storytelling (TPRS)

The foreign language classroom affords conversations related to heteronormativity, language, and power, but instructional approaches often center upon discrete aspects of grammar and vocabulary. Te...
Glucocorticoid Receptor-DNA Dissociation Kinetics Measured in vitro Reveal Exchange on the Second Timescale

The glucocorticoid receptor (GR) is a member of the steroid receptor family of ligand-activated transcription factors. Recent live cell imaging studies have revealed that GR interactions with chromatin are highly dynamic, with receptor residence times on the order of seconds. These findings were surprising since early in vitro studies suggested that GR-DNA interactions were more static, with receptor-DNA exchange occurring on the order of minutes to hours. However, these latter analyses were carried out without the modern-day advantages of recombinant receptor expression, established purification protocols or rigorous characterization methods. Here we examine the DNA dissociation kinetics of full-length human GR, using highly purified and homogenous receptor preparations. We find that in vitro dissociation kinetics are not slow as previously reported, but are quite fast, with calculated receptor-DNA residence times of seconds to tens of seconds. These findings are observed at both isolated response elements and the multisite mouse mammary tumor virus (MMTV) promoter used in live cell imaging. However, we also find that dissociation kinetics are identical for all response elements and are biphasic in character. These results indicate that differences in GR affinity toward these sequences are not due to differences in off-rate but on-rate, and further suggest that GR exists in multiple and interconverting states when bound to DNA. Since we previously established that GR-DNA binding affinity is a primary determinant of transcriptional activity at these sequences, the current findings implicate DNA sequence in controlling the extent of receptor interconversion and hence extent of transcriptional activation.
Tuba1a is uniquely important for axon guidance through midline commissural structures

Abstract Developing neurons undergo dramatic morphological changes to appropriately migrate and extend axons to make synaptic connections. The microtubule cytoskeleton, made of α/β-tubulin dimers, drives neurite outgrowth, promotes neuronal growth cone responses, and facilitates intracellular transport of critical cargoes during neurodevelopment. TUBA1A constitutes the majority of α-tubulin in the developing brain and mutations to TUBA1A in humans cause severe brain malformations accompanied by varying neurological defects, collectively termed tubulinopathies. Studies of TUBA1A function in vivo have been limited by the presence of multiple genes encoding highly similar tubulin proteins, which prevents TUBA1A-specific antibody generation and makes genetic manipulation challenging. Here we present a novel tagging method for studying and manipulating TUBA1A in cells without impairing tubulin function. Using this tool, we show that a TUBA1A loss-of-function mutation TUBA1AN102D (TUBA1AND), reduced the amount of TUBA1A protein and prevented incorporation of TUBA1A into microtubule polymers. Reduced Tuba1a α-tubulin in heterozygous Tuba1aND/+ mice significantly impacted axon extension and impaired formation of forebrain commissures. Neurons with reduced Tuba1a caused by Tuba1aND had altered microtubule dynamics and slower neuron outgrowth compared to controls. Neurons deficient in Tuba1a failed to localize microtubule associated protein-1b (Map1b) to the developing growth cone, likely impacting reception of developmental guidance cues. Overall, we show that reduced Tuba1a is sufficient to support neuronal migration, but not axon guidance, and provide mechanistic insight as to how TUBA1A tunes microtubule function to support neurodevelopment.
Reliability and validity of the Assessment for Disaster Engagement with Partners Tool (ADEPT) for local health departments.

a ABSTRACT Objective. This study presents reliability and validity findings for the Assess­ ment for Disaster Engagement with Partners Tool (ADEPT), an instrument that can be used to monitor the frequency and nature of collaborative activities between local health departments (LHDs) and community­based organiza­ tions (CBOs) and faith­based organizations (FBOs) for disaster preparedness, response, and recovery. Methods. We used formative research to develop the instrument by ranking LHDs according to their disaster outreach and engagement activities. We validated the scale through a 2011 national survey of disaster preparedness coordinators (n5 273) working in LHDs. We reduced the original measure of 25 items to a final measure comprising 15 items with four dimensions: ( 1) commu­ nication outreach and coordination, (2) resource mobilization, (3) organizational capacity building, and (4) partnership development and maintenance. We used internal consistency reliability m correlation and factor analysis to validate the measure. Results. Using internal consistency reliability, we found reasonable inter­item reliability for the four hypothesized dimensions (Cronbach's alpha: 0.71-0.88). These four dimensions were confirmed through correlation and factor analysis (Varimax rotation). Conclusion. Higher scores on all four dimensions of ADEPT for organizational respondents suggest that more activities were conducted for inter­organiza­ tional preparedness in those organizations than in organizations whose respon­ dents had lower scores. This finding implies that organizations with higher ADEPT scores have more active relationships with CBOs/FBOs in the realm of preparedness, a key element for creating community resilience for emergencies and disaster preparedness.
Long-term effects of penicillin-induced developmental seizures on learning and memory capacity of rats

Objective To explore the long-term effects of penicillin-induced developmental seizures on learning and memory capacity of rats. Methods The rats were randomly divided into the recurrent-seizure group (RS) and the control group. Penicillin was used to induce seizure attack. At postnatal day 29(P29), the recurrent seizures induced once two day for consecutive eleven days. At P51～P56,P81～P84,P92～P95, Morris water-maze test were performed to evaluate spatial learning and memory capacity. Results ①Vertex sharp transient wave and sharp wave were detected in RS group by electrocorticogram. ②Escape latency:in the first Morris water-maze test, there was a decreasing trend of escape latency in two groups, and the escape latency of RS group in d5 was much longer than that of control group(P＜0.05); the difference of escape latency in d1 of the second and d2 of the third Morris water-maze tests were also significantly different compared with that of control.③Memory test:as for the value of distance in origin platform quadrant to total distance, the RS group seemed better than the control group in three maze tests(P＜0.01). Conclusions Recurrent developmental seizures induced by penicillin could cause long-term effects on learning and memory. Key words: Seizure; Morris water-maze; Learning and memory; Penicillin
Active Learning in an Inequitable Learning Environment Can Increase the Gender Performance Gap: The Negative Impact of Stereotype Threat

In the past few decades, educators and physics education researchers have been developing and evaluating instructional approaches designed to improve students’ conceptual understanding and problem-solving skills in physics for students with different prior preparation and backgrounds. These instructional approaches often require students to be active participants in their learning, and are often developed through research, which provides evidence for their effectiveness. Hence, we refer to them as “Evidence-Based Active Engagement” (EBAE) strategies.
Modeling and Restoring the Tear Film

This review summarizes the major factors currently implicated in the pathogenesis of tear film related ocular disorders, including dysfunctional adhesions, inflammatory factors, and insufficient lubrication by ocular surface mucins, and highlights the potential of in vitro models to propel more effective treatments into the clinic while improving fundamental understanding of ocular surface biology. The cornea and conjunctiva form a continuous ocular surface that shields the visual system from environmental threats. Because of its precise composition and organization, the ocular surface also refracts and focuses light rays, enabling clear vision. In many ocular surface diseases such as dry eye, tear film homeostasis is disrupted, causing inflammation, dryness, and epithelial damage. These friction-driven phenomena result in negative feedback loops in the eye that cause significant discomfort and compromise visual acuity over time. Despite the prevalence of lubrication-related eye disorders, much remains unknown about disease initiation and progression, a knowledge gap reflected in the limited treatment options currently available. As novel therapeutics are developed to treat these conditions, scalable, cost-effective model systems that sufficiently recapitulate the complexities of the native ocular surface are needed to streamline drug screening and clinical translation.
A survey of CH2DOH towards starless and pre-stellar cores in the Taurus molecular cloud

Recent observations indicate that organic molecules are prevalent towards starless and prestellar cores. Deuteration of these molecules has not been well-studied during the starless phase. Published observations of singly-deuterated methanol, CH$_2$DOH, have only been observed in a couple of well-studied, dense and evolved prestellar cores (e.g. L1544, L183). Since the formation of gas-phase methanol during this cold phase is believed to occur via desorption from the icy grain surfaces, observations of CH$_2$DOH may be useful as a probe of the deuterium fraction in the ice mantles of dust grains. We present a systematic survey of CH$_2$DOH towards 12 starless and prestellar cores in the B10 region of the Taurus Molecular Cloud. Nine of the twelve cores are detected with [CH$_2$DOH]/[CH$_3$OH] ranging from $< 0.04$ to $0.23^{+0.12}_{-0.06}$ with a median value of $0.11$. Sources not detected tend to have larger virial parameters and larger methanol linewidths than detected sources. The results of this survey indicate that deuterium fractionation of organic molecules, such as methanol, during the starless phase may be more easily detectable than previously thought.
Investigating the evolution of water-soluble organic carbon in evaporating cloud water

Cloud cycling plays a key role in the evolution of atmospheric particles and gases, producing secondary aerosol mass and transforming the optical properties and impacts of aerosols globally. In this study, bulk cloud water samples collected at Whiteface Mountain (Wilmington, NY) in the summer of 2017 were aerosolized, dried to 50% RH, and analyzed for the evaporative loss of water soluble organic carbon (WSOC) and for brown carbon (BrC) formation. Systematic WSOC evaporation occurred in all cloud water samples, while no evidence for drying induced BrC formation was observed. On average, 11% (±3%) of WSOC evaporated when the aerosolized cloud droplets were dried to 50% RH, though this represents a lower bound on the WSOC reversibly partitioned to clouds due to experimental constraints. To our knowledge, this represents the first direct measurements of organic evaporation from actual cloud water undergoing drying. Formate and acetate contributed 19%, on average, to the evaporated WSOC, while no oxalate evaporation occurred. GECKO-A model simulations were carried out to predict the production of WSOC compounds that reversibly partition to cloud water from photooxidation of an array of VOCs. The model results suggest that precursor VOC identity and oxidation regime (VOC:NOx) have a dramatic effect on the reversible partitioning of WSOC to cloud water and the abundance of aqSOA precursors, though the higher abundance of reversibly partitioned WSOC predicted by the model may be due to aqueous production of low-volatility material in the actual cloud samples. This study underscores the importance of the large fraction of unidentified compounds that contribute to WSOC in cloud water and their aqueous processing.
Integrated sample-handling and mounting system for fixed-target serial synchrotron crystallography.

Serial synchrotron crystallography (SSX) is enabling the efficient use of small crystals for structure–function studies of biomolecules and for drug discovery. An integrated SSX system has been developed comprising ultralow background-scatter sample holders suitable for room and cryogenic temperature crystallographic data collection, a sample-loading station and a humid `gloveless' glovebox. The sample holders incorporate thin-film supports with a variety of designs optimized for different crystal-loading challenges. These holders facilitate the dispersion of crystals and the removal of excess liquid, can be cooled at extremely high rates, generate little background scatter, allow data collection over >90° of oscillation without obstruction or the risk of generating saturating Bragg peaks, are compatible with existing infrastructure for high-throughput cryocrystallography and are reusable. The sample-loading station allows sample preparation and loading onto the support film, the application of time-varying suction for optimal removal of excess liquid, crystal repositioning and cryoprotection, and the application of sealing films for room-temperature data collection, all in a controlled-humidity environment. The humid glovebox allows microscope observation of the sample-loading station and crystallization trays while maintaining near-saturating humidities that further minimize the risks of sample dehydration and damage, and maximize working times. This integrated system addresses common problems in obtaining properly dispersed, properly hydrated and isomorphous microcrystals for fixed-orientation and oscillation data collection. Its ease of use, flexibility and optimized performance make it attractive not just for SSX but also for single-crystal and few-crystal data collection. Fundamental concepts that are important in achieving desired crystal distributions on a sample holder via time-varying suction-induced liquid flows are also discussed.
Primary Care Provider Density and Elective Total Joint Replacement Outcomes.

Abstract Background Primary care physicians (PCPs) are often gatekeepers to specialist care. This study assessed the relationship between PCP density and total knee (TKA) and total hip arthroplasty (THA) outcomes. Methods We obtained patient-level data from an institutional registry on patients undergoing elective primary TKA and THA for osteoarthritis, including Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores at baseline and 2 years. Using geocoding, we identified the number of PCPs in the patient’s census tract (communities). We used Augmented Inverse Probability Weighting and Cross-validated Targeted Minimum Loss-Based Estimation to compare provider density and outcomes adjusting for potential confounders. Results Our sample included 3606 TKA and 4295 THA cases. The median number of PCPs in each community was similar for both procedures: TKA 2 (interquartile range 1, 6) and for THA 2 (interquartile range 1, 7). Baseline and 2-year follow-up WOMAC pain, function, and stiffness scores were not statistically significantly different comparing communities with more than median number of PCPs to those with less than median number of PCPs. In sensitivity analyses, adding 1 PCP to a community with zero PCPs would not have statistically significantly improved baseline or 2-year follow-up WOMAC pain, function, and stiffness scores. Conclusions In this sample of patients who underwent elective TKA or THA for osteoarthritis, we found no statistically significant association between PCP density and pain, function, or stiffness outcomes at baseline or 2 years. Further studies should examine what other provider factors affect access and outcomes in THA and TKA.
Brief communication: monitoring a soft-rock coastal cliff using webcams and strain sensors

Abstract. In this brief communication, we describe a case study about monitoring a soft-rock coastal cliff using webcams and strain sensors, located in the Apulia region (southeastern Italy). In this urban and touristic area, coastal recession is extremely rapid and rockfalls are very frequent. Using low-cost and open source hardware and software, we are monitoring the area, trying to correlate both meteorological information with measures obtained from crack-meters and webcams, aiming to recognize potential precursor signals that may trigger instability phenomena.
Exercise 8: Rabbit and Mouse Immunizations: Preparation of Polyclonal Antibodies and Screening Assays

Polyclonal antibodies in general are specific to multiple epitopes on a single antigen and may also be specific to several epitopes on different antigens. Monospecific polyclonal antibodies can also be prepared. These antibodies are usually prepared against a single purified protein and the specificity is usually against different epitopes on the protein. These antibodies are different from monoclonal antibodies which are the products of single B cell clones and are much more specific usually for a single epitope on an antigen. The production of monoclonal antibodies has become a routine part of many immunology laboratories. However, it is a complex, labor-intensive process requiring tissue culture methods and often expensive reagents and equipment (we will discuss monoclonal antibodies in the tissue culture section).
Nuclear Medicine Cardiac Imaging

Nuclear medicine cardiac imaging includes modalities that are capable of evaluating the ventricular wall motion, global and regional left and right ventricular ejection fraction, myocardial perfusion, and myocardial metabolic activity (viability).
The Normal Fluid Fraction in the Adsorbed Helium Film

The resonant frequency of a thickness-shear mode oscillating quartz crystal is lowered by virtue of the mass loading of any film laid down on its surfaces.1,2 For a uniformly deposited, thin solid film with thickness less than 1% or so of the crystal thickness this change Δf, is given by the formula $$ - \Delta f = 2(2{f^2}/c{\rho _q})\sigma $$ (1) Here σ represents that part of the mass per unit area which remains rigidly coupled to the substrate motion, f is the resonant frequency, c is the shear wave velocity in the crystal, and ρ q is the density of the quartz.
A novel polylocus method for linkage analysis using the lod-score or affected sib-pair method.

A novel approach to combining data from multiple linked loci is proposed that can provide substantial increases in power over normal two-point linkage analysis or sib-pair analysis, with a substantial saving in computing time over traditional multipoint methods
Metric Geometry in Normed Spaces

Banach’s book, p. 160, gives a theorem of Mazur and Ulam that an isometry of one normed space onto another which carries 0 to 0 is linear. This is true only for real-linear spaces, and is proved by characterizing the midpoint of a segment in a normed space in terms of the distance function. Using the same proof a slightly stronger result can be attained.
Reading between the lines: lessons from the SDMI challenge

The Secure Digital Music Initiative is a consortium of parties interested in preventing piracy of digital music, and to this end they are developing architectures for content protection on untrusted platforms. SDMI recently held a challenge to test the strength of four watermarking technologies, and two other security technologies. No documentation explained the implementations of the technologies, and neither watermark embedding nor detecting software was directly accessible to challenge participants. We nevertheless accepted the challenge, and explored the inner workings of the technologies. We report on our results here.
Recurrence rates of volcanism in basaltic volcanic fields: An example from the Springerville volcanic field, Arizona

A spatio-temporal near-neighbor model is used to identify and map variations in the recurrence rate of volcanism in the Springerville volcanic field, Arizona, a large field on the Colorado Plateau boundary. Detailed mapping of individual lava flows and their associated vents, together with radiometric and paleomagnetic dating, demonstrates that 366 volcanic events have formed the Springerville volcanic field. These volcanic events consist of mapped units that erupted between 2.1 and 0.3 Ma over an area of 3000 km 2 . Cumulatively, the rate of vent formation in the Springerville field waxed prior to 1.5 Ma, was near steady state from 1.5 to 0.75 Ma, and has waned since 0.75 Ma. The increase in the rate of vent formation at ca. 1.5 Ma coincided with a shift in the locus of Springerville magmatism from west to east and an increase in the alkalic nature of the magma, including eruption of mugearites and benmoreites. The volume of flows, inferred from lava-flow areas, was steady state from 1.75 to 0.75 Ma. A near-neighbor spatio-temporal recurrence-rate model using seven near-neighbor volcanoes and a 0.5 m.y. time window reveals that (1) areas of waxing and waning magmatism in the Springerville volcanic field are much more localized and (2) volcanic activity within these areas is much more intense than implied by field-wide temporal trends. These volcano clusters are 10–20 km in diameter; they were commonly active for less than 0.25 m.y. Mugearites and benmoreites are limited to these areas of high recurrence rate. This clustered and petrologically distinctive, rather than distributed or random, volcanic activity suggests that individual source regions for the magma also are localized and short-lived compared with the area and longevity of the entire field. Because volcanic activity is spatially and temporally clustered, forecasting subsequent activity is more successful if the spatio-temporal recurrence-rate model is used, rather than the average recurrence rates. This success indicates that spatio-temporal recurrence-rate models are useful tools for the quantification of long-term volcanic hazards in basaltic volcanic fields.
Clinical consequences and economic costs of untreated obstructive sleep apnea syndrome.

Abstract Objective To provide an overview of the healthcare and societal consequences and costs of untreated obstructive sleep apnea syndrome. Data sources PubMed database for English-language studies with no start date restrictions and with an end date of September 2014. Methods A comprehensive literature review was performed to identify all studies that discussed the physiologic, clinical and societal consequences of obstructive sleep apnea syndrome as well as the costs associated with these consequences. There were 106 studies that formed the basis of this analysis. Conclusions Undiagnosed and untreated obstructive sleep apnea syndrome can lead to abnormal physiology that can have serious implications including increased cardiovascular disease, stroke, metabolic disease, excessive daytime sleepiness, work-place errors, traffic accidents and death. These consequences result in significant economic burden. Both, the health and societal consequences and their costs can be decreased with identification and treatment of sleep apnea. Implications for practice Treatment of obstructive sleep apnea syndrome, despite its consequences, is limited by lack of diagnosis, poor patient acceptance, lack of access to effective therapies, and lack of a variety of effective therapies. Newer modes of therapy that are effective, cost efficient and more accepted by patients need to be developed.
Deciphering the association between gene function and spatial gene-gene interactions in 3D human genome conformation

A number of factors have been investigated in the context of gene function prediction and analysis, such as sequence identity, gene expressions, and gene co-evolution. However, three-dimensional (3D) conformation of the genome has not been tapped to analyse gene function, probably largely due to lack of genome conformation data until recently. We construct the genome-wide spatial gene-gene interaction networks for three different human B-cells or cell lines from their chromosomal contact data generated by the Hi-C chromosome conformation capturing technique. The G-SESAME and Fast-SemSim are used to calculate function similarity between interacted / non-interacted genes. The Gene Ontology statistics computed from the gene-gene interaction networks is used for gene function prediction. We compare the function similarity of gene pairs that do not spatially interact and that have interactions. We find that genes that have strong spatial interactions tend to have highly similar function in terms of biological process, molecular function and cellular component of the Gene Ontology. And even though the level of gene-gene interactions generally have no or weak correlation with either sequential genomic distance or sequence identity between genes, the interacted genes with high function similarity tend to have stronger interactions, somewhat shorter genomic distance and significantly higher sequence identity. And combining genomic distance or sequence identity with spatial gene-gene interaction information informs gene-gene function similarity much better than using either one of them alone, suggesting gene-gene interaction information is largely complementary with genomic distance and sequence identity in the context of gene function analysis. We develop and evaluate a new gene function prediction method based on gene-gene interacting networks, which can predict gene function well for a large number of human genes. In this work, we demonstrate that the spatial conformation of the human genome is relevant to gene function similarity and is useful for gene function prediction.
Computational Interpretation of Megagauss-Magnetic-Field-Induced Metallic Surface Plasma Initiation and Evolution

Numerical simulations of experiments in which plasma is formed on an aluminum surface by megagauss magnetic fields provide the first computational demonstration of a magnetic-field threshold that must be reached for aluminum plasma to begin to form. The computed times of plasma initiation agree reasonably well with the observations across the full range of rod diameters, leading to the conclusion that plasma formation is a thermal process. Computationally, plasma forms first in low-density material that is resistive enough to expand across the magnetic field and yet conductive enough that Ohmic heating exceeds expansion cooling.
JTT-501, a novel oral antidiabetic agent, improves insulin resistance in genetic and non-genetic insulin-resistant models

We investigated whether JTT-501 (4-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]-3,5-isoxazolidinedione) would improve insulin resistance in genetic (Zucker fatty rats) and non-genetic (high-fat fed rats) rodent models of obesity. JTT-501 (10–100 mg kg−1 day−1) was administered orally to Zucker fatty rats for 7–21 days. In the high-fat fed rat model, JTT-501 (100 mg kg−1 day−1) was administered orally for 7 days. In both models, JTT-501 improved metabolic abnormalities by enhancing insulin action during the glucose tolerance test and the euglycaemic-hyperinsulinaemic clamp study. In ex vivo assays, JTT-501 ameliorated the impaired insulin-sensitive glucose oxidation and lipid synthesis in peripheral tissues. Furthermore, JTT-501 enhanced insulin receptor autophosphorylation in hindlimb muscle. JTT-501 reduced serum leptin concentrations in both models, but did not affect body weight or epididymal fat weight. Our observations indicate that JTT-501 improves the metabolic abnormalities in both genetic and non-genetic insulin-resistant models by enhancing insulin action in peripheral tissues. These effects of JTT-501 are due, at least in part, to enhanced insulin receptor autophosphorylation. In addition, JTT-501 is able to reduce serum leptin concentrations in hyperleptinaemia of the insulin-resistant model. We expect JTT-501 to show promise for treating non-insulin dependent diabetes mellitus patients with insulin resistance.
Effect of thiazides on the thyroid gland of rats

Abstract Male rats fed 300 ppm or 600 ppm of hydrochlorothiazide in an iodide-deficient diet for 8 weeks had thyroid weight to body weight ratios of 23% and 47%, respectively, above that of controls given the iodide-deficient diet alone. In spite of increases in thyroid weight ratio, gross manifestations of hypothyroidism were absent in that growth rate, resting oxygen consumption, food intake, and serum cholesterol concentration were similar to those of controls. In a second experiment, male rats were given a commercial laboratory chow containing either 1900 ppm or 3800 ppm of chlorothiazide and 0.20 M NaCl solution to drink for 39 weeks. The ratio of thyroid weight to body weight increased 4% and 36%, respectively, above that of the controls. The growth rate of rats given the higher dosage was reduced. Urinary excretion of I131 was measured in water-loaded, male rats to determine whether the increase in thyroid weight ratio accompanying drug administration was associated with excessive iodide excretion. Drug-treated rats received either 10 mg/kg or 25 mg/kg of hydrochlorothiazide intraperitoneally, while controls received the vehicle used to dissolve the drug. All rats received intraperitoneal injections of carrier-free NaI131 (7 μc) and a water load equal to 3% of body weight. Excretion of urine, I131, sodium, chloride, and potassium were measured for 5 hours thereafter. Both dosages of hydrochlorothiazide significantly increased the excretion of urine, I131, sodium, potassium, and chloride above control levels. Treatment with hydrochlorothiazide at the dosages used appears to induce a state of compensated hypothyroidism which may arise initially as a result of increased urinary iodide loss. Administration of these compounds for longer periods of time or at higher dosages (3800 ppm of chlorothiazide in the diet) may produce frank hypothyroidism in rats.
Sheath over a finely structured divertor plate

Abstract The surface of a divertor plate typically has fine structure. Depending on the material and the duration of exposure to the plasma, the characteristic size of the surface imperfections may vary over a broad range. In this paper, we consider the case where these structures have a scale height h that is greater than the electron gyroradius ρ e . The magnetic field intersects the divertor plate at a shallow angle α ≪ 1. The present paper demonstrates that the combination of these two factors, fine surface structures and strongly tilted magnetic field, gives rise to many interesting new phenomena in the sheath. It is shown that the fraction of the surface `wetted' by the plasma electrons is much less than that `wetted' by the plasma ions. It is noted that, for α ≪ 1, secondary electron emission for a rough surface may be considerably larger than for a flat surface. A description of a dedicated experiment for the study of plasma interaction with structured surfaces in a tilted magnetic field is presented.
An alternative interpretation of the amyloid Aβ hypothesis with regard to the pathogenesis of Alzheimer's disease

Alzheimer's disease is a complex neurodegenerative process that is believed to be due to the accumulation of short, hydrophobic peptides derived from amyloid precursor proteins by proteolytic cleavage. It is widely believed that these Aβ peptides are secreted into the extracellular spaces of the CNS, where they assemble into toxic oligomers that kill neurons and eventually form deposits of senile plaques. This essay explores the possibility that a fraction of these Aβ peptides never leave the membrane lipid bilayer after they are generated, but instead exert their toxic effects by competing with and compromising the functions of intramembranous segments of membrane-bound proteins that serve many critical functions. Based on the presence of shared amino acid sequences containing GxxG motifs, I speculate that accumulations of intramembranous Aβ peptides might affect the functions of amyloid precursor protein itself and the assembly of the PS1, Aph1, Pen 2, Nicastrin complex.
Ultrastructural immunocytochemical localization of the N-methyl-d-aspartate receptor and tyrosine hydroxylase in the shell of the rat nucleus accumbens

The N-methyl-d-aspartate (NMDA)-type glutamate receptors in the shell region of the nucleus accumbens (ACB) have been implicated in the modulation of dopamine release and in amphetamine-induced neurotoxicity. We used electron microscopic immunocytochemistry to determine the anatomical sites for NMDA-mediated effects of glutamate and for their potential interactions with dopaminergic afferents identified by the presence of tyrosine hydroxylase (TH) in this region of the rat brain. Immunogold and immunoperoxidase methods were used to localize antisera against the R1 subunit of the NMDA receptor (NMDAR1) alone or combined with TH. In single labeling experiments, approximately half of the NMDAR1-like immunoreactivity (NMDAR1-LI) was localized to extrasynaptic plasma membranes of neuronal processes, many (92 out of 215) of which were dendrites, and only 33 out of 215 were unmyelinated axons or terminals. Surprisingly, the neuronal labeling of NMDAR1 was almost equaled by that seen in astrocytic processes (88 out of 215). Dual labeling for TH and NMDAR1 was rarely observed and was only seen in axons. However, in favorable planes of section, NMDAR1 was noted along intervaricose segments of axons in which TH was more readily seen in the varicosity. This differential intra-axonal distribution suggests an underestimation of dual labeling in single coronal sections through unmyelinated axons and terminals. The TH-immunoreactive terminals were more often seen apposed to NMDA-immunoreactive astrocytic processes and dendrites. These results provide the first ultrastructural evidence for presynaptic modulation of dopamine release by NMDA receptors in the shell of the nucleus accumbens. They also indicate that NMDA receptors modulate postsynaptic neurons receiving input from the dopaminergic afferents and suggest a previously unsuspected functional association involving glial NMDA receptors and dopaminergic afferents in this brain region.
A note on multiple roots of the Tobit log likelihood

Abstract We show that negative definiteness of the Hessian matrix of the log likelihood is preserved at any stationary point under any one-to-one and onto parameter transformation which is differentiable. This rules out the possibility, suggested by Greene (1990), of multiple roots of the likelihood equations for the Tobit as well as the truncated regression models.