cssi/SciSciGPT-SciSciNet huggingface dataset:
Integrating germline and somatic variation information using genomic data for the discovery of biomarkers in prostate cancer

Prostate cancer (PCa) is the most common diagnosed malignancy and the second leading cause of cancer-related deaths among men in the United States. High-throughput genotyping has enabled discovery of germline genetic susceptibility variants (herein referred to as germline mutations) associated with an increased risk of developing PCa. However, germline mutation information has not been leveraged and integrated with information on acquired somatic mutations to link genetic susceptibility to tumorigenesis. The objective of this exploratory study was to address this knowledge gap. Germline mutations and associated gene information were derived from genome-wide association studies (GWAS) reports. Somatic mutation and gene expression data were derived from 495 tumors and 52 normal control samples obtained from The Cancer Genome Atlas (TCGA). We integrated germline and somatic mutation information using gene expression data. We performed enrichment analysis to discover molecular networks and biological pathways enriched for germline and somatic mutations. We discovered a signature of 124 genes containing both germline and somatic mutations. Enrichment analysis revealed molecular networks and biological pathways enriched for germline and somatic mutations, including, the PDGF, P53, MYC, IGF-1, PTEN and Androgen receptor signaling pathways. Integrative genomic analysis links genetic susceptibility to tumorigenesis in PCa and establishes putative functional bridges between the germline and somatic variation, and the biological pathways they control.
Mesoscopic Traffic Flow Model for Agent-Based Simulation

Abstract Traffic simulation is a key element of agent based models as the various agents decisions impact and are impacted by the realized travel times and delays in the traffic network. Here we present the mesoscopic traffic flow model implemented in POLARIS transportation systems simulator. The model is mesoscopic in an attempt to obtain enough for applications that requires microscopic data while still inheriting the computational efficiency of macroscopic traffic flow models. The model is macroscopic at the link-level with dynamics based on the Newells Model and microscopic at the node level. We present link-level and network-level results for one mid-sized traffic network. The results show that the model can combine accuracy, level of details and computational efficiency.
Loss of endosomal recycling factor RAB11 coupled with complex regulation of MAPK/ERK/AKT signaling in postmortem spinal cord specimens of sporadic amyotrophic lateral sclerosis patients

Synaptic abnormalities, perturbed endosomal recycling mediated by loss of the small GTPase RAB11, and neuroinflammatory signaling have been associated with multiple neurodegenerative diseases including the motor neuron disease, amyotrophic lateral sclerosis (ALS). This is consistent with the neuroprotective effect of RAB11 overexpression as well as of anti-inflammatory compounds. However, most studies were in animal models, and this phenomenon has not been demonstrated in human patients. Moreover, crosstalk between endosomal trafficking and inflammatory signaling pathways in ALS remains enigmatic. Here, we investigated RAB11 expression and MAPK/ERK/AKT signaling in 10 post-mortem spinal cord specimens from patients with sporadic ALS and age-matched controls. All 10 ALS patients showed TDP-43 pathology, whereas two specimens showed an overlapping FUS pathology and one had an acquired Q331K mutation in TDP-43. There was consistent RAB11 downregulation in all ALS cases, while p-AKT and phospho-ribosomal S6 kinase (p-p90RSK) were upregulated. Furthermore, competition between AKT and ERK pathways was observed in ALS, suggesting subtle differences among the TDP-43-ALS subtypes, which may influence patient therapeutic responses. Our findings demonstrate a complex regulation/perturbation pattern of signaling cascades involving MAPK/AKT/RAB11 in spinal cord tissue from ALS patients. These results underscore the relationships between ALS pathology, altered neuronal trafficking, and inflammation.
Ceramide: a novel inducer for neural tube defects.

Background Circulating plasma ceramides, a class of bioactive sphingolipids, are elevated in metabolic disorders, including obesity. Infants of women with these disorders are at 2- to 3-fold greater risk for developing a neural tube defect (NTD). This study aimed to test the effects of embryonic exposure to C2-ceramides (C2) during neural tube closure. Preliminary data shows an increase in NTDs in chick embryos after C2 exposure, and addresses potential mechanisms. Results Cell and embryo models were used to examine redox shifts after ceramide exposure. While undifferentiated P19 cells were resistant to ceramide exposure, neuronally differentiated P19 cells exhibited an oxidizing shift. Consistent with these observations, GSH E h curves revealed a shift to a more oxidized state in C2 treated embryos without increasing apoptosis or changing Pax3 expression, however cell proliferation was lower. Neural tube defects were observed in 45% of chick embryos exposed to C2, compared to 12% in control embryos. Conclusions C2 exposure during critical developmental stages increased the frequency of NTDs in the avian model. Increased ROS generation in cell culture, along with the more oxidative GSH E h profiles of C2 exposed cells and embryos, support a model wherein ceramide affects neural tube closure via altered tissue redox environments.
Scale Analysis of Moist Thermodynamics in a Simple Model and the Relationship between Moisture Modes and Gravity Waves

AbstractObservations and theory of convectively coupled equatorial waves suggest that they can be categorized into two distinct groups. Moisture modes are waves whose thermodynamics are governed by...
Assessment of rejection risk following subtherapeutic calcineurin inhibitor levels after pediatric heart transplantation.

CNIs are the mainstay of immunosuppressive therapy after pediatric HTx. While regular laboratory surveillance is performed to ensure blood levels are within targeted range, the risk of acute rejection associated with subtherapeutic CNI levels has never been quantified. This is a retrospective single-center review of 8413 CNI trough levels in 138 pediatric HTx recipients who survived >1 year after HTx. Subtherapeutic CNI levels were defined as 12 months post-transplant) rejection following recipients' subtherapeutic CNI levels was assessed using time-varying multivariable Cox proportional hazards analysis. We found that 79 of 138 recipients (57%) had at least one subtherapeutic CNI level on routine surveillance laboratories during a mean follow-up of 5.5 ± 3.6 years. Following an episode of subtherapeutic levels, 17 recipients (22%) had biopsy-proven rejection within the next 3 months; the majority (9/17) within the first 2 weeks. After presenting with subtherapeutic CNI levels, recipients incurred a 6.1 times increased risk of acute rejection in the following 3 months (HR = 6.11 [2.41, 15.51], P = 12 months after pediatric HTx. Recipients who present with subtherapeutic CNI levels on surveillance monitoring are 6.1 times more likely to develop rejection in the following 3 months.
Canopy Near-infrared Observation Project

The Canopy Near-infrared Observing Project (CaNOP) will utilize a multispectral pushbroom imager in a 3U CubeSat to carry out spectrally resolved imaging of global forest regions with spectral resolution sufficient to reproduce the LandSat 8 mission and calculate vegetation indices. The project provides an educational experience for undergraduate students to design, build, test, and operate a 3U CubeSat. Using concepts from fields such as physics, engineering, and computer science, students were to link the electrical, mechanical, and software components of the satellite together to create a flawless flow of information and power across the entirety of the satellite and its corresponding ground stations to which the images of the global forest regions will be transferred and analyzed. Two vegetation indices; the Normalized Difference Vegetation Index (NDVI) and the Enhanced Vegetation Index (EVI) will be used in combination with the Net Primary Production (NPP) of any forest to produce the Gross Primary Production (GPP), which will then provide the information required to answer the argument that the CaNOP team’s hypothesis proposes: An old-growth forest will absorb more carbon than a newly grown secondary forest.
Stationarity Diagnostics using Functional Expansion Tallies

Abstract A methodology for determining fission source stationarity is presented that characterizes the behavior of higher order spatial moments of the fission source distribution using Functional Expansional Tallies (FET’s). The computation of these FET’s does not require a meshing scheme like traditional methods do (e.g Shannon entropy), and is computed natively within the Monte Carlo tallying routine. To determine the efficacy of this new diagnostic, stationarity behavior is analyzed for a variety of one-dimensional and two-dimensional test cases that mimic typical reactor problems. For most problems, the results from an FET-based approach are in close agreement with those from an entropy-based approach. However, for more realistic reactor configurations with higher dimensionality and strong asymmetries, a stationary fission source distribution is better predicted using an FET-based approach.
Greater Prevalence of Mental Health Conditions in Septic Revision Total Knee Arthroplasty: A Call to Action.

The purpose of this study was to compare the prevalence of mental health conditions among patients undergoing (1) primary total knee arthroplasty (pTKA), (2) septic revision total knee arthroplasty (rTKA), and (3) aseptic revision total knee arthroplasty (TKA). The State Inpatient Databases were queried for all TKAs from 2005 to 2014 yielding 563,144 patients. Patients were separated into the following cohorts: primary, septic revision, and aseptic revision. Diagnoses of any mental health condition and the following specific conditions were compared between the three cohorts: schizophrenia/delusion, bipolar disorder, depression/mood disorder, personality disorder, anxiety/somatic/dissociative disorder, eating disorders, attention deficit hyperactivity disorder /conduct/impulse control, alcohol abuse, and drug abuse. Throughout the study period, an increase in the prevalence of mental health conditions was observed in septic and aseptic revision patients. Overall, there was a significantly higher prevalence of mental health conditions in the septic revision cohort (22.7%) compared with the primary (17.8%, p < 0.001) and aseptic revision (20.0%, p < 0.001) cohorts. Specifically, septic revision TKA patients had a higher prevalence of depression (p < 0.001), alcohol abuse (p < 0.001), drug abuse (p < 0.001), schizophrenia (p = 0.0007), and bipolar disorder (p < 0.001), compared with primary TKA patients. Additionally, there was a significantly higher prevalence of depression (p < 0.001), alcohol abuse (p < 0.001), and drug abuse (p < 0.001) among septic revision patients compared with aseptic revision patients. Mental health conditions were significantly higher among septic revision patients. Alcohol and drug abuse were approximately twice as prevalent in septic revision patients compared with primary and aseptic revision patients. These findings should serve as a call to action for mental health support for patients suffering from PJI.
County-Level Poverty and Barriers to Breast and Cervical Cancer Screening in a Health Education and Patient Navigation Program for Rural and Border Texas Residents

The study examined the impact of (1) county-level poverty rates and (2) patient navigation on breast and cervical cancer screening outcomes for women in rural and border counties in Texas reporting barriers to screening. Univariate analyses described the distribution and screening prevalence rates in the sample, while a series of random intercept logistic regression models analyzed mammogram (N = 2326 women aged 40+) and Papanicolaou (Pap; N = 2959 women aged 21–64) screening separately. Mammogram and Pap screening prevalence rates were highest among women who were aged 40–64, Spanish-speaking Latinas, lower educated, attending cancer education events because of the cost of the screenings, patient navigation recipients, living in the south region of Texas, and in counties with high poverty. Although models indicated significant variability in screening rates by county, county-level poverty was only significantly associated with odds of getting Pap screening in adjusted models. Not receiving patient navigation vs. receiving it was associated with lower odds for both mammogram (OR: 0.51, CI: 0.38–0.70) and Pap (OR: 0.69, CI: 0.50–0.94) screenings. County-level variation in screening rates exists for both mammogram and Pap tests and should be considered in the development and implementation of screening interventions in rural and border areas. However, other factors beyond poverty levels may explain the variation.
Effect of compositional variations on electrical properties in phase switching (Pb, La)(Zr, Ti, Sn)O3 thin and thick films

The composition-dependent electrical properties in (Pb,La)(Zr,Ti,Sn)O3 antiferroelectric-ferroelectric phase switching thin and thick films have been systematically studied and compared with bulk ceramics. The films were deposited on Pt-buffered silicon substrates by a sol-gel method. The results show that the dependence of low-field dielectric properties on compositions in the films is similar to that in bulk ceramics but the variation of high field properties (polarization or hysteresis loops) is quite different, which may be attributed to the special mechanical boundary condition of the films. While all the films with compositions in the antiferroelectric tetragonal region in the phase diagram demonstrate the existence of remanent polarization in the hysteresis loops, the films with zero remanent polarization can be obtained in the antiferroelectric orthorhombic region. This is because the films are under high tensile stress due to the thermal mismatch between the film and substrate, which tends to stabilize the ferroelectric phase and causes the retention of ferroelectric phase for the films in the antiferroelectric tetragonal region because of their relatively small free energy difference between the antiferroelectric phase and ferroelectric phase.
A perspective on the application of operando characterization to probe the structure, performance, and dynamics of membranes under realistic operating conditions

Abstract Operando membrane characterization is a relatively new experimental research methodology that is expected to have a significant impact on membrane science and engineering in the coming years because of its unique ability to probe the structure, performance, and dynamics of membranes under realistic operating conditions. It combines in-situ characterization of the atomic/molecular-scale structure of a membrane with simultaneous measurement of permeation rates on the same sample under realistic operating conditions. By performing both in-situ characterization and permeation measurements simultaneously on the same sample, operando membrane characterization allows one to directly correlate membrane structure to its performance, which conventional membrane testing and ex-situ characterization approaches cannot achieve. In this Perspective, the key components of the operando membrane characterization experimental setup are described, and three case studies are presented to demonstrate the utility and versatility of combining in-situ membrane characterization with permeation measurements. The future opportunities, challenges, and limitations of operando membrane characterization are also discussed.
Hold the Phone! Cell Phone-Related Injuries in Children, Teens, and Young Adults Are On the Rise.

We describe trends in cell phone-related injuries in patients 21 years of age and under presenting to United States Emergency Departments. We calculated age-adjusted rates of cell phone-related inj...
Gait in Elderly Glaucoma: Impact of Lighting Conditions, Changes in Lighting, and Fear of Falling.

Purpose The purpose of this study was to characterize the impact of lighting changes on gait in elderly patients with glaucoma and evaluate whether associations are mediated by fear of falling (FOF). Methods Gait initiation and parameters measured with the GAITRite Electronic Walkway were captured in normal indoor light, then in dim light, and again in normal light (normal post dim [NPD]). Participants' right and left eye visual fields (VFs) were merged into integrated VF (IVF) sensitivities. FOF was evaluated using a Rasch-analyzed questionnaire. Multivariable regression models evaluated whether IVF sensitivity was associated with lighting-dependent gait changes and if this relationship was mediated by FOF. Results In 213 participants (mean age = 71.4 years), gait initiation in dim light took longer with more VF damage (P = 0.02). Greater VF damage was associated with slower gait in dim (P < 0.001) and NPD (P = 0.003) lighting, as well as shorter strides (P = 0.02), broader stance (P = 0.003), and more variable stride velocity and length in all lighting (all P < 0.03). When moving from normal to dim lighting, those with more VF damage slowed gait and cadence, shortened stride length, and lengthened double support time (all P < 0.001). Velocity, cadence, and double support time did not return to baseline in NPD lighting (all P < 0.05). Fear of falling did not appear to mediate the relationship between IVF sensitivity and lighting-dependent gait changes. Conclusions Patients with more VF damage demonstrate gait degradation in extreme or changing lighting, which is not mediated by FOF. Translational Relevance Quantitative spatiotemporal gait evaluation reveals lighting-associated impairment, supporting patient-reported difficulty with nonideal lighting and equipping providers to advise patients about limitations.
Outcomes of Ventricular Assist Device Use in Children for Bridge to Heart Retransplantation

Purpose As the use of pediatric ventricular assist devices (VAD) has increased, more children are being supported with VADs for transplant graft failure as a bridge to heart re-transplant (HT). Little is known about VAD outcomes for graft failure where left ventricular (LV) function is preserved, and LV chamber dilation is uncommon. We sought to examine VAD outcomes as a bridge to HT for this important subset of HF patients. Methods Organ Procurement and Transplant Network (OPTN) data were used to identify all children ≤21 years who underwent VAD placement between 2004 and 2020 as a bridge to heart re-transplant. Cox proportional hazard modeling was used to identify risk factors for mortality. Results Of 723 children listed for heart re-transplant, 144 were supported with MCS (87 with a VAD and 57 with ECMO alone). Of 87 VAD recipients, 41 (68%) received an LVAD alone, 29 (33%) received BIVADs, 9 (10%) received an TAH, and 7 (8%) an isolated RVAD. The most common isolated LVAD used was the Berlin Heart (N=16, 39%), a percutaneous LVAD (Impella or Tandem, N=11, 26%), and Heartware HVAD (N=6, 15%). The most common BIVAD configuration was bilateral Berlin Hearts (N=15, 52%) and bilateral CentriMag (10%). Since 2011 (when complete VAD survival data become available), overall survival to HT was 72%, with 61% reaching transplant while 11% remained on the waitlist. Survival was significantly worse compared to pediatric VAD patients supported for DCM and comparable to children with CHD (P=0.31) (Figure). For children supported with the Berlin Heart, outcomes for LVAD and BIVAD patients were similar (P=0.69) in contrast to other diagnoses where BIVAD outcomes are typically inferior to LVAD outcomes. Conclusion VAD outcomes for bridge to re-transplant are significantly worse than DCM patients and comparable to outcomes for CHD. While BIVAD outcomes are typically worse than LVAD outcomes for most cardiac diagnoses, outcomes appear similar for children supported for graft failure.
E2ETag: An End-to-End Trainable Method for Generating and Detecting Fiducial Markers

Existing fiducial markers solutions are designed for efficient detection and decoding, however, their ability to stand out in natural environments is difficult to infer from relatively limited analysis. Furthermore, worsening performance in challenging image capture scenarios - such as poor exposure, motion blur, and off-axis viewing - sheds light on their limitations. E2ETag introduces an end-to-end trainable method for designing fiducial markers and a complimentary detector. By introducing back-propagatable marker augmentation and superimposition into training, the method learns to generate markers that can be detected and classified in challenging real-world environments using a fully convolutional detector network. Results demonstrate that E2ETag outperforms existing methods in ideal conditions and performs much better in the presence of motion blur, contrast fluctuations, noise, and off-axis viewing angles. Source code and trained models are available at this https URL.
Differences in the Utilization of Glycerol and Glucose by Mycobacterium phlei

A basic difference was found in the kinetics of uptake and utilization of glucose and glycerol by washed suspensions of Mycobacterium phlei. With glucose, the rates of uptake, respiration, and assimilation were saturated at low external substrate concentration. With glycerol, these rates were found to increase with increasing substrate concentration and did not show saturation at any concentration tested. Qualitatively similar patterns were observed for cells grown on either glycerol or glucose. Above a saturation concentration, ratios of cell (14)C to CO(2) (14)C for uniformly labeled (14)C-glucose were constant at a value of 0.96. Glycerol-U-(14)C, on the other hand, yielded cell-(14)C/CO(2)-(14)C ratios which were highest at the lowest glycerol concentration tested, and decreased with increasing substrate concentration. The distribution of the glucose and glycerol carbons assimilated into M. phlei were qualitatively similar. Quantitatively, however, the uptake and assimilation of glycerol was far more rapid than that of glucose for all substrate concentrations employed. These quantitative differences in the utilization of glycerol and glucose could account for the increased content of nonessential lipid and polysaccharide found in glycerol-grown M. phlei.
Ridge-crossing mantle plumes and gaps in tracks

[1] Hot spot tracks approach, cross, and leave ridge axes. The complications of this process make it difficult to determine the track followed by a plume and the evolution of its vigor. When a plume is sufficiently near the ridge axis, buoyant plume material flows along the base of the lithosphere toward the axis, forming an on-axis hot spot. The track of the on-axis hot spot is a symmetric V on both plates and an unreliable indication of the path followed by the plume. Aseismic ridges form more or less along flowlines from a plume to a ridge axis when channels form at the base of the lithosphere. A dynamic effect is that off-axis hot spots appear to shut off at the time that an on-axis hot spot becomes active along an axis-approaching track. This produces a gap in the obvious track and a jump of the hot spot to the ridge axis. The gap results from the effects of ponded plume material on intraplate (membrane) stress. Membrane tension lets dikes ascend efficiently to produce obvious tracks of edifices. An off-axis hot spot shuts down when the plume is sufficiently near the ridge axis that plume material flows there, putting the nearby lithosphere above the plume into compression, preventing dikes. In addition, the off-axis thickness of plume material, which produces membrane tension, decreases as the slope of the base of the lithosphere increases beneath young lithosphere. Slow spreading rates favor gaps produced in this way. Gaps are observed near both fast and slow ridges.
NAADP mediated calcium release from acidic stores plays a critical role in downstream physiological responses of naïve CD4 and CD8 T cells (IRM10P.757)

Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca2+ mobilizing second messenger discovered to date and has been implicated in Ca2+ signaling in human Jurkat lymphoma T cells via ryanodine receptor activation. In contrast, the role of NAADP in Ca2+ signaling or the identity of the Ca2+ stores targeted by NAADP in conventional naive T cells has not been investigated. In the current study, we demonstrated for the first time to our knowledge the importance of NAADP in the generation of Ca2+ signals in murine conventional naive T cells. Combining live-cell imaging methods and a pharmacological approach using the NAADP antagonist Ned-19, we addressed the impact of NAADP on the generation of Ca2+ signals evoked by TCR stimulation and the role of this signal in downstream physiological endpoints such as proliferation, cytokine production, and other responses to stimulation of murine naive T cells. Moreover, we demonstrated that acidic stores in addition to the endoplasmic reticulum are the relevant Ca2+ stores that were sensitive to NAADP in naive T cells.
Replicability of Experiment

The replicability of experiment is routinely offered as the gold standard of evidence. I argue that it is not supported by a universal principle of replicability in inductive logic. A failure of replication may not impugn a credible experimental result; and a successful replication can fail to vindicate an incredible experimental result. Rather, employing a material approach to inductive inference, the evidential import of successful replication of an experiment is determined by the prevailing background facts. Commonly, these background facts do support successful replication as a good evidential guide and this has fostered the illusion of a deeper, exceptionless principle.
A compressão do mercado matrimonial e o aumento das uniões consensuais no Brasil

The marriage squeeze and the rise in informal marriage in Brazil. Throughout the world, populations experience shortage of one sex or the other in the age group in which people generally marry, usually as a result of a decline in mortality. The solutions to this problem vary with the cultural context: reduction in the age difference between husband and wife, increase in the value of dowries, and polygamy are three ways of reestablishing an equilibrium in the marriage market. Our hypothesis is that in Brazil the marriage market is balanced by the "recycling” of men through instable consensual union. With censun data from the last forty years and the PNAD of 1984, we show the link between the marriage squeeze and the increase in the number of informal marriage. A competing risks analysis of the chance of remaining single versus entering a formal marriage or consensual union provides evidence that the marriage squeeze has affected both the possibility of entering any type of union and the type of marriage entered.
Instructional Course Lectures, The American Academy of Orthopaedic Surgeons - Specialized Exposure for Revision Total Knee Arthroplasty: Quadriceps Snip and Patellar Turndown*†

Adequate exposure of the knee is the first step in the successful performance of a revision total knee arthroplasty. In order to safely and expeditiously remove the implants that are in place and insert trial and actual components, flexion well beyond 90 degrees (to about 110 degrees) is needed13. In addition, it is preferable to be able to evert the patella and dislocate the tibia anteriorly. If a patient has less than 80 to 90 degrees of passive flexion under anesthesia, the standard medial parapatellar approach may not provide adequate exposure. Initially, it is useful to start the midline incision more proximally than the previous incision in order to establish normal tissue planes proximal to the extensor mechanism. It is also useful to take additional time to define the borders of the rectus femoris tendon and the vastus lateralis and medialis insertions into the patella. The medial parapatellar capsular incision begins at the proximal extent of the rectus tendon and ends distally one centimeter medial to the tibial tubercle. After a medial arthrotomy, release of any adhesions in the suprapatellar pouch and the medial and lateral gutters should be performed. Careful release or excision of scarred or contracted tissue leads to increased flexion and easier eversion of the patella and provides adequate exposure in many patients. Access to the lateral gutter is more difficult after a standard medial arthrotomy. A medial capsular release from the tibia is typically extended past the mid-coronal plane, usually to the posteromedial corner of the knee just anterior to the semimembranosus insertion. External rotation of the tibia after medial release and clearing of the gutters and the suprapatellar pouch usually increases knee flexion to some degree. The next maneuver that improves exposure is the application of traction on the patella as the knee …
Compound Deficiencies in Multiple Fibroblast Growth Factor Signalling Components Differentially Impact the Murine Gonadotrophin-Releasing Hormone System

Gonadotrophin-releasing hormone (GnRH) neurones control the onset and maintenance of fertility. Aberrant development of the GnRH system underlies infertility in Kallmann syndrome [KS; idiopathic hypogonadotropic hypogonadism (IHH) and anosmia]. Some KS patients harbour mutations in the fibroblast growth factor receptor 1 (Fgfr1) and Fgf8 genes. The biological significance of these two genes in GnRH neuronal development was corroborated by the observation that GnRH neurones were severely reduced in newborn transgenic mice deficient in either gene. In the present study, we hypothesised that the compound deficiency of Fgf8 and its cognate receptors, Fgfr1 and Fgfr3, may lead to more deleterious effects on the GnRH system, thereby resulting in a more severe reproductive phenotype in patients harbouring these mutations. This hypothesis was tested by counting the number of GnRH neurones in adult transgenic mice with digenic heterozygous mutations in Fgfr1/Fgf8, Fgfr3/Fgf8 or Fgfr1/Fgfr3. Monogenic heterozygous mutations in Fgfr1, Fgf8 or Fgfr3 caused a 30-50% decrease in the total number of GnRH neurones. Interestingly, mice with digenic mutations in Fgfr1/Fgf8 showed a greater decrease in GnRH neurones compared to mice with a heterozygous defect in the Fgfr1 or Fgf8 alone. This compounding effect was not detected in mice with digenic heterozygous mutations in Fgfr3/Fgf8 or Fgfr1/Fgfr3. These results support the hypothesis that IHH/KS patients with digenic mutations in Fgfr1/Fgf8 may have a further reduction in the GnRH neuronal population compared to patients harbouring monogenic haploid mutations in Fgfr1 or Fgf8. Because only Fgfr1/Fgf8 compound deficiency leads to greater GnRH system defect, this also suggests that these fibroblast growth factor signalling components interact in a highly specific fashion to support GnRH neuronal development.
Meeting the needs of mistreated youths

James Garbarino, Ph.D., is Fellow at the Center for the Study of Youth Development, Boys Town, Nebraska. PATTERNS OF ABUSE The current medical, psychological, increasing public pressure to do some and social welfare establishments have thing for and about these teenagers delineated the mistreatment of chiland their families. The relatively new dren and adolescents as a discrete soawareness of adolescent abuse af cial problem. As well-defined public fords these professionals the chance to issues, the abuse and neglect of chilavoid some of the false starts, blind dren are young, dating from the early alleys, and misconceived programs 1960s. Moreover, only since the 1970s that have plagued efforts to under have social service professionals and stand and deal with child abuse and the public "discovered" the abuse and neglect, neglect of adolescents, although teen agers as well as children have always been subject to mistreatment by their parents, guardians, and custodians.1 The mistreatment of adolescents is a Because of the growing concern for problem endemic to the institutional mistreated adolescents, social service and cultural structure of American professionals now seek to broaden the life, iiot an ephemeral phenomenon, definition of mistreatment. They have Patterns of abuse can be divided into raised the following question: Under the following categories: 2 what circumstances and at what stage ■ Mistreatment that begins with the of the life cycle is one protected from onset of puberty, mistreatment by law, custom, and ■ Mistreatment that represents a practice? change in the quality or form of pun This article attempts to bring toishment (for example, from slapping gether the factual information and to punching), a change in parental theories concerning the mistreatment affect (from tolerance to rejection), of adolescents as a basis for offering or a change in sexual conduct (from the best strategies to meet the needs normal kissing to genital fondling), of these youths, aged 12-18. Although ■ Mistreatment that is present only this article is not a review of the litwhen the child is in the "terrible
A NEW SERIES FOR THE DENSITY OF ABUNDANT NUMBERS

A natural number n is called abundant if the sum of proper divisors of n exceeds n. In 1933 Behrend determined bounds for the natural density d&#x1d49c; of abundant numbers, with subsequent improvements leading to the 1998 bounds of Deleglise, 0.2474 < d&#x1d49c; < 0.2480. We present a new infinite series expression for the density of abundant numbers which can be used to calculate an improved lower bound.
Abstract 3574: Studies of castrate resistant 22Rv1 cells identifies AR regulated interrelated networks of transcription factors, co-regulators, chromatin, and nuclear scaffolding proteins.

Prostate cancer development, progression and acquisition of castrate resistance are reliant on the activity of the androgen receptor (AR), a transcription factor that governs the proliferation of prostate cancer cells. Multiple studies have focused on the principle components that are critical for cell cycle transversal and these studies have identified members of the E2F/RB family, c-Myc, cyclins and cyclin dependent kinase inhibitors as key proteins that are instrumental in prostate cell proliferation and development of castrate resistance. But the mechanism by which the AR dominates this process is unclear. To identify the link between the AR and cell cycle control we used 22Rv1 cells which are castrate resistant due to the expression of low molecular weight AR forms that are missing the ligand binding domain. However, a siRNA mediated decrease in AR expression induces a growth arrest confirming that proliferation is AR dependent. RNA-seq analysis of gene expression at castrate levels of androgen and following AR ablation identified transcripts that were AR dependent. This methodology reduced the number of AR regulated transcripts, by excluding transcripts regulated by super-physiological levels of androgens. The AR regulated transcripts included previously identified genes (PMEPA1, C1orf116, PCDH7, APP) including NFAT a gene shown to be regulated by a low molecular weight AR isoform. The analysis also revealed that interrelated networks of transcription factors and co-factors were AR transactivated or repressed. These included proteins such as the LBR, LMNB, TMPO and SATB1 that do not directly promote transcription, but rather link chromatin to the nuclear membrane or scaffolding, suggesting that the AR may modulate gene expression through epigenetics mechanisms. Network analysis showed connections between these proteins and cell cycle components including E2Fs and Myc where a number of the regulated transcripts are known E2F or Myc targets. In addition, this analysis identified a number of non-coding RNAs; some that have been previously described and some that have yet to be annotated. qPCR studies found that a number of the transcripts regulated in 22Rv1 cells are also AR regulated in LNCaP cells. Coupled with ChIP-seq data, the study characterizes the link between the AR and the cell cycle machinery and chromatin modulating proteins. Citation Format: Maria Mudryj, Stephen J. Libertini, Alan P. Lombard. Studies of castrate resistant 22Rv1 cells identifies AR regulated interrelated networks of transcription factors, co-regulators, chromatin, and nuclear scaffolding proteins. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3574. doi:10.1158/1538-7445.AM2013-3574
Vacuum Rabi splitting as a feature of linear-dispersion theory: Analysis and experimental observations.

The spectral and temporal response of an optical cavity resonantly coupled to an ensemble of barium atoms has been investigated experimentally. The empty-cavity trnasmission resonances are found to split in the presence of the atoms and, under these conditions, the cavity's temporal response is found to be oscillatory. These effects may be viewed as a manifestation of a vacuum-field Rabi splitting, or as a simple consequence of the linear absorption and dispersion of the intracavity atoms.
Using the personal influence model to guide theory building for participatory communication in Africa

Abstract This article argues that the personal influence model (PIM) be used strategically to resolve conflicts and social crises in Africa. It presents PIM as a complementary, analytic discourse to participatory communication, a development paradigm commonly used globally in a variety of social programs. That discourse, as a framework for theory building, is grounded in Africa's emerging and enduring realities: (a) the growing interest of the international community to assist Africa to meet the U.N. Millennium Development Goals, whose focus is to reduce extreme poverty by 2015; (b) the ephemeral nature of Africa's political and social stability that necessitates reducing fear, improving community security, nurturing public trust, and building inter-group relationships, all as preconditions for attaining social development, and for using a community-agency- contracts-partnerships approach to deliver development services; and (c) the palpable congruence of PIM with Africa's extensive social networks, which...
Preparation and Characterization of Unusual Levitation Tl-Ba-Ca-Cu-O Samples

A preparation procedure for the Tl-Ba-Ca-Cu-O superconducting samples which can be levitated above or beneath a magnet is described. X-ray powder diffraction data for these samples are presented and discussed. Their electronic and magnetic properties are presented. The explanation for the unusual levitation is briefly discussed.
Binding of Thrombospondin to Human Plasma Lipoproteins

Immunohistochemical studies have localized thrombospondin (TSP), a platelet adhesive protein, to the atherosclerotic plaque. To investigate how TSP may become incorporated in the plaque, we evaluated the interaction of TSP with human plasma lipoproteins and apolipoproteins. Chylomicrons, VLDL, LDL, HDL, and apolipoproteins AI, AII, C were immobilized on microtiter plates. Binding to TSP was measured directly with [125I]TSP. Labeled TSP bound saturably to all the plasma lipoproteins tested, showing the highest capacity for binding to VLDL. This binding to VLDL was maximal in the presence of 1 mM CaCl2 and MgCl2 and only partially inhibited with EDTA. The binding was inhibited totally by incubation with fluid-phase lipoproteins, apolipoproteins or anti-TSP monoclonal antibodies. The dissociation constants (Kd) for VLDL and apo C were 153 nM and 150 nM, respectively. Thus, TSP exhibits specific and saturable binding with high affinity to VLDL, perhaps mediated by its surface apo C. This binding may facilitate TSP incorporation into nascent atherosclerotic plaques and delivery of VLDL cholesterol into these lesions.
Bariatric surgery, ethical obligation, and the life cycle of medical innovation.

Hofmann's essay highlights the range of complicated and portentous social, ethical, clinical, and economic implications of weight-reduction surgery and should serve as a useful starting point for s...
There and back again: consequences of biofilm specialization under selection for dispersal

Experimental evolution paired with modern sequencing can be a powerful approach to identify the mechanisms by which bacteria adapt to discrete environmental conditions found in nature or during infections. We used this approach to identify mechanisms enabling biofilm specialists of the opportunistic respiratory pathogen Burkholderia cenocepacia to regain planktonic fitness. Seven mutants producing wrinkly (W) small-colony variants by mutations in the wrinkly-spreader operon (wsp) cluster, but with varying duration of biofilm adaptation, served as ancestors of this experiment. Following planktonic growth, each W ancestor produced smooth (S) mutants with distinct fitness effects across planktonic, biofilm, and dispersal-phase environments. The causes of the S phenotype traced to mutations in three gene clusters: wsp, Bcen2424_1436, an uncharacterized two-component transcriptional regulator which appears to be critical for wsp signaling, and a cohort of genes involved in polysaccharide synthesis. The genetic pathway from W to S also associated with evolutionary history in the biofilm environment. W mutants isolated from long-term biofilm selection usually produced S types via secondary wsp mutations, whereas S types evolved from less adapted W ancestors by a wider scope of mutations. These different genetic pathways to suppress the W phenotype suggest that prolonged biofilm adaptation limits routes to subsequent planktonic adaptation, despite common initial mechanisms of biofilm adaptation. More generally, experimental evolution can be used as a nuanced screen for gain-of-function mutations in multiple conditions that illustrate tensions that bacteria may face in changing environments or hosts.
Response to Harold R. Kerbo and L. Richard Della Fave's Corporate Linkage and Control of the Corporate Economy: New Evidence and a Reinterpretation Published in the Spring, 1983, Issue of TSQ

(1984). Response to Harold R. Kerbo and L. Richard Della Fave's Corporate Linkage and Control of the Corporate Economy: New Evidence and a Reinterpretation Published in the Spring, 1983, Issue of TSQ. The Sociological Quarterly: Vol. 25, No. 2, pp. 273-277.
Inhibition of reduced nicotinamide adenine dinucleotide peroxide formation by superoxide dismutase.

The reaction between NADH and oxygen to form NADH peroxide has been found to be stimulated by light and inhibited by superoxide dismutase. These results indicate that singlet oxygen is involved in the formation of NADH peroxide and that the energy associated with singlet oxygen can be effectively dissipated by superoxide dismutase.
LogDiver: A Tool for Measuring Resilience of Extreme-Scale Systems and Applications

This paper presents LogDiver, a tool for the analysis of application-level resiliency in extreme-scale computing systems. The tool has been implemented to handle data generated by system monitoring tools in Blue Waters, the petascale machine in production at the University of Illinois' National Center for Supercomputing Applications. The tool is able: i) to filter, extract, and classify error data from different sources of information, such as system logs, hardware sensors and workload logs; ii) to extract signals from the categorized errors; iii) to consolidate user application data and decode application and job exit status, highlighting the reasons for the application/job exit; and iv) to correlate application failures with errors using a mix of empirical and analytical techniques. To the best of our knowledge, this is the first tool capable of measuring application-level resiliency in extreme-scale machines. We also demonstrate the power of the tool by showing that XK applications are more vulnerable to failures when compared to XE applications.
Influence of Mg2+ on CaCO3 precipitation during subsurface reactive transport in a homogeneous silicon-etched pore network

Calcium carbonate (CaCO3) geochemical reactions exert a fundamental control on the evolution of porosity and permeability in shallow-to-deep subsurface siliciclastic and limestone rock reservoirs. As a result, these carbonate water-rock interactions play a critically important role in research on groundwater remediation, geological carbon sequestration, and hydrocarbon exploration. A study was undertaken to determine the effects of Mg2+ concentration on CaCO3 crystal morphology, precipitation rate, and porosity occlusion under flow and mixing conditions similar to those in subsurface aquifers.
Reliability and validity of the psychiatry resident in-training examination.

The Psychiatry Resident In-Training Examination (PRTTE) has been produced annually since 1979. On each test from 1980 through 1987, the Kuder-Richardson reliability coefficient for the global score in psychiatry was above .90. This is adequate reliability for making comparisons among individual examinees. The reliability coefficients for the neurology score and psychiatry subscores were lower and correlated with subtest length. Small differences in these scores may reflect measurement error. Mean raw scores showed statistically significant increases across groups of examinees with increasing levels of training completed. This supports the presence of construct validity.
NEIGHBORHOOD RACIAL COMPOSITION AND MORTGAGE LENDING: City and Suburban Differences

: Racially discriminatory mortgage lending patterns have been documented in several cities, despite the fact that such practices are illegal under the Federal Fair Housing Act and other federal and state laws. This study finds that in Milwaukee, as in several other metropolitan areas, racial composition of neighborhood is negatively associated with mortgage lending activity by depository institutions even after the effects of income, condition of housing, and related population and neighborhood characteristics are taken into consideration. However, the effects of race are not linear and are different in the city and in the suburbs. In the city, the effects of race were largest in integrated areas, whereas in the suburbs the effects of race were positive when few minorities were present and negative in those areas having large concentrations of minority residents.
"I'm Not Like My Friends": Understanding How Children with a Chronic Illness Use Technology to Maintain Normalcy

Children diagnosed with a chronic illness, such as cancer, experience a vastly different childhood than their healthy counterparts. They may struggle with accepting that they are no longer seen as "normal". We surveyed 10 children who have a chronic illness and interviewed 15 healthcare professionals and 7 parents of chronically ill children to understand their communication practices and challenges of how these patients stay connected with their peers. We found that due to the nature of their illness and constant hospitalization, pediatric patients often use various communication technologies to stay in touch with friends and try to maintain normalcy in their lives. Some patients also had to create a "new normal" that balanced life before and after being diagnosed. Based on these results, we suggest opportunities for technology to help patients connect to others and retain a sense of normalcy or to encourage them to embrace their "new normal".