cssi/SciSciGPT-SciSciNet huggingface dataset:
AT-51PHASE I STUDY OF PANOBINOSTAT AND FRACTIONATED STEREOTACTIC RE-IRRADIATION THERAPY (FSRT) FOR RECURRENT HIGH GRADE GLIOMAS

PURPOSE: To perform a phase I study to evaluate the safety, and tolerability of panobinostat, an HDAC inhibitor, when combined with fractionated stereotactic re-irradiation therapy (FSRT) for recurrent gliomas. METHODS: Patients with recurrent gliomas (WHO grade II-IV) were eligible for this trial. FSRT was prescribed to 30-35 Gy delivered in 10 daily fractions. Panobinostat was administrated orally once daily every Monday, Wednesday, and Friday concurrently with radiation treatment. The panobinostat dose was escalated from 10 to 30 mg using a 3 + 3 trial design. RESULTS: A total of 16 patients were enrolled on the trial. Four patients were excluded. There were no treatment related grade 3 or higher toxicities in the 10 mg or 20 mg cohort. In the 30 mg panobinostat cohort, one patient developed grade 3 leukopenia and grade 4 neutropenia which was possibly related to the treatment. The minimum follow up of the living patients is 8.5 m. The 4-m progression survival (PFS) of all the evaluable patients is 87%, and 6-m PFS of 56%. The medial overall survival is 9.5 m. There is a suggestion of dose response to the panobinostat. The 4-m PFS is 100%, 100%, and 67% for 30 mg, 20 mg, and 10 mg cohort respectively. The 6-m PFS is 83%, 33%, and 67% for 30 mg, 20 mg, and 10 mg cohort respectively. The overall survival for the 30 mg cohort is not reached with a median follow up of 11.5 m. CONCLUSIONS: Panobinostat administrated with FSRT is well tolerated at a 30 mg dose. There is a suggestion of a dose response with panobinostat. The median overall survival is not reached with a median follow up of 11.5 m for the 30 mg cohort. A phase II trial is warranted to confirm the efficacy of combining panobinostat with FSRT for recurrent gliomas.
Brain Monoamine Metabolism of Turkey Hens in Various Stages of Their Reproductive Life Cycle

The metabolism of dopamine (DA), norepinephrine (NE), epinephrine (E), and serotonin (5-HT) was determined in the brains of female turkeys before and after light stimulation, and during various phases of reproductive activity. Ten days of light stimulation increased oviduct weight 3.5 fold (P<0.05). This was associated with a significant elevation of both NE and E synthesis. However, such treatment was without significant changes in either DA or 5-HT metabolism. As female turkeys progressed from the laying phase of the reproductive cycle to broodiness, the ovarian and oviduct weights decreased progressively. DA synthesis was found to increase during gonadal regression, and 5-HT synthesis was elevated in birds with complete ovarian regression. BIOLOGY OF REPRODUCTION 15, 254-259 (1976)
Clinical Indicators for Endotracheal Suctioning in Adult Patients Receiving Mechanical Ventilation

Background Critically ill patients who need mechanical ventilation require endotracheal suctioning. Guidelines recommend coarse crackles over the trachea and/or the presence of a sawtooth pattern on the flow-volume loop of the ventilator waveform as the best indicators. Objective To determine clinical cues for endotracheal suctioning in patients who require mechanical ventilation. Methods A descriptive study of 42 adult patients receiving mechanical ventilation. After baseline endotracheal suctioning with a closed-system device, patients were assessed hourly up to 4 hours for guideline-based cues for endotracheal suctioning and lung sounds were auscultated. Endotracheal suctioning was done when cues were detected or 4 hours after baseline suctioning. Secretions were collected, measured, and weighed. Results Most patients were male (62%) and white (93%). Mean age was 51 years, and mean duration of mechanical ventilation was 7.5 days. The median time to endotracheal suctioning was 2 hours, and a mean of 4.4 mL of secretions was removed. Three patients had no cues identified but had 1.0 mL or more of secretions. The most frequent cues were crackles over the trachea (88%), sawtooth waveform (33%), coughing (29%), and visible secretions (5%). Cues resolved and physiological parameters improved after suctioning. Coarse lung sounds did not improve. Conclusions Patients receiving mechanical ventilation should be routinely assessed for coarse crackles over the trachea, the most common indicator for endotracheal suctioning. Despite common practice, assessment of lung sounds to identify the need for suctioning is not supported.
The COURAGE Trial in Perspective

The indications for percutaneous coronary intervention (PCI) continue to evolve because of the steady improvement in technology, broadened patient and lesion selection criteria, and new evidence from clinical trials. Recently, the role of PCI in patients with chronic stable angina has received considerable scrutiny and has been the subject of great controversy. In these patients, the goals of therapy include the relief of symptom, treatment of ischemia, and reducing the need for subsequent interventions. Medical therapy is the cornerstone in the management of coronary artery disease and should be optimized in all patients. The COURAGE trial investigated the efficacy of combined PCI and optimal medical therapy (OMT) versus OMT alone in patients with stable disease. The trial confirmed several issues that have been already well delineated: (1) in low risk patients, the hard endpoints of death and MI are relatively infrequent and are not reduced by PCI - for prevention of these, OMT may be sufficient, (2) crossover from OMT to PCI is frequent, even in low risk patients, (3) PCI is very effective in reducing symptoms and myocardial ischemia, and (4) significant untreated ischemia is associated with greater likelihood of death and MI.
George Bernard Rabb

Editor's note.—On 27 July 2017, George Rabb, zoologist and director of the Brookfield Zoo, passed away at the age of 87. He was one of the greatest champions of conservation, and we honor his legacy by reprinting this Historical Perspective that appeared in Copeia (103:1086–1092).
Dimensions of Responsibility

What does it mean to say that a person is “responsible” for an event? Does it mean that the person caused the occurrence? that the person should be held legally accountable? that despite any decisions that might or might not be reached by the legal system, the person should be held morally accountable for the event? The question of responsibility, like the question of causality, is a complex one. Consider an example: Suppose that a person raises a loaded rifle, takes careful aim, pulls the trigger, and the bullet that is fired kills another person. Is the one who pulled the trigger “responsible?”
Toil and Struggle: Mrs. Mendoza and Asian American Education

(1989). Toil and Struggle: Mrs. Mendoza and Asian American Education. Amerasia Journal: Vol. 15, No. 1, pp. 281-282.
Suppression of the Saratoga Spittlebug, Aphrophora saratogensis (Fitch), with Malathion in Michigan Pine Plantations

The Saratoga spittlebug causes “flagging,” severe stunting, and tree mortality in pine plantations. The recommended control, 1 lb DDT/acre, has certain undesirable characteristics. This study was made to test the qualities of malathion with its shorter residual life as an effective substitute. Five replications of each of the following treatments were established in 3 infested red pine plantations: (1) Check, (2) 1 lb DDT/gal/acre, (3) 1 lb malathion/gal/acre, and (4) ½ lb malathion/gal/acre. Adult population estimates were made before and after treatment. The results showed that ½ lb malathion/gal/acre controlled adult Saratoga spittlebugs as well as did 1 lb DDT/gal/acre.
In vitro effects of aprotinin on activated clotting time measured with different activators.

The effects in vitro of aprotinin on the activated clotting time measured with both celite- and kaolin-activated tubes were investigated in 21 consecutive patients requiring cardiopulmonary bypass. Four whole-blood samples (2 ml per sample) from each patient were tested simultaneously with Hemochron automated timing systems (International Technidyne Corp., Edison, N.J.) before, during, and after cardiopulmonary bypass. One tenth milliliter of either aprotinin (at a final concentration of 80, 120, or 180 KIU/ml) or saline solution was mixed in vitro with blood samples before determination of the activated clotting time. Aprotinin had no inhibitory effect on the activated clotting times of unheparinized blood. After heparin administration, aprotinin in the above concentrations prolonged the activated clotting times measured with celite-activated tubes by 47% to 71%, as compared with the measurements of the activated clotting time without the addition of aprotinin. The activated clotting times in kaolin-activated tubes were not increased, however, by the in vitro addition of aprotinin. Our in vitro results indicate that aprotinin in concentrations from 80 to 180 KIU/ml does not significantly enhance the inhibitory effects of heparin on the intrinsic coagulation system as evaluated by measurement of the activated clotting times in kaolin-activated tubes. The anticoagulation effect of heparin in patients receiving aprotinin infusion should be monitored with kaolin-activated instead of celite-activated tubes because the celite makes the measured activated clotting time unreliable in patients receiving aprotinin therapy. These in vitro results require confirmation in vivo in patients receiving aprotinin therapy. (J T horac C ardiovasc S urg 1992;104:1135-40)
Cell-Wall Formation in Fucus Zygotes: A Model System to Study the Assembly and Localization of Wall Polymers

Alterations in cell-wall structure and metabolism are closely coupled to the developmental processes of growth, differentiation, and morphogenesis. Although the structure and function of the cell wall have been studied extensively, relatively little attention has been devoted to the mechanisms by which a cell wall is initially assembled outside the plasma membrane. Understanding the steps and pattern in which various polymers are assembled into an extracellular structure will be helpful in elucidating a chemical and physical model of the cell wall. This developmental or inductive approach should complement that used by Albersheim, in which an existing cell wall is dissected with chemical and enzymatic techniques. From this, Albersheim’s group can deduce the chemical architecture of an already existing structure (Keegstra et al., 1973). Unfortunately, wall assembly in angiosperms is not amenable to biochemical experimentation, since most cases of initial wall construction occur within complex tissue masses and are difficult to isolate from other concurrent biochemical events. For example, in meristems, the construction of new cross-walls during telophase has been described cytologically, but to identify individual wall polymers and how they are linked to other polymers, as well as how the process of wall assembly is directed to only the sites of new plasma-membrane formation (i.e., the “end walls”), is difficult to approach.
Energetic N-Nitramino/N-Oxyl-Functionalized Pyrazoles with Versatile π–π Stacking: Structure–Property Relationships of High-Performance Energetic Materials

N-Nitramino/N-oxyl functionalization strategies were employed to investigate structure–property relationships of energetic materials. Based on single-crystal diffraction data, π–π stacking of pyrazole backbones can be tailored effectively by energetic functionalities, thereby resulting in diversified energetic compounds. Among them, hydroxylammonium 4-amino-3,5-dinitro-1H-pyrazol-1-olate and dipotassium N,N′-(3,5-dinitro-1H-pyrazol-1,4-diyl)dinitramidate, with unique face-to-face π–π stacking, can be potentially used as a high-performance explosive and an energetic oxidizer, respectively.
Iterative image reconstruction using geometrically ordered subsets with list-mode data

In positron emission tomography (PET), the format in which the data is stored has a major influence on the image reconstruction procedure. The use of the list-mode format preserves all of the measured attributes of the detected photon pairs but the events are stored in the order that they were measured, which allows only sequential access to the data. This fact limits the number of applicable algorithms and often computing speed or memory capacity constraints require the use of algorithms that do not make full use of the original precise information in the data. In this paper we show how through a change of the format in which the data is stored one can keep all the initial information about the individual events while providing random access to subsets of events belonging to given geometrical regions, thus making possible the use of maximum likelihood ordered subsets (OSEM) type algorithms with data provided as a collection of individual events (list-mode), and facilitating the adaptation of other types of algorithms. The structured data format also allows for more compact (compressed) storage of the information compared to the simple list-mode format.
What You Want Versus What's Good for You: Paternalistic Motivation in Children's Helping Behavior.

Children help others to complete their goals. Yet adults are sometimes motivated to help others in a "paternalistic" way, overriding a recipient's desires if they conflict with the recipient's best interests. Experiments investigated whether 5-year-olds (n = 100) consider a recipient's desire, and the consequences of fulfilling this desire, when helping. Children overrode a request for chocolate in favor of giving fruit snacks, if chocolate would make the recipient sick. Children did not override a request for chocolate in favor of carrots, even if chocolate would make the recipient sick, but they gave carrots if the recipient requested them. By age 5, children balance different motivations when helping, considering the recipient's desires, consequences of fulfilling them, and alternative forms of helping available.
Inferring the Impact of Regulatory Mechanisms that Underpin CD8+ T Cell Control of B16 Tumor Growth In vivo Using Mechanistic Models and Simulation.

A major barrier for broadening the efficacy of immunotherapies for cancer is identifying key mechanisms that limit the efficacy of tumor infiltrating lymphocytes. Yet, identifying these mechanisms using human samples and mouse models for cancer remains a challenge. While interactions between cancer and the immune system are dynamic and non-linear, identifying the relative roles that biological components play in regulating anti-tumor immunity commonly typically relies on human intuition alone, which can be limited by cognitive biases. To assist natural intuition, modeling and simulation play an emerging role in identifying therapeutic mechanisms. To illustrate the approach, we developed a multi-scale mechanistic model to describe the control of tumor growth by a primary response of CD8+ T cells against defined tumor antigens using the B16 C57Bl/6 mouse model for malignant melanoma. The mechanistic model was calibrated to data obtained following adenovirus-based immunization and validated to data obtained following adoptive transfer of transgenic CD8+ T cells. More importantly, we use simulation to test whether the postulated network topology, that is the modeled biological components and their associated interactions, is sufficient to capture the observed anti-tumor immune response. Given the available data, the simulation results also provided a statistical basis for quantifying the relative importance of different mechanisms that underpin CD8+ T cell control of B16F10 growth. By identifying conditions where the postulated network topology is incomplete, we illustrate how this approach can be used as part of an iterative design-build-test cycle to expand the predictive power of the model.
Combining Genome-Scale Experimental and Computational Methods To Identify Essential Genes in Rhodobacter sphaeroides

ABSTRACT Rhodobacter sphaeroides is one of the best-studied alphaproteobacteria from biochemical, genetic, and genomic perspectives. To gain a better systems-level understanding of this organism, we generated a large transposon mutant library and used transposon sequencing (Tn-seq) to identify genes that are essential under several growth conditions. Using newly developed Tn-seq analysis software (TSAS), we identified 493 genes as essential for aerobic growth on a rich medium. We then used the mutant library to identify conditionally essential genes under two laboratory growth conditions, identifying 85 additional genes required for aerobic growth in a minimal medium and 31 additional genes required for photosynthetic growth. In all instances, our analyses confirmed essentiality for many known genes and identified genes not previously considered to be essential. We used the resulting Tn-seq data to refine and improve a genome-scale metabolic network model (GEM) for R. sphaeroides. Together, we demonstrate how genetic, genomic, and computational approaches can be combined to obtain a systems-level understanding of the genetic framework underlying metabolic diversity in bacterial species. IMPORTANCE Knowledge about the role of genes under a particular growth condition is required for a holistic understanding of a bacterial cell and has implications for health, agriculture, and biotechnology. We developed the Tn-seq analysis software (TSAS) package to provide a flexible and statistically rigorous workflow for the high-throughput analysis of insertion mutant libraries, advanced the knowledge of gene essentiality in R. sphaeroides, and illustrated how Tn-seq data can be used to more accurately identify genes that play important roles in metabolism and other processes that are essential for cellular survival. Author Video: An author video summary of this article is available.
Engineering Approach to the Study of Short Term Periodicities in Human Metabolism

Abstract An engineering system analysis of “the input-output relationships” has been adapted to the study of metabolic fluctuations in man, on an hourly basis. All subjects, normal controls and those paralysed due to spinal cord injury, were studied for 14-31 day periods in the controlled environment of a metabolic ward. In order to separate the effects of meals, body position changes and “diurnal clocks” on the urine excretion patterns, body temperature and heart rate, “synthetic living schedules” were designed and applied as part of the input control of the subjects. These included: (a) a "nibbling schedule", with meals served every 4 hours day and night, (b) a "19-hr. schedule", in which one large meal was given every 19 hours, (c) a "random schedule", with meals separated by random spacings. The collection and numerical analysis of the required volume of data (up to 2000 hourly data per Week) was made possible by the development of an "Automated 25-Channel Data Acquisition System" linked to a computing facility. This allowed us (a) to uncover the diurnal rhythms in renal function, heart rate and body temperature, (b) to isolate various renal excretion patterns as influenced by various external factors (like diet composition, meal scheduling and body position), (c) to quantitate the periodicity strength and the level of the "noise component" in data obtained during physiological monitoring, (d) to assess the effects of diurnal rhythms and food intake on steroid regulation of urinary excretion of metabolites.
On Robust Concepts and Small Neural Nets

The universal approximation theorem for neural networks says that any reasonable function is well-approximated by a two-layer neural network with sigmoid gates but it does not provide good bounds on the number of hidden-layer nodes or the weights. However, robust concepts often have small neural networks in practice. We show an efficient analog of the universal approximation theorem on the boolean hypercube in this context. We prove that any noise-stable boolean function on n boolean-valued input variables can be well-approximated by a two-layer linear threshold circuit with a small number of hidden-layer nodes and small weights, that depend only on the noise-stability and approximation parameters, and are independent of n. We also give a polynomial time learning algorithm that outputs a small two-layer linear threshold circuit that approximates such a given function. We also show weaker generalizations of this to noise-stable polynomial threshold functions and noise-stable boolean functions in general.
On the Continuous Singularity of the Limit Distribution of Products of I.I.D. d×d Stochastic Matrices

This article gives sufficient conditions for the limit distribution of products of i.i.d. d×d random stochastic matrices, d finite and ≥2, to be continuous singular, when the support of the distribution of the individual random matrices is finite or countably infinite. Proofs are based on applications of the multivariate Central Limit Theorem.
Risk Score Based Pre-Screening of Breast Tumor Using Compression Induced Sensing System

A pre-screening device that quantifies mechanical properties of tumors will be used as an early stage breast tumor warning system. In this paper, a compression induced sensing system (CISS) is developed, which determines the mechanical properties of tumors. The optical sensing probe of CISS is made of transparent elastomer and works on the total internal reflection principle. 3-D interpolation method and deformation index computation method are developed to estimate the size of the tumor and deformation of the sensing tip due to the applied pressure. After having satisfactory phantom tests using CISS and the developed algorithms, in vivo clinical studies of twenty-one patients were performed. Based on the estimated mechanical properties, a risk score range is developed which can be used to pre-screen or classify breast tumors as malignant or benign. The quantified results were correlated with the pathology report of the test cases. The developed system showed an accuracy of 90.5% in classifying the breast tumor cases.
Targeted methylation sequencing of plasma cell-free DNA for cancer detection and classification.

Abstract Background Targeted methylation sequencing of plasma cell-free DNA (cfDNA) has a potential to expand liquid biopsies to patients with tumors without detectable oncogenic alterations, which can be potentially useful in early diagnosis. Patients and methods We developed a comprehensive methylation sequencing assay targeting 9223 CpG sites consistently hypermethylated according to The Cancer Genome Atlas. Next, we carried out a clinical validation of our method using plasma cfDNA samples from 78 patients with advanced colorectal cancer, non-small-cell lung cancer (NSCLC), breast cancer or melanoma and compared results with patients’ outcomes. Results Median methylation scores in plasma cfDNA samples from patients on therapy were lower than from patients off therapy (4.74 versus 85.29; P = 0.001). Of 68 plasma samples from patients off therapy, methylation scores detected the presence of cancer in 57 (83.8%), and methylation-based signatures accurately classified the underlying cancer type in 45 (78.9%) of these. Methylation scores were most accurate in detecting colorectal cancer (96.3%), followed by breast cancer (91.7%), melanoma (81.8%) and NSCLC (61.1%), and most accurate in classifying the underlying cancer type in colorectal cancer (88.5%), followed by NSCLC (81.8%), breast cancer (72.7%) and melanoma (55.6%). Low methylation scores versus high were associated with longer survival (10.4 versus 4.4 months, P Conclusions Comprehensive targeted methylation sequencing of 9223 CpG sites in plasma cfDNA from patients with common advanced cancers detects the presence of cancer and underlying cancer type with high accuracy. Methylation scores in plasma cfDNA correspond with treatment outcomes.
Diabetic Retinopathy Proliferative

Introduction and Definition Proliferative diabetic retinopathy (PDR) is an advanced form of diabetic retinopathy characterized by the growth of new vessels arising from the optic disc, surface of the retina, iris, or anterior chamber angle. It is associated with a significant loss of vision and at least 12 % of the new cases of blindness each year in the United States (Albert et al. 2008). Growth of new vessels at the disc is known as neovascularization of the disc (NVD), whereas origin of new vessels from retinal vasculature elsewhere is neovascularization elsewhere (NVE). As the disease progresses, fibrous tissue around the vessels increases, and when this fibrous tissue contracts, it can lead to tractional retinal detachment and vitreous hemorrhage, which are the leading causes of visual loss associated with PDR (Yanoff and Duker 2014). The prevalence of diabetic eye disease is steadily increasing. More than 150 million people around the world suffer from diabetes, and this number is expected to double by the year 2030. In the background of this diabetes tsunami, diabetic retinopathy and its complications remain a major medical and social challenge.
The Fascination of Statistics. Edited by Richard J. Brook

(1987). The Fascination of Statistics. Edited by Richard J. Brook. The American Mathematical Monthly: Vol. 94, No. 8, pp. 806-809.
Comments on “Solubility and thermodynamic properties of maltol in different pure solvents”

Abstract Errors are discovered in the tabulated thermodynamic properties of dissolution reported by Li and coworkers. Specifically, the properties do not obey the standard thermodynamic relationship of ΔdissG = ΔdissH − T ΔdissS, where ΔdissG, ΔdissH and ΔdissS are respectively the Gibbs energy of dissolution, the enthalpy of dissolution, and the entropy of dissolution of maltol in the organic solvent at the solution temperature, T.
Genetic Testing by Sports Medicine Physicians in the United States: Attitudes, Experiences, and Knowledge.

It remains unknown whether and how sports medicine physicians currently utilize genetic testing in their clinical practice. This study sought to assess knowledge of, experience with, and attitudes towards genetic testing by sports medicine physicians in the United States (US). An email with a survey hyperlink was distributed twice to members of the American Medical Society for Sports Medicine (AMSSM) listserv in September 2016, with approximately a 10% response rate. Questions focused on knowledge of, experience with, and attitudes towards testing for different genes related to sports proficiency, injury risk, and disease risk. Few AMSSM physicians believe that genetic testing to adapt training (12%) or to choose a sport (2%) is ready for clinical adoption. Most respondents self-reported minimal knowledge about, and limited experience with, genetic testing. The main exception was screening for sickle cell trait (SCT) for which most (84%) reported moderate/significant/expert knowledge and over two-thirds had ordered testing. Although most respondents thought it appropriate to counsel and test for health conditions associated with cardiac and connective tissue disorders in the setting of a positive family history, only a minority had been asked to do so. Five or fewer respondents (2%) had been asked to test for performance-associated variants (Angiotensin Converting Enzyme (ACE) II and Alpha-Actinin 3 (ACTN3)), and five or fewer (2%) would recommend changes based on the results. Our study provides a baseline of current US sports medicine physicians’ minimal experiences with, and knowledge of, genetic testing. The findings of our study indicate that sports medicine physicians require further genetics education as it relates to sports and exercise in order to be prepared to competently engage with their patients and to develop sound professional organizational policies.
Women covered in ink: tattoo collecting as serious leisure

Robert Stebbins has created a theory around ‘serious leisure’ (as differentiated from “casual leisure”), which has six particular qualities related to the extent of investment and efforts, benefits elicited, and the social world of the activity. Collecting tattoos, especially for serious collectors, can be considered a leisure activity that ranged from casual to serious, along with the collectors’ commitment to the activity. The act of becoming ‘heavily tattooed,’ with its historical association with deviant subcultures, continued to maintain a social stigma and evoke negative sanctions from observers. This is especially so for women—the participants of this study—who must also contend with gender norms in this subculture, which has previously been associated with other masculine groups. Besides gender norms, the tattoo world has specific ethos which divides the serious subcultural member from those more casually connected to it. The physical parameter of the subculture finds people gathering in tattoo studios and at tattoo conventions, as well as consuming tattoo-oriented media, such as magazines and television shows. This study is based on qualitative interviews with 36 participants across the United States who consider themselves serious tattoo collectors. From their stories, we learn about the importance of participating in this leisure activity and how becoming heavily tattooed impacts their sense of self and identity.
Reversing the typical pH stability profile of the Trp‐cage

The Trp-cage, an 18-20 residue miniprotein, has emerged as a primary test system for evaluating computational fold prediction and folding rate determination efforts. As it turns out, a number of stabilizing interactions in the Trp-cage folded state have a strong pH dependence; all prior Trp-cage mutants have been destabilized under carboxylate-protonating conditions. Notable among the pH dependent stabilizing interactions within the Trp-cage are: (1) an Asp as the helix N-cap, (2) an H-bonded Asp9/Arg16 salt bridge, (3) an interaction between the chain termini which are in close spatial proximity, and (4) additional side chain interactions with Asp9. In the present study, we have prepared Trp-cage species that are significantly more stable at pH 2.5 (rather than 7) and quantitated the contribution of each interaction listed above. The Trp-cage structure remains constant with the pH change. The study has also provided measures of the stabilizing contribution of indole ring shielding from surface exposure and the destabilizing effects of an ionized Asp at the C-terminus of an α-helix.
New Alkenyldiarylmethanes with Enhanced Potencies as Anti-HIV Agents Which Act as Non-Nucleoside Reverse Transcriptase Inhibitors

Twenty-two new alkenyldiarylmethanes (ADAMs) were synthesized and evaluated for inhibition of HIV-1 replication. The most potent compound proved to be methyl 3',3"-dichloro-4',4"-dimethoxy-5', 5"-bis(methoxycarbonyl)-6,6-diphenyl-5-hexenoate (ADAM II), which displayed an EC50 of 13 nM for inhibition of the cytopathic effect of HIV-1RF in CEM-SS cells. ADAM II inhibited HIV-1 reverse transcriptase with an IC50 of 0.3 microM but was inactive as an inhibitor of HIV-1 attachment/fusion to cells, protease, integrase, and the nucleocapsid protein. Molecular target-based and cell-based assays revealed that ADAM II acted biologically as a nonnucleoside reverse transcriptase inhibitor (NNRTI). ADAM II inhibited replication of a wide variety of laboratory, clinical, and clade-representative isolates of HIV-1 in T cell lines and cultures of peripheral blood mononuclear cells or monocyte/macrophages. Mutations that conferred resistance to ADAM II clustered at residues 101, 103, 108, 139, 179, 181, and 188, which line the nonnucleoside binding pocket of HIV-1 reverse transcriptase. However, HIV-1 NL4-3 strain expressing a mutation at residue 100 of reverse transcriptase, and an AZT-resistant virus, displayed increased sensitivity to ADAM II. Thus, ADAM II could serve as an adjunct therapy to AZT and NNRTIs that select for L100I resistance mutations.
The TLR7/8 agonist R848 remodels tumor and host responses to promote survival in pancreatic cancer

A priority in cancer research is to innovate therapies that are not only effective against tumor progression but also address comorbidities such as cachexia that limit quality and quantity of life. We demonstrate that TLR7/8 agonist R848 induces anti-tumor responses and attenuates cachexia in murine models of pancreatic ductal adenocarcinoma (PDAC). In vivo, tumors from two of three cell lines were R848-sensitive, resulting in smaller tumor mass, increased immune complexity, increased CD8+ T-cell infiltration and activity, and decreased Treg frequency. R848-treated mice demonstrated improvements in behavioral and molecular cachexia manifestations, resulting in a near-doubling of survival duration. Knockout mouse studies revealed that stromal, not neoplastic, TLR7 is requisite for R848-mediated responses. In patient samples, we found Tlr7 is ubiquitously expressed in stroma across all stages of pancreatic neoplasia, but epithelial Tlr7 expression is relatively uncommon. These studies indicate immune-enhancing approaches including R848 may be useful in PDAC and cancer-associated cachexia. In the treatment of pancreatic ductal adenocarcinoma (PDAC), comorbidities such as cachexia limit quality of life and survival. Here, the authors show TLR7/8 agonist R848 remodels host and tumour immune responses, promoting survival and attenuating cachexia in murine models of PDAC.
How Many Interviews Do I Need to Be Safe? Is It Same for Prelim and Advanced Programs?

The residency program’s motive for interviewing an applicant is to know them beyond his/her accomplishments on the application. Hence, an interview is a key factor in the ranking of an applicant, and the question arises regarding having a perfect number to get successfully matched. The contiguous ranking is the applicant’s program rank order list having programs of the same desired specialty before they rank other specialties. According to NRMP data, the more the applicants rank programs of their desired specialty, the higher the chances of the matching outcome. Both US and non-US IMGs who matched to their preferred specialties have longer contiguous rank lists than those who did not match in almost all specialties.
Dielectric Polymer Property Prediction Using Recurrent Neural Networks with Optimizations

Despite the growing success of machine learning for predicting structure-property relationships in molecules and materials, such as predicting the dielectric properties of polymers, it is still in its infancy. We report on the effectiveness of solving structure-property relationships for a computer-generated database of dielectric polymers using recurrent neural network (RNN) models. The implementation of a series of optimization strategies was crucial to achieving high learning speeds and sufficient accuracy: (1) binary and nonbinary representations of SMILES (Simplified Molecular Input Line System) fingerprints and (2) backpropagation with affine transformation of the input sequence (ATransformedBP) and resilient backpropagation with initial weight update parameter optimizations (iRPROP- optimized). For the investigated database of polymers, the binary SMILES representation was found to be superior to the decimal representation with respect to the training and prediction performance. All developed and optimized Elman-type RNN algorithms outperformed nonoptimized RNN models in the efficient prediction of nonlinear structure-activity relationships. The average relative standard deviation (RSD) remained well below 5%, and the maximum RSD did not exceed 30%. Moreover, we provide a C++ codebase as a testbed for a new generation of open programming languages that target increasingly diverse computer architectures.
A More-Than-Human History of Apartheid-Era Planning in Etosha-Kaokoveld, Namibia, c.1960–1970s

Following the release and implementation of the ‘Report of the Commission of Enquiry into South West Africa Affairs’ (Odendaal Plan) in 1964, humans and non-humans in Etosha-Kaokoveld (northwest Na...
Governance structures in wheat supply chains and their impacts on productivity and profitability of wheat producers in Ethiopia

This study aims to supplement the literature on the factors affecting wheat producer productivity and profitability by focusing on the role of governance structures and asymmetric information – an issue that is rarely discussed in developing countries. The study thoroughly explores the effect of governance structures and asymmetric information to model a hypothesis for Ethiopia. The study area enables an exemplary case study as it is one of the top wheat-producing areas in both Ethiopia and all of Africa. The study area has also been registered as a wheat belt region in Sub-Saharan Africa. This study used personal interviews to collect primary data from actors. Mixed sampling techniques (i.e., random, census, and purposive) were used to select sampling units. Multiple linear regression models were used to analyse the data. The results show that governance structures, Farm-gate transactions, and asymmetric information have a significant effect on wheat productivity and profitability. Asymmetric information significantly reduces the profit and yield of wheat producers. The study implies that the government should apply a policy related to institutional arrangements to enhance productivity and profitability in wheat supply chains.
Learning, Dispersion of Beliefs, and Risk Premiums in an Arbitrage-Free Term Structure Model

This paper studies an arbitrage-free dynamic term structure model of a Bayesian learner who presumes that dispersion of beliefs is priced in Treasury markets and that measured dispersion has forecasting power for future Treasury yields. The estimated learning rule reveals which aspects of risk and the state of the economy agents learn about and which aspects they (evidently) know from information embedded in the current yield curve. Moreover, we quantify the effect of learning on measured risk premiums in Treasury markets, as well as how an agent pricing with the fitted stochastic discount factor would have adjusted the parameters of her learning rule over business cycles and as the measured degree of disagreement changed over time. Our {\em real-time} model-based learning rule substantially outperforms the consensus forecasts of market professionals over the past twenty-five years, particularly during the years following recessions in the U.S. economy. Moreover, we find that the informativeness of dispersion in beliefs about future yields is distinct from information about the macroeconomy.
Staging the Uncanny: Phantasmagoria in Post-Unification Italy

The present text discusses the separation between the natural sciences and the public sphere around the end of the 19th century, focusing on popular shows in which spirits are evoked with technical media. The main focus is on the theatrical spectacles in the Milanese Randegonda Theatre, in which scientists, magicians and magnetists shared the stage. In Italy, these phantasmagorias were closely related to the political rhetoric of that time, as can be gathered from the discourse in political journals of the 1860-1870s in Italy.
Early Ultra structural Findings in Experimentally Produced Varicocele in the Monkey Testis

Varicocele was produced in adult male macaque monkeys (Macaca fascicularls) by partial occlusion of the left renal vein. Left varicoceie was verified by palpation. An increase In temperature of the left testicle was noted. Bilateral testicular biopsies were obtained at six, nine, and 18-month intervals for morphologic studies. Early morphologic damage was not appreciated with the light microscope, but was found using transmission electron microscopy. The early ultrastructural damage consisted of loss in thickness and lamination of the basal lamina, cellular organelie degeneration, and enlargement of the intercellular spaces between basal cells of the seminiferous tubules. Later, ultrastructural damage was seen in the adluminal areas. At 18 months, ultrastructural damage had progressed to the right testis. Reflux of adrenal metabolites had no effect on the early ultrastructural damage.
The Image Science and Mission Operations Center

The Imager for Magnetopause-to-Aurora Global Exploration (IMAGE) will produce forefront science by quantifying the response of the magnetosphere to the time variable solar wind. It will acquire, for the first time, a variety of three-dimensional images of magnetospheric boundaries and plasma distributions extending from the magnetopause to the inner plasmasphere. The images will be produced on time scales needed to answer important questions about the interactions of the solar wind and the magnetosphere. The IMAGE team will provide open access to all IMAGE data. Thus there will be no proprietary rights or periods. All IMAGE data products will be archived and available to the scientific research community. The IMAGE mission will operate with a near 100% duty cycle with all instruments in their baseline operational modes. A Science and Mission Operations Control Center or SMOC has been developed at the NASA Goddard Space Flight Center (GSFC) to be the main data and command processing system for IMAGE. The IMAGE Level-0 data will be processed into Level 0.5 and Level-1 data and browse products within 24 hours after their receipt of raw data in the SMOC. These data products will be transferred to the NSSDC., for long-term archiving, and posted immediately on the world-wide-web for use by the international scientific community and the public.
Improving Neural Network Training Based on Jacobian Rank Deficiency

Analysis and experimental results obtained in [1] have revealed that many network training problems are ill-conditioned and may not be solved efficiently by the Gauss-Newton method. The Levenberg-Marquardt algorithm has been used successfully in solving nonlinear least squares problems, however only for reasonable size problems due to its significant computation and memory complexities within each iteration. In the present paper we develop a new algorithm in the form of a modified Gauss-Newton which on one hand takes advantage of the Jacobian rank deficiency to reduce computation and memory complexities, and on the other hand, still has similar features to the Levenberg-Marquardt algorithm with better convergence properties than first order methods.
Metabolic Bone Diseases

Bone scintigraphy has traditionally been considered to be nonspecific and less reliable than radiography in the diagnosis of metabolic bone diseases. However, aided with the pinhole technique this test can often display some characteristic features in osteomalacia and systemic osteoporosis caused by seniscense and menopause. Needless to say, it is a highly sensitive and convenient means of detecting the pseudofractures or fractures in osteomalacia and osteoporosis. In addition, the whole-body scan is ideal for the delineation of the systemic changes of osteomalacia, rickets, and renal osteodystrophy on a single view display.
A comparative evaluation of tibial component designs of total knee prostheses.

Three-dimensional finite-element stress analyses were used to compare the fixation of tibial component configurations of surface-replacement-type total knee prostheses, bases on the stresses in the cancellous bone, in the polymethylmethacrylate, and at the bone cement-bone interface. The results indicate that, in general, metal components provide lower system stresses than polyethylene components, particularly in the methacrylate and the cancellous bone, and that one-piece designs give lower bone cement-bone interface stresses compared with those with separated condylar components. Of the designs considered, a single-post, metal-backed design provided the lowest system stresses over-all. Clinical Relevance: a great and confusing variety of tibial component design exists today, with more in the process of development. Short of long term clinical trials, there are few objective methods by which these designs can be evaluated and long-term performance predicted. There is evidence from clinical results that excessively high stresses in the systems can lead to loosening of the tibial component. The finite-element method provides a method for comparing prosthetic designs using system stresses a s a design criterion. On this basis, we analyzed the stress distribution for several types of tibial components and discuss the advantages and disadvantages of their designs.
Systems That Control the Burrowing Behaviour of a Sea Anemone

The sand-dwelling sea anemone, Phyllactis concinnata , buries itself by attaching sand grains to the lower column as this is bent under the anemone by a travelling peristaltic wave. Some of the sand is then released as the column expands laterally. Once buried, the anemone increases in length over a period of several hours until the pedal disc finally attaches to a buried shell. Burrowing is controlled by bursts of pulses generated by the through-conducting nerve net. These pulses produce column shortening and peristalsis. Regular intervals between pulses and between bursts suggest that pacemakers are driving the nerve net. Pulse patterns are modified after sand has surrounded the column and when the pedal disc touches hard substratum. A second conducting system (the SS2) can, under specific experimental conditions, respond to mechanical and chemical stimuli and inhibit nerve net discharge, but its function during burrowing is not known, even though it produces a distinctive pattern of pulses. After the column has been buried, an anemone may contract spontaneously and rapidly. Two other types of behaviour, pharynx eversion and antiperistaltic behaviour (crawling), usually precede burrowing and each is associated with its own characteristic pattern of pulses.
Molecular Origins of Elastomeric Friction

Frictional properties of soft elastomers have been in question for over half of a century. Early studies on natural rubber originated for the sole purpose of tabulating properties for bulk consumer applications, such as viscoelastic adhesives, tires, and windshield wipers, to name a few. Empirical tabulation of frictional properties persisted until the early 1950’s, when Roth et al. and Thirion began experiments towards a fundamental understanding of rubbery sliding. Quantitative physical analysis began with the observation that the classic Coulombic laws obeyed consistently at rigid body interfaces fail at the interface between a rigid solid and a rubber. Even today, there remains an incomplete understanding of the molecular level parameters that control the frictional behavior of elastomeric surfaces. With this chapter, we explore the historical developments in elastomeric friction and discuss the evolution of an unresolved triborheological complexity. We work from an initial macroscopic perspective toward a microscopic one that describes dissipation process in terms of molecular phenomena at frictional contacts. Readers are urged to consider a competition between these molecular processes, where for soft matter, internal cohesion is comparable to interfacial adhesion. While cohesion may dominate adhesion, or visa versa, we develop a picture for elastomeric friction that encompasses both.
Female mate choice and songbird song repertoires

Males of many songbird species use song repertoires that contain multiple song types. A commonly encountered evolutionary explanation for this trait and its recurrent appearance among songbird species is that repertoires have arisen in response to widespread female preference for mates with larger song or syllable repertoires. To assess whether the available evidence supports this hypothesis, we reviewed the literature on the relationship between mate choice and song repertoire size. Our review revealed an array of results that was ultimately inconclusive with regard to the generality of the mate choice hypothesis. Given the ambiguity of these results, we also examined patterns of song use and development and found that some patterns (e.g. overproduction during song ontogeny, repertoires of non-interchangeable songs, hidden repertoires and the prevalence of small repertoires) are at odds with outcomes expected if female preference for larger repertoires were common. We conclude that these cross-species patterns of song use suggest that female preference for larger repertoires is not widespread. We propose that song repertoires have generally arisen not through selection for repertoire size per se, but rather as a by-product of social conditions that favoured the evolution of complex signalling systems.