cssi/SciSciGPT-SciSciNet huggingface dataset:
Comment on Winke T et al. J Assist Reprod Genet DOI 10.1007/S10815-008-9277-3

In a recent original contribution paper by Winke and colleagues published in JARG [1], the authors examine the association between male age and sperm DNA integrity as a potential co-factor affecting fertility. Based on basic semen analysis and DFI measurement via PI staining, they conclude that there is no direct age effect in sperm parameters, neither in normal (340) nor in control (84) individuals. In the discussion section, the authors attribute this contradictory finding to several causes. In particular, with regard to the study by our group [2], they attribute our positive correlation outcome to the limited patient sample used and the application of the TUNEL assay. As to the first suggestion, it is a classic concept in biostatistics that limited sampling may decrease study power, rendering it harder to exhibit existent differences among compared groups (hence the term ¨statistically indicative¨ used to describe findings with a p value between 0.1 and 0.05, which could have been shown to be statistically significant if a bigger sample was used to limit standard error). However, the opposite cannot be true and, thus, if a difference reaches statistical significance despite the small study sample, this is only indicative of its considerable extension. As far as the use of the TUNEL assay is concerned, this is a classic molecular technique used to detect apoptotic cells due to their special feature of DNA strand breaks. It is true that some partial or localized strand breaks may not be detected by TUNEL (although, to our knowledge, there is no large scale head to head comparative study between the various DNA fragmentation estimation assays using the same reference sample) but these would normally not be expected to cause significant effects in the clinical setting. Therefore, we think it is important to distinguish between pro-apoptotic fragmentation, which may be predictive of fertility potential and seems to be age-dependent and overall DNA integrity status, which also includes minor distortions, possibly present in all age groups and potentially counteracted by housekeeping mechanisms. As far as sperm concentration is concerned, it is evident that this is largely affected by accessory gland function, which is known to be age-(and androgen-) dependent, although numerous environmental factors (e.g. drugs, hydration status, infections) may also affect this parameter. To conclude, it is our belief that DNA fragmentation is an important factor when attempting to evaluate sperm quality and fertility potential in an infertile couple. However, its estimation requires sophisticated techniques to distinguish baseline and excessive activity, which hinders generalized application as part of routine assessment in infertility clinics at present.
Biogenesis and cell cycle relationship of poly(A)- actin mRNA in mouse ascites cells.

Abstract A variety of rapidly growing mammalian cells contain a substantial portion of their actin mRNA in a poly(A)− form. We have used DNA-driven hybridization of a cloned actin cDNA-containing plasmid with pulse-labeled RNA from mouse S-180 ascites cells to examine newly synthesized actin mRNA. Our results indicate that the same proportion of newly synthesized and steady-state actin mRNA (approx. 40%) exists in a poly(A)-deficient form. This suggests that the poly(A)− form arises by some process other than slow cytoplasmic de-adenylation of a poly(A)+ precursor. We have also examined cell cycle-enriched populations of S-180 ascites cells for the presence of poly(A)− actin mRNA. Results from these experiments indicate that cells in G1 phase of the cell cycle contain predominantly poly(A)+ actin mRNA, while the poly(A)− form is restricted to late-S and post-S phase Cells.
Role Conflict in Correctional Institutions

The divergent and often incompatible goals of treatment and custody within correctional organizations frequently result in ambiguous role expectations and role conflict among prison personnel. Hypotheses that role conflict is significantly greater among staff in treatment institutions than among staff in custodv institutions. Is significantly greater among treatment staff than among custody staff, and is significantly related to both job satisfaction and punitive attitudes toward inmates are tested with questionnaire data obtained from 336 treatment and custody personnel within 6 adult correctional facilities. Although the bivariate analyses provide support for each of the hypotheses, subsequent analyses indicate that role conflict is more likely to be the product of the organizational goals of the institution than of the treatment or custody staff positions within those institutions. These findings are related to previous analyses of the treatment-custody dilemma within institutions, and the implications for future research are discussed.
Clinical feasibility of using an EPID in CINE mode for image-guided verification of stereotactic body radiotherapy.

Purpose: To introduce a novel method for monitoring tumor location during stereotactic body radiotherapy (SBRT) while the treatment beam is on by using a conventional electronic portal imaging device (EPID). Methods and Materials: In our clinic, selected patients were treated under a phase I institutional review board– approved SBRT protocol for limited hepatic metastases from solid tumors. Before treatment planning multiple gold fiducial markers were implanted on the periphery of the tumor. During treatment the EPID was used in cine mode to collect the exit radiation and produce a sequence of images for each field. An in-house program was developed for calculating the location of the fiducials and their relative distance to the planned locations. Results: Three case studies illustrate the utility of the technique. Patient A exhibited a systematic shift of 4 mm during one of the treatment beams. Patient B showed an inferior drift of the target of approximately 1 cm from the time of setup to the end of the fraction. Patient C had a poor setup on the first day of treatment that was quantified and accounted for on subsequent treatment days. Conclusions: Target localization throughout each treatment beam can be quickly assessed with the presented technique. Treatment monitoring with an EPID in cine mode is shown to be a clinically feasible and useful tool. 2007 Elsevier Inc. SBRT, Respiratory motion, Organ motion, EPID.
Discovering ligands for a microRNA precursor with peptoid microarrays

We have screened peptoid microarrays to identify specific ligands for the RNA hairpin precursor of miR-21, a microRNA involved in cancer and heart disease. Microarrays were printed by spotting a library of 7680 N-substituted oligoglycines (peptoids) onto glass slides. Two compounds on the array specifically bind RNA having the sequence and predicted secondary structure of the miR-21 precursor hairpin and have specific affinity for the target in solution. Their binding induces a conformational change around the hairpin loop, and the most specific compound recognizes the loop sequence and a bulged uridine in the proximal duplex. Functional groups contributing affinity and specificity were identified, and by varying a critical methylpyridine group, a compound with a dissociation constant of 1.9 μM for the miR-21 precursor hairpin and a 20-fold discrimination against a closely-related hairpin was created. This work describes a systematic approach to discovery of ligands for specific pre-defined novel RNA structures. It demonstrates discovery of new ligands for an RNA for which no specific lead compounds were previously known by screening a microarray of small molecules.
Developmental upregulation of inducible hsp70 transcripts, but not the cognate form, during pupal diapause in the flesh fly, Sarcophaga crassipalpis

Partial clones of the Sarcophaga crassipalpis heat shock protein 70 (hsp70) and of heat shock cognate 70 (hsc70) were developed by RT-PCR and library screening respectively. These clones were used to probe total RNA northern blots for the expression of transcripts in response to high and low temperature stress and in conjunction with the entry into an overwintering pupal diapause. In nondiapausing individuals, hsp70 was highly expressed in response to a 40 degrees C heat shock, while hsc70 was unaffected by the heat stress. In contrast, both hsp70 and hsc70 were upregulated in nondiapausing flies following a -10 degrees C cold shock. In diapausing pupae, hsp70 was highly upregulated during diapause, even at a non-stress temperature of 20 degrees C. Upregulation was initiated at the onset of diapause and persisted throughout diapause. During diapause, heat shock did not further elevate the level of hsp70 expression. Within 12 h after diapause was terminated, hsp70 ceased to be expressed. The expression of hsc70 was unaltered by diapause. The developmental regulation of hsp70 in relation to diapause suggests a critical role for this stress protein during insect dormancy.
Spacing Chevrons on Horizontal Curves

The chevron alignment sign is an important traffic control device used to warn drivers of the severity of a curve by delineating the alignment of the road around that curve. FHWA's Manual on Uniform Traffic Control Devices for Streets and Highways provides the following guidance on the spacing of chevrons around a curve: "The Chevron Alignment sign should be spaced such that the road user always has at least two in view, until the change in alignment eliminates the need for the signs" and "the Chevrons should be visible for a sufficient distance to provide the road user with adequate time to react to the change in alignment." This guidance is broad to account for geometric design features and site obstructions such as steep vertical curvature or heavy vegetation. It also allows flexibility based on site characteristics and available funds, and the use of this verbiage creates a lower liability risk than there would be if a spacing chart were used. However, the broad wording allows for inconsistencies in the roadway system and provides little guidance for maintenance personnel. A field study was conducted to investigate the impacts of varying the number of chevrons in view around a curve. A spacing chart was then developed to simplify maintenance personnel's responsibility for choosing appropriate chevron spacing. The results of the field study indicated that having more than two chevrons in view around the curve provided a benefit in the form of a reduction in speed of about 3 mph at night. Smaller speed reductions were observed during daylight.
The Natural History of a Branch Duct Intraductal Papillary Mucinous Neoplasm in a Patient with Lady Windermere Syndrome: A Case Report

Context "Low-risk" branch duct intraductal papillary mucinous neoplasm (IPMN) is defined as pancreatic epithelial cellular proliferation of small branch ducts that lack malignant characteristics. At present, our understanding of the natural history of "low-risk" branch duct IPMN is still evolving. Lady Windermere syndrome is a disorder seen in non-smoking women with no pre-existing pulmonary disease affecting the lingula and/or right middle lobe with Mycobacterium avium-intracellulare complex. We present a case with pancreatic adenocarcinoma after a six-year surveillance of "low-risk" branch duct IPMN in an asymptomatic elderly white woman with Lady Windermere syndrome. Case report A 79-year-old woman was referred to our institution because of pancreatic cystic abnormalities and elevated carbohydrate antigen 19-9 (CA 19-9). While at our institution, she was also diagnosed with Lady Windermere syndrome. Multiple abdominal imaging studies, endoscopic retrograde cholangiopancreatography, computer tomography, and magnetic resonance cholangiopancreatography (MRCP) were performed in the ensuing 6 years, all consistent with "low-risk" branch duct IPMN. No progression was seen until year 6 when MRCP showed a 2 cm pancreatic cancer. Because of multiple comorbidities, the patient chose chemotherapy over a pancreaticoduodenectomy. She developed respiratory failure and died after one cycle of gemcitabine. Conclusions "Low-risk" branch duct IPMN may be a heterogeneous disease in which some cases can transform into malignant pancreatic neoplasms despite the absence of the so-called "high risk" features on imaging studies. Clinical management, therefore, requires individualized flexibility. In addition, when there is coexistence of Lady Windermere syndrome and pancreatic cancer, prompt diagnosis and treatment of Lady Windermere syndrome should be considered prior to chemoradiotherapy or surgery. Image: CA 19-9 level during follow-up of "low-risk" branch-duct IPMN.
A Brief History of Judging: From the Big Bang to Cosmic Constitutional Theory

Cosmic Constitutional Theory serves as a worthy embodiment of Judge Wilkinson’s quarter-century of minimalist jurisprudence on the Fourth Circuit, and offers salient and vigorous critiques of today’s most popular schools of constitutional thought. However, where the book falters is by failing to come to grips with the foundation of Judge Wilkinson’s own anti-jurisprudence.
Discussion of On-Line Monitoring Technique for High-Voltage SF_6 Circuit Breaker

The monitoring methods about SF6 pressure and water content,insulation performance and conductive loop’s connect status of high-voltage circuit breaker as well as the testing method for its mechanical performance are introduced.The shortcomings in terms of relevant parameters and performance testing of high-voltage circuit breaker are summarized,and the development prospect of on-line monitoring technology is analyzed.
The Readability of Online Patient Information About Mohs Micrographic Surgery.

BACKGROUNDMohs micrographic surgery has become increasingly used in the treatment of cutaneous malignancies over the past decade. Concurrently, more patients are using the Internet as a resource for medical information than ever before. The average American adult reads at an eighth grade level. The
The Private Sector Role in Offensive Cyber Operations: Benefits, Issues and Challenges

This paper explores the role that companies play in supporting offensive cyber operations. It finds that contractors play critical roles in two key functions: intelligence/reconnaissance and planning/mission support. The reliance of the U.S. military on cyber contractors brings both benefits and risks. Benefits include access to rapidly evolving technologies and the ability to obtain access to in-demand skills sets quickly and easily. Challenges fall into two categories: domestic policy and international relations. In the former case, the main issues are over-reliance on non-government personnel and challenges in oversight of cyber contractors, which could result in undesirable financial and strategic outcomes. Within the international arena, cyber contractors may affect the balance of power of states. The most likely outcome is that the use of contractors will exacerbate existing power discrepancies between developed and developing countries. However, it is possible that wealthy but less developed states could rely on private sector capability to quickly develop their cyber attack capabilities. Another issue that may affect international relations is uncertainty about the legal status of cyber contractors as combatants. A final concern surrounds the observation that companies may find themselves on both sides of a cyber operation. To accrue the benefits and address the challenges posed by contractor support to offensive cyber operations, several actions should be taken. There needs to be a public debate about the proper role of cyber contractors in military operations. Companies should have a voice in this debate due to their increasingly important role in cyberspace. In addition, the US government and international community must provide guidance to cyber contractors on the role that they should play in offensive cyber operations. Export controls are helpful but they are blunt tools that often bring heavy costs and do not always accomplish their desired outcomes. More precise direction is needed, most likely beginning with norms of behavior.
Aristotle on Making Other Selves

(1987). Aristotle on Making Other Selves. Canadian Journal of Philosophy: Vol. 17, No. 2, pp. 361-376.
Optical Screening for Rapid Antimicrobial Susceptibility Testing and for Observation of Phenotypic Diversity among Strains of the Genetically Clonal Species Bacillus anthracis.

ABSTRACT During high-impact events involving Bacillus anthracis, such as the Amerithrax incident of 2001 or the anthrax outbreaks in Russia and Sweden in 2016, critical decisions to reduce morbidity and mortality include rapid selection and distribution of effective antimicrobial agents for treatment and postexposure prophylaxis. Detection of antimicrobial resistance currently relies on a conventional broth microdilution method that requires a 16- to 20-h incubation time for B. anthracis. Advances in high-resolution optical screening offer a new technology to more rapidly evaluate antimicrobial susceptibility and to simultaneously assess the growth characteristics of an isolate. Herein, we describe a new method developed and evaluated as a rapid antimicrobial susceptibility test for B. anthracis. This method is based on automated digital time-lapse microscopy to observe the growth and morphological effects of relevant antibiotics with an optical screening instrument, the oCelloScope. B. anthracis strains were monitored over time in the presence or absence of penicillin, ciprofloxacin, or doxycycline. Susceptibility to each antibiotic was determined in ≤4 h, 75 to 80% less than the time required for conventional methods. Time-lapse video imaging compiled from the optical screening images revealed unexpected differences in growth characteristics among strains of B. anthracis, which is considered to be a clonal organism. This technology provides a new approach for rapidly detecting phenotypic antimicrobial resistance and for documenting growth attributes that may be beneficial in the further characterization of individual strains.
Electromagnetic pulse excitation of finite- and infinitely-long lossy conductors over a lossy ground plane

AbstractThis paper details a model for the response of a finite- or an infinite-length wire interacting with a conducting ground to an electromagnetic pulse excitation. We develop a frequency–domain method based on transmission line theory that we name ATLOG – Analytic Transmission Line Over Ground. This method is developed as an alternative to full-wave methods, as it delivers a fast and reliable solution. It allows for the treatment of finite or infinite lossy, coated wires, and lossy grounds. The cases of wire above ground, as well as resting on the ground and buried beneath the ground are treated. The reported method is general and the time response of the induced current is obtained using an inverse Fourier transform of the current in the frequency domain. The focus is on the characteristics and propagation of the transmission line mode. Comparisons with full-wave simulations strengthen the validity of the proposed method.
Bioinspired Magnetic Navigation Using Magnetic Signatures as Waypoints

Diverse taxa use Earth’s magnetic field in conjunction with other sensor modes to accomplish navigation tasks that range from local homing to long-distance migration across continents and ocean basins. However, despite extensive research, animal magnetoreception remains a poorly understood, and active research area. Concurrently, Earth’s magnetic field offers a signal that engineered systems can leverage for navigation and localization in environments where man-made systems such as GPS are either unavailable or unreliable. Using a proxy for Earth’s magnetic field, and inspired by migratory animal behavior, this work implements behavioral strategies to navigate through a series of magnetic waypoints. The strategies are able to navigate through a closed set of points, in some cases running through several “laps”. Successful trials were observed in both a range of environmental parameters, and varying levels of sensor noise. The study explores several of these parameter combinations in simulation, and presents preliminary results from a version of the strategy implemented on a mobile robot platform. Alongside success, limitations of the simulated and hardware algorithms are discussed. The results illustrate the feasibility of either an animal, or engineered platform to use a set of waypoints based on the magnetic field to navigate. Additionally, the work presents an engineering/quantitative biology approach that can garner insight into animal behavior while simultaneously illuminating paths of development for engineered algorithms and systems.
Band warping, band non-parabolicity, and Dirac points in electronic and lattice structures

Abstract We illustrate at a fundamental level the physical and mathematical origins of band warping and band non-parabolicity in electronic and vibrational structures. We point out a robust presence of pairs of topologically induced Dirac points in a primitive-rectangular lattice using a p -type tight-binding approximation. We analyze two-dimensional primitive-rectangular and square Bravais lattices with implications that are expected to generalize to more complex structures. Band warping is shown to arise at the onset of a singular transition to a crystal lattice with a larger symmetry group, which allows the possibility of irreducible representations of higher dimensions, hence band degeneracy, at special symmetry points in reciprocal space. Band warping is incompatible with a multi-dimensional Taylor series expansion, whereas band non-parabolicities are associated with multi-dimensional Taylor series expansions to all orders. Still band non-parabolicities may merge into band warping at the onset of a larger symmetry group. Remarkably, while still maintaining a clear connection with that merging, band non-parabolicities may produce pairs of conical intersections at relatively low-symmetry points. Apparently, such conical intersections are robustly maintained by global topology requirements, rather than any local symmetry protection. For two p -type tight-binding bands, we find such pairs of conical intersections drifting along the edges of restricted Brillouin zones of primitive-rectangular Bravais lattices as lattice constants vary relatively to each other, until these conical intersections merge into degenerate warped bands at high-symmetry points at the onset of a square lattice. The conical intersections that we found appear to have similar topological characteristics as Dirac points extensively studied in graphene and other topological insulators, even though our conical intersections have none of the symmetry complexity and protection afforded by the latter more complex structures.
Membrane Fusion in Relation to Sperm-Egg Association

Publisher Summary This chapter describes the relationship between membrane fusion and sperm–egg association. At the inception of the zygote, the external rather than the cytoplasmic sides of the plasma membranes are the first to be involved. In species with vitelline envelopes, the meeting of plasma membranes takes place beneath the envelope so that a part of the egg plasma membrane that meets the sperm plasma membrane is in a sense also a newly exposed surface. However, in algae, the gametes are recently shed cells so that both membranes are newly exposed ones. The parts of the plasma membrane that begin the fusion are newly exposed exterior surfaces. As a result of the fusion, the content of the vesicle is conducted out of the cell without coming in contact with the cytoplasm.
Are They Celebrity Followers? Examining the Third-Person Perception of Celebrity-Endorsed Advertising

ABSTRACTThis study explored how consumers' presumed influences mediated the impacts of source credibility and advertising skepticism on purchase intention in the context of celebrity-endorsed advertising (CEA). A national media consumer panel (N = 445) indicated the third-person perception (TPP) were positively correlated to celebrity expertise and attractiveness, but negatively influenced by advertising skepticism. Moreover, three celebrity credibility variables and advertising skepticism yielded direct effects on purchase intention. Indirect effects by the TPP were also generated on purchase intention. The TPP would mediate the impacts of celebrity credibility and advertising skepticism on purchase intention in response to various desirable/undesirable endorsers. Moreover, the TPP would decrease the impact of celebrity credibility, but increase the impact of advertising skepticism on purchase intention, indicating that the third persons' attitudes toward CEA may become a key reference in consumers' purc...
Constrained Regression Estimates of Technology Effects on Fuel Economy

Practical aspects of linear regression modeling are reviewed, explicitly incorporating knowledge about the signs and ordering of the regression parameters. Statistical properties of equality and inequality constrained estimators are presented. This co..
The Life Cycle of the Uterine Fibroid Myocyte

Uterine fibroids are common benign tumors of women in the USA and worldwide, yet the biological nature and pathogenesis of these tumors remain largely unknown. This review presents our view of the stages in the life cycle of a subset of uterine fibroid myocytes, introduces hypothetical concepts and morphological data to explain these changes, and relates these changes in individual myocytes to the phases of fibroid tumor development. The observations gained from light and electron microscopic, immunohistochemical, and morphometric studies in our laboratory have led to the hypothesis that fibroid changes over time may relate to the excessive production of collagen by phenotypically transformed myocytes. This accumulation of collagen results in decreased microvessel density, followed by myocyte injury and atrophy, with eventual senescence and involution through ischemic cellular degeneration and inanition. Uterine leiomyomas, or fibroids, are characterized by two histologic features—proliferation of myocytes and production of an extracellular collagenous matrix. In the larger tumors, the collagenous matrix is often abundant. Within those regions in which the accumulating collagen is excessive, the myocytes are progressively separated from their blood supply, resulting in myocyte atrophy and eventually cell death. It is within these hypocellular, hyalinized areas that the complete lifecycle of the fibroid myocyte is realized. It begins with the phenotypic transformation of a contractile cell to one characterized by proliferation and collagen synthesis, progresses through an intermediate stage of atrophy related to interstitial ischemia, and eventuates in cell death due to inanition. Lastly, resorption of inanotic cells appears to occur by a non-phagocytic, presumably enzymatic process of degradation and recycling that we refer to as reclamation.
Transfer Operators on L1 and L2

Given a transfer operator (R, σ), it is of interest to find the measures μ such that both R and σ induce operators in the corresponding L p spaces, i.e., in \(L^p(X, {\mathcal B}, \mu )\). We turn to this below, but our main concern are the cases p = 1, p = 2, and p = ∞. When R is realized as an operator in \(L^2(X, {\mathcal B}, \mu )\), for a suitable choice of μ, then it is natural to ask for the adjoint operator R∗ where “adjoint” is defined with respect to the L2(μ)-inner product.
Physiological principles of electrical stimulation

Electrical energy is applied to living tissue in a number of procedures for diagnosis, therapy, or functional restoration. Biological responses depend on the nature of the tissue and characteristics of the applied stimulus. An ionic internal environment and the presence of semipermeable cellular membranes result in charge separation and intrinsic electrical fields in the body. These fields can be manipulated by electronically generated electrical stimuli. This chapter discusses the physiological basis of excitable body tissues and electrical stimulation in the context of neuroprosthetics. It begins with an overview of target tissues at macro- and microscopic levels and functional aspects of biochemistry and biophysics of excitable tissues. It later covers electrical activation of nerve and muscle tissue and interactive aspects of stimulation electrodes.
The Theory of Fluid and Crystallized Intelligence in Relation to Concepts of Cognitive Psychology and Aging in Adulthood

The principal purpose of this chapter is to lay out some of the major results and conclusions of a series of studies conducted by this investigator and his coworkers (principally Donaldson, Engstrom, and Mason) over the last few years. To comprehend these results and conclusions it is necessary to have some appreciation of the theory and assumptions on which the research has been based. These ideas are not major themes in the research and theory of mainstream cognitive developmental psychology. It is probably worthwhile, therefore, to sketch at the outset some features of the research that is to be reviewed.
Pesticide interactions in higher plants

Simultaneous or sequential applications of herbicides, fungicides, and insecticides are common in the production of many food and fiber crops. Whenever feasible, growers or commercial applicators choose to apply combinations of chemicals for obvious economic reasons. The fewer trips across the field, the less the expenditure of labor and equipment. In addition, combinations of chemicals frequently improve the spectrum of plant pests that is controlled.
Child Abduction: Aged-Based Analyses of Offender, Victim, and Offense Characteristics in 550 Cases of Alleged Child Disappearance

Crimes against children, particularly cases involving abduction and/or homicide, continue to be problematic as both a social phenomenon and judicial responsibility. Such cases routinely receive immense community and media attention and rapidly overwhelm investigative resources. Research in the area of childhood victimization, however, has only recently gained national prominence. While numerous studies on child abuse and neglect have been conducted, research on child abduction and homicide remains scant. Previous studies examining child abduction suffer from limited geographical scope or fail to base predictive analyses on victim characteristics. The current study reports the results of a nationally representative sample (47 states, the District of Columbia, and Puerto Rico) of 550 cases of alleged child abduction obtained from Federal Bureau of Investigation files for the period 1985 through 1995. Study results demonstrate that both offender and offense characteristics vary significantly according to victim age, gender, and race. Such differences appear critical to crime reconstruction, criminal profiling, and investigative resolution. Additionally, these data suggest that current child abduction prevention programs may emphasize inaccurate offender traits.
The Importance of Solvent Effects on the Mechanism of the Pfeiffer Effect

The Pfeiffer effect is observed when an optically active compound such as an amino acid is introduced to a solution containing a labile racemic metal complex, and an equilibrium shift is obtained. The “perturbation” results in an excess of one enantiomer over the other. The shift is a result of a preferential outer sphere interaction between the introduced chiral species and one enantiomeric form (Λ or ∆) of a labile metal complex. Speculations regarding the mechanism of the Pfeiffer effect have attributed observations to a singular factor such as pH, solvent polarity, or numerous other intermolecular interactions. Through the use of the lanthanide(III) complexes [Tb(DPA)3]3− and [Eu(DPA)3]3− (where DPA = 2,6-pyridinedicarboxylate) and the amino acids l-serine and l-proline; it is becoming clear that the mechanism is not so simply described as per the preliminary findings that are discussed in this study. It appears that the true mechanism is far more complicated than the attribute just a singular factor. This work attempts to shine light on the fact that understanding the behavior of the solvent environment may hypothetically be the key to offering a more detailed description of the mechanism.
Trauma-Informed Knowledge and Practices in School Psychology: A Pilot Study and Review

Growing acknowledgement that adverse childhood experiences are widespread and can threaten healthy development has led to advocacy for schools to systematically incorporate trauma-sensitive practic...
Small Molecule SOS1 Agonists Modulate MAPK and PI3K Signaling via Independent Cellular Responses

Activating mutations in RAS can lead to oncogenesis by enhancing downstream signaling, such as through the MAPK and PI3K pathways. Therefore, therapeutically targeting RAS may perturb multiple signaling pathways simultaneously. One method for modulating RAS signaling is to target the activity of the guanine nucleotide exchange factor SOS1. Our laboratory has discovered compounds that bind to SOS1 and activate RAS. Interestingly, these SOS1 agonist compounds elicit biphasic modulation of ERK phosphorylation and simultaneous inhibition of AKT phosphorylation levels. Here, we utilized multiple chemically distinct compounds to elucidate whether these effects on MAPK and PI3K signaling by SOS1 agonists were mechanistically linked. In addition, we used CRISPR/Cas9 gene-editing to generate clonally derived SOS1 knockout cells and identified a potent SOS1 agonist that rapidly elicited on-target molecular effects at substantially lower concentrations than those causing off-target effects. Our findings will allow u...
Strategies for developing and optimizing cancer vaccines

With the spotlight on cancer immunotherapy and the expanding use of immune checkpoint inhibitors, strategies to improve the response rate and duration of current cancer immunotherapeutics are highly sought. In that sense, investigators around the globe have been putting spurs on the development of effective cancer vaccines in humans after decades of efforts that led to limited clinical success. In more than three decades of research in pursuit of targeted and personalized immunotherapy, several platforms have been incorporated into the list of cancer vaccines from live viral or bacterial agents harboring antigens to synthetic peptides with the hope of stronger and durable immune responses that will tackle cancers better. Unlike adoptive cell therapy, cancer vaccines can take advantage of using a patient’s entire immune system that can include more than engineered receptors or ligands in developing antigen-specific responses. Advances in molecular technology also secured the use of genetically modified genes or proteins of interest to enhance the chance of stronger immune responses. The formulation of vaccines to increase chances of immune recognition such as nanoparticles for peptide delivery is another area of great interest. Studies indicate that cancer vaccines alone may elicit tumor-specific cellular or humoral responses in immunologic assays and even regression or shrinkage of the cancer in select trials, but novel strategies, especially in combination with other cancer therapies, are under study and are likely to be critical to achieve and optimize reliable objective responses and survival benefit. In this review, cancer vaccine platforms with different approaches to deliver tumor antigens and boost immunity are discussed with the intention of summarizing what we know and what we need to improve in the clinical trial setting.
Stretched Earlobe Piercings Negatively Impact Casual Observer Perceptions.

Patients with stretched earlobes seek reconstruction to mitigate social stigma. To date, there have been no studies measuring the impact of stretched earlobe piercings on casual observer perceptions. One-hundred seventy-three casual observers were enrolled via public-access web sites. Participants were randomly shown frontal and profile views of six subjects with stretched earlobe piercings and four controls. Participants evaluated photos for first impressions using a survey containing choices regarding personal attributes. Latent class analysis was performed to categorize observer ratings. Analysis of variance (ANOVA), bootstrap analysis, and permutations testing were used to evaluate the relationship between perceived attractiveness, success, and approachability scoring and stretched earlobe status. Latent class analysis categorized responses into three classes: positive, negative, and neutral. Patients with stretched earlobe piercings were significantly less likely to be classified as positive by observers without body modifications (i.e., tattoos and piercings) in comparison to control photos (30.9 and 40.1%, p = 0.007) and more likely to be classified as negative (38.5 and 28.1%, p = 0.002). These changes were abolished when photos were evaluated by observers with body modifications (p > 0.05). ANOVA revealed that stretched earlobe piercings and observer body modification status have a significant effect on rated approachability (F [1,1726] = 4.08, p = 0.04) and successfulness (F[1,1726] = 9.67, p = 0.002; F [1,1726] = 70.33, p 0.05). Patients with stretched earlobe piercings were more likely to be classified as having negative affect display and being less approachable and successful compared with controls when evaluated by observers without body modifications. This effect was abolished when photos were evaluated by observers with body modifications. These findings validate patient motivations for seeking stretched earlobe repair.
Noise-tolerant instance-based learning algorithms

Several published reports show that instancebased learning algorithms yield high classification accuracies and have low storage requirements during supervised learning applications. However, these learning algorithms are highly sensitive to noisy training instances. This paper describes a simple extension of instancebased learning algorithms for detecting and removing noisy instances from concept descriptions. This extension requires evidence that saved instances be significantly good classifiers before it allows them to be used for subsequent classification tasks. We show that this extension's performance degrades more slowly in the presence of noise, improves classification accuracies, and further reduces storage requirements in several artificial and real-world database applications.
Germline-Specific Repetitive Elements in Programmatically Eliminated Chromosomes of the Sea Lamprey (Petromyzon marinus)

The sea lamprey (Petromyzon marinus) is one of few vertebrate species known to reproducibly eliminate large fractions of its genome during normal embryonic development. This germline-specific DNA is lost in the form of large fragments, including entire chromosomes, and available evidence suggests that DNA elimination acts as a permanent silencing mechanism that prevents the somatic expression of a specific subset of “germline” genes. However, reconstruction of eliminated regions has proven to be challenging due to the complexity of the lamprey karyotype. We applied an integrative approach aimed at further characterization of the large-scale structure of eliminated segments, including: (1) in silico identification of germline-enriched repeats; (2) mapping the chromosomal location of specific repetitive sequences in germline metaphases; and (3) 3D DNA/DNA-hybridization to embryonic lagging anaphases, which permitted us to both verify the specificity of elements to physically eliminated chromosomes and characterize the subcellular organization of these elements during elimination. This approach resulted in the discovery of several repetitive elements that are found exclusively on the eliminated chromosomes, which subsequently permitted the identification of 12 individual chromosomes that are programmatically eliminated during early embryogenesis. The fidelity and specificity of these highly abundant sequences, their distinctive patterning in eliminated chromosomes, and subcellular localization in elimination anaphases suggest that these sequences might contribute to the specific targeting of chromosomes for elimination or possibly in molecular interactions that mediate their decelerated poleward movement in chromosome elimination anaphases, isolation into micronuclei and eventual degradation.
Is Coding a Relevant Metaphor for Building AI

Brette contends that the neural coding metaphor is an invalid basis for theories of what the brain does. Here, we argue that it is an insufficient guide for building an artificial intelligence that learns to accomplish short- and long-term goals in a complex, changing environment.
Planning the Production

The planning process is always much more time consuming than the actual production process. In fact, some have stated that 99% of a producer's time is spent planning or in pre-production, leaving 1% for the actual production process.
Excretion, Mass Balance, and Metabolism of [14C]LY3202626 in Humans: An Interplay of Microbial Reduction, Reabsorption, and Aldehyde Oxidase Oxidation That Leads to an Extended Excretion Profile

The mass balance, excretion, and metabolism of LY3202626 were determined in healthy subjects after oral administration of a single dose of 10 mg of (approximately 100 μCi) [14C]LY3202626. Excretion of radioactivity was slow and incomplete, with approximately 75% of the dose recovered after 504 hours of sample collection. The mean total recovery of the radioactive dose was 31% and 44% in the feces and urine, respectively. Because of low plasma total radioactivity, plasma metabolite profiling was conducted by accelerator mass spectrometry. Metabolism of LY3202626 occurred primarily via O-demethylation (M2) and amide hydrolysis (M1, M3, M4, and M5). Overall, parent drug, M1, M2, and M4 were the largest circulating components in plasma, and M2 and M4 were the predominant excretory metabolites. The slow elimination of total radioactivity was proposed to result from an unusual enterohepatic recirculation pathway involving microbial reduction of metabolite M2 to M16 in the gut and reabsorption of M16, followed by hepatic oxidation of M16 back to M2. Supporting in vitro experiments showed that M2 is reduced to M16 anaerobically in fecal homogenate and that M16 is oxidized in the liver by aldehyde oxidase to M2. LY3202626 also showed a potential to form a reactive sulfenic acid intermediate. A portion of plasma radioactivity was unextractable and presumably bound covalently to plasma proteins. In vitro incubation of LY3202626 in human liver microsomes in the presence of NADPH with dimedone as a trapping agent implicated the formation of the proposed sulfenic acid intermediate. SIGNIFICANCE STATEMENT The excretion of radioactivity in humans after oral administration of a single dose of 10 mg of [14C]LY3202626 was very slow. The results from in vitro experiments suggested that an interplay between microbial reduction, reabsorption, and aldehyde oxidase oxidation (M2 → M16 → M2) could be a reason for extended radioactivity excretion profile. In vitro metabolism also showed that LY3202626 has the potential to form a reactive sulfenic acid intermediate that could potentially covalently bind to plasma protein and result in the observed unextractable radioactivity from plasma.
The efficacy of first-line chemotherapy in endocrine-resistant hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer.

Combinations of endocrine therapy (ET) and targeted therapy (CDK4/6 or mTOR inhibitors) are standard of care for HR+/HER2− metastatic breast cancer (MBC). When ET is not effective, chemotherapy is commonly used. However, clinical outcomes of chemotherapy in the endocrine-resistant setting are limited. The purpose of this study was to identify predictive factors and the compare efficacies of chemotherapy agents in endocrine-resistant MBC. We conducted a retrospective study of patients with HR+/HER2− MBC who received chemotherapy after progression on ET with or without targeted therapy at MD Anderson Cancer Center from 1999 to 2017. We collected baseline clinicopathological and all treatment data. Primary endpoint was time to treatment failure (TTF) of first-line chemotherapy for MBC. For the 1258 patients analyzed, mean age was 55.3 years (range 21–91). Previous treatment with targeted therapy was recorded for 390 patients (31%): 264 with CDK4/6 inhibitor, 205 with mTOR inhibitor, and 79 treated with both. The most frequent chemotherapy agents were capecitabine (48.9%) and taxanes (28.6%). After adjustment for all factors in a multivariate model, previous treatment with a CDK4/6 inhibitor had the strongest negative effect on TTF regardless of ET duration (hazard ratio [HR] 1.84; 95%CI 1.49–2.27; p < 0.001). Conversely, capecitabine had significantly longer median TTF than taxanes regardless of whether patients had prior exposure to taxanes in primary setting (6.1 vs 4.9 months; HR 0.64; 95%CI 0.55–0.75; p < 0.001). Previous exposure to CDK4/6 inhibitor had a negative predictive effect for the efficacy of chemotherapy. Capecitabine had the best efficacy against endocrine-resistant breast cancer.
Creating an Agile Hardware Design Flow

Although an agile approach is standard for software design, how to properly adapt this method to hardware is still an open question. This work addresses this question while building a system on chip (SoC) with specialized accelerators. Rather than using a traditional waterfall design flow, which starts by studying the application to be accelerated, we begin by constructing a complete flow from an application expressed in a high-level domain-specific language (DSL), in our case Halide, to a generic coarse-grained reconfigurable array (CGRA). As our under-standing of the application grows, the CGRA design evolves, and we have developed a suite of tools that tune application code, the compiler, and the CGRA to increase the efficiency of the resulting implementation. To meet our continued need to update parts of the system while maintaining the end-to-end flow, we have created DSL-based hardware generators that not only provide the Verilog needed for the implementation of the CGRA, but also create the collateral that the compiler/mapper/place and route system needs to configure its operation. This work provides a systematic approach for desiging and evolving high-performance and energy-efficient hardware-software systems for any application domain.
Comment on 'effects of acetaminophen on risk taking'.

The article by Keaveney et al. entitled 'Effects of acetaminophen on risk taking' was published in July of 2020 and concluded that using acetaminophen increased risk-taking behaviors, potentially by reducing perceived risk. We believe that there is not enough data to support the generalization of this association and feel that the conclusions were presented without acknowledgement of the limitations of this study. Media articles often further dramatized these findings, presenting the potential correlation between acetaminophen and risk taking as fact. It is unfair to readers to sensationalize the associations seen in controlled experiments in an attempt to generalize the study's findings. As scientists, we need to assure that the discussions and conclusions presented in publications appropriately highlight the limitations of studies. We must also work to assure that the public does not sensationalize preliminary and limited research results.