cssi/SciSciGPT-SciSciNet huggingface dataset:
Expanding constructions of elder abuse and neglect: older mothers' subjective experiences

This study examines elder abuse within the broader framework of parenting in later life and focuses on the experience of mothers with "difficult" adult children. The sample is low-income and minority older women (>62). Using constructive grounded theory, the analysis reveals that the women's lens as mothers informs their explanations for not being able to take action to limit their adult children's difficult/abusive behaviors. The author suggests the utility of incorporating a feminist framework that highlights adult child-to-mother violence as a means of increasing self-reporting of elder abuse and older women's willingness to accept services.
Abstract W P99: A Time Window of Heightened Plasticity to Training After Ischemic Stroke in the Mouse is Extended By Fluoxetine if Provided Within the First Week After Stroke

Background: and purpose - Data in humans and in non-human animal models suggest that most recovery from motor impairment occurs in the first 4 weeks after stroke and is mediated in part by increased responsiveness to training in this short time period. We tested the hypothesis that there is a gradient of diminishing responsiveness to training in the first week after stroke in the mouse. We then tested whether fluoxetine can extend the time window over which large training-related gains can be expected. Methods: Adult C57Bl/6 mice were trained to perform a skilled prehension task to an asymptotic level of performance after which they underwent photocoagulation-induced stroke or sham stroke in the caudal forelimb area (CFA can be considered rodent primary motor cortex). The mice were then retrained after a 1- or 7-day delay in the presence or absence of fluoxetine injected IP daily beginning after a 1- or 7-day delay. Results: Training-associated recovery of prehension was complete if training was initiated after a 1-day delay but incomplete if training was initiated after a 7-day delay, even with additional training days. Daily fluoxetine administration after stroke was associated with complete recovery of prehension even if training was delayed 7 days but only if fluoxetine was administered beginning 1 day but not 7 days after stroke. Conclusions: We conclude that there is a sensitive period 7 days after stroke during which motor training is more likely to promote recovery and that this period can be extended by fluoxetine only if administration begins during the first week after stroke. Our mouse model, with all of the attendant genetic benefits, may allow us to determine at the cellular and molecular level how behavioral training and endogenous plasticity interact to mediate recovery.
Technology Integration in Elementary Classrooms: Teaching Practices of Student Teachers.

This study examines how and why student teachers integrated technology to enhance instruction in elementary classrooms. The participants were 31 student teachers who completed an assignment of eight weeks. Multiple data sets including observation notes of 347 lessons were obtained from three key groups for data triangulation. Results reveal that the primary technological means used to enhance teaching was to provide visuals for attention, engagement and interaction. All participants chose to integrate technology but varied substantially in their teaching practices. They applied technology for a number of reasons: student engagement, time management, motivation and meeting individual students' needs. Variables such as influence of mentor teachers, technology access, skills, pedagogical competence and personal attitudes had an impact on their application. While most of them followed their mentor's practices, some student teachers took initiative and made contributions to their mentors' professional development in technology integration. Implications on teacher preparation programs are discussed.
Abstract 2173: Negative transcriptional regulation of the human type III TGFβ receptor in ccRCC

Renal cell carcinoma (RCC) accounts for 3% of all malignancies reported each year making it the sixth leading cause of cancer death in the United States. Within this year more than 50,000 individuals will be diagnosed with RCC and around 12,000 will die from this disease. Out of these RCCs the most frequently diagnosed form is clear cell renal cell carcinoma (ccRCC) which accounts for approximately 80% of all RCCs. We have previously identified through genomic profiling that loss of the type II and III TGFβ receptors in the progression of this disease lead to loss of TGFβ responsiveness and suggests a role for dysregulated TGFβ signaling in RCC progression and metastasis. Restoration of the TGFβ receptor type III (TβRIII) leads to apoptosis in RCC cell lines (Margulis et al. 2007) suggesting that re-expression of TβRIII is an attractive method for intervention of ccRCC. Recently we identified that loss of TβRIII is an early event in ccRCC and that this loss is not through epigenetic silencing but due to the loss of transcriptional regulation. The transcription factor GATA3 was identified to be a positive regulator of TβRIII expression through its actions on the proximal promoter of TβRIII. Through deletion analysis we have now identified a region within the proximal promoter that contains a number of putative transcription factor binding sites that are capable of negatively regulating the expression of TβRIII. We have identified that one of these transcription factors is over-expressed in ccRCC patient matched renal tissue samples and that silencing of this transcription factor through lentiviral shRNA, leads to a three fold induction of endogenous TβRIII in ccRCC cell lines. Furthermore, loss of this transcription factor in ccRCC cell lines leads to decreased cell proliferation when compared to non-target infected controls. Further evaluation of these putative negatively regulating transcription factors and their actions upon the proximal promoter of TβRIII are being analyzed utilizing EMSA and ChIP assays. These investigations will identify novel molecular targets that through their dysregulation will have the potential to up-regulate TβRIII in ccRCC inducing apoptosis within these cells. Together these findings will allow for a deeper molecular understanding of the events taking place in ccRCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2173. doi:10.1158/1538-7445.AM2011-2173
Abstract 1844: CD43 normally expressed on the surface of leukocytes is expressed in the cytoplasm and nucleus of breast cancer and is a novel therapeutic target

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL One in eight of the female population of the United States will be diagnosed with breast cancer in their lifetime. This statistic defines breast cancer as the most common cancer affecting American women. Advances in breast cancer treatment will be facilitated by the identification and targeting of the causative molecular defects. We have found that breast cancer is characterized by expression of CD43. This sialoglycoprotein is normally only produced by leukocytes. Strikingly, an N-terminal domain of CD43 that is extracellular in leukocytes is expressed predominantly in the cytoplasm of breast cancers. The C-terminal domain that is expressed in the nucleus of leukocytes only upon activation exhibits constitutive nuclear localization in breast cancer. Segregation of the N and C terminal domains of CD43 between different subcelluar compartments suggests that in breast cancer it is subjected to specific proteolytic cleavage events. The normal function of CD43 is to regulate leukocyte adhesion, apoptosis and migration. We reasoned that if these normal functions are extrapolated to breast cancer, then CD43 could contribute to disease progression and, therefore, represent a novel therapeutic target. We tested this hypothesis by using small-interfering RNA to target CD43 expressed by the breast cancer cell line MCF7. This targeting resulted in cancer cells exhibiting increased susceptibility to apoptosis and increased vulnerability to lysis by natural killer cells. In addition, targeting demonstrated that CD43 likely facilitates metastasis by inhibiting homotypic adhesion and driving transendothelial migration. Using an othrotopic mouse model, we demonstrate that CD43-targeting reduces the size of primary tumors by 76%. Taken together, our results indicate that expression of CD43 is a robust breast cancer biomarker and its targeting has the potential to be developed into a new breast cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1844. doi:1538-7445.AM2012-1844
Potassium currents in octopus cells of the mammalian cochlear nucleus.

Octopus cells in the posteroventral cochlear nucleus (PVCN) of mammals are biophysically specialized to detect coincident firing in the population of auditory nerve fibers that provide their synapt...
Nucleotide Excision Repair Genes from the Yeast Saccharomyces Cerevisiae

The genetics of nucleotide excision repair in the yeast Saccharomyces cerevisiae is complex, apparently requiring at least 10 genes. We have isolated 5 of these genes (designated RAD1, RAD2, RAD3, RAD4, and RAD1O) by molecular cloning and plan to overexpress them in order to generate proteins for biochemical study. We have sequenced four of these five genes and have noted regions of homology with other proteins in the predicted amino acid sequence of some of them. In particular, there is striking homology between Rad3 protein and a number of prokaryotic and eukaryotic proteins that bind nucleotides and hydrolyze ATP or GTP. Mutations in this region of the RAD3 gene render cells defective in the nucleotide excision repair function. In addition to its role in nucleotide excision repair, the RAD3 gene is essential for the viability of haploid cells in the absence of DNA damage. The nature of the essential function is unknown. The RAD1 and RAD3 genes are not inducible by DNA damaging agents. However, exposure of cells to UV radiation, 4-nitroquinoline 1-oxide, or γ radiation results in 4- to 6-fold enhanced expression of the RAD2 gene.
Reliability and Validity of 3 Methods of Assessing Orthopedic Resident Skill in Shoulder Surgery

Objective Traditional measures for evaluating resident surgical technical skills (e.g., case logs) assess operative volume but not level of surgical proficiency. Our goal was to compare the reliability and validity of 3 tools for measuring surgical skill among orthopedic residents when performing 3 open surgical approaches to the shoulder. Methods A total of 23 residents at different stages of their surgical training were tested for technical skill pertaining to 3 shoulder surgical approaches using the following measures: Objective Structured Assessment of Technical Skills (OSATS) checklists, the Global Rating Scale (GRS), and a final pass/fail assessment determined by 3 upper extremity surgeons. Adverse events were recorded. The Cronbach α coefficient was used to assess reliability of the OSATS checklists and GRS scores. Interrater reliability was calculated with intraclass correlation coefficients. Correlations among OSATS checklist scores, GRS scores, and pass/fail assessment were calculated with Spearman ρ . Validity of OSATS checklists was determined using analysis of variance with postgraduate year (PGY) as a between-subjects factor. Significance was set at p Results Criterion validity was shown between the OSATS checklists and GRS for the 3 open shoulder approaches. Checklist scores showed superior interrater reliability compared with GRS and subjective pass/fail measurements. GRS scores were positively correlated across training years. The incidence of adverse events was significantly higher among PGY-1 and PGY-2 residents compared with more experienced residents. Conclusion OSATS checklists are a valid and reliable assessment of technical skills across 3 surgical shoulder approaches. However, checklist scores do not measure quality of technique. Documenting adverse events is necessary to assess quality of technique and ultimate pass/fail status. Multiple methods of assessing surgical skill should be considered when evaluating orthopedic resident surgical performance.
Bioenergetic Insufficiencies Due to Metabolic Alterations Regulated by the Inhibitory Receptor PD-1 Are an Early Driver of CD8+ T Cell Exhaustion

Summary Dynamic reprogramming of metabolism is essential for T cell effector function and memory formation. However, the regulation of metabolism in exhausted CD8 + T (Tex) cells is poorly understood. We found that during the first week of chronic lymphocytic choriomeningitis virus (LCMV) infection, before severe dysfunction develops, virus-specific CD8 + T cells were already unable to match the bioenergetics of effector T cells generated during acute infection. Suppression of T cell bioenergetics involved restricted glucose uptake and use, despite persisting mechanistic target of rapamycin (mTOR) signaling and upregulation of many anabolic pathways. PD-1 regulated early glycolytic and mitochondrial alterations and repressed transcriptional coactivator PGC-1α. Improving bioenergetics by overexpression of PGC-1α enhanced function in developing Tex cells. Therapeutic reinvigoration by anti-PD-L1 reprogrammed metabolism in a subset of Tex cells. These data highlight a key metabolic control event early in exhaustion and suggest that manipulating glycolytic and mitochondrial metabolism might enhance checkpoint blockade outcomes.
Photodynamic Therapy for Non-Melanoma Skin Cancers

Non-melanoma skin cancer (NMSC) is traditionally treated with surgical excision. Nonsurgical methods such as cryotherapy and topical chemotherapeutics, amongst other treatments, are other options. Actinic keratosis (AKs) are considered precancerous lesions that eventually may progress to squamous cell carcinoma (SCC). Photodynamic therapy (PDT) offers an effective treatment for AKs, and is also effective for superficial basal cell carcinoma (BCC). Nodular BCC and Bowen's disease (SCC in situ) have shown acceptable response rates with PDT, although recurrence rates are higher for these two NMSC subtypes. Methylaminolevulinate (MAL) PDT is a more effective treatment option than 5-aminolevulinic acid (ALA) PDT for nodular BCC. Several studies have shown that PDT results in superior cosmetic outcomes compared to surgical treatment. PDT is overall well-tolerated, with pain being the most common side effect.
Cerebral Blood Flow Autoregulation in Sepsis for the Intensivist Why Its Monitoring May Be the Future of Individualized Care

Cerebral blood flow (CBF) autoregulation maintains consistent blood flow across a range of blood pressures (BPs). Sepsis is a common cause of systemic hypotension and cerebral dysfunction. Guidelines for BP management in sepsis are based on historical concepts of CBF autoregulation that have now evolved with the availability of more precise technology for its measurement. In this article, we provide a narrative review of methods of monitoring CBF autoregulation, the cerebral effects of sepsis, and the current knowledge of CBF autoregulation in sepsis. Current guidelines for BP management in sepsis are based on a goal of maintaining mean arterial pressure (MAP) above the lower limit of CBF autoregulation. Bedside tools are now available to monitor CBF autoregulation continuously. These data reveal that individual BP goals determined from CBF autoregulation monitoring are more variable than previously expected. In patients undergoing cardiac surgery with cardiopulmonary bypass, for example, the lower limit of autoregulation varied between a MAP of 40 to 90 mm Hg. Studies of CBF autoregulation in sepsis suggest patients frequently manifest impaired CBF autoregulation, possibly a result of BP below the lower limit of autoregulation, particularly in early sepsis or with sepsis-associated encephalopathy. This suggests that the present consensus guidelines for BP management in sepsis may expose some patients to both cerebral hypoperfusion and cerebral hyperperfusion, potentially resulting in damage to brain parenchyma. The future use of novel techniques to study and clinically monitor CBF autoregulation could provide insight into the cerebral pathophysiology of sepsis and offer more precise treatments that may improve functional and cognitive outcomes for survivors of sepsis.
The role of pulse repetition frequency in ultrasonic contrast agent stability and cell death

Ultrasound exposure of phagocytic cells with contrast agent microbubbles attached can cause cell death. The influence of pulse repetition frequency (PRF) on the occurrence of such cell death was studied. Phagocytic cells of mouse macrophage cell line RAW-264.7 were grown as monolayers on thin Mylar sheets by standard culture methods. These cells retain contrast agent when incubated with 5% Optison/sup /spl reg// (Amersham Health, Princeton NJ) for 15 minutes and then rinsed to remove unattached microbubbles. A sealed chamber was formed with a second thin sheet placed 1 mm from the first sheet containing cells. Focused ultrasound exposures were implemented at a frequency of 2.25 MHz with 46 cycle pulses and PRF's of 1 kHz, 100 Hz, 10 Hz, 1 Hz, and 0.1 Hz. All ultrasound exposures were performed with a peak rarefactional pressure of 2 MPa in a degassed water bath. A 1 MHz receiver transducer measured the scattered signal from the monolayer containing cells and contrast agent. The signals were captured using a high speed digitizing board and range gated from within the chamber. The frequency spectrum was then computed and normalized to a control spectrum from linear scatterers (Zerdine/sup TM/, CIRS, Norfolk, VA). Photomicrographs of the cell monolayer were made in the ultrasound beam area before and after exposure, and a dye exclusion test (Trypan Blue) was used to find the percentage of blue stained cells indicating loss of cell membrane integrity and cell death. Cell death (counted as both the absent and stained cells) was examined and related to acoustic emission. Acoustic scattering power was higher for Pulse #1 than that for Pulse #2. For 5% Optison/sup /spl reg//, cell death at 1 kHz PRF was lower that that for 100 Hz, 10 Hz, 1 Hz, 0.1 Hz.
Engineering innovation through rhetorical invention

Teaching engineering students to innovate—to develop novel solutions, new applications, or original designs for solving problems—is becoming a more central concern in engineering education. Many programs are increasing the number of project-based courses, to provide students with the conditions in which innovation might occur, yet innovation remains difficult to teach directly. In one such course in Chemical Engineering, we introduced a framework to aid students in exploring the central questions of their projects, from how to define the problem, to how to recognize the value of previous approaches to specific technical challenges, to how to interpret the results of innovative research. This framework, which we call a "What-How-Why" diagram, integrates the thinking that chemical engineers need to cover as they design the work of a project, with the thinking that they need to do in order to communicate that work to an audience. We have found that this framework helps students to plan their work, to recognize potential areas for specific innovation, to better recognize the significance of variations in research design, and to communicate innovative solutions more effectively.
How do undergraduate STEM mentors reflect upon their mentoring experiences in an outreach program engaging K-8 youth?

Many university students are becoming involved in mentoring programs, yet few studies describe the impact of mentoring on the mentor. Additionally, many studies report that students graduating from college are not prepared to enter the workforce in terms of key career skills and/or content knowledge. Herein, we examine the impact of our program, NE STEM 4U (Nebraska Science, Technology, Engineering and Math for You), in which undergraduate (UG) mentors engage K-8 youth in after-school STEM experiments. The UGs reflected upon their experiences using post-mentoring evaluations, 12- and 24-week interviews, and exit surveys. Many of the questions asked of the mentors related directly to their own professional development, such as self-evaluation of communication, organization, and problem-solving skills, while other questions related to content knowledge and reflection. Post-mentoring, UGs reflected on the delivery/teaching significantly more (p ≤ 0.001 for each) than other variables (i.e., their own content knowledge gains, the students’ content knowledge gains, scaffolding the lessons, or overall professional growth). By analyzing the evaluations and interviews together, some significant, self-reported gains emerged. For example, 94.15% of the UG reported that the experience was beneficial to their education. Additionally, UG mentors self-reported significant gains (p ≤ 0.01 for each) moving from 12- to 24-weeks in the program in the categories of organization, STEM content knowledge, preparedness to teach, and engagement in the program. However, UG did not report significant gains in dependability. Importantly, when mentors ranked themselves at 24-weeks, they were blinded to (unaware of) the ranking they gave themselves at 12-weeks. This study helps to fill a gap in the literature by providing insight into the gains UG mentors report attaining after mentoring to K-8 students. These data suggest that participation by UGs in this program promoted self-reflection as well as self-reported gains related to career preparedness and STEM content knowledge.
Emmanuel Anati, Intellectual and Spiritual Expression of Non-Literate Peoples: Proceedings of the XVII UISPP World CongressF. Pimenta et al., Stars and Stones: Voyages in Archaeoastronomy and Cultural Astronomy

Rock art studies and cultural astronomy have at least one thing in common: the complaint made, even by some of their own participants, that they remain outside the conventional house of knowledge l...
Pharmacological, Physiochemical, and Drug-Relevant Biological Properties of Short Chain Fatty Acid Hexosamine Analogues Used in Metabolic Glycoengineering

In this study, we catalog structure activity relationships (SAR) of several short chain fatty acid (SCFA)-modified hexosamine analogues used in metabolic glycoengineering (MGE) by comparing in silico and experimental measurements of physiochemical properties important in drug design. We then describe the impact of these compounds on selected biological parameters that influence the pharmacological properties and safety of drug candidates by monitoring P-glycoprotein (Pgp) efflux, inhibition of cytochrome P450 3A4 (CYP3A4), hERG channel inhibition, and cardiomyocyte cytotoxicity. These parameters are influenced by length of the SCFAs (e.g., acetate vs n-butyrate), which are added to MGE analogues to increase the efficiency of cellular uptake, the regioisomeric arrangement of the SCFAs on the core sugar, the structure of the core sugar itself, and by the type of N-acyl modification (e.g., N-acetyl vs N-azido). By cataloging the influence of these SAR on pharmacological properties of MGE analogues, this stud...
Shedding light on surface effects: nonlinear probes of complex materials

The refinement of materials to facilitate their use in a broad range of applications is dependent on a detailed characterization and understanding of their interaction with light. This is especially true for the properties of materials’ surfaces and interfacial regions where deviations from the bulk structure significantly impact the flow of energy. Adding to the complexity of this problem is the fact that these regions contain an overall small number of reporters resulting in undetectable signal buried under the massive bulk response. To directly overcome these challenges, electronic sum frequency generation (eSFG) can selectively probe interfacial species, defects, and ordering. The sensitivity of this technique arises from the requirement that second order nonlinear signals originate from noncentrosymmetry that is inherent at surfaces and interfaces. Further, the enhancement of eSFG signal due to resonance of material transitions with any one of the three electric fields involved generates a spectrum analogous to linear absorption but originating solely from these regions of interest. Here we present our instrumental implementation of this technique which centers around the use of supercontinuum from a photonic crystal fiber for broadband spectral analysis and a microscopic apparatus to limit, and eventually probe, sample heterogeneity. Finally our application of this instrument to multiple crystalline materials provides new information to inform future design directions.
Pájaro y caracol: lo (solo del) animal en la poesía de Olvido García Valdés

Las raices animales de lo humano y el extranamiento de la naturaleza han sido importantes temas filosoficos de la Modernidad occidental. Este articulo explora las diferentes formas en que la poesia...
Centennial of Röntgen's discovery of x-rays.

November 8, 1995, marked the 100th anniversary of Wilhelm Conrad Rontgen's discovery of x-rays. This remarkable scientific achievement has had an effect on medicine and science that has been matched by few other advances. I will briefly review the events leading up to Rontgen's discovery and the subsequent development of radiology as a discipline.
CD163 Identifies a Unique Population of Ramified Microglia in HIV Encephalitis (HIVE)

The idea that CNS ramified microglia are quiescent has been challenged by studies that show that microglia without the classic signs of activation can be phagocytic and appear with shorter, thicker ramifications. These semi-activated cells may constitute a form of microglia that has not been previously recognized in neuropathological conditions and may contribute to the pathology and dysfunction in these disorders. This study investigated the expression of CD 163, a cell surface marker whose normal expression is restricted to monocytes/macrophages, in cases of HIV or SIV encephalitis (HIVE/SIVE), Alzheimer disease, and variant Creutzfeldt-Jakob disease. In HIVE/SIVE, in addition to reacting with CNS macrophages, CD163 antibody staining was shown to highlight ramified microglia. Such reactivity was especially notable in grey matter ramified microglia and was greater than that of another typically used marker, HLA-DR. CD163 expression was only observed in infected/affected tissue, in contrast to that shown with another microglia marker, GLUT5, which has recently been shown to identify all microglia regardless of disease state. Although activated microglia were present in the other disorders, as evidenced by strong HLA-DR expression, there was very little CD163 immunoreactivity. The activation state identified by CD163 has not been previously recognized and may have a positive or negative impact on neuronal damage shown in HIV-associated dementia.
Phase Domain Size and Continuity in Sequential IPN’s: A Review

An interpenetrating polymer network, IPN, is defined as a combination of two polymers in network form, at least one of which is synthesized and/or crosslinked in the immediate presence of the other. While an IPN is closely related to polymer blends, grafts, and blocks, it can be distinguished in two ways: (1) An IPN swells, but does not dissolve in solvents, and (2) creep and flow are suppressed.
SPADE: support for provenance auditing in distributed environments

SPADE is an open source software infrastructure for data provenance collection and management. The underlying data model used throughout the system is graph-based, consisting of vertices and directed edges that are modeled after the node and relationship types described in the Open Provenance Model. The system has been designed to decouple the collection, storage, and querying of provenance metadata. At its core is a novel provenance kernel that mediates between the producers and consumers of provenance information, and handles the persistent storage of records. It operates as a service, peering with remote instances to enable distributed provenance queries. The provenance kernel on each host handles the buffering, filtering, and multiplexing of incoming metadata from multiple sources, including the operating system, applications, and manual curation. Provenance elements can be located locally with queries that use wildcard, fuzzy, proximity, range, and Boolean operators. Ancestor and descendant queries are transparently propagated across hosts until a terminating expression is satisfied, while distributed path queries are accelerated with provenance sketches.
Thrombocytopenia in the Intensive Care Unit and After Solid Organ Transplantation

Thrombocytopenia is common among patients in the intensive care unit (ICU) and the post-solid organ transplantation (SOT) setting. Although such patients may be vulnerable to any of the causes of thrombocytopenia that affect individuals in other settings, certain etiologies are of particular prevalence and clinical relevance. In this chapter, we review the causes and management of, and our diagnostic approach to, thrombocytopenia in ICU and SOT patients. Major etiologies of thrombocytopenia in the ICU include sepsis, drug-induced thrombocytopenia, disseminated intravascular coagulation, dilutional thrombocytopenia, heparin-induced thrombocytopenia, posttransfusion purpura, extracorporeal circuitry, intravascular devices, and surgery. We present an algorithm for determining the likelihood of these respective causes that takes into account the severity of thrombocytopenia, its timing of onset with respect to exposure to drugs and transfusions, the pace of the fall in platelet count, and the presence of thrombosis or hemorrhage. Important diagnostic considerations after SOT comprise drug-induced thrombocytopenia, viral infection, thrombotic microangiopathy, infection-induced hemophagocytic syndrome, post-transplant lymphoproliferative disorder, graft-versus-host disease, and immune thrombocytopenia. The time of onset of thrombocytopenia after SOT and specific laboratory or pathologic testing is helpful in discerning the diagnosis among these causes.
Cantilever Sensors for Pathogen Detection

In this chapter we summarize briefly the use of cantilever sensors for pathogen detection. Both micro- and macro-cantilever sensors have been investigated for detecting pathogens in liquid samples. In this review we examine previous work and summarize progress on using piezoelectric-excited millimeter-sized cantilever (PEMC) sensors developed in the author’s laboratory. PEMC sensors immobilized with an antibody specific to the target pathogen has been shown to be very highly sensitive for detecting one cell per mL in one liter samples and 10 cells per mL in 10,mL samples, both in buffers and at similar concentrations in food matrices. After a brief introduction, the physics of sensing is reviewed, followed by a characterization of PEMC sensors, and finally the results from detection experiments are described.
Minkowski Space and Quantum Mechanics

A paradigm shift distinguishes general relativity from classical mechanics. In general relativity the energy-momentum tensor is the effective cause of the ontological space-time curvature and vice-versa, while in classical physics, the structure of space-time is treated as an accidental cause, serving only as a backdrop against which the laws of physics unfold. This split in turn is inherited by quantum mechanics, which is usually developed by changing classical (including special relativity) Hamiltonians into quantum wave equations.
Acute and chronic methylphenidate administration in intact and VTA-specific and nonspecific lesioned rats.

Methylphenidate (MPD) is a psychostimulant used for the treatment of ADHD and works by increasing the bioavailability of dopamine (DA) in the brain. As a major source of DA, the ventral tegmental area (VTA) served as the principal target in this study as we aimed to understand its role in modulating the acute and chronic MPD effect. Forty-eight male Sprague–Dawley rats were divided into control, sham, electrical lesion, and 6-OHDA lesion groups. Given the VTA’s implication in the locomotive circuit, three locomotor indices—horizontal activity, number of stereotypy, and total distance—were used to measure the animals’ behavioral response to the drug. Baseline recording was obtained on experimental day 1 (ED 1) followed by surgery on ED 2. After recovery, the behavioral recordings were resumed on ED 8. All groups received daily intraperitoneal injections of 2.5 mg/kg MPD for six days after which the animals received no treatment for 3 days. On ED 18, 2.5 mg/kg MPD was re-administered to assess for the chronic effect of the psychostimulant. Except for one index, there was an increase in locomotive activity in all experimental groups after surgery (in comparison to baseline activity), acute MPD exposure, induction with six daily doses, and after MPD re-challenge. Furthermore, the increase was greatest in the electrical VTA lesion group and lowest in the 6-OHDA VTA lesion group. In conclusion, the results of this study suggest that the VTA may not be the primary nucleus of MPD action, and the VTA plays an inhibitory role in the locomotive circuit.
Diazaquinomycin Biosynthetic Gene Clusters from Marine and Freshwater Actinomycetes.

Tuberculosis is an infectious disease of global concern. Members of the diazaquinomycin (DAQ) class of natural products have shown potent and selective activity against drug-resistant Mycobacterium tuberculosis. However, poor solubility has prevented further development of this compound class. Understanding DAQ biosynthesis may provide a viable route for the generation of derivatives with improved properties. We have sequenced the genomes of two actinomycete bacteria that produce distinct DAQ derivatives. While software tools for automated biosynthetic gene cluster (BGC) prediction failed to detect DAQ BGCs, comparative genomics using MAUVE alignment led to the identification of putative BGCs in the marine Streptomyces sp. F001 and in the freshwater Micromonospora sp. B006. Deletion of the identified daq BGC in strain B006 using CRISPR-Cas9 genome editing abolished DAQ production, providing experimental evidence for BGC assignment. A complete model for DAQ biosynthesis is proposed based on the genes ident...
4 Functional and Nonfunctional Pituitary Adenomas

Pituitary adenomas are slow-growing, benign tumors that arise from the cells of the pituitary gland. They can be nonfunctional or functional depending on whether they secrete hormones. For non-prolactin-secreting adenomas that are symptomatic through mass effect on local structures or hormonal hypersecretion, or nonfunctional adenomas large enough to warrant elective treatment, surgery is typically recommended. The endoscopic endonasal approach provides safe and thorough exposure of the sella and any tumors within it. Here, we review the process of evaluating patients with pituitary tumors, including the necessary laboratory and radiographic tests for these patients, and the technical aspects of endoscopic endonasal surgery for pituitary tumors, including preoperative considerations, operative technique and nuances, and postoperative complications. In the hands of an experienced neurosurgeon, the endoscopic endonasal technique is quite successful at resecting these common tumors and helping patients improve or maintain their quality of life.
Linking diffusion tensor imaging, microstructures and Parkinson's disease

Abstract Diffusion tensor imaging allows measuring fractional anisotropy and similar microstructural indices of brain white matter, in which lower than normal fractional anisotropy is associated with loss of microstructural integrity and degeneration. It has been argued whether anisotropy is higher or lower than normal in early Parkinson's disease and to what extent the abnormal anisotropy is detected. This study, by analyzing imaging datasets from the Parkinson's progression markers initiative, reveals a complex pattern of vulnerable microstructural alterations in early Parkinson's disease. Also, the abnormal reduction and elevation of fractional anisotropy coexist across the brain. The divergency of these abnormalities depends on the stage of disease and the age at disease onset. This chapter also discusses the utilities of diffusion tensor imaging in detecting microstructural changes in dopaminergic sites and pathway, and the roles of diffusion tensor imaging in tracking disease progression and medication effects.
cancerAlign: Stratifying tumors by unsupervised alignment across cancer types

Tumor stratification, which aims at clustering tumors into biologically meaningful subtypes, is the key step towards personalized treatment. Large-scale profiled cancer genomics data enables us to develop computational methods for tumor stratification. However, most of the existing approaches only considered tumors from an individual cancer type during clustering, leading to the overlook of common patterns across cancer types and the vulnerability to the noise within that cancer type. To address these challenges, we proposed cancerAlign to map tumors of the target cancer type into latent spaces of other source cancer types. These tumors were then clustered in each latent space rather than the original space in order to exploit shared patterns across cancer types. Due to the lack of aligned tumor samples across cancer types, cancerAlign used adversarial learning to learn the mapping at the population level. It then used consensus clustering to integrate cluster labels from different source cancer types. We evaluated cancerAlign on 7,134 tumors spanning 24 cancer types from TCGA and observed substantial improvement on tumor stratification and cancer gene prioritization. We further revealed the transferability across cancer types, which reflected the similarity among them based on the somatic mutation profile. cancerAlign is an unsupervised approach that provides deeper insights into the heterogeneous and rapidly accumulating somatic mutation profile and can be also applied to other genome-scale molecular information.
Inpainting Radar Missing Data Regions with Deep Learning

Abstract. Missing and low-quality data regions are a frequent problem for weather radars. They can stem from a variety of sources: beam blockage, instrument failure, near-ground blind zones, and many others. Filling-in missing data regions is often useful for estimating local atmospheric properties and application of high-level data processing schemes without the need for preprocessing and error-handling steps; feature detection and tracking for instance. Interpolation schemes are typically used for this task, though they tend to produce unrealistically spatially-smoothed results that are not representative of the atmospheric turbulence and variability that are usually resolved by weather radars. Recently, Generative Adversarial Networks (GANs) have achieved impressive results in the area of photo inpainting. Here, they are demonstrated as a tool for infilling radar missing data regions. These neural networks are capable of extending large-scale cloud and precipitation features that border missing data regions into the regions while hallucinating plausible small scale variability. In other words, they can inpaint missing data with accurate large-scale features and plausible local small-scale features. This method is demonstrated on a scanning C-band and vertically pointing Ka-band radar that were deployed as part of the Cloud Aerosol and Complex Terrain Interactions (CACTI) field campaign. Three missing data scenarios are explored: infilling low-level blind zones and short outage periods for the Ka-band radar, and infilling beam blockage areas for the C-band radar. Two deep learning based approaches are tested, a Convolutional Neural Network (CNN) and a GAN that optimize pixel level error or combined pixel level error and adversarial loss respectively. Both deep learning approaches significantly outperform traditional inpainting schemes under several pixel-level and perceptual quality metrics.
Pharmaco-Metabolomics of Inhaled Corticosteroid Response in Individuals with Asthma

Metabolomic indicators of asthma treatment responses have yet to be identified. In this study, we aimed to uncover plasma metabolomic profiles associated with asthma exacerbations while on inhaled corticosteroid (ICS) treatment. We determined whether these profiles change with age from adolescence to adulthood. We utilized data from 170 individuals with asthma on ICS from the Mass General Brigham Biobank to identify plasma metabolites associated with asthma exacerbations while on ICS and examined potential effect modification of metabolite-exacerbation associations by age. We used liquid chromatography–high-resolution mass spectrometry-based metabolomic profiling. Sex-stratified analyses were also performed for the significant associations. The age range of the participating individuals was 13–43 years with a mean age of 33.5 years. Of the 783 endogenous metabolites tested, eight demonstrated significant associations with exacerbation after correction for multiple comparisons and adjusting for potential confounders (Bonferroni p value < 6.2 × 10−4). Potential effect modification by sex was detected for fatty acid metabolites, with males showing a greater reduction in their metabolite levels with ICS exacerbation. Thirty-eight metabolites showed suggestive interactions with age on exacerbation (nominal p-value < 0.05). Our findings demonstrate that plasma metabolomic profiles differ for individuals who experience asthma exacerbations while on ICS. The differentiating metabolites may serve as biomarkers of ICS response and may highlight metabolic pathways underlying ICS response variability.
Isolation of L-Forms of Bacillus subtilis Which Grow in Liquid Medium

L-forms of Bacillus subtilis can be isolated by treatment of the parent strain sequentially with N-methyl-N'-nitro-N-nitrosoguanidine and lysozyme and selection of the surviving protoplasts on semisolid medium containing 2,000 units of penicillin per ml. Some of these clones can be adapted to grow in liquid cultures containing 1.2 m NaCl. This method will aid in the isolation of cell wall mutants which require hypertonic medium for growth.
The Effects of Sediment Transport and Deposition on Infauna: Results Obtained in a Specially Designed Flume

Surprisingly little is known about the effects of steady sediment transport or of natural rates of deposition on the process of deposit feeding. This situation persists despite the theoretical reasons for believing that sediment supply by physical processes in many environments is important or dominant in controlling food supply to individual deposit feeders (Miller et al. 1984), despite newly collected field evidence suggesting that sediment transport rate overwhelms processing rates by deposit feeders in environments of both U.S. coasts (Grant 1983; Miller 1985 and in review), and despite the name “deposit feeders.” The reasons are several. One is the technological difficulty of building laboratory devices that realistically can simulate field transport conditions. Another is the difficulty of observing deposit-feeder responses when sediments move. Three other reasons are more subtle. First, it is easy to avoid thinking about sediment movement because it does not occur when one walks out on a sand- or mudflat, and one often avoids it in diving situations as well. Second, very little is known about the mechanics of particle deposition in water, so one cannot extrapolate readily to its biological effects. Third, in the heyday of natural history observations made for their own sake, most observations were done in still water, so the full repertoire of animal behaviors is unknown from classic natural history. Some of these impediments can be overcome simply by being aware of them, while others require more effort. We will focus on the latter.
Tetrahymena Macronuclear Genome Mapping: Colinearity of Macronuclear Coassortment Groups and the Micronuclear Map on Chromosome 1L

The genetics of the ciliate Tetrahymena thermophila are richer than for most other eukaryotic cells, because Tetrahymena possesses two genomes: a germline (micronuclear) genome that follows a Mendelian model of genetic transmission and a somatic (macronuclear) genome, derived from the micronuclear genome by fragmentation, which follows a different genetic transmission model called phenotypic assortment. While genetic markers in the micronucleus fall into classical linkage groups under meiotic recombination and segregation, the same markers in the macronucleus fall into coassortment groups (CAGs) under phenotypic assortment by the random distribution of MAC chromosome pieces. We set out to determine whether genomic mapping in the macronucleus by genetic means is feasible. To investigate the relationship between the micronuclear map and coassortment groups, we systematically placed into CAGs all of the markers lying on chromosome 1L that are also found in the macronucleus. Sixteen CAGs were identified, 7 of which contain at least two loci. We have concluded that CAGs represent a fundamental genetic feature of the MAC. The MIC and MAC maps on 1L are colinear; that is, CAGs consist exclusively of markers that map to a continuous segment in a given region of the micronuclear map, with no intervening markers from other CAGs. These findings provide a solid foundation for exploiting the MAC chromosome pieces to build a physical map of the Tetrahymena genome.
Striated muscle hamartoma: Description of two cases

We saw two newborn infants with striated muscle hamartoma. One patient had numerous associated congenital anomalies. The clinical appearance of both lesions was that of a soft fibroma. Histologically, striated muscle fibers and nerve bundles were seen in the central core and also at the periphery of the lesion, below the epidermis. A marked number of sebaceous glands, vellus hair follicles, and eccrine glands were also present. We propose the term striated muscle hamartoma, which points out the most remarkable feature of these lesions.
The calcium sensing receptor: from calcium sensing to signaling.

The Ca2+-sensing receptor (the CaSR), a G-protein-coupled receptor, regulates Ca2+ homeostasis in the body by monitoring extracellular levels of Ca2+ ([Ca2+]o) and responding to a diverse array of stimuli. Mutations in the Ca2+-sensing receptor result in hypercalcemic or hypocalcemic disorders, such as familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism, and autosomal dominant hypocalcemic hypercalciuria. Compelling evidence suggests that the CaSR plays multiple roles extending well beyond not only regulating the level of extracellular Ca2+ in the human body, but also controlling a diverse range of biological processes. In this review, we focus on the structural biology of the CaSR, the ligand interaction sites as well as their relevance to the disease associated mutations. This systematic summary will provide a comprehensive exploration of how the CaSR integrates extracellular Ca2+ into intracellular Ca2+ signaling.