cssi/SciSciGPT-SciSciNet huggingface dataset:
Oral Delivery of Bioencapsulated Factor IX Protects From Inhibitor Formation and Anaphylaxis in Protein Replacement Therapy for Hemophilia B.

Abstract Abstract 222 While the incidence of inhibitor formation against the infused coagulation factor is overall relatively low in factor IX-deficiency (1–4% of patients), 9–23% of patients with severe hemophilia B form inhibitors, which seriously complicates treatment. Factor IX (F.IX) inhibitors tend to be high titer and not effectively eliminated by immune tolerance induction protocols, and are often associated with serious anaphylactic reactions. Inhibitor formation and anaphylaxis is more typical for patients with F9 gene deletions or early stop codons. We sought to develop a novel approach to induction of antigen-specific immune tolerance that is safe, not based on immune suppression, and does not require knowledge of specific T cell epitopes. Chloroplast transgenic plants expressing human F.IX were generated. Because the plant cell provides bioencapsulation, the recombinant polypeptide is protected from acids and enzymes in the stomach and released in the gut. The hF.IX coding sequences were fused with the transmucosal carrier CTB. The fusion gene cassettes were expressed from the light-regulated psbA 5′ untranslated region/promoter in order to achieve hyper-expression. To prevent steric hindrance, a GPGP hinge was introduced between CTB and FIX. A furin cleavage site was also introduced in one of the constructs. Plasmid DNA was bombarded on nicotine-free tobacco leaves via a particle-mediated method using the gene gun, resulting in transgene integration into the chloroplast genome by homologous recombination. Transformed tissues were repeatedly cultured on selective media, and transplastomic plants were regenerated. Chloroplast transplastomic lines were examined by Southern blot analysis in order to confirm site-specific integration and to test for homoplasmic lines. Transplastomic lines of CTB-GPGP-hFIX (F1) and CTB-GPGP-Furin-hFIX (F2) had expression levels of up to 3.8% and 0.28% fusion protein, respectively, in the total soluble protein. Control and transplastomic plant materials (250 mg) were fed twice per week for 8 weeks by oral gavage to Hemophilia B mice, known to develop strong antibody responses against hF.IX (C3H/HeJ F9−/− mice with targeted F9 gene deletion). For the F2 material, this was equivalent to 2 μg of hF.IX per dose. After 4 weeks, animals received weekly infusions of hF.IX (Benefix) at 1 IU per dose for 4 weeks (1 IP followed by 3 IV doses). As expected, ≥80% of mice control groups had developed significant inhibitors at titers of 4–10 BU (average titers were 5.5 BU for wild-type material fed and 7 BU for unfed controls). In contrast, all F1 and F2 fed mice (n=15 and n=14, respectively) had undetectable or at most very low titer inhibitors (≤2 BU) and showed normal clearance of hF.IX. Some F2 fed mice (n=9) was subjected to 1 more month of weekly IV infusions of hF.IX. At the end of this experiment, inhibitor titers remained undetectable to low ( Disclosures: Daniell: Chlorogen Inc: Technical founder.
Sam Harris: A Producing Patron of Innovation

Sam H. Harris (1872–1941) and George M. Cohan (1878–1942) were extremely active in cultivating early musical comedy, focusing on a performer-centred type of book musical. Harris collaborated with composer-lyricist-performer Irving Berlin (1888–1989) on the series of Music Box Revues during the 1920s and with playwright George S. Kaufman (1889–1961), among others, on satirical and inventive shows in the 1930s.
Use of Anti-VEGF Agents in Glaucoma Surgery

A number of antivascular endothelial growth factor agents are currently available to treat various ocular conditions. These agents have similar, but distinct, biologic qualities and have been explored in the management of neovascular glaucoma and in glaucoma surgery. Several different delivery methods are described, and because these medications are routinely given as intraocular injections, some benefits over traditional antifibrotic medications when used in glaucoma surgery are noted. These agents effectively induce regression of anterior segment neovascularization and facilitate initial surgical management of neovascular glaucoma, but the long-term outcome of this condition remains dependent on definitive management of the underlying process. Use in trabeculectomy or tube shunt procedures for other types of glaucoma has shown promise in modulating bleb morphology but has not yet been found to be as effective as traditional antifibrotic agents. There are reports of persistently raised intraocular pressure after repeated use of the anti-VEGF agents, possibly related to frequency of injection. These medications have wide application in the field of surgical glaucoma, but a definitive role has yet to be defined.
From Barriers to Belonging for People with Disabilities: Promising Pathways Toward Inclusive Ministry

Faith communities are called to be places of hospitality, reciprocity, and belonging. Yet many congregations still struggle to welcome and weave people with disabilities and their families deeply into all aspects of community life. This chapter addresses promising pathways through which congregations might make movements to invite and support the full participation of people with intellectual and developmental disabilities. Six areas of emphasis are explored—reflecting, inviting, preparing, participating, serving, and belonging. Avenues for future research in this emerging area of scholarship are described, along with recommendations for congregations interested in investing more deeply in this area of ministry.
International Monetary Instability All Over Again

One of the signature developments of 2016 was the move from globalization and market integration toward nationalism and protection. A headline in the Financial Times (April 13, 2017) read, “‘Sword of protectionism hangs over trade’, says IMF.” The headline demonstrates “Silo-ism”. The Fund does not recognize that the demand for import barriers in countries with large trade deficits and high unemployment have resulted from massive imbalances in international payments. Monetary instability in the 1920s and the 1930s was reflected in the overvaluation of the British pound, the undervaluation of the French franc and subsequent overvaluation of the U.S. dollar. Britain voted to leave the European Union in June 2016, in part because the high price of the British pound depressed exports and wages in manufacturing. U.S. gross domestic product (GDP) has doubled since 1980, yet manufacturing employment has declined by eight million. The demand for protection in the U.S. has increased because the more rapid growth of imports than exports has led to the decline of three to four million U.S. manufacturing jobs.
Safety-oriented bicycling and traffic accident involvement

Abstract Many U.S. bicyclists are killed or injured in traffic accidents annually. Based on analysis of available research and published reports on traffic accidents, it was theorized that adherence to six safety-oriented on-road bicycling practices will reduce involvement in traffic accidents. This study investigated whether adherence to these safety-oriented bicycling practices is associated with reduced involvement in traffic accidents. U.S. adult bicycle riders responded to an anonymous on-line survey covering bicycling practices, recent traffic accident experiences, and potential confounding variables. Participants were recruited via on-line announcements to bicycling-related organizations. The results suggested that neither vigilance nor cautiousness will protect adult bicycle riders from traffic accident involvement, but predictability might reduce accident risk, particularly for younger adults. Results should be interpreted cautiously due to limitations in the study methodology. Further research of this type is warranted. This paper is a re-formulation of research originally presented as a conference paper and oral presentation at the International Cycling Safety Conference in Bologna, Italy, 3–4 November 2016.
Social Status of Roles within the Christian Community1

Two surveys were conducted among 213 college students to determine whether or not they would differentiate between the relative status of various Christian roles, and if so, what type of hierarchy ...
Nutritional status and dietary management of elderly diabetic patients.

Elderly diabetic patients are likely to be at high risk for the development of nutritional deficiencies. The nutritional status in this subgroup of patients has not yet been directly evaluated. The best estimate of the nutritional status of elderly diabetic patients must be extrapolated from data from studies of elderly subjects and middle-aged diabetic patients. This article presents general recommendations for the dietary management of elderly diabetic patients that have been based on such approximations.
Soft X-Ray Laser Holographic Imaging With Sub-Micron Resolution

We have demonstrated Gabor holography with a spatial resolution of ~ 380nm using a table top soft X-Ray laser. The hologram was recorded in a high spatial resolution photoresist and subsequently digitized using an atomic force microscope. The final reconstruction was performed using a Fresnel propagator.
Drug delivery using wireless MEMS

Abstract: Drug delivery is essential for the treatment of chronic conditions. Implantable site-specific drug delivery devices offer direct delivery to the site of therapy, improving treatment outcomes while reducing side effects and overall associated healthcare costs. Microelectromechanical systems (MEMS) miniaturize infusion pumps such that they are implantable; wirelessly-powered to eliminate the use of bulky, limited lifetime batteries; and volume efficient. Wireless communication allows remote monitoring of device status and performance, and remotely initiated changes to the drug regimen for patient tailored therapy. Requirements for a MEMS drug delivery device with wireless powering and data communication are presented along with an example of such a device.
Seismic Rehabilitation of Coastal Dikes By Sheet-pile Enclosures

Past experience has shown that by far the most widespread source of earthquake-induced damage to coastal dikes and embankments has been liquefaction of the loose, saturated, sandy foundation soils that often prevail throughout the marine environment. In this paper, the potential of using sheet-pile walls for mitigating the adverse effects of foundation liquefaction on overlying coastal dikes-embankments is investigated through a series of heavily instrumented, dynamic centrifuge physical modeling tests. Mechanisms of earthquake-induced marine foundation liquefaction and associated hazards on a typical dike section are discussed based on the recorded dynamic response. The effectiveness of underground sheet-pile walls as retrofit is evaluated based on additional modeling tests.
Age Moderates the Effect of Self-Paced Exercise on Exercise Adherence among Overweight Adults:

Objective: The present study tested the hypothesis that the effect of self-paced exercise on adherence to exercise programs is more pronounced with increasing age. Method: Fifty-nine low-active overweight adults (18-65 years) were encouraged to walk 30 to 60 min/day and randomized to either self-paced (n = 30) or prescribed moderate-intensity (n = 29) conditions. Results: The effect of study condition was moderated by age (main effect: b = 6.14, SE = 2.54, p = .02; Condition × Age: b = -11.55, SE = 3.77, p 50 years, those in the self-paced condition exercised 6 more min/day than participants in the prescribed moderate-intensity condition (p = .02), whereas among participants <50 years, those in the self-paced condition exercised 5.4 fewer min/day compared with those in the moderate-intensity condition (p = .05). Affective response to physical activity did not mediate the moderating effect of age. Discussion: As age increases, adults may be more likely to adhere to self-paced versus prescribed moderate-intensity exercise.
Wednesday, September 26, 2018 7:35 AM–9:00 AM ePosters: P179. Osteoporotic fractures of the spine compared to osteoporotic fractures of the distal radius: a review of patient risk factors

BACKGROUND CONTEXT Low energy distal radius and vertebral fragility fractures (VFF) are common injuries in the osteoporotic patient. In this study, the Own the Bone (OTB) database was examined to (1) examine the specific demographics of patients presenting with a VFF or a distal radius fracture and, (2) compare fracture-specific risk factors between patients with VFF against patients with a distal radius fracture. PURPOSE To determine whether or not there are differences between patients sustaining VFF versus distal radius fractures. STUDY DESIGN/SETTING This study uses data from the Own the Bone registry which is the largest, multicenter data registry in the United States to analyze patients presenting with fragility fractures. METHODS This study used the American Orthopaedic Assocation's OTB program registry which contains data on 42,862 patients presenting with insufficiency fractures. After excluding all other fracture types, there were 4,841 VFF and 2,557 distal radius fractures. These fracture types account for 11.2% and 6.0% of the preseting fractures at OTB enrollment. RESULTS The majority of both VFF and distal radius fracture patients were Caucasian, postmenopausal females (72.8% and 80.6%, respectively). Multivariate analysis demonstrated that patients with a prior history of at least one distal radius fracture are more likely to sustain an additional distal radius fracture (OR 2.25, p CONCLUSIONS VFF and distal radius fractures remain common sites for insufficiency fractures. Multiple patient-related factors significantly increase the risk of vertebral fragility fracture compared to distal radius fractures including vitamin D insufficiency and active smoking. Patients with a history of a fragility fracture of the vertebral column after age 50 had a substantially increased risk of sustaining a secondary vertebral fracture. Interestingly, patients with a previous history of a vertebral fracture after age 50 as well as a previous distal radius fracture were more likely to sustain an additional vertebral fragility fracture. Understanding the risk factors unique to these fracture types is critical in allowing physicians to appropriately treat these patients to mitigate the negative sequelae of osteoporosis in this patient population.
Developing a computer-aided image analysis and visualization tool to predict region-specific brain tissue “at risk” for developing acute ischemic stroke

Advent of advanced imaging technology and better neuro-interventional equipment have resulted in timely diagnosis and effective treatment for acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, objective clinicoradiologic correlate to identify appropriate candidates and their respective clinical outcome is largely unknown. The purpose of the study is to develop and test a new computer-aided detection algorithm to quantify region-specific AIS and “at risk” brain volumes prior to thrombectomy using CT perfusion imaging protocol. Fourteen patients with LVO related AIS and assessed radiologically for their eligibility to undergo mechanical thrombectomy was retrospectively analyzed for the study. First, the scheme automatically categorizes images into multiple series of scans acquired from a section of brain. Each image in series is labeled to a specified brain location. Next, image segmentation is performed to separate brain region from skull. The brain is then split into left and right hemispheres, followed by detecting amount of blood in each hemisphere. Last, comparison between amount of blood in each hemisphere over the series of scans is made to observe the wash-in and wash-out rate of blood to assess the extent of already damaged and “at risk” brain tissue. By integrating the scheme into a user graphic interface, the study builds a unique image feature analysis and visualization tool to observe and quantify the delayed or reduced blood flow (brain “at risk” to develop AIS) in the corresponding hemisphere, which has potential to assist radiologists to quickly visualize and more accurately assess the extent of AIS.
Vaccine development: how scientific collaboration and communication help prevent the spread of disease: an interview with Erol Fikrig, MD.

Erol Fikrig, MD, is a Waldemar Von Zedtwitz Professor of Medicine in Infectious Diseases, as well as a Professor of Epidemiology (Microbial Diseases) and Microbial Pathogenesis at the Yale School of Medicine. Dr. Fikrig received both his BA and MD from Cornell University. From there, he was an Internal Medicine resident at Vanderbilt University Hospital, and then completed a fellowship in Infectious Diseases at Yale University. Dr. Fikrig now is a senior research scientist at Yale, where he acts as a Howard Hughes Medical Institute investigator and Section Chief for Infectious Diseases. Over the course of his career, Dr. Fikrig has had a broad impact on our understanding of Lyme disease and played a key role in the development of the first and only Lyme disease vaccine to be brought to market. Currently, his laboratory focuses on studying vector-borne diseases such as Lyme disease, human granulocytic ehrlichiosis, and West Nile virus. In this interview, Dr. Fikrig discusses his background and interest in the molecular pathogenesis of infectious diseases. He shares with us a unique story about the development of the Lyme disease vaccine and the hurdles that arose during this process. Additionally, he comments on the current status of vaccination in the United States and what struggles remain in educating the public on the benefits of such preventive measures.
Administration of interleukin-2 (IL-2) results in increased plasma concentrations of IL-5 and eosinophilia in patients with cancer

Peripheral eosinophilia is almost invariably observed during the course of interleukin-2 (IL-2) therapy and is frequently accompanied by the development of a capillary leak syndrome characterized by edema, weight gain, and oliguria. We studied five patients with advanced malignancy treated with IL-2. Eosinophilia was not present initially but developed in all patients late in the course of therapy, with counts ranging from 2,328/mm3 to 15,958/mm3. In all patients, there was a temporal relationship between the infusion of IL-2 and the appearance of elevated plasma concentrations of IL-5, a growth factor for eosinophils. Granulocyte-macrophage colony-stimulating factor was not detectable in plasma. IL-4 and gamma-interferon plasma levels were variably elevated. Plasma concentrations of major basic protein, a toxic eosinophil granule protein, began increasing before eosinophil counts increased. By the time of the third IL-2 infusion, high concentrations of major basic protein were present in all five patients (up to 5,600 ng/mL) and skin biopsies showed major basic protein deposition in the dermis. Four patients developed significant capillary leak syndrome and all of these patients showed markedly elevated major basic protein levels. The lowest peak plasma concentration of major basic protein (1,751 ng/mL) was observed in the one patient who did not develop edema and weight gain. These results suggest that IL-2 induces IL-5 leading to marked peripheral eosinophilia and extravascular eosinophil degranulation. The release of toxic eosinophil products at extravascular sites and in the circulation may contribute to the pathogenesis of the capillary leak syndrome complicating IL-2 therapy.
Sleep in Geriatric Psychiatry Inpatients

A majority of the geriatric population experiences some type of chronic sleep problem, which can lead to persistent sleep loss and negatively impact cognitive and physiological functioning. Recognition of factors that both promote and impair sleep is particularly important in hospitalized geriatric patients with psychiatric illnesses. This chapter reviews the changes that occur in sleep with aging and the environmental and intrinsic factors that can affect sleep. This chapter also addresses sleep disorders which impact psychiatric functioning and offers suggestions for therapeutic interventions.
TiO2 exposure alters transition metal ion quota in Rhodococcus ruber GIN-1

After exposure to micron-sized TiO2 particles, anatase and/or rutile, Rhodococcus ruber GIN-1 accumulates an increased concentration (2.2 ± 0.2 mg kg−1) of mobilized Ti into its biomass with concomitant decreases in cellular biometals Fe, Zn, and possibly Mn, while levels of Cu and Al are unaffected.
ZBTB38 is dispensable for hematopoiesis and antibody responses

Members of the broad complex, tram track, bric-a-brac and zinc finger (BTB-ZF) family of transcription factors, such as BCL-6, ZBTB20, and ZBTB32, regulate antigen-specific B cell differentiation, plasma cell longevity, and the duration of antibody production. We found that ZBTB38, a different member of the BTB-ZF family that binds methylated DNA at CpG motifs, is highly expressed by germinal center B cells and plasma cells. To define the functional role of ZBTB38 in B cell responses, we generated mice conditionally deficient in this transcription factor. Germinal center B cells lacking ZBTB38 dysregulated very few genes relative to wild-type and heterozygous littermate controls. Accordingly, mice with hematopoietic-specific deletion of Zbtb38 showed normal germinal center B cell numbers and antibody responses following immunization with hapten-protein conjugates. Memory B cells from these animals functioned normally in secondary recall responses. Despite expression of ZBTB38 in hematopoietic stem cells, progenitors and mature myeloid and lymphoid lineages were also present in normal numbers in mutant mice. These data demonstrate that ZBTB38 is dispensable for hematopoiesis and antibody responses. These conditional knockout mice may instead be useful in defining the functional importance of ZBTB38 in other cell types and contexts.
Approximate Local Poincaré Spacetime Symmetry in General Relativity

How does general relativity reduce, or explain the success of, special relativity? Answering this question, which Einstein took as a desideratum in the formulation of the former, is of acknowledged importance, yet there continues to be disagreement about how exactly it is best answered. I advocate here that part of the best answer involves showing that every relativistic spacetime has an approximate local Poincare spacetime symmetry group, the spacetime symmetry group of Minkowski spacetime. This explains the application of Minkowski spacetime concepts that depend on, e.g., the conserved quantities that spacetime symmetries guarantee. I contrast this approach with another that instead invokes the strong equivalence principle, which focuses on the distinct notion of Poincare invariance of dynamical equations. After showing with some examples that neither notion is necessary for the other, I use those examples to illuminate contrasting positions on the explanatory role of local approximate spacetime geometry, defending Torretti (1996) against criticisms by Brown and Pooley (2001). Finally, I acknowledge that establishing approximate local Poincare spacetime symmetry is not a complete answer to the explanatory question with which I led, discussing in the concluding section further work that could lead to a complete answer. This includes specifying the circumstances under which matter fields in a general relativistic spacetime “behave” locally like those in Minkowski spacetime.
A New State Record for Triatoma sanguisuga (Leconte) (Hemiptera: Reduviidae) from Wyoming, U.S.A.

Kissing bugs (Hemiptera: Reduviidae) are blood-feeding ectoparasites found primarily in the tropics and subtropics of the Americas. These bugs are vectors of Trypanosomatidae to their mammalian hosts, including humans. The distribution of Triatoma spp. in the Nearctic region is still not fully known, and their relevance as possible vectors of Trypanosoma cruzi to humans and animals is of growing concern. We report the first record of Triatoma sanguisuga from Wyoming, the northern-most reported collection in the western United States, and include collection records for Triatoma protracta in Colorado that were previously unclear.
Globally deimmunized lysostaphin evades human immune surveillance and enables highly efficacious repeat dosing

There is a critical need for novel therapies to treat methicillin-resistant Staphylococcus aureus (MRSA) and other drug-resistant pathogens, and lysins are among the vanguard of innovative antibiotics under development. Unfortunately, lysins' own microbial origins can elicit detrimental antidrug antibodies (ADAs) that undermine efficacy and threaten patient safety. To create an enhanced anti-MRSA lysin, a novel variant of lysostaphin was engineered by T cell epitope deletion. This "deimmunized" lysostaphin dampened human T cell activation, mitigated ADA responses in human HLA transgenic mice, and enabled safe and efficacious repeated dosing during a 6-week longitudinal infection study. Furthermore, the deimmunized lysostaphin evaded established anti-wild-type immunity, thereby providing significant anti-MRSA protection for animals that were immune experienced to the wild-type enzyme. Last, the enzyme synergized with daptomycin to clear a stringent model of MRSA endocarditis. By mitigating T cell-driven antidrug immunity, deimmunized lysostaphin may enable safe, repeated dosing to treat refractory MRSA infections.
In Their Own Voices: Identity and Racial Socialization Experiences of Young Adult Chinese Adoptees:

This qualitative study explored the experiences of transracial Chinese adoptees who were born in China, separated from their biological families, raised in the United States by White families, and ...
Implications of Multigene Panel Testing on Psychosocial Outcomes: A Comparison of Patients With Pancreatic and Breast or Ovarian Cancer

PURPOSENational Comprehensive Cancer Network guidelines for germline genetic testing have included pancreatic cancer in the context of additional family cancer history for many years but this was n...
Evidence of an Anomalous Thomson Effect

Research completed since the title of this paper was submitted indicates that a more correct title would have been “Evidence of an Anomalous Peltier Effect.”
A de novo frameshift variant of ANKRD11 (c.1366_1367dup) in a Chinese patient with KBG syndrome.

KBG syndrome is a rare autosomal dominant genetic disease mainly caused by pathogenic variants of ankyrin repeat domain-containing protein 11 (ANKRD11) or deletions involving ANKRD11. Herein, we report a novel de novo heterozygous frameshift ANKRD11 variant via whole exome sequencing in a Chinese girl with KBG syndrome. A 2-year-2-month-old girl presented with a short stature and developmental delay. Comprehensive physical examinations, endocrine laboratory tests and imaging examination were performed. Whole‐exome sequencing and Sanger sequencing were used to detect and confirm the variant associated with KBG in this patient, respectively. The pathogenicity of the variant was further predicted by several in silico prediction tools. The patient was diagnosed as KBG syndrome with a short stature and developmental delay, as well as characteristic craniofacial abnormalities, including a triangular face, long philtrum, wide eyebrows, a broad nasal bridge, prominent and protruding ears, macrodontia of the upper central incisors, dental crowding, and binocular refractive error. Her skeletal anomalies included brachydactyly, fifth finger clinodactyly, and left-skewed caudal vertebrae. Electroencephalographic results generally showed normal background activity with sporadic spikes and slow wave complexes, as well as multiple spikes and slow wave complexes in the bilateral parietal, occipital, and posterior temporal regions during non-rapid-eye-movement sleep. Brain MRI showed a distended change in the bilateral ventricles and third ventricle, as well as malformation of the sixth ventricle. Whole exome sequencing revealed a novel heterozygous frameshift variant in the patient, ANKRD11 c.1366_1367dup, which was predicted to be pathogenic through in silico analysis. The patient had received physical therapy since 4 months of age, and improvement of gross motor dysfunction was evident. The results of this study expand the spectrum of ANKRD11 variants in KBG patients and provide clinical phenotypic data for KBG syndrome at an early age. Our study also demonstrates that whole exome sequencing is an effective method for the diagnosis of rare genetic disorders.
Rational Addiction and Video Games

As video games become more popular the extent to which they can and should be considered addictive has become controversial. I adapt the classic Becker-Murphy model of rational addiction for video games and apply it to a micro-data panel collected from the online video game Team Fortress 2. I find evidence of significant rational addiction; past and future consumption are important in determining the amount an individual plays today. These data also allow for the identification of individual potential addicts in a way consistent with the rational addiction model. Finally, including learning-by-doing provides evidence of a feedback loop: playing improves the skill of an individual which reinforces his decision to play in the future.
Sample Preparation for Detection of Different Bacterial Strains by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) provides a fast and easy means to identify culturable microorganisms to the species level. The sample preparation of microbial colonies for MALDI-TOF analysis requires a suitable protein extraction method. While standard MALDI-TOF sample preparation methods are well suited for the identification of and the discrimination between microorganisms belonging to different species, they are not disruptive enough to allow the discrimination between different strains of the same microorganism. More disruptive protein extraction methods lead to better discrimination power because they allow a better breakdown of bacterial cell membrane and a more efficient extraction of conserved microbial proteins that are specific to each species and strain. Here we describe how to extract proteins from single microbial colonies using formic acid and acetonitrile to disrupt cells prior to placing them on a target plate for MALDI-TOF MS analysis. Contrary to other sample preparation methods for MALDI-TOF MS, this approach allows the discrimination between different strains of microorganisms of the same species. Our approach also provides the groundwork data for building algorithms that allow the detection of specific microbial strains of interest, with a great potential for diagnostic applications in clinical settings. © 2021 Wiley Periodicals LLC. Basic Protocol: Protein extraction and MALDI-TOF bio-typing of phenotypically distinct bacterial species.
Vibrational two-photon microscopy for tissue imaging: Short-wave infrared surface-enhanced resonance hyper-Raman scattering.

Multiphoton microscopy using short-wave infrared (SWIR) radiation offers nondestructive and high-resolution imaging through tissue. Two-photon fluorescence (TPF), for example, is commonly employed to increase the penetration depth and spatial resolution of SWIR imaging, but the broad spectral peaks limit its multiplexing capabilities. Hyper-Raman scattering, the vibrational analog of TPF, yields spectral features on the order of 20 cm-1 and reporter-functionalized noble metal nanoparticles (NPs) provide a platform for both hyper-Raman signal enhancement and selective targeting in biological media. Herein we report the first tissue imaging study employing surface-enhanced resonance hyper-Raman scattering (SERHRS), the two-photon analog of surface-enhanced resonance Raman scattering. Specifically, we employ multicore gold-silica NPs (Au@SiO2 NPs) functionalized with a near infrared-resonant cyanine dye, 3,3'-diethylthiatricarbocyanine iodide as a SERHRS reporter. SWIR SERHRS spectra are efficiently acquired from mouse spleen tissue. SWIR SERHRS combines two-photon imaging advantages with narrow vibrational peak widths, presenting future applications of multitargeted bioimaging.
Hoboes: Bindlestiffs, Fruit Tramps, and the Harvesting of the West

Review of: "Hoboes: Bindlestiffs, Fruit Tramps, and the Harvesting of the West," by Mark Wyman.
Temperature dependence of the ESR spectrum of NiSnCl6· 6H2O

Abstract : The electron spin resonance spectrum of single-crystal NiSnCl6-6H2O has been measured at X-band at temperatures between 4.2 and 370 K. The results are consistent with low-temperature magnetic and thermal measurements that indicate a singlet ground state for the Ni(H2O)6(2+) complex. Linewidth measurements below 300 K indicate contributions from spin-lattice relaxation and from both isotropic and anisotropic exchange. Linewidth measurements in the vicinity of D = 0 exhibit narrowing due to vanishing of the isotropic exchange contribution and broadening by cross-relaxation.
Tailored light-matter interaction through epsilon-near-zero modes

We use epsilon-near-zero modes in semiconductor nanolayers to design a system whose spectral properties are controlled by their interaction with multi-dipole resonances. This design flexibility renders our platform attractive for efficient nonlinear composite materials.
Consultation-liaison psychiatry: Possibilities for the 1990s☆

Abstract In order for consultation-liaison ( C L ) psychiatry to enhance its acceptance and funding, carefully designed outcome studies that will demonstrate its clinical effectiveness to other disciplines in medicine, departments of psychiatry, hospital administration, third-party payors, and patients are required. The development of alternative methods of funding C L services is described: (1) high-risk screening, renal transplant, geriatric units (Medicare); (2) salary stipends from collaborating disciplines, e.g., medicine, ENT, neoplastics; (3) consultation fees; (4) ambulatory C L clinics (Medicaid); and (5) grants from collaborative research. With a change in structure when it can be employed (from consultation to the screen methodology), the development of scientifically derived outcome data of C L psychiatry interventions, adequate documentation of the evaluation and treatment by C L psychiatry, and the new tools biological psychiatry and psychopharmacology will provide, the 1990s could and should be an exciting time for this subspecialty of psychiatry.
Zeeman Study of the Jahn-Teller Effect in the T 2 g 3 State of Al 2 O 3 : V 3 +

The fine structure of the zero-phonon $^{3}T_{2g}$ state of ${\mathrm{Al}}_{2}$${\mathrm{O}}_{3}$: ${\mathrm{V}}^{3+}$ arising from the trigonal field and spin-orbit coupling is anomalously small. Ligand-field theory predicts a 400-${\mathrm{cm}}^{\ensuremath{-}1}$ splitting, while the observed levels, first fully identified by Scott and Sturge, span only 14 ${\mathrm{cm}}^{\ensuremath{-}1}$. This has been attributed to a large tetragonal Jahn-Teller effect, and a detailed analysis of the zero-phonon levels was made by Scott and Sturge on the basis of Ham's model calculations for octahedral molecules. We have made new measurements on the 0-0 $^{3}T_{2g}$ band, including the axial spectrum, which shows one $\ensuremath{\sigma}$-polarized transition to be magnetic dipole in origin, and the Zeeman effect of the $\ensuremath{\pi}$ and $\ensuremath{\sigma}$ spectra at 10\ifmmode^\circ\else\textdegree\fi{}K in fields up to 40 kG parallel and perpendicular to the trigonal axias. The validity of the Ham-Scott-Sturge model has also been further investigated. We have shown that the details of the Scott-Sturge theory require modification, and that it is possible to explain the observed zero-field level pattern within the framework of Ham's general model if, but only if, the assumption of equal quenching of first-order trigonal field and spin-orbit splittings is dropped. In addition, we have obtained values of the first- and second-order trigonal field and spin-orbit coupling energies which reproduce quantitatively the zero-field energies, Zeeman behavior, selection rules, and intensities of all transitions. It is found that the first-order spin-orbit splitting is some four times less quenched than the first-order trigonal-field splitting.
Notes on family caregiving in acute and critical care.

Having spent more than 15 years of our careers observing patient care and communication in the ICU setting, we recognize the important role family caregivers play at the bedside of acute and critically ill older adults. Over these years, like many of you, we have also experienced the privilege and pathos of serving as family caregivers for older adult family members during hospitalization and at home. While this is a normal part of life and love and being in family, recent evidence points to the importance of re-examining what we mean by “family-centered care,” particularly in critical care environments, with the goal of preventing potentially detrimental long-term consequences affecting family caregivers of critically ill patients. Critical illness has immediate and prolonged psychological effects on family caregivers. This is true for family caregivers of ICU survivors as well as for bereaved family members of patients who die in the ICU. Post-intensive care syndrome in family caregivers (PICS-F) is a constellation of mental health problems, e.g., anxiety, depression, sleep disorders, post-traumatic stress disorder, and complicated grief, experienced by family caregivers arising from and persisting for 1-year or more after a patient’s critical illness 1
Inhibition of agrin-induced acetylcholine-receptor aggregation by heparin, heparan sulfate, and other polyanions

Heparin and heparan sulfate have been shown to block nerve-induced acetylcholine-receptor (AChR) aggregation at developing neuromuscular junctions. We found that heparin, heparan sulfate, and a wide variety of other polyanions also inhibited agrin-induced AChR aggregation. The more highly charged the polyanion, the more potent it was as an inhibitor. Inhibition of agrin-induced AChR aggregation was due, at least in part, to the formation of a complex between the polyanion and agrin that was inactive. These findings are consistent with the hypothesis that nerve-induced aggregation of AChRs is mediated by the release of agrin, or a closely related protein, from axon terminals and suggest that a polyanion, such as a sulfated proteoglycan, may be involved in the interaction of agrin with its receptor on the myotube surface.
Mechanisms of capacitative calcium entry

Capacitative Ca(2+) entry involves the regulation of plasma membrane Ca(2+) channels by the filling state of intracellular Ca(2+) stores in the endoplasmic reticulum (ER). Several theories have been advanced regarding the mechanism by which the stores communicate with the plasma membrane. One such mechanism, supported by recent findings, is conformational coupling: inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) receptors in the ER may sense the fall in Ca(2+) levels through Ca(2+)-binding sites on their lumenal domains, and convey this conformational information directly by physically interacting with Ca(2+) channels in the plasma membrane. In support of this idea, in some cell types, store-operated channels in excised membrane patches appear to depend on the presence of both Ins(1,4,5)P(3) and Ins(1,4,5)P(3) receptors for activity; in addition, inhibitors of Ins(1,4,5)P(3) production that either block phospholipase C or inhibit phosphatidylinositol 4-kinase can block capacitative Ca(2+) entry. However, the electrophysiological current underlying capacitative Ca(2+) entry is not blocked by an Ins(1,4,5)P(3) receptor antagonist, and the blocking effects of a phospholipase C inhibitor are not reversed by the intracellular application of Ins(1,4,5)P(3). Furthermore, cells whose Ins(1,4,5)P(3) receptor genes have been disrupted can nevertheless maintain their capability to activate capacitative Ca(2+) entry channels in response to store depletion. A tentative conclusion is that multiple mechanisms for signaling capacitative Ca(2+) entry may exist, and involve conformational coupling in some cell types and perhaps a diffusible signal in others.
Systems and Distinctions; Duality and Complementarity

The world does not present itself to us neatly divided into systems, subsystems, environments, and so on. These are divisions which we make ourselves, for various purposes, often subsumed under the general purpose evoked by saying “for convenience.” It is evident that different people find it convenient to divide the world in different ways, and even one person will be interested in different systems at different times, for example, now a cell, with the rest of the world its environment, and later the postal system, or the economic system, or the atmospheric system.
Sulfur Metabolism Actively Promotes Initiation of Cell Division in Yeast

Background Sulfur metabolism is required for initiation of cell division, but whether or not it can actively promote cell division remains unknown. Methodology/Principal Findings Here we show that yeast cells with more mtDNA have an expanded reductive phase of their metabolic cycle and an increased sulfur metabolic flux. We also show that in wild type cells manipulations of sulfur metabolic flux phenocopy the enhanced growth rate of cells with more mtDNA. Furthermore, introduction of a hyperactive cystathionine-β-synthase (CBS) allele in wild type cells accelerates initiation of DNA replication. Conclusions/Significance Our results reveal a novel connection between a key sulfur metabolic enzyme, CBS, and the cell cycle. Since the analogous hyperactive CBS allele in human CBS suppresses other disease-causing CBS mutations, our findings may be relevant for human pathology. Taken together, our results demonstrate the importance of sulfur metabolism in actively promoting initiation of cell division.
Physiologic correlates of the heart rate response to upright isotonic exercise: Relevance to rate-responsive pacemakers

Rate-responsive cardiac pacing requires a sensitive physiologic variable that is closely correlated with the heart rate-oxygen uptake relation, particularly in patients with heart failure whose cardiac output response to exercise is more dependent on heart rate. Accordingly, the heart rate response to upright exercise was measured in 81 patients with heart failure or hypertension, or both, and in 27 normal subjects. Oxygen uptake (VO2), minute ventilation (VE), cardiac output, right heart pressures and the mixed venous temperature, oxygen saturation (SvO2) and pH were analyzed throughout exercise. Linear regression analysis of these variables with heart rate revealed the following: 1) There was a highly linear heart rate-VO2 relation in each subject (the average slope of this relation was greater [p less than 0.05] in patients with more severe failure). 2) VE was highly correlated with exercise heart rate, and its slope was not different between normal subjects and patients. 3) Mixed venous temperature and pH were poor predictors of exercise heart rate, particularly at low or moderate levels of work; however, SvO2 was highly correlated with heart rate for all levels of work. Thus, in normal subjects and patients with heart failure or hypertension, or both, heart rate increases linearly with isotonic leg exercise. Minute ventilation and mixed venous oxygen saturation are highly correlated with this response and may serve as potential sensors for rate-responsive pacemakers.
Diagnostic Value of Albumin Gene Expression in Liver Tumors: Case Report and Review of the Literature

Management of a solitary liver mass necessitates reliable distinction between primary hepatocellular carcinoma and metastatic lesions. The histologic differentiation can be difficult even with special stains such as α-fetoprotein, cytokeratin, and carcinoembryonic antigen. Albumin is a specific product of hepatocytes, and in situ hybridization to reveal albumin messenger RNA (mRNA) is highly specific and sensitive for the diagnosis of primary hepatocellular carcinoma. This technique can be used on histopathologic specimens and in cytologic diagnosis. Herein we describe a patient with synchronous renal and hepatic masses, in whom the distinction had to be made between metastatic renal cell carcinoma and two separate primary tumors—one in the liver and one in the kidney. In situ hybridization for albumin mRNA proved helpful in making this distinction. In addition, we review the literature on the diagnostic use of albumin gene expression in liver tumors.
Barotropic Waves in Straight Parallel Flow with Curved Velocity Profile

The paper contains a study of the dynamics of two-dimensional straight parallel flow with a continuously curved profile. The differential equation for the stream-function of a neutral wave disturbance is used as an analytical tool to investigate the properties and the evolution of waves having a certain initial configuration of the flow. The behaviour of the waves is explained by using an extension of the method applied by Holmboe (1953) in his study of the Kelvin and Rayleigh waves. In order to do that, the problem has been approached from a point of view which deviates somewhat from the customary treatment. The method is first illustrated by a model with a hyperbolic tangent profile ( Th -flow), which is shown to have a very simple analytical solution for the stationary wave L 8 . The form of the solution makes it possible to interpret it for other wave lengths ( L ? L 8 ) as a forced stationary wave which is the resultant of a non stationary physical wave and a Rayleigh wave induced by the proper infinite sliding vorticities at the central level. When this foreign field is removed from the solution, the remaining field, which now is a physically possible initial configuration of the flow, will propagate with different speed from level to level. As the tilt develops the wave will begin to amplify if L > L 8 , and it will be damped if L < L 8 . So the stationary wave represents the transition from short stability waves to long instability waves as had been anticipated by Fjortoft (1). The method is then extended to more general types of profiles. Some general results on the conditions for the existence of stationary waves, which were proved or anticipated by Rayleigh (1880), Fjortoft (1950) and Hoiland (1951), are given a unified treatment. It is finally shown that, if a system has stationary waves, they represent the transition from damped to amplified waves. If the number of stationary waves is even, both the shortest and the longest waves are damped waves, and the intermediate intervals of the spectrum are alternate bands of amplified and damped Iwaves. If the number of stationary waves is odd, the longest waves in the spectrum are amplified. DOI: 10.1111/j.2153-3490.1956.tb01197.x
Coding of nonsense vs the detection of patterns

Two theories are contrasted: coding information into arbitrary characters vs extracting patterns from a flux of stimulation. It is argued that coding is the process people use to memorize nonsense and, for that reason, is a poor model for the applied psychology of learning. The contrasting idea, that Ss perceive patterns and extract information. can be used to improve education by leading teachers to organize their material. It is also argued that most demonstrations of coding can be interpreted as examples of pattern perception.