cssi/SciSciGPT-SciSciNet huggingface dataset:
Hexokinase 1 and retinitis pigmentosa: insights into the retina and the molecule.

Retinitis pigmentosa (RP) represents a group of inherited retinal dystrophies characterized by night blindness followed by progressive narrowing of the visual fields, often culminating in vision loss. Retinitis pigmentosa is genetically heterogeneous; currently mutations in at least 63 genes have been implicated.1 Identification of these genes and mutations causing RP has provided unique insights not only into the pathophysiology of retinal degenerations, but also into the basic biology of the retina and the visual pathways within it. Sullivan et al.2 identified a Glu847Lys hexokinase 1 (HK1) mutation in five families with autosomal recessive retinitis pigmentosa (adRP), all of which shared a common extended haplotype, suggesting common ancestry. The severity of RP in affected family members was highly variable, with one individual homozygous for the mutation having severe retinal disease, although no extraocular abnormalities were identified in any individual affected with RP. The Glu847Lys mutation is on the surface of the HK1 molecule, far from any identified functional site, and is not predicted to impair either enzymatic activity or protein stability. Absence of the nonspherocytic hemolytic anemia seen in autosomal recessive HK1 deficiency in affected individuals is consistent with preservation of kinase activity and normal glucose metabolism in the Glu847Lys mutant HK1, and the absence of extraretinal abnormalities suggests gain of a deleterious property specific to the retina. There is precedent for this, as mutations in HK1 have also been associated with Russe hereditary motor and sensory neuropathy,3 and HK1 is known to interact with a number of proteins active in regulating apoptosis, including VDAC1, DREAM, RANBP2, and COX11. While requiring functional confirmation, in addition to expanding our understanding of the genetic architecture of RP, this report suggests that although heavily studied for decades, HK1 has a previously unknown molecular function perhaps active in a novel metabolic or regulatory pathway critical to retinal homeostasis and function.
Circum-Caribbean Sedimentary Basin Development and Timing of Hydrocarbon Maturation as a Function of Caribbean Plate Tectonic Evolution

Sedimentary basin development in the Caribbean region is closely tied to the region’s plate tectonic evolution, which involved (1) Jurassic rifting and passive margin development between North and South America, and (2) Late Cretaceous to Recent relative eastward migration of the Caribbean Plate from the eastern Pacific area to its present position between North and South America. Two primary stratigraphic suites of rock occur in the Caribbean region: (1) an autochthonous suite of Jurassic, Cretaceous, and Cenozoic passive margin sediments that was deposited along the rifted margins of North and South American basement after Jurassic continental breakup, and (2) an allochthonous suite consisting of oceanic crustal and magmatic arc rocks and overlying sedimentary units of the Caribbean Plate. The boundary of these suites coincides roughly with the limit of circumCaribbean thrust belts of metamorphic/mafic rock above the formerly passive Proto-Caribbean shelf rocks. Most of the sediments of the allochthonous Caribbean Plate were deposited during the relative eastward translation between the Americas, and the older sections (Cretaceous) were deposited while thePlate was still in the eastern Pacific realm. Primary source rocks in both suites were deposited in the early Late Cretaceous, well after rifting and plate separation in the Proto-Caribbean Seaway between the Americas.
Medication Errors in HIV-Infected Hospitalized Patients: A Pharmacist's Impact

BACKGROUNDTreatment with highly active antiretroviral therapy (HAART) decreases morbidity and mortality associated with HIV infection. Unfortunately, HAART medication errors are prevalent in hospitalized patients with HIV infection. Appropriate regimen administration and adherence are essential for treatment success.OBJECTIVETo assess the impact of pharmacist interventions on the rate of medication errors in HIV-infected hospitalized patients who had been prescribed HAART in the outpatient setting.METHODSHospitalized patients aged 18 years or older receiving HAART and/or opportunistic infection (OI) prophylaxis were screened for inclusion. Data collection for each enrolled patient included demographic information, pertinent laboratory results, and inpatient and outpatient medication regimens. Patient medication profiles were reviewed within 72 hours of admission. HAART and/or OI prophylaxis errors were classified by type and frequency. Following the pharmacist intervention, prescribers' responses to each ...
Gastric Acid, Calcium Absorption, and Their Impact on Bone Health

Calcium balance is essential for a multitude of physiological processes, ranging from cell signaling to maintenance of bone health. Adequate intestinal absorption of calcium is a major factor for maintaining systemic calcium homeostasis. Recent observations indicate that a reduction of gastric acidity may impair effective calcium uptake through the intestine. This article reviews the physiology of gastric acid secretion, intestinal calcium absorption, and their respective neuroendocrine regulation and explores the physiological basis of a potential link between these individual systems.
Emotion judgments do not differ as a function of perceived nationality

This article reports three studies concerning the relationship between emotion judgments and perceived nationality of the expressors being judged. Study 1 demonstrated that observers do not reliably make implicit assumptions about the nationalities of the expressors in judgment tasks. Study 2 examined judgments of Americans and Japanese observers who were told that Caucasian and Asian expressors were Americans and Japanese, respectively, and who made fixed‐choice judgments and intensity ratings. Study 3 examined judgments of Americans given similar instructions and who used a multiscalar rating task. Neither Studies 2 nor 3 provided evidence that nationality information affected judgments. These findings have implications not only for basic emotion theory, but also for international and intercultural communication training. Cet article rapporte trois etudes concernant la relation entre les jugements d'emotions et la nationalite percue des expressions qui doivent etre jugees. L'etude 1 a demontre que les o...
Access Control Policy Misconfiguration Detection in Online Social Networks

The ability to stay connected with friends online and share information, has accounted for the popularity of online social networking websites. However, the overwhelming task of access control policy management for information shared on these websites has resulted in various mental models of sharing with a false sense of privacy. The misalignment between a user's intended and actual privacy settings causes access control misconfigurations, raising the risk of unintentional privacy leaks. In this paper, we propose a scheme to extract the user's mental model of sharing, enhance this model using information learned from their existing policies, and enable them to compose misconfiguration free policies. We present the possible misconfiguration patterns based on which we scan the Facebook user's access control policies. We implemented a prototype Facebook application of our scheme and conducted a pilot study using Amazon Mechanical Turk. Our preliminary results show that the users' intended policies were significantly different than their actual policies. Our scheme was able to detect the misconfiguration patterns in album policies. However, the reduction in the number of misconfigurations after using our approach was not significant. Participants' perceptions of our proposed policy misconfiguration patterns and the usability of our scheme was positive.
Environmental Effects on Developing Wheat as Sensed by Near-Infrared Reflectance of Mature Grains

ABSTRACT For 30 years, near-infrared (NIR) spectroscopy has routinely been applied to the cereal grains for the purpose of rapidly measuring concentrations of constituents such as protein and moisture. The research described herein examined the ability of NIR reflectance spectroscopy on harvested wheat to determine weather-related, quality-determining properties that occurred during plant development. Twenty commercial cultivars or advanced breeding lines of hard red winter and hard white wheat (Triticum aestivum L.) were grown in 10 geographical locations under prevailing natural conditions of the U.S. Great Plains. Diffuse reflectance spectra (1,100–2,498 nm) of ground wheat from these samples were modeled by partial least squares one (PLS1) and multiple linear regression algorithms for the following properties: SDS sedimentation volume, amount of time during grain fill in which the temperature or relative humidity exceeded or was less than a threshold level (i.e., >30, >32, >35, 80%, <40% rh). ...
Exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus

Abstract Exercise is an important facet of behavior that enhances brain health and function. Increased expression of the plasticity molecule brain-derived neurotrophic factor (BDNF) as a response to exercise may be a central factor in exercise-derived benefits to brain function. In rodents, daily wheel-running exercise increases BDNF gene and protein levels in the hippocampus. However, in humans, exercise patterns are generally less rigorous, and rarely follow a daily consistency. The benefit to the brain of intermittent exercise is unknown, and the duration that exercise benefits endure after exercise has ended is unexplored. In this study, BDNF protein expression was used as an index of the hippocampal response to exercise. Both daily exercise and alternating days of exercise increased BDNF protein, and levels progressively increased with longer running duration, even after 3 months of daily exercise. Exercise on alternating days was as effective as daily exercise, even though exercise took place only on half as many days as in the daily regimen. In addition, BDNF protein remained elevated for several days after exercise ceased. Further, after prior exercise experience, a brief second exercise re-exposure insufficient to cause a BDNF change in naive animals, rapidly reinduced BDNF protein to levels normally requiring several weeks of exercise for induction. The protein reinduction occurred with an intervening “rest” period as long as 2 weeks. The rapid reinduction of BDNF by an exercise stimulation protocol that is normally subthreshold in naive animals suggests that exercise primes a molecular memory for BDNF induction. These findings are clinically important because they provide guidelines for optimizing the design of exercise and rehabilitation programs, in order to promote hippocampal function.
Healthcare Reform After SCOTUS: Hard Decisions Needed to Avoid Health Sector Meltdown.

he Supreme Court upheld most of the Affordable Care Act (ACA), giving the White House cause to breathe a sigh of relief. The Court ruled the individual mandate to buy insurance constitutional, requiring only that we call the penalty for noncompliance a tax. The only real setback was in Medicaid. The federal government’s threat to take away all Medicaid funding from a state that did not expand eligibility to everyone with incomes below 133% of the poverty level was declared coercive and unconstitutional. With that caveat, proponents claim that the Obama healthcare reform will proceed as scheduled. Don’t bet on it. The Supreme Court may have settled some issues, but its decision opened up new areas of uncertainty. Will the renamed individual mandate penalty/tax be effective in leading both healthy and unhealthy people to buy insurance? Will states, facing serious fiscal problems, expand eligibility for Medicaid? More fundamentally, will the myriad changes called for by the ACA be implemented on time and with the impact promised by the White House? We have already seen a major component of the ACA fail because it promised more than it could deliver. The Community Living Assistance Services and Supports Act (better known as the CLASS Act) was a government long-term care insurance program that could not be made financially solvent and was eventually shelved.
The Influence of Dietary Alfalfa Meal on the Availability of Phosphorus from Curacao Island Phosphate to the Chick

Abstract ASSAY techniques differ not only in the . calcium and phosphorus content of the assay diet, but also in feedstuffs used in the assay diet and the actual procedures. Ammerman et al. (1960) suggested a fourday depletion period followed by a six-day phosphorus supplementation period for a rapid assay of inorganic phosphates with chicks. Motzok et al. (1967) fed chicks four weeks when studying utilization of calcium and phosphorus from soft phosphate. Damron and Harms (1969) fed chicks the same diet from one to 21 days of age in developing a standard curve for Curacao Island phosphate Equally as confusing is the variety of feedstuffs used in the assay basal diet. Corn is generally used as the primary energy source, but some workers have used ground yellow corn (Motzok et al., 1967; Nelson and Peeler, 1961) while others have used degerminated corn meal (Ammerman et al., 1960; Dilworth and Day,…
Pathology of Tumors of the External Ear in Mice Induced by Ultraviolet Radiation

This paper deals with the gross and histologic features of tumors of the external ear induced in male mice of strain A by ultraviolet radiation according to the technique discussed in the preceding paper (1). Details of dosage, intensity, and incidence data may be found therein. Tumors of the external ear have been adopted as the basis for incidence studies since in a total of 147 tumor-bearing mice the external ear has been involved in 144. Tumors of the eye have developed in 6 mice, 3 in combination with tumors of the ear and 3 without tumor elsewhere. These latter have not been included in the incidence data, and the 3 animals bearing tumors of both eye and ear have been listed as positive for statistical purposes only when the tumor of the ear appeared. When a tumor appeared on the external ear the animal was killed by cervical dislocation, and both ears and cervical lymph nodes were immediately placed in Zenker's fluid containing 5 percent of acetic acid. Histologic examination of the Bars and cervical nodes was made in every instance, and any other lesions observed at autopsy were allo examined histologically. Tissues were embedded in paraffin. The haematoxylin-eosin stain was employed routinely; other stains employed on occasion were Mallory's phosphotungstic-acid haematoxylin, Mallory's aniline blue, and Wilder's or Foot's methodsfordemonstrating reticulum.
Inductive Approaches to Structural Safety

The limitations of conventional systems of (structural) safety, which are based on the definition: safety: mathematical reliability, are pointed out. In substitution, more general inductive systems are proposed which consider safety as a subjective feeling, inclusive of sociological and psychological conditionings; human judgement is an essential linking element of these systems. The widely documented suboptimality of human inference, when compared with normative rules is considered, and ways are suggested to improve its coherence by using Bayes' theorem in various formulations. Descriptive models of human information processing are also reviewed. The opinion is expressed that inductive models create an appropriate ground on which probabilistic and nonprobabilistic approaches to (structural) safety can be reconciled.
Vector serotype screening for use in ovine perinatal lung gene therapy.

Abstract Purpose Successful in utero or perinatal gene therapy for congenital lung diseases, such as cystic fibrosis and surfactant protein deficiency, requires identifying clinically relevant viral vectors that efficiently transduce airway epithelial cells. The purpose of the current preclinical large animal study was to evaluate lung epithelium transduction of adeno-associated viral (AAV) vector serotypes following intratracheal delivery. Methods Six different AAV vector serotypes (AAV1, AAV5, AAV6, AAV8, AAV9, and AAVrh10) expressing the green fluorescent protein (GFP) as the transgene were injected into the right upper lobe of perinatal sheep via bronchoscopy. At 1 week, samples were harvested, analyzed by fluorescent stereomicroscopy and immunohistochemistry, and quantified using a radial grid and quantitative real-time polymerase chain reaction (qPCR). Results Fluorescent stereomicroscopy demonstrated GFP expression in the right upper lobe following injection of all AAV serotypes assessed except AAV5. Immunohistochemistry analysis confirmed GFP expression in small- and medium-sized airways following intratracheal injection of AAV1, 6, 8, 9, and rh10. However, only AAV8 and AAVrh10 resulted in transgene expression in large airways. These results were confirmed by qPCR, yet, after 40 cycles, AAV1 did not show GFP gene amplification. Conclusion Adeno-associated viral vector serotypes 6, 8, 9, and rh10 demonstrated efficient GFP transgene expression at early time points, and AAV8 demonstrated efficient transduction of all airway sizes with high pulmonary GFP expression tested using qPCR.
Acoustic Analogy for Oscillations Induced by Supersonic Flow over a Forward-Facing Nose Cavity

The development of a spring-mass-damper acoustic analogy for oscillations induced by supersonic flow over a hemispherical nose with a cylindrical nose cavity is presented. The acoustic analogy is verified against computational fluid dynamics (CFD) simulations in which cavity oscillations develop due to sinusoidal freestream flow perturbations. The verification involves examination of parametric sensitivities including freestream perturbation noise frequency and amplitude, cavity length-todiameter (L/D) ratio, freestream Mach number, and nose-to-cavity diameter ratio. Fluid mechanic and acoustic physical arguments are offered to explain the parametric sensitivities, as well as the onset of self-sustained oscillations for sufficiently deep cavities (i.e., oscillations without freestream flow perturbations). The CFD flow solver is validated for prediction of the onset of self-sustained oscillations against experimental data obtained in the Mach 4 Purdue Quiet Flow LudwiegTube (PQFLT).
Ubiquitous assembly of amphiphilic baskets into unilamellar vesicles and their recognition characteristics.

An amphiphilic basket of type 1 (339 A(3)) has been found to assemble into unilamellar vesicles in water. The assembled host encapsulates organophosphonates (OPs) (119-185 A(3)) with a particularly high affinity (Ka ∼ 10(5) M(-1)) toward dimethyl phenylphosphonate (185 A(3)) whose size and shape resemble that of soman (186 A(3)). Importantly, the entrapment of OPs prompts a phase transformation of vesicular 1 into nanoparticles or larger vesicles as a function of the shape of the host-guest complex.
Simultaneous improvements in wear resistance and mechanical properties of UHMWPE nanocomposite fabricated via a facile approach

Abstract To meet the high demand for enhanced tribological and mechanical properties of ultra-high molecular weight polyethylene (UHMWPE), the incorporation of nano-reinforcements has generally been applied. However, the conventional processing techniques are not readily applicable to the fabrication of UHMWPE nanocomposites because of the extremely high viscosity of UHMWPE and poor filler-matrix interactions. In this study, we report a facile and effective approach to the fabrication of UHMWPE nanocomposites reinforced with graphite nanoplatelets (GNPs). The modification of GNP surfaces with organosilane was found to effectively disperse the GNP in the polymer matrix and to improve interfacial interactions between phases. As a result, simultaneous improvements in wear resistance and storage modulus have been realized for the UHMWPE nanocomposites with silanized GNPs, up to 980% and 170%, respectively.
Development of Non-Hodgkin’s Lymphoma As Second Primary Cancer in Hepatitis C Virus-Infected Patients with a Different Primary Malignancy – a Case Series

Background: Hepatitis C virus (HCV) is carcinogenic and infected patients are at increased risk of developing hepatocellular carcinoma (HCC) and non-Hodgkin’s lymphoma (NHL). HCC can develop as a as a second primary cancer (SPC) in HCV-infected cancer patients with a nonliver first primary cancer. However, reports on HCV-infected patients who develop NHL as SPC are lacking. Methods: Records of patients with chronic HCV infection who were seen at MD Anderson Cancer Center, Houston, TX, between 01/2008 - 5/2014 were reviewed. Patients who developed NHL in the setting of a different primary malignancy were described in this case series. HCV therapy did not include newly approved antivirals. Results: Eighty four patients with HCV-associated NHL were seen during the study period. Among, them, six (7%) developed NHL as SPC; most were men (n=4; 67%), Caucasians (n=5; 83%), and had genotype 1 infection (two patients had genotype known; both had genotype 1b infection). All patients had solid first primary cancers, mostly prostate cancer (n=3; 50%), followed by choriocarcinoma (n=1; 17%), chondrosarcoma (n=1; 17%), and squamous cell carcinoma of larynx (n=1; 17%). Most patients (n=5; 83%) had their first primary cancers in complete remission, and only 1 had cirrhosis at lymphoma diagnosis. Surgery (n=3; 50%) and chemotherapy (n=2; 34%) were the main treatment modalities for first primary malignancies, with leuprolide acetate and carboplatin as the only chemotherapeutic agents administered. The types of NHL developed as SPC were diffuse large B cell lymphoma (n=3; 50%), marginal zone B cell lymphoma (n=2; 33%), and mantle cell lymphoma (n=1; 17%). None of the patients had a family history of lymphoma. NHL was not suspected and was found incidentally in all patients at a median of 34 months (range, 2 – 410 months) after the diagnosis of the first primary malignancy. Hepatitis B core antibodies were detected in 4 (67%) patients. A majority of patients had persistent HCV viremia (n=4; 67%) when NHL was diagnosed. Two of the 3 patients who were treated for HCV infection had attained sustained virological response (regarded as virological cure). Conclusions: NHL may develop as SPC in HCV-infected patients with a different primary malignancy, especially in patients who have primary solid tumors or unresolved infection. Therefore, surveillance not only for the development of HCC but also NHL as SPCs should be continued in HCV-infected patients with different primary malignancy. Eradication of this carcinogenic virus with better tolerated and more efficacious antivirals may potentially reduce the risk of NHL development as SPC. Disclosures Torres: Gilead Sciences: Consultancy; Merck & Co., Inc. : Consultancy, Research Funding; Vertex Pharmaceuticals: Consultancy, Research Funding; Genentech,: Consultancy.
Decompressive craniectomy, reperfusion, or a combination for early treatment of acute "malignant" cerebral hemispheric stroke in rats? Potential mechanisms studied by MRI.

Background and Purpose —Both early reperfusion and decompressive craniectomy have proved beneficial in the treatment of large space-occupying “malignant” hemispheric stroke. The aim of this study was to directly compare the benefit of reperfusion with that of craniectomy and to study the effects of combined treatment in a rat model of focal cerebral ischemia. Methods —Cerebral ischemia was introduced in 28 rats. Four groups were investigated: (1) no treatment, (2) decompressive craniectomy, (3) reperfusion, and (4) reperfusion and craniectomy as treatment at 1 hour after middle cerebral artery occlusion. Perfusion- and diffusion-weighted MRI were performed serially from 0.5 to 6 hours after middle cerebral artery occlusion. Results —The 6-hour DWI-derived hemispheric lesion volumes in the reperfusion group (10.2±3.9%), the craniectomy group (23.0±6.4%), and the combination group (21.8±12.4) were significantly smaller than that in the control group (44.1±5.4%) ( P <0.05). Reperfusion, craniectomy, and combined treatment led to higher perfusion in the cortex compared with the control group, whereas only reperfused animals achieved significantly higher perfusion in the basal ganglia. In 5 animals, combined reperfusion and decompressive craniectomy resulted in an early contrast media enhancement. Conclusions —Early reperfusion and craniectomy were shown to be effective in decreasing infarction volume by improving cerebral perfusion. Reperfusion remains the best therapy in malignant hemispheric stroke. Combined treatment yields no additional benefit compared with single treatment, probably because of early blood-brain barrier breakdown.
By "fancy or agreement": Locke's theory of money and the justice of the global monetary system

Locke argues that the consent of market participants to the introduction of money justifies the economic inequalities resulting from monetarization. This paper shows that Locke’s argument fails to justify such inequalities. My critique proceeds in two parts. Regarding the consequences of the consent to money, neo-Lockeans wrongly take consent to justify inequalities in the original appropriation of land. In contrast, I defend the view that consent can only justify inequalities resulting directly from monetized commercial exchange. Secondly, regarding the nature of consent, neo-Lockeans uncritically accept Locke’s account of money as a natural institution. In contrast, I argue that money is an irreducibly political institution and that monetary economies cannot develop in the state of nature. My political account of money has far-reaching implications for the normative analysis of the global monetary system and the justification of the economic inequalities consequent upon it.
Laboratory Reports: Communicating Results and Conclusions

“One could argue that the most critical aspect of forensic science is the product of a report.”
P82 Comparison of rsv hospitalisation in preterm infants with chronic lung disease who do not qualify for palivizumab prophylaxis with those who qualify in nottingham, uk

Introduction Palivizumab prophylaxis reduces the likelihood of serious respiratory tract infection by Respiratory Syncytial Virus (RSV) in ex-preterm infants with Chronic Lung Disease (CLD). The Nottingham CLD service follows the Joint Committee on Vaccination and Immunisation (JCVI) guidelines for Palivizumab prophylaxis based on gestation, respiratory status and chronological age at the beginning of RSV season. This retrospective observational study was conducted to compare the RSV hospitalisations in preterm infants with CLD who are offered Palvizumab to those with milder CLD. Materials and Methods We hypothesised that the RSV hospitalisation rate and length of hospital stay (LOS) within the 1 st year of life between preterm babies in home oxygen with CLD immunised according to the JCVI criteria and babies with moderate CLD not discharged in home oxygen would be comparable. Our cohort included babies born in Nottingham UK between 2009 and 2015. Data was collected from hospital records and the Nottingham CLD database, and analysed using Fisher’s exact test for proportions and Mann-Whitney test for continuous data. Results In total there were 3478 babies born preterm ( Conclusion The RSV hospitalisation rate was lower in preterm infants who did not qualify for Palivizumab compared to infants who qualified according to JCVI guideline but this difference was not statistically significant. A large prospective multi-centre study is required to ascertain the clinical and economic benefits of including the wider group for Palivizumab prophylaxis.
Preservation of structural and functional polarity in isolated epithelial cells

We describe a method to isolate epithelial cells from gallbladders of Necturus maculosus with preserved structural and functional polarity. Isolation was carried out with a mixture of collagenase and protease, with only a brief exposure to a divalent-cation-free medium. About 40% of the isolated epithelial cells had a "figure-eight" shape and retained metabolic and cell membrane integrity. Figure-eight cells display features consistent with preserved polarity for several hours, including the following: 1) the "apical" and "basolateral" membrane domains were differentially labeled by a hydrophobic fluorescent dye; 2) freeze fracture electron microscopy verified two plasma membrane domains differing in the presence of microvilli and folds and separated by tight junctions; 3) proteins such as ZO-1, NHE3, and Na(+)-K(+)-ATPase remained localized in the junctional, apical, and basolateral regions, respectively; 4) after apical surface exposure to wheat germ agglutinin, the label remained in the apical membrane after cell isolation; and 5) patch-clamp experiments demonstrated polarized expression of K+ channels. Polarity was rapidly lost after removal of extracellular Ca2+, exposure to trypsin, or ATP depletion. Therefore, this preparation allows for structural and functional studies of epithelial transport in single cells retaining the essential features present in the assembled epithelium.
Death and gastrointestinal bleeding complicate encephalomyelitis in mice with delayed appearance of CNS IgM after intranasal alphavirus infection.

Central nervous system (CNS) infection of C57BL/6 mice with the TE strain of Sindbis virus (SINV) provides a valuable animal model for studying the pathogenesis of alphavirus encephalomyelitis. While SINV TE inoculated intracranially causes little mortality, 20–30 % of mice inoculated intranasally (IN) died 8 to 11 days after infection, the period during which immune cells typically infiltrate the brain and clear infectious virus. To examine the mechanism behind the mortality, mice infected IN with SINV TE were monitored for evidence of neurological disease, and those with signs of severe disease (moribund) were sacrificed and tissues collected. Mice showing the usual mild signs of encephalomyelitis were concurrently sacrificed to serve as time-matched controls (sick). Sixty-eight per cent of the moribund mice, but none of the sick mice, showed upper gastrointestinal bleeding due to gastric ulceration. Clinical disease and gastrointestinal pathology could not be attributed to direct viral infection of tissues outside of the CNS, and brain pathology and inflammation were comparable in sick and moribund mice. However, more SINV antigen was present in the brains of moribund mice, and clearance of infectious virus from the CNS was delayed compared to sick mice. Lower levels of SINV-specific IgM and fewer B220+ B cells were present in the brains of moribund mice compared to sick mice, despite similar levels of antiviral IgM and IgG in serum. These findings highlight the importance of the local antibody response in determining the outcome of viral encephalomyelitis and offer a model system for understanding individual variation in this response.
Radiation carcinogenesis in the whole-body system

The objectives of the trip were: to take part in and to give the summary of a Symposium on Radiation Carcinogenesis at Tokyo, and to give a talk at the National Institute of Radiological Sciences at Chiba. The breadth of the aspects considered at the conference was about as broad as is possible, from effects at the molecular level to human epidemiology, from the effects of tritium to cancer induction by heavy ions. The events induced by cancer that lead to cancer and the events that are secondary are beginning to come into better focus but much is still not known. Interest in suppressor genes is increasing rapidly in the studies of human tumors and many would predict that the three or four suppressor genes associated with cancer are only the first sighting of a much larger number.
TIKHONOV REGULARIZATION OF LARGE LINEAR PROBLEMS

Many numerical methods for the solution of linear ill-posed problems apply Tikhonov regularization. This paper presents a new numerical method, based on Lanczos bidiagonalization and Gauss quadrature, for Tikhonov regularization of large-scale problems. An estimate of the norm of the error in the data is assumed to be available. This allows the value of the regularization parameter to be determined by the discrepancy principle.
Current Status of Practical Applications: Pets

Probiotics are marketed in the human food sector as being beneficial to gut health. As is often the case, this led to similar trends in the pet food and supplement markets. Although it is difficult to incorporate probiotics into pet diets because of processing problems, supplements and diets containing probiotics are now available. There is limited oversight of these products, however, so their application in a clinical setting is limited. Despite this situation, research on the topic is continuing to increase, and more outcomes regarding gut health are being evaluated. Overall, many of the probiotics evaluated in dogs and cats had positive effects on immune health, and some strains reduced potentially pathogenic bacterial species in the large bowel, all without affecting nutrient digestibility. There is more research needed, especially in regard to animals in diseased states, the determination of efficacious dosages for each bacterial strain, and evaluating the use of symbiotics.
NetCentre Company Smart Card Issuance for IBM’s NetCentre Network Computers

Network Computers (NCs) have generated a lot of press, both positive and negative, over the last year. The NC’s promise of low cost of ownership, ease of administration, and high security has captured the interest of many UT professionals. Since its debute at fall ’96 Comdex, the NetCentre NC platform has received rave reviews at numerous international trade shows and OEM/customer engagements. It has been recognized by UT experts and analysts as a cutting-edge platform for building a variety of NC devices. One reason for this response can be found in the NetCentre’s use of smart cards (SCs).
Site-Directed Mutagenesis Using Uracil-Containing Double-Stranded DNA Templates and DpnI Digestion

DpnI can cleave fully methylated parental DNA while leaving hemi-methylated DNA intact. Based on this observation, we developed a rapid site-directed mutagenesis method using uracil-containing, dou...
In the matter of J Hendrik Schön

The physicists have known sin” J. Robert Oppenheimer is famously said to have said. That was on the occasion of the first nuclear explosion. Sin in the form of faking scientific data seemed to be reserved to biology and related sciences, not physics. I used to think I understood why.
Reliability study of Stirling engines for solar dish/heat engine systems

The objective of this study was to examine the reliability of existing and improved Stirling engine concepts for dispersed solar dish-electric applications in the 25-50 kWe range. Five current kinematic Stirling engine designs have the capability to meet or exceed the 32% efficiency goal of the DOE Solar Thermal Program. A review of historical Stirling engine data illustrated that the three major reliability issues with kinematic Stirling engines are the piston-rod seals, engine hot parts (i.e., heater head, regenerator and cylinders) and power control/drive system. The most significant reliability issue associated with achieving the 50,000 hour operating life goal involves piston-rod seals. A specific kinematic engine concept that appears to have the potential for meeting the 50,000 hour operating lifetime requirement of solar power systems is the STM4-120 engine. This engine has a pressurized crankcase to reduce piston-rod seal problems, an indirect heat pipe hot-end section to smooth out temperature gradients in the heater tubes, and a variable angle swashplate for power control.
Acoustic evidence for gestural overlap in consonant sequences

Acoustic evidence for temporal overlap of the two closure gestures in the environment VC ≠ CV was investigated. It was hypothesized that evidence of C2 would be found in the VC formant transitions and would increasingly dominate the transitions as rate (and, by hypothesis, overlap) increased. Twenty repetitions (10 at a normal rate and 10 at a rapid rate) of word pairs where the first word ended in /d/ and the second began with /p/, /t/, or /k/ were elicited in a sentence context from four subjects. F2 and F3 transitions from the midpoint of V1, to just before closure were then measured. In all environments, C2 had a clear influence on the VC formant transitions. The rate effects were less clear. For the /d ≠ k/ environment, a significant correlation was found between more prominent velar transitions and increasing ratio of vowel duration to consonant closure duration, which may be considered a measure of increasing consonant overlap. The acoustic influence of C2 on V1, suggests considerable temporal overlap of the two closure gestures, and at least for the /d ≠ k/ case, increasing overlap as a function of one strategy for increasing rate.
Detection and measurement of low levels of prothrombin. Use of a procoagulant from Echis carinatus venom.

Abstract The ability of a procoagulant fraction from the venom of the saw-scaled viper ( Echis carinatus sochureki ) to convert prothrombin to thrombin in the absence of Ca2+ or other cofactors was used as the basis of a sensitive test method for prothrombin. Incubation of a test sample with prothrombin-free human fibrinogen and the procoagulant fraction resulted in clotting if prothrombin was present in the test sample; clotting time was a function of the amount of prothrombin over the range 0.02 – 1.0 unit. The test method appears valuable for detecting and quantitating low levels of prothrombin contamination in therapeutic products and in laboratory preparations of coagulation factors.
A Unified Theory of Trust and Collaboration

We consider a type of applications where collaboration and trust are tightly coupled with the need to protect sensitive information. Existing trust management technologies have been limited to offering generic mechanisms for enforcing access control policies based on exchanged credentials, and rarely deal with the situated meaning of trust in a specific collaborative context. Towards trust management for highly dynamic and collaborative activities, this paper describes a theory of trust intention and semantics that makes explicit connections between collaborative activities and trust. The model supports inferring trust state based on knowledge about state of collaborative activity. It is the first step towards a unified approach for computer-mediated trust communication in the context of collaborative work.
Treatment of Tonsillar Carcinoma following Nononcologic Tonsillectomy: Efficacy of Transoral Robotic Revision Tonsillectomy:

ObjectiveTo evaluate whether transoral robotic surgery (TORS) is a suitable treatment approach for patients diagnosed with tonsillar carcinoma after a standard palatine tonsillectomy.Study DesignRe...
Betrixaban for first-line venous thromboembolism prevention in acute medically ill patients with risk factors for venous thromboembolism

INTRODUCTION Compared to other direct oral anticoagulants, betrixaban has a longer half-life, smaller peak-trough variance, minimal renal clearance, and minimal hepatic Cytochrome P (CYP) metabolism. The Acute Medically Ill VTE Prevention with Extended Duration Betrixaban (APEX) trial evaluated the efficacy and safety of extended duration betrixaban compared to standard duration enoxaparin in acutely ill hospitalized patients. Areas covered: This article describes the role of betrixaban in the prevention of venous thromboembolism (VTE) in acutely ill medical patients. This article provides a consolidated summary of the primary APEX study findings as well as prespecified and exploratory substudies. This article also provides a review of the results of studies in which other direct factor Xa inhibitors have been evaluated in an extended duration regimen in this patient population. Expert commentary: While previous agents have demonstrated that extended duration VTE prophylaxis can be efficacious, betrixaban is the first agent to demonstrate efficacy without an increase in major bleeding. The totality of the data from the APEX trial supports extended duration betrixaban for VTE prophylaxis in the acute medically ill patient population. As such, betrixaban has been approved in the USA for extended VTE prophylaxis in at-risk acute medically ill patients.
Novel Treatments in Lupus

Purpose of Review The treatment of systemic lupus erythematosus (SLE) still depends on non-specific immunosuppression. Herein, we review promising targeted therapies that have the potential to change this therapeutic paradigm.
Utility of radiation after neoadjuvant chemotherapy for surgically resectable esophageal cancer.

172Background: Neoadjuvant chemotherapy (NAC) is the gold standard approach for locally advanced esophageal cancer (EC), however the addition of radiation remains largely controversial. We sought t...
Shell-Ornament Production in Ejutla: Implications for highland–coastal interaction in ancient Oaxaca

Findings from recent survey and excavation projects in Ejutla, Oaxaca, enable a broader examination of marine shell use and exchange in ancient Mesoamerica. A variety of shell ornaments were manufactured from Pacific Coast species at the Ejutla site during the Terminal Formative/Early Classic periods. Comparisons of the Ejutla mollusc assemblage with shell ornaments found at other highland Oaxaca sites indicate shifts in the nature of shell-ornament manufacture and exchange during the Formative and Early Classic periods. These changes, in conjunction with other findings, signal shifting relationships late in the Formative period among Monte Alban, the Ejutla Valley, and the Pacific Coast. The recognized shifts in highland-lowland Oaxaca relations generally coincide with an expanded importance of Pacific Coast shell at Teotihuacan and in the Lowland Maya region.
Molecular cloning of pp120/ECTO-ATPase, an endogenous substrate of the insulin receptor kinase.

In recent years, a great deal of attention has been devoted to dissecting intracellular pathways of insulin action following activation of the insulin receptor kinase (1). Several laboratories have reported the identification of protein substrates of the insulin receptor tyrosine kinase (2). Here, we review our studies of pp120/ecto-ATPase, a liver-specific glycoprotein of Mr-120,000 which was originally identified by us as a substrate of the insulin receptor tyrosine kinase in cell-free phosphorylation assays (3). Independently, other laboratories have identified the same protein as a hepatic enzyme capable of hydrolyzing extracellular ATP and GTP. Recently, cDNA and genomic cloning studies have contributed to elucidate the structure of this protein and to formulate hypotheses on its function. This chapter will focus on the potential role of pp120/ecto-ATPase in mediating actions of insulin in the liver.
Cas9 Cleavage of Viral Genomes Primes the Acquisition of New Immunological Memories

Type II CRISPR-Cas systems defend prokaryotes from bacteriophage infection through the acquisition of short viral DNA sequences known as spacers, which are transcribed into short RNA guides to specify the targets of the Cas9 nuclease. To counter the potentially devastating propagation of escaper phages with mutations in the target sequences, the host population acquires many different spacers. Whether and how pre-existing spacers in type II systems affect the acquisition of new ones is unknown. Here, we demonstrate that previously acquired spacers promote additional spacer acquisition from the vicinity of the target DNA site cleaved by Cas9. Therefore, CRISPR immune cells acquire additional spacers at the same time as they destroy the infecting virus. This anticipates the rise of escapers or related viruses that could escape targeting by the first spacer acquired. Our results thus reveal Cas9's role in the generation of immunological memories.
Abstract 176: Genetic Ablation of Cyclophilin-D in Mice Increases Physical and Cognitive Performance During Hypoxia

Introduction: We previously reported that silencing of the mitochondrial peptidyl-prolyl isomerase Cyclophilin-D (Cyp-D) in HEK 293T cells reduces oxygen consumption (VO2). In vivo Cyp-D ablation u...
Endothelial prolyl hydroxylase 2 is necessary for angiotensin II-mediated renal fibrosis and injury

Angiotensin II (ANG II) is the key contributor to renal fibrosis and injury. The present study investigated the role of endothelium prolyl hydroxylase 2 (PHD2) in ANG II-mediated renal fibrosis and injury. In vitro, endothelial cells (ECs) were isolated from PHD2f/f control [wild-type (WT)] mice or PHD2 EC knockout (PHD2ECKO) mice. In vivo, WT and PHD2ECKO mice were infused with ANG II (1,000 ng·kg-1·min-1) for 28 days. Renal fibrosis, reactive oxygen species (ROS), and iron contents were measured. Knockout of PHD2 resulted in a significant increase in the expression of hypoxia-inducible factor (HIF)-1α and HIF-2α in ECs. Intriguingly, knockout of PHD2 significantly reduced expression of the ANG II type 1 receptor (AT1R) in ECs. WT mice infused with ANG II caused increases in renal fibrosis, ROS formation, and iron contents. ANG II treatment led to a downregulation of PHD1 expression and upregulation of HIF-1α and HIF-2α in the renal cortex and medulla. Knockout of PHD2 in EC blunted ANG II-induced downregulation of PHD1 expression. Furthermore, knockout of PHD2 in ECs attenuated ANG II-induced expression of HIF-1α, HIF-2α, transforming growth factor-β1, p47phox, gp91phox, heme oxygenase-1, and ferroportin. This was accompanied by a significant suppression of renal fibrosis, ROS formation, and iron accumulation. In summary, knockout of endothelial PHD2 suppressed the expression of AT1R in ECs and blunted ANG II-induced downregulation of PHD1 and upregulation of HIF-α in the kidney. Our study, for the first time, demonstrates a necessary role of endothelial PHD2 in ANG II-mediated renal fibrosis and injury.
Higher Child Body Mass Index Is Associated with Greater School-Based Health Center Utilization.

Background: Children with overweight status and obesity seek care for acute illnesses more often than normal weight peers. School-based health centers (SBHCs) have a role in acute and chronic disea...
Development and implementation of competency-based assessment for urological ultrasound training using SonoSim: A preliminary evaluation.

Introduction: Urology residents are encouraged to learn ultrasound (U/S) imaging, yet there are few tools available for teaching and assessing a resident's competence. The aim of this study was to test the new SonoSim LiveScan® and to propose a competency-based assessment model for the urology graduate medical education. Materials and Methods: Urology residents attended an interactive training session covering the urological U/S techniques guided by the assessment model developed by the authors. Faculty members evaluated the residents using defined objectives, and the residents were surveyed on their comfort level for performing each of the model tasks. A subset of the residents then underwent a structured testing using the SonoSim LiveScan device 6 months following the training. The model developed assessed: general U/S setup, structure identification, and pathologic clinical scenarios. Results: The residents felt most comfortable in identifying the bladder (4.73/5) and the kidneys (4.53/5) during the training sessions. They felt least comfortable while testing for total ureteric obstruction (3.13/5). All the residents were confident that additional U/S training sessions would improve their comfort level in performing the assessed objectives. Resident's assessment performed at 6 months had a median test score of 15.5/20 and the assessment scores increased with resident seniority. Self-reported comfort, however, did not seem to correlate with seniority. In general, the residents felt that the SonoSim device was highly functional (4.4/5) and the pathologic assessments in particular were very helpful (4.4/5). Conclusions: Through pilot testing, we propose that a competency-based assessment used with the SonoSim LiveScan could guide the resident's education through the acquisition of U/S skills and warrants testing in a larger cohort.