Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Consequences of the SERPINH1/HSP47 Mutation in the Dachshund Natural Model of Osteogenesis Imperfecta*

Background: The collagen chaperone HSP47 is implicated in recessive osteogenesis imperfecta (OI). Results: In OI dachshunds, an HSP47(L326P) mutation affects the post-translational modification, secretion, and cross-linking of collagen type I. Conclusion: Impaired chaperone function, ER stress, and aberrant bone collagen cross-linking are implicated in the disease mechanism. Significance: Our findings are relevant for the diagnosis and pathological understanding of OI caused by an HSP47 defect. Osteogenesis imperfecta (OI) is a heritable connective tissue disease characterized by bone fragility and increased risk of fractures. Up to now, mutations in at least 18 genes have been associated with dominant and recessive forms of OI that affect the production or post-translational processing of procollagen or alter bone homeostasis. Among those, SERPINH1 encoding heat shock protein 47 (HSP47), a chaperone exclusive for collagen folding in the ER, was identified to cause a severe form of OI in dachshunds (L326P) as well as in humans (one single case with a L78P mutation). To elucidate the disease mechanism underlying OI in the dog model, we applied a range of biochemical assays to mutant and control skin fibroblasts as well as on bone samples. These experiments revealed that type I collagen synthesized by mutant cells had decreased electrophoretic mobility. Procollagen was retained intracellularly with concomitant dilation of ER cisternae and activation of the ER stress response markers GRP78 and phospho-eIF2α, thus suggesting a defect in procollagen processing. In line with the migration shift detected on SDS-PAGE of cell culture collagen, extracts of bone collagen from the OI dog showed a similar mobility shift, and on tandem mass spectrometry, the chains were post-translationally overmodified. The bone collagen had a higher content of pyridinoline than control dog bone. We conclude that the SERPINH1 mutation in this naturally occurring model of OI impairs how HSP47 acts as a chaperone in the ER. This results in abnormal post-translational modification and cross-linking of the bone collagen.
Replication and Reanalysis of Offenbacher's School Enrollment Study: Implications for the Weber and Merton Theses

Martin Offenbacher's statistical study comparing the school enrollment of German Protestants to Catholica plays a significant role in the articulation of the Weber and Merton theses. The current study provides an overdue correction of obvious flaws in Offenbacher's data. There follows a subsequent reassessment of that recalculated data indicating a now diminished difference between Catholic and Protestant school 'preference. ' Any remaining disparity between the denominations' school 'choice'is seen here as attributable to operative practical factors as opposed to Weber's and Merton's long-standing attribution to differing religious values. The paper argues more generally that the theoretical appeal enjoyed by the conceptually linked Weber and Merton theses in sociology may have invited the all too facile acceptance of idealist interpretation at the expense of practical factors in explanations for discrete denominational behaviors.
Characteristics of Optical Channel for Underwater Optical Wireless Communication System

To understand an underwater optical communication, it is necessary to describe the optical path of the light underwater and the refractive index of water. In the present work the receiver signal power underwater has been calculated using free space optical wireless communication formula. This procedure has been used to calculate the link margin, data rate as a function of the distance link. Types of water have been taken in the consideration. Our results show that the signal to noise ratio most parameter in communication systems in the distance link, particularly for the refractive index n ≤ 1.4. The data rate, signal to noise ratio decreases as the refractive index of water and distance link increases.
Overexpression of the Mg-chelatase H subunit in guard cells confers drought tolerance via promotion of stomatal closure in Arabidopsis thaliana

The Mg-chelatase H subunit (CHLH) has been shown to mediate chlorophyll biosynthesis, as well as plastid-to-nucleus and abscisic acid (ABA)-mediated signaling. A recent study using a novel CHLH mutant, rtl1, indicated that CHLH specifically affects ABA-induced stomatal closure, but also that CHLH did not serve as an ABA receptor in Arabidopsis thaliana. However, the molecular mechanism by which CHLH engages in ABA-mediated signaling in guard cells remains largely unknown. In the present study, we examined CHLH function in guard cells and explored whether CHLH expression might influence stomatal aperture. Incubation of rtl1 guard cell protoplasts with ABA induced expression of the ABA-responsive genes RAB18 and RD29B, as also observed in wild-type (WT) cells, indicating that CHLH did not affect the expression of ABA-responsive genes. Earlier, ABA was reported to inhibit blue light (BL)-mediated stomatal opening, at least in part through dephosphorylating/inhibiting guard cell H+-ATPase (which drives opening). Therefore, we immunohistochemically examined the phosphorylation status of guard cell H+-ATPase. Notably, ABA inhibition of BL-induced phosphorylation of H+-ATPase was impaired in rtl1 cells, suggesting that CHLH influences not only ABA-induced stomatal closure but also inhibition of BL-mediated stomatal opening by ABA. Next, we generated CHLH-GFP-overexpressing plants using CER6 promoter, which induces gene expression in the epidermis including guard cells. CHLH-transgenic plants exhibited a closed stomata phenotype even when brightly illuminated. Moreover, plant growth experiments conducted under water-deficient conditions showed that CHLH transgenic plants were more tolerant of drought than WT plants. In summary, we show that CHLH is involved in the regulation of stomatal aperture in response to ABA, but not in ABA-induced gene expression, and that manipulation of stomatal aperture via overexpression of CHLH in guard cells improves plant drought tolerance.
Treating depression in disabled, low‐income elderly: a conceptual model and recommendations for care

The treatment of depression in low‐income older adults who live in poverty is complicated by several factors. Poor access to resources, disability, and mild cognitive impairment are the main factors that moderate treatment effects in this population. Interventions that not only address the depressive syndrome but also manage social adversity are sorely needed to help this patient population recover from depression.
Monte Carlo and experimental relative dose determination for an Iridium-192 source in water phantom

Ir source is presented for real energy spectrum and monochromatic at 356 keV. Materials and Methods: The dose distribution has been calculated around the 192 Ir located in the center of 30 cm ×30 cm ×30 cm water phantom using MCNP4C code by Monte Carlo method. Relative dose variation has been measured by using Gafchromic Rtqa along X and Y axis, as well. Percentage depth dose (PDD) variation along the different axis parallel and perpendicular the source were calculated. Finally, F (5cm, θ|) dosimetry parameters of TG-43 protocol were determined. Results: The results showed that the Monte Carlo method could calculate dose deposition in high gradient region, near the source, accurately. The isodose curves and dosimetric characteristics obtained for 192
Personal Factors That Influence the Voluntary Withdrawal of Undergraduates with Disabilities.

This qualitative study explored personal factors students with invisible disabilities (SWIDs) associate with their voluntary withdrawal from a mid-western state land grant university (LGU) after completing 60 or more college credits. In-depth, semi-structured interviews were used to gather data from the five participants, all former students with invisible disabilities. The data were coded and contrastive thematic analysis was conducted across all the cases. Nine common factors were identified within participants’ descriptions of their college withdrawal experience. These factors included: disability characteristics, medical reasons, feelings of inadequacy, little sense of belonging, small college desire, self-advocacy, disclosure to faculty and staff, involvement in campus social life, and finances. The complex interconnectedness of a number of the factors is central to many of the participant’s experiences, emphasizing the need for a multifaceted approach to retention strategies for SWIDs.
Compressed Pattern Databases

A pattern database (PDB) is a heuristic function implemented as a lookup table that stores the lengths of optimal solutions for subproblem instances. Standard PDBs have a distinct entry in the table for each subproblem instance. In this paper we investigate compressing PDBs by merging several entries into one, thereby allowing the use of PDBs that exceed available memory in their uncompressed form. We introduce a number of methods for determining which entries to merge and discuss their relative merits. These vary from domain-independent approaches that allow any set of entries in the PDB to be merged, to more intelligent methods that take into account the structure of the problem. The choice of the best compression method is based on domain-dependent attributes. We present experimental results on a number of combinatorial problems, including the four-peg Towers of Hanoi problem, the sliding-tile puzzles, and the Top-Spin puzzle. For the Towers of Hanoi, we show that the search time can be reduced by up to three orders of magnitude by using compressed PDBs compared to uncompressed PDBs of the same size. More modest improvements were observed for the other domains.
Explaining perceived performance of the World Wide Web: uncertainty and the task-technology fit model

The performance of the World Wide Web is evaluated as an information resource in a specific information domain. The theoretical framework underpinning this approach recognises the contribution of information‐seeking behaviour from the discipline of information science and models of information systems success from the discipline of information systems in explaining World Wide Web usage as an information resource. A model integrating the construct of uncertainty and the task‐technology fit model is presented. A questionnaire‐based empirical study is used to test this integrated approach. Our results confirm that richer models representing the broad context of World Wide Web usage are required to evaluate usage of the World Wide Web as an information resource. Usage for travel tasks, uncertainty reduction, the Web as an information resource, and mediation all have a significant impact on users' perception of performance, explaining 46 per cent of the variance.
Sentiments and rationalizability

Sentiments are characteristics of players' beliefs. I propose two notions of sentiments, confidence and optimism, and I study their role in shaping the set of rationalizable strategy profiles in (incomplete information) games with complementarities. Confidence is related to a player's perceived precision of information; optimism is the sentiment that the outcome of the game will be ``favorable. '' I prove two main results on how sentiments and payoffs interact to determine the size and location of the set of rationalizable profiles. The first result provides an explicit upper bound on the size of the set of rationalizable strategy profiles, relating complementarities and confidence; the second gives an explicit lower bound on the change of location, relating complementarities and optimism. I apply these results to four areas. In models of currency crisis, the results suggest that the most confident investors may drive financial markets. In models of empirical industrial organization, the paper provides a classification of the parameter values for which the model is identified. In non-Bayesian updating, the results clarify the strategic implications of certain biases. Finally, the results generalize and clarify the uniqueness result of global games.
On the Effects of Entry in Cournot Markets

In the framework of symmetric Cournot oligopoly, this paper provides two minimal sets of assumptions on the demand and cost functions that imply respectively that, as the number of firms increases, the minimal and maximal equilibria lead to (i) decreasing industry price and increasing or decreasing per-firm output; and (ii) increasing industry price (and decreasing per-firm output). In both cases, per-firm profits are decreasing. The analysis relies crucially on lattice-theoretic methods and yields general, unambiguous and easily interpretable conclusions of a global nature. As a byproduct of independent interest, new insight into existence of Cournot equilibrium is developed.
Pregnancy failure in patients with obstetric antiphospholipid syndrome with conventional treatment: the influence of a triple positive antibody profile

Conventional treatment of obstetric antiphospholipid syndrome fails in approximately 20–30% of pregnant women without any clearly identified risk factor. It is important to identify risk factors that are associated with these treatment failures. This study aimed to assess the impact of risk factors on pregnancy outcomes in women with obstetric antiphospholipid syndrome treated with conventional treatment. We carefully retrospectively selected 106 pregnancies in women with obstetric antiphospholipid syndrome treated with heparin + aspirin. Pregnancy outcomes were evaluated according to the following associated risk factors: triple positivity profile, double positivity profile, single positivity profile, history of thrombosis, autoimmune disease, more than four pregnancy losses, and high titers of anticardiolipin antibodies and/or anti-βeta-2-glycoprotein-I (aβ2GPI) antibodies. To establish the association between pregnancy outcomes and risk factors, a single binary logistic regressions analysis was performed. Risk factors associated with pregnancy loss with conventional treatment were: the presence of triple positivity (OR = 5.0, CI = 1.4–16.9, p = 0.01), high titers of aβ2GPI (OR = 4.4, CI = 1.2–16.1, p = 0.023) and a history of more than four pregnancy losses (OR = 3.5, CI = 1.2–10.0, p = 0.018). The presence of triple positivity was an independent risk factor associated with gestational complications (OR = 4.1, CI = 1.2–13.9, p = 0.02). Our findings reinforce the idea that triple positivity is a categorical risk factor for poor response to conventional treatment.
The Paradoxes of Octave Identities

My study highlights an interesting phenomenon: that of the octave paradoxes. As is known, it is a commonplace in musical thinking that musical sounds an octave apart have the same pitch quality. That is indicated by the periodic repetition of pitch names by octaves. There are, however, scholarly endeavours pointing out that the awareness of the octaves as having two sounds of similar quality was the product of a historical process and there existed cultures in which the fact of octave identities was not evident, in which the octave had no distinguished role in structuring the musical relations. It is a common experience of music teachers that musically untrained people sometimes mistake the fifth or fourth for the octave. All this suggests that the recognition of octave identities is an acquired ability, without disproving that the phenomenon of the identity of octaves is based on psychoacoustic foundations. There have been animal experiments to prove that when eliciting a conditioned reflex implanted as a response to a definite pitch, the octave were sometimes confused, that is, pitches an octave apart mediate identical information to the experimental animals. ' The question is: whether the similarity of the stimuli, or the pecularities of auditory sensations account for the mistaken octaves.2
Comparison of the effects of long-term pimobendan and benazepril administration in normal cats

Pimobendan (PIMO) can cause adverse effects, such as mitral valve degeneration, in dogs; however, it is unclear whether these effects occur in cats. Therefore, we aimed to determine whether PIMO or benazepril produces adverse cardiac effects in healthy cats. This was a blinded, randomized, prospective parallel study. Twelve cats were randomly divided into two groups of six cats, namely, an angiotensin-converting-enzyme inhibitor group that received benazepril and a PIMO group. Cats were administered their respective treatments for 506 days, and we evaluated cardiac parameters, blood biochemistry and glomerular filtration rates during that time. At the end of the trial, the cats were euthanized, and histopathological examinations were performed by a pathologist who was blinded to the treatment groups. No significant changes were observed in any of the parameters measured in either of the groups. In particular, no significant cardiac lesions were observed in either of the groups. In healthy cats, neither PIMO nor benazepril appears to cause cardiac lesions, but future studies are needed to examine the effects of PIMO in cats with heart disease.
Diagnosing Eosinophilic Colitis: Histopathological Pattern or Nosological Entity?

Reports of “eosinophilic colitis”—raised colonic mucosal eosinophil density in patients with lower gastrointestinal symptoms—have increased markedly over the last fifteen years, though it remains a rarity. There is no consensus over its diagnosis and management, and uncertainty is compounded by the use of the same term to describe an idiopathic increase in colonic eosinophils and an eosinophilic inflammatory reaction to known aetiological agents such as parasites or drugs. In patients with histologically proven colonic eosinophilia, it is important to seek out underlying causes and careful clinicopathological correlation is advised. Because of the variability of eosinophil density in the normal colon, it is recommended that histological reports of colonic eosinophilia include a quantitative morphometric assessment of eosinophil density, preferably across several sites. Few reported cases of “eosinophilic colitis” meet these criteria. As no correlation has been shown between colonic eosinophil density and symptoms in older children or adults, it is suggested that treatment should be directed towards alleviation of symptoms and response to treatment assessed clinically rather than by histological estimates of intramucosal eosinophils.
PAIN. PSYCHOLOGICAL AND PSYCHIATRIC ASPECTS

Current Concepts in Breast Cancer. Edited by A. SEGALOFF, K. K. MEYER and S. DEBAKEY. Pp. 378 illustrated. Baltimore: Williams & Wilkins. Edinburgh and London: E. & S. Livingstone. 1967. £7 12s. 6d. The Treatment of Carcinoma of the Breast. Edited by A. S. JARRETT. Proceedings of Symposium held at Cambridge, 1967 under the auspices ofthe Institute of Hormone Biology and Syntex Pharmaceuticals. Published for Syntex Pharmaceuticals by Excerpta Medica Foundation. Pp. 64 illustrated. London: H. K. Lewis. 1968. 14s. Some Recent Advances in Inborn Errors of Metabolism. Edited by K. S. HOLT and V. P. COFFEY. Pp. vii + 167 illustrated. Edinburgh and London: E. & S. Livingstone. 1968. 30s. Malabsorption Syndromes. By A. C. FRAZER. Pp. viii + 111 illustrated. London: William Heinemann Medical Books. 1968. 30s. Biological Psychiatry. A Review of Recent Advances. By J. R. SMYTHIES with the collaboration of A. COPPEN and N. KREITMAN. Pp. viii + 112 illustrated. London: William Heinemann Medical Books. 1968. 30s. Heredity and Environment in the Functional Psychoses. An Epidemiological Clinical Twin Study. By EINAR KRINGLEN. Pp. 200. London: William Heinemann Medical Books. 1968. 65s. Pharmacological Principles and Practice. By W. M. D. PATON and J. P. PAYNE. Pp. ix + 417 illustrated. London: J. & A. Churchill. 1968. 75s. Insulin, Membranes and Metabolism. By P. REISER. Pp. 156. Baltimore: Williams & Wilkins. Edinburgh and London: E. & S. Livingstone. 1968. 77s. 6d. Cross-Reacting Antigens and Neoantigens (with Implications for Autoimmunity and Cancer Immunity). Edited by J. J. TRENTIN. A conference sponsored by the Committee on Tissue Transplantation. May 1967. Pp. 122 illustrated. Baltimore: Williams & Wilkins. Edinburgh and London: E. & S. Livingstone. 1968. 62s. 6d. (bound edition available at 85s.). Phenotypic Expression. Immunological, Biochemical and Morphological. A symposium organized by M. N. GOLDSTEIN. Publication of the Tissue Culture Association. Pp. xi + 170 illustrated. Baltimore: Williams & Wilkins. Edinburgh and London: E. & S. Livingstone. 1968. 87s. 6d.
Ubiquitin/SUMO modification of PCNA promotes replication fork progression in Xenopus laevis egg extracts

The homotrimeric DNA replication protein proliferating cell nuclear antigen (PCNA) is regulated by both ubiquitylation and sumoylation. We study the appearance and the impact of these modifications on chromosomal replication in frog egg extracts. Xenopus laevis PCNA is modified on lysine 164 by sumoylation, monoubiquitylation, and diubiquitylation. Sumoylation and monoubiquitylation occur during the replication of undamaged DNA, whereas diubiquitylation occurs specifically in response to DNA damage. When lysine 164 modification is prevented, replication fork movement through undamaged DNA slows down and DNA polymerase δ fails to associate with replicating chromatin. When sumoylation alone is prevented, replication occurs normally and neither monoubiquitylation nor sumoylation are required for the replication of simple single-strand DNA templates. Our findings expand the repertoire of functions for PCNA ubiquitylation and sumoylation by elucidating a role for these modifications during the replication of undamaged DNA. Furthermore, they suggest that PCNA monoubiquitylation serves as a molecular gas pedal that controls the speed of replisome movement during S phase.
Telavancin for the treatment of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA)

Telavancin is a bactericidal lipoglycopeptide antibiotic that is structurally related to vancomycin. It demonstrates in vitro activity against a variety of Gram-positive pathogens including, but not limited to, methicillin-resistant Staphylococcus aureus (MRSA). Telavancin is currently FDA-approved for the treatment of complicated skin and skin-structure infections. Recently, two randomized clinical trials demonstrated the efficacy and safety of telavancin compared to vancomycin for the treatment of nosocomial pneumonia. Overall, telavancin has a favorable safety profile. However, mild gastrointestinal disturbances and reversible increases in serum creatinine were observed in clinical studies. Additional clinical studies are needed to evaluate telavancin’s efficacy and safety in comparison to other antistaphylococcal agents for the treatment of infections such as bacteremia and endocarditis.