Miracle-dz/UniFAR-FTUs huggingface dataset:
TWO FORMS OF ALANINE AMINOTRANSFERASE IN RAT BRAIN DURING ONTOGENY

Abstract— Alanine aminotransferase activity in subcellular fractions of rat brains was investigated during ontogenic development. The activity rose from the prenatal period until adulthood, the highest increase being observed during the period of morphological metabolic and functional maturation of the brain. The rise of the total activity was due predominantly to a rise in the activity of the cytosblic enzyme; the activity of the mitochondrial enzyme did not change markedly during ontogeny. CI‐ions and elevated temperature (55°C) inhibited the activity only of the mitochondrial enzyme. Raised temperature stimulated the activity of the cytosolic enzyme while CI‐ions did not influence its activity. Our results indicate that 2 alanine aminotransferase isoenzlmes are already present in the rat brain in the prenatal period. It is assumed that the cytosolic enzyme is involved in the regulation of tissue glycol)sis and alanine formation, while the mitochondrial enzyme plays a role in the amino nitrogen transport between mitochondria and cytosol.
Molecular Confirmation of the Origin and Invasive Status of West Indian Raccoons

Abstract Raccoons occur on a number of islands in the Bahamas and the Lesser Antilles in the West Indies. Zooarcheological studies have long suggested that these animals are not native to the West Indies. Originally, Caribbean populations were described as endemic insular species Procyon maynardi (Bahamas), P. minor (Guadeloupe), and P. gloveralleni (Barbados), a classification that was recognized throughout much of the 20th century. More recently, studies of qualitative morphology and a review of historical publications and documents have been used to bolster arguments that these populations of raccoons are not unique species worthy of special conservation attention, but invasive populations of the North American raccoon (P. lotor) introduced in recent centuries. Raccoons in the Bahamas and the French Antilles appear to be spreading onto other islands with human assistance, but the population on Barbados is now apparently extinct. We present evidence from the mitochondrial control region, including sequence data from the extinct population on Barbados generated using ancient DNA protocols, indicating that all 3 major insular populations of West Indian raccoons are conspecific with P. lotor and probably originated via recent translocations from eastern North America. Like nonnative populations of raccoons that have been established elsewhere (e.g., in Alaska, Japan, and Europe), the raccoons of the West Indies deserve no special taxonomic recognition or conservation status. They may be destructive to native wildlife on West Indian islands where they have been introduced, particularly if their spread to and across other islands continues.
The role of healthcare providers in the roll out of preexposure prophylaxis

Purpose of reviewTo review the most recent studies assessing the preparedness of healthcare practitioners to provide anti-HIV preexposure prophylaxis (PrEP) and suggest areas for future implementation research. Recent findingsAs PrEP is a biobehavioral intervention, healthcare providers are likely to play a critical role in implementing PrEP in care settings. Studies suggest that many specialized providers are aware of PrEP and support its provision as a public health intervention, though knowledge and acceptance are less among generalists. Therefore, utilization of PrEP by clinicians has been limited to a few early adopters. Concerns about the efficacy and long-term safety of PrEP, and perceived barriers to prescribing PrEP, could limit prescribing behaviors and intentions. Resistance to performing routine HIV risk assessments by clinicians is an additional barrier to implementing PrEP, although innovative tools to help clinicians routinely perform risk assessments, are being developed. SummaryInterventions are needed to engage a broader array of healthcare providers in PrEP provision. Utilizing a framework based on diffusion of innovation theory, this review proposes strategies that can be implemented and evaluated to increase PrEP prescribing by healthcare providers. If resources are invested in training clinicians to provide PrEP, then these stakeholders could enhance the use of PrEP as part of a prevention package by primary providers.
Phase II study of MLN8237 (Alisertib) in advanced/metastatic sarcoma.

BACKGROUND Aurora kinase A (AURKA) is commonly overexpressed in sarcoma. The inhibition of AURKA by shRNA or by a specific AURKA inhibitor blocks in vitro proliferation of multiple sarcoma subtypes. MLN8237 (alisertib) is a novel oral adenosine triphosphate-competitive AURKA inhibitor. PATIENTS AND METHODS This Cancer Therapy Evaluation Program-sponsored phase II study of alisertib was conducted through the Alliance for Clinical Trials in Oncology (A091102). Patients were enrolled into histology-defined cohorts: (i) liposarcoma, (ii) leiomyosarcoma, (iii) undifferentiated sarcoma, (iv) malignant peripheral nerve sheath tumor, or (v) other. Treatment was alisertib 50 mg PO b.i. d. d1-d7 every 21 days. The primary end point was response rate; progression-free survival (PFS) was secondary. One response in the first 9 patients expanded enrollment in a cohort to 24 using a Simon two-stage design. RESULTS Seventy-two patients were enrolled at 24 sites [12 LPS, 10 LMS, 11 US, 10 malignant peripheral nerve sheath tumor (MPNST), 29 Other]. The median age was 55 years; 54% were male; 58%/38%/4% were ECOG PS 0/1/2. One PR expanded enrollment to the second stage in the other sarcoma cohort. The histology-specific cohorts ceased at the first stage. There were two confirmed PRs in the other cohort (both angiosarcoma) and one unconfirmed PR in dedifferentiated chondrosarcoma. Twelve-week PFS was 73% (LPS), 44% (LMS), 36% (US), 60% (MPNST), and 38% (Other). Grade 3-4 adverse events: oral mucositis (12%), anemia (14%), platelet count decreased (14%), leukopenia (22%), and neutropenia (42%). CONCLUSIONS Alisertib was well tolerated. Occasional responses, yet prolonged stable disease, were observed. Although failing to meet the primary RR end point, PFS was promising. TRIAL REGISTRATION ID NCT01653028.
Genetic counselors' practices and confidence regarding variant of uncertain significance results and reclassification from BRCA testing

Studies indicate variant of uncertain significance (VUS) results are challenging for genetic counselors and patients, often resulting in negative patient outcomes. Genetic counselors' current practices regarding VUS are unknown. This study utilized a national survey of genetic counselors (n = 932) to examine current practices and confidence related to disclosing BRCA VUS results and reclassification information. For participants (n = 398), descriptive statistics were calculated regarding patient demographic characteristics, practices and confidence, and cross tabulation was used to identify participant's actions when receiving a reclassified VUS. Upon receiving a BRCA VUS report, the majority reported providing patients with information about the frequency with which their VUS was seen and patient ancestry, but a minority discussed DNA banking. Most were confident in their understanding of, and ability to explain, VUS results to patients, but felt less confident about achieving high levels of patient understanding. Upon reclassification, the majority reported calling the patient and mailing the results, but when the reclassification was deleterious, the majority also met with the patient face‐to‐face. Given the lack of standard professional guidelines about informing patients of initial and reclassified VUS results, this overview provides important insight into genetic counselors' current practices and confidence.
The Functional Neuroanatomy of Episodic Memory: The Role of the Frontal Lobes, the Hippocampal Formation, and Other Areas

Because it allows direct mapping of synaptic activity during behavior in the normal subject, functional neuroimaging with the activation paradigm, especially positron emission tomography, has recently provided insight into our understanding of the functional neuroanatomy of episodic memory over and above established knowledge from lesional neuropsychology. The most striking application relates to the ability to distinguish the structures implicated in the encoding and the retrieval of episodic information, as these processes are extremely difficult to differentiate with behavioral tasks, either in healthy subjects or in brain-damaged patients. Regarding encoding and retrieval, the results from most studies converge on the involvement of the prefrontal cortex in these processes, with a hemispheric encoding/retrieval asymmetry (HERA) such that the left side is preferentially involved in encoding, and the right in retrieval. However, there are still some questions, for instance, about bilateral activation during retrieval and a possible specialization within the prefrontal cortex. More expected from human and monkey lesional data, the hippocampal formation appears to play a role in both the encoding and the retrieval of episodic information, but the exact conditions which determine hippocampal activation and its fine-grained functional neuroanatomy have yet to be fully elucidated. Other structures are activated during episodic memory tasks, with asymmetric activation that fits the HERA model, such as preferentially left-sided activation of the association temporal and posterior cingulate areas in encoding tasks and preferentially right-sided activation of the association parietal cortex, cerebellum, and posterior cingulate in retrieval tasks. However, this hemispheric asymmetry appears to depend to some extent on the material used. These new data enhance our capacity to comprehend episodic memory deficits in neuropsychology, as well as the neural mechanisms underlying the age-related changes in episodic memory performances.
Developments in allogeneic peripheral blood progenitor cell transplantation.

It is now over 5 years since the first use of peripheral blood progenitor cells (PBPC) for allogeneic transplantation (Russell et al, 1993; Dreger et al, 1993), and 3 years since the first detailed reports appeared which confirmed the feasibility of this approach (Schmitz et al, 1995; Bensinger et al, 1995; Korbling et al, 1995a). During the intervening period a conservative estimate of the total number of allogeneic PBPC transplants performed would be at least 3000. Data reported to the EBMT in 1996 shows 1141 allogeneic PBPC transplants were performed which represented 26% of the total number of allografts, whereas in 1991 all allogeneic transplants performed were bone marrow derived (Gratwohl et al, 1998). Allogeneic PBPC transplants are increasingly being used for ‘newer’ indications for allogeneic transplantation such as lymphoma and myeloma and in these conditions PBPC was the source of haemopoietic stem cells in >40% of allogeneic transplants reported to the EBMT (Gratwohl et al, 1998). Also the use of PBPC transplants comprise the majority of mismatched allografts being performed in Europe. This usage may reflect two perceptions, firstly that what has been termed the ‘engraftability’ of PBPC is superior to that of bone marrow; secondly that PBPC may result in a superior graft-versusleukaemia (tumour) effect. The purpose of this article is to assess the current status of allogeneic PBPC transplantation in the light of the last 5 years experience and to update the reader on developments which have taken place since this topic was last reviewed (Russell et al, 1996).
Surface-step-induced magnetic anisotropy in thin epitaxial Fe films on W(001).

Ultrathin epitaxial Fe films grown on W(001) surfaces prepared to yield uniform 25-A-wide terraces are shown to exhibit layer-dependent in-plane uniaxial magnetic anisotropy having an easy axis perpendicular to the steps. Hysteresis loops measured by magneto-optical techniques when steps are aligned parallel to the applied field H manifest the flip of magnetization that occurs near H=0. The absence of magneto-optic effects for films less than or equal to one monolayer thick is consistent with recent ab initio calculations that predict significant moment reduction resulting from strong film-substrate hybridization
A North Dakota prevalence study of schizophrenia presenting in childhood.

Abstract Prevalence studies have yet to be completed for many of the DSM-III diagnoses. The diagnosis of childhood schizophrenia is not included in the DSM-III. In DSM-III the same diagnostic criteria for schizophrenia are used for both children and adults. In this report the authors first sought to determine whether schizophrenia presenting in childhood (SC) occurs among a population of children with an early history of pervasive developmental disorder. When no patients with SC were identified, the authors sought to determine the prevalence rate of SC in North Dakota children in general. No patients with SC were found in this population either. About a year after the prevalence study, two children (both male) from the authors' practice developed DSM-III schizophrenia. The authors discuss the use of DSM-III criteria in the diagnosis of SC.
MAPK Signaling Up-regulates the Activity of Hypoxia-inducible Factors by Its Effects on p300*

Hypoxia-inducible factors (HIF) are a family of heterodimeric transcriptional regulators that play pivotal roles in the regulation of cellular utilization of oxygen and glucose and are essential transcriptional regulators of angiogenesis in solid tumor and ischemic disorders. The transactivation activity of HIF complexes requires the recruitment of p300/CREB-binding protein (CBP) by HIF-1α and HIF-2α that undergo oxygen-dependent degradation. HIF activation in tumors is caused by several factors including mitogen-activated protein kinase (MAPK) signaling. Here we investigated the molecular basis for HIF activation by MAPK. We show that MAPK is required for the transactivation activity of HIF-1α. Furthermore, inhibition of MAPK disrupts the HIF-p300 interaction and suppresses the transactivation activity of p300. Overexpression of MEK1, an upstream MAPK activator, stimulates the transactivation of both p300 and HIF-1α. Interestingly, the C-terminal transactivation domain of HIF-1α is not a direct substrate of MAPK, and HIF-1α phosphorylation is not required for HIF-CAD/p300 interaction. Taken together, our data suggest that MAPK signaling facilitates HIF activation through p300/CBP.
Leucine/Valine Residues Direct Oxygenation of Linoleic Acid by (10R)- and (8R)-Dioxygenases

Linoleate (10R)-dioxygenase (10R-DOX) of Aspergillus fumigatus was cloned and expressed in insect cells. Recombinant 10R-DOX oxidized 18:2n-6 to (10R)-hydroperoxy-8(E),12(Z)-octadecadienoic acid (10R-HPODE; ∼90%), (8R)-hydroperoxylinoleic acid (8R-HPODE; ∼10%), and small amounts of 12S(13R)-epoxy-(10R)-hydroxy-(8E)-octadecenoic acid. We investigated the oxygenation of 18:2n-6 at C-10 and C-8 by site-directed mutagenesis of 10R-DOX and 7,8-linoleate diol synthase (7,8-LDS), which forms ∼98% 8R-HPODE and ∼2% 10R-HPODE. The 10R-DOX and 7,8-LDS sequences differ in homologous positions of the presumed dioxygenation sites (Leu-384/Val-330 and Val-388/Leu-334, respectively) and at the distal site of the heme (Leu-306/Val-256). Leu-384/Val-330 influenced oxygenation, as L384V and L384A of 10R-DOX elevated the biosynthesis of 8-HPODE to 22 and 54%, respectively, as measured by liquid chromatography-tandem mass spectrometry analysis. The stereospecificity was also decreased, as L384A formed the R and S isomers of 10-HPODE and 8-HPODE in a 3:2 ratio. Residues in this position also influenced oxygenation by 7,8-LDS, as its V330L mutant augmented the formation of 10R-HPODE 3-fold. Replacement of Val-388 in 10R-DOX with leucine and phenylalanine increased the formation of 8R-HPODE to 16 and 36%, respectively, whereas L334V of 7,8-LDS was inactive. Mutation of Leu-306 with valine or alanine had little influence on the epoxyalcohol synthase activity. Our results suggest that Leu-384 and Val-388 of 10R-DOX control oxygenation of 18:2n-6 at C-10 and C-8, respectively. The two homologous positions of prostaglandin H synthase-1, Val-349 and Ser-353, are also critical for the position and stereospecificity of the cyclooxygenase reaction.
Value of Lying-Down Nystagmus in the Lateralization of Horizontal Semicircular Canal Benign Paroxysmal Positional Vertigo

Background: Horizontal canal benign paroxysmal positional vertigo is characterized by horizontal direction-changing nystagmus induced by lateral head turning in supine position. According to Ewald's second law, the direction of head turning that creates a stronger response represents the affected side in geotropic nystagmus and the healthy side in apogeotropic nystagmus. However, it may not always be possible to lateralize the involved ear only by comparing the intensity of the nystagmus. We studied the values of nystagmus induced by position change from sitting to supine in the lateralization of horizontal canal benign paroxysmal positional vertigo. Methods: A retrospective study of 54 patients who had been diagnosed as having horizontal canal benign paroxysmal positional vertigo at the Dizziness Clinic of Seoul National University Bundang Hospital from May 2003 to February 2004 was performed. The directions of the nystagmus induced by lying down were compared with those determined by Ewald's second law. Results: Of the 54 patients, 32 (20 apogeotropic and 12 geotropic) showed horizontal nystagmus induced by lying down. The nystagmus tended to be ipsilesional in apogeotropic patients (80%) and contralesional in their geotropic counterparts (75%). Conclusion: In horizontal canal benign paroxysmal positional vertigo, lying-down nystagmus mostly beats toward the involved ear in the apogeotropic type and directs to the healthy ear in the geotropic type. The direction of lying-down nystagmus may help lateralizing the involved ear in horizontal canal benign paroxysmal positional vertigo.
Mechanisms of Corneal Graft Rejection: The Sixth Annual Thygeson Lecture, Presented at the Ocular Microbiology and Immunology Group Meeting, October 21, 2000

The history of corneal transplantation reaches back over 150 years. Kissam performed one of the first penetrating keratoplasties when he transplanted a pig cornea onto a human in 1838. Only two interrupted sutures were used, and the surgery was performed without anesthesia! In retrospect, no one would be surprised to learn that the porcine corneal xenograft was rejected. Thirty years later, May transplanted rabbit corneal grafts to humans, but concluded that the failures in the first 24 attempts were the result of “imperfect technique and the inability to keep the eyes properly bandaged. ” The first documented report of a successful penetrating keratoplasty in a human subject was performed by Zirm in 1905. As we enter the new millennium, corneal transplantation remains the oldest, most common, and, arguably, the most successful form of solid tissue transplantation. In the United States alone, approximately 36,000 corneal transplants are performed each year. The success rate for corneal transplants is in excess of 90% in uncomplicated cases, even though HLA tissue typing is not performed and systemic immunosuppressive drugs are not administered. In spite of this extraordinary success, immune rejection remains the leading cause of corneal graft failure. Many inferences about the immunobiology of corneal graft rejection have been based on clinical observations; however, confirmation of these hypotheses requires prospective studies under controlled settings. The prudent use of animal models has fostered analytic studies on the immunobiology of corneal allografts without the complicating and confounding effects of topical steroids that are typically used on most keratoplasty patients. Although animal models of penetrating keratoplasty have been in use for almost a half-century, until recently, progress in understanding the immune mechanisms of corneal graft rejection has been slow. However, the widespread use of rodent models of orthotopic corneal transplantation has shed new light on the pathogenesis of corneal graft rejection.
Insoluble or slightly soluble chemicals as molluscicides.

Individuals engaged in bilharziasis work have been using soluble substances as a routine practice for killing the aquatic snail vectors of schistosomes. At present, copper sulfate (CuSo4) and sodium pentachlorophenate (NaPCP) are the most commonly used molluscicides. The advantages and disadvantages of the two chemicals are well known and depend on several circumstances, some of them of a local nature. The existing molluscicides, when properly applied, even in rather low concentrations, may be highly effective in controlling snails. In spite of good results obtained in the field, the shortcomings of CuSO, and NaPCP have been pointed out by several investigators. Problems of application, lack of uniform dispersion, cost, toxicity to animals and man, and inactivation by contact with natural waters are the main factors limiting the widespread routine use of these molluscicides for controlling bilharziasis in countries with extensive endemic areas. To all the factors mentioned above, one should add the lack of slight residual effect of these compounds. To ensure persistent action in flowing waters, maintenance of lethal concentrations of these molluscicides for an adequate period of time is required, and this involves complex technical and economic problems on which little progress has been made. Reasons for failure in the use of these molluscicides are not completely understood. Differences, from complete success to utter failure, have sometimes been reported by one and the same author. The effectiveness of NaPCP reported by Dobrovolny & Barbosa,a for example, varied a great deal. Taking it for granted that the molluscicides have been correctly applied, failures reported may be due to local situations such as the ecological characteristics of the habitat or the biology of the snail itself. This is particularly true of north-eastern