Miracle-dz/UniFAR-FTUs huggingface dataset:
New directions in cancer therapy based on aberrant expression of glycosphingolipids: anti-adhesion and ortho-signaling therapy.

Essentially all tumors express aberrantly glycosylated glycosphingolipids and glycoproteins, more commonly known as "tumor-associated carbohydrate antigens. " In this article I propose two new forms of cancer therapy, anti-adhesion therapy and ortho-signaling therapy, which exploit these tumor-associated carbohydrates in distinct ways. The aim of anti-adhesion therapy is to disrupt the requisite carbohydrate-initiated interactions that occur between tumor cells and other cell types (e.g., endothelial cells, platelets) as tumors progress and metastasize. Candidate anti-adhesion agents include purified carbohydrates or glycosphingolipids representing H, Ley, sialosyl-Lex (or -Lea) GM3, or LacCer antigens, and monoclonal antibodies directed to these structures. The aim of ortho-signaling therapy is to disrupt mitogenic signaling pathways in tumor cells that are regulated by glycosphingolipids and/or their derivatives, including pathways involving receptor protein-kinases and protein kinase C. Candidate ortho-signaling agents are the glycosphingolipid regulator PDMP (1-phenyl-2-[decanoylamino]-3-morpholino-1-propanol) and the protein kinase C inhibitor DMS (N,N-dimethylsphingosine), both of which show antitumor activity in vitro and in animal studies.
Fade of the response to prolonged glutamate application in the rat hippocampal slice

The effect of prolonged glutamate (GLU) application was examined on 60 CA1 pyramidal neurons in the in vitro rat hippocampal slice preparation. Continuous application of L‐GLU, either by bath perfusion (0.5–2mM) of the slices or iontophoresis (200 mM) into the dendritic region of the neurons, elicited a transient depolarization which faded to a mean of 53% of the initial peak amplitude despite continued exposure to the agonist. Membrane depolarization to aspartate (ASP) and the d‐isomer of GLU also faded with time. In contrast, the depolarizing response to the excitatory amino acid agonists N‐methyl‐D, L‐aspartate (NMA), quisqualate (QUIS), and kainate (KA) did not fade significantly during continuous application. The fade of the GLU depolarization was not affected by the NMDA antagonist D‐2‐amino‐5‐phosphonovalerate (APV) or by blocking synaptic transmission with tetrodotoxin. At the time of maximum fade of the GLU depolarization, there was no change in input resistance or GLU reversal potential. In addition, fade of the response was not a consequence of changes in extracellular potassium concentration, GLU uptake mechanisms, or the electrogenic pump. The most likely explanation for fade is postsynaptic receptor desensitization.
Genomic Analysis of the Evolution of Phototrophy among Haloalkaliphilic Rhodobacterales

Abstract A characteristic feature of the order Rhodobacterales is the presence of a large number of photoautotrophic and photoheterotrophic species containing bacteriochlorophyll. Interestingly, these phototrophic species are phylogenetically mixed with chemotrophs. To better understand the origin of such variability, we sequenced the genomes of three closely related haloalkaliphilic species, differing in their phototrophic capacity and oxygen preference: the photoheterotrophic and facultatively anaerobic bacterium Rhodobaca barguzinensis, aerobic photoheterotroph Roseinatronobacter thiooxidans, and aerobic heterotrophic bacterium Natronohydrobacter thiooxidans. These three haloalcaliphilic species are phylogenetically related and share many common characteristics with the Rhodobacter species, forming together the Rhodobacter-Rhodobaca (RR) group. A comparative genomic analysis showed close homology of photosynthetic proteins and similarity in photosynthesis gene organization among the investigated phototrophic RR species. On the other hand, Rhodobaca barguzinensis and Roseinatronobacter thiooxidans lack an inorganic carbon fixation pathway and outer light-harvesting genes. This documents the reduction of their photosynthetic machinery towards a mostly photoheterotrophic lifestyle. Moreover, both phototrophic species contain 5-aminolevulinate synthase (encoded by the hemA gene) incorporated into their photosynthesis gene clusters, which seems to be a common feature of all aerobic anoxygenic phototrophic Alphaproteobacteria. Interestingly, the chrR-rpoE (sigma24) operon, which is part of singlet oxygen defense in phototrophic species, was found in the heterotrophic strain Natronohydrobacter thiooxidans. This suggests that this organism evolved from a photoheterotrophic ancestor through the loss of its photosynthesis genes. The overall evolution of phototrophy among the haloalkaliphilic members of the RR group is discussed.
Phylogenetic changes in soil microbial and diazotrophic diversity with application of butachlor

We investigated changes in population and taxonomic distribution of cultivable bacteria and diazotrophs with butachlor application in rice paddy soils. Population changes were measured by the traditional plate-count method, and taxonomic distribution was studied by 16S rDNA sequencing, then maximum parsimony phylogenic analysis with bootstrapping (1,000 replications). The bacterial population was higher after 39 than 7 days of rice cultivation, which indicated the augmentation of soil microbes by rice root exudates. The application of butachlor increased the diazotrophic population in both upper (0–3 cm) and lower (3–15 cm) layers of soils. Especially at day 39, the population of diazotrophs was 1.8 and 1.6 times that of the control in upper and lower layer soils, respectively. We found several bacterial strains only with butachlor application; examples are strains closest to Bacillus arsenicus, B. marisflavi, B. luciferensis, B. pumilus, and Pseudomonas alvei. Among diazotrophs, three strains closely related to Streptomyces sp. or Rhrizobium sp. were found only with butachlor application. The population of cultivable bacteria and the species composition were both changed with butachlor application, which explains in part the contribution of butachlor to augmenting soil nitrogen-fixing ability.
Adipocytokines and the risk of ischemic stroke: The PRIME Study

Adipocytokines are hormones secreted from adipose tissue that possibly link adiposity and the risk of cardiovascular disease, but limited prospective data exist on plasma adipocytokines and ischemic stroke risk. We investigated associations and predictive properties of 4 plasma adipocytokines, namely resistin, adipsin, leptin, and total adiponectin, with regard to incident ischemic stroke in the PRIME Study.
Forced Expression of the Fc Receptor γ-Chain Renders Human T Cells Hyperresponsive to TCR/CD3 Stimulation 1

High level expression of FcεRIγ chain replaces the deficient TCR ζ-chain and contributes to altered TCR/CD3-mediated signaling abnormalities in T cells of patients with systemic lupus erythematosus. Increased responsiveness to Ag has been considered to lead to autoimmunity. To test this concept, we studied early signaling events and IL-2 production in fresh cells transfected with a eukaryotic expression vector encoding the FcεRIγ gene. We found that the overexpressed FcεRIγ chain colocalizes with the CD3ε chain on the surface membrane of T cells and that cross-linking of the new TCR/CD3 complex leads to a dramatic increase of intracytoplasmic calcium concentration, protein tyrosine phosphorylation, and IL-2 production. We observed that overexpression of FcεRIγ is associated with increased phosphorylation of Syk kinase, while the endogenous TCR ζ-chain is down-regulated. We propose that altered composition of the CD3 complex leads to increased T cell responsiveness to TCR/CD3 stimulation and sets the biochemical grounds for the development of autoimmunity.
Essential Biodiversity Variables

A global system of harmonized observations is needed to inform scientists and policy-makers. Reducing the rate of biodiversity loss and averting dangerous biodiversity change are international goals, reasserted by the Aichi Targets for 2020 by Parties to the United Nations (UN) Convention on Biological Diversity (CBD) after failure to meet the 2010 target (1, 2). However, there is no global, harmonized observation system for delivering regular, timely data on biodiversity change (3). With the first plenary meeting of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) soon under way, partners from the Group on Earth Observations Biodiversity Observation Network (GEO BON) (4) are developing—and seeking consensus around—Essential Biodiversity Variables (EBVs) that could form the basis of monitoring programs worldwide.
Visceral adiposity is negatively associated with bone density and muscle attenuation.

BACKGROUND The storage of adipose tissue in ectopic compartments is a hallmark attribute linking greater body mass index (BMI) with cardiometabolic diseases. Despite ample evidence to confirm that increased visceral adipose tissue (VAT) deposition occurs with obesity, the interrelations between altered fat partitioning and regional muscle and bone quality are less well understood. OBJECTIVE We examined the association between adiposity and spinal muscle and bone quality across a large, heterogeneous cohort of adults. DESIGN We identified 8833 thoracic or abdominal computed tomography scans from patients in the University of Michigan Health System who were aged 18-64.9 y. We measured trabecular bone densities, cortical bone densities, VAT areas, and subcutaneous adipose tissue (SAT) areas at vertebral levels T7 to L5. Psoas muscle attenuation (an indicator of fat infiltration in muscle) was measured at the L4 level. RESULTS Muscle attenuation as well as trabecular and cortical bone densities revealed negative correlations with BMI, SAT, and VAT. The correlation between BMI and psoas attenuation was -0.321, between BMI and the density of cortical bone was -0.250, and between BMI and trabecular bone was -0.143 (all P < 0.001). However, correlations between VAT and lower muscle attenuation were stronger as were those between VAT and lower bone densities. Inverse correlations between VAT and densities of psoas muscle and cortical and trabecular bone were -0.460, -0.407, and -0.434, respectively (P < 0.001). Even after adjustment for age, sex, and BMI, partial correlations between VAT, muscle attenuation, and bone densities remained significant at -0.250, -0.119, and -0.216, respectively (P < 0.001). CONCLUSIONS Contrary to previous reports that high body mass is associated with increased bone quality, our data show a significant negative association between BMI and muscle and bone densities, suggesting fat infiltration into these tissues. More importantly, correlations between VAT and decreased bone and muscle densities remained statistically significant even after adjustment for age, sex, and BMI.
Invited Article: Nervous system pathology in sporadic Parkinson disease

Sporadic Parkinson disease (PD) is, after Alzheimer disease (AD), the second most frequent neurodegenerative disorder.1 The pathologic process in PD is progressive and takes years to reach its full extent. It does not affect nonhuman vertebrates or organ systems other than the nervous system, and, apparently, it does not go into remission. Unlike AD, however, the pathology is distributed throughout the entire nervous system—that is, not only the central but also the peripheral and the enteric nervous systems (CNS, PNS, ENS). As a result, PD has come to be acknowledged as more than a monosystemic disorder with preferential obliteration of nigral dopaminergic neurons.2–8,e1-e3 In the clinically recognizable, i.e., motor, phase of sporadic PD, most patients display signs of motor dysfunction (hypo- or bradykinesia, cogwheel rigidity, postural instability, resting tremor),9,e4,e5 but these symptoms also occur in other disorders associated with dopamine loss in the nigrostriatal system.e6,e7 Familial forms of parkinsonism exist,3,e8,e9 and the syndrome may also develop as a sequel to intoxication, trauma, vascular alterations, metabolic disease, or infection.e3,e10-e14 In addition, parkinsonism can develop in tauopathies, including corticobasal degeneration and progressive supranuclear palsy,e15-e17 or in synucleinopathies, such as multiple system atrophy and Lewy body disease.10,11,e18-e20 Lewy body disease has been subdivided further into pure autonomic failure, dementia with Lewy bodies, and sporadic PD.11,12 The latter two entities are nearly indistinguishable at neuropathologic examination, and there is a growing consensus that, clinically, they are closely related, if not identical.13–17 Here, we refer only to the Lewy body pathology associated with the synucleinopathy sporadic (or idiopathic) PD, the most widespread form of parkinsonism.1,8,e25 In PD, typical α-synuclein immunoreactive inclusions (Lewy neurites [LNs], Lewy bodies [LBs]) develop within specific types of projection neurons in all portions of the …
Optimization of Hot-Wire Airflow Sensors on an Out-of-Plane Glass Bubble for 2-D Detection

This paper presents design, analysis, fabrication, and measurement of airflow sensors with three hot-wire resistors on an out-of-plane glass bubble. The fabrication process is based on etching cavities in silicon wafer, followed by anodic bonding of a thin Pyrex glass wafer to the etched silicon wafer. The bonded wafers are then heated inside a furnace at a temperature above the softening point of the glass, and because of the expansion of the trapped gas in the silicon cavities, the glass is blown into three-dimensional (3-D) spherical glass bubbles. Resistors patterned on the glass wafer above the cavities are elevated above the base during the glass bubble blowing process. An optimization analysis on the structure and geometry of the sensor, fabrication process, and properties of multilayer thin-film resistors on glass has been conducted in an attempt to improve the sensitivity.
SiGe-on-insulator symmetric lateral bipolar transistors

We report the first demonstration of thin-base symmetric lateral NPN bipolar transistors built on 8-inch SiGe-on-insulator (SiGe-OI) wafers with CMOS-like process. Such devices achieve the same collector current as the SOI bipolar transistor at ~130 mV lower VBE from effective bandgap lowering, translating into lower voltage operation and power dissipation. Various techniques of Emitter engineering were studied and a novel partial HBT device structure was demonstrated with 3× reduction of hole injection into the emitter.
Effect of exercise training on loss of bone mineral density during lactation.

PURPOSE During lactation, women transfer approximately 200 mg of calcium per day to breast milk. For 6 months, this is equivalent to 3%-9% of bone mineral density (BMD) loss at trabecular-rich sites. Bone mass usually returns to prepregnancy levels with cessation of lactation but not in all women. Therefore, the purpose of this study was to determine whether exercise slows bone loss from 4 to 20 wk postpartum (PP). METHODS At 4 wk PP, women were randomized to either an exercise group [EG, n = 10, weight bearing aerobic exercise (3 d·wk(-1), 45 min·d(-1)) and 3 d·wk(-1) of resistance exercise] or a control group (CG, n = 10, no exercise) for 16 wk. Body composition and BMD were measured by dual-energy x-ray absorptiometry at the lumbar spine (LS), hip, and total body. Maximal strength and predicted maximal oxygen consumption (VO2max) were determined by 1-repetition maximum and submaximal treadmill test, respectively. Repeated-measures ANOVA was used to test for time and time by group differences. RESULTS EG lost significantly less LS BMD than CG (-4.8 ± 0.6% vs -7.0 ± 0.3%, P < 0.01). There were no significant differences in total body and hip BMD. Both groups lost fat mass (EG = -2.9 ± 0.7 kg, CG = -1.8 ± 0.4 kg); however, EG lost less lean body mass (-0.7 ± 0.3 vs -1.6 ± 0.3 kg, P = 0.05). Maximal strength increased by 34% to 221% for all exercises in EG, whereas CG changed -5.7% to 12%. Predicted VO2max increased in both groups (EG = 11.4 ± 2.0, CG = 6.9 ± 1.7%). CONCLUSIONS These results suggest that resistance and aerobic exercise may slow bone loss during lactation.
A Case of Disseminated Peritoneal Leiomyomatosis Developing after Laparoscope-Assisted Myomectomy

A 36-year-old nulliparous woman developed multiple extra-uterine fibroids in the pelvic cavity years after laparoscopic myomectomy. Molecular genetic analysis by methylation-specific polymerase chain reaction (MSPCR) of the human X-linked androgen receptor gene and loss of heterozygosity (LOH) analysis at 5 microsatellite loci was performed on the tumors. All tumors showed an identical non-random X-chromosome inactivation pattern by MSPCR and an identical pattern of LOH was found in all the tumors by LOH analysis. This demonstrated that 3 fibroids resected 2 years later and 14 fibroids resected 6 years later were all metastatic tumors originating from the uterine leiomyoma found during the initial surgery, suggesting that morcellation before removal of the leiomyoma nodule during laparoscopic myomectomy may have been associated with the pathogenesis of this case.
Age Factors Influencing Response–Response Compatibility in Reaction Time Tasks

Unlike stimulus–response compatibility, which has been explored for aging effects, the motor behavior issue of response–response (R–R) compatibility has not been addressed in the gerontological literature. R–R compatibility refers to the ease with which two responses can be prepared together either simultaneously or as choice alternatives. In the present study, young, middle-aged, and elderly adult female subjects were tested in a two-choice reaction-time (RT) paradigm involving four types of finger movements paired in every possible choice combination, creating different levels of R–R compatibility. Significant age differences increased as R–R compatibility decreased. The practical significance of this study is to establish R–R compatibility as an important factor influencing task difficulty to which older adults are particularly sensitive and to encourage recognition of this factor when prescribing progressive motor-skill training in elderly clients.
Relationship between entry into child welfare and mental health service use.

OBJECTIVE This study examined the relationship between initiation of outpatient mental health service use and level of child welfare involvement. METHODS Three levels of child welfare involvement were examined: in-home care and no child welfare services beyond an initial investigation, in-home care and additional child welfare services, and placement in out-of-home care (foster care). Longitudinal data were collected for a subsample of children (N=3,592) aged two through 14 years who were enrolled in the National Survey of Child and Adolescent Well-Being, a nationally representative sample of children undergoing investigation for abuse or neglect. Event history analysis was used to model relative risk of initiation of mental health service use over time. RESULTS Hazard functions revealed a large increase in onset of mental health services immediately after the time of the initial contact with child welfare, varying by level of child welfare involvement and leveling off by three months after the initial contact. The multivariate Cox proportional-hazards model indicated that compared with children who were placed in out-of-home care, those in in-home care who did not receive any further child welfare services were about one-third as likely to use mental health services and those in in-home care who received additional child welfare services were one-half as likely to use mental health services. Other covariates in the model predicted mental health service use, including being older, being Caucasian, having a history of maltreatment (specifically, physical abuse, physical neglect, or abandonment), being uninsured, and need for mental health services, as measured by the Child Behavior Checklist. CONCLUSIONS Contact with child welfare functions as a gateway into mental health services for children in child welfare, even when need for such services is controlled for.
Choreatic movements first appear in Huntington's disease associated with brain cortex lesion due to subdural hematoma

Sirs: Generalized chorea has rarely been reported as a manifestation of subdural hematoma [1–4]. Here we report the case of a patient with bilateral subdural hematomas who presented with generalized chorea of abrupt onset, which subsequently was attributed to hitherto unsuspected Huntington’s disease (HD). A 71-year-old male patient with a history of type II diabetes and prostatic hypertrophy presented with sudden chorea as well as after minor head trauma 1 month earlier. As asserted from his wife and general practitioner the patient was entirely free from dyskinesias up to 2 days prior to the admission. There was no history of neurological illness in the patient’s generation or the preceding three generations on the maternal side but the paternal heritage was unknown because of unknown paternity. On examination, he was fully alert and oriented. On the MiniMental State Examination [5] he missed one point of the full score of 30 because of inattention in the serial sevens task. Generalized choreatic dyskinesias involved the limbs, face, tongue and neck. His lower limbs were moderately weak and showed bilateral extensor plantar responses. Physical examination was otherwise unremarkable. The full blood count, sedimentation rate, glucose, electrolytes, and TSH were normal. Emergency head computed tomography revealed bilateral chronic subdural hematomas with minor shift of the brain stem (Fig. 1a). After immediate surgical evacuation the patient’s paraparesis improvedwithin a few hours. His choreatic movements subsided completely too, yet reappeared 2 days later and persisted.Magnetic resonance imaging a week later revealed no basal ganglia abnormality (Fig. 1b). Genetic testing, which was performed with appropriate genetic counseling, disclosed an expansion to 41 CAG triplet repeats on the IT 15 gene [6]. In retrospect, the patient’swife reported a history of impulsiveness and jealousy for several years. Follow-up after 2 years revealed slight progression of chorea and impulsivity. Previous reports of chorea with subdural hematoma have attributed it a causative role because of resolution of the dyskinesia after surgical treatment [1–4]. However, the underlying mechanism is not clear. Chorea is classically understood as the result of hypofunction of the indirect pathway from the putamen to the internal globus pallidus, leading to inappropriate disinhibition of thalamic projections to premotor and motor cortex. Subdural hematoma may cause direct mechanical compression, vascular disturbances and metabolic changes of the basal ganglia but was also found to reduce local blood flow in the adjacent cortical surface [7]. Correspondingly, EEG in two patients showed bilateral diffuse slowing in the frontotemporal and central regions [3,4]. Thus, interruption of excitatory connections from cerebral cortex to basal ganglia may contribute to the development of
Promoting Personalization in Social Care Services for Older People

This article presents findings on 4 themes associated with the personalization of social care for older people: integration of health and social care services; initiatives that prevent the need for more costly interventions; services to maintain people at home; and systems that promote choice, control, and flexibility. The quantitative study utilized data from a national postal survey conducted in England. Findings suggest variable progress regarding the range and style of support available to older people. These are discussed in the context of service integration, community-based services, and consumer-directed care. Implications for service development and future research are highlighted.