gebhart/patrepeval huggingface dataset:
Segmentation of dynamic PET images using cluster analysis (2002)

Quantitative PET studies can provide in-vivo measurements of dynamic physiological and biochemical processes in humans. A limitation of PET is its inability to provide precise anatomic localisation due to relatively poor spatial resolution when compared to MR imaging. Manual placement of regions of interest (ROIs) is commonly used in the clinical and research settings in analysis of PET datasets. However, this approach is operator dependent and time-consuming. Semi- or fully-automated ROI delineation (or segmentation) methods offer advantages by reducing operator error and subjectivity and thereby improving reproducibility. In this work, the authors describe an approach to automatically segment dynamic PET images using cluster analysis, and they validate their approach with a simulated phantom study and asses its performance in segmentation of dynamic lung data. The authors' preliminary results suggest that cluster analysis can be used to automatically segment tissues in dynamic PET studies and has the potential to replace manual ROI delineation.
Treatment of Graft-Versus-Host Disease After Liver Transplantation with Basiliximab Followed by Bowel Resection (2003)

Graft-versus-host disease (GVHD) after orthotopic liver transplantation (OLT) is a serious complication with mortality rates over 80%. Two patients with established GVHD after OLT were treated with Basiliximab, a chimeric murine human monoclonal antibody which binds to the alpha-chain of interleukin-2 receptor (IL-2R). Two males, aged 45 and 56 years, presented after OLT with a clinical picture consistent with GVHD. Quantitative measurements of recipient peripheral blood donor lymphocyte chimerism were carried out by flow cytometric analysis, and showed peak chimerism levels of 5% and 8%, respectively. Treatment comprised 3 doses of 1 g methyl prednisolone followed by 2 doses of 20 mg of Basiliximab. In both, treatment resulted in complete disappearance of macro-chimerism in blood. There was resolution of skin rash by day 7; however, diarrhea persisted. White cell scan showed increased uptake in the terminal ileum and small-bowel resection was performed in both patients. One patient is alive and well 36 months after OLT. The other patient had resolution of GVHD, but died of recurrent hepatitis C 1 year after OLT. The combination of immunological and surgical treatment for GVHD following solid organ transplantation has not previously been described.
Immunoaffinity purification of factor IX (Christmas factor) by using conformation-specific antibodies directed against the factor IX-metal complex. (1985)

Factor IX is a vitamin K-dependent blood clotting zymogen that is functionally defective or absent in patients with hemophilia B. A method of immunoaffinity chromatography has been developed for a one-step high yield purification of factor IX directly from plasma. The technique utilizes conformation-specific antibodies that bind solely to the metal-stabilized factor IX conformer, but not to the conformer of factor IX found in the absence of metal ions. Anti-factor IX-Ca(II) antibodies were immobilized on an agarose matrix. Human plasma in the presence of 7.5 mM MgCl2 was applied to the antibody-agarose column. The factor IX that binds to these antibodies was specifically eluted by metal chelation with EDTA. This immunopurification resulted in a 10,000-fold one-step purification of the fully functional zymogen. Purified factor IX yielded a single band upon gel electrophoresis in Na-DodSO4 and had a specific activity of 120-150 units/mg. The purified factor IX was separated from other vitamin K-dependent blood clotting proteins and hepatitis virus; no activated factor IX was detected. This method has application for the large scale purification of factor IX for the treatment of hemophilia B.
Cumulus cells are required for the increased apoptotic potential in oocytes of aged mice (1997)

Recent studies with female ICR mice have suggested that oocyte DNA fragmentation is one reason for poor oocyte quality and lower fertility associated with ageing. Since it was not determined if this increased 'apoptotic' potential in aged oocytes is due to changes within the oocyte itself or within the microenvironment of cumulus cells (CC) surrounding the germ cell, we sought to clarify if CC were required to affect the rate of apoptosis in oocytes maintained in vitro. Intact cumulus-oocyte complexes (COC) were retrieved by superovulation of virgin female ICR mice at 7 weeks ('young') or 34-35 weeks ('aged') of age. One-half of the COC in each group were incubated at 37 degrees C in human tubal fluid medium under paraffin oil for 24 h. The other half of the COC in each group were denuded of CC and incubated under the same conditions (denuded oocytes; DO). Following incubation, COC were stripped of adherent CC by gentle pipetting. All DO were then fixed and checked by light microscopy for morphological changes characteristic of apoptosis. In young mice, the presence of CC had no significant effect on oocyte death rate (18 +/- 9% and 14 +/- 6% apoptotic oocytes in COC and DO, respectively; P > 0.05). However, in aged mice the percentage of CC-enclosed oocytes that underwent apoptosis was significantly greater as compared to the death rate in DO (48 +/- 3% versus 19 +/- 8% apoptotic oocytes, respectively; P < 0.05). This increased death potential was due to the presence of CC since the occurrence of apoptosis in DO of aged versus young mice was not significantly different (19 +/- 8% versus 14 +/- 6% apoptotic oocytes, respectively; P > 0.05). These results demonstrate that the age-dependent acceleration of apoptosis in oocytes maintained in vitro requires the CC.
Linearity and low-noise performance of SOI MOSFETs for RF applications (2002)

The MOSFET parameters important for RF application at GHz frequencies: a) transition frequency, b) noise figure, and c) linearity are analyzed and correlated with substrate type. This work demonstrates that, without process changes, high-resistivity silicon-on-insulator (high-/spl rho/ SOI) substrates can successfully enhance the RF performance of on-chip inductors and fully depleted (FD)-SOI devices in terms of reducing substrate losses and parasitics. The linearity limitations of the SOI low-breakdown voltage and "kink" effect are addressed by judicious device and circuit design. Criteria for device optimization are derived. A NF = 1.7 dB at 2.5 GHz for a 0.25 /spl mu/m FD-SOI low-noise amplifier (LNA) on high-/spl rho/ SOI substrate obtained the lowest noise figure for applications in the L and S-bands.
Exploiting the engine of C4 photosynthesis (2011)

Ever since the discovery of C(4) photosynthesis in the mid-1960s, plant biologists have envisaged the introduction of the C(4) photosynthetic pathway into C(3) crops such as rice and soybeans. Recent advances in genomics capabilities, and new evolutionary and developmental studies indicate that C(4) engineering will be feasible in the next few decades. Furthermore, better understanding of the function of C(4) photosynthesis provides new ways to improve existing C(4) crops and bioenergy species, for example by creating varieties with ultra-high water and nitrogen use efficiencies. In the case of C(4) engineering, the main enzymes of the C(4) metabolic cycle have already been engineered into various C(3) plants. In contrast, knowledge of the genes controlling Kranz anatomy lags far behind. Combining traditional genetics, high-throughput sequencing technologies, systems biology, bioinformatics, and the use of the new C(4) model species Setaria viridis, the discovery of the key genes controlling the expression of C(4) photosynthesis can be dramatically accelerated. Sustained investment in the research areas directly related to C(4) engineering has the potential for substantial return in the decades to come, primarily by increasing crop production at a time when global food supplies are predicted to fall below world demand.
Comprehensive biophysical and functional study of ziv-aflibercept: characterization and forced degradation (2020)

Aflibercept (AFL) is an Fc fusion protein used in the treatment of colorectal cancers and different ophthalmological diseases. There are two medicines in which AFL is the active substance: Zaltrap and Eylea, referred as ziv-AFL and AFL respectively. No proper accelerated degradation studies were published on either AFL or ziv-AFL. These studies are essential during research, development and manufacturing stages. Here, we characterized ziv-AFL and submitted it to different stress conditions: light, 60 °C, freeze-thaw cycles, changes in pH, high hypertonic solution and strong denaturing conditions. We used an array of techniques to detect aggregation (SE-HPLC/DAD and DLS), changes in secondary structure (Far-UV circular dichroism), changes in conformation or tertiary structure (Intrinsic tryptophan fluorescence) and alterations in functionality (ELISA). Results indicate that aggregation is common degradation pathway. Two different types of aggregates were detected: dimers and high molecular weight aggregates attributed to β-amyloid-like structures. Secondary structure was maintained in most of the stress tests, while conformation was altered by almost all the tests except for the freeze-thaw cycles. Functionality, evaluated by its immunochemical reaction with VEGF, was found to be stable but with decrease when exposed to light and with likely partial inactivation of the drug when pH was altered.
Acute Kidney Injury, Mortality, Length of Stay, and Costs in Hospitalized Patients (2005)

The marginal effects of acute kidney injury on in-hospital mortality, length of stay (LOS), and costs have not been well described. A consecutive sample of 19,982 adults who were admitted to an urban academic medical center, including 9210 who had two or more serum creatinine (SCr) determinations, was evaluated. The presence and degree of acute kidney injury were assessed using absolute and relative increases from baseline to peak SCr concentration during hospitalization. Large increases in SCr concentration were relatively rare (e.g., >or=2.0 mg/dl in 105 [1%] patients), whereas more modest increases in SCr were common (e.g., >or=0.5 mg/dl in 1237 [13%] patients). Modest changes in SCr were significantly associated with mortality, LOS, and costs, even after adjustment for age, gender, admission International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis, severity of illness (diagnosis-related group weight), and chronic kidney disease. For example, an increase in SCr >or=0.5 mg/dl was associated with a 6.5-fold (95% confidence interval 5.0 to 8.5) increase in the odds of death, a 3.5-d increase in LOS, and nearly 7500 dollars in excess hospital costs. Acute kidney injury is associated with significantly increased mortality, LOS, and costs across a broad spectrum of conditions. Moreover, outcomes are related directly to the severity of acute kidney injury, whether characterized by nominal or percentage changes in serum creatinine.
Biological Assessment and Mri Monitoring of the Therapeutic Efficacy of a Monoclonal Anti-T Cd4 Antibody in Multiple Sclerosis Patients (1996)

An initial group of 21 patients plus a second group of 14 patients with active multiple sclerosis (MS) (18 progressive and 17 relapsing-remitting forms) were treated with a murine monoclonal anti-T CD4/BF5 antibody as part of a phase I open trial. Tolerance was relatively good: minor general side-effects occurred in 22 patients only upon the first mAb infusion. One year later, functional disability was stabilised in only six of the 35 patients and after 2 years in two patients only (among 21). One year after treatment, nine of the 17 relapsing-remitting patients were relapse-free. CD4 counts decreased dramatically 2 h after treatment. These counts were back to baseline counts at 3 months. A transient increase was found in IL-6 and TNF alpha levels 2 h after treatment, which probably accounts for the observed side effects. Cell adhesion molecule levels were not modified. Serial MRI scans were performed in the second group of 14 patients. In all of these patients, lesion modifications were observed in the three scans performed prior to treatment. Yet, no changes in the lesions were noted on the MRI scans performed over the following 3 months. These findings demonstrate the feasibility of this treatment insofar as it induced a marked CD4 lymphocyte depletion. However, it did not seem to stabilise the evolution of the disease--although one must be careful in drawing such conclusions in a phase I trial--or to curb the evolution of MRI-documented lesions.
Influenza A Virus Polymerase Recruits the RNA Helicase DDX19 to Promote the Nuclear Export of Viral mRNAs (2016)

Enhancing the knowledge of host factors that are required for efficient influenza A virus (IAV) replication is essential to address questions related to pathogenicity and to identify targets for antiviral drug development. Here we focused on the interplay between IAV and DExD-box RNA helicases (DDX), which play a key role in cellular RNA metabolism by remodeling RNA-RNA or RNA-protein complexes. We performed a targeted RNAi screen on 35 human DDX proteins to identify those involved in IAV life cycle. DDX19 was a major hit. In DDX19-depleted cells the accumulation of viral RNAs and proteins was delayed, and the production of infectious IAV particles was strongly reduced. We show that DDX19 associates with intronless, unspliced and spliced IAV mRNAs and promotes their nuclear export. In addition, we demonstrate an RNA-independent association between DDX19 and the viral polymerase, that is modulated by the ATPase activity of DDX19. Our results provide a model in which DDX19 is recruited to viral mRNAs in the nucleus of infected cells to enhance their nuclear export. Information gained from this virus-host interaction improves the understanding of both the IAV replication cycle and the cellular function of DDX19.
Endothelial nitric oxide synthase is critical for ischemic remodeling, mural cell recruitment, and blood flow reserve (2005)

The genetic loss of endothelial-derived nitric oxide synthase (eNOS) in mice impairs vascular endothelial growth factor (VEGF) and ischemia-initiated blood flow recovery resulting in critical limb ischemia. This result may occur through impaired arteriogenesis, angiogenesis, or mobilization of stem and progenitor cells. Here, we show that after ischemic challenge, eNOS knockout mice [eNOS (-/-)] have defects in arteriogenesis and functional blood flow reserve after muscle stimulation and pericyte recruitment, but no impairment in endothelial progenitor cell recruitment. More importantly, the defects in blood flow recovery, clinical manifestations of ischemia, ischemic reserve capacity, and pericyte recruitment into the growing neovasculature can be rescued by local intramuscular delivery of an adenovirus encoding a constitutively active allele of eNOS, eNOS S1179D, but not a control virus. Collectively, our data suggest that endogenous eNOS-derived NO exerts direct effects in preserving blood flow, thereby promoting arteriogenesis, angiogenesis, and mural cell recruitment to immature angiogenic sprouts.
Targeted genome engineering via zinc finger nucleases (2010)

With the development of next-generation sequencing technology, ever-expanding databases of genetic information from various organisms are available to researchers. However, our ability to study the biological meaning of genetic information and to apply our genetic knowledge to produce genetically modified crops and animals is limited, largely due to the lack of molecular tools to manipulate genomes. Recently, targeted cleavage of the genome using engineered DNA scissors called zinc finger nucleases (ZFNs) has successfully supported the precise manipulation of genetic information in various cells, animals, and plants. In this review, we will discuss the development and applications of ZFN technology for genome engineering and highlight recent reports on its use in plants.
PP.15.24 (2015)

Objective: To investigate the prevalence, status of hypertension control and the related risk factors of hypertensive women in Gansu Province of China. Design and method: A random stratified cluster sampling hypertensive investigation for women aged 15 years or older was conducted in 14 regions of Gansu Province of China in 2014. The totals of 12271 female residents were investigated by face-to-face questionnaires, and physical measurements at the same time. All of the investigators and statisticians were well trained before the survey. The data of the results were statistical analyzed by using SPSS statistics 19.0. Results: The prevalence of female hypertension in Gansu Province was 22.57% and the standardized prevalence of hypertension was 20.29%. There were not significant differences in the prevalence of female hypertension between urban and rural areas (23.09% vs 21.99%, p > 0.05). The awareness, treatment and the control rate were 49.8%, 38.2% and 19.5% respectively. Multivariate logistic regression showed that age, education attainment, alcohol consumption, body mass index (BMI), age of menopause and physical exercise were associated with hypertension. Conclusions: The prevalence of female hypertension in Gansu Province of China increases in recent ten years but the awareness, treatment and the control rate are still lower. Many efforts should be done in this area.
The First Intron of the Human Osteopontin Gene Contains a C/EBP-Beta-Responsive Enhancer (2003)

The osteopontin (OPN) protein is found expressed at high level in several processes including fibrotic evolution of organ injuries, tumorigenesis, and immune response. The molecular mechanisms that underly overexpression, especially at the transcriptional level, have been only partially clarified. Therefore, this study was undertaken in search for additional DNA elements in the regulatory regions of the OPN gene and cognate transcription factors. Our results on the region upstream of the transcription start site confirmed that essential elements are located within the first 100 bp. Analysis of the sequence that includes the first untranslated exon and first intron revealed that it could enhance the promoter activity. Experiments of transfection of constructs containing different fragments of this sequence showed that most of the enhancer activity was confined in the terminal 30-bp tract of the first intron, although it was not functioning in a myofibroblast cell line. DNA/protein binding assays and cotransfection experiments showed that the C/EBP-beta transcription factor was able to bind a recognition sequence in this 30-bp segment. We found a bi-allelic sequence polymorphism at +245 in the first intron, which did not show a significant functional effect, but is a useful tool for future association studies.
Distributed sensor networks for detection of mobile radioactive sources (2004)

The ability to track illicit radioactive transport through an urban environment has obvious national security applications. This goal may be achieved by means of individual portal monitors, or by a network of distributed sensors. We have examined the distributed sensing problem by modeling a network of scintillation detectors measuring a Cesium-137 source. We examine signal-to-noise behavior that arises in the simple combination of data from networked radiation sensors. We find that, in the ideal case, large increases in signal-to-noise compared to an individual detector can be achieved, even for a moving source. We also discuss statistical techniques for localizing and tracking single and multiple radioactive sources.
Cu doped V2O5 flowers as cathode material for high-performance lithium ion batteries (2013)

Hierarchical Cu doped vanadium pentoxide (V2O5) flowers were prepared via a simple hydrothermal approach followed by an annealing process. The flower precursors are self-assembled with 1D nanobelts surrounding a central core. The morphological evolution is investigated and a plausible mechanism is proposed. As the cathode material for lithium ion batteries, the Cu doped V2O5 samples exhibit improved electrochemical performance compared to the un-doped ones. Among them Cu0.02V1.98O5 delivered higher reversible specific capacities, better cycling stabilities and excellent rate capabilities, e.g. 97 mA h g(-1) at 20.0 C.
Modeling the human MTM1 p.R69C mutation in murine Mtm1 results in exon 4 skipping and a less severe myotubular myopathy phenotype (2011)

X-linked myotubular myopathy (MTM) is a severe neuromuscular disease of infancy caused by mutations of MTM1, which encodes the phosphoinositide lipid phosphatase, myotubularin. The Mtm1 knockout (KO) mouse has a severe phenotype and its short lifespan (8 weeks) makes it a challenge to use as a model in the testing of certain preclinical therapeutics. Many MTM patients succumb early in life, but some have a more favorable prognosis. We used human genotype-phenotype correlation data to develop a myotubularin-deficient mouse model with a less severe phenotype than is seen in Mtm1 KO mice. We modeled the human c.205C>T point mutation in Mtm1 exon 4, which is predicted to introduce the p.R69C missense change in myotubularin. Hemizygous male Mtm1 p.R69C mice develop early muscle atrophy prior to the onset of weakness at 2 months. The median survival period is 66 weeks. Histopathology shows small myofibers with centrally placed nuclei. Myotubularin protein is undetectably low because the introduced c.205C>T base change induced exon 4 skipping in most mRNAs, leading to premature termination of myotubularin translation. Some full-length Mtm1 mRNA bearing the mutation is present, which provides enough myotubularin activity to account for the relatively mild phenotype, as Mtm1 KO and Mtm1 p.R69C mice have similar muscle phosphatidylinositol 3-phosphate levels. These data explain the basis for phenotypic variability among human patients with MTM1 p.R69C mutations and establish the Mtm1 p.R69C mouse as a valuable model for the disease, as its less severe phenotype will expand the scope of testable preclinical therapies.
Preliminary experience with Brown-Roberts-Wells (BRW) computerized tomography stereotaxic guidance system (1983)

The production model of the Brown-Roberts-Wells (BRW) computerized tomography (CT) stereotaxic guidance system is described. Hardware and software modifications to the original prototype now allow the system to be used independently of the CT scanner after an initial scan with the localizing components fixed to the skull. The system is simple and efficient, can be used universally with all CT scanners, and includes a phantom simulator system for target verification. Preliminary experience with 74 patients at two institutions is described. It is concluded that CT stereotaxic guidance systems will become important tools in the neurosurgical armamentarium, as they allow accurate approach to any target identifiable on the CT scan.