gebhart/patrepeval huggingface dataset:
Adapting molecular inversion probe (MIP) technology for allele quantification in childhood leukemia (2007)

9530 Background: Leukemia accounts for ∼40% of newly diagnosed pediatric malignancies, and relapsed leukemia is the leading cause of death in childhood cancer. Genomic instability events contribute to neoplastic development and have been used to classify and risk stratify non-leukemic adult and pediatric tumors. Analyzing leukemic blasts for gene copy changes with advanced molecular techniques could prove useful in further risk stratifying and developing new treatment strategies for pediatric leukemia. Methods: Molecular Inversion Probes (MIPs) analyze genetic target sequences in parallel with high specificity and sensitivity at the highest genomic resolution, and were originally designed for single nucleotide genotyping. The MIP assay was adapted to analyze both gene copy number and loss of heterozygosity (LOH) events in pediatric leukemia samples (pre-B ALL, T-ALL, AML). DNA was extracted (100 ng) from paired bone marrow (diagnosis) and peripheral blood (remission) samples (n = 40). The MIP assay was run with a customized Affymetrix 20K Cancer Panel (representing oncogenes, tumor suppressor, DNA repair, cell growth, and metabolism genes). Gene copy number changes were identified by comparing probe signal intensity between leukemia samples and normal cell-lines. LOH events were determined by identifying genotype changes between matched leukemic and remission samples. Results: Each sample had unique patterns of multiple gene copy changes and LOH events distributed across all chromosomes. Additionally, samples were found to have overlapping copy number changes and LOH regardless of leukemia type. AML samples had fewer LOH events and could be separated by unsupervised clustering from the other leukemia samples. Conclusions: MIPs represent novel genotyping technology that can be adapted for gene copy analysis of childhood leukemia. Unique and distinguishing signatures of allelic imbalance can be determined between ALL and AML clinical samples using MIP technology. The unexpected overlap of LOH and deleted genes may represent a common molecular mechanism that requires further investigation. No significant financial relationships to disclose.
Methyl Jasmonate Induces Defense Responses in Grapevine and Triggers Protection against Erysiphe necator (2006)

Grapevine is subject to a number of diseases that affect yield and wine quality. To limit the excessive use of phytochemicals in the vineyard, alternative strategies have to be developed. Plant treatment with signaling molecules like elicitors stimulates their natural defense mechanisms. To improve grapevine tolerance against fungal pathogens, Vitis vinifera plants were treated with a natural exogenous elicitor, methyl jasmonate (MeJA). MeJA-treated leaves (Cabernet Sauvignon foliar cuttings) reacted by increasing transcript levels coding pathogenesis-related proteins (acidic class IV chitinase, serine protease inhibitor, polygalacturonase-inhibiting protein, and beta-1,3-glucanase) and coding enzymes involved in phytoalexin biosynthesis (one phenylalanine ammonia lyase and one stilbene synthase). This was correlated with the accumulation of stilbenes (antimicrobial compounds). The eliciting activity of MeJA was confirmed by enhanced tolerance of grapevine foliar cuttings and vineyard against powdery mildew (75% and 73%, respectively). On the basis of these original results, MeJA can therefore act as an efficient elicitor in an alternative strategy of grapevine protection.
Cutaneous infection in normal and immunocompromised mice (1986)

Since a model of staphylococcal skin infection adequately reflecting human disease was unavailable, a self-limiting animal infection model specific for virulent Staphylococcus species was developed. A virulent strain of S. aureus, NCTC 9789 (ATCC 27700), was used to develop an infection model in adult, male CF-1 mice treated with 0 to 150 mg of cyclophosphamide (CY) per kg 4 days before challenge. Bacteria were inoculated onto the dorsal side of shaved mice at 0 to 10(6) CFU per mouse. Simultaneously, the skin was gently scraped to remove the superficial layers without drawing blood. The wound was occluded with impermeable film secured with surgical tape. At a CY dose of 50 mg/kg and an inoculum of 10(5) CFU, 89% of the mice (96 of 108) developed large abscesses (approximately 15-mm diameter). Mice which were not immunocompromised developed fewer abscesses (20 of 68). Generally, no abscesses formed when the mice were not wounded (1 of 62), occluded (0 of 89), or inoculated (11 of 50). The abscesses developed 24 to 48 h after challenge and persisted for 2 to 3 weeks. The challenge organism was isolated from the abscesses. The rates of abscess formation of three additional S. aureus strains varied widely in normal and CY-treated mice. Three strains of S. epidermidis, one of Micrococcus varians, and one of S. saprophyticus failed to cause abscesses. Bacterial proliferation studies demonstrated that a strain of S. aureus and a strain of S. epidermidis proliferated to the same levels 48 h after challenge. Immunosuppression and wounding had little effect on the levels of proliferation of S. aureus (P greater than 0.2). Without occlusion, however, S. aureus proliferated to significantly lower levels (P less than 0.005). This model may be be useful for screening topical anti-infective agents or studying the mechanisms of bacterial pathogenesis and host response.
Lipophilic siRNA targets albumin in situ and promotes bioavailability, tumor penetration, and carrier-free gene silencing (2017)

Clinical translation of therapies based on small interfering RNA (siRNA) is hampered by siRNA's comprehensively poor pharmacokinetic properties, which necessitate molecule modifications and complex delivery strategies. We sought an alternative approach to commonly used nanoparticle carriers by leveraging the long-lived endogenous serum protein albumin as an siRNA carrier. We synthesized siRNA conjugated to a diacyl lipid moiety (siRNA-L<sub>2</sub>), which rapidly binds albumin in situ. siRNA-L<sub>2</sub>, in comparison with unmodified siRNA, exhibited a 5.7-fold increase in circulation half-life, an 8.6-fold increase in bioavailability, and reduced renal accumulation. Benchmarked against leading commercial siRNA nanocarrier in vivo jetPEI, siRNA-L<sub>2</sub> achieved 19-fold greater tumor accumulation and 46-fold increase in per-tumor-cell uptake in a mouse orthotopic model of human triple-negative breast cancer. siRNA-L<sub>2</sub> penetrated tumor tissue rapidly and homogeneously; 30 min after i.v. injection, siRNA-L<sub>2</sub> achieved uptake in 99% of tumor cells, compared with 60% for jetPEI. Remarkably, siRNA-L<sub>2</sub> achieved a tumor:liver accumulation ratio >40:1 vs. <3:1 for jetPEI. The improved pharmacokinetic properties of siRNA-L<sub>2</sub> facilitated significant tumor gene silencing for 7 d after two i.v. doses. Proof-of-concept was extended to a patient-derived xenograft model, in which jetPEI tumor accumulation was reduced fourfold relative to the same formulation in the orthotopic model. The siRNA-L<sub>2</sub> tumor accumulation diminished only twofold, suggesting that the superior tumor distribution of the conjugate over nanoparticles will be accentuated in clinical situations. These data reveal the immense promise of in situ albumin targeting for development of translational, carrier-free RNAi-based cancer therapies.
Diode Predistortion Linearization for Power Amplifier RFICs in Digital Radios (2000)

The recent trend in modern information technology has been towards the increased use of portable and handheld devices such as cellular telephones, personal digital assistants (PDAs), and wireless networks. This trend presents the need for compact and power efficient radio systems. Typically, the most power inefficient device in a radio system is the power amplifier (PA). PA inefficiency requires increased battery reserves to supply the necessary DC bias current, resulting in larger devices. Alternatively, the length of time between battery charges is reduced for a given battery size, reducing mobility. In addition, communications channels are becoming increasingly crowded, which presents the need for improved bandwidth efficiency. In order to make more efficient use of the frequency spectrum allocated for a particular system, there is a push towards complex higher order digital modulation schemes in modern radio systems, resulting in stricter linearity requirements on the system. Since power efficient amplifiers are typically nonlinear, this poses a major problem in realizing a bandwidth and power efficient radio system. However, by employing various linearization techniques, the linearity of a high efficiency PA may be improved. The work presented in this thesis focuses on diode predistortion linearization, particularly for PA RFICs in digital radios. Background discussion on common linearization techniques available to the PA designer is presented. In addition, a discussion of traditional and modern methods of nonlinearity characterization is presented, illustrating the nonlinear PA effects on a modulated signal. This includes the use of two-tone analysis and the more modern envelope analysis. The operation of diode predistortion linearizers is discussed in detail, along with diode optimization procedures for PA linearization with minimum impact on return loss and gain. This diode optimization is effective in improving the ability to integrate the predistorter into a single, linearized PA RFIC chip. MESFET and HBT based diode linearizers are studied for use with corresponding MESFET and HBT based PAs in the 2.68 GHz and 1.95 GHz frequency bands, respectively. Results show an improvement in adjacent channel power ratio (ACPR) due to the linearizer in both MESFET and HBT cases. A fully integrated 1.95 GHz linearizer and PA RFIC in HBT technology is also presented. Design considerations, simulations, and layouts for this design are presented. Finally, several recommendations are made for continued research in this area.
Treatment with the xanthine oxidase inhibitor febuxostat lowers uric acid and alleviates systemic and glomerular hypertension in experimental hyperuricaemia (2007)

These results suggest that Fx merits further evaluation for the treatment of hypertension and renal alterations induced by hyperuricaemia.
Tumor infiltrating lymphocytes in lymph node melanoma metastases: a histopathologic prognostic indicator and an expression of local immune response. (1996)

In lymph node melanoma metastases, the expansive proliferation of tumor cells may be compared, structurally and cytologically, to the vertical growth phase (VGP) observed in primary melanoma. Both in VGP and in nodal metastases, tumor infiltrating lymphocytes (TILs) may be present with different patterns. In the evaluation of the primary tumor, these patterns have been defined as brisk, non-brisk, and absent. The histologic slides of regional lymph node metastases, the site of first recurrence in 99 consecutive melanoma patients, were reviewed. Disease-free survival of these cases and whether or not they were treated with rIFN alpha-2A was recorded to identify any relationship among different patterns of TILs, therapy, and prognosis. Of 99 cases, 16 were classified as brisk, 37 as non-brisk, and 46 as absent. At 30 months of follow-up the disease-free survival was 81.3% for brisk cases, 46.8% for non-brisk cases, and 29.3% for absent groups (p = .007). Multivariate analysis confirmed the prognostic value of TILs in predicting disease-free survival in patients with regional node metastases. The difference according to the presence or absence of relapse is particularly evident when comparison is made between treated and untreated patients. In conclusion the evaluation of first-recurrence regional node melanoma metastases for TILs, using the same histopathologic criteria as in VGP of primary melanoma, subdivides the cases in brisk, non-brisk, and absent groups. Also, the presence of these patterns in metastatic node melanoma deposits is correlatable to disease-free survival. Our results further stress the difference of prognosis patients treated with rIFN alpha-2A compared to the untreated group. The TILs evaluation may prove useful in selecting those melanoma stage II patients who will best respond to therapy with biologic response modifiers, because the TILs may be the local immune effector cell targets of rIFN alpha-2A or of other biologic agents.
Rice Triosephosphate Isomerase Gene 5[prime] Sequence Directs [beta]-Glucuronidase Activity in Transgenic Tobacco but Requires an Intron for Expression in Rice (1994)

In rice (Oryza sativa L.), cytosolic triosephosphate isomerase (TPI) is encoded by a single gene. TPI catalyzes a vital step in glycolysis, and RNA blots showed that the tpi gene is expressed in all vegetative tissues (root, culm, and leaves) and in rice suspension cells. No effect of light on expression was detected, but submergence of rice seedlings resulted in elevated levels of TPI mRNA in roots and culms. The 2767-bp 5[prime] upstream sequence of the tpi gene was fused translationally with the [beta]-glucuronidase (gusA) gene, and the resulting construct, TPI-GUS, was found to express constitutive, high levels of GUS activity in transgenic tobacco (Nicotiana tabacum) plants. However, the same construct yielded no GUS activity in stably transformed rice plants, and RNA blots showed that no GUS mRNA could be detected even though stable integration of functional copies of the construct was confirmed by Southern blot and genomic polymerase chain reaction analyses. Transient assays using particle bombardment yielded high levels of GUS expression from the TPI-GUS construct in tobacco leaves, but essentially no expression in rice, barley, or maize leaves. When the first intron of the tpi gene was included in the construct (TPI-int1-GUS), transient GUS activity was routinely obtained in rice leaves, revealing that the first intron of the rice tpi gene is crucial for its expression in rice. TPI-int1-GUS also directed transient GUS expression in maize and barley leaves, but little or no activity was obtained from this construct in tobacco, tomato, or soybean leaves. These results with the rice tpi promoter are in accordance with mounting evidence that differences in gene expression exist between monocots and dicots.
Correlation between E-cadherin abnormal expressions in different types of cancer and the process of metastasis. (2009)

Cell-cell adhesion plays a critical role in the establishment and maintenance of cell polarity and cell society. Reduced cell-cell adhesiveness allows cancer cells to disobey the social order, resulting in destruction of the histological structure, the morphological hallmark of malignant tumors. Morbidity in most cancer patients is not due to primary cancer but to metastatic disease. Thus, understanding the progression of tumors to metastatic state and the changes that take place in highly aggressive cells is important in the development of novel approaches to the diagnosis and treatment of progressive malignancies. Cell adhesion molecules are implicated in human carcinogenesis. E-cadherin is a calcium-dependent cell adhesion molecule the intact function of which is crucial for the establishment and maintenance of epithelial tissue polarity and structural integrity. The gene encoding E-cadherin (CDH1, on chromosome 16q22.1) was one of the first to be considered as an invasion-suppressor gene. Mutations in CDH1 occur in diffuse type gastric cancer, lobular breast cancer, and endometrial cancer. In human cancers, partial or complete loss of E-cadherin expression correlates with malignancy. Through immunohistochemical analysis it has been assessed the abnormal expressions of E-cadherin in three types of cancer: gastric carcinoma, lobular breast carcinomas and cutaneous melanoma and the correlation with the multistep process of metastasis.
Low Density Lipoprotein Receptor-related Protein 1 Promotes Anti-apoptotic Signaling in Neurons by Activating Akt Survival Pathway (2009)

The low density lipoprotein receptor-related protein 1 (LRP1) is a multi-ligand receptor abundantly expressed in neurons. Previous work has shown that brain LRP1 levels are decreased during aging and in Alzheimer disease. Although mounting evidence has demonstrated a role for LRP1 in the metabolism of apolipoprotein E/lipoprotein and amyloid-beta peptide, whether LRP1 also plays a direct role in neuronal survival is not clear. Here, we show that LRP1 expression is critical for the survival of primary neurons under stress conditions including trophic withdrawal, the presence of apoptosis inducers, or amyloid-beta-induced neurotoxicity. Using lentiviral short hairpin RNA to knock down endogenous LRP1 expression, we showed that a depletion of LRP1 leads to an activation of caspase-3 and increased neuronal apoptosis, an effect that was rescued by a caspase-3 inhibitor. A correlation between decreased Akt phosphorylation and the activation of caspase-3 was demonstrated in LRP1 knocked down neurons. Notably, LRP1 knockdown decreased insulin receptor levels in primary neurons, suggesting that decreased neuronal survival might be a consequence of an impaired insulin receptor signaling pathway. Correspondingly, both insulin receptor and phospho-Akt levels were decreased in LRP1 forebrain knock-out mice. These results demonstrate that LRP1 mediates anti-apoptotic function in neurons by regulating insulin receptor and the Akt survival pathway and suggest that restoring LRP1 expression in Alzheimer disease brain might be beneficial to inhibiting neurodegeneration.
Completing the family portrait of the anti‐apoptotic Bcl‐2 proteins: Crystal structure of human Bfl‐1 in complex with Bim (2008)

Evasion of apoptosis is recognized as a characteristic of malignant growth. Anti-apoptotic B-cell lymphoma-2 (Bcl-2) family members have therefore emerged as potential therapeutic targets due to their critical role in proliferating cancer cells. Here, we present the crystal structure of Bfl-1, the last anti-apoptotic Bcl-2 family member to be structurally characterized, in complex with a peptide corresponding to the BH3 region of the pro-apoptotic protein Bim. The structure reveals distinct features at the peptide-binding site, likely to define the binding specificity for pro-apoptotic proteins. Superposition of the Bfl-1:Bim complex with that of Mcl-1:Bim reveals a significant local plasticity of hydrophobic interactions contributed by the Bim peptide, likely to be the basis for the multi specificity of Bim for anti-apoptotic proteins.
Optimum FIR digital filter implementations for decimation, interpolation, and narrow-band filtering (1975)

In this paper a general theory of multistage decimators and interpolators for sampling rate reduction and sampling rate increase is presented. A set of curves and the necessary relations for optimally designing multistage decimators is also given. It is shown that the processes of decimation and interpolation are duals and therefore the same set of design curves applies to both problems. Further, it is shown that highly efficient implementations of narrow-band finite impulse response (FIR) filters can be obtained by cascading the processes of decimation and interpolation. Examples show that the efficiencies obtained are comparable to those of recursive elliptic filter designs.
Lessons learned from gene expression profiling of cutaneous T-cell lymphoma (2013)

Gene expression studies of cutaneous T-cell lymphoma (CTCL) span a decade, yet the pathogenesis is poorly understood and diagnosis remains a challenge. This review examines the varied approaches to gene expression analysis of CTCL, with emphasis on cell populations, control selection and expression data collection. Despite discordant results, several dysregulated genes have been identified across multiple studies, including PLS3, KIR3DL2, TWIST1 and STAT4. Here, we provide an overview of the most consistently expressed genes across different studies and bring them together through common pathways biologically relevant to CTCL. Four pathways - evasion of activation-induced cell death, T helper 2 lymphocyte differentiation, transforming growth factor-β receptor expression, and tumour necrosis factor receptor ligands - appear to encompass the most frequently affected genes, hypothetically providing insight into the disease pathogenesis.
Postischemic PKC activation rescues retrograde and anterograde long-term memory (2009)

Therapeutics for cerebral ischemia/hypoxia, which often results in ischemic stroke in humans, are a global unmet medical need. Here, we report that bryostatin-1, a highly potent protein kinase C (PKC) activator, interrupts pathophysiological molecular cascades and apoptosis triggered by cerebral ischemia/hypoxia, enhances neurotrophic activity, and induces synaptogenesis in rats. This postischemic therapeutic approach is further shown to preserve learning and memory capacity even 4 months later as well as long-term memory induced before the ischemic event. Our results of electromicroscopic and immunohistochemical analyses of neuronal and synaptic ultra-structure are consistent with a PKC-mediated synaptic remodeling and repair process that confers long-lasting preservation of spatial learning and memory before and after the cerebral ischemic/hypoxic event, suggesting a previously undescribed therapeutic modality for cerebral ischemia/hypoxia and ischemic stroke.
Clinical spectral characterisation of colonic mucosal lesions using autofluorescence and δ aminolevulinic acid sensitisation (1999)

The in vivo point measurements imply that a good discrimination between normal tissue and adenomatous polyps can be obtained using the LIF technique. Excitation at 337 nm and at 405 nm or 436 nm using ALA gives good results. LIF also shows potential for distinguishing adenomatous from hyperplastic polyps. The number of detection wavelengths could be reduced if chosen properly.
Understanding Renewable Energy Systems (2016)

By mid-century, renewable energy must cover all of our energy supply if we are to phase out nuclear and successfully stop climate change. Now updated and expanded, the 2nd edition of this textbook covers the full range of renewable energy systems and now also includes such current trends as solar power storage, power-to-gas technologies, and the technology paths needed for a successful and complete energy transition. The topics are treated in a holistic manner, bringing together maths, engineering, climate studies and economics, and enabling readers to gain a broad understanding of renewable energy technologies and their potential.Numerous examples are provided for calculations, and graphics help visualize the various technologies and mathematical methodologies. Understanding Renewable Energy Systems is an ideal companion for students of renewable energy at universities or technical colleges on courses such as renewable energy, electrical engineering, engineering technology, physics, process engineering, building engineering, environment, applied mechanics and mechanical engineering, as well as scientists and engineers in research and industry.
Proximal Small Intestinal Microbiota and Identification of Rod-Shaped Bacteria Associated With Childhood Celiac Disease (2009)

Rod-shaped bacteria, probably of the indicated species, constituted a significant fraction of the proximal small intestine microbiota in children born during the Swedish CD epidemic and may have been an important risk factor for CD contributing to the fourfold increase in disease incidence in children below 2 years of age during that time.