gebhart/patrepeval huggingface dataset:
Feasibility and limitations of the rat model by C6 gliomas implanted at the subcutaneous region (2002)

Although rat models implanted with C6 glioma cells have been widely utilized for the assessment of new therapeutic modalities, a convenient in vivo model is still required. We implanted C6 glioma cells into the brains and the abdominal subcutaneous regions of Wistar rats, and evaluated the volumes of the growing tumors. The cultures of 5 x 10(6) cells had successfully formed tumors at 100% (52/52) of sites in the subcutaneous regions on day 5 after implantation. It was easy to measure the visible tumors with a sliding caliper. The tumor volume at the subcutaneous region reached a maximum volume (950 mm3+/-167 SE) on day 15, after which it diminished. In contrast, tumors implanted in the intracerebral region showed a maximum volume on day 20 after the implantation of 1 x 10(5) cultured cells. Pathological examinations of the subcutaneous and intracranial tumors on day 15 showed similar findings exhibiting high nuclear cell ratio, mitosis and pseudopalisading with small populations of GFAP positive cells. The results suggested that rat C6 glioma models with implantation into the subcutaneous abdomen are available from day 5 to day 15 as a convenient model for the assessment of anti-proliferative drugs. The usefulness and the limitations of the rat C6 glioma model are discussed in this manuscript.
Minimal Residual Disease Status Before Allogeneic Bone Marrow Transplantation Is an Important Determinant of Successful Outcome for Children and Adolescents With Acute Lymphoblastic Leukemia (1998)

The efficacy of allografting in acute lymphoblastic leukemia (ALL) is heavily influenced by remission status at the time of transplant. Using polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis, we have investigated retrospectively the impact of submicroscopic leukemia on outcome in 64 patients receiving allogeneic bone marrow transplantation (BMT) for childhood ALL. Remission BM specimens were taken 6 to 81 days (median, 23) before transplant. All patients received similar conditioning therapy; 50 received grafts from unrelated donors and 14 from related donors. Nineteen patients were transplanted in first complete remission (CR1) and 45 in second or subsequent CR. MRD was analyzed by PCR of Ig or T-cell receptor δ or γ rearrangements, electrophoresis, and allele-specific oligoprobing. Samples were rated high-level positive (clonal band evident after electrophoresis; sensitivity 10−2 to 10−3), low-level positive (MRD detected only after oligoprobing; sensitivity 10−3 to 10−5), or negative. Excluding 8 patients transplanted in CR2 for isolated extramedullary relapse (all MRD−), MRD was detected at high level in 12 patients, low level in 11, and was undetectable in 33. Two-year event-free survival for these groups was 0%, 36%, and 73%, respectively (P &lt; .001). Follow-up in patients remaining in continuing remission is 20 to 96 months (median, 35). These results suggest that MRD analysis could be used routinely in this setting. This would allow identification of patients with resistant leukemia (who may benefit from innovative BMT protocols) and of those with more responsive disease (who may be candidates for randomized trials of BMT versus modern intensive relapse chemotherapy).
A review of microfabricated devices for gene-based diagnostics. (1995)

The next technologic revolution may well be the miniaturization of solution phase experimentation through the marriage of microelectronics and molecular biology. Already researchers leading this rapidly emerging technology are developing prototype biochemical "microlaboratories" that offer a millionfold reduction of scale; that is, biochemical analyses are being conducted with picoliter sample volumes rather than conventional microliter formats. Such miniaturization is achieved by exploiting the well-honed tools of microelectronics that accommodate highly parallel automated assays, ultrasensitive detection, high throughput, integrated data acquisition, computation, and distributed data storage/retrieval. The subject of this paper is to survey this evolving bioelectronic miniaturization technology with applications to gene-based diagnostics. Several pioneering microchips are described and compared to traditional biochemical methods. Specifically, miniaturized examples of various diagnostic processes such as sample preparation (PCR), assays (electrophoresis and probe arrays), and detection (integrated CCDs) are presented. Although these microdevices are rather embryonic they represent the first steps toward fabricating a fully integrated diagnostic system on a microchip.
A new look at impact ionization-Part I: A theory of gain, noise, breakdown probability, and frequency response (1999)

Impact ionization in thick multiplication regions is adequately described by models in which the ionization coefficients are functions only of the local electric field. In devices with thin multiplication lengths, nonlocal effects become significant, necessitating new models that account for the path that a carrier travels before gaining sufficient energy to impact ionize. This paper presents a new theory that incorporates history-dependent ionization coefficients, and it is shown that this model can be utilized to calculate the low-frequency properties of avalanche photodiodes (APD's) (gain, noise, and breakdown probability in the Geiger mode) and the frequency response. A conclusion of this work is that an ionization coefficient is not a fundamental material characteristic at a specific electric field and that any experimental determination of ionization coefficients is valid only for the particular structure on which the measurement was performed.
Fibroblast function in psoriatic arthritis. II. Increased expression of beta platelet derived growth factor receptors and increased production of growth factor and cytokines. (1994)

Our data demonstrate an increased expression of beta PDGF receptor, and production of IL-1 beta and PDGF by psoriatic fibroblasts. The findings provide further support for an active role of this cell line in the pathogenesis of psoriasis and psoriatic arthritis.
Iminosugar-Based Inhibitors of Glucosylceramide Synthase Increase Brain Glycosphingolipids and Survival in a Mouse Model of Sandhoff Disease (2011)

The neuropathic glycosphingolipidoses are a subgroup of lysosomal storage disorders for which there are no effective therapies. A potential approach is substrate reduction therapy using inhibitors of glucosylceramide synthase (GCS) to decrease the synthesis of glucosylceramide and related glycosphingolipids that accumulate in the lysosomes. Genz-529468, a blood-brain barrier-permeant iminosugar-based GCS inhibitor, was used to evaluate this concept in a mouse model of Sandhoff disease, which accumulates the glycosphingolipid GM2 in the visceral organs and CNS. As expected, oral administration of the drug inhibited hepatic GM2 accumulation. Paradoxically, in the brain, treatment resulted in a slight increase in GM2 levels and a 20-fold increase in glucosylceramide levels. The increase in brain glucosylceramide levels might be due to concurrent inhibition of the non-lysosomal glucosylceramidase, Gba2. Similar results were observed with NB-DNJ, another iminosugar-based GCS inhibitor. Despite these unanticipated increases in glycosphingolipids in the CNS, treatment nevertheless delayed the loss of motor function and coordination and extended the lifespan of the Sandhoff mice. These results suggest that the CNS benefits observed in the Sandhoff mice might not necessarily be due to substrate reduction therapy but rather to off-target effects.
Prevention of postherpetic neuralgia with varicella‐zoster hyperimmune globulin (2002)

Recovery after an acute attack of herpes zoster is followed by postherpetic neuralgia (PHN) in 9-14% of all patients. Depending on the patient's age, the severity of the acute attack of herpes zoster and the dermatome involved, the incidence of PHN may be as high as 65%. The purpose of our study was to ascertain the incidence of PHN after a prophylactic intravenous injection of varicella-zoster hyperimmune globulin (VZV-IG) (Varitect Biotest Pharma). For this double-blind placebo-controlled randomised investigation we defined PHN as pain confined to the dermatome previously affected by herpes zoster, and we required a pain intensity of at least 15% points on a visual analogue scale (VAS) for this dermatome. The inclusion criteria were the dermatological diagnosis of herpes zoster together with age over 50 years. On Day 1, 20 patients received a single intravenous infusion of VZV-IG in a dose of 2mL/kg body weight, 20 patients (control group) received a single infusion of human albumin 5% in a dose of 2mL/kg body weight. All patients received acyclovir intravenously in a dose of 15mg/kg body weight per 24h for 5 days. The patients were followed up for a total of 42 days. The incidence of PHN at Day 42 was selected as the main outcome criterion for assessing the efficacy of prophylaxis. On reaching a significant difference between the groups (t test; alpha<0.05) in favour of the active treatment group, prophylaxis of PHN by VZV-IG was assessed as effective. Pain was assessed on a VAS and a NAS. As auxiliary outcome criteria, we used the McGill Pain-Rating Questionnaire in its German version, the revised multidimensional pain scale (RMSS) and the Freiburg symptom list (FBL). All results were assessed by the t test (alpha<0.05). The frequency of PHN in the placebo group was 70% (14/20), in the active treatment group it was 35% (7/20) at Day 42. The results of the McGill test showed the variability of the perception of pain in the placebo group significantly greater. No significant group differences were found in the FBL. Being tested with the RMSS, the patients of the placebo group assessed their pains as significantly "more obstinate" (p=0.047). The results can be summed up by saying that VZV-IG not only reduces the incidence of PHN, but also that in certain respects the patients' assessments of their pain experience were different. In our study we found a 50% reduction in PHN incidence However, the outcome time point of our trial was so close to the acute phase of the zoster illness that spontaneous remissions of PHN still have to be taken into account. Despite the widely varied approaches to the problem, reliably effective therapy, let alone 100% prevention of PHN, is still not feasible.
Analyses of disease-related GNPTAB mutations define a novel GlcNAc-1-phosphotransferase interaction domain and an alternative site-1 protease cleavage site (2015)

Mucolipidosis II (MLII) and III alpha/beta are autosomal-recessive diseases of childhood caused by mutations in GNPTAB encoding the α/β-subunit precursor protein of the GlcNAc-1-phosphotransferase complex. This enzyme modifies lysosomal hydrolases with mannose 6-phosphate targeting signals. Upon arrival in the Golgi apparatus, the newly synthesized α/β-subunit precursor is catalytically activated by site-1 protease (S1P). Here we performed comprehensive expression studies of GNPTAB mutations, including two novel mutations T644M and T1223del, identified in Brazilian MLII/MLIII alpha/beta patients. We show that the frameshift E757KfsX1 and the non-sense R587X mutations result in the retention of enzymatically inactive truncated precursor proteins in the endoplasmic reticulum (ER) due to loss of cytosolic ER exit motifs consistent with a severe clinical phenotype in homozygosity. The luminal missense mutations, C505Y, G575R and T644M, partially impaired ER exit and proteolytic activation in accordance with less severe MLIII alpha/beta disease symptoms. Analogous to the previously characterized S399F mutant, we found that the missense mutation I403T led to retention in the ER and loss of catalytic activity. Substitution of further conserved residues in stealth domain 2 (I346 and W357) revealed similar biochemical properties and allowed us to define a putative binding site for accessory proteins required for ER exit of α/β-subunit precursors. Interestingly, the analysis of the Y937_M972del mutant revealed partial Golgi localization and formation of abnormal inactive β-subunits generated by S1P which correlate with a clinical MLII phenotype. Expression analyses of mutations identified in patients underline genotype-phenotype correlations in MLII/MLIII alpha/beta and provide novel insights into structural requirements of proper GlcNAc-1-phosphotransferase activity.
Room-Temperature Preparation, Characterization, and Photoluminescence Measurements of Solid Solutions of Various Compositionally-Defined Single-Crystalline Alkaline-Earth-Metal Tungstate Nanorods (2008)

The current report describes the systematic synthesis of single-crystalline alkaline-earth-metal tungstate AWO4 (A = Ca, Sr, Ba) nanorods as well as a series of their crystalline solid−solution analogues Sr1-xCaxWO4 and Ba1-xSrxWO4 (0 < x < 1) with controllable chemical composition and morphology using a modified template-directed methodology under ambient room-temperature conditions. Extensive characterization of the resulting nanorods has been performed using diffraction, X-ray photoelectron spectroscopy, electron microscopy, and optical spectroscopy. The composition-modulated luminescence properties of these alkaline-earth-metal tungstate solid−solution nanorods provide for a fundamental understanding of the intrinsic optical and optoelectronic properties of these systems, suggesting, therefore, the possibility of their rational incorporation into functional nanoscale devices.
New Strategies for Treatment of ALK-Rearranged Non–Small Cell Lung Cancers (2011)

The identification of oncogenic alterations in subsets of patients with non-small cell lung cancer (NSCLC) is transforming clinical care. Genomic rearrangements in anaplastic lymphoma kinase (ALK) are detected in 3% to 7% of patients with NSCLC. The ALK tyrosine kinase inhibitor crizotinib has demonstrated clinical efficacy in ALK-rearranged NSCLC patients and was recently approved by the U.S. Food and Drug Administration. Crizotinib is currently under additional phase III clinical development as both initial and second-line therapy for advanced ALK-rearranged NSCLC. However, new challenges in the diagnosis and treatment of this subset of NSCLC have emerged, including the need to determine the most effective means of diagnosing ALK-rearranged NSCLC and the emergence of acquired drug resistance to crizotinib. In this review, we discuss current strategies for treatment and diagnosis, as well as the current knowledge about mechanisms of acquired resistance to crizotinib. Finally, we discuss the strategies that are underway to clinically overcome acquired drug resistance.
The small RNA GlmY acts upstream of the sRNA GlmZ in the activation of glmS expression and is subject to regulation by polyadenylation in Escherichia coli (2008)

In Escherichia coli the glmS gene encoding glucosamine 6-phosphate (GlcN-6-P) synthase GlmS is feedback regulated by GlcN-6-P in a pathway that involves the small RNA GlmZ. Expression of glmS is activated by the unprocessed form of GlmZ, which accumulates when the intracellular GlcN-6-P concentration decreases. GlmZ stabilizes a glmS transcript that derives from processing. Overexpression of a second sRNA, GlmY, also activates glmS expression in an unknown way. Furthermore, mutations in two genes, yhbJ and pcnB, cause accumulation of full-length GlmZ and thereby activate glmS expression. The function of yhbJ is unknown and pcnB encodes poly(A) polymerase PAP-I known to polyadenylate and destabilize RNAs. Here we show that GlmY acts indirectly in a way that depends on GlmZ. When the intracellular GlcN-6-P concentration decreases, GlmY accumulates and causes in turn accumulation of full-length GlmZ, which finally activates glmS expression. In glmZ mutants, GlmY has no effect on glmS, whereas artificially expressed GlmZ can activate glmS expression also in the absence of GlmY. Furthermore, we show that PAP-I acts at the top of this regulatory pathway by polyadenylating and destabilizing GlmY. In pcnB mutants, GlmY accumulates and induces glmS expression by stabilizing full-length GlmZ. Hence, the data reveal a regulatory cascade composed of two sRNAs, which responds to GlcN-6-P and is controlled by polyadenylation.
RFCMOS Unit Width Optimization Technique (2007)

In this paper, we demonstrate a unit width ( W <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">f</sub> ) optimization technique based on their unity short-circuit current gain frequency (f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sub> ) unilateral power gain frequency (f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">MAX</sub> )? and high-frequency (HF) noise for RFCMOS transistors. Our results show that the trend for the above figures-of-merit (FOMs) with respect to the W <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">f</sub> change is different; hence, some tradeoff is required to obtain the optimum W <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">f</sub> value. During the HF noise analysis, a new FOM is proposed to study the W <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">f</sub> effect on the HF noise performance. In our experiment, the flicker noise of the transistor is also measured and the result shows that the change in W <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">f</sub> does not affect the noise spectral density at the low-frequency range. This technique enables RF engineers to optimize the transistor's layout and helps to select the optimum Wf for transistors used in specific circuit design such as the low-noise amplifier, voltage-controlled oscillator, and mixer. Furthermore, by using layout optimized transistors in the RF circuit, the optimal circuit's performance can be easily achieved and, thus, greatly reduced the circuit development time. In the aspect of RF device modeling, by knowing the optimum W <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">f</sub> for a particular process or technology, the number of transistors to model is reduced and, hence, greatly shortens the RF modeling development time for existing and future technologies.
B-cell Activation versus Tolerance - The Central Role of Immunoglobulin Receptor Engagement and T-cell Help (1997)

The critical variables responsible for the decision between activation and tolerance in the B-cell compartment were studied in the well-characterised hen egg lysozyme:antilysozyme transgenic model. Mature B-cells exposed to a low antigenic signal, which resulted in a receptor occupancy of between 5% and 25%, remained 'indifferent' (i.e. were neither activated nor tolerant), had a normal lifespan and recirculated through B-cell follicles. When receptor occupancy reached a critical threshold of approximately 50%, the B-cells became activated and moved to the outer T-cell zones where they died. This threshold appeared to be lower in the case of immature B-cells. On addition of T-cell help, however, the B-cells were rescued, proliferated and secreted antibody. Thus the outcome of the interaction between B-cells and antigen (self or foreign) is determined largely by the degree of antigen receptor engagement and availability of T-cell help.
Prävention der erektilen Dysfunktion (2009)

Die wichtigste gesicherte Maßnahme zur Prävention der erektilen Dysfunktion ist die Aufrechterhaltung der Funktion des arteriellen Systems und somit die Vermeidung der Atherosklerose. Weniger gut gesichert, aber aus vielerlei Gründen plausibel, ist die Verbesserung der Oxygenierung der Schwellkörper durch regelmäßige Erektionen. Ob die Häufigkeit, Dauer und Qualität der Erektionen pharmakologisch (Phosphodiesterase-5-Hemmer vor der Bettruhe, gegebenenfalls kombiniert mit abendlicher Applikation einer kleineren Testosterondosis) oder durch andere Maßnahmen verbessert wird, ist dabei vermutlich sekundär. Sowohl dem Geschlechtsverkehr als auch der Masturbation wird ein protektiver Effekt zugeschrieben. Der pharmakologische Ansatz ist zumindest insofern charmant, als die Verbesserung der Oxygenierung der Schwellkörper ohne eigenes Zutun  spontan und im Schlaf  erfolgt. Ob, und wenn ja für welche Risikogruppe bzw. ab welchem Alter solche Maßnahmen empfohlen werden können, wurde bislang noch nicht untersucht, sodass generelle Empfehlungen derzeit noch nicht gegeben werden können.
Pan B‐cell markers are not redundant in analysis of chronic lymphocytic leukemia (CLL) (2003)

Variable patterns and intensity of staining were seen for FMC7, CD20, and CD79b in this cohort of CLL samples. Dim or negative staining was most consistently seen for FMC7 (93% of specimens). Although FMC7 staining intensity was moderately correlated with CD20, CD79b intensity was poorly correlated with either CD20 or FMC7, and thus, may provide some independent information.
Integrated fingerprint verification method using a composite signature-based watermarking technique (2007)

We propose a composite signature-based digital watermarking technique for fingerprint verification and identity extraction applications. In a two-step process, our scheme attempts to integrate three modalities of authentication-"what you know," "what you have," and "what you are." Using a signature extracted from the Fourier phase of an original image, we hide an encoded signature back into the original image using a frequency domain bit-plane embedding technique. Additionally, other identity information is embedded in the spatial domain using a spread-spectrum method. The detection process computes the Fourier transform of the watermarked image, then extracts the embedded signature and correlates it with a calculated signature. The embedding of a composite signature ensures robustness against any chosen form of distortion. Simulation results for the signature and identity embedding and detection are provided for the Fingerprint Verification Competition (FVC) fingerprint image database.
Inhibition of a constitutive translation initiation factor 2α phosphatase, CReP, promotes survival of stressed cells (2003)

Phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) on serine 51 is effected by specific stress-activated protein kinases. eIF2alpha phosphorylation inhibits translation initiation promoting a cytoprotective gene expression program known as the integrated stress response (ISR). Stress-induced activation of GADD34 feeds back negatively on this pathway by promoting eIF2alpha dephosphorylation, however, GADD34 mutant cells retain significant eIF2alpha-directed phosphatase activity. We used a somatic cell genetic approach to identify a gene encoding a novel regulatory subunit of a constitutively active holophosphatase complex that dephosphorylates eIF2alpha. RNAi of this gene, which we named constitutive repressor of eIF2alpha phosphorylation (CReP, or PPP1R15B), repressed the constitutive eIF2alpha-directed phosphatase activity and activated the ISR. CReP RNAi strongly protected mammalian cells against oxidative stress, peroxynitrite stress, and more modestly against accumulation of malfolded proteins in the endoplasmic reticulum. These findings suggest that therapeutic inhibition of eIF2alpha dephosphorylation by targeting the CReP-protein-phosphatase-1 complex may be used to access the salubrious qualities of the ISR.