gebhart/patrepeval huggingface dataset:
Thyroid Hormones Directly Alter Human Hair Follicle Functions: Anagen Prolongation and Stimulation of Both Hair Matrix Keratinocyte Proliferation and Hair Pigmentation (2008)

Thus, we present the first evidence that human HFs are direct targets of thyroid hormones and demonstrate that T3 and/or T4 modulate multiple hair biology parameters, ranging from HF cycling to pigmentation.
Both Type I and II Insulin-Like Growth Factor Receptor Binding Increase during Lactogenesis in Bovine Mammary Tissue* (1988)

Bovine GH is a potent stimulant of lactation, and the insulin-like growth factors I and II (IGF-I and -II) are believed to mediate GH's growth-promoting actions. Since all of IGF's known actions are mediated through its receptor subtypes, we analyzed the distribution of IGF receptor subtypes in lactating and nonlactating bovine mammary tissue. Analysis of competition curves showed that IGF-I had greater potency than IGF-II in competing with [125I]IGF-I for binding to membranes prepared from both lactating and nonlactating animals. An insulin concentration of 4 micrograms/ml displaced less than 40% of the [125I]IGF-I bound to membranes prepared from both lactating and nonlactating animals, indicating that a high percentage of [125I]IGF-I was bound to the type II receptor. Lactation was associated with an increase in the total amount of [125I]IGF-I bound, and this change was due to an increase in binding to both receptor subtypes. Specifically, membranes prepared from lactating animals had a 3-fold increase in binding competed for by insulin and a 2-fold increase in binding not competed for by insulin. Affinity cross-linking of [125I]IGF-I to membranes prepared from both lactating and nonlactating animals, followed by polyacrylamide gel electrophoresis (PAGE) and autoradiography, showed that 260K and 135K bands were present. Competition experiments indicated that unlabeled IGF-I effectively competed for binding to the 260K band, whereas insulin did not. Binding to the 135K band could be inhibited by both IGF-I and insulin. The intensity of the labeled bands showed that type II receptors were relatively more abundant than type I receptors in membranes from both lactating and nonlactating animals. Membranes prepared from lactating animals showed both 135K and 127K species of the type I receptor, whereas nonlactating animals showed only the 135K band. We conclude that type I and II receptors are present in bovine mammary tissue, and type II predominate. Lactation is associated with increases in the concentration of both receptor subtypes, especially type I receptors. Lactation may be associated with structural changes in the type I receptor. These changes in receptor distribution could play a role in modulating the physiological effects of the IGFs on mammary tissue.
Vibration isolation design for Benaroya Hall (1998)

Location of the new Seattle Concert Hall, Benaroya Hall, directly over an existing Burlington Northern railroad tunnel required development of a very effective vibration and noise isolation system. The first step in the design was to measure the ground-borne vibration and noise levels from trains via boreholes at the site and in the basement levels of nearby buildings located over the tunnel. From the measured vibration, the expected sound level in the performance space was projected for comparison with the criterion established for acceptable level and inaudibility. This comparison determined the amount and frequency range for the reduction required. The degree of reduction of structure-borne noise required determined that the design required two parts, a massive foundation mat for coupling loss and an isolation system with 4-5 Hz effective natural frequency and full reduction over a wide frequency range. Achieving the needed attenuation required a structure with very high mechanical impedance and isolators which provide a low acoustical impedance over a broad frequency range, leading to the use of heavy concrete structure and natural rubber isolation bearings. Details of the design parameters and materials are presented along with results from measurements with the completed isolation system and partially completed hall.
Negative trans-regulation of T-cell antigen receptor/T3 complex mRNA expression in murine T-lymphoma somatic cell hybrids. (1986)

The antigen-specific T-cell receptor (TCR) is composed of variable antigen-recognition chains TCR-alpha and TCR-beta in noncovalent association with the invariant T3 multimer. The TCR-alpha and TCR-beta chains are encoded by gene segments that must be juxtaposed by rearrangement in order to be expressed. To examine whether mechanisms other than gene rearrangement might regulate TCR/T3 gene expression, somatic cell hybrids were formed among closely related murine SL12 T-lymphoma clones that differ in TCR/T3 mRNA levels. In hybrid cells formed between cell clones in which one parent is TCR-beta+ and the other is TCR-beta-, the resultant hybrid cells lack detectable TCR-beta transcripts. Since the protein synthesis inhibitor cycloheximide partially reverses TCR-beta repression in the hybrid cells, we postulate that a labile repressor protein is involved. The amount of mRNA encoding one of the T3 polypeptide chains, T3-delta, is also strongly negatively transregulated in the same hybrid cells in which TCR-beta mRNA expression is repressed. The negative trans-regulation of TCR-beta and T3-delta mRNA expression is relatively specific, since the levels of TCR-alpha mRNA and several thymocyte surface antigens are not repressed in somatic cell hybrids. Our results indicate that rearrangement of the TCR genes alone is not sufficient for TCR-beta expression and that trans-acting factors regulate the amounts of both TCR-beta and T3-delta mRNA in this system.
Phase I/II study of the tumor-targeting human L19-IL2 monoclonal antibody-cytokine fusion protein in patients with advanced renal cell carcinoma (2008)

16032 Background: L19-IL2 is a tumor targeted immunocytokine constituted by a single chain Fragment variable (scFv) format directed against the ED-B domain of fibronectin and the human cytokine interleukin-2 (IL2). We carried out a phase I/II study in patients with solid tumors to assess safety, pharmacokinetics (PK), and early signs of activity of L19-IL2 monotherapy. Methods: L19-IL2 was administered as an i.v. infusion at doses of 5 (n=1), 10 (n=1), 22.5 (n=15) and 30 MioIU IL2 equivalent dose (n=1) on days 1, 3 and 5 every 21 days. Serum samples for PK assessment were collected on day 1, 3, 5 and 10 of each cycle. Flow cytometry (marker panels: T-cells CD71/CD8/CD3/CD4; NK/B-cells CD71/CD19/CD3/CD56; IL-2R-positive T-cells CD25/-CD122/CD3/CD4) and assessment of human antifusion protein antibodies to L19 (HAFA) were performed at screening and on day 1, 3, 5 and 10 of each cycle. Data on safety and activity were evaluated using CTC v3.0 and RECIST criteria, respectively. Results: Among the total 33 patients,18 had progressive advanced renal clear-cell carcinoma (RCC). Of these, 6 were treated in the phase I and a further 12 planned patients with RCC in the phase II part of the study. The 30 MiU IL2 equivalent dose was considered toxic. The 22.5 MiU dose was determined to be the MTD, which was selected to be the RD. Total/median number of cycles was 62/4 (2–6). Median age was 62 years (52–74). 15 of 18 patients had received prior systemic therapy. We recorded three grade 3 toxicities: 1 hypertension and hypoxia, 1 dyspnoea, and 1 renal failure. All other toxicities were moderate and transient. There were no treatment-related deaths. 16 patients are evaluable for response. We observed stable disease in 13 patients (81%) and progressive disease in 3 (19%) after six infusions of L19-IL2. Immunophenotyping analysis showed stimulation of NK cells being by far the strongest, followed by T4 cells and CTLs. Pharmacokinetic analysis and HAFA development data will be shown. Conclusions: The part II of this study confirms that L19-IL2 can be safely administered repeatedly in patients with advanced RCC at 22.5 Mio IU IL2 equivalent dose. Preliminary evaluation suggests clinical activity in these mostly pretreated patients. Toxicity was manageable and reversible. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Philogen, Philogen SPA Philogen SPA Bayer, Schering AG Philogen SPA
Tumor necrosis factor enhances HLA-A,B,C and HLA-DR gene expression in human tumor cells. (1987)

Tumor necrosis factor-alpha (TNF-alpha) exerts multiple biologic activities, which include such diverse effects as direct tumoricidal activity and stimulation of metabolic activities as well as expression of cell surface antigens on nonmalignant cells. We report here that in various human tumor cells TNF-alpha upregulates constitutively expressed HLA genes. Further, in a priori HLA-negative tumor cells, TNF-alpha enhances IFN-gamma-induced class I and class II HLA gene expression. In vitro transcription, Northern blot, and immunofluorescence analysis performed with the leukemic cell line K 562 reveal that TNF-alpha reversibly enhances IFN-gamma-induced HLA gene expression at the level of mRNA transcription. In addition, a posttranscriptional regulation of HLA gene expression by TNF-alpha is suggested from enhancement of HLA class I membrane expression in Colo 205 cells without measurable changes in steady state mRNA levels. Therefore, it is conceivable that TNF-alpha, similar to IFN-gamma, might provoke tumor rejection not only via direct tumoricidal action but also via enhancement of HLA antigens and induction of tumor-specific immune responses.
Flow approaches towards sustainability (2014)

Green chemistry and flow chemistry are ideal partners for accessing novel chemical spaces and define highly efficient synthetic tools.
Role of Mitochondria in Prostate Cancer (2005)

Most malignant cells are highly glycolytic and produce high levels of reactive oxygen species (ROS) compared to normal cells. Mitochondrial glycerophosphate dehydrogenase (mGPDH) participates in delivering reducing equivalents from this molecule into the electron transport chain, thus sustaining of glycolysis. Here we investigate the role of mGPDH in maintaining an increased rate of glycolysis and evaluate glycerophosphate-dependent ROS generation in prostate cancer cell lines (LNCaP, DU145, PC3, and CL1). Immunoblot, Real Time RTPCR, polarographic, and spectrophotometric analysis revealed that mGPDH abundance and activity was significantly elevated in prostate cancer cell lines when compared to normal prostate epithelial cell line PNT1A. Furthermore, both the glycolytic capacity and glycerophosphate-dependent ROS production was increased 1.68-4.44 fold and 5-7 fold, respectively in prostate cancer cell lines when compared to PNT1A cells. Overall, these data demonstrate that mGPDH is involved in maintaining a high rate of glycolysis and is an important site of electron leakage leading to ROS production in prostate cancer cells.
Correlated Double Sampling CMOS Readout Circuit for Medical X-ray Imaging (2008)

This paper presents a new hybrid current-programmed, current-output active pixel sensor (APS) suitable for real time x- ray imaging (fluoroscopy) and an off-panel CMOS readout circuit. The pixel circuit is designed using hydrogenated amorphous silicon (a-Si:H) thin film transistor (TFT) technology. The simulation results based on the measured characteristics of a- Si:H TFTs show that the proposed pixel circuit can successfully compensate for characteristic variations (e.g. mobility and threshold voltage shift) in a-Si:H TFTs under prolonged gate voltage stress. The readout circuit exploits correlated double sampling (CDS) technique to reduce the offset current, low frequency noise and fixed-pattern noise (FPN) on the array operation. I. INTRODUCTION Active matrix flat panel technology based on a-Si:H TFTs has been extensively applied to digital x-ray diagnostic medical imaging. The technology has several desirable attributes such as uniformity, low temperature fabrication and economical construction. The active matrix used for addressing and readout consists of many pixels each responsible for efficient transfer of collected charge to the external readout electronics. The collected charge is proportional to the x-ray radiation and can be obtained by both direct and indirect conversion methods (1). So far, the most widely used and simplest circuit topology for each pixel is the passive pixel sensor (PPS) (2). Although the PPS topology offers a very compact circuit, it is a destructive scheme which does not permit multiple readouts to reduce noise and is incapable of in situ signal amplification. As a result, the pixel dynamic range is relatively poor. To cope with this problem a 3-TFT active pixel sensor (APS) has been previously presented (3). Although this pixel circuit provides on-pixel amplification, it does not completely compensate for the threshold voltage shift in the a-Si:H TFTs caused by their inherent instability (4). In this paper, new hybrid 3-TFT current programmed APS pixel circuit suitable for real-time x-ray imaging along with the corresponding CMOS current-mode readout circuit suitable for performing CDS are presented. The pixel circuit extends the application of a-Si:H TFT from conventional switching element to on-pixel amplifier for enhanced signal-to-noise ratio and higher imager dynamic range. The capability of operation in both passive and active modes as well as being able to compensate for inherent instabilities of the TFTs makes the architecture a good candidate for x-ray imaging modalities with a wide range of incoming x-ray intensities. This paper is organized as follows: Section II introduces and discusses the operation of the 3-TFT pixel circuit. In section III the implementation of a CMOS readout circuit capable of performing double sampling and the performance simulation results are presented and conclusions drawn in section VI.
The role of fluoroquinolones in the management of skin, soft tissue, and bone infections. (1989)

The fluoroquinolones are a group of potent antimicrobials with marked in vitro activity against gram negative bacteria and, to a lesser extent, staphylococci. Their major advantages include the availability of oral preparations, relative safety, and excellent tissue penetration. Controlled clinical studies have shown that the oral quinolones are as effective as cephalexin in mild skin and soft tissue infections, and that ciprofloxacin is as effective as cefotaxime in more severe infections. Uncontrolled studies chiefly with ciprofloxacin in patients with acute and chronic osteomyelitis with staphylococci and gram negative bacteria have resulted in cure rates of 60-85%. The quinolones offer definite advances in the management of gram negative osteomyelitis and could be substituted for the aminoglycosides or third generation cephalosporins in nosocomial soft tissue infections. However, the quinolones offer no advantage over standard therapy for mild skin and soft tissue infections, particularly those caused by streptococci or methicillin-sensitive staphylococci. Development of resistant mutants may become a problem with indiscriminate use of these agents.
Percutaneous Peripheral Neuromodulation in the Treatment of Fecal Incontinence (2003)

A percutaneous access to the S(3) spinal region was achieved through the posterior tibial nerve. Improvement of FI was achieved in 78.2%. The technique is simple, easy, without complications and cost-effective. It can be done as an outpatient procedure or by the patient at home. The results need to be reproduced on a large number of patients.
Dramatic attenuation of hypusine formation on eukaryotic initiation factor 5A during senescence of IMR‐90 human diploid fibroblasts (1997)

Deoxyhypusine synthase catalyzes the conversion of lysine to deoxyhypusine residue on the eukaryotic initiation factor 5A (eIF-5A) precursor using spermidine as the substrate. Subsequent hydroxylation of the deoxyhypusine residue completes hypusine formation on eIF-5A. Hypusine formation is one of the most specific polyamine-dependent biochemical events in eukaryotic cells. Although changes in polyamine metabolism have been demonstrated in human diploid fibroblasts during senescence (Chen and Chang, 1986, J. Cell. Physiol., 128:27–32.), it is unclear whether or not polyamine-dependent hypusine formation itself is an age-dependent biochemical event. In the present study, hypusine-forming activity was measured by a radiolabeling assay in cells whose polyamines have been depleted by prior treatment of α-difluoromethyl ornithine (DFMO). In addition, an in vitro cross-labeling assay was developed for simultaneous measurement of the deoxyhypusine synthase activity and protein substrate (eIF-5A precursor) amount. We showed that the hypusine-forming activity in low-passage presenescent IMR-90 cells [population doubling level (PDL) = 15–23, termed young cells] was prominently induced by serum whereas little or no hypusine-forming activity could be detected in late-passage senescent cells (PDL = 46–54, termed old cells). The striking difference in hypusine-forming activity between young and old cells was due to changes in both deoxyhypusine synthase activity and eIF-5A precursor amount in IMR-90 cells during senescence. However, Northern blot analysis showed no significant difference in the eIF-5A messenger RNA (mRNA) between young and old cells, suggesting that the age-dependent attenuation of eIF-5A precursor protein may be regulated at either translational or posttranslational level. J. Cell. Physiol. 170:248–254, 1997. © 1997 Wiley-Liss, Inc.
Molybdenum cofactor negative mutants of Escherichia coli use citrate anaerobically (1990)

Anaerobically, Escherichia coli cannot grow using either glycerol or citrate as sole carbon and energy source. However, it has been reported that a mixture of glycerol and citrate will support growth. We have found that wild-type strains of E. coli K-12 do not grow on glycerol plus citrate anaerobically. However, growth eventually occurs due to the frequent appearance of mutants. We found that such Cit+ mutants were defective in anaerobic respiration with nitrate or trimethylamine-N-oxide and were chlorate resistant (i.e. molybdenum cofactor deficient). Conversely, well characterized mutants in any of chlA, B, D, E, G and N were also able to use citrate anaerobically. No anaerobic growth differences between wild type and chl mutants were observed either with fermentable sugars or with glycerol plus fumarate or glycerol plus tartrate. Citrate lyase was induced anaerobically by citrate and repressed by glucose in both wild type strains and chl mutants. Furthermore, levels of citrate lyase, fumarate reductase, malate dehydrogenase, fumarase and alcohol dehydrogenase were similar in both types of strains under anaerobic conditions. It is conceivable that a functioning molybdenum cofactor prevents use of citrate by keeping citrate lyase in the inactive form.
Interaction of kindlin-2 with integrin β3 promotes outside-in signaling responses by the αVβ3 vitronectin receptor (2015)

The bidirectional signaling and hemostatic functions of platelet αIIbβ3 are regulated by kindlin-3 through interactions with the β3 cytoplasmic tail. Little is known about kindlin regulation of the related "vitronectin receptor," αVβ3. These relationships were investigated in endothelial cells, which express αVβ3 and kindlin-2 endogenously. "β3ΔRGT" knock-in mice lack the 3 C-terminal β3 tail residues, whereas in "β3/β1(EGK)" mice, RGT is replaced by the corresponding residues of β1. The wild-type β3 tail pulled down kindlin-2 and c-Src in vitro, whereas β3ΔRGT bound neither protein and β3/β1(EGK) bound kindlin-2, but not c-Src. β3ΔRGT endothelial cells, but not β3/β1(EGK) endothelial cells, exhibited migration and spreading defects on vitronectin and reduced sprouting in 3-dimensional fibrin. Short hairpin RNA silencing of kindlin-2, but not c-Src, blocked sprouting by β3 wild-type endothelial cells. Moreover, defective sprouting by β3ΔRGT endothelial cells could be rescued by conditional, forced interaction of αVβ3ΔRGT with kindlin-2. Stimulation of β3ΔRGT endothelial cells led to normal extracellular ligand binding to αVβ3, pin-pointing their defect to one of outside-in αVβ3 signaling. β3ΔRGT mice, but not β3/β1(EGK) mice, exhibited defects in both developmental and tumor angiogenesis, responses that require endothelial cell function. Thus, the β3/kindlin-2 interaction promotes outside-in αVβ3 signaling selectively, with biological consequences in vivo.
Chemical feature-based pharmacophores and virtual library screening for discovery of new leads. (2003)

During the past years, efforts in the pharmaceutical industry have focused on optimizing the early phase hit-to-lead development of the drug discovery process. In silico-based high-throughput screening (HTS) approaches emerged, with a number of issues arising, such as the need for efficient search algorithms, library design, diversity, drug- and/or lead-likeness. These problems were addressed in numerous publications. This review focuses on the generation and use of virtual compound libraries, and on studies in which chemical feature-based pharmacophore models are used in combination with in silico screening. These procedures are generally used to obtain hits (or leads) that are more likely to give successful clinical candidates.
Delivery by caesarean section and risk of obesity in preschool age children: a prospective cohort study (2012)

Infants delivered by caesarean section may be at increased risk of childhood obesity. Further studies are needed to confirm our findings and to explore mechanisms underlying this association.
Cell‐free production and streamlined assay of cytosol‐penetrating antibodies (2016)

Antibodies that target intracellular proteins hold great promise in the development of novel therapeutic interventions for various diseases. In particular, antibodies that can cross cellular membranes have potential applications in controlling disease-related intracellular protein-protein interactions. Given the large number of cytosolic proteins and complicated interactions that are potentially involved in disease development, discovery of antibodies targeting intracellular proteins requires iterative cycles of expression and assessment of candidate antibodies. Because current cell-based expression methods do not provide sufficient throughput for production and assay of cytosol-penetrating antibodies, we integrated a cell-free protein synthesis system designed to provide optimal conditions for production of functional antibodies with a cytosol-penetration assay. The proposed approach of consolidating cell-free synthesis and cell-based assay will substantially expand the capability of discovering and engineering antibodies that can cross the cell membrane and effectively control protein-mediated cellular functions. Biotechnol. Bioeng. 2016;113: 2107-2112. © 2016 Wiley Periodicals, Inc.
Environmentally stable Kerr-type mode-locked erbium fiber laser producing 360-fs pulses (1994)

We demonstrate an environmentally stable Kerr-type mode-locked erbium fiber laser producing 360-fs near-bandwidth-limited pulses. Environmentally stable operation is possible in the presence of nonpolarization-maintaining fiber components provided that their overall length is short compared with the length of the polarization-maintaining fiber components. The pulses are generated at a stable repetition rate of 27 MHz and have an energy content of 60 pJ.
MRI of the diabetic foot: differentiation of infection from neuropathic change (2007)

The aim of this review is to illustrate the magnetic resonance imaging features that can help differentiate osteomyelitis from neuropathic osteoarthropathy in the foot.