gebhart/patrepeval huggingface dataset:
Genetic complexity in sickle cell disease (2008)

Sickle cell disease (SCD) was the first human monogenic disorder to be characterized at the molecular level (1). It results from the substitution of glutamic acid by valine at position 6 of the β-chain of hemoglobin. The clinical manifestations of SCD arise from the tendency of sickle hemoglobin (known as HbS or α2βS2) to polymerize at reduced oxygen tensions and deform red cells into the characteristic rigid sickle cell shape. Such inflexible red cells cannot pass through the microcirculation efficiently, and this results in anemia (due to destruction of the red cells) and intermittent vasoocclusion causing tissue damage and pain (2). Although all patients with homozygous SCD have exactly the same molecular defect, there is considerable clinical variation, ranging from death in early childhood (3) to a normal life span with few complications (4). Genetic modifiers of SCD include α-thalassemia (5), and it has been known for many years that patients with increased levels of fetal Hb (HbF or α2γ2) often tend to have a relatively mild clinical course (2) because HbF reduces the tendency of HbS to polymerise within the red cell. Increased HbF may result from rare deletions within the β-globin gene cluster or from point mutations in the promoters of the fetal γ-globin genes (hereditary persistence of fetal hemoglobin, HPFH), but additional loci are known to increase HbF levels in adult life. Identifying such loci has been a painstaking task, but a combination of genome-wide analysis within a large kindred (6) and within twin pairs (7) has identified two quantitative trait loci (QTL) with major influences on fetal hemoglobin levels in adults. In this issue of PNAS, Lettre et al. (8) now show that a significant proportion of the variation in HbF levels and the frequency of painful crises in patients with SCD is accounted for by five common single-nucleotide polymorphisms (SNPs) at these loci (Fig. 1).
Constitutive Expression and Role of the TNF Family Ligands in Apoptotic Killing of Tumor Cells by Human NK Cells (1999)

Natural killer cells mediate spontaneously secretory/necrotic killing against rare leukemia cell lines and a nonsecretory/apoptotic killing against a large variety of tumor cell lines. The molecules involved in nonsecretory/apoptotic killing are largely undefined. In the present study, freshly isolated, nonactivated, human NK cells were shown to express TNF, lymphotoxin (LT)-alpha, LT-beta, Fas ligand (L), CD27L, CD30L, OX40L, 4-1BBL, and TNF-related apoptosis-inducing ligand (TRAIL), but not CD40L or nerve growth factor. Complementary receptors were demonstrated to be expressed on the cell surface of solid tumor cell lines susceptible to apoptotic killing mediated by NK cells. Individually applied, antagonists of TNF, LT-alpha1beta2, or FasL fully inhibited NK cell-mediated apoptotic killing of tumor cells. On the other hand, recombinant TNF, LT-alpha1beta2, or FasL applied individually or as pairs were not cytotoxic. In contrast, a mixture of the three ligands mediated significant apoptosis in tumor cells. These findings demonstrate that human NK cells constitutively express several of the TNF family ligands and induce apoptosis in tumor cells by simultaneous engagement of at least three of these cytotoxic molecules.
Role of Hypoxic Drive in Regulation of Postapneic Ventilation during Sleep in Patients with Obstructive Sleep Apnea (1991)

To elucidate the role of chemoresponsiveness in determining postapneic ventilation in sleep-disordered periodic breathing, we measured ventilatory response associated with apnea-induced arterial oxygen desaturation during sleep and compared it with the awake hypoxic ventilatory response (HVR) in 12 male patients with obstructive sleep apnea (OSA). Awake HVR was measured at a slight hypocapnic level (end-tidal PCO2 = 37 +/- 1 mm Hg, mean +/- SEM), and separately at a PCO2 of 45 mm Hg. During non-REM sleep both the ventilatory rate (VE) and the average respiratory frequency (f) in the ventilatory phase between apneic episodes were inversely correlated with the nadir of arterial oxygen saturation (nSaO2) produced by the preceding apneic phase in all patients (VE versus nSaO2; r = -0.74 +/- 0.03, mean +/- SEM; f versus nSaO2, r = -0.56 +/- 0.04). The average tidal volume (VT) also was correlated with nSaO2 in 10 of the patients (r = -0.56 +/- 0.05). During REM sleep VE was correlated with nSaO2 in 11 patients (r = -0.75 +/- 0.03, p less than 0.02). The response of VE to nSaO2 (delta VE/delta nSaO2) varied widely among the patients (non-REM, 0.52 to 2.16; REM, 0.29 to 1.44 L/min/%) and was significantly lower during REM than non-REM sleep (p less than 0.01). The value of delta VE/delta nSaO2 during both non-REM and REM sleep was correlated with awake HVR at an end-tidal PCO2 of 45 mm Hg (non-REM, r = 0.83, p less than 0.02; REM, r = 0.76, p less than 0.05) but not with that at the hypocapnic level.(ABSTRACT TRUNCATED AT 250 WORDS)
ZAK inhibits human lung cancer cell growth via ERK and JNK activation in an AP‐1‐dependent manner (2010)

Novel mixed-lineage kinase protein zipper sterile-alpha-motif kinase (ZAK) was first cloned by our laboratory. Lung cancer is the leading cause of cancer-related death in the world, including in Taiwan. Here, we wanted to investigate whether ZAK plays a potential role in lung cancer development. First, Western blot analysis results demonstrated that four cell lines expressed high levels of ZAK from among a panel of 10 lung cancer cell lines, and two of three normal lung cells expressed ZAK. ZAK gene expressions were down-regulated in lung cancers by real-time PCR analysis. Overexpression of ZAK suppressed cell proliferation in parallel with increased phosphorylated levels of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). In contrast, ZAK silencing cells inhibited the expressions of phosphorylated ERK and JNK without affecting the expression of phosphorylated p38. The effect of the decreased cell growth rate was significantly but incompletely reversed when ZAK-overexpressing cells were treated with a specific ERK or JNK inhibitor. Moreover, c-Fos and c-Jun, the major downstream components of MAPKs, were up-regulated by ERK and JNK, respectively. When ZAK-overexpressing cells introduced with c-Jun RNA interference (RNAi), the activator protein-1 (AP-1) transcription activity detected by a secreted alkaline phosphatase (SEAP) assay was suppressed and the decreased cell number was reversed compared with the control RNAi-treated group. More importantly, ZAK significantly depressed tumor growth in in vivo study. Taken together, results from both in vitro and in vivo studies indicated that the decrease of lung cancer cell proliferation by ZAK may involve the ERK and JNK pathways via an AP-1 transcription factor.
<title>Optimization of hologram computation for real-time display</title> (1992)

Several methods of increasing the speed and simplicity of the computation of off-axis transmission holograms are presented, with applications to the real-time display of holographic images. A bipolar intensity approach enables a linear summation of interference fringes, a factor of two speed increase, and the elimination of image noise caused by object self- interference. An order of magnitude speed increase is obtained through the use of precomputed look-up tables containing a large array of elemental interference patterns corresponding to point source contributions from each of the possible locations in image space. Results achieved using a data-parallel supercomputer to compute horizontal-parallax- only holographic patterns containing 6 megasamples indicate that an image comprised of 10,000 points with arbitrary brightness (grayscale) can be computed in under one second.
Process-Oriented Approach for Validating Asset Value for Evaluating Information Security Risk (2009)

To provide a systematic means of identifying and assessing information security risks, organizations typically adopt asset-driven (or asset-oriented) risk assessment schemes. These schemes require organizations to identify their information assets, find out potential incidents to those assets, and assess expected losses associated with those incidents. While asset value is important in determining loss expectancies for associated incidents, the accuracy of asset valuation is crucial. Although numerous guidelines exist regarding how best to evaluate asset value, current risk assessment schemes generally overlook how to validate assessments of asset value. Consequently, this work presents a process-oriented approach that organizations can employ to validate and adjust asset value. The approach presented in this study can help organizations represent their business processes and information assets used in those processes using flowcharts, and also mark dependencies among assets based on confidentiality, integrity, and availability requirements on flowcharts. Organizations can use the markings of dependencies to validate and correct results associated with asset valuation. If organizations can more accurately evaluate asset value, they can improve the effectiveness of their risk assessment. Therefore, the approach presented in this study can hopefully help improve organizational information security.
Expanding or Restricting the Target Site Repertoire of Zinc-finger Nucleases: The Inter-domain Linker as a Major Determinant of Target Site Selectivity (2008)

Precise manipulations of complex genomes by zinc-finger nucleases (ZFNs) depend on site-specific DNA cleavage, which requires two ZFN subunits to bind to two target half-sites separated by a spacer of 6 base pairs (bp). ZFN subunits consist of a specific DNA-binding domain and a nonspecific cleavage domain, connected by a short inter-domain linker. In this study, we conducted a systematic analysis of 11 candidate-based linkers using episomal and chromosomal targets in two human cell lines. We achieved gene targeting in up to 20% of transfected cells and identified linker variants that enforce DNA cleavage at narrowly defined spacer lengths and linkers that expand the repertoire of potential target sites. For instance, a nine amino acid (aa) linker induced efficient gene conversion at chromosomal sites with 7- or 16-bp spacers, whereas 4-aa linkers had activity optima at 5- and 6-bp spacers. Notably, single aa substitutions in the 4-aa linker affected the ZFN activity significantly, and both gene conversion and ZFN-associated toxicity depended on the linker/spacer combination and the cell type. In summary, both sequence and length of the inter-domain linker determine ZFN activity and target-site specificity, and are therefore important parameters to account for when designing ZFNs for genome editing.
The effect of a task-oriented intervention on arm function in people with stroke: a randomized controlled trial (2006)

A task-oriented intervention did not improve voluntary movement or manual dexterity of the affected arm in people with chronic stroke.
Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors. (1993)

The mechanism of action of macrophage colony-stimulating factor (M-CSF) in osteoclast development was examined in a co-culture system of mouse osteoblastic cells and spleen cells. In this co-culture, osteoclast-like multinucleated cells (MNCs) were formed within 6 d in response to 10 nM 1 alpha,25(OH)2D3 added only for the final 2 d of culture. Simultaneously adding hydroxyurea for the final 2 d completely inhibited proliferation of cultured cells without affecting 1 alpha,25(OH)2D3-stimulated MNC formation. Autoradiographic examination using [3H]-thymidine revealed that osteoclast progenitors primarily proliferated during the first 4 d, whereas their differentiation into MNCs occurred predominantly during the final 2 d of culture in response to 1 alpha,25(OH)2D3. When anti-M-CSF antibody or anti-M-CSF receptor antibody was added either for the first 4 d or for the final 2 d, the MNC formation was similarly inhibited. In co-cultures of normal spleen cells and osteoblastic cells obtained from op/op mice, which cannot produce functionally active M-CSF, the lack of M-CSF either for the first 4 d or for the final 2 d failed to form MNCs in response to 1 alpha,25(OH)2D3 added for the last 2 d. These results clearly indicate that M-CSF is indispensable for both proliferation of osteoclast progenitors and their differentiation into mature osteoclasts.
Responses of Heart Rate Variability to Acute Pain After Minor Spinal Surgery (2014)

This study suggests that, after MSS, values of LF>298 m and LF/HF>3.1 denote acute pain (NRS>3). These HRV parameters are significantly correlated with NRS.
Integrated Gravity Modeling of Salt Features in the Mississippi Salt Basin (1996)

ABSTRACT Recent exploration in portions of the Mississippi Salt Basin indicates that some models used in the interpretation of surface and subsurface data may be inadequate to explain several salt features. Models are important in interpretation due to the depth of the objectives and the complexity of the salt ridges. Significant oil and gas reserves trapped by the salt and related faults in Upper Jurassic reservoirs were discovered from the late 1960's to the early 1980's. Early models show concordant overburden on the flanks of a simple, symmetrical salt anticline. However, in the course of further drilling, Upper Jurassic formations and the underlying salt were not encountered where predicted by the anticlinal model suggesting that many of the salt ridges in the basin are more complex. Well log data indicate that the flanks of such salt features may dip at rates greater than that proposed by the symmetrical anticline model. A study utilizing an integrated approach to test the viability of a more complex salt ridge model was conducted to aid in the interpretation of surface and subsurface data in the Mississippi Salt Basin. Gravity data in conjunction with seismic reflection data and well log information form the data base from which salt models were created. Seismic reflection data and well control provide a reasonable estimate of the depth of the sources of the gravity anomalies. The gravity data, on the other hand, have been used to help constrain the interpretation of the seismic data by providing a better geometric framework for the salt bodies observed on the seismic data. Eucutta Field and Diamond Field were selected as test areas for the salt models based on the availability of data. The two fields are located along different types of parallel salt ridges. Eucutta is located deeper in the basin in an area of large salt features while Diamond is located closer to the rim of the basin where smaller salt features are more common. Results of the study indicate that an asymmetrical pattern exists in which the flanks of the ridges may dip at different rates. Both the Eucutta and Diamond salt ridges exhibit a steeply dipping flank on the basinward side of the salt ridge and a more gently dipping landward flank. The salt ridges also appear to have a complex along strike variation in the structure of the salt. The variations of the salt features in both the strike and dip directions appear to reflect the variations in the way the overlying sediments were deposited.
Frequency Comparison of Two High-AccuracyAl+Optical Clocks (2010)

We have constructed an optical clock with a fractional frequency inaccuracy of 8.6x10{-18}, based on quantum logic spectroscopy of an Al+ ion. A simultaneously trapped Mg+ ion serves to sympathetically laser cool the Al+ ion and detect its quantum state. The frequency of the {1}S{0}<-->{3}P{0} clock transition is compared to that of a previously constructed Al+ optical clock with a statistical measurement uncertainty of 7.0x10{-18}. The two clocks exhibit a relative stability of 2.8x10{-15}tau{-1/2}, and a fractional frequency difference of -1.8x10{-17}, consistent with the accuracy limit of the older clock.
A New Multidisciplinary Separated-Sector Cyclotron Facility (1977)

A separated-sector cyclotron with a maximum proton energy of 200 MeV has been proposed for a multidisciplinary accelerator facility for the Republic of South Africa. At energies up to 100 MeV, proton and deuteron currents of the order of 100 microamps will be available for routine isotope production and neutron therapy. Light-ion beams for particle physics and chemistry will be delivered with maximum currents of about 10 microamps and maximum energies in excess of 50 MeV per nucleon. Heavy-ion beams of between 15 and 50 MeV per nucleon are planned with maximum intensities of between 10 particle-nanoamps and 1 particle-microamp, depending on the type of ion. This proposal has recently been approved and progress in the design of the cyclotron and related aspects of the proposed facility is reported here.
Haloarcula quadrata sp. nov., a square, motile archaeon isolated from a brine pool in Sinai (Egypt) (1999)

The motile, predominantly square-shaped, red archaeon strain 801030/1T, isolated from a brine pool in the Sinai peninsula (Egypt), was characterized taxonomically. On the basis of its polar lipid composition, the nucleotide sequences of its two 16S rRNA genes, the DNA G+C content (60.1 mol%) and its growth characteristics, the isolate could be assigned to the genus Haloarcula. However, phylogenetic analysis of the two 16S rRNA genes detected in this organism and low DNA-DNA hybridization values with related Haloarcula species showed that strain 801030/1T is sufficiently different from the recognized Haloarcula species to warrant its designation as a new species. A new species, Haloarcula quadrata, is therefore proposed, with strain 801030/1T (= DSM 11927T) as the type strain.
Fatal acute pulmonary fibrosis in a patient treated by danazol for thrombocytopenia (1996)

has prognostic value in lymphoid malignancies such as multiple myeloma and CLL. High P2m values in CLL have been found to correlate mainly with stage of disease and high lymphocyte count 131. Prolymphocytic leukemia is a disease of activated B lymphocytes more differentiated than B-CLL cells. PLL cells express B cell activation antigens CD25, CD38, CD71, FMC7, PCAl, and RABl 141. We found a significantly higher level of p2m in PLL than in CLL patients. Our results indicate that P2m levels may be an additional marker of B-cell activation to further characterize lymphoid diseases arrested in different stages of maturation.
Scheduling of time constrained dual-arm cluster tools with wafer revisiting (2013)

This work intends to schedule a dual-arm cluster tool for the atomic layer deposition (ALD) process with wafer residency time constraints. ALD is a typical wafer revisiting process. Based on the analysis of system properties, a novel scheduling strategy called modified 1-wafer cyclic scheduling is derived. With this strategy, necessary and sufficient schedulability conditions are established. If schedulable, scheduling algorithms are presented to obtain a feasible and optimal schedule. By the proposed method, a schedule can be found by just simple calculation. An illustrative example is given to show the application of the proposed approach.
PARP inhibitors in ovarian cancer: evidence, experience and clinical potential (2017)

Inhibitors of poly(ADP-ribose) polymerase (PARP) are considered one of the most active and exciting new therapies for the treatment of ovarian cancer. The anticancer activity of PARP inhibitors is based on the DNA repair vulnerability of many ovarian cancer cells, and multiple mechanisms of action of PARP inhibitors have been identified. As single agents, PARP inhibitors have demonstrated their greatest activity in ovarian cancer cells that harbor mutations in <i>BRCA</i> genes. Additionally, recent phase III studies have shown that single-agent PARP inhibitor activity extends beyond BRCA-related cancers and can benefit patients with ovarian cancers that do not have known <i>BRCA</i> mutations, especially when clinical characteristics such as platinum sensitivity and high-grade serous histology are present. PARP inhibitors have also been combined with chemotherapy, however, overlapping myelosuppression observed with PARP inhibitor and chemotherapy combinations has hampered development of these combinations. Contrariwise, PARP inhibitor and biologic agent combinations, specifically antiangiogenic agents, appear well tolerated and show promising activity in both <i>BRCA</i> mutated (<i>BRCA</i>m) and <i>BRCA</i> wild-type (<i>BRCA</i>wt) cancers. Currently, multiple clinical trials are underway examining the antitumor activity of PARP inhibitor combination therapy.
Pulmonary perfusion measured by means of electrical impedance tomography (1998)

Electrical impedance tomography (EIT) is a recent imaging technique based on electrical impedance, offering the possibility of measuring pulmonary perfusion. In the present study the influence of several pulmonary haemodynamical parameters on the EIT signal were investigated. First, the influence on the systolic wave of the EIT signal (delta Zsys) of stroke volume, large pulmonary artery distensibility (both assessed by means of MRI) and the extent of the pulmonary peripheral vascular bed in 11 emphysematous patients (reduced peripheral vascular bed) and 9 controls (normal peripheral vascular bed) was investigated. Second, the influence of hypoxic pulmonary vasoconstriction on delta Zsys was examined in 14 healthy subjects. Finally, the origin of the diastolic wave was examined in three patients with atrioventricular dissociation. Multiple regression analysis showed that delta Zsys was only dependent on the variable emphysema (p < 0.02), but not dependent on stroke volume (p < 0.3) or pulmonary artery distensibility (p > 0.9). The mean value of delta Zsys for emphysematous patients (131 +/- 32 arbitrary units (AU)) was significantly lower (p < 0.001) than in the control group (200 +/- 39). In the group of healthy subjects delta Zsys decreased significantly (p < 0.001) during hypoxia (193 +/- 38 AU) compared with rest measurements (260 +/- 62 AU). The absence of the diastolic wave in the cardiological patients suggests the influence of reverse venous blood flow on the EIT signal. It is concluded that volume changes in the small pulmonary vessels contribute significantly to the EIT signal. Moreover, the hypoxia induced decrease in delta Zsys indicates the potential of EIT for measuring pulmonary vascular responses to external stimuli.