gebhart/patrepeval huggingface dataset:
Is Esterase-P Encoded by a Cryptic Pseudogene In Drosophila melanogaster? (1996)

We have amplified and sequenced the gene encoding Esterase-P (Est-P) in 10 strains of Drosophila melanogaster. Three premature termination codons occur in the coding region of the gene in two strains. This observation, together with other indirect evidence, leads us to propose that Est-P may be a pseudogene in D. melanogaster. Est-P would be a "cryptic" pseudogene, in the sense that it retains intact the coding sequence (without stop codons and other alterations usually observed in pseudogenes) in most D. melanogaster strains. We conjecture that the beta-esterase cluster may consist in other Drosophila species of functional and nonfunctional genes. We also conjecture that the rarity of detected pseudogenes in Drosophila may be due to the difficulty of discovering them, because most of them are cryptic.
Multiple Layers of Regulation of Human Heat Shock Transcription Factor 1 (1995)

Upon heat stress, monomeric human heat shock transcription factor 1 (hHSF1) is converted to a trimer, acquires DNA-binding ability, is transported to the nucleus, and becomes transcriptionally competent. It was not known previously whether these regulatory changes are caused by a single activation event or whether they occur independently from one another, providing a multilayered control that may prevent inadvertant activation of hHSF1. Comparison of wild-type and mutant hHSF1 expressed in Xenopus oocytes and human HeLa cells suggested that retention of hHSF1 in the monomeric form depends on hydrophobic repeats (LZ1 to LZ3) and a carboxy-terminal sequence element in hHSF1 as well as on the presence of a titratable factor in the cell. Oligomerization of hHSF1 appears to induce DNA-binding activity as well as to uncover an amino-terminally located nuclear localization signal. A mechanism distinct from that controlling oligomerization regulates the transcriptional competence of hHSF1. Components of this mechanism were mapped to a region, including LZ2 and nearby sequences downstream from LZ2, that is clearly separated from the carboxy-terminally located transcription activation domain(s). We propose the existence of a fold-back structure that masks the transcription activation domain in the unstressed cell but is opened up by modification of hHSF1 and/or binding of a factor facilitating hHSF1 unfolding in the stressed cell. Activation of hHSF1 appears to involve at least two independently regulated structural transitions.
Progesterone Receptor (hPR) Upregulates the Fibronectin Promoter Activity in Human Decidual Fibroblasts (2003)

Previous studies have shown that progestin induces the production of fibronectin (FN) and its mRNA content in human endometrial stromal cells. The mechanism of the upregulation was unclear. In the present study, we provide evidence that hPR regulates the FN promoter activity mainly through the CRE/AP1 site located in the proximal region of the promoter in human decidual fibroblasts. Various lengths of the proximal region of the FN promoter were linked to the reporter vector to construct promoter-reporter plasmids and were then transfected into human decidual fibroblasts. Deletion and mutation analysis showed that CRE/AP1 and Sp1 sites in the proximal region mediated the basal promoter activity. To evaluate progestin-mediated transcriptional activation, decidual fibroblasts were transfected with p300 (FN promoter-reporter construct) and hPR expression vector. Cells treated with medroxyprogesterone acetate (MPA) increased the promoter activity ranging from 2.5- to 9-fold determined in 10 decidual specimens. hPRA enhanced activation was stronger than that of hPRB. Structural analysis of hPR showed that DNA and ligand binding domains are essential for the activation, and missing the TAF1 domain weakens the activation. The proximal promoter region of the FN gene lacks a canonical PRE site. Mutation at the CRE/AP1 site eliminated the upregulation by progestin. To evaluate the interaction of hPR with the CRE/AP1 site, the CRE/AP1 site was mutated to the consensus AP1 cis-element (TGACGTCA, -172 to -165 bp, mutated to TGAC_TCA) which eliminated the CREB binding. FN promoter activity derived from p300AP1 mutant was found to be higher than that of p300. These results showed that hPR interacts with the AP1 binding proteins, but not with CREB. Progestin treatment or overexpression hPR did not alter appreciably the content of c-jun or c-fos in decidual fibroblasts nuclear extracts. Antibody to hPR (hPRa3), which precipitated hPR also coprecipitated c-jun and c-fos, whereas CREB was not precipitated by hPRa3. The observation implies that hPRs are brought to the FN promoter region by AP1 proteins to enhance the transcription. In summary, this study provides molecular evidence that the CRE/AP1 site and c-jun/c-fos in decidual fibroblasts mediate the hPR-enhanced activation of FN transcription.
Inhibition of HIV-1 Ribonuclease H by a Novel Diketo Acid, 4-[5-(Benzoylamino)thien-2-yl]-2,4-dioxobutanoic Acid (2003)

Human immunodeficiency virus-type 1 (HIV-1) reverse transcriptase (RT) coordinates DNA polymerization and ribonuclease H (RNase H) activities using two discrete active sites embedded within a single heterodimeric polyprotein. We have identified a novel thiophene diketo acid, 4-[5-(benzoylamino)thien-2-yl]-2,4-dioxobutanoic acid, that selectively inhibits polymerase-independent RNase H cleavage (IC(50) = 3.2 microm) but has no effect on DNA polymerization (IC(50) > 50 microm). The activity profile of the diketo acid is shown to be distinct from previously described compounds, including the polymerase inhibitor foscarnet and the putative RNase H inhibitor 4-chlorophenylhydrazone. Both foscarnet and the hydrazone inhibit RNase H cleavage and DNA polymerization activities of RT, yet neither inhibits the RNase H activity of RT containing a mutation in the polymerase active site (D185N) or an isolated HIV-1 RNase H domain chimera containing the alpha-C helix from Escherichia coli RNase HI, suggesting these compounds affect RNase H indirectly. In contrast, the diketo acid inhibits the RNase H activity of the isolated RNase H domain as well as full-length RT, and inhibition is not affected by the polymerase active site mutation. In isothermal titration calorimetry studies using the isolated RNase H domain, binding of the diketo acid is independent of nucleic acid but strictly requires Mn(2+) implying a direct interaction between the inhibitor and the RNase H active site. These studies demonstrate that inhibition of HIV-1 RNase H may occur by either direct or indirect mechanisms, and they provide a framework for identifying novel agents such as 4-[5-(benzoylamino)thien- 2-yl]-2,4-dioxobutanoic acid that specifically targets RNase H.
Pharmacological treatment in pregnant women with moderate symptoms of coronavirus disease 2019 (COVID-19) pneumonia (2021)

In our cohort, prompt initiation of remdesivir in pregnant women hospitalized with moderate symptoms of COVID-19 pneumonia within 48 hours of admission prevented worsening and allowed a fast clinical recovery by HD7. Deferring remdesivir for >48 hours after hospitalization and duration of symptoms >4 days before admission were independently associated with delayed clinical recovery and longer hospital admission. Ultrasound evaluation of the amniotic fluid in patients recovering from COVID-19 hospitalization should be considered.
Chemical inducers and transcriptional markers of oligodendrocyte differentiation (2010)

Oligodendrocytes generate and maintain myelin, which is essential for axonal function and protection of the mammalian central nervous system. To advance our molecular understanding of differentiation by these cells, we screened libraries of pharmacologically active compounds and identified inducers of differentiation of Oli-neu, a stable cell line of mouse oligodendrocyte precursors (OPCs). We identified four broad classes of inducers, namely, forskolin/cAMP (protein kinase A activators), steroids (glucocorticoids and retinoic acid), ErbB2 inhibitors, and nucleoside analogs, and confirmed the activity of these compounds on rat primary oligodendrocyte precursors and mixed cortical cultures. We also analyzed transcriptional responses in the chemically induced mouse and rat OPC differentiation processes and compared these with earlier studies. We confirm the view that ErbB2 is a natural signaling component that is required for OPC proliferation, whereas ErbB2 inhibition or genetic knockdown results in OPC differentiation.
A novel 120‐kDa antigen shared by immature human thymocytes and long‐term‐activated T cells (1994)

In this study we report the characterization of monoclonal antibody (mAb) 8B4/20, raised against immature human thymocytes, that identifies a novel leukocyte antigen. The molecular characterization of the antigen by immunoprecipitation and immunoblotting yields, under nonreducing conditions, a specific band of 120 kDa which, under reducing conditions, displays a slightly lower molecular mass (110 kDa. mAb 8B4/20 detects a molecule found on the majority of thymocytes with an inverted gradient of expression when compared to CD3. It appears at high density on the CD3-/low thymocytes, at reduced density on the CD3med and double-positive thymocytes, and is absent on CD3hi and single-positive thymocytes and on peripheral blood T cells. Immunohistochemistry on frozen sections demonstrates cortical staining of the thymic lobules. Flow cytometric analysis of the different subsets of peripheral blood mononuclear cells shows that mAb 8B4/20 detects an antigen expressed only on CD56+/CD16+ natural killer cells and on a fraction of CD14+ monocytes. T cells, B cells, erythrocytes, granulocytes and platelets are consistently negative. The expression of the molecule on tumor cell lines does not show lineage restriction. Analysis of phytohemagglutinin plus recombinant interleukin-2-activated peripheral blood lymphocytes shows that mAb 8B4/20 identifies an antigen expressed on CD3+ cells by week 3 of culture. Thus, it recognizes a very late activation antigen (VLA) on mature T cells. The cell distribution and the electrophoretic pattern of the molecule identified by mAb 8B4/20 is distinct from that of known CD and of integrin/VLA molecules. Its function on thymocytes is so far unknown; however, the binding of mAb 8B4/20 to tumor lines induces changes in the morphology and adhesive properties of the 8B4/20+ cells growing in suspension. We suggest that mAb 8B4/20 recognizes a molecule that may be involved in interactions between thymocytes and other thymic structures that may be relevant for the selection process.
Improving Face-Based Age Estimation With Attention-Based Dynamic Patch Fusion (2022)

With the increasing popularity of convolutional neural networks (CNNs), recent works on face-based age estimation employ these networks as the backbone. However, state-of-the-art CNN-based methods treat each facial region equally, thus entirely ignoring the importance of some facial patches that may contain rich age-specific information. In this paper, we propose a face-based age estimation framework, called Attention-based Dynamic Patch Fusion (ADPF). In ADPF, two separate CNNs are implemented, namely the AttentionNet and the FusionNet. The AttentionNet dynamically locates and ranks age-specific patches by employing a novel Ranking-guided Multi-Head Hybrid Attention (RMHHA) mechanism. The FusionNet uses the discovered patches along with the facial image to predict the age of the subject. Since the proposed RMHHA mechanism ranks the discovered patches based on their importance, the length of the learning path of each patch in the FusionNet is proportional to the amount of information it carries (the longer, the more important). ADPF also introduces a novel diversity loss to guide the training of the AttentionNet and reduce the overlap among patches so that the diverse and important patches are discovered. Through extensive experiments, we show that our proposed framework outperforms state-of-the-art methods on several age estimation benchmark datasets.
<title>Visible hyperspectral imaging: monitoring the systemic effects of shock and resuscitation</title> (2002)

Hyperspectral (HS) imaging has been useful in the monitoring of several medical conditions, which to date have generally involved changes in skin oxygenation in isolated regions of interest such as skin flaps or small burns. Here, by contrast, we present a study in which HSI was used to assess the cutaneous manifestations of significant systemic events. HS imaging of the ventral surface of the lower jaw was used to monitor changes in skin oxygenation during hypovolemic shock induced by pulmonary contusion and hemorrhage in a porcine model, and to monitor the subsequent recovery of oxygenation following resuscitation. Changes are seen both quantitatively, in the level of skin oxygenation as determined by the fitting of reference hemoglobin and deoxyhemoglobin spectra to sample spectra, and qualitatively, in the observed spatial distribution or pattern of oxygenation-related changes in the skin. Linear regression was used to correlate these changes with invasively obtained parameters to include mixed venous oxygen saturation and systemic arterial blood pressure. Historically, the assessment of skin color and mottling has been an important, albeit inexact, component of resuscitation algorithms. Now, it is possible to analyze these variables during shock and resuscitation in an objective manner. The clinical utility of these advances needs to be determined.
Rapid emission tomography reconstruction (2003)

We present new implementations of the Maximum Likelihood Expectation Maximization (EM) algorithm and the related Ordered Subset EM (OSEM) algorithm. Our implementation is based on modern graphics hardware and achieves speedups of over eight times current software implementation, while reducing the RAM required to practical amounts for today's PC's. This is significant as it will make this algorithm practical for clinical use. In order to achieve a large speed up, we present bit splitting over different color channels as an accumulation strategy. We also present a novel hardware implementation for volume rendering emission data without loss of accuracy. Improved results are achieved through incorporation of attenuation correction with only a small speed penalty.
Whole Blood Transfusion (2018)

Whole blood is the preferred product for resuscitation of severe traumatic hemorrhage. It contains all the elements of blood that are necessary for oxygen delivery and hemostasis, in nearly physiologic ratios and concentrations. Group O whole blood that contains low titers of anti-A and anti-B antibodies (low titer group O whole blood) can be safely transfused as a universal blood product to patients of unknown blood group, facilitating rapid treatment of exsanguinating patients. Whole blood can be stored under refrigeration for up to 35 days, during which it retains acceptable hemostatic function, though supplementation with specific blood components, coagulation factors or other adjuncts may be necessary in some patients. Fresh whole blood can be collected from pre-screened donors in a walking blood bank to provide effective resuscitation when fully tested stored whole blood or blood components are unavailable and the need for transfusion is urgent. Available clinical data suggest that whole blood is at least equivalent if not superior to component therapy in the resuscitation of life-threatening hemorrhage. Low titer group O whole blood can be considered the standard of care in resuscitation of major hemorrhage.
Central sleep apnea in untreated hypothyroidism: A rare association (2016)

Obstructive sleep apnea (OSA) has been reported with untreated hypothyroidism. Here, we report a young patient referred to us due to prolonged apneas detected during recovery from minor surgery done under a short-acting general anesthetic drug. Polysomnography (PSG) was suggestive of severe OSA with high central index. He was later found to have severe hypothyroidism. Thyroxine replacement for 3 months followed by a repeat PSG showed persisting severe OSA but with no central events. This case highlights the rare association of central sleep apnea in untreated hypothyroidism which can be easily overlooked.
THE MECHANISM OF WATER BINDING IN STRATUM CORNEUM (1968)

SUMMARY.— The results presented in this paper confirm the published observations by others that the hygroscopic water-soluble substances within the corneum are responsible for much of the water binding ability of the horny layer. The ability of corneum to bind water is reduced when it is extracted with solvents, which remove lipid, and then with water, which removes the water-soluble substances. Our interpretation of this is that the water-soluble substances are retained within the corneum by a lipid-containing semipermeable membrane system which allows these substances to take up water by osmosis and protects them from dissolution when the intact corneum is immersed in water. Our experiments show that isolated corneum from guinea-pig footpads and from human palms, soles and abdomen can take up and lose water by osmosis. Powdering the corneum allows water to extract the water-soluble substances without a prior solvent extraction. The powdering procedure ruptures the cell walls of the corneum cells and we propose that it is the cell walls which make up the lipid containing semi permeable membrane system. A method for measuring extensibility of isolated strips of corneum in a humid atmosphere has been developed. Using this technique it has been shown that it is the water held by the water-soluble substances that is responsible for most of the extensibility of corneum.
Kinetic Analysis of DNA and RNA Strand Transfer Reactions Catalyzed by Vaccinia Topoisomerase (1997)

Vaccinia topoisomerase binds duplex DNA and forms a covalent DNA-(3'-phosphotyrosyl) protein adduct at the sequence 5'-CCCTT downward arrow. The enzyme reacts readily with a 36-mer CCCTT strand (DNA-p-RNA) composed of DNA 5' and RNA 3' of the scissile bond. However, a 36-mer composed of RNA 5' and DNA 3' of the scissile phosphate (RNA-p-DNA) is a poor substrate for covalent adduct formation. Vaccinia topoisomerase efficiently transfers covalently held CCCTT-containing DNA to 5'-OH-terminated RNA acceptors; the topoisomerase can therefore be used to tag the 5' end of RNA in vitro. Religation of the covalently bound CCCTT-containing DNA strand to a 5'-OH-terminated DNA acceptor is efficient and rapid (krel > 0.5 s-1), provided that the acceptor DNA is capable of base pairing to the noncleaved DNA strand of the topoisomerase-DNA donor complex. The rate of strand transfer to DNA is not detectably affected by base mismatches at the 5' nucleotide of the acceptor strand. Nucleotide deletions and insertions at the 5' end of the acceptor slow the rate of religation; the observed hierarchy of reaction rates is as follows: +1 insertion > -1 deletion > +2 insertion >> -2 deletion. These findings underscore the importance of a properly positioned 5'-OH terminus in transesterification reaction chemistry, but they also raise the possibility that topoisomerase may generate mutations by sealing DNA molecules with mispaired or unpaired ends.
Interactive 3D registration of ultrasound and magnetic resonance images based on a magnetic position sensor (1999)

The use of stereotactic systems has been one of the main approaches for image-based guidance of the surgical tool within the brain. The main limitation of stereotactic systems is that they are based on preoperative images that might become outdated and invalid during the course of surgery. Ultrasound (US) is considered the most practical and cost-effective intraoperative imaging modality, but US images inherently have a low signal-to-noise ratio. Integrating intraoperative US with stereotactic systems has recently been attempted. In this paper, we present a new system for interactively registering two-dimensional US and three-dimensional magnetic resonance (MR) images. This registration is based on tracking the US probe with a dc magnetic position sensor. We have performed an extensive analysis of the errors of our system by using a custom-built phantom. The registration error between the MR and the position sensor space was found to have a mean value of 1.78 mm and a standard deviation of 0.18 mm. The registration error between US and MR space was dependent on the distance of the target point from the US probe face. For a 3.5-MHz phased one-dimensional array transducer and a depth of 6 cm, the mean value of the registration error was 2.00 mm and the standard deviation was 0.75 mm. The registered MR images were reconstructed using either zeroth-order or first-order interpolation. The ease of use and the interactive nature of our system (approximately 6.5 frames/s for 344 x 310 images and first-order interpolation on a Pentium II 450 MHz) demonstrates its potential to be used in the operating room.
Headache Prevention Outcome and Body Mass Index (2005)

A population-based longitudinal study suggests that obesity is a strong risk factor for the development of headaches on 15 or more days per month. Little is know about the influence of weight on the response to headache preventive treatment. Herein we prospectively assessed the influence of the baseline body mass index (BMI) on the response to headache preventive treatment. We included adults with episodic or chronic migraine (ICHD-2), or transformed migraine (Silberstein and Lipton criteria) that sought care in a headache clinic. BMI was assessed in the first visit. Baseline information included headache frequency, number of days with severe headache (prospectively obtained over 1 month), and headache-related disability (HIT-6). The same information was obtained after 3 months of preventive treatment. Subjects were categorized based on BMI in: normal weight (</=24.9), overweight (25-29.9), or obese (>/=30). We contrasted the headache end-points using anova with post-test and Kruskal-Wallis with post-test. We used logistic regression to model BMI and headache parameters adjusting for covariates. Our sample consisted of 176 subjects (79.5% women, mean of 44.4 years). At baseline 40.9% had normal weight, 29.5% were overweight and 27.3% were obese. No significant differences were observed in the number of headache days at baseline. After treatment, frequency declined in the entire population, but no significant differences were found by BMI group. Regarding the number of days with severe pain per month, there were also no significant differences at baseline (normal = 6.1, overweight = 6.5, obese = 6.7), and improvement overall (P = 0.01). However, changes were greater in the obese (reduction in 2.7 days with treatment) and overweight (3.9) vs. normal (1.5, P < 0.01). Finally, HIT scores at baseline did not differ by BMI group (normal weight = 63.8, overweight = 64.1, obese = 63.6). However, compared with the normal weighted group, change in HIT scores (follow-up baseline) were greater in the obese (6.4 vs. 3.5, P < 0.05) and overweight groups (6.8 vs. 3.5, P < 0.05). In the logistic regression model, BMI did not account for changes in disability, headache frequency, or in the number of days with severe headache per month, after adjusting for covariates. Contrary to what we hypothesized, obesity at baseline does not seem to be related to follow-up refractoriness to preventive treatment.