gebhart/patrepeval huggingface dataset:
Release of prostaglandin F-2α and the timing of events associated with luteolysis in ewes with oestrous cycles of different lengths (1988)

Ewes (N = 32) were bled every 2 h from 5 days before expected oestrus until the end of oestrus. Plasma concentrations were determined for progesterone to monitor luteal activity and for the prostaglandin F-2 alpha (PGF-2 alpha) metabolites, 15-keto-13,14-dihydro-PGF-2 alpha and 11-ketotetranor-PGF to determine uterine synthesis and release of PGF-2 alpha. Most of the variation in cycle length was associated with the time of onset of luteolysis, the timing of events after luteolysis being constant and not related to cycle length. The time of occurrence of the first PGF-2 alpha pulse and the interval between this pulse and the start of luteolysis were the two main determinants responsible for oestrous cycle length. Several PGF-2 alpha pulses with interpulse intervals of 15.9 h occurred before the onset of functional luteolysis compared with 7.7 h for pulses associated with luteolysis. The numbers of PGF-2 alpha pulses and interpulse intervals were similar for oestrous cycles of different lengths. While a gradual decline in progesterone concentrations was observed before functional luteolysis in the ewes with longer cycles, this did not appear to be an integral part of the stimulus which initiates the pulse frequency of PGF-2 alpha required for luteolysis. We therefore suggest that differences in oestrous cycle length in the ewe are determined by the time of the onset of PGF-2 alpha pulsatile release, and especially by the time of increased pulse frequency.
A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines (2013)

An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367-606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients' lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection.
Molecular and pharmacokinetic properties associated with the therapeutics of bcl-2 antisense oligonucleotide G3139 combined with free and liposomal doxorubicin. (2000)

Bcl-2 is a key apoptosis-regulating protein that has been implicated in mechanisms of chemoresistance for a variety of malignancies by blocking programmed cell death. This study investigated the activity of the Bcl-2 antisense oligodeoxynucleotide (AS ODN) G3139 combined with free doxorubicin (F-DOX) or sterically stabilized liposomal doxorubicin (SL-DOX) to determine the role that drug pharmacodistribution properties may have on antitumor activity using a Bcl-2-expressing human breast solid tumor xenograft model. Administration of G3139 was able to delay the growth of MDA435/LCC6 cells compared with control ODN-treated animals; however, in all of the cases, tumors reestablished after AS ODN treatment. Western blot analyses of Bcl-2 levels of solid tumors showed a sequence-specific down-regulation of the Bcl-2 protein after four daily doses of G3139, which correlated with histological evidence of tumor cell death. Interestingly, the expression of Bcl-2 returned to pretreatment levels during the course of subsequent ODN administration, which suggested the development of resistance to continued Bcl-2 ODN treatment. The antitumor activity of ODN given in conjunction with either F-DOX or SL-DOX was also examined. The combination of G3139 and F-DOX was able to suppress the growth of MDA435/LCC6 cells beyond that obtained with either of the treatments given alone, indicative of synergistic action. Examination of the pharmacokinetics of F-DOX with systemic G3139 administration revealed that elevated tumor drug DOX levels were obtained compared with DOX treatment in the absence of G3139. This effect was sequence-specific and plasma DOX levels were unaffected by G3139 treatment, which indicated possible positive ODN-drug interactions at the tumor site. Combining G3139 with SL-DOX further increased the degree of antitumor activity. The improved efficacy of this combination was attributed to increased tumor drug levels that arise from the ability of SL-DOX to passively accumulate in solid tumors. These results suggest that additional benefits of Bcl-2 antisense ODN may be obtained when it is combined with liposomal formulations of anticancer drugs such as DOX.
Inflammatory and Anti-glioma Effects of an Adenovirus Expressing Human Soluble Fms-like Tyrosine Kinase 3 Ligand (hsFlt3L): Treatment with hsFlt3L Inhibits Intracranial Glioma Progression (2004)

Glioblastoma multiforme is an intracranial tumor that has very poor prognosis. Patients usually succumb to their disease 6 to 12 months after they are diagnosed despite very aggressive treatment modalities. We tested the efficacy of a potent differentiation and proliferation factor for the professional antigen-presenting dendritic cells (DCs), i.e., Flt3L, for its potential role as a novel therapy for gliomas. We investigated the ability of recombinant adenoviral vectors encoding human soluble Flt3L (hsFlt3L) to improve the survival of Lewis rats bearing intracranial syngeneic CNS-1 gliomas. We show that RAdhsFlt3L can improve survival in a dose-dependent manner. Seventy percent of rats survive when treated with 8 x 10(7) pfu RAdhsFlt3L (P < 0.0005). In addition we demonstrate in both naive Lewis rats and C57BL/6 mice the presence of increased numbers of cells bearing DC markers (OX62 and MHCII, in rats, or CD11C, 33D1, MHCII, and F4/80, but not DEC205, in mice) in sites of brain delivery of RAdhsFlt3L. These results show that expression of hsFlt3L in the brain leads to the presence of cells displaying DC markers. We demonstrate that treatment with hsFlt3L leads to inhibition of tumor growth and significantly increased life span of animals implanted with syngeneic CNS-1 glioma cells. Animals that had survived for long periods, i.e., 6 months, had eliminated the implanted tumors after neuropathological analysis; on the other hand, some of the 3-month survivors still appeared to harbor brain tumors. Our results have profound implications for immune-mediated brain tumor therapy and also suggest the ability to recruit DC-like cells within the brain parenchyma in response to the local expression of Flt3L from adenoviral vectors.
Making Healthy Behaviors the Easy Choice for Employees (2012)

As employers look for ways to reduce rising health care costs, worksite health promotion interventions are increasingly being used to improve employee health behaviors. An alternative approach to traditional worksite health promotion programs is the implementation of environmental and/or policy changes to encourage employees to adopt healthier behaviors. This review examines the evidence for the effectiveness of worksite health promotion programs using environmental and/or policy changes either alone or in combination with individually focused health behavior change strategies. A review of the relevant literature, published between 1995 and 2010, identified 27 studies that met all inclusion criteria. Limited evidence was found for the effectiveness of environmental and/or policy changes alone (n = 11) to change employee behavior, but more promising results were identified with multicomponent interventions (n = 16). There is a strong need for improvement in the design and evaluation of future health promotion programs focusing solely on environmental and/or policy changes at the worksite.
Neutralizing Anti-IL-10 Antibody Blocks the Protective Effect of Tapeworm Infection in a Murine Model of Chemically Induced Colitis (2005)

There is increasing evidence that parasitic helminth infection has the ability to ameliorate other disease conditions. In this study the ability of the rat tapeworm, Hymenolepis diminuta, to modulate dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice is assessed. Mice receiving DNBS (3 mg intrarectally) developed colitis by 72 h after treatment. Mice infected 8 days before DNBS with five H. diminuta larvae were significantly protected from the colitis, as gauged by reduced clinical disease, histological damage scores, and myeloperoxidase levels. This anticolitic effect was dependent on a viable infection and helminth rejection, because no benefit was observed in mice given killed larvae or in infected STAT6 knockout mice or rats, neither of which eliminate H. diminuta. The anticolitic effect of H. diminuta was associated with increased colonic IL-10 mRNA and stimulated splenocytes from H. diminuta- plus DNBS-treated mice produced more IL-10 than splenocytes from DNBS-only treated mice. Coadministration of an anti-IL-10 Ab blocked the anticolitic effect of prophylactic H. diminuta infection. Also, mice infected 48 h after DNBS treatment showed an enhanced recovery response. Finally, using a model of OVA hypersensitivity, we found no evidence of concomitant H. diminuta infection enhancing enteric responsiveness to subsequent ex vivo OVA challenge. The data show that a viable infection of H. diminuta in a nonpermissive system exerts a profound anticolitic effect (both prophylactically and as a treatment) that is mediated at least in part via IL-10 and does not predispose to enhanced sensitivity to bystander proteins.
Zero-Shot Knowledge Distillation in Deep Networks (2019)

Knowledge distillation deals with the problem of training a smaller model (Student) from a high capacity source model (Teacher) so as to retain most of its performance. Existing approaches use either the training data or meta-data extracted from it in order to train the Student. However, accessing the dataset on which the Teacher has been trained may not always be feasible if the dataset is very large or it poses privacy or safety concerns (e.g., bio-metric or medical data). Hence, in this paper, we propose a novel data-free method to train the Student from the Teacher. Without even using any meta-data, we synthesize the Data Impressions from the complex Teacher model and utilize these as surrogates for the original training data samples to transfer its learning to Student via knowledge distillation. We, therefore, dub our method "Zero-Shot Knowledge Distillation" and demonstrate that our framework results in competitive generalization performance as achieved by distillation using the actual training data samples on multiple benchmark datasets.
Cloning and Characterization of a Periplasmic Nuclease of Vibrio vulnificus and Its Role in Preventing Uptake of Foreign DNA (2001)

We have cloned a nuclease gene, vvn, from Vibrio vulnificus, an estuarine bacterium that causes wound infections and septicemia in humans and eels. The gene contained a 696-bp open reading frame encoding 232 amino acids (aa), including a signal sequence of 18 aa. The deduced amino acid sequence of the mature nuclease predicted a molecular mass of 25 kDa, which was confirmed by vital stain, and a pI of 8.6. Vvn was produced in the periplasm of either V. vulnificus or recombinant Escherichia coli strains and was active in the oxidized (but not the reduced) form. This nuclease was able to digest DNA and RNA, with differential thermostability in DNase and RNase activities. Expression of Vvn in E. coli DH5alpha reduced the frequencies of transformation with the divalent ion-treated cells and electroporation by about 6 and 2 logs, respectively. In addition, the transformation frequency of a Vvn-deficient V. vulnificus mutant (ND) was 10-fold higher than that of the parent strain. These data suggested that Vvn may be involved in preventing uptake of foreign DNA by transformation. However, Vvn expressed in the recipients had little effect on the conjugation frequency in either E. coli or V. vulnificus. Some other DNase(s) may be present in the periplasm and responsible for a residual DNase activity, which was about one-fourth of that of the parent strain, detected in the ND mutant. We also demonstrated that Vvn was not required for the virulence of V. vulnificus mice.
Cell Surface Vimentin Is an Attachment Receptor for Enterovirus 71 (2014)

This study delivers important findings on the roles of vimentin filaments in relation to EV71 infection and provides information that not only improves our understanding of EV71 pathogenesis but also presents us with potentially new strategies for the treatment of diseases caused by EV71 infections.
Incorporation of polyhedral oligosilsesquioxane in chemically amplified resists to improve their reactive ion etching resistance (2001)

A chemically amplified (CA) methacrylate resist containing polyhedral oligosilsesquioxane (POSS) has been synthesized by AIBN-initiated free radical polymerization. While the polymer of low POSS concentrations showed little improvement in reactive ion etching (RIE) resistance, incorporation of 20.5 wt % of the POSS monomer into methacrylate-based CA resists significantly improved their RIE resistance in the O2 plasma. High-resolution transmission electron microscopy revealed that the RIE resistance improvement was due to the formation of rectangular crystallite-constituting networks of the silica cages uniformly distributed within the polymer matrix.
Synthesis of 6H-pyrrolo[3′,4′:2,3][1,4]diazepino[6,7,1-hi]indole-8,10(7H,9H)-diones using 3-bromo-4-(indol-1-yl)maleimide scaffold (2003)

Series of 3-arylalkyl- or 3-alkylamino-4-(indol-1-yl)maleimides and bis(indol-1-yl)maleimides were synthesised. The cyclization of the 3-substituted 4-(indol-1-yl)maleimides under the action of acids resulted in the formation of diazepine[1,4] derivatives with indoline and maleimide nuclei annelated. These compounds readily produced the corresponding indolomaleimidodiazepines[1,4] after dehydrogenation.
Eradication of HIV in infected patients: some potential approaches. (2004)

Although at present, highly active antiretroviral therapy (HAART) has greatly reduced the number of viral copies to an undetectable level and has slowed down the progress of the disease in patients with human immunodeficiency virus (HIV) infection, the HIV-infected cells are not eradicated by this therapy. Virus replication rebounds once the drug therapy is terminated, regardless of duration of the therapy, primarily due to the establishment of a viral reservoir. Therefore, viral suppressive therapy is a lifelong task and may be accompanied by many as yet unidentified serious side effects. In addition, the maximum therapeutic benefits of HAART appear to have been reached recently in the U. S, and the incidences of multi-drug resistant viral strain infections are slowly but steadily increasing. Without an effective vaccine, which has already proved to be very difficult to develop, for the protection of the uninfected population and a feasible eradication strategy to cure infected patients, the number of HIV-infected persons will inevitably continue to rise. While the vast majority of endeavors are focused on developing new drugs that target different steps of HIV replication for suppressive therapy, researchers need to find a therapeutic strategy that directly aims at HIV-infected cells to cure the disease. In this article, I review and discuss some potential approaches to eradicate HIV-infected cells from the patients.
Noninvasive calculation of the aortic blood pressure waveform from the flow velocity waveform: a proof of concept (2015)

Estimation of aortic and left ventricular (LV) pressure usually requires measurements that are difficult to acquire during the imaging required to obtain concurrent LV dimensions essential for determination of LV mechanical properties. We describe a novel method for deriving aortic pressure from the aortic flow velocity. The target pressure waveform is divided into an early systolic upstroke, determined by the water hammer equation, and a diastolic decay equal to that in the peripheral arterial tree, interposed by a late systolic portion described by a second-order polynomial constrained by conditions of continuity and conservation of mean arterial pressure. Pulse wave velocity (PWV, which can be obtained through imaging), mean arterial pressure, diastolic pressure, and diastolic decay are required inputs for the algorithm. The algorithm was tested using 1) pressure data derived theoretically from prespecified flow waveforms and properties of the arterial tree using a single-tube 1-D model of the arterial tree, and 2) experimental data acquired from a pressure/Doppler flow velocity transducer placed in the ascending aorta in 18 patients (mean ± SD: age 63 ± 11 yr, aortic BP 136 ± 23/73 ± 13 mmHg) at the time of cardiac catheterization. For experimental data, PWV was calculated from measured pressures/flows, and mean and diastolic pressures and diastolic decay were taken from measured pressure (i.e., were assumed to be known). Pressure reconstructed from measured flow agreed well with theoretical pressure: mean ± SD root mean square (RMS) error 0.7 ± 0.1 mmHg. Similarly, for experimental data, pressure reconstructed from measured flow agreed well with measured pressure (mean RMS error 2.4 ± 1.0 mmHg). First systolic shoulder and systolic peak pressures were also accurately rendered (mean ± SD difference 1.4 ± 2.0 mmHg for peak systolic pressure). This is the first noninvasive derivation of aortic pressure based on fluid dynamics (flow and wave speed) in the aorta itself.
Copper Response Element and Crr1-Dependent Ni 2+ -Responsive Promoter for Induced, Reversible Gene Expression in Chlamydomonas reinhardtii (2003)

The Cpx1 and Cyc6 genes of Chlamydomonas reinhardtii are activated in copper-deficient cells via a signal transduction pathway that requires copper response elements (CuREs) and a copper response regulator defined by the CRR1 locus. The two genes can also be activated by provision of nickel or cobalt ions in the medium. The response to nickel ions requires at least one CuRE and also CRR1 function, suggesting that nickel interferes with a component in the nutritional copper signal transduction pathway. Nickel does not act by preventing copper uptake/utilization because (i) holoplastocyanin formation is unaffected in Ni(2+)-treated cells and (ii) provision of excess copper cannot reverse the Ni-dependent activation of the target genes. The CuRE is sufficient for conferring Ni-responsive expression to a reporter gene, which suggests that the system has practical application as a vehicle for inducible gene expression. The inducer can be removed either by replacing the medium or by chelating the inducer with excess EDTA, either of which treatments reverses the activation of the target genes.
Human endothelial cells produce orosomucoid, an important component of the capillary barrier (1999)

The serum protein orosomucoid (alpha1-acid glycoprotein) is needed to maintain the high capillary permselectivity required for normal homeostasis. It is not known how the protein executes its action, but it seems to contribute to the charge barrier. Moreover, recent studies suggest that the endothelial glycocalyx is essential for the charge barrier. The main site of orosomucoid synthesis is the liver, but we wanted to explore the possibility that orosomucoid was synthesized in endothelial cells. Primary cultures of human microvascular endothelial cells (HMVEC) from dermal tissue were established. Human liver cells were used as positive controls, and total RNA was prepared from both cell types. Reverse transcription-polymerase chain reaction (RT-PCR) was performed and demonstrated orosomucoid expression. After RT-PCR, the identities of the PCR products were confirmed by sequencing. RNase protection assay performed on total RNA from the HMVEC confirmed the results from the RT-PCR, i.e., orosomucoid mRNA is expressed by endothelial cells. Synthesis of orosomucoid in both liver and endothelial cells was demonstrated by immunoprecipitation. In conclusion, endothelial cells normally produce orosomucoid, which is essential for capillary charge selectivity. We suggest that orosomucoid exerts its effect by interacting with other components of the endothelial glycocalyx.
Pharmacological plasticity of GABAA receptors at dentate gyrus synapses in a rat model of temporal lobe epilepsy (2004)

In the lithium-pilocarpine model (Li-pilocarpine) of temporal lobe epilepsy, GABA(A) receptor-mediated inhibitory postsynaptic currents (GABA(A) IPSCs) were recorded in dentate gyrus granule cells (GCs) from adult rat hippocampal slices. The properties of GABA(A) IPSCs were compared before and after superfusion of modulators in control conditions (Li-saline rats) and in Li-pilocarpine rats 24-48 h and 3-5 months (epileptic rats) after status epilepticus (SE). The mean peak amplitude of GABA(A) IPSCs increased by about 40% over Li-saline values in GCs 24-48 h after SE and remained higher in epileptic rats. In Li-pilocarpine rats, studied at 24-48 h after SE, diazepam (1 microm) lost 65% of its effectiveness at increasing the half-decay time (T(50%)) of GABA(A) miniature IPSCs (mIPSCs). Diazepam had no effects on mIPSC T(50%) in epileptic rats. The benzodiazepine ligand flumazenil (1 microm), acting as an antagonist in Li-saline rats, exhibited a potent inverse agonistic effect on GABA(A) mIPSCs of GCs from Li-pilocarpine rats 24-48 h and 3-5 months after SE. The neurosteroid allopregnanolone (100 nm), which considerably prolonged GABA(A) mIPSCs in Li-saline rats, totally lost its effect in rats studied 24-48 h after SE. However, this decrease in effectiveness was transient and was totally restored in epileptic rats. In addition to the up-regulation in the number of receptors at individual GC synapses, we propose that these 'epileptic' GABA(A) receptors possess benzodiazepine binding sites with altered allosteric properties. The failure of benzodiazepine and neurosteroid to potentiate inhibition early after SE may be a critical factor in the development of epileptogenesis and occurrence of seizures.
Adalimumab effectively controlled recalcitrant generalized pustular psoriasis in an adolescent (2005)

Generalized pustular psoriasis is a rare form of psoriasis which may be serious and can be fatal. We report here the treatment of an adolescent girl who responded to adalimumab after failing to respond to a combination of methotrexate, cyclosporin and isotretinoin, and having had a pustular reaction that followed the use of etanercept, but might have been triggered by an infection.