Miracle-dz/UniFAR-FTUs huggingface dataset:
The protein disulfide isomerase AGR2 is essential for production of intestinal mucus

Protein disulfide isomerases (PDIs) aid protein folding and assembly by catalyzing formation and shuffling of cysteine disulfide bonds in the endoplasmic reticulum (ER). Many members of the PDI family are expressed in mammals, but the roles of specific PDIs in vivo are poorly understood. A recent homology-based search for additional PDI family members identified anterior gradient homolog 2 (AGR2), a protein originally presumed to be secreted by intestinal epithelial cells. Here, we show that AGR2 is present within the ER of intestinal secretory epithelial cells and is essential for in vivo production of the intestinal mucin MUC2, a large, cysteine-rich glycoprotein that forms the protective mucus gel lining the intestine. A cysteine residue within the AGR2 thioredoxin-like domain forms mixed disulfide bonds with MUC2, indicating a direct role for AGR2 in mucin processing. Mice lacking AGR2 were viable but were highly susceptible to colitis, indicating a critical role for AGR2 in protection from disease. We conclude that AGR2 is a unique member of the PDI family, with a specialized and nonredundant role in intestinal mucus production.
Effect of Posterior Cruciate Ligament Deficiency on in vivo Translation and Rotation of the Knee during Weightbearing Flexion

Background The effect of posterior cruciate ligament (PCL) deficiency on 6 degrees of freedom in vivo knee-joint kinematics is unclear. Hypothesis In addition to constraining anterior-posterior translation, the PCL also functions to constrain the medial-lateral translation and rotation of the knee during weightbearing flexion of the knee. Study Design Controlled laboratory study. Methods Eight patients with a PCL injury in 1 knee and the other intact were scanned with magnetic resonance imaging, and 3-dimensional models of the femur and tibia were created for both knees. Each knee was imaged during quasistatic weightbearing flexion (from 0° to 105°) using a dual-orthogonal fluoroscopic system. The translation and rotation of the PCL-deficient knee were compared with the intact contralateral control. Results Posterior cruciate ligament deficiency caused an increase in posterior tibial translation beyond 30° of flexion compared with the intact contralateral knees. At 90° of flexion, PCL deficiency increased posterior tibial translation by 3.5 mm (P < .05). In the medial-lateral direction, PCL deficiency resulted in a 1.1 mm increase in lateral tibial translation at 90° of flexion (P < .05). With regard to rotation, PCL deficiency caused a significantly lower varus rotation (on average, 0.6° lower) at 90° of flexion. Posterior cruciate ligament deficiency caused a decreased internal tibial rotation throughout the range of flexion, but no significant difference was detected. Conclusions This study quantitatively describes the effect of PCL injury on 6 degrees of freedom kinematics of the knee during quasistatic weightbearing flexion. Using the intact contralateral side as a control, we found that PCL injuries not only affect anterior-posterior tibial translation but also medial-lateral translation and rotation of the knee. Clinical Relevance These data provide baseline knowledge of the in vivo kinematics of the knee after PCL injury. Surgical reconstruction of the injured PCL, either using single-bundle or double-bundle technique, should not only focus on restoration of posterior stability of the knee but also the medial-lateral stability as well as the rotational stability. These findings may help to explain the long-term degenerative changes seen in PCL-deficient knees.
Local Intra-arterial Fibrinolysis of Thromboemboli Occurring During Neuroendovascular Procedures With Recombinant Tissue Plasminogen Activator

Background and Purpose— There is a lack of systematic data regarding local intra-arterial fibrinolysis (LIF) of thromboemboli occurring during neuroendovascular procedures with the use of recombinant tissue plasminogen activator (rtPA). We report our technique for treating LIF of intracerebral thromboemboli occurring during neuroendovascular procedures. Methods— Nine of 723 patients (1.2%) who underwent neuroendovascular procedures during the period from January 1997 to September 2002 suffered thromboembolic complications. These patients were treated by LIF with a maximum dose of 0.9 mg rtPA per kilogram body weight. Recanalization was categorized as successful (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3) versus unsuccessful (TIMI grade 0 or 1), and clinical outcome was categorized as independent (Rankin Scale score 0 to 2) versus dependent or dead (Rankin Scale score 3 to 6). Results— The minimum time between thrombus detection and beginning of LIF was 10 minutes, and the maximum time was 90 minutes. Successful recanalization was achieved in 4 of 9 patients (44%). All 9 patients suffered cerebral ischemic infarctions, and none of the patients sustained intracerebral hemorrhage. Two patients (22%) died from malignant brain infarctions. Four patients (44%) remained moderately disabled, and 3 patients (33%) were severely disabled 3 months after LIF. Conclusions— Although we used relatively high doses of rtPA, the recanalization rates and clinical outcome of LIF in our patients were not satisfactory. Strategies for the prevention of thromboemboli during neuroendovascular procedures must be improved, and novel fibrinolytic or thrombolytic techniques should be developed.
Insulin sensitivity and lipolysis in adolescent girls with poorly controlled type 1 diabetes: effect of anticholinergic treatment

Objectives Increased GH secretion could be one factor behind the impaired glycaemic control often seen in adolescent girls with type 1 diabetes. Because GH induces insulin resistance, treatment with anticholinergic agents, such as pirenzepine (PZP), has been used to reduce GH secretion. However, in a previous study of adolescent girls with type 1 diabetes, we observed an improvement in glycaemic control during 12 weeks of PZP therapy despite unchanged excretion of GH in urine. Considering the complex mechanisms behind urinary GH excretion, the effects of PZP on pituitary GH secretion or secretory pattern cannot be excluded. Thus, to assess the effect of anticholinergic treatment on metabolic control in adolescent girls with diabetes, we have investigated GH secretion, insulin sensitivity and lipolysis before and during treatment with PZP.
Disproportionate early fetal growth predicts postnatal thymic size in humans

Prenatal events can affect neonatal thymus size and adult immune function. The causal insults are unknown, although fetal nutrient restriction is suspected. We used ultrasound at three time points during pregnancy (14, 19 and 30 weeks) to measure the growth of six fetal dimensions in rural Bangladeshi women participating in the Maternal and Infant Nutrition Interventions, Matlab study. Postnatal ultrasound was used to calculate thymic index (TI) at birth, 2, 6 and 12 m. Of the 3267 women recruited, 2861 participated by providing data at least at one fetal biometry and one TI time point. Patterns of fetal growth were summarized using principal components calculated from fetal dimension z-scores. Random effects regression, controlling for infant size and season of measurement were used to relate these patterns to TI. We found that smaller leg length relative to head circumference, characteristic of head-sparing growth restriction, was predictive of lower TI. This association was significant at all time points but strongest in earlier pregnancy. Each standard deviation increase in leg–head proportion was associated with an increase in TI of ∼5%. We conclude that growth patterns typical of poor fetal nutrition are associated with poor thymic development. The greater strength of this association in the first trimester is consistent with a period of vulnerability during the early ontogeny of the thymus and suggests that preventative intervention would need to be given in early pregnancy.
Assessing military veterans for posttraumatic stress disorder: A guide for primary care clinicians

Purpose: To educate primary care providers on the physical effects of posttraumatic stress disorder (PTSD), explain why military veterans are at great risk, and describe how to identify PTSD in primary care clients. Data sources: Current scientific and psychiatric literature on PTSD. Conclusions: PTSD is prevalent in the military community because of the frequency and type of trauma seen in the combat zone. With the ongoing military deployments, assessment for the presence of PTSD is increasingly important for comprehensive and high‐quality primary care. Clients with trauma histories, such as veterans, are at increased risk for physical disorders such as heart disease and psychological disorders such as anxiety, depression, and PTSD. Implications for practice: Primary care clinicians, including those outside the military health system, are essential in identifying trauma histories and directing clients to appropriate care.
Contact force control of dual-rotor helicopter with protect frame

This paper proposes a contact force control system for a dual-rotor helicopter. Force control of a helicopter allows for achieving aerial tasks that include contact motions with objects. Although one-degree-of-freedom force control systems have been already developed, multi-degree-of-freedom systems have not been achieved yet. Therefore, in this paper, a force control system for a dual-rotor helicopter is proposed, and its validity is verified by simulations and experiments.
Urinary C peptide creatinine ratio in pregnant women with normal glucose tolerance and type 1 diabetes: evidence for insulin secretion

Hypothesis In pregnancy, urinary C peptide creatinine ratio (UCPCR) reflects endogenous insulin secretion in women with normal glucose tolerance and type 1 diabetes. Research design and methods UCPCR and serum C peptide were measured in 90 glucose-tolerant women at 0 and 120 min during a 75 g oral glucose tolerance test (OGTT) at 28 weeks of gestation. UCPCR was measured in 2 samples obtained over 10 weeks apart in 7 pregnant women with longstanding type 1 diabetes. Results UCPCROGTT and serum C peptideOGTT of glucose-tolerant women were significantly correlated at 0 and 120 min (rs0.675, 0.541 respectively, p<0.0001). All 7 pregnant women with type 1 diabetes had detectable first sample UCPCR (median (range) 49 (6–1038) pmol/mmol) that rose in 6 women by 477 (29–1491) pmol/mmol. Conclusions Detectable UCPCR in pregnant women with normal glucose tolerance and type 1 diabetes is likely to reflect endogenous insulin secretion and hence β-cell activity.
Induction of potent CD4+ T cell‐mediated antitumor responses by a helper HER‐2/neu peptide linked to the Ii‐Key moiety of the invariant chain

The Ii‐Key fragment from the MHC class II‐associated invariant chain (or Ii protein) has been shown to facilitate direct charging of MHC class II epitopes to the peptide binding groove. The purpose of the present study was to test the potential of a series of Ii‐Key/HER‐2/neu(776–790) hybrid peptides to generate increased frequencies of peptide‐specific CD4+ T cells over the native peptide in mice transgenic (Tg) for a chimeric human mouse class II molecule (DR4‐IE) (H‐2b) as well as their antitumor potency. Following in vivo priming, such hybrid peptides induced increased proliferation and frequencies of IFN‐γ producing CD4+ T cells in response to either syngeneic dendritic cells pulsed with native peptide, or HLA‐DR4+ human tumor cell lines expressing HER‐2/neu. Hybrid peptides were more stable in an off‐rate kinetics assay compared to the native peptide. In addition, antigen‐specific CD4+ T cells from hybrid peptide immunized DR4‐IE Tg mice synergized with HER‐2/neu(435–443)‐specific CD8+ T cells from HLA‐A2.1 Tg HHD (H‐2b) mice in producing antitumor immunity into SCID mice xenografted with the HER‐2/neu+, HLA‐A2.1+ and HLA‐DR4+ FM3 human melanoma cell line. High proportions of these adoptively transferred HER‐2/neu peptide‐specific CD4+ and CD8+ T cells infiltrated FM3‐induced tumors (tumor infiltrating lymphocytes; TIL) in SCID mice. CD8+ TIL exhibited long‐lasting antitumor activity when cotransferred with CD4+ TIL, inducing regression of FM3 tumors in a group of untreated, tumor‐bearing SCID mice, following adoptive transfer. Our data show that Ii‐Key modified HER‐2/neu(776–790) hybrid peptides are sufficiently potent to provide antigen‐specific CD4+ TH cells with therapeutic antitumor activity. © 2007 Wiley‐Liss, Inc.
Feasibility of Tool Condition Monitoring on Micro-Milling Using Current Signals

This paper reviewed existing studies in the area of tool condition monitoring. The review revealed the substantial amount of works that have been done in the area of tool condition monitoring in machine tool. However, it was observed that investigating the feasibility of using the main spindle and feed motor currents for tool condition monitoring in micromachining has not been carried out despite their advantage of low cost and simplicity. Therefore this study went further to investigate spindle and feed motor current signals as to their ability for sensing and monitoring tool wear progression on a micro milling machine. This initial investigation revealed some promising process signals for monitoring tool wear progression in micro milling.
2.4-GHz 8.5mW 3.7-dB NF 100-kHz 1/f corner direct-conversion receiver using double-balanced passive mixer

A 2.4-GHz direct-conversion receiver (DCR) is demonstrated using 0.18-µm CMOS technology. A passive mixer is used in this work to avoid the 1/ƒ noise problem. Besides, a single-to-differential transformer is also used between the low-noise amplifier (LNA) and the passive mixer to perform better isolation. In addition, vertical-NPN transistors, which can be obtained in deep-n-well CMOS process without extra mask, are employed at the transconductance stage of the IF amplifiers to achieve a higher gain and lower 1/ƒ noise than the NMOS transistors. The receiver achieves a conversion gain of 49 dB and double-sideband noise figure of 3.7 dB when the dc power consumption is 8.5 mW at a 1.8-V supply. The I/Q amplitude mismatch and phase error are below 0.3 dB and 2°, respectively, when LO frequency ranges from 2 to 3 GHz.
Identifying Diseases, Drugs, and Symptoms in Twitter

Social media sites, such as Twitter, are a rich source of many kinds of information, including health-related information. Accurate detection of entities such as diseases, drugs, and symptoms could be used for biosurveillance (e.g. monitoring of flu) and identification of adverse drug events. However, a critical assessment of performance of current text mining technology on Twitter has not been done yet in the medical domain. Here, we study the development of a Twitter data set annotated with relevant medical entities which we have publicly released. The manual annotation results show that it is possible to perform high-quality annotation despite of the complexity of medical terminology and the lack of context in a tweet. Furthermore, we have evaluated the capability of state-of-the-art approaches to reproduce the annotations in the data set. The best methods achieve F-scores of 55-66%. The data analysis and the preliminary results provide valuable insights on identifying medical entities in Twitter for various applications.
On Variable Scope of Parity Protection in Disk Arrays

In a common form of a RAID 5 architecture, data is organized on a disk array consisting of N+1 disks into stripes of N data blocks and one parity block (with parity block locations staggered so as to balance the number of parity blocks on each disk). This allows data to be recovered in the event of a single disk failure. Here we consider an extension to this architecture in which parity information applies to arbitrary subsets of the data blocks in each stripe. Using several simplifying assumptions, we present simulation and analytic results that provide estimates of the improvement using this approach, in terms of total I/O operations, as compared to 1) conventional RAID 5 under a random single-block write workload, and 2) the use of a log-structured file system in which data is written out in stripes. Results on the reduction of disk recovery costs are also presented.
Severe Acute Respiratory Syndrome-Associated Coronavirus Vaccines Formulated with Delta Inulin Adjuvants Provide Enhanced Protection while Ameliorating Lung Eosinophilic Immunopathology

ABSTRACT Although the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) epidemic was controlled by nonvaccine measures, coronaviruses remain a major threat to human health. The design of optimal coronavirus vaccines therefore remains a priority. Such vaccines present major challenges: coronavirus immunity often wanes rapidly, individuals needing to be protected include the elderly, and vaccines may exacerbate rather than prevent coronavirus lung immunopathology. To address these issues, we compared in a murine model a range of recombinant spike protein or inactivated whole-virus vaccine candidates alone or adjuvanted with either alum, CpG, or Advax, a new delta inulin-based polysaccharide adjuvant. While all vaccines protected against lethal infection, addition of adjuvant significantly increased serum neutralizing-antibody titers and reduced lung virus titers on day 3 postchallenge. Whereas unadjuvanted or alum-formulated vaccines were associated with significantly increased lung eosinophilic immunopathology on day 6 postchallenge, this was not seen in mice immunized with vaccines formulated with delta inulin adjuvant. Protection against eosinophilic immunopathology by vaccines containing delta inulin adjuvants correlated better with enhanced T-cell gamma interferon (IFN-γ) recall responses rather than reduced interleukin-4 (IL-4) responses, suggesting that immunopathology predominantly reflects an inadequate vaccine-induced Th1 response. This study highlights the critical importance for development of effective and safe coronavirus vaccines of selection of adjuvants based on the ability to induce durable IFN-γ responses. IMPORTANCE Coronaviruses such as SARS-CoV and Middle East respiratory syndrome-associated coronavirus (MERS-CoV) cause high case fatality rates and remain major human public health threats, creating a need for effective vaccines. While coronavirus antigens that induce protective neutralizing antibodies have been identified, coronavirus vaccines present a unique problem in that immunized individuals when infected by virus can develop lung eosinophilic pathology, a problem that is further exacerbated by the formulation of SARS-CoV vaccines with alum adjuvants. This study shows that formulation of SARS-CoV spike protein or inactivated whole-virus vaccines with novel delta inulin-based polysaccharide adjuvants enhances neutralizing-antibody titers and protection against clinical disease but at the same time also protects against development of lung eosinophilic immunopathology. It also shows that immunity achieved with delta inulin adjuvants is long-lived, thereby overcoming the natural tendency for rapidly waning coronavirus immunity. Thus, delta inulin adjuvants may offer a unique ability to develop safer and more effective coronavirus vaccines.
Secure Transmission in the Presence of Full-Duplex Active Eavesdropper

We propose a secure transmission scheme for a wiretap channel, where a source transmits to a legitimate destination in the presence of a full- duplex eavesdropper. We assume that the full- duplex eavesdropper performs both eavesdropping and malicious jamming simultaneously. In order to combat the full-duplex active eavesdropper, the source transmits artificial noise (AN) signals, apart from information signals, to confuse the eavesdropper. We adopt the hybrid outage probability as the performance metric, which takes both the transmission outage probability and the secrecy outage probability into consideration. We derive a compact expression for the hybrid outage probability. Utilizing the derived expression, we determine the optimal power allocation factor between information signals and AN signals that minimizes the hybrid outage probability. We also examine the asymptotic hybrid outage probability in the high signal-to-noise ratio regime. Furthermore, we compare the secrecy performance achieved by a full-duplex active eavesdropper with that achieved by a passive eavesdropper, showing that active eavesdropping can be more harmful to the legitimate system.
ADReCS-Target: target profiles for aiding drug safety research and application

Abstract Delivering safe and effective therapeutic treatment to patients is one of the grand challenges in modern medicine. However, drug safety research has been progressing slowly in recent years, compared to other fields such as biotechnologies and precision medicine, due to the mechanistic complexity of adverse drug reactions (ADRs). To fill up this gap, we develop a new database, the Adverse Drug Reaction Classification System-Target Profile (ADReCS-Target, http://bioinf.xmu.edu.cn/ADReCS-Target), which provides comprehensive information about ADRs caused by drug interaction with protein, gene and genetic variation. In total, ADReCS-Target includes 66,573 pairwise relations, among which 1710 are protein–ADR associations, 2613 are genetic variation–ADR associations, and 63,298 are gene–ADR associations. In a case study of exploring the mechanism of rash, we find that HLAs, C1QA and APOA1 are the key gene players and thus can be potential targets (or biomarkers) in monitoring or countermining rashes. In summary, ADReCS-Target can be a useful resource for the biomedical scientific community by serving researchers in the fields of drug development, clinical pharmacology, precision medicine, and from web lab to high-throughput computational platform. Particularly, it helps to identify drug with better ADR profile and design safer drug therapy regimen.
Skin absorption studies of octyl-methoxycinnamate loaded poly(D,L-lactide) nanoparticles: Estimation of the UV filter distribution and release behaviour in skin layers

New formulation strategies have to be developed to limit the skin penetration of UV-filter. Nanoparticles (NP) are very suitable for that purpose. In this study, the skin distribution, at different times (1, 2 and 3 h), of octyl-methoxycinnamate (OMC) from loaded PLA-nanoparticles was compared to a classical formulation containing non-encapsulated OMC, using the Franz cell method. The results showed that the OMC penetration was clearly impeded by stratum corneum and that the major part of the OMC-NP was accumulated at the skin surface (>80%). A significant lower OMC amount was quantified in viable skin with NP compared to the OMC emulgel. To accurately determine the real OMC amount in close contact with viable skin layers two solvents were used to extract OMC from the skin compartments. Acetone (ACET) allowed quantifying both OMC in NP and OMC released from the particles, while isopropylmyristate (IPM), a non-solvent of the NP polymer (PLA), allowed quantifying only OMC released from the particles. Using IPM as an extraction solvent, it appeared that the OMC released from NP, in contact with viable skin, was 3-fold lower than free OMC diffused from the emulgel. Lastly, a sustained release was observed when nanoparticles were used.
Phoenix rising: gene therapy makes a comeback

Abstract Despite the first application of gene therapy in 1990, gene therapy has until recently failed to meet the huge expectations set forth by researchers, clinicians, and patients, thus dampening enthusiasm for an imminent cure for many life-threatening genetic diseases. Nonetheless, in recent years we have witnessed a strong comeback for gene therapy, with clinical successes in young and adult subjects suffering from inherited forms of blindness or from X-linked severe combined immunodeficiency disease. In this review, various gene therapy vectors progressing into clinical development and pivotal advances in gene therapy trials will be discussed.