gebhart/patrepeval huggingface dataset:
Selective Ablation of Proliferating Microglial Cells Exacerbates Ischemic Injury in the Brain (2007)

Here we report in vivo evidence of a neuroprotective role of proliferating microglial cells in cerebral ischemia. Using transgenic mice expressing a mutant thymidine kinase form of herpes simplex virus driven by myeloid-specific CD11b promoter and ganciclovir treatment as a tool, we selectively ablated proliferating (Mac-2 positive) microglia after transient middle cerebral artery occlusion. The series of experiments using green fluorescent protein-chimeric mice demonstrated that within the first 72 h after ischemic injury, the Mac-2 marker [unlike Iba1 (ionized calcium-binding adapter molecule 1)] was preferentially expressed by the resident microglia. Selective ablation of proliferating resident microglia was associated with a marked alteration in the temporal dynamics of proinflammatory cytokine expression, a significant increase in the size of infarction associated with a 2.7-fold increase in the number of apoptotic cells, predominantly neurons, and a 1.8-fold decrease in the levels of IGF-1. A double-immunofluorescence analysis revealed a approximately 100% colocalization between IGF-1 positive cells and Mac-2, a marker of activated/proliferating resident microglia. Conversely, stimulation of microglial proliferation after cerebral ischemia by M-CSF (macrophage colony stimulating factor) resulted in a 1.9-fold increase in IGF-1 levels and a significant increase of Mac2+ cells. Our findings suggest that a postischemic proliferation of the resident microglial cells may serve as an important modulator of a brain inflammatory response. More importantly, our results revealed a marked neuroprotective potential of proliferating microglia serving as an endogenous pool of neurotrophic molecules such as IGF-1, which may open new therapeutic avenues in the treatment of stroke and other neurological disorders.
Clinical Staging: A Heuristic and Practical Strategy for New Research and Better Health and Social Outcomes for Psychotic and Related Mood Disorders (2010)

Most mental illnesses emerge during adolescence and early adulthood, with considerable associated distress and functional decline appearing during this critical developmental phase. Our current diagnostic system lacks therapeutic validity, particularly for the early stages of mental disorders when symptoms are still emerging and intensifying and have not yet stabilized sufficiently to fit the existing syndromal criteria. While this is, in part, due to the difficulty of distinguishing transient developmental or normative changes from the early symptoms of persistent and disabling mental illness, these factors have contributed to a growing movement for the reform of our current diagnostic system to more adequately inform the choice of therapeutic strategy, particularly in the early stages of a mental illness. The clinical staging model, which defines not only the extent of progression of a disorder at a particular point in time but also where a person lies currently along the continuum of the course of an illness, is particularly useful as it differentiates early, milder clinical phenomena from those that accompany illness progression and chronicity. This will not only enable clinicians to select treatments relevant to earlier stages of an illness, where such interventions are likely to be more effective and less harmful than treatments delivered later in the course of illness, but also allow a more efficient integration of our rapidly expanding knowledge of the biological, social, and psychological vulnerability factors involved in the development of mental illness into a useful diagnostic framework.
High Abundance Proteins Depletion vs Low Abundance Proteins Enrichment: Comparison of Methods to Reduce the Plasma Proteome Complexity (2011)

Our results show that the two approaches give complementary results. However, the enrichment of low abundance proteins has the great advantage of obtaining much larger amount of material that can be used for further fractionations and analyses and emerges also as a cheaper and technically simpler approach. Collectively, these data indicate that the enrichment approach seems more suitable as the first stage of a complex multi-step fractionation protocol.
Impaired dimerization of von Willebrand factor subunit due to mutation A2801D in the CK domain results in a recessive type 2A subtype IID von Willebrand disease (2006)

The CK domain of von Willebrand factor (VWF) is involved in the dimerization of the protein. We identified the homozygous substitution A2801D of the CK domain in two siblings. Patients had low levels of VWF in plasma, abnormal ristocetin-induced binding to platelets and abnormal multimeric pattern with a lack of high molecular weight (HMW) forms and the presence of intervening bands between normal multimers. Accordingly, they were classified in type 2A, subtype IID, von Willebrand disease (VWD). Both asymptomatic parents carried the mutation at the heterozygous state. Their plasmaVWF exhibited the full range of multimers found in normal plasma. When analyzed by high resolution gel electrophoresis, very faint bands corresponding to the position of intervening bands of the propositus can be observed. The mutated recombinant (r)VWF-D2801, the hybrid rVWF-A/D2801 and the mutated C-terminal VWF fragment rSPII-D2801 were expressed in COS-7 cells. rVWF-D2801 showed an abnormal multimeric distribution similar to that of the propositus'VWF with intervening bands and a lack of HMW species. rVWF-A/D2801 exhibited the full range of multimers and the aberrant sized forms observed both in propositus'VWF and in rVWF-D2801. rSPII-WT assembled correctly into a dimer of 220 kDa. rSPII-D2801 appeared as a mixture of monomeric and dimeric forms which may be related to the abnormal multimeric pattern of the propositus and both mutated rVWF. We concluded that mutation A2801D disturbs the folding of the CK domain, which may result in a mixture of monomers and dimers of VWF. Multimers containing either an odd or even number of mature subunits are produced, and the presence of monomers appears to limit the degree of multimerization. In the heterozygousVWF, the presence of normal dimers improves the multimerization process. In conclusion, the mutation A2801D appears to be responsible for a recessive type 2A, subtype IID, VWD.
Spinous process plate fixation as a salvage operation for failed anterior cervical fusion (2006)

The purpose of this retrospective review was to demonstrate the effectiveness of simple spinous process plate fixation as a salvage operation for failed anterior cervical fusion (ACF). In this technique, the spinous processes are securely sandwiched between a pair of plates with thorns, which are squeezed together by tightening screws that extend through the plates. The authors salvaged six failed ACFs (nonunion of bone graft, plate migration, or bone graft dislodgment) by conducting this fixation without bone grafting, or with an anterior or posterior local bone graft only. Anterior bone union was attained within 6 months in all cases. This technique is easy to perform and probably provides more mechanical strength than does conventional spinous process wiring, resulting in prompt fusion without the need for a new massive bone graft. This technique is a practical option in salvage operations for failed ACF.
Adaptive Permutation Invariant Training with Auxiliary Information for Monaural Multi-Talker Speech Recognition (2018)

In this paper, we extend our previous work on direct recognition of single-channel multi-talker mixed speech using permutation invariant training (PIT). We propose to adapt the PIT models with auxiliary features such as pitch and i-vector, and to exploit the gender information with multi-task learning which jointly optimizes for the speech recognition and speaker-pair prediction. We also compare CNN-BLSTMs against BLSTM-RNNs used in our previous PIT-ASR model. The experimental results on the artificially mixed two-talker AMI data indicate that our proposed model improvements can reduce word error rate (WER) by ~ 10.0% relative to our previous work for both speakers in the mixed speech. Our results also confirm that PIT can be easily combined with advanced techniques to improve the performance on multi-talker speech recognition.
Hector: Detecting Resource-Release Omission Faults in error-handling code for systems software (2013)

Omitting resource-release operations in systems error handling code can lead to memory leaks, crashes, and deadlocks. Finding omission faults is challenging due to the difficulty of reproducing system errors, the diversity of system resources, and the lack of appropriate abstractions in the C language. To address these issues, numerous approaches have been proposed that globally scan a code base for common resource-release operations. Such macroscopic approaches are notorious for their many false positives, while also leaving many faults undetected. We propose a novel microscopic approach to finding resource-release omission faults in systems software. Rather than generalizing from the entire source code, our approach focuses on the error-handling code of each function. Using our tool, Hector, we have found over 370 faults in six systems software projects, including Linux, with a 23% false positive rate. Some of these faults allow an unprivileged malicious user to crash the entire system.
CHEMICAL TREATMENTS OF POLYPROPYLENE FIBER SURFACES USED IN FIBER REINFORCED CONCRETES (1989)

This paper reports the results of an experimental investigation to determine the effects of chemical treatment of polypropylene fibers (PPF) used in reinforced concretes. The control group concrete was designed at 4,000 psi. The chemical solution used to treat the fiber surfaces was a basic solution of linear alcohol alkoxylates. The investigation included comparison of some static strength as well as the interfacial bond characteristics of unreinforced, plain fiber reinforced, and chemically treated fiber reinforced concretes that were cured for two different periods of 28 and 45 days. Three separate methods of testing were conducted to ascertain the mechanical measures of the concrete samples: compression testing (ASTM 4.02, C-39), flexure strength tests (ASTM 4.02, C-78), and splitting tensile tests (ASTM 4.02, C-496). A random sampling of the failed PPF specimens was prepared and observed using the scanning electron microscopy (SEM) technique. The interfacial features of the fiber surfaces were evaluated to determine the bonding characteristics between the fiber and the concrete matrix. A correlation between the chemical surface treatment of the PPF and the mechanical measures were statistically analyzed.
Transurethral Microwave Hyperthermia for Benign Prostatic Hyperplasia: Preliminary Clinical and Pathological Results (1990)

Transurethral microwave hyperthermia is a new conservative treatment modality for benign prostatic hyperplasia. We treated 15 patients with 915 MHz. microwaves delivered transurethrally by a helical applicator. Of the patients 12 showed substantial objective and subjective improvement of obstructive outflow parameters. Significant improvement in objective study parameters included increased mean flow rate (p less than 0.00021), decreased mean residual volume (p less than 0.00001) and decreased mean prostatic volume (p less than 0.0077). Analysis of patterns of failure showed chronic bladder atony, prostate asymmetry and middle lobe configuration as important factors that could explain the failure of hyperthermia in 3 patients. Toxicity was mild, consisting of bladder spasms, perineal pain, dysuria and hematuria. Hyperthermia-induced pathological changes in prostatic tissues, causing periurethral shrinking and secondary dilatation of the prostatic urethra, are described. The reported clinical results of this phase I study are preliminary due to the short followup. A phase II study to optimize transurethral hyperthermia currently is underway. A phase III study is to be phased in comparing hyperthermia with transurethral resection of the prostate.
Structure-activity relationships of adrenomedullin in the adrenal gland (1998)

Human adrenomedullin (ADM) is a 52-amino acid hypotensive peptide, originally isolated from human pheochromocytomas, which is expressed in a wide array of tissues, including blood vessels and adrenal medulla (1). Like other regulatory peptides contained in the adrenal medulla (2), ADM affects the secretory activity of the adrenal cortex probably acting in a paracrine manner. It has been demonstrated that ADM specifically inhibits angiotensin-II (ANG-II)-stimulated aldosterone secretion of dispersed human adrenocortical cells, through a mechanism which is likely to involve the impairment of Ca2+ influx (3,4). ADM possesses a disulfide bridge-formed six-memberedring in 16–21 position, which, along with the N-terminal and C-terminal amino-acid sequences, seems to play a key role in its vascular effects (5–7). Analogous strcture-activity relationship studies are not available as far as the antimineralocorticoid action of ADM is concerned. This prompted us to investigate the effects of several ADM fragments (synthesized in the Peptide Research Labs of the Tulane University), containing or not the six-membered ring structure and the N- or C-terminal sequences, on the aldosterone response to ANG-II of dispersed human adrenocortical cells.Autoradiography showed the presence of abundant [125I]ADM(1–52) binding sites in the zona glomerulosa (ZG) of human adrenals, which were completely displaced not only by cold ADM(1–52), but also by both ADM(13–52) and ADM(22–52); ADM fragments 1–12, 15–22 and 16–31 were ineffective. ADM(1–52) and ADM(13–52), but not other fragments, concentration-dependenly inhibited ANGII-stimulated
The Role of the Amino Group in Subunit Association and Receptor Site Interaction for Ovine Luteinizing Hormone as Studied by Acylation (1974)

Abstract The positively charged amino groups (in physiological pH range) of ovine luteinizing hormone (oLH) and its subunits (oLHα and oLHβ) were acylated to produce negatively charged (maleylated) or neutral groups (carbamylated) in their place. In both reactions, the number of modified e-lysine amino groups in luteinizing hormone (LH), LHα, and LHβ was 10, 9, and 2, respectively. The NH2 termini were also completely acylated in both reactions. Maleylation or carbamylation did not alter the hydrodynamic volume of oLH or oLHβ significantly, although a greater Stokes radius was obtained with the oLHα derivatives compared to native oLHα as judged by Kav values from molecular exclusion chromatography. Maleylated LHβ combined with native LHα as well as the native subunits recombine, but maleylated LHα recombined with native LHβ less effectively. Efficiency of recombination was judged by the quantity of material with a hydrodynamic volume similar to LH under specified recombination conditions. Maleylated LHα and maleylated LHβ recombined very poorly. The series of recombination products with carbamylated subunits were all obtained in yields comparable to those observed with the recombination of the native subunits. Biological activities of the various recombined products were examined by both the in vivo ovarian ascorbic acid depletion assay and the in vitro radioligand receptor assay and the results agreed. Intact oLH which had been carbamylated or maleylated, as well as the recombined subunit derivatives from these reactions were completely inactive. Either the carbamylated or maleylated oLHα plus native oLHβ, and native oLHα plus maleylated oLHβ gave a low biological activity with response characteristics different from that of the native hormone. The recombined native subunits, or native oLHα plus carbamylated oLHβ, gave products that were slightly less potent than native oLH, with response characteristics that paralleled those of the native hormone. These results suggest that the charges on lysine e-amino groups in the oLHα play a role in the recombination with oLHβ, but that the charge on the oLHβ amino groups is not crucial for subunit-subunit interaction. It may also be concluded that the charge on the free amino groups of oLHβ must be positive or neutral for receptor site interaction. At least a portion of the amino groups on the oLHα must carry a positive charge for maximum hormone-receptor site interaction.
In Vitro Digestion of Bloat-Safe and Bloat-Causing Legumes by Rumen Microorganisms: Gas and Foam Production (1980)

Leaves of three bloat-safe legumes -- birdsfoot trefoil (Lotus corniculatus L.), sainfoin (Onobrychis viciaefolia Scop.), and cicer milkvetch (Astralagus cicer L.) -- and of three bloat-causing legumes -- alfalfa (Medicago sativa L.), red clover (Trifolium pratense L.), and white clover (Trifolium repens L.) -- were incubated with strained rumen fluid or with mixed rumen fluid and solids. Gas released was measured during the early period (0 to 22 h) of this in vitro digestion. Gas volume was greater with a 1:1 (wt/vol) mixture of solid and fluid rumen contents than with rumen fluid alone. It was greater with whole and chewed leaves from the bloat-causing legumes than with whole leaves from the bloat-safe legumes. However, when leaves were homogenized, volumes of gas from bloat-causing and bloat-safe legumes were similar. More gas was released from homogenized leaves than from the same weight of whole leaves. The amount of foam produced on chewed herbage and homogenized leaves of bloat-causing legumes was greater than on those of bloat-safe legumes. These results are consistent with the rate of disintegration and digestion of legumes by rumen bacteria being an important determinant in pasture bloat. Measurement of gas produced early in in vitro digestion may provide a useful bioassay for evaluating the bloat-causing potential of legumes in breeding selections if variability of the method can be reduced.
Physical Interaction between the Herpes Simplex Virus Type 1 Exonuclease, UL12, and the DNA Double-Strand Break-Sensing MRN Complex (2010)

The herpes simplex virus type 1 (HSV-1) alkaline nuclease, encoded by the UL12 gene, plays an important role in HSV-1 replication, as a UL12 null mutant displays a severe growth defect. The HSV-1 alkaline exonuclease UL12 interacts with the viral single-stranded DNA binding protein ICP8 and promotes strand exchange in vitro in conjunction with ICP8. We proposed that UL12 and ICP8 form a two-subunit recombinase reminiscent of the phage lambda Red α/β recombination system and that the viral and cellular recombinases contribute to viral genome replication through a homologous recombination-dependent DNA replication mechanism. To test this hypothesis, we identified cellular interaction partners of UL12 by using coimmunoprecipitation. We report for the first time a specific interaction between UL12 and components of the cellular MRN complex, an important factor in the ATM-mediated homologous recombination repair (HRR) pathway. This interaction is detected early during infection and does not require viral DNA or other viral or cellular proteins. The region of UL12 responsible for the interaction has been mapped to the first 125 residues, and coimmunoprecipitation can be abolished by deletion of residues 100 to 126. These observations support the hypothesis that cellular and viral recombination factors work together to promote efficient HSV-1 growth.
Noradrenergic Function in Panic Anxiety (1984)

Yohimbine, an alpha 2-adrenergic receptor antagonist that increases noradrenergic function, was administered to 20 healthy subjects and 39 drug-free patients with agoraphobia and panic attacks. Following drug administration, changes in plasma levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), BP, pulse rate, and subjective ratings of feelings and somatic symptoms were examined during a four-hour period. Yohimbine produced significantly greater increases in patient-rated anxiety, nervousness, palpitations, hot and cold flashes, restlessness, tremors, piloerection, and sitting systolic BP in the total patient group compared with healthy subjects. There were significant correlations between the yohimbine-induced rise in plasma MHPG level and patient-rated anxiety and nervousness and the frequency of reported panic attacks. Patients experiencing frequent panic attacks (greater than 2.5 per week) had a significantly greater plasma MHPG response to yohimbine than the healthy subjects and patients having less frequent panic attacks. These observations support a hypothesis of increased sensitivity to augmented noradrenergic function in anxiety states associated with panic, and they suggest that impaired presynaptic noradrenergic neuronal regulation may exist in patients with frequent panic attacks.
Cutting Edge: JAK3 Activation and Rescue of T Cells from HIV gp120-Induced Unresponsiveness (1998)

In early HIV disease, immunodeficiency is characterized by the inability of CD4+ T cells to produce a critical cytokine, IL-2, and to express the receptor for IL-2 (IL-2R) in response to antigenic or mitogenic stimulation. The shared common gamma-chain (gamma(c)) of IL-2R and its associated Janus kinase, JAK3, are indispensable for normal T cell function. Here, we show that the inhibition of IL-2R expression and proliferation induced by ligation of CD4 by HIV envelope glycoprotein, gp120, is correlated with inhibition of expression and activation of JAK3. Stimulation through the gamma(c)-related cytokine receptors restores JAK3 expression and activation and rescues CD4-mediated T cell unresponsiveness. Collectively, these data argue that inhibition of JAK3 expression and activation may, in part, explain the T cell dysfunction seen in early HIV disease. In addition, rescue from gp120-mediated T cell unresponsiveness by activation of JAK3 suggests a novel therapeutic approach for enhancing immune function in HIV disease.
Inactivation of catecholamines by superoxide gives new insights on the pathogenesis of septic shock (2000)

A major feature of septic shock is the development of a vascular crisis characterized by nonresponsiveness to sympathetic vasoconstrictor agents and the subsequent irreversible fall in blood pressure. In addition, sepsis, like other inflammatory conditions, results in a large increase in the production of free radicals, including superoxide anions (O(2)) within the body. Here we show that O(2) reacts with catecholamines deactivating them in vitro. Moreover, this deactivation would appear to account for the hyporeactivity to exogenous catecholamines observed in sepsis, because administration of a superoxide dismutase (SOD) mimetic to a rat model of septic shock to remove excess O(2) restored the vasopressor responses to norepinephrine. This treatment with the SOD mimetic also reversed the hypotension in these animals; suggesting that deactivation of endogenous norepinephrine by O(2) contributes significantly to this aspect of the vascular crisis. Indeed, the plasma concentrations of both norepinephrine and epinephrine in septic rats treated with the SOD mimetic were significantly higher than in untreated rats. Interestingly, the plasma concentrations for norepinephrine and epinephrine were inversely related to the plasma concentrations of adrenochromes, the product of the autoxidation of catecholamines initiated by O(2). We propose, therefore, that the use of a SOD mimetic represents a new paradigm for the treatment of septic shock. By removing O(2), exogenous and endogenous catecholamines are protected from autoxidation. As a result, both hyporeactivity and hypotension are reversed, generation of potentially toxic adrenochromes is reduced, and survival rate is improved.